bluuebunny/crossref_metadata_2025 huggingface dataset:
Down‐regulation of miR‐200c attenuates AngII‐induced cardiac hypertrophy via targeting the MLCK‐mediated pathway
Authors: Hu Shan , Cheng Mian , Guo Xin , Wang Shun , Liu Beilei , Jiang Hong , Huang Congxin , Wu Gang
Published: January 2019

Background

MicroRNAs (miRNAs) have been shown to commonly contribute to cardiac hypertrophy (CH). The aim of this study was to test the hypothesis that miR‐200c plays an important role in the progression of CH by targeting myosin light chain kinase (MLCK/MYLK).

Methods and results

Cardiac hypertrophy was induced by aortic banding (AB) in rats. Cellular hypertrophy in neonatal rat cardiomyocytes (NCMs) was induced by AngII treatment. Echocardiography, histology and molecular measurements were used to assess the results of the experiments. The levels of apoptosis and reactive oxygen species (ROS) were also measured. Quantitative real‐time PCR (qRT‐PCR) and Western blotting were used to measure mRNA and protein levels respectively. The present results showed that miR‐200c expression was increased in response to CH both in vivo and in vitro. The down‐regulation of miRNA‐200c by a specific inhibitor markedly ameliorated CH resulting from AngII treatment, and the mRNA levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain were simultaneously decreased. Notably, minimal apoptosis and ROS accumulation were identified in AngII‐induced hypertrophic cardiomyocytes. Conversely, the up‐regulation of miR‐200c using specific mimics reversed these effects. Mechanistic investigations demonstrated that the MLCK gene is a direct target of miR‐200c; an increase in miR‐200c levels led to a decrease in the expression of MLCK and its downstream effector, p‐MLC2, while miR‐200c inhibition increased the expression of these proteins. Furthermore, inhibiting MLCK impaired the anti‐hypertrophic effects contributions produced by the knockdown of miR‐200c.

Conclusion

Our studies suggest that miR‐200c may serve as a potential therapeutic target that could delay hypertrophy. We have also uncovered a relationship between miR‐200c and MLCK, identifying MLCK as a direct mediator of miR‐200c.
Aquaporin‐4 deficiency reduces TGF‐β1 in mouse midbrains and exacerbates pathology in experimental Parkinson's disease
Authors: Xue Xue , Zhang Weiwei , Zhu Jifeng , Chen Xiaojun , Zhou Sha , Xu Zhipeng , Hu Gang , Su Chuan
Published: January 2019

Aquaporin‐4 (AQP4), the main water‐selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced Parkinson's disease (PD) model, AQP4‐deficient (AQP4−/−) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH+)‐positive neurons than did wild‐type AQP4 (AQP4+/+) controls. Microglia are the most important immune cells that mediate immune inflammation in PD. However, recently, few studies have reported why AQP4 deficiency results in more severe hypermicrogliosis and neuronal damage after MPTP treatment. In this study, transforming growth factor‐β1 (TGF‐β1), a key suppressive cytokine in PD onset and development, failed to increase in the midbrain and peripheral blood of AQP4−/− mice after MPTP treatment. Furthermore, the lower level of TGF‐β1 in AQP4−/− mice partially resulted from impairment of its generation by astrocytes; reduced TGF‐β1 may partially contribute to the uncontrolled microglial inflammatory responses and subsequent severe loss of TH+ neurons in AQP4−/− mice after MPTP treatment. Our study provides not only a better understanding of both aetiological and pathogenical factors implicated in the neurodegenerative mechanism of PD but also a possible approach to developing new treatments for PD via intervention in AQP4‐mediated immune regulation.
Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
Authors: Dickel H. , Bruckner T. , Höxtermann S. , Dickel B. , Trinder E. , Altmeyer P.
Published: January 2019

Background

Fumaric acid esters (FAEs) are used to treat psoriasis and are known to cause lymphopenia in roughly 60% of the patients. Much remains to be elucidated about the biological effects ofFAEs on lymphocytes.

Objective

To evaluate the influence of long‐termFAE(Fumaderm®) treatment on peripheral bloodCD4+andCD8+T cells,CD19+B cells andCD56+natural killer (NK) cells in psoriasis.

Methods

In this single‐centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiatingFAEtherapy in 371 psoriasis patients (mean age, 47.8 years; 63.3% males) and monitored them during treatment (mean treatment duration, 2.9 years). Multiparametric flow cytometry was used for immunophenotyping.

Results

FAEs significantly reduced the numbers ofCD4+T,CD8+T,CD19+B andCD56+NKcells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest forCD8+T cells, with a peak of 55.7% after 2 years of therapy. The risk of T‐cell lymphopenia increased significantly with the age of the psoriasis patients at the time thatFAEtherapy was initiated. It was significantly decreased for the combination therapy with methotrexate and folic acid (vitamin B9) supplementation. Supporting evidence was found suggesting that T‐cell lymphopenia enhances the effectiveness ofFAEtherapy.

Conclusions

Monitoring distinct T‐cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both theFAEtreatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoringCD4+andCD8+T‐cell counts at regular intervals, especially in patients of middle to older age. Thus, further prospective studies are needed to establish evidence‐based recommendations to guide dermatologists in the management of psoriasis patients who are takingFAEs and who develop low absolute T‐cell counts.
A cryptic splicing mutation in the INF2 gene causing Charcot‐Marie‐Tooth disease with minimal glomerular dysfunction
Authors: Echaniz‐Laguna Andoni , Latour Philippe
Published: January 2019

Heterozygous mutations in the inverted formin‐2 (INF2) gene provoke focal segmental glomerulosclerosis (FSGS) and intermediate Charcot‐Marie‐Tooth (CMT) disease with FSGS. Here, we report four patients from a three‐generation family with a new cryptic splicing INF2 mutation causing autosomal dominant intermediate CMT with minimal glomerular dysfunction. Three males and one female with a mean age of 51 years (26‐87) presented with a slowly progressive sensorimotor polyneuropathy, pes cavus, and kyphoscoliosis. Mean age at CMT disease onset was 11.5 years (3‐17), and electrophysiological studies showed demyelinating and axonal features consistent with intermediate CMT. Plasma albumin and creatinine were normal in all four cases, and urine protein was normal in one case and mildly raised in three patients (mean: 0.32 g/L [0.18‐0.44], N < 0.14). Genetic analysis found a c.271C > G (p. Arg91Gly) variation in INF2 exon 2, and in vitro splicing assays showed the deletion of the last 120 nucleotides of INF2 exon 2 leading to a 40 amino acids in‐frame deletion (p. Arg91_p. Gln130del). This report expands the genetic spectrum of INF2‐associated disorders and demonstrates that INF2 mutations may provoke isolated CMT with no clinically relevant kidney involvement. Consequently, INF2 mutation analysis should not be restricted to individuals with coincident neuropathy and renal disease.
A Relative Noncontrast CT Map to Detect Early Ischemic Changes in Acute Stroke
Authors: Srivatsan Aditya , Christensen Søren , Lansberg Maarten G.
Published: January 2019

BACKGROUND AND PURPOSE

Early ischemic changes on noncontrast computed tomography (NCCT) are often subtle. We developed a novel postprocessing technique that aids in detecting such changes.

METHODS

NCCT maps were generated that display the relative density difference between corresponding voxels in contralateral hemispheres (ratio maps of the NCCT [rNCCT]). Voxels with a relative density difference below .95 were designated as infarct. We pilot tested the rNCCT for infarct segmentation on 6 consecutive subjects enrolled in the CT Perfusion to predict Response in Ischemic Stroke Project (CRISP) study and applied the inclusion criteria of an adequate quality NCCT and successful endovascular reperfusion. rNCCT infarct segmentation was compared to baseline NCCT, baseline CTP, and day‐5 follow‐up fluid‐attenuated inversion recovery (FLAIR).

RESULTS

Five of the six selected cases met the inclusion criteria. Their median time from symptom onset to CT was 4.95 hours (standard deviation [SD], ±3.5; range, 1.05‐10.45), and median NIHSS was 13. Early ischemic changes were identified on the rNCCT in all five cases and on the standard NCCT in three of the five cases. Lesions outlined by the rNCCT maps trended toward a better estimation of the day‐5 FLAIR volume (median difference = 6.2 mL) than the ischemic core volumes assessed on baseline CTP (median difference = 51.7 mL) in the four cases with a day‐5 FLAIR (P = .1).

CONCLUSION

In this proof‐of‐concept study, the rNCCT appears promising for detecting and quantifying early ischemic changes. These findings should be confirmed in a larger cohort.
Spatial patterns and drivers of fish and benthic reef communities at São Tomé Island, Tropical Eastern Atlantic
Authors: Maia Hugulay A. , Morais Renato A. , Quimbayo Juan Pablo , Dias Murilo S. , Sampaio Claudio L. S. , Horta Paulo A. , Ferreira Carlos Eduardo L. , Floeter Sergio R.
Published: January 2019

Marine communities vary across spatial scales due to changes in habitat structure, wave exposure, depth and anthropogenic activities. Here, we quantitatively characterized, for the first time, the reef fish assemblages and benthic communities in six sites around São Tomé Island, in the Tropical Eastern Atlantic region. We performed 139 underwater visual census and 112 photo‐quadrats across six sites around the island to explore the relative importance of exposure, depth and topographic complexity as drivers of fish and benthic reef communities. Planktivores were the most important trophic group, in terms of both fish abundance and biomass. Small fishes (0–7 cm) dominated the abundance, whereas biomass was mainly concentrated in 8–15 and 16–30 cm body size classes. About 30% of the total benthic cover was composed of turf algae and circa of 28% of calcareous coralline algae, whereas corals were comparably less abundant (only 8%). Among these, Montastraea cavernosawas the most abundant coral (46% of the coral cover and 4% of total benthic cover). Wave exposure was the most important driver of the reef fish assemblages and was also important for benthic communities. Also, fish species composition seemed to respond, although weakly, to benthic composition. Topographic complexity had little effect on the indicators of fish assemblages but seemed to drive some changes in benthic cover. Overall, our results evidence the dominance of small planktivorous reef fish assemblages and of turf algal communities in São Tomé. Taken together, they support the idea of benthic communities shaped by wave action, with minor importance of corals, and of important energetic contribution from planktonic material. We also suggest that the relatively low biomass of medium and large fish species reflects the long‐term fishing pressure in São Tomé Island.
Nursing staff's experiences of intensive care unit diaries: a qualitative study
Authors: Johansson Maria , Wåhlin Ingrid , Magnusson Lennart , Hanson Elizabeth
Published: January 2019

Background

Diaries as an intervention to aid psychological recovery among intensive care patients have been used for about 20 years, and findings tend to be positive. The provision of a diary directed at the patient may clarify the story of the intensive care unit (ICU) even for the family members and the family members of non‐survivors. Members of nursing staff are the primary authors, but how they themselves experience the use of ICU diaries has been minimally explored.

Aims and objectives

This study aimed to explore how nursing staff experienced the use of ICU patient diaries.

Design

Qualitative design using focus group interviews.

Methods

A qualitative methodology was used. Six focus group interviews were conducted with 27 nursing staff recruited from one university and two county hospitals. The data were analysed via thematic content analysis.

Findings

One overarching theme, ‘An effort to do good in words and actions’, and four interconnected themes were derived from the analysis. By creating the diary, nursing staff had to deal with a variety of ethical and practical dilemmas, but feedback from patients, family members and ICU follow‐up services reinforced the feeling of doing good. This overarching feeling of beneficence encouraged diary authoring and increased motivation and commitment to strive towards excellent patient care. To sustain the use of ICU diaries, collegiate and organizational support was deemed essential.

Conclusions

Nursing staff strived to do good in words and actions for patients and their families when writing the diaries. Positive feedback from patients, family members and ICU follow‐up services reinforced feelings of doing good, which served to enhance work satisfaction and a commitment to good‐quality nursing care. Experiential‐based education was recommended to help sustain ICU diary writing.

Relevance to clinical practice

Nursing staff requested mentoring and group discussions concerning the format, content and communication channels of the diary.
Benefits of extra food to reproduction depend on maternal condition
Authors: Podofillini Stefano , Cecere Jacopo G. , Griggio Matteo , Corti Margherita , De Capua Enrico L. , Parolini Marco , Saino Nicola , Serra Lorenzo , Rubolini Diego
Published: January 2019

The amount of food resources available to upper‐level consumers can show marked variations in time and space, potentially resulting in food limitation. The availability of food resources during reproduction is a key factor modulating variation in reproductive success and life‐history tradeoffs, including patterns of resource allocation to reproduction versus self‐maintenance, ultimately impacting on population dynamics. Food provisioning experiments constitute a popular approach to assess the importance of food limitation for vertebrate reproduction. In this study of a mesopredatory avian species, the lesser kestrel Falco naumanni, we provided extra food to breeding individuals from egg laying to early nestling rearing. Extra food did not significantly affect adult body condition or oxidative status. However, it increased the allocation of resources to flight feathers moult and induced females to lay heavier eggs. Concomitantly, it alleviated the costs of laying heavier eggs for females in poor body condition, and reduced their chances of nest desertion (implying complete reproductive failure). Extra food provisioning improved early nestling growth (body mass and feather development). Moreover, extra food significantly reduced the negative effects of ectoparasites on nestling body mass, while fostering forearm (a flight apparatus trait) growth among highly parasitized nestlings. Our results indicate that lesser kestrels invested the extra food mainly to improve current reproduction, suggesting that population growth in this species can be limited by food availability during the breeding season. In addition, extra food provisioning reduced the costs of the moult–breeding overlap and affected early growth tradeoffs by mitigating detrimental ectoparasite effects on growth and enhancing development of the flight apparatus with high levels of parasitism. Importantly, our findings suggest that maternal condition is a major trait modulating the benefits of extra food to reproduction, whereby such benefits mostly accrue to low‐quality females with poor body condition.
Predictors of nurses’ stress working with older people admitted to acute care setting
Authors: El‐Hneiti Mamdouh , Shaheen Abeer M. , Bani Salameh Ayman , Al‐Hussami Mahmoud , Ahmad Muayyad
Published: January 2019

Aim

To identify the predictors of nurses’ work stressors who care for older people (i.e., over age 65 years) in Jordan.

Background

Nurses sometimes experience stress which could occur as results of caring for older people, for example, with multiple physical and psychological needs. This stress could affect the job satisfaction and reduce the quality of care provided to older people. Thus, identifying sources of stress and predictors that cause stress for nurses is required to enhance quality of care for older people.

Design

A cross‐sectional design.

Methods

Cluster random sampling was used to select study settings (i.e., 3 public hospitals, 3 private hospitals and 17 healthcare centres) in Amman, Jordan. A convenience sampling method was used to select 485 nurses. The Quality‐Work‐Competence questionnaire and Nurses’ Working Life Questionnaire were used. Multiple linear regressions were used to identify predictors of job stress for nurses providing care for older people. The data were collected between June 2016 and January 2017.

Results

Job satisfaction, competence, development skills, gender, organisational climate and employee development, all have demonstrated significant correlations with stress. The regression analysis showed that the model significantly predicted a sizable portion of variance (R2 = 0.27, p < 0.001) in the physical and psychological stress among nurses working in the older people care settings.

Conclusion

The nursing profession and the employing agencies should support nurses who care for older people in practice by conducting special training programmes to cope with stress. Interventional studies should be conducted to confirm the association between the nurses’ work stress who care for older people and job satisfaction, competence, development skills, gender, organisational climate and employee development.

Implications for practice

It is recommended that rotating appropriate competent nurses who care for older people, in particular dementia patients who are usually very ill may have greater needs due to their cognitive status, through other wards would temporarily reduce the nurses’ stress. The nursing profession and the employing agencies should support nurses who care for older people in practice by conducting special training programmes focusing on the teaching skills and knowledge of how to deal with stress.
Balancing the physics of radiation: Challenges to the system of quantities and units in radiological protection
Authors: David Mariano Gazineu , Corrêa Mônica Ferreira , Videira Antonio Augusto Passos
Published: January 2019

Ionizing radiation is present in various situations in the contemporary world. Defining the quantities and units for this field is a complex scientific task, especially the quantities used in radiological protection (RP) to estimate the damage caused to individuals exposed to radiation (detriment). This article highlights the lack of consensus in the scientific RP community regarding the quantities and units employed in practice from the perspective of the philosophy of science. The basic concepts related to the system of quantities are presented, followed by the problems and criticisms addressed by experts in the field. Several reasons for these problems are identified. The article discusses the scant interest on the part of philosophy of science in RP. The philosophy of science is still dominated by an analytical–conceptual perspective that pays little attention to the actual influence of certain structures better understood when considered from the institutional viewpoint, which is here exemplified by the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA).
Position, Preference and Personality: A Microlevel Explanation of Negativity in Day‐To‐Day Politics
Authors: Ketelaars Pauline
Published: January 2019

While many scholars investigate the determinants of negativity in the political sphere, it remains largely unclear why some politicians are more negative than others. Studies thus far lack explanations at the individual level, and they almost exclusively focus on negativity during electoral races. Surveying national and regional representatives in Belgium (N = 228), this study seeks to explain individual politicians’ willingness to go negative during everyday politics. The results show that negativity is not so much related to institutionally driven differences between representatives but more to politicians’ personal characteristics and preference roles. Negative politics, hence, is not an inevitable result of institutional structures, rules, and norms, but rather depends on the characteristics and motivations of the individual representatives citizens elect.
Recent advances in bovine sperm cryopreservation techniques with a focus on sperm post‐thaw quality optimization
Authors: Grötter Laura Guadalupe , Cattaneo Luciano , Marini Patricia Estela , Kjelland Michael E. , Ferré Luis B.
Published: January 2019

Contents

Sperm cryopreservation facilitates the storage and transport of germplasm for its use in artificial insemination (AI) and other advanced reproductive technologies. The cryopreservation process can damage sperm and compromise functionality. Several cryobiological studies have found that the physical and biological factors that affect sperm survival at low temperatures during the cryopreservation process often involve the integrity of sperm membrane. In this review, the behaviour of the sperm membrane against cooling, cold shock, ice crystal formation, oxidative stress, osmotic changes, reorganization of the lipid bilayer and addition of cryoprotective agents (CPA) is discussed. In addition, the phenomenon of reactive oxygen species (ROS) and its relationship with the cryopreservation process is also described. Semen cryopreservation techniques have progressed slowly in past years, and the current performance, measured as post‐thawed survival, is not very different compared to past decades. Recent advances in understanding the structure of the cell membrane, its function and metabolism have driven to new conservation systems, including lyophilization and vitrification. However, none of these technologies is commercially available, although its future appears very promising.
Downregulated Rac1 promotes apoptosis and inhibits the clearance of apoptotic cells in airway epithelial cells, which may be associated with airway hyper‐responsiveness in asthma
Authors: Wan Jie , Cao Yuwen , Abdelaziz Mohamed Hamed , Huang Lan , Kesavan Dinesh Kumar , Su Zhaoliang , Wang Shengjun , Xu Huaxi
Published: January 2019

The accumulation of airway apoptotic cells may be an important factor causing airway hyper‐responsiveness (AHR). Whether the apoptotic cells can be promptly removed is related to the occurrence and course of asthma. In recent years, studies have shown that Rac1 is involved in many cellular biological activities including the formation and elimination of apoptotic cells. In this study, based on the analysis of airway local cells and related factors in asthmatic mice, we evaluated the expression of Rac1 in airway epithelial cells or phagocytes and analysed its relationship with the incidence of apoptosis or scavenging of apoptotic cells. Our data showed that the expression level of Rac1 in asthmatic mice decreased significantly, while the expression of IL‐33 increased obviously. The airway epithelial cell line was stimulated by curcumin at 50 μmol/L for 24‐48 hours; more than 50% of the cells were apoptotic, and of which, about 20% were late apoptosis. Rac1 inhibitor (NSC23766) can enhance the apoptosis effect. In addition, the ability of phagocytosis and migration in the epithelial cells or macrophages was increased following the application of Rac1 inhibitors or specific siRNA in a dose‐dependent manner, and the expression level of IL‐33 was simultaneously increased after blocking Rac1. It is suggested that the down regulation of Rac1 in asthma may contribute to the apoptosis of airway epithelial cells and affect the clearance of apoptotic cells, which will lead to the aggregation of the apoptotic cells in the respiratory tract and participate in AHR.
To the knowledge of oribatid mites (Acari, Oribatida) of Samoa
Authors: Ermilov Sergey G. , Friedrich Stefan
Published: January 2019

A new species of oribatid mites of the family Galumnidae (Acari, Oribatida) is described from Samoa; Pergalumna enricoi sp. nov. differs from Pergalumna foveolata Hammer, 1973 by the elongate oval, transversely oriented notogastral porose areas Aa and heavily tuberculate prodorsum. An identification key to the known species of the genus Pergalumna from the Australian region is presented. A list of oribatid mite taxa of the Samoan Islands, including 77 species/subspecies from 56 genera and 29 families, is provided.
Autoscore: An open-source automated tool for scoring listener perception of speech
Authors: Borrie Stephanie A. , Barrett Tyson S. , Yoho Sarah E.
Published: January 2019

Speech perception studies typically rely on trained research assistants to score orthographic listener transcripts for words correctly identified. While the accuracy of the human scoring protocol has been validated with strong intra- and inter-rater reliability, the process of hand-scoring the transcripts is time-consuming and resource intensive. Here, an open-source computer-based tool for automated scoring of listener transcripts is built (Autoscore) and validated on three different human-scored data sets. Results show that not only is Autoscore highly accurate, achieving approximately 99% accuracy, but extremely efficient. Thus, Autoscore affords a practical research tool, with clinical application, for scoring listener intelligibility of speech.
Diffraction of a spherical wave by a hard half-plane: Approximation of the edge field in the frequency domain
Authors: Ouis Djamel
Published: January 2019

The diffraction of a spherical sound wave by a thin hard half-plane is considered. The total field at any position in the space surrounding the edge of the half-plane is composed of three components, two of which are expressed from pure geometrical considerations, and a third component which seems to originate from fictive sound sources situated on the edge of the half plane. This paper takes the expression of the edge-diffracted field as formulated in the Biot-Tolstoy theory of diffraction for the case of a doublet sound signal emanating from the sound source [Biot and Tolstoy (1957). J. Acoust. Soc. Am. 29, 381–391] but rearranged later in a more tractable form by Medwin [(1981). J. Acoust. Soc. Am. 69, 1060–1064] for the more general case of a Dirac-like pulse. Hence a development in the frequency domain of the Fourier transform of the exact expression of the edge-diffracted field in the time domain takes into consideration a part with known special mathematical functions, and a part containing a serial development. This latter also expressed in some special mathematical functions, converges quite rapidly to the numerical Fourier transform of the exact time-domain expression. The presented solution may be used as a good approximation in simulations and in real case predictions of sound attenuation by thin hard barriers.
Biomaterials for tissue repair
Authors: Christman Karen L.
Published: January 2019

Biomaterials can promote endogenous healing without delivering cells or therapeutics
Fake news on Twitter during the 2016 U.S. presidential election
Authors: Grinberg Nir , Joseph Kenneth , Friedland Lisa , Swire-Thompson Briony , Lazer David
Published: January 2019

Finding facts about fake news

There was a proliferation of fake news during the 2016 election cycle. Grinberg
et al.
analyzed Twitter data by matching Twitter accounts to specific voters to determine who was exposed to fake news, who spread fake news, and how fake news interacted with factual news (see the Perspective by Ruths). Fake news accounted for nearly 6% of all news consumption, but it was heavily concentrated—only 1% of users were exposed to 80% of fake news, and 0.1% of users were responsible for sharing 80% of fake news. Interestingly, fake news was most concentrated among conservative voters.

Science
, this issue p.
374
; see also p.
348
The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Authors: Holth Jerrah K. , Fritschi Sarah K. , Wang Chanung , Pedersen Nigel P. , Cirrito John R. , Mahan Thomas E. , Finn Mary Beth , Manis Melissa , Geerling Joel C. , Fuller Patrick M. , Lucey Brendan P. , Holtzman David M.
Published: January 2019

Sleep may protect the brain from AD

Two main proteins accumulate in the brain in Alzheimer's disease (AD), β-amyloid (Aβ) and tau. Aβ appears to instigate AD, but tau appears to drive brain damage and cognitive decline. Sleep deprivation is known to increase Aβ acutely and chronically. Now, Holth
et al.
show that chronic sleep deprivation strongly increases tau acutely over hours and also drives tau pathology spreading in the brains of mice and humans (see the Perspective by Noble and Spires-Jones). Thus, sleep appears to have a direct protective effect on a key protein that drives AD pathology.

Science
, this issue p.
880
; see also p.
813
We are the (communication) champions
Championing Science
Roger D. Aines and Amy L. Aines
University of California Press, 2019. 265 pp.
Authors: Reczek Peter R.
Published: January 2019

Emotional intelligence and other “soft skills” are key to convincing science stakeholders
Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-Attenuating Mutations
Authors: Pham Cau D. , Sharpe Samera , Schlanger Karen , St. Cyr Sancta , Holderman Justin , Steece Richard , Soge Olusegun O. , Masinde Godfred , Arno Janet , Schmerer Matthew , Kersh Ellen N. ,   the SURRG Working Group
Published: January 2019

The nimbleness of
Neisseria gonorrhoeae
to evade the effect of antibiotics has perpetuated the fight against antibiotic-resistant gonorrhea for more than 80 years. The ability to develop resistance to antibiotics is attributable to its indiscriminate nature in accepting and integrating exogenous DNA into its genome.
Src Family Kinase Inhibitors Block Translation of Alphavirus Subgenomic mRNAs
Authors: Broeckel Rebecca , Sarkar Sanjay , May Nicholas A. , Totonchy Jennifer , Kreklywich Craig N. , Smith Patricia , Graves Lee , DeFilippis Victor R. , Heise Mark T. , Morrison Thomas E. , Moorman Nathaniel , Streblow Daniel N.
Published: January 2019

Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts.
Expression of the Pseudorabies Virus gB Glycoprotein Triggers NK Cell Cytotoxicity and Increases Binding of the Activating NK Cell Receptor PILRβ
Authors: De Pelsmaeker Steffi , Dierick Evelien , Klupp Barbara , Mettenleiter Thomas C. , Cantoni Claudia , Vitale Massimo , Favoreel Herman W.
Published: January 2019

Natural killer (NK) cells display a prominent cytolytic activity against virus-infected cells and are indispensable in the innate antiviral response, particularly against herpesviruses. Despite their importance in the control of alphaherpesvirus infections, relatively little is known about the mechanisms that trigger NK cell cytotoxicity against alphaherpesvirus-infected cells. Here, using the porcine alphaherpesvirus pseudorabies virus (PRV), we found that the conserved alphaherpesvirus glycoprotein gB triggers NK cell-mediated cytotoxicity, both in virus-infected and in gB-transfected cells. In addition, we report that gB expression results in increased cell surface binding of porcine paired immunoglobulin-like type 2 receptor beta (PILRβ), an activating NK cell receptor. The interaction between PILRβ and viral gB may have consequences that stretch beyond the interaction with NK cells, including virus entry into host cells. The identification of gB as an NK cell-activating viral protein may be of importance in the construction of future vaccines and therapeutics requiring optimized interactions of alphaherpesviruses with NK cells.
Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note
Authors: Zawadzki Michal , Walecki Jerzy , Kostkiewicz Boguslaw , Kostyra Kacper , Pearl Monica Smith , Solaiyappan Meiyappan , Walczak Piotr , Janowski Miroslaw
Published: January 2019

Patients with malignant brain tumors have a poor prognosis. The blood–brain barrier (BBB) is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has recently been shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma supplied by the catheter and facilitates predictable drug targeting. Moreover, PET imaging has shown that IA rather than intravenous delivery of bevacizumab results in accumulation in the brain, providing a strong rationale for using the IA route. We present a patient with recurrent butterfly glioblastoma enrolled in a first-in-man MRI-guided neurointervention for targeted IA drug delivery.
Idiopathic tumoral calcinosis presenting in early childhood
Authors: Gupta Mudita , Thakur Saru , Sharma Reena , Gupta Archit
Published: January 2019

Idiopathic calcinosis (IC) is deposition of calcium hydroxyapatite crystals or amorphous calcium with no predisposing cause. IC presents in juxta-articular tissue in a tumour-like fashion is known as idiopathic tumoral calcinosis (ITC). Recurrent trauma and chronic pressure are thought to be the triggering factors. It usually presents in adolescents and adults. Presentation in early childhood is a rarity. We are reporting ITC in an 8-year-old child with the onset at 4 years of age.
Pancoast tumour presenting as shoulder pain with Horner’s syndrome
Authors: Shanmugathas Nimlan , Rajwani Kapil Mohan , Dev Shumontha
Published: January 2019

A 54-year-old man presented to the emergency department with a 4-week history of right shoulder pain radiating down his arm, with some associated sensory loss. Further questioning and examination in the department revealed a classical Horner’s syndrome; miosis, partial ptosis and hemifacial anhidrosis. An initial chest X-ray was deemed to be unremarkable; however, further review by a radiologist noted asymmetrical right apical thickening. A subsequent high-resolution CT scan of the chest revealed a right-sided Pancoast tumour. This case highlights the importance of a thorough history and examination in identifying a rare cause of shoulder and/or back pain.
Association of fried food consumption with all cause, cardiovascular, and cancer mortality: prospective cohort study
Authors: Sun Yangbo , Liu Buyun , Snetselaar Linda G , Robinson Jennifer G , Wallace Robert B , Peterson Lindsay L , Bao Wei
Published: January 2019

Objective

To examine the prospective association of total and individual fried food consumption with all cause and cause specific mortality in women in the United States.

Design

Prospective cohort study.

Setting

Women’s Health Initiative conducted in 40 clinical centers in the US.

Participants

106 966 postmenopausal women aged 50-79 at study entry who were enrolled between September 1993 and 1998 in the Women’s Health Initiative and followed until February 2017.

Main outcome measures

All cause mortality, cardiovascular mortality, and cancer mortality.

Results

31 558 deaths occurred during 1 914 691 person years of follow-up. For total fried food consumption, when comparing at least one serving per day with no consumption, the multivariable adjusted hazard ratio was 1.08 (95% confidence interval 1.01 to 1.16) for all cause mortality and 1.08 (0.96 to 1.22) for cardiovascular mortality. When comparing at least one serving per week of fried chicken with no consumption, the hazard ratio was 1.13 (1.07 to 1.19) for all cause mortality and 1.12 (1.02 to 1.23) for cardiovascular mortality. For fried fish/shellfish, the corresponding hazard ratios were 1.07 (1.03 to 1.12) for all cause mortality and 1.13 (1.04 to 1.22) for cardiovascular mortality. Total or individual fried food consumption was not generally associated with cancer mortality.

Conclusions

Frequent consumption of fried foods, especially fried chicken and fried fish/shellfish, was associated with a higher risk of all cause and cardiovascular mortality in women in the US.
The WHO-INTEGRATE evidence to decision framework version 1.0: integrating WHO norms and values and a complexity perspective
Authors: Rehfuess Eva A , Stratil Jan M , Scheel Inger B , Portela Anayda , Norris Susan L , Baltussen Rob
Published: January 2019

Introduction

Evidence-to-decision (EtD) frameworks intend to ensure that all criteria of relevance to a health decision are systematically considered. This paper, part of a series commissioned by the WHO, reports on the development of an EtD framework that is rooted in WHO norms and values, reflective of the changing global health landscape, and suitable for a range of interventions and complexity features. We also sought to assess the value of this framework to decision-makers at global and national levels, and to facilitate uptake through suggestions on how to prioritise criteria and methods to collect evidence.

Methods

In an iterative, principles-based approach, we developed the framework structure from WHO norms and values. Preliminary criteria were derived from key documents and supplemented with comprehensive subcriteria obtained through an overview of systematic reviews of criteria employed in health decision-making. We assessed to what extent the framework can accommodate features of complexity, and conducted key informant interviews among WHO guideline developers. Suggestions on methods were drawn from the literature and expert consultation.

Results

The new WHO-INTEGRATE (INTEGRATe Evidence) framework comprises six substantive criteria—balance of health benefits and harms,human rights and sociocultural acceptability,health equity,equality and non-discrimination,societal implications,financial and economic considerations, andfeasibility and health system considerations—and the meta-criterionquality of evidence. It is intended to facilitate a structured process of reflection and discussion in a problem-specific and context-specific manner from the start of a guideline development or other health decision-making process. For each criterion, the framework offers a definition, subcriteria and example questions; it also suggests relevant primary research and evidence synthesis methods and approaches to assessing quality of evidence.

Conclusion

The framework is deliberately labelled version 1.0. We expect further modifications based on focus group discussions in four countries, example applications and input across concerned disciplines.
Qualitative evidence synthesis for complex interventions and guideline development: clarification of the purpose, designs and relevant methods
Authors: Flemming Kate , Booth Andrew , Garside Ruth , Tunçalp Özge , Noyes Jane
Published: January 2019

This paper is one of a series exploring the implications of complexity for systematic reviews and guideline development, commissioned by the WHO. The paper specifically explores the role of qualitative evidence synthesis. Qualitative evidence synthesis is the broad term for the group of methods used to undertake systematic reviews of qualitative research evidence. As an approach, qualitative evidence synthesis is increasingly recognised as having a key role to play in addressing questions relating to intervention or system complexity, and guideline development processes. This is due to the unique role qualitative research can play in establishing the relative importance of outcomes, the acceptability, fidelity and reach of interventions, their feasibility in different settings and potential consequences on equity across populations. This paper outlines the purpose of qualitative evidence synthesis, provides detail of how qualitative evidence syntheses can help establish understanding and explanation of the complexity that can occur in relation to both interventions and systems, and how qualitative evidence syntheses can contribute to evidence to decision frameworks. It provides guidance for the choice of qualitative evidence synthesis methods in the context of guideline development for complex interventions, giving ‘real life’ examples of where this has occurred. Information to support decision-making around choice qualitative evidence synthesis methods in the context of guideline development is provided. Approaches for reporting qualitative evidence syntheses are discussed alongside mechanisms for assessing confidence in the findings of a review.
Synthesising quantitative and qualitative evidence to inform guidelines on complex interventions: clarifying the purposes, designs and outlining some methods
Authors: Noyes Jane , Booth Andrew , Moore Graham , Flemming Kate , Tunçalp Özge , Shakibazadeh Elham
Published: January 2019

Guideline developers are increasingly dealing with more difficult decisions concerning whether to recommend complex interventions in complex and highly variable health systems. There is greater recognition that both quantitative and qualitative evidence can be combined in a mixed-method synthesis and that this can be helpful in understanding how complexity impacts on interventions in specific contexts. This paper aims to clarify the different purposes, review designs, questions, synthesis methods and opportunities to combine quantitative and qualitative evidence to explore the complexity of complex interventions and health systems. Three case studies of guidelines developed by WHO, which incorporated quantitative and qualitative evidence, are used to illustrate possible uses of mixed-method reviews and evidence. Additional examples of methods that can be used or may have potential for use in a guideline process are outlined. Consideration is given to the opportunities for potential integration of quantitative and qualitative evidence at different stages of the review and guideline process. Encouragement is given to guideline commissioners and developers and review authors to consider including quantitative and qualitative evidence. Recommendations are made concerning the future development of methods to better address questions in systematic reviews and guidelines that adopt a complexity perspective.
Access to mobile phone and willingness to receive mHealth services among patients with diabetes in Northwest Ethiopia: a cross-sectional study
Authors: Jemere Adamu Takele , Yeneneh Yohannes Ezezew , Tilahun Biniam , Fritz Fleur , Alemu Shitaye , Kebede Mihiretu
Published: January 2019

Objectives

This study aimed at determining access to mobile phone and willingness to receive mobile phone-based diabetes health services as well as identify associated factors in Northwest Ethiopia.

Design

An institution-based cross-sectional survey was conducted from February to March 2016.

Participants

Systematic randomly selected 423 patients with diabetes.

Setting

University of Gondar Hospital diabetic clinic.

Main outcome measures

The main outcome measure was willingness to receive diabetic health service via mobile phone voice call or messaging services.

Results

Out of 423 patients with diabetes, 329 (77.8%) had access to a mobile phone. Among the latter, 232 (70.5%) were willing to receive mobile phone-based health services. The educational status of patients (adjusted OR (AOR): 2.6 (95% CI: 1.2 to 5.58)), route of medication (AOR: 3.2 (95% CI: 1.44 to 7.1)), transportation mechanism (AOR: 4.1 (95% CI: 1.2 to 13.57)), travel time to health facility (AOR: 0.3 (95% CI: 0.12 to 0.82)), current use of mobile phone as appointment reminder (AOR: 2.6 (95% CI: 1.07 to 6.49)) and locking mobile phone with passwords (AOR: 4.6 (95% CI: 1.63 to 12.95)) were significantly associated with the willingness to receive mobile phone-based diabetic health services.

Conclusion

Access to a mobile phone and willingness to receive mobile phone-based health services were high. Educational status, route of medication, transportation mechanism, time to reach the service, using mobile phone as appointment reminder and locking mobile phone with passwords were significantly associated factors. Given the high proportion of access and willingness of patients to receive mobile phone-based health services, mHealth interventions could be helpful.
Advance care planning for patients with advanced illnesses attending hospital outpatient clinics study: a study protocol for a randomised controlled trial
Authors: Rhee Joel , Meller Anne , Krysinska Karolina , Gonski Peter , Naganathan Vasi , Zwar Nicholas , Hayen Andrew , Cullen John , O’Keefe Julie-Ann , McDonald Julie , Harris-Roxas Ben , Caplan Gideon A
Published: January 2019

Introduction

It is unclear whether advance care planning (ACP) undertaken with patients living in the community can improve patient care and avoid unwanted interventions and hospital admissions. We have designed a randomised controlled trial (RCT) to examine if ACP undertaken with patients with advanced illnesses attending hospital outpatient clinics can reduce unplanned hospital admissions and improve patient and caregiver well-being.

Methods and analysis

Pragmatic RCT involving patients from subspecialty outpatient clinics at five clinical sites in Sydney, Australia. Participants will be ≥18 years screened as potentially having palliative care needs and at risk of dying in 6–12 months. The patients will be randomised to intervention or control group. Intervention group will undertake ACP discussions facilitated by a trained health professional. The control group will receive written information on ACP, representing the current standard of care. The primary outcome is the number of unplanned hospital admissions at the 6-month follow-up. Secondary outcomes include: (i) patient’s health-related quality-of-life and quality of chronic disease care; (ii) caregiver’s health-related quality-of-life and caregiver burden and (iii) other health outcomes including ambulance usage, emergency department presentations, hospital admissions, resuscitation attempts, intensive care unit admissions, deaths, documentation of patient wishes in patient records and audit of ACP discussions and documents. The staff’s self-reported attitudes and knowledge of ACP will also be measured. The data will be collected using self-report questionnaires, hospital records audit, audit of ACP documentation and data linkage analysis. Semistructured interviews and focus group discussions with patients, caregivers and healthcare professionals will explore the acceptability and feasibility of the intervention.

Ethics and dissemination

Approved by South-East Sydney Local Health District Human Research Ethics Committee and NSW Population and Health Services Research Ethics Committee. Results will be disseminated via conference presentations, journal publications, seminars and invited talks.

Trial registration number

ACTRN12617000280303.