bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-wave Ultraviolet Ray Promotes Inflammation in Keloid-derived Fibroblasts by Activating P38-NFκB1 Signaling Pathway
Authors: Niu Xingtang , Lin Xunxun , Chen Xiaoqian , Xu Shuqia , Huang Zhipeng , Tang Qing
Published: May 2020

One of the main mechanisms of keloid formation is the persistent chronic inflammation, which initiates the activation of keloid-derived fibroblasts (KFs) and boosts the production of extracellular matrix. Meanwhile, 95% of the ultraviolet rays that reach the earth are long-wave ultraviolet (UVA). However, the effect of UVA on keloids is currently unclear. The objective of our research is to investigate UVA’s impact on keloids. Cell viability assay, migration assay, and cell cycle analysis were conducted. UVA’s impacts on gene expressions were detected by real-time quantitative polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence. Our results indicated that UVA inhibited the proliferation and migration of KFs. In addition, after UVA irradiation, the expressions of matrix metallopeptidase 1 and matrix metallopeptidase 2 markedly increased in KFs. Moreover, the expression of α-smooth muscle actin and collagen I decreased. Furthermore, KFs with UVA irradiation secreted more interleukin-6 and interleukin-8 in the culture medium. And it was confirmed that the protein expressions of inflammation-related factors, including P38, CK2A, NFκB1, and P65, increased observably in KFs with UVA irradiation. The protein expression of IKBα, also known as NFκB inhibitor α, decreased. All these observations suggested that UVA irradiation could inhibit cellular activity and collagen production in KFs while promoting inflammation by activating P38-NFκB1 signal pathway.
Morphological and molecular analyses reveal three new endemic species of the freshwater crab genus Buea Cumberlidge, Mvogo Ndongo, Clark & Daniels, 2019 (Crustacea: Brachyura: Potamonautidae) from a rainforest biodiversity hotspot in Cameroon, Central Africa
Authors: Mvogo Ndongo Pierre A , von Rintelen Thomas , Tomedi-Tabi Eyango Minette , Cumberlidge Neil
Published: May 2020

Three new species of the Cameroonian endemic freshwater crab genus Buea  Cumberlidge, Mvogo Ndongo, Clark & Daniels, 2019 are described. The new species were collected from protected areas in the Southwest region of Cameroon, the Korup and Bakossi National Parks and the Mt. Nlonako Ecological Reserve. These species are distinguished from each other and from the type species of the genus, Buea asylos (Cumberlidge, 1993), by a combination of morphological characters (carapace, thoracic sternum, chelipeds, and male first gonopod) and by partial sequences of three mitochondrial DNA genes (COI, 12S rRNA, and 16S rRNA). A phylogenetic analysis that included representatives of all other freshwater crab genera found in Cameroon recovered each of the new species as a well-supported distinct lineage. An identification key is also provided for the four species of Buea and the conservation status of the new species is discussed.
The European System of Human Rights Protection: No Rolls-Royce, but a Solid Engine Fit for the Future? In Conversation with Council of Europe Insiders
Authors: Speck Anne-Katrin
Published: May 2020

The European Convention system has a unique structure among regional human rights regimes. Not only does it have a full-time Court and a Parliamentary Assembly, it is also the only system to have a political body, the Committee of Ministers, tasked with monitoring the implementation of judgments issued by the Court. While the day-to-day work is carried out by the Department for the Execution of Judgments (‘Execution Department’), the ministers’ deputies meet quarterly to examine the implementation (or ‘execution’) of (selected) judgments. How effective has this distinctive institutional arrangement been, and what challenges does it face in an era of increasing hostility to supranational human rights bodies? Anne-Katrin Speck, Research Associate with the Human Rights Law Implementation Project, discussed these questions with Andrew Drzemczewski, former Head of the Legal Affairs and Human Rights Department of the Parliamentary Assembly of the Council of Europe; Christos Giakoumopoulos, Director General of Human Rights and Rule of Law of the Council of Europe; and Michael O’Boyle, former Deputy Registrar of the European Court of Human Rights.
Monitoring, Cajoling and Promoting Dialogue: What Role for Supranational Human Rights Bodies in the Implementation of Individual Decisions?
Authors: Sandoval Clara , Leach Philip , Murray Rachel
Published: May 2020

This article analyses the role of supranational human rights bodies in the implementation of their orders and recommendations in individual cases. It elicits the means, roles and impact of supranational mechanisms in triggering implementation processes by looking at the practice of UN treaty bodies and the three regional systems, through the in-depth study of specific cases and semi-structured interviews with relevant stakeholders. The article argues that supranational bodies are doing more than monitoring implementation of orders and recommendations in individual cases despite the scarcity of resources. They use different tools, both persuasive and coercive. Dialogue is central to their work, a dialogue that at times is opened to other actors such as civil society organizations, national human rights institutions and others. However, supranational bodies could do more to enhance the role they have promoting implementation by states of their orders and recommendations.
The Inter-American Commission on Human Rights and Implementation of Recommendations in Individual Cases
Authors: Abi-Mershed Elizabeth
Published: May 2020

This practice note reflects on the tendencies in implementation that can be identified in relation to recommendations of the Inter-American Commission on Human Rights in individual cases. It discusses some opportunities and challenges using the Commission’s experience with certain cases to illustrate the points.
Until We Find Marco Antonio
Authors: Theissen Lucrecia Molina
Published: May 2020

This practice note reflects on the impact of the Inter-American Court’s judgment in the case of Molina Theissen, the way it impacted domestically in Guatemala, and the way it empowered the victims in the case. It also notes the key role that has been played by victims in the fight for justice and helps in the understanding of how implementation challenges unfold in practice.
The asymmetric relationships of the distribution of conspecific saplings and adults in forest fragments
Authors: Liu Jinliang , Zhong Yuchen , Zhong Lei , Wei Boliang , Zheng Shilu , Xie Yuchu , Jin Yi , Yu Mingjian
Published: May 2020

Aims

With the increase of land-use change, habitat fragmentation has become a major factor affecting plant diversity. Generally, when the adult density is high, the survival rate of conspecific saplings may decline and provide more resources and space for other species to maintain a high local species diversity. Therefore, the spatial relationship of conspecific saplings and adults (SRCSA) can regulate plant diversity. However, very few studies have assessed SRCSA within fragmented forests, and we still largely unknown the relationship between SRCSA and species diversity in fragmented landscapes.

Methods

We calculated the mean strength of SRCSA using the spatial distribution data of saplings and adults with a log-transformed hierarchical offset-power model on 27 islands in a land-bridge island system. The higher strength of SRCSA reflects a more negative relationship between the density of conspecific saplings and adults on an island (i.e. the looser pattern of SRCSA). We tested the relationships among island attributes (i.e. island area, the distance to the mainland—MD, and the distance to the nearest island—ND), SRCSA and species diversity.

Important Findings

The strength of SRCSA increased with ND. Meanwhile, the species diversity significantly increased with the strength of SRCSA, and island area and the strength of SRCSA independently explained 26% and 6% of variation of species diversity, respectively, and their interactions explained 8%. Shade-intolerant and low-abundant species showed looser patterns of SRCSA. Our study suggests that SRCSA may have the effect of excluding species with a relatively low abundance in isolated island forests, which illustrates the importance of biotic interactions in maintaining plant diversity in fragmented forests. Our results also emphasize that we should consider forest connectivity when testing the conspecific negative density dependence.
The β-ketoacyl-CoA synthase KCS13 regulates the cold response in cotton by modulating lipid and oxylipin biosynthesis
Authors: Wang Qiongshan , Du Xueqiong , Zhou Ying , Xie Lijuan , Bie Shu , Tu Lili , Zhang Na , Yang Xiyan , Xiao Shi , Zhang Xianlong
Published: May 2020

Cold stress is a key environmental factor that affects plant development and productivity. In this study, RNA-seq in cotton following cold-stress treatment resulted in the identification of 5239 differentially expressed genes (DEGs) between two cultivars with differing sensitivity to low temperatures, among which GhKCS13 was found to be involved in the response. Transgenic plants overexpressing GhKCS13 showed increased sensitivity to cold stress. KEGG analysis of 418 DEGs in both GhKCS13-overexpressing and RNAi lines after treatment at 4 °C indicated that lipid biosynthesis and linoleic acid metabolism were related to cold stress. ESI-MS/MS analysis showed that overexpression of GhKCS13 led to modifications in the composition of sphingolipids and glycerolipids in the leaves, which might alter the fluidity of the cell membrane under cold conditions. In particular, differences in levels of jasmonic acid (JA) in GhKCS13 transgenic lines suggested that, together with lysophospholipids, it might mediate the cold-stress response. Our results suggest that overexpression of GhKCS13 probably causes remodeling of lipids in the endoplasmic reticulum and biosynthesis of lipid-derived JA in chloroplasts, which might account for the increased sensitivity to cold stress in the transgenic plants. Complex interactions between lipid components, lipid signaling molecules, and JA appear to determine the response to cold stress in cotton.
Structure and instability of the ionization fronts around moving black holes
Authors: Sugimura Kazuyuki , Ricotti Massimo
Published: May 2020

In this paper, we focus on understanding the physical processes that lead to stable or unstable ionization fronts (I-fronts) observed in simulations of moving black holes (BHs). The front instability may trigger bursts of gas accretion, rendering the BH significantly more luminous than at steady state. We perform a series of idealized three-dimensional radiation hydrodynamics simulations resolving the I-fronts around BHs of mass MBH and velocity $v$∞ accreting from a medium of density nH. The I-front, with radius RI, transitions from D-type to R-type as the BH velocity becomes larger than a critical value $v_\mathrm{R}\sim 40\, \mathrm{km\,s}^{-1}$. The D-type front is preceded by a bow-shock of thickness ΔRI that decreases as $v$∞ approaches $v$R. We find that both D-type and R-type fronts can be unstable given the following two conditions: (i) for D-type fronts the shell thickness must be ΔRI/RI < 0.05 (i.e. $v_\infty \gtrsim 20\, \mathrm{km\,s}^{ -1}$), while no similar restriction holds for R-type fronts; (ii) the temperature jump across the I-front must be TII/TI > 3. This second condition is satisfied if $T_\mathrm{I}\lt 5000\, \mathrm{K}$ or if $n_\mathrm{H}\, M_\mathrm{BH} \gtrsim 10^6\, M_\odot \, \mathrm{cm^{-3}}$. Due to X-ray pre-heating typically $T_\mathrm{I} \sim 10^4\, \mathrm{K}$, unless the D-type shell is optically thick to X-rays, which also happens when $n_\mathrm{H}\, M_\mathrm{BH}$ is greater than a metallicity-dependent critical value. We thus conclude that I-fronts around BHs are unstable only for relatively massive BHs moving trough very dense molecular clouds. We briefly discuss the observational consequences of the X-ray luminosity bursts likely associated with this instability.
Measuring the mass of the supermassive black hole of the lenticular galaxy NGC 4546
Authors: Ricci T V , Steiner J E
Published: May 2020

Most galaxies with a well-structured bulge host a supermassive black hole (SMBH) in their centre. Stellar kinematics models applied to adaptive optics (AO) assisted integral field unit observations are well-suited to measure the SMBH mass (MBH) and also the total mass-to-light ratio [(M/L)TOT] and possible anisotropies in the stellar velocity distribution in the central region of galaxies. In this work, we used new AO assisted Near-Infrared Integral Field Spectrometer (NIFS) observations and also photometric data from the Hubble Space Telescope Legacy Archive of the galaxy NGC 4546 in order to determine its SMBH mass. To do this, we applied the Jeans Anisotropic Modelling (JAM) method to fit the average second velocity moment in the line of sight $(\overline{v^2_{\mathrm{ los}}})$ of the stellar structure. In addition, we also obtained (M/L)TOT and the classical anisotropy parameter βz = 1-(σz/σR)2 for this object within a field of view of 200 × 200 pc2. Maps of the stellar radial velocity and of the velocity dispersion were built for this galaxy using the penalized pixel fitting (ppxf) technique. We applied the Multi Gaussian Expansion procedure to fit the stellar brightness distribution. Using JAM, the best-fitting model for $\overline{v^2_{\mathrm{ los}}}$ of the stellar structure was obtained with (M/L)TOT = 4.34 ± 0.07 (Johnson’s R band), MBH = (2.56 ± 0.16) × 108 M⊙ and βz = −0.015 ± 0.03 (3σ confidence level). With these results, we found that NGC 4546 follows the MBH × σ relation. We also measured the central velocity dispersion within a radius of 1 arcsec of this object as σc = 241 ± 2 km s−1.
The velocity structure of Cygnus OB2
Authors: Arnold Becky , Goodwin Simon P , Wright Nicholas J
Published: May 2020

The kinematic structure of the Cygnus OB2 association is investigated. No evidence of expansion or contraction is found at any scale within the region. Stars that are within ∼0.5 pc of one another are found to have more similar velocities than would be expected by random chance, and so it is concluded that velocity substructure exists on these scales. At larger scales velocity substructure is not found. We suggest that bound substructures exist on scales of ∼0.5 pc, despite the region as a whole being unbound. We further suggest that any velocity substructure that existed on scales > 0.5  pc has been erased. The results of this study are then compared to those of other kinematic studies of Cygnus OB2.
Sub-Neptune formation: the view from resonant planets
Authors: Choksi Nick , Chiang Eugene
Published: May 2020

The orbital period ratios of neighbouring sub-Neptunes are distributed asymmetrically near first-order resonances. There are deficits of systems – ‘troughs’ in the period ratio histogram – just short of commensurability, and excesses – ‘peaks’ – just wide of it. We reproduce quantitatively the strongest peak-trough asymmetries, near the 3:2 and 2:1 resonances, using dissipative interactions between planets and their natal discs. Disc eccentricity damping captures bodies into resonance and clears the trough, and when combined with disc-driven convergent migration, draws planets initially wide of commensurability into the peak. The migration implied by the magnitude of the peak is modest; reductions in orbital period are ∼10 per cent, supporting the view that sub-Neptunes complete their formation more-or-less in situ. Once captured into resonance, sub-Neptunes of typical mass $\sim \,$5–15M⊕ stay captured (contrary to an earlier claim), as they are immune to the overstability that afflicts lower mass planets. Driving the limited, short-scale migration is a gas disc depleted in mass relative to a solar-composition disc by three to five orders of magnitude. Such gas-poor but not gas-empty environments are quantitatively consistent with sub-Neptune core formation by giant impacts (and not, e.g. pebble accretion). While disc-planet interactions at the close of the planet formation era adequately explain the 3:2 and 2:1 asymmetries at periods $\gtrsim \, $5–15 d, subsequent modification by stellar tides appears necessary at shorter periods, particularly for the 2:1.
Crystal structure and interactions of the Tof1–Csm3 (Timeless–Tipin) fork protection complex
Authors: Grabarczyk Daniel B
Published: May 2020

The Tof1–Csm3 fork protection complex has a central role in the replisome—it promotes the progression of DNA replication forks and protects them when they stall, while also enabling cohesion establishment and checkpoint responses. Here, I present the crystal structure of the Tof1–Csm3 complex from Chaetomium thermophilum at 3.1 Å resolution. The structure reveals that both proteins together form an extended alpha helical repeat structure, which suggests a mechanical or scaffolding role for the complex. Expanding on this idea, I characterize a DNA interacting region and a cancer-associated Mrc1 binding site. This study provides the molecular basis for understanding the functions of the Tof1–Csm3 complex, its human orthologue the Timeless–Tipin complex and additionally the Drosophila circadian rhythm protein Timeless.
Neuro-Oncology Practice Clinical Debate: long-term antiepileptic drug prophylaxis in patients with glioma
Authors: Stocksdale Brian , Nagpal Seema , Hixson John D , Johnson Derek R , Rai Prashant , Shivaprasad Akhil , Tremont-Lukats Ivo W
Published: May 2020

Patients with primary brain tumors often experience seizures, which can be the presenting symptom or occur for the first time at any point along the illness trajectory. In addition to causing morbidity, seizures negatively affect independence and quality of life in other ways, for example, by leading to loss of driving privileges. Long-term therapy with antiepileptic drugs (AEDs) is the standard of care in brain tumor patients with seizures, but the role of prophylactic AEDs in seizure-naive patients remains controversial. In this article, experts in the field discuss the issues of AED efficacy and toxicity, and explain their differing recommendations for routine use of prophylactic AEDs.
Microbial Etiology of Pyogenic Vertebral Osteomyelitis According to Patient Characteristics
Authors: Kim Dong Youn , Kim Uh Jin , Yu Yohan , Kim Seong-Eun , Kang Seung-Ji , Jun Kang-Il , Kang Chang Kyung , Song Kyoung-Ho , Choe Pyoeng Gyun , Kim Eu Suk , Kim Hong Bin , Jang Hee-Chang , Jung Sook In , Oh Myoung-don , Park Kyung-Hwa , Kim Nam Joong
Published: May 2020

Background

It is difficult to select an appropriate empirical antibiotic treatment regimen for patients with culture-negative pyogenic vertebral osteomyelitis (PVO). Having knowledge of the distribution of microorganisms according to patient characteristics can help clinicians make informed choices regarding empirical antibiotics. The aim of this study was to determine the microbial distribution among individuals with PVO according to their demographic and clinical characteristics.

Methods

We reviewed the medical records of patients admitted to our hospital with culture-confirmed PVO between January 2005 and December 2017 and collected data on demographics, underlying diseases, and radiographic and microbiological results. Statistical analysis was performed to identify associations between specific bacteria and specific patient characteristics.

Results

A total of 586 patients were included in the study. The prevalence of Staphylococcus aureus infections was higher in young patients than in old patients, while gram-negative bacterial infections and Enterococcus were more prevalent in older patients. Gram-negative bacterial infections were more common in women than in men (32.1% vs 16.4%; P < .05), in patients with cirrhosis than in those without (32.7% vs 21.1%; P < .05), and in patients with a solid tumor than in those without (31.0% vs 20.7%; P < .05). Methicillin-resistant S. aureus infections were more prevalent in patients with chronic renal disease than in those without (34.4% vs 14.7%; P < .05).

Conclusions

The microbial etiology of PVO varies according to patient characteristics. Patient characteristics should thus be considered when choosing empirical antibiotics in patients with culture-negative PVO.
The Origin of Plagiogranites: Coupled SIMS O Isotope Ratios, U–Pb Dating and Trace Element Composition of Zircon from the Troodos Ophiolite, Cyprus
Authors: Morag Navot , Golan Tzahi , Katzir Yaron , Coble Matthew A , Kitajima Kouki , Valley John W
Published: May 2020

U–Pb ages, trace element content and oxygen isotope ratios of single zircons from five plagiogranite intrusions of the Troodos ophiolite were measured to determine their crystallization age and assess the importance of fractional crystallization versus crustal anatexis in their petrogenesis. The results indicate that oceanic magmatism in Troodos took place at 94·3 ± 0·5 Ma, about 3 Myr earlier than previously recognized. Later hydrothermal alteration has affected most of the Troodos plagiogranitic rocks, resulting in growth of new zircon and/or partial alteration of zircon domains, causing slightly younger apparent crystallization ages. The new age inferred for seafloor spreading and ocean crust accretion in Troodos nearly overlaps that of the Semail ophiolite in Oman (95–96 Ma), strengthening previous indications for simultaneous evolution of both ophiolites in similar tectonic settings. Average δ18O(Zrn) values in the Troodos plagiogranites range between 4·2 and 4·8 ‰. The lower values in this range are lower than those expected in equilibrium with mantle-derived melt (5·3 ± 0·6 ‰), indicating variable contribution from hydrothermally altered, deep-seated oceanic crust in most of the Troodos plagiogranite intrusions. The inferred substantial involvement of crustal component is consistent with the existence of a shallow axial magma chamber, typical of fast-spreading mid-ocean ridge settings, within the Troodos slow-spreading ridge environment. This apparent contradiction may be reconciled by episodically intense magmatism within an otherwise slow, magmatically deprived spreading axis.
The Handwriting of Fifteenth-Century Privy Seal and Council Clerks
Authors: Sobecki Sebastian
Published: May 2020

Although most scholars of medieval English palaeography are familiar with the hand of the Privy Seal clerk and poet Thomas Hoccleve, almost nothing is known about the handwriting of his fellow clerks. This article is the first attempt to identify and describe the hands of a number of clerks who wrote for the Privy Seal and for the Council in the fifteenth century. In Part 1, I identify the handwriting of Hoccleve’s fellow clerks, including William Alberton, Henry Benet, John Claydon, John Hethe, John Offord, and Richard Priour, adding writs, letters, charters, and manuscripts in their hands. I also identify the hand of the Council clerk Richard Caudray and attribute further records to the Council and Privy Seal clerk Robert Frye. Part 2 offers a reconsideration of the features of Hoccleve’s handwriting in the light of the new findings. This article also identifies the scribal stints and hands in four documents produced by Privy Seal clerks: British Library, MS Add. 24,062 (Hoccleve’s Formulary); BL, MS Cotton Cleopatra F. iii (Part 1 of the Book of the Council); BL, MS Harley 219; and Edinburgh University Library, MS 183 (Privy Seal and Signet formulary, or ‘Royal Letter Book’). This article reveals the extent to which Privy Seal clerks participated in the copying of literature and offers a more nuanced understanding of the varieties of the secretary script used by government scribes.
The program and policy change framework: A new tool to measure research use in low- and middle-income countries
Authors: Fowle Karen , Wells Brent , Day Melissa , Kumar Anjali , Bess Cameron , Bingham Brian , Wayman Annica
Published: May 2020

Organizations that fund research to address global development challenges are increasingly interested in measuring the social and economic outcomes of research. However, traditional metrics for measuring research outputs are often insufficient for capturing the outcomes targeted by international assistance organizations. To address this, the Center for Development Research (CDR), part of the U.S. Global Development Lab at the United States Agency for International Development (USAID), has designed a new tool: the Program and Policy Change (PPC) framework for tracking and quantifying the influence of research on program and policy change in international development. The framework draws on existing conceptual frameworks of evidence uptake and the literature on policy change. This article describes the design of the PPC framework and presents the results of applying the framework to two USAID research programs. The benefits of the framework include applicability across research sectors, focus on evidence-informed policy at various levels of geographical influence, and inclusion of a numeric scoring system that enables quantification of outcomes.
Do Neighborhoods Affect the Credit Market Decisions of Low-Income Borrowers? Evidence from the Moving to Opportunity Experiment
Authors: Miller Sarah , Soo Cindy K
Published: May 2020

This paper isolates the causal impact of neighborhood environment on the credit outcomes of low-income borrowers by analyzing the participants of the Moving to Opportunity (MTO) experiment. MTO was a unique, large-scale experiment that offered families vouchers to move to better neighborhoods via randomized lottery. We find higher credit scores and use among those required to move to the lowest poverty areas as young children. For those who moved as adults, we find that better neighborhoods lead to a reduction of overdue debts and delinquencies, but only among those given unrestricted neighborhood choice.
Molecular mechanisms associated with quinolone resistance in Enterobacteriaceae: review and update
Authors: Azargun Robab , Gholizadeh Pourya , Sadeghi Vahid , Hosainzadegan Hasan , Tarhriz Vahideh , Memar Mohammad Yousef , Pormohammad Ali , Eyvazi Shirin
Published: May 2020

Background

Quinolones are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. During recent decades, the wide use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains. Herein, we present the development of quinolone antibiotics, their function and also the different quinolone resistance mechanisms in Enterobacteriaceae by reviewing recent literature.

Methods

All data were extracted from Google Scholar search engine and PubMed site, using keywords; quinolone resistance, Enterobacteriaceae, plasmid-mediated quinolone resistance, etc.

Results and conclusion

The acquisition of resistance to quinolones is a complex and multifactorial process. The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug-binding affinity of target enzymes. Other mechanisms of quinolone resistance are overexpression of AcrAB-tolC multidrug-resistant efflux pumps and downexpression of porins as well as plasmid-encoded resistance proteins including Qnr protection proteins, aminoglycoside acetyltransferase (AAC(6′)-Ib-cr) and plasmid-encoded active efflux pumps such as OqxAB and QepA. The elucidation of resistance mechanisms will help researchers to explore new drugs against the resistant strains.
Implantation Time Has No Effect on the Morphology and Extent of Previously Reported “Degradation” of Prolene Pelvic Mesh
Authors: Thames Shelby F. , Blanton Michael D. , Williams Eric B. , White Joshua B. , Stoner Kirsten E. , Ong Kevin L.
Published: May 2020

(Abstracted from Female Pelvic Med Reconstr Surg 2020;26:128–136)

The use of polypropylene (PP) mesh products and mesh types decreased complications of surgical repair procedures for pelvic organ prolapse (POP) over the years. However, increasing reports regarding pain and other serious mesh-related long-term adverse effects as well as widespread litigation by thousands of women led the US Food and Drug Administration to announce in April 2019 that manufacturers should discontinue production and distribution of urogynecologic transvaginal POP mesh products.
Maternal Diabetes During Pregnancy and Early Onset of Cardiovascular Disease in Offspring: Population Based Cohort Study With 40 Years of Follow Up
Authors: Yu Yongfu , Arah Onyebuchi A. , Liew Zeyan , Cnattingius Sven , Olsen Jørn , Sørensen Henrik Toft , Qin Guoyou , Li Jiong
Published: May 2020

(Abstracted from BMJ 2019;367:l6398)

The primary cause of worldwide mortality and morbidity is cardiovascular disease (CVD). Recently, increases in CVD have disproportionately affected children and young adults, who have experienced the most drastic upticks in disease incidence.
Perioperative Care of Patients at High Risk for Stroke During or After Non-cardiac, Non-neurological Surgery: 2020 Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care
Authors: Vlisides Phillip E. , Moore Laurel E. , Whalin Matthew K. , Robicsek Steven A. , Gelb Adrian W. , Lele Abhijit V. , Mashour George A.
Published: May 2020

Perioperative stroke is associated with considerable morbidity and mortality. Stroke recognition and diagnosis are challenging perioperatively, and surgical patients receive therapeutic interventions less frequently compared with stroke patients in the outpatient setting. These updated guidelines from the Society for Neuroscience in Anesthesiology and Critical Care provide evidence-based recommendations regarding perioperative care of patients at high risk for stroke. Recommended areas for future investigation are also proposed.
A Systematic Review of Risk Factors for Sleep Disruption in Critically Ill Adults
Authors: Honarmand Kimia , Rafay Hammad , Le Jamie , Mohan Sindu , Rochwerg Bram , Devlin John W. , Skrobik Yoanna , Weinhouse Gerald L. , Drouot Xavier , Watson Paula L. , McKinley Sharon , Bosma Karen J.
Published: May 2020

Objectives:

Numerous risk factors for sleep disruption in critically ill adults have been described. We performed a systematic review of all risk factors associated with sleep disruption in the ICU setting.

Data Sources:

PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central Register for Controlled Trials, and Cochrane Database of Systematic Reviews.

Study Selection:

English-language studies of any design published between 1990 and April 2018 that evaluated sleep in greater than or equal to 10 critically ill adults (> 18 yr old) and investigated greater than or equal to 1 potential risk factor for sleep disruption during ICU stay. We assessed study quality using Newcastle-Ottawa Scale or Cochrane Risk of Bias tool.

Data Extraction:

We abstracted all data independently and in duplicate. Potential ICU sleep disruption risk factors were categorized into three categories based on how data were reported: 1) patient-reported reasons for sleep disruption, 2) patient-reported ratings of potential factors affecting sleep quality, and 3) studies reporting a statistical or temporal association between potential risk factors and disrupted sleep.

Data Synthesis:

Of 5,148 citations, we included 62 studies. Pain, discomfort, anxiety/fear, noise, light, and ICU care-related activities are the most common and widely studied patient-reported factors causing sleep disruption. Patients rated noise and light as the most sleep-disruptive factors. Higher number of comorbidities, poor home sleep quality, home sleep aid use, and delirium were factors associated with sleep disruption identified in available studies.

Conclusions:

This systematic review summarizes all premorbid, illness-related, and ICU-related factors associated with sleep disruption in the ICU. These findings will inform sleep promotion efforts in the ICU and guide further research in this field.
Rise of the Robots
Authors: Watson Daniel , Womack Joshua , Papadakos Suzanne
Published: May 2020

Much like other aspects of health care, nursing has become increasingly saturated with technology over the past several decades. Existing technology has advanced nursing in many ways and contributed to patient safety but at the cost of decreasing nurse-patient interaction. As health care technology progresses to the inclusion of artificial intelligence (AI), the future impact on nursing and direct patient care remains largely unknown, unexplored, and difficult to predict. This article aims to explore the relevance of nursing in a technologically advanced postmodern health care system. The relevance of nursing in the future is solidified by the unique nature of nursing that includes the embodiment of human caring and emotional intelligence. Nurses' abilities to intervene before patient deterioration, care for patients holistically, and manage various aspects of care will be heightened by the adoption of AI. Nurses should embrace AI technology, as we predict that it will decrease nurse workload and cognitive overload and allow for increased patient-nurse interaction. Current and future nurses should take the lead on determining how it augments nursing practice.
A Long-Term Study of Persistent Sézary Syndrome: Evidence for Antigen Shift by Multiparameter Flow Cytometry and Its Significance in Overall Survival
Authors: Hoffmann Jenny C. , Atwater Susan K. , Hong Eric , Kumar Jyoti , Khodadoust Michael , Kim Youn , Ohgami Robert S.
Published: May 2020

Sézary syndrome (SS) is a peripheral T-cell lymphoma characterized by erythroderma, diffuse lymphadenopathy, and circulating neoplastic T cells, which classically show a helper T-cell immunophenotype with loss of CD7 and CD26. Flow cytometry is often used to identify and enumerate populations of Sézary cells in the peripheral blood; however, the significance and frequency of antigen shift over time is unclear. In this article, we follow the immunophenotype of the neoplastic T-cell population from 28 patients with SS across 415 flow cytometry studies. Antigen shift for each patient was assigned as none, minimal = 1–2 markers by 1°, moderate = up to 3 markers, or marked ≥ 4 markers. Sixty-four percent (18/28) of patients showed antigen shift, and among those with antigen shift, the majority showed minimal (8/18) or moderate antigen shift (7/18) with fewer demonstrating marked shift (3/18). Patients without antigen shift showed a trend toward improved overall survival in comparison with patients demonstrating any degree of antigen shift. Antigen shift is seen in a significant proportion of cases of SS with long-term follow-up and may be a marker of more aggressive disease.
Activation of Paraventricular Melatonin Receptor 2 Mediates Melatonin-Conferred Cardioprotection Against Myocardial Ischemia/Reperfusion Injury
Authors: Zhang Chao , Yang Jin-Bao , Quan Wei , Feng Ying-Da , Feng Jian-Yu , Cheng Liu-Siyuan , Li Xiao-Qiang , Zhang Hui-Nan , Chen Wen-Sheng
Published: May 2020

Previous studies have shown that melatonin (Mel) can effectively ameliorate myocardial ischemia/reperfusion (MI/R) injury, but the mechanism is yet to be fully elucidated. Mel receptors are expressed in the paraventricular nucleus (PVN), which is also involved in regulating cardiac sympathetic nerve activity. The aim of this study was to examine whether Mel receptors in the PVN are involved in the protective effects of Mel against MI/R injury. The results of quantitative polymerase chain reaction, western blot, and immunofluorescence assays indicated that Mel receptor 2 (MT2) expression in the PVN was upregulated after MI/R. Intraperitoneal administration of Mel significantly improved post-MI/R cardiac function and reduced the infarct size, whereas shRNA silencing of MT2 in the PVN partially blocked this effect. Intraperitoneal administration of Mel reduced sympathetic nerve overexcitation caused by MI/R, whereas shRNA silencing of MT2 in the PVN partially diminished this effect. Furthermore, enzyme-linked immunosorbent assay and western blot results indicated that intraperitoneal administration of Mel lowered the levels of inflammatory cytokines in the PVN after MI/R injury, whereas the application of sh-MT2 in the PVN reduced this effect of Mel. Mel significantly reduced the levels of NF-κB after astrocyte oxygen and glucose deprivation/reoxygenation injury, and this effect was offset when MT2 was silenced. The above experimental results suggest that MT2 in the PVN partially mediated the protective effects of Mel against MI/R injury, and its underlying mechanisms may be related to postactivation amelioration of PVN inflammation and reduction of cardiac sympathetic nerve overexcitation.
HLA-B*58:01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia
Authors: Low Dyoi E , Nurul-Aain Ahmad Fauzi , Tan Wooi Chiang , Tang Jyh Jong , Bakhtiar Mohammed Faizal , Murad Shahnaz , Chang Choong Chor , Too Chun Lai , Tang Min Moon
Published: May 2020

Objective

The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined.

Methods

We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).

Results

HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6–164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9–470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5–169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3–1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8–619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6–442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.

Conclusion

Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN
Cost-effectiveness analysis of pretreatment screening for NUDT15 defective alleles
Authors: Zarca Kevin , Chansavang Albain , Loriot Marie-Anne , Durand-Zaleski Isabelle , Pallet Nicolas
Published: May 2020

Background

Nucleotide triphosphate diphosphatase (NUDT15) genetic testing in addition to thiopurine methyl transferase (TPMT) is recommended to reduce the incidence of adverse severe myelotoxicity episodes induced by thiopurines.

Objective

We assessed the cost-effectiveness ratio of combined screening for TMPT and NUDT15 defective alleles by genotyping or next-generation sequencing (NGS) using TPMT genotyping as the reference. Because of the genetic differences in thiopurine toxicity, we tested the screening strategies on individuals of Caucasian and Asian descent.

Methods

A decision tree compared conventional TPMT genotyping with combined TPMT/NUDT15 genotyping or NGS using a Monte-Carlo microsimulation model of patients with inflammatory bowel disease. The main outcome was the incremental cost-effectiveness ratios (ICER) with effectiveness being one averted severe myelotoxicity requiring hospitalization.

Results

The mean estimated cost of the TPMT genotyping for one year is twice in Asian compared with Caucasian patients (980 euro/patient versus 488 euro/patient), and the effectiveness of TPMT genotyping in Caucasian avoided 43 severe myelosuppressions per 10 000 patients over a year compared with 3.6 per 10 000 patients in Asian. Combined TPMT/NUDT15 genotyping compared with TPMT genotyping had an ICER of 7 491 281 euro per severe myelotoxicity averted in Caucasian, compared to 619 euro in Asian. The ICER of the NGS-based screening strategy is disproportionally high compared with genotyping, irrespective of ethnic descent.

Conclusion

With a low cost-effectiveness threshold, combined screening for NUDT15 and TPMT defective alleles is cost-effective compared to TMPT screening alone in patients of Asian descent, but is unrealistic from a cost-effectiveness point of view in Caucasians.
Acute gastroinstinal bleeding: a review
Authors: Weledji Elroy P.
Published: May 2020

Blood loss from the gut may be acute requiring emergency resuscitation, investigation, and management, or chronic and occult resulting in anemia. The upper gastrointestinal (GI) tract is more commonly a source of hemorrhage than the lower GI tract. Endoscopy is the mainstay of investigation and management. New endoscopic techniques and radiologic embolization have decreased the role of surgery in management, but collaboration between the endoscopist and the surgeon remains. In this review the management of acute blood loss in the GI tract is discussed. The importance of resuscitation, clinically diagnosing, and treating the underlying problem is emphasized.
ASSOCIATION OF SERUM VASOGENIC AND PROINFLAMMATORY FACTORS WITH CLINICAL RESPONSE TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR FOR DIABETIC MACULAR EDEMA
Authors: Brito Pedro S. , Costa Jorge V. , Barbosa-Matos Catarina , Costa Sandra M. , Correia-Pinto Jorge , Silva Rufino M.
Published: May 2020

Purpose:

To study the role of serum biomarkers as prognostic factors for qualitative and quantitative response to anti–vascular endothelial growth factor injections for diabetic macular edema (DME).

Methods:

Sixty-seven eyes with DME were treated with intravitreal bevacizumab during a 12-month follow-up period. All cases underwent a baseline workup consisting of 12 inflammatory, metabolic and prothrombotic factors. The following outcomes were evaluated at 3-month intervals until 1 year of follow-up: visual acuity, central subfield thickness (CST), macular volume (MV), % of change from baseline in CST, occurrence of a CST change < 10%, a CST change >20%, and a CST <330 µm, achieving an improvement ≥2 lines of visual acuity, achieving visual acuity ≥20/40.

Results:

A significant improvement in CST and visual acuity was seen from third month onwards. Twenty-eight (48.1%) cases were classified as “early responders,” 24 (35.8%) as “late responders”, and 15 (22.4%) as “poor responders.” Serum vascular endothelial growth factor–A levels were significantly lower in “poor responders” (P = 0.006). C-reactive protein (hsCRP) was associated with a limited anatomic response (<10% CST change) (P = 0.002, OR = 1.845, cutoff value of hsCRP = 1.84 mg/L). hsCRP was also negatively associated with obtaining a final CST <330 µm (P = 0.04, r2 = 0.112, OR = 0.643). Baseline visual acuity was significantly associated with 12th month visual acuity (P < 0.001, r2 = 0.602) and also with an improvement ≥2 visual acuity lines (P = 0.009, OR = 20.54).

Conclusion:

Increased high-sensitivity C-reactive protein was associated with limited anatomic response to anti–vascular endothelial growth factor treatment and persistent DME. Poor responders had significantly lower values of serum vascular endothelial growth factor–A, suggesting an alternative pathogenic pathway for persisting DME.
A Prospective Analysis of iStent Inject Microstent Implantation: Surgical Outcomes, Endothelial Cell Density, and Device Position at 12 Months
Authors: Gillmann Kevin , Mansouri Kaweh , Ambresin Aude , Bravetti Giorgio E. , Mermoud André
Published: May 2020

Precis:

The surgical outcome of iStent inject devices is associated with device protrusion within the anterior chamber. Schlemm canal (SC) dilatation has a prognostic value. iStent inject devices do not move within the first year after implantation.

Introduction:

The iStent inject is a device designed to be implanted ab-interno through the trabecular meshwork. The present study follows up on our preliminary report, using successive in vivo anterior segment optical coherence tomography (AS-OCT) imaging to analyze the associations between stent positioning, iridocorneal angle structures, and surgical outcomes.

Methods:

In total, 54 eyes of 42 patients (73.3±7.4 y) with cataract and mild-to-moderate open-angle glaucoma were examined in this prospective study. All patients underwent implantation of 2 iStent inject devices combined with phacoemulsification. Patients were followed up over a 12-month period. AS-OCT was performed after 3 and 12 months. Thirty unoperated fellow eyes served as control eyes.

Results:

Intraocular pressure (IOP) decreased from 16.5±4.2 mm Hg at baseline to 15.1±3.7 mm Hg at 12 months (−8.7%; P=0.004), while medications decreased from 1.8±1.0 to 0.5±0.9 (−72.2%; P<0.001). Unmedicated IOP≤18 mm Hg was achieved in 58.8% of operated eyes. No sight-threatening complications were reported. On AS-OCT, 44.9% of devices were buried within the trabeculum. Device position was unchanged between scans. Regression analysis elicited significant predictors: SC dilatation effect [risk ratio (RR)=0.230; P=0.003], greatest SC diameter (RR=0.991; P=0.049), extrusion of the most anterior device (RR=0.993; P=0.012), gonioscopically visible devices (RR=0.406; P=0.040), baseline treatments (RR=2.214; P=0.001), and baseline IOP (RR=0.184; P=0.006). Endothelial cell density decreased by 14.6% at 12 months (P<0.001).

Conclusions:

This study demonstrates the IOP-lowering and medication-lowering potential of iStent inject surgery in primary open-angle and pseudoexfoliative glaucoma. It confirms that surgical outcomes are positively associated with device protrusion within the anterior chamber, and suggests SC dilatation effect as a favorable prognostic indicator. It shows that stents are stable in time, highlighting the importance of the initial implantation location.
Endogenous Vancomycin-Resistant Enterococcus gallinarum Endophthalmitis in Hematologic Malignancy
Authors: Shahin Alexander V. , Elkhayat Adam I. , Greene John N.
Published: May 2020

Patients with hematologic malignancy are immunocompromised either due to the underlying disease or from chemotherapy, resulting in an increased risk for opportunistic infections. Neutropenic patients with vancomycin-resistant Enterococci colonization are at risk of bacteremia with rare endogenous dissemination, which can result in hematogenous spread to the eye. We describe a patient with a hematologic malignancy with treatment-related neutropenia who developed endogenous vancomycin-resistant Enterococcus gallinarum endophthalmitis along with a review of the literature related to this case.