bluuebunny/crossref_metadata_2025 huggingface dataset:
Sentinel approach to detect emerging causes of work-related respiratory diseases
Authors: Zhou A Y , Seed M , Carder M , Money A , Van Tongeren M , Agius R
Published: December 2019

Background

The world of work is continually changing, and this could result in new and emerging risks being introduced, including those that may cause work-related respiratory diseases (WRRD).

Aims

To describe recently emerging and new cases of WRRD and the relevant methodology using data in a national occupational respiratory disease surveillance scheme in the UK.

Methods

Incident cases of respiratory diseases reported by physicians to the Surveillance of Work-related and Occupational Respiratory Disease (SWORD) between January 2015 and December 2017 were included. Potentially emerging respiratory hazards manifesting in SWORD data were identified with the following hierarchical approach: (i) new respiratory disease not previously associated with work, (ii) specific exposure/agent not previously associated with WRRD and (iii) industry and/or occupation not previously associated with WRRD.

Results

A total of 1215 cases of WRRD were reported to SWORD between January 2015 and December 2017. No new WRRD were identified. Thirteen potentially emerging causes of occupational asthma were identified, including exposures to agents such as ninhydrin. Four potential new causes were identified for interstitial pneumonia, which included wood and brass dust. Two potentially emerging causes of WRRD were identified for inhalational accidents (green coffee and nitrocellulose), hypersensitivity pneumonitis (diphenylmethane diisocyanate and salami mould), rhinitis (morphine and Amaranthus quitensis) and sarcoidosis (prions and horses).

Conclusions

Continuous monitoring and reporting of any new work-related disease is a critical function of any occupational disease reporting scheme. Potential emerging causes of work-related health risks have been identified by using a simple and systematic way of detecting emerging causes of WRRDs.
On Categories and the Countability of Things Bureaucratic: Turning From Wilson (Back) to Interpretation
Authors: Carpenter Daniel
Published: December 2019

The formulation and application of categories was the handiwork of frontier scholars of public management and remains the essential task of scholars of bureaucracy and regulation. These scholars, exemplified by James Q. Wilson, pioneered the development of categories in three domains: (1) the inductive assignment of observed objects to conceptual groups (a form of Weberian categorization), (2) the deductive assignment of incentives and styles to conceptual groups (type-dependent theorization), and (3) the empirical assignment of observed objects to applied analytic categories (behavioralist measurement). I find in Varieties of Police Behavior (1968) the origins of his enduring categories in Bureaucracy (1988). His classification of agency personnel into executives, managers, and operators remains perhaps his crowning achievement in administrative research. Yet Wilson examined these categories with greater care than is often demonstrated by his successors, as he was careful to condition his comparisons across and within categories. The extension of truly “Wilsonian” principles of analysis to bureaucratic organization requires not simply the development of conceptual structures and the careful consideration of bureaucratic incentives, but also a reappreciation of administrative routines, practices, concepts, and technologies. It may compel the admission that some quantitative and qualitative comparisons are literally, even mathematically, nonsensical.
Public Management in an Era of the Unprecedented: Dominant Institutional Logics as a Barrier to Organizational Sensemaking
Authors: Nowell Branda , Stutler Joseph
Published: December 2019

In an era when unprecedented events are occurring with increasing frequency, public management theory is challenged to consider whether it is possible to better prepare agencies to respond to situations previously neither expected, nor even seriously imagined. In this paper, we consider the case of the 2016 Chimney Tops 2 wildfire that contributed to the destruction of neighborhoods in and around Gatlinburg, TN. We argue this case illuminates a critical gap in extant organizational theory concerning the factors that impede sensemaking processes, which are fundamental to models of high reliability organizations during unprecedented events. Specifically, based on insights from this case considered through an institutional lens, we theorize that the nature of unprecedented events undermines an adaptive response through both structural and cultural/institutional processes. Structurally, we demonstrate how public agencies evolve to the contingencies of their normal task environment, which we should anticipate will be maladapted to the task demands of an unprecedented event. However, we theorize the greater challenge lies in the processes by which these structural features of the agency, over time, create, and reinforce a dominant institutional logic which can delay and weaken sensemaking processes, even when discrepant environmental cues are present. We conclude with a discussion of remedies that may facilitate earlier recognition, and thus more effective agency response, when the unprecedented is occurring.
Mineralized collagen-modified PMMA cement enhances bone integration and reduces fibrous encapsulation in the treatment of lumbar degenerative disc disease
Authors: Yang Long , Kong Jianjun , Qiu Zhiye , Shang Tieliang , Chen Siyu , Zhao Rui , Raucci Maria Grazia , Yang Xiao , Wu Zhanyong
Published: December 2019

As a minimally invasive surgery, percutaneous cement discoplasty (PCD) is now contemplated to treat lumbar disc degeneration disease in elder population. Here, we investigated whether the osteogenic mineralized collagen (MC) modified polymethylmethacrylate (PMMA) cement could be a suitable material in PCD surgery. Injectability, hydrophilicity and mechanical properties of the MC-modified PMMA (PMMA-MC) was characterized. The introduction of MC did not change the application and setting time of PMMA and was easy to be handled in minimally invasive operation. Hydrophilicity of PMMA-MC was greatly improved and its elastic modulus was tailored to complement mechanical performance of bone under dynamic stress. Then, PCD surgery in a goat model with induced disc degeneration was performed with implantation of PMMA-MC or PMMA. Three months after implantation, micro-computed tomography analysis revealed a 36.4% higher circumferential contact index between PMMA-MC and bone, as compared to PMMA alone. Histological staining confirmed that the surface of PMMA-MC was in direct contact with new bone, while the PMMA was covered by fibrous tissue. The observed gathering of macrophages around the implant was suspected to be the cause of fibrous encapsulation. Therefore, the interactions of PMMA and PMMA-MC with macrophages were investigated in vitro. We discovered that the addition of MC could hinder the proliferation and fusion of the macrophages. Moreover, expressions of fibroblast-stimulating growth factors, insulin-like growth factor, basic fibroblast growth factor and tumor necrosis factor-β were significantly down-regulated in the macrophages cocultured with PMMA-MC. Together, the promoted osteointegration and reduced fibrous tissue formation observed with PMMA-MC material makes it a promising candidate for PCD surgery.
Advertising, Attention, and Financial Markets
Authors: Focke Florens , Ruenzi Stefan , Ungeheuer Michael
Published: December 2019

Using daily advertising data, we analyze the short-term effects of advertising on investor attention and on financial market outcomes. Based on various investor attention proxies, we show that advertising positively affects attention. However, it has only little impact on turnover and liquidity. Most importantly, short-term stock returns are not significantly influenced by advertising. Further results suggest that previous findings of an economically significant positive relation between advertising and returns are due to reverse causality. Thus, the belief that stock prices can be temporarily inflated via advertising is misguided.
False positives in the ultrasound diagnosis of giant cell arteritis: some diseases can also show the halo sign
Authors: Fernández-Fernández Elisa , Monjo-Henry Irene , Bonilla Gema , Plasencia Chamaida , Miranda-Carús María-Eugenia , Balsa Alejandro , De Miguel Eugenio
Published: December 2019

Objectives

To describe the frequency and causes for the presence of a halo sign on the ultrasound of patients without a diagnosis of GCA.

Methods

In total, 305 patients with temporal artery colour Doppler ultrasound showing the presence of halo sign (intima-media thickness ≥0.34 mm for temporal arteries [TAs] and ≥1 mm for axillary arteries) were included, and their medical records were reviewed. The clinical diagnosis based on the evolution of the patient over at least one year was established as the definitive diagnosis.

Results

Fourteen of the 305 (4.6%) patients included showed presence of the halo sign without final diagnosis of GCA: 12 patients in the TAs (86%), and two patients with isolated AAs involvement (14%). Their diagnoses were PMR (n = 4, 29%); atherosclerosis (n = 3, 21%); and non-Hodgkin lymphoma type T, osteomyelitis of the skull base, primary amyloidosis associated with multiple myeloma, granulomatosis with polyangiitis, neurosyphilis, urinary sepsis and narrow-angle glaucoma (n = 1 each, 7%).

Conclusion

The percentage of halo signs on the ultrasound of patients without GCA is low, but it does exist. There are conditions that may also show the halo sign (true positive halo sign), and we must know these and always correlate the ultrasound findings with the patient’s clinic records.
Warm-season annual forages in forage-finishing beef systems: II. Animal performance and carcass characteristics
Authors: Harmon Deidre D , Hancock Dennis W , Stewart R Lawton , Lacey Jenna L , Mckee Robert W , Hale John D , Thomas Chevise L , Ford Elyse , Segers Jacob R , Teutsch Chris D , Stelzleni Alexander M
Published: December 2019

More information on expected animal performance and carcass traits of forage-finished steers grazing warm-season annual forages is needed. To achieve this objective, a grazing trial was conducted in 2014, 2015, and 2016 (70, 63, and 56 d, respectively), with variation in length of grazing based on forage availability. Sixteen pastures (0.81 ha) were assigned to 1 of 4 forage treatments in a randomized complete block design. Forage treatments were brown midrib sorghum × sudangrass (BMR; Sorghum bicolor var. bicolor*bicolor var. sudanense), sorghum × sudangrass (SS), pearl millet [PM; Pennisetum glaucum (L.)R.Br.], or pearl millet planted with crabgrass [PMCG; Digitaria sanguinalis (L.) Scop.]. Each year, British-cross beef steers (n = 32; 3 y average: 429 ± 22 kg) were stratified by weight and randomly assigned to 1 of the 16 pastures for forage finishing. Each pasture was subdivided into two 0.405-ha paddocks for rotational stocking and a put-and-take stocking method was used to maintain a forage allowance of 116 kg forage dry matter/100 kg body weight (BW). Shrunk body weight and ultrasonically measured carcass composition were recorded at the initiation, middle, and end of each grazing season. Steers were harvested once forage availability became limited and chilled carcasses (24 h) were evaluated for yield grade and quality grade attributes. Statistical analysis was conducted using the GLIMMIX procedure in SAS 9.4 (Cary, NC) with main effects of treatment, year, and the interaction. Pasture and block were considered random effects while date was assessed as a main effect when applicable. Daily stocking densities were greater (P < 0.04) for SS than PMCG in the first 20 d of 2014 and 2015. Forage treatment did not affect (P > 0.17) total gain, total average daily gain, or body weight at any time point. Ultrasound composition traits of loin muscle area, 12th rib fat thickness, intramuscular fat, and rump fat were impacted (P < 0.01) by scanning date. No differences (P > 0.08) in forage treatments were observed for carcass characteristics associated with yield grade or quality grade. The findings suggest that forage-finished cattle during the summer months on BMR, SS, PM, and PMCG perform similarly, giving producers the option to use the most economical or practical forage type for their production system.
Comparative Genomics Screen Identifies Microbe-Associated Molecular Patterns from ‘Candidatus Liberibacter’ spp. That Elicit Immune Responses in Plants
Authors: Chen Yuan , Bendix Claire , Lewis Jennifer D.
Published: December 2019

Citrus huanglongbing (HLB), caused by phloem-limited ‘Candidatus Liberibacter’ bacteria, is a destructive disease threatening the worldwide citrus industry. The mechanisms of pathogenesis are poorly understood and no efficient strategy is available to control HLB. Here, we used a comparative genomics screen to identify candidate microbe-associated molecular patterns (MAMPs) from ‘Ca. Liberibacter’ spp. We identified the core genome from multiple ‘Ca. Liberibacter’ pathogens, and searched for core genes with signatures of positive selection. We hypothesized that genes encoding putative MAMPs would evolve to reduce recognition by the plant immune system, while retaining their essential functions. To efficiently screen candidate MAMP peptides, we established a high-throughput microtiter plate-based screening assay, particularly for citrus, that measured reactive oxygen species (ROS) production, which is a common immune response in plants. We found that two peptides could elicit ROS production in Arabidopsis and Nicotiana benthamiana. One of these peptides elicited ROS production and defense gene expression in HLB-tolerant citrus genotypes, and induced MAMP-triggered immunity against the bacterial pathogen Pseudomonas syringae. Our findings identify MAMPs that boost immunity in citrus and could help prevent or reduce HLB infection.
Genome Editing of a Deoxynivalenol-Induced Transcription Factor Confers Resistance to Fusarium graminearum in Wheat
Authors: Brauer Elizabeth K. , Balcerzak Margaret , Rocheleau Hélène , Leung Winnie , Schernthaner Johann , Subramaniam Rajagopal , Ouellet Thérèse
Published: December 2019

Deoxynivalenol (DON) is a mycotoxin virulence factor that promotes growth of the Fusarium graminearum fungus in wheat floral tissues. To further our understanding of the effects of DON exposure on plant cell function, we characterized DON-induced transcriptional changes in wheat spikelets. Four hundred wheat genes were differentially expressed during infection with wild-type F. graminearum as compared with a Δtri5 mutant strain that is unable to produce DON. Most of these genes were more induced by the DON-producing strain and included genes involved in secondary metabolism, signaling, transport, and stress responses. DON induction was confirmed for a subset of the genes, including TaNFXL1, by treating tissues with DON directly. Previous work indicates that the NFXL1 ortholog represses trichothecene-induced defense responses and bacterial resistance in Arabidopsis, but the role of the NFXL family has not been studied in wheat. We observed greater DON-induced TaNFXL1 gene expression in a susceptible wheat genotype relative to the F. graminearum–resistant genotype Wuhan 1. Functional testing using both virus-induced gene silencing and CRISPR-mediated genome editing indicated that TaNFXL1 represses F. graminearum resistance. Together, this suggests that targeting the TaNFXL1 gene may help to develop disease resistance in cultivated wheat.
Rutaecarpine derivative R3 attenuates atherosclerosis via inhibiting NLRP3 inflammasome‐related inflammation and modulating cholesterol transport
Authors: Luo Jinque , Wang Xiao , Jiang Xinhai , Liu Chao , Li Yongzhen , Han Xiaowan , Zuo Xuan , Li Yining , Li Ni , Xu Yanni , Si Shuyi
Published: December 2019

Atherosclerosis is a chronic disease characterized by lipid deposition and inflammatory response. NOD‐, LRR‐ and pyrin domain‐containing protein 3 (NLRP3) inflammasome‐facilitated inflammatory responses are crucial in the pathogenesis of atherosclerosis, and thus new therapeutic approaches are emerging that target NLRP3 and inflammation. Here, we explored the anti‐atherosclerotic effect and mechanisms of a new rutaecarpine derivative, 5‐deoxy‐rutaecarpine (R3) in vitro and in vivo. R3 treatment attenuated atherosclerosis development and increased plaque stability in Apoe−/− mice fed a high‐fat diet, and decreased levels of inflammatory mediators, such as interleukin‐1β, in the serum of Apoe−/− mice and in oxidized low‐density lipoprotein (ox‐LDL)‐stimulated murine macrophages. R3 treatment inhibited NLRP3 inflammasome activation in the livers of Apoe−/− mice and ox‐LDL‐stimulated murine macrophages by inhibiting NF‐κB and MAPK pathways. Additionally, R3 significantly decreased total cholesterol in the serum and livers of Apoe−/− mice and promoted cholesterol efflux in murine macrophages through upregulating protein expression of ATP‐binding cassette subfamily A member 1 and scavenger receptor class B type I/human CD36 and lysosomal integral membrane protein‐II analogous‐1. Our results demonstrated that R3 prevented atherosclerotic progression via attenuating NLRP3 inflammasome‐related inflammation and modulating cholesterol transport.
Subcellular trafficking of tubular MDM2 implicates in acute kidney injury to chronic kidney disease transition during multiple low‐dose cisplatin exposure
Authors: Su Hua , Ye Chen , Lei Chun‐Tao , Tang Hui , Zeng Jie‐Yu , Yi Fan , Zhang Chun
Published: December 2019

Acute kidney injury (AKI) is the leading cause of renal failure, and quite a few patients will advance to chronic kidney disease (CKD) in the long term. Here, we explore the roles and mechanisms of tubular epithelial cells (TECs) during repeated cisplatin (CP) induced AKI to CKD transition (AKI‐CKD). Previously, we reported that murine double minute 2 (MDM2), an E3‐ubiquitin ligase, is involved in tubulointerstitial fibrosis. However, whether tubular MDM2 is implicated in AKI‐CKD is undefined. Currently, we confirmed that during AKI‐CKD, MDM2 shifts from nucleus to cell membrane in TECs both in vivo and in vitro. Whereas regulating MDM2 distribution chemically or genetically has a prominent impact on tubular disorders. And then we investigated the mechanisms of the above findings. First, in the nucleus, repeated CP administration leads to MDM2 reduction with escalated p53 and cell cycle G2/M arrest. On the other hand, multiple CP treatment increases the level of membranous MDM2 with ensuing integrin β8 degradation and TGF‐β1 activation. More interestingly, anchoring MDM2 on cell membranes can mimic the reduction of integrin β8 arousing by repeated CP exposure. Collectively, our findings provided the evidence that tubular MDM2 subcellular shuttling is involved in AKI‐CKD through p53‐G2/M arrest and integrin β8 mediated TGF‐β1 activation.
Cardiolipin is essential for early embryonic viability and mitochondrial integrity of neurons in mammals
Authors: Kasahara Takaoki , Kubota‐Sakashita Mie , Nagatsuka Yasuko , Hirabayashi Yoshio , Hanasaka Tomohito , Tohyama Koujiro , Kato Tadafumi
Published: December 2019

Cardiolipin (CL) is a hallmark phospholipid of mitochondria and plays a significant role in maintaining the mitochondrial structure and functions. Despite the physiological importance of CL, mutant organisms, yeast, Arabidopsis, C elegans, and Drosophila, which lack CL synthase (Crls1) gene and consequently are deprived of CL, are viable. Here we report conditional Crls1‐deficient mice using targeted insertion of loxP sequences flanking the functional domain of CRLS1 enzyme. Homozygous null mutant mice exhibited early embryonic lethality at the peri‐implantation stage. We generated neuron‐specific Crls1 knockout (cKO) mice by crossing with Camk2α‐Cre mice. Neuronal loss and gliosis were gradually manifested in the forebrains, where CL levels were significantly decreased. In the surviving neurons, malformed mitochondria with bubble‐like or onion‐like inner membrane structures were observed. We showed decreased supercomplex assembly and reduced enzymatic activities of electron transport chain complexes in the forebrain of cKO mice, resulting in affected mitochondrial calcium dynamics, a slower rate of Ca2+ uptake and a smaller calcium retention capacity. These observations clearly demonstrate indispensable roles of CL as well as of Crls1 gene in mammals.
Interactions between non‐structured domains of FG‐ and non‐FG‐nucleoporins coordinate the ordered assembly of the nuclear pore complex in mitosis
Authors: Konishi Hide A. , Yoshimura Shige H.
Published: December 2019

In this study, we examined how channel‐forming subunits of the nuclear pore complex (NPC) are assembled into a selective channel within a highly structured scaffold ring during postmitotic assembly. We focused on non‐structured domains of the scaffold Nups and performed in vitro self‐assembled particle assays with those derived from channel‐forming FG‐Nups. We found that non‐structured domains of ELYS and Nup35N interacted with channel‐forming FG‐Nups to form a self‐assembled particle. Sequential addition of FG‐Nups into the scaffold particle revealed that ELYS, which initiates postmitotic NPC reassembly, interacts with early assembling FG‐Nups (Nups98 and 153) but not middle stage‐assembling FG‐Nups (Nups58 and 62). Nup35, which assembles between the early and middle stages, facilitated the assembly of Nup62 into the early assembling Nups both in vitro and in vivo. These results demonstrate that ELYS and Nup35 have a role of facilitator in the ordered assembly of channel‐forming FG‐Nups during mitosis.
Neutrophil recruitment and function in endometriosis patients and a syngeneic murine model
Authors: Symons Lindsey K. , Miller Jessica E. , Tyryshkin Kathrin , Monsanto Stephany P. , Marks Ryan M. , Lingegowda Harshavardhan , Vanderbeck Kaitlin , Childs Timothy , Young Steven L. , Lessey Bruce A. , Koti Madhuri , Tayade Chandrakant
Published: December 2019

Endometriosis is a chronic inflammatory, gynecological disease characterized by the presence of endometrial‐like tissue lesions outside of the uterus. Neutrophils are elevated in the systemic circulation and peritoneal fluid of endometriosis patients; however, whether and how neutrophils contribute to endometriosis pathophysiology remain poorly understood. With emerging roles for neutrophils in chronic and sterile inflammatory conditions, we sought to provide in‐depth characterization of neutrophil involvement in endometriosis. We demonstrate that neutrophils reside within patient endometriotic lesions and that patient lesions possess a microenvironment that may influence neutrophil recruitment and function. We also provide the first evidence that systemic circulating neutrophils from endometriosis patients display distinct transcriptomic differences compared neutrophils from healthy control subjects. Time course characterization of our syngeneic, immunocompetent mouse model of endometriosis revealed that neutrophils are rapidly recruited to the peritoneal environment early after endometriotic lesion establishment and remain present in murine lesions long term. In vivo neutrophil depletion altered the systemic and peritoneal immune microenvironment of mice with endometriosis as demonstrated by changes in pro‐inflammatory and angiogenic mediators. Taken together, these findings highlight a novel role for neutrophils in early events such as angiogenesis and modulation of the local inflammatory environment associated with endometriosis pathogenesis.
International Policy Frameworks for Consent in Minimal-risk Pragmatic Trials
Authors: Symons Tanya J. , Zeps Nikolajs , Myles Paul S. , Morris Jonathan M. , Sessler Daniel I.
Published: December 2019

There is intense debate around the use of altered and waived consent for pragmatic trials. Those in favor argue that traditional consent compromises the internal and external validity of these trials. Those against, warn that the resultant loss of autonomy compromises respect for persons and could undermine trust in the research enterprise.

This article examines whether international ethical guidelines and the policy frameworks in three countries—the United States, England, and Australia—permit altered and waived consent for minimal-risk pragmatic trials conducted outside the emergency setting. Provisions for both are clearly articulated in U.S. regulations, but many countries do not have equivalent frameworks. Investigators should not assume that all consent models permitted in the United States are legal in their jurisdictions, even if they are deemed ethically defensible.

The authors summarize ethical and regulatory considerations and present a framework for investigators contemplating trials with altered or waived consent.
Tumor lysis syndrome associated with bortezomib: A post-hoc analysis after signal detection using the US Food and Drug Administration Adverse Event Reporting System
Authors: Sanagawa Akimasa , Hotta Yuji , Kondo Masahiro , Nishikawa Ryohei , Tohkin Masahiro , Kimura Kazunori
Published: December 2019

Tumor lysis syndrome (TLS) is a cancer chemotherapy-associated oncologic emergency. Although there have recently been substantial developments in cancer chemotherapy, these may increase the risk of TLS. In this study, we aimed to identify anticancer agents that increase TLS risk, as classified by a TLS panel consensus, using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. TLS reports were retrieved from the FAERS database, and reporting odds ratios (RORs) were used to estimate associations between TLS and old and new anticancer agents or their combinations. We identified 1615 TLS cases among 4 330 807 case reports covering the period from the first quarter of 2004 through to the first quarter of 2014. Using RORs, we detected significant risk signals for 56 of 64 anticancer agents (37 and 19 cytotoxic and molecular-targeted drugs, respectively). Bortezomib in particular was found to be associated with a high ROR and numerous TLS events relative to those of other molecular-targeted drugs (161 TLS events, ROR = 28.89, 95% confidence interval: 24.53–34.02). The main indication of bortezomib is multiple myeloma, a low-risk disease for TLS occurrence. We conducted a detailed analysis focusing on regimens containing bortezomib, lenalidomide, and thalidomide. Bortezomib-containing treatment regimens were more frequently associated with TLS events than were other multiple myeloma treatment regimens (cytotoxic chemotherapy, lenalidomide, and thalidomide). Although the risk of TLS in patients with multiple myeloma is generally considered low, a cautious evaluation of TLS risk is recommended for patients receiving bortezomib-containing therapy.
Rare Case of Lipomatous Mixed Tumor With Follicular Differentiation
Authors: Doan Linda , Pham Christine , Elsensohn Ashley , Kraus Christina , Binder Scott
Published: December 2019

Cutaneous mixed tumors are adnexal neoplasms characterized by a mixture of epithelial, myoepithelial, and stromal components of varying proportions. The diagnosis may be of little challenge when chondroid or myxoid components are dominant. However, there are variants of the cutaneous mixed tumor where more uncommon features predominate, making the diagnosis more challenging. Here, we present a case of a rare variant of the cutaneous mixed tumor with extensive adipocytic and follicular differentiation. This is the second case of such a tumor reported to literature to our knowledge.
Stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and risk of cardiovascular disease events: systematic review, meta-analysis, and estimation of population etiologic fraction of prospective cohort studies
Authors: Han Minghui , Chen Qing , Liu Leilei , Li Quanman , Ren Yongcheng , Zhao Yang , Liu Dechen , Zhang Dongdong , Liu Feiyan , Chen Xu , Cheng Cheng , Guo Chunmei , Zhou Qionggui , Tian Gang , Qie Ranran , Huang Shengbing , Wu Xiaoyan , Liu Yu , Li Honghui , Sun Xizhuo , Lu Jie , Hu Dongsheng , Zhang Ming
Published: December 2019

Background:

Epidemiological studies reported an inconsistent association between stage 1 hypertension (SBP 130–139 mmHg or DBP 80–89 mmHg) defined by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and cardiovascular disease (CVD) events. In addition, the proportion of CVD events that could be prevented with effective control of stage 1 hypertension is unknown.

Objectives:

To assess the association between stage 1 hypertension and CVD events and estimate the population etiologic fraction.

Methods:

PubMed, Embase, and Web of Science databases were searched from 1 January 2017 to 22 September 2019. Normal BP was considered SBP less than 120 mmHg and DBP less than 80 mmHg. Hazard ratios and 95% confidence intervals (95% CIs) were pooled by using a random-effects model.

Results:

We included 11 articles (16 studies including 3 212 447 participants and 65 945 events) in the analysis. Risk of CVD events was increased with stage 1 hypertension versus normal BP (hazard ratio 1.38, 95% CI 1.28–1.49). On subgroup analyses, stage 1 hypertension was associated with coronary heart disease (CHD) (hazard ratio 1.30, 95% CI 1.20–1.41), stroke (1.39, 1.27–1.52), CVD morbidity (1.42, 1.32–1.53), and CVD mortality (1.34, 1.05–1.71). The population etiologic fraction for the association of CVD events, CHD, stroke, CVD morbidity, and CVD mortality with stage 1 hypertension was 12.90, 10.48, 12.71, 14.03, and 11.69%, respectively.

Conclusion:

Stage 1 hypertension is associated with CVD events, CVD morbidity, CVD mortality, CHD, and stroke. Effective control of stage 1 hypertension could prevent more than 10% of CVD events.
Natural Killer Cell Hypo-responsiveness in Chronic Lymphocytic Leukemia can be Circumvented In Vitro by Adequate Activating Signaling
Authors: Hofland Tom , Endstra Sanne , Gomes Calum K.P. , de Boer Renate , de Weerdt Iris , Bobkov Vladimir , Riedl Jurgen A. , Heukers Raimond , Smit Martine J. , Eldering Eric , Levin Mark-David , Kater Arnon P. , Tonino Sanne H.
Published: December 2019

Chronic lymphocytic leukemia (CLL) is characterized by an acquired immune dysfunction, which may underlie the hampered efficacy of cellular immunotherapy. Most data on dampened immune responses in CLL come from studies investigating CLL and T cell interactions. Natural killer (NK) cells may be an attractive alternative source of effector cells in immunotherapy in CLL, provided that functionality is retained within the CLL micro-environment. Despite their important role in anti-tumor responses, NK cells are not extensively characterized in CLL. Here, we studied the expression of activating and inhibitory receptors on CLL-derived and healthy control (HC) NK cells, and their functional response towards several stimuli.

NK cells from CLL patients have an increased maturation stage, with an expansion of NKG2C+ NK cells in CMV seropositive individuals. The cytotoxicity receptor NKG2D is downregulated, and the killing capacity through this receptor was markedly reduced in CLL-derived NK cells. In contrast, activation via CD16 (FCγRIII) led to adequate activation and functional responses in CLL-derived NK cells. These findings indicate that NK cells in CLL are not intrinsically defect and still perform effector functions upon adequate activating signaling. Clinical relevance of this finding was shown by treatment with novel nanobody-Fc constructs, which induced cytotoxic responses in both CLL- and HC-derived NK cells via CD16. Our results show that NK cells, in contrast to the T cell compartment, retain their function within the CLL micro-environment, provided that they receive an adequate activating signal. These findings warrant future studies on NK cell mediated immunotherapeutic strategies in CLL.
Meibomian Gland Dysfunction in a Hospital-Based Population in Central India
Authors: Chatterjee Samrat , Agrawal Deepshikha , Sharma Arpit
Published: December 2019

Purpose:

To estimate the prevalence of meibomian gland dysfunction (MGD) in a hospital-based population in India.

Methods:

This cross-sectional study screened 3410 subjects ≥20 years or older attending the outpatient department by systematic random sampling. The patients were subjected to a comprehensive eye examination, Ocular Surface Disease Index questionnaire, fluorescein tear film breakup time, Schirmer I test, lissamine green stain, lid margin changes, and meibomian gland expression. MGD was diagnosed when 1 or both of the following was present in at least 1 eye: reduced or absent meibum secretion and cloudy to inspissated toothpaste-like secretion on digital pressure over the eyelids.

Results:

The study included 570 subjects with a mean age of 49.3 ± 16.2 (20–84) years. MGD was diagnosed in 317 (55.61%) subjects, of whom 272 (47.7%) had only MGD and 45 (7.9%) had coexisting MGD and aqueous tear deficiency. The age-adjusted prevalence rate of MGD was 48.4% (95% confidence interval: 43.9–52.1). This rate increased significantly with age (P < 0.001) in both men (P < 0.001) and women (P < 0.001). The crude and age-adjusted prevalence of symptomatic MGD (Ocular Surface Disease Index score ≥13) was 26.1% (71/272) and 32.9% (95% confidence interval: 27.4–38.6), respectively. The prevalence of symptomatic MGD significantly declined with increasing age (P = 0.003), and this was reflected in both men (P = 0.013) and women (P = 0.179) but was not statistically significant in the latter.

Conclusions:

The prevalence of MGD was higher in Indian subjects than that previously reported. Although the total MGD prevalence increased with age, the prevalence of symptomatic MGD decreased. Asymptomatic MGD was more common than symptomatic MGD.
Functional and anatomical deficits in visceral nociception with age: a mechanism of silent appendicitis in the elderly?
Authors: Cibert-Goton Vincent , Kung Victor W.S. , McGuire Cian , Hockley James R.F. , Tranter Michael M. , Dogra Harween , Belai Abi , Blackshaw L. Ashley , Sanger Gareth J. , Knowles Charles H. , Araujo Eduardo J.A. , Winchester Wendy J. , Bulmer David C.
Published: December 2019

The ability to sense visceral pain during appendicitis is diminished with age leading to delay in seeking health care and poorer clinical outcomes. To understand the mechanistic basis of this phenomenon, we examined visceral nociception in aged mouse and human tissue. Inflamed and noninflamed appendixes were collected from consenting patients undergoing surgery for the treatment of appendicitis or bowel cancer. Supernatants were generated by incubating samples in buffer and used to stimulate multiunit activity in intestinal preparations, or single-unit activity from teased fibres in colonic preparations, of young and old mice. Changes in afferent innervation with age were determined by measuring the density of calcitonin gene-related peptide-positive afferent fibres and by counting dorsal root ganglia back-labelled by injection of tracer dye into the wall of the colon. Finally, the effect of age on nociceptor function was studied in mouse and human colon. Afferent responses to appendicitis supernatants were greatly impaired in old mice. Further investigation revealed this was due to a marked reduction in the afferent innervation of the bowel and a substantial impairment in the ability of the remaining afferent fibres to transduce noxious stimuli. Translational studies in human tissue demonstrated a significant reduction in the multiunit but not the single-unit colonic mesenteric nerve response to capsaicin with age, indicative of a loss of nociceptor innervation. Our data demonstrate that anatomical and functional deficits in nociception occur with age, underpinning the atypical or silent presentation of appendicitis in the elderly.
Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support
Authors: VanderPluym Christina J. , Cantor Ryan S. , Machado Desiree , Boyle Gerald , May Lindsay , Griffiths Eric , Niebler Robert A. , Lorts Angela , Rossano Joseph , Sutcliffe David L. , Lytrivi Irene D. , Buchholz Holger , Fynn-Thompson Francis , Hawkins Beth , Conway Jennifer
Published: December 2019

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1–215 months) weighing 8.6 kg (2.8–150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.
Defining sarcopenia: some caveats and challenges
Authors: Sanchez-Rodriguez Dolores , Marco Ester , Cruz-Jentoft Alfonso J.
Published: December 2019

Purpose of review

To summarize the latest advances and caveats in defining sarcopenia and discuss the implications of the most recent worldwide initiatives which are trying to harmonize the definition.

Recent findings

The evolution over time of the definitions of sarcopenia is discussed, with a focus on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) definition and the Sarcopenia Definitions and Outcomes Consortium (SDOC) conference. The EWGSOP2 and the SDOC agree on the overall concept of sarcopenia, which involves both impaired function (low muscle strength) and structural damage (low muscle mass/quality). However, physical performance is considered as a diagnostic criterion (EWGSOP), a severity grading assessment (EWGSOP2) or an outcome (SDOC) pending on the definition used. Muscle strength has been recognized as the best predictor of health outcomes. Muscle mass alone, as part of the definition of cachexia, sarcopenia and malnutrition, is a nondefining parameter. Furthermore, there is a lack of precision in measurement techniques and variability of the cut-off points in defining it.

We discuss the relationship of sarcopenia with cachexia, malnutrition and frailty, and the areas that are hampering agreement. We summarize key scientific evidence, consider future study of this nutrition-related disease and raise concern about the need for a universal definition of sarcopenia.
Enhancing the Patient Experience for Individuals Undergoing Endoscopic Procedures Using Virtual Reality
Authors: Palanica Adam , Leier McKenzie , Lee Andrew , Fossat Yan , Docktor Michael J.
Published: December 2019

The results of medical procedures can often be difficult to translate into comprehensible and engaging information for patients. This randomized controlled trial evaluated the satisfaction and perceived value of a technology, called HealthVoyager, which creates a personalized virtual reality (VR) experience of a patient's endoscopy or colonoscopy findings in comparison to the standard practice (ie, reviewing printed reports). The platform allows gastroenterologists to create a customized VR patient report to help translate medical knowledge and procedural information to the patient. Forty‐one patients (17 HealthVoyager [test]; 24 standard practice [control]) completed a self‐report survey assessing their experience for receiving medical information. Results demonstrated that patients were significantly more satisfied in learning about their gastrointestinal condition and procedural results using HealthVoyager rather than with the standard of care. These results have implications for improving the knowledge translation of medical findings between healthcare providers and patients in various disease states and patient populations.
International Nursing
Authors: Khatony Alireza , Zakiei Ali , Khazaie Habibolah , Rezaei Mohsen , Janatolmakan Maryam
Published: December 2019

The objective of this study was to evaluate sleep quality and its relationship to cognitive factors among nurses. Sleep quality among nurses is an important issue, which requires more extensive study. Its correlation with cognitive ability has not been sufficiently considered. Five hundred forty nurses (66.3% female) working in 6 hospitals were selected as the sample of the study. Results show that nurses do not experience good quality of sleep. That is, 77.4% of the sample population of nurses have a poor quality of sleep, and nurses working the night shift have more sleep problems than other nurses. The results show that there is a relationship between dysfunctional beliefs and attitudes about sleep and metacognitive process and the quality of sleep, and that these variables can predict sleep quality. Based on the results of the study, it can be said that cognitive and metacognitive processes play an important role in sleep quality. Lack of sufficient sleep can create numerous problems for nurses and patients. Attention to the role of cognitive and metacognitive processes can help improve the sleep quality of nurses.
Always a Nurse
Authors: Sanford Kathleen D.
Published: December 2019

A single career in nursing may encompass numerous and very different positions. Nurses are aware they can select from a variety of specialties, as they choose to learn additional skills or pursue new opportunities. Today's nurses use their intelligence, experience, and holistic concern for all people in more diverse arenas than ever before. This article is followed by a series of first-person accounts of jobs that may not, on first consideration, look like nursing roles. These professionals have not left nursing. They have carried their healing energy, grounding in the nursing process, as well as a desire to improve the well-being of others with them, because they are nurses.
Linking the mitochondrial genotype to phenotype: a complex endeavour
Authors: Ghiselli Fabrizio , Milani Liliana
Published: December 2019

Finding causal links between genotype and phenotype is a major issue in biology, even more in mitochondrial biology. First of all, mitochondria form complex networks, undergoing fission and fusion and we do not know how such dynamics influence the distribution of mtDNA variants across the mitochondrial network and how they affect the phenotype. Second, the non-Mendelian inheritance of mitochondrial genes can have sex-specific effects and the mechanism of mitochondrial inheritance is still poorly understood, so it is not clear how selection and/or drift act on mtDNA genetic variation in each generation. Third, we still do not know how mtDNA expression is regulated; there is growing evidence for a convoluted mechanism that includes RNA editing, mRNA stability/turnover, post-transcriptional and post-translational modifications. Fourth, mitochondrial activity differs across species as a result of several interacting processes such as drift, adaptation, genotype-by-environment interactions, mitonuclear coevolution and epistasis. This issue will cover several aspects of mitochondrial biology along the path from genotype to phenotype, and it is subdivided into four sections focusing on mitochondrial genetic variation, on the relationship among mitochondria, germ line and sex, on the role of mitochondria in adaptation and phenotypic plasticity, and on some future perspectives in mitochondrial research.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Pronounced somatic bottleneck in mitochondrial DNA of human hair
Authors: Barrett Alison , Arbeithuber Barbara , Zaidi Arslan , Wilton Peter , Paul Ian M. , Nielsen Rasmus , Makova Kateryna D.
Published: December 2019

Heteroplasmy
is the presence of variable mitochondrial DNA (mtDNA) within the same individual. The dynamics of heteroplasmy allele frequency among tissues of the human body is not well understood. Here, we measured allele frequency at heteroplasmic sites in two to eight hairs from each of 11 humans using next-generation sequencing. We observed a high variance in heteroplasmic allele frequency among separate hairs from the same individual—much higher than that for blood and cheek tissues. Our population genetic modelling estimated the somatic bottleneck during embryonic follicle development of separate hairs to be only 11.06 (95% confidence interval 0.6–34.0) mtDNA segregating units. This bottleneck is much more drastic than somatic bottlenecks for blood and cheek tissues (136 and 458 units, respectively), as well as more drastic than, or comparable to, the germline bottleneck (equal to 25–32 or 7–10 units, depending on the study). We demonstrated that hair undergoes additional genetic drift before and after the divergence of mtDNA lineages of individual hair follicles. Additionally, we showed a positive correlation between donor's age and variance in heteroplasmy allele frequency in hair. These findings have important implications for forensics and for our understanding of mtDNA dynamics in the human body.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Powerhouses in the cold: mitochondrial function during thermal acclimation in montane mayflies
Authors: Havird Justin C. , Shah Alisha A. , Chicco Adam J.
Published: December 2019

Mitochondria provide the vast majority of cellular energy available to eukaryotes. Therefore, adjustments in mitochondrial function through genetic changes in mitochondrial or nuclear-encoded genes might underlie environmental adaptation. Environmentally induced plasticity in mitochondrial function is also common, especially in response to thermal acclimation in aquatic systems. Here, we examined mitochondrial function in mayfly larvae (BaetisandDrunellaspp.) from high and low elevation mountain streams during thermal acclimation to ecologically relevant temperatures. A multi-substrate titration protocol was used to evaluate different respiratory states in isolated mitochondria, along with cytochrome oxidase and citrate synthase activities. In general, maximal mitochondrial respiratory capacity and oxidative phosphorylation coupling efficiency decreased during acclimation to higher temperatures, suggesting montane insects may be especially vulnerable to rapid climate change. Consistent with predictions of the climate variability hypothesis, mitochondria fromBaetiscollected at a low elevation site with highly variable daily and seasonal temperatures exhibited greater thermal tolerance thanBaetisfrom a high elevation site with comparatively stable temperatures. However, mitochondrial phenotypes were more resilient than whole-organism phenotypes in the face of thermal stress. These results highlight the complex relationships between mitochondrial and organismal genotypes, phenotypes and environmental adaptation.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.