bluuebunny/crossref_metadata_2025 huggingface dataset:
Observed and projected trends of extreme precipitation and maximum temperature during 1992–2100 in Isfahan province, Iran using REMO model and copula theory
Authors: Mirakbari Maryam , Mesbahzadeh Tayyebeh , Soleimani Sardoo Farshad , Miglietta Mario M. , Krakauer Nir Y. , Alipour Nahid
Published: February 2020

Meteorological extreme events have a major impact on water resources, economic development, and ecosystem health. In this study, maximum precipitation and maximum temperature indices were derived for Isfahan province, in central Iran, over the historical (1992–2017) and future (2020–2100) periods. Precipitation and maximum temperature data from the REMO model under RCP4.5 scenario were used to investigate changes in extreme values over the future period. The results showed that extreme precipitation in the historical and future periods has respectively a decreasing and increasing trend. Based on the extreme indices, temperature in the study area has a significant increasing trend in the baseline and future period. Various combinations of extreme precipitation indicators were created for joint modeling by copula theory. Copula modeling for the three weather stations for which REMO had satisfactory performance in simulating extremes over the historic period showed that the average return period of extreme precipitation combinations will be reduced in the future period compared to the historical period at Daran and Shahreza, while the average return period of combinations will have both increasing and decreasing trends at Naeen.

Recommendations for Resource Managers

Knowing information about the probability of occurrence of extreme precipitation with a certain value that exceeds a certain threshold will help planning for water resource systems under drought conditions and future increasing temperature.

The joint return period of extreme precipitation can help to know the return period of extreme events such as floods and droughts.

The findings of this study are important to assess the prediction of climate extreme. Also, these results can be useful to provide the appropriate strategies for water resources managers in drought conditions under future increasing temperature.
Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts
Authors: Zhao Zhen‐qun , Liu Wan‐lin , Guo Shi‐bing , Bai Rui , Yan Jing‐long
Published: February 2020

Objective

To study the role of primary cilia formation disorder and osteoblasts autophagy in the pathogenesis of steroid‐induced avascular necrosis of the femoral head (SANFH).

Methods

Osteoblasts were isolated from rabbit bones and treated with 1 μM Methylprednisolone for 0, 12, 24, 48, and 72 h. The Beclin1, MAP1LC3, Atg‐5, Atg‐12, IFT20 and OFD1 mRNAs and proteins were detected by PCR and Western blotting, and their correlation was statistically analyzed. The lengths of osteoblast cilia were measured under a laser confocal microscope, and the autophagy flux was tracked by transfecting the osteoblasts with GFP‐RFP‐LC3 lentivirus.

Results

Methylprednisolone significantly upregulated Beclin1, MAP1LC3, Atg‐5, Atg‐12 and OFD1 mRNAs and proteins in a time‐dependent manner, and decreased that of IFT20 (P < 0.05). In addition, the autophagy flux in the osteoblasts also increased and the ciliary length decreased in a time‐dependent manner after Methylprednisolone treatment. The length of the cilia were 5.46 ± 0.11 um at 0 h, 4.08 ± 0.09 um at 12 h, 3.07 ± 0.07 um at 24 h, 2.31 ± 0.10 um at 48 h, and finally 1.15 ± 0.04 um at 72 h. Methylprednisolone treatment also affects primary cilium numbers in cultures, for 0 to 72 h. The autophagy regulatory genes, Beclin1, MAP1LC3, Atg‐5 and Atg‐12, were found to be negatively correlated with IFT20, with an average correlation coefficient of −0.81. A negative correlation was also found between OFD1 and IFT20, with an average correlation coefficient of −0.53.

Conclusion

Methylprednisolone inhibits primary cilia formation and promotes autophagy, which could be the pathological basis of SANFH. The exact regulatory mechanism needs to be further studied in vivo.
Moving towards a better understanding of iterative evolution: an example from the late Silurian Monograptidae (Graptolithina) of the Baltic Basin
Authors: Whittingham Misha , Radzevičius Sigitas , Spiridonov Andrej
Published: February 2020

Iterative evolution has proved a difficult evolutionary phenomenon to study and interpret. Inferences of causality vary from study to study and quantitatively based phylogenetic reconstruction has never been attempted. In an effort to better understand iterative evolution we employed stratocladistics, gap analysis and disparity analysis to study the case of the Monograptidae in the aftermath of the late SilurianCyrtograptus lundgreniextinction event. Our combination of gap analytical and stratocladistic techniques allowed us to elucidate the evolutionary relationships between the studied taxa. Based on our stratocladistic results we recommend the generic reassignment of five monograptid taxa. The stratocladistic results, in conjunction with morphological disparity analysis suggest the presence of a persistent developmental potential for the emergence of iteratively evolving characters. This persistent potential appears to be limited by extrinsic ecological constraints, which would have relaxed in the aftermath of theC. lundgreniextinction event. Our findings indicate that iterative evolution in the late Silurian Monograptidae is a product of the interaction of both intrinsic and extrinsic constraints on the acquisition of the iteratively evolving character, with the exact causality being dependent on the particular character.
A Novel Combination Technique: Three Points of Epiduroscopic Laser Neural Decompression and Percutaneous Laser Disc Decompression With the Ho:YAG Laser in an MSU Classification 3AB Herniated Disc
Authors: Beyaz Serbülent Gökhan , Ülgen Ali Metin , Kaya Burak , İnanmaz Mustafa Erkan , Ergönenç Tolga , Eman Ali , Doğan Burcu
Published: February 2020

Aim

The aim of this study was to examine the effects of simultaneous epiduroscopic laser neural disc decompression (ELND) and percutaneous laser disc decompression (PLDD) applications using a holmium:yttrium‐aluminum‐garnet (Ho:YAG) laser in Michigan State University (MSU) classification 3AB herniated discs on VAS and Oswestry Disability Index (ODI) scores.

Methods

In this prospective observational study, ELND and PLDD procedures performed between January 2016 and December 2017 were examined. Preoperative, postoperative week 2, postoperative month 2, and postoperative month 6 ODI and VAS scores were obtained from patient files, and postoperative month 12 ODI and VAS scores were obtained from face‐to‐face interviews with patients and recorded.

Results

The data of 41 patients treated with simultaneous ELND and PLDD using a Ho:YAG laser were included in this study. Postoperative VAS scores of the patients were compared with preoperative values, and it was found that postoperative week 2, postoperative month 2, postoperative month 6, and postoperative month 12 VAS and ODI scores were significantly different compared to preoperative scores (P = 0.001;P < 0.01). 17.1% (n = 7) of the patients had a history of postoperative open surgery. Although dural puncture occurred in 7 patients (17%), only 1 patient had headache.

Conclusion

We believe that the new combined technique of ELND and PLDD using a Ho:YAG laser is a reliable method in patients with MSU classification 3AB herniated discs, with an acceptable success rate and a low complication rate within 12 months after treatment. We think that randomized controlled studies are required for this method to be included in treatment algorithms.
Generation and analysis of novel Reln‐deleted mouse model corresponding to exonic Reln deletion in schizophrenia
Authors: Sawahata Masahito , Mori Daisuke , Arioka Yuko , Kubo Hisako , Kushima Itaru , Kitagawa Kanako , Sobue Akira , Shishido Emiko , Sekiguchi Mariko , Kodama Akiko , Ikeda Ryosuke , Aleksic Branko , Kimura Hiroki , Ishizuka Kanako , Nagai Taku , Kaibuchi Kozo , Nabeshima Toshitaka , Yamada Kiyofumi , Ozaki Norio
Published: February 2020

Aim

A Japanese individual with schizophrenia harboring a novel exonic deletion in RELN was recently identified by genome‐wide copy‐number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether Reln deficiency is associated with the pathogenesis of schizophrenia.

Methods

A mouse line with a novel RELN exonic deletion (Reln‐del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed.

Results

The phenotype of homozygous Reln‐del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln‐del mice was approximately half of that in wild‐type mice. Conversely, behavioral analyses in heterozygous Reln‐del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three‐chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln‐del mice.

Conclusion

The present results in novel Reln‐del mice modeled after our patient with a novel exonic deletion in RELN are expected to contribute to the development of reelin‐based therapies for schizophrenia.
The science behind wet wipes for infant skin: Ingredient review, safety, and efficacy
Authors: Rodriguez Karien J. , Cunningham Corey , Foxenberg Robert , Hoffman Douglas , Vongsa Rebecca
Published: February 2020

In the diapered area, the continuous exposure to excess moisture and irritants from urine and feces weakens the stratum corneum, making the skin more susceptible to irritation. The use of wet wipes for infants (baby wipes) is a common practice to clean skin after urine or a bowel movement, and this practice even extends to cleaning the hands and face, resulting in repeated daily use. Therefore, ensuring that baby wipes contain ingredients that are safe and mild on skin is important to help minimize skin irritation and discomfort. While disposable baby wipes have been shown to be effective and gentle at cleaning infant skin, even the skin of premature infants, there is growing public concern regarding their safety and tolerability. Not all products are made the same, as differences exist in manufacturing processes, ingredients, materials, safety, and quality testing. Therefore, it is important that healthcare professionals have accessible evidenced‐based information on the safety and tolerability of common ingredients found in baby wipes to optimally educate their patients and families. Herein, we provide a review on best practices for ingredient selection, safety, and efficacy of baby wipes.
Relationship among independence of daily living, human relationships, and preparation for bereavement among healthy elderly Japanese people
Authors: Fukutake Mayumi , Shimamura Misako , Namba Mineko , Ogino Tetsuya
Published: February 2020

Background

Given Japan's rapidly ageing society, an increasing number of elderly people live in their communities with mutual support after the death of their spouse. The purpose of this study is to clarify the relationship among independence of daily living, human relationships, and preparation for bereavement.

Methods

An anonymous, self‐administered questionnaire was given to 864 community‐dwelling elderly people aged 65 and older who attended an Elderly Citizens' Welfare Study Group. A total of 404 responses (effective response ratio: 46.8%) were analyzed. Their mean ± SD age was 75.6 ± 5.1 years. The purpose of the questionnaire was to obtain demographic information as well as information about three scales: independence of daily living, human relationships, and preparation for bereavement. The factor structure of the scales was studied by using exploratory and confirmatory factor analysis. Structural equation modelling was used to investigate the relationship among independence of daily living, human relationships, and preparation for bereavement. This study's protocol was approved by the Ethics Committee of Okayama Prefectural University.

Results

Factor analysis indicated a three‐factor second‐order factor model for independence of daily living and human relationships and a one‐factor model for preparation for bereavement. Structural equation modelling showed that independence of daily living was significantly correlated with human relationships (r = 0.261, P < 0.001), and human relationships was significantly correlated with preparation for bereavement (r = 0.295, P < 0.001). There was no significant direct correlation between the independence of daily living and preparation for bereavement.

Conclusions

Encouraging elderly people to form good human relationships may help their preparation for bereavement. Further studies are required to determine whether this actually attenuates difficulties after bereavement.
Reference values for high attenuation areas on chest CT in a healthy, never‐smoker, multi‐ethnic sample: The MESA study
Authors: Easthausen Imaani , Podolanczuk Anna , Hoffman Eric , Kawut Steven , Oelsner Elizabeth , Kim John S. , Raghu Ganesh , Stukovsky Karen Hinckley , Redline Susan , McClelland Robyn L. , Barr R Graham , Lederer David J.
Published: February 2020

Background and objective

Normative values for HAA—a quantitative, CT‐based measure of subclinical ILD—in healthy adults are needed to improve interpretability in clinical and research settings.

Methods

HAA was measured on full‐lung CT in 3110 participants in the MESA study. Clinical prediction models were developed using a healthy never‐smoker subset with normal spirometry (n = 696). RMSE on cross‐validation was used as the primary criterion for model selection. Parametric and non‐parametric methods were considered. z‐Scores were calculated for the entire study sample. Associations between z‐scores and several ILD features were estimated.

Results

In the healthy never‐smoker subset, the mean age was 69 years with a range of 54–93 years. The median HAA was 4.3% with a range of 2.7–17.8%. Linear regression had better predictive performance than other methods. The final model included race, height, weight, age and sex. The standard error of the estimate was 1.62 with a cross‐validated RMSE of 1.64 and an adjusted R2 of 0.139. z‐Scores were associated with several ILD outcomes in adjusted models, including ILA (OR: 1.40 per z‐unit; 95% CI: 1.30, 1.52), exertional dyspnoea (OR: 1.08 per z‐unit; 95% CI: 1.02, 1.15) and FVC (expected increase per z‐unit: −2.49; 95% CI: −2.95, − 2.03).

Conclusion

We present a reference equation and z‐scores to define expected values of HAA on full‐lung CT to aid HAA interpretation in middle‐aged and older adults.
Barotropic instability of shear flows
Authors: Lin Zhiwu , Yang Jincheng , Zhu Hao
Published: February 2020

We consider barotropic instability of shear flows for incompressible fluids with Coriolis effects. For a class of shear flows, we develop a new method to find the sharp stability conditions. We study the flow with Sinus profile in details and obtain the sharp stability boundary in the whole parameter space, which corrects previous results in the fluid literature. Our new results are confirmed by more accurate numerical computation. The addition of the Coriolis force is found to bring fundamental changes to the stability of shear flows. Moreover, we study dynamical behaviors near the shear flows, including the bifurcation of nontrivial traveling wave solutions and the linear inviscid damping. The first ingredient of our proof is a careful classification of the neutral modes. The second one is to write the linearized fluid equation in a Hamiltonian form and then use an instability index theory for general Hamiltonian partial differential equations. The last one is to study the singular and nonresonant neutral modes using Sturm‐Liouville theory and hypergeometric functions.
Predicting 2‐year weight loss through temporally specific earlier losses, relevant behaviors, and their psychological correlates: Implications for behavioral treatment architectures
Authors: Annesi James J.
Published: February 2020

Maintaining loss of weight beyond an initial 6–9 months remains problematic, with research indicating little recent progress. A poor understanding of how and when prior weight loss, behavioral changes, and psychosocial predictors are associated with long‐term weight changes persists. To better‐inform behavioral treatments for long‐term success with weight loss, women with obesity (N = 86; Mage = 48.6 years) volunteered for research incorporating community‐based weight‐management treatments. They were assessed at months 6, 12, and 24 on theory‐based psychosocial and behavioral factors, and over 24 months on weight. Considering the included times and temporal ranges, it was found that change in weight from month 6–24 was the strongest predictor of 24‐month weight change, and physical activity and fruit/vegetable intake at month 24 best predicted that change in weight. Self‐regulation, self‐efficacy, and mood at month 24 best predicted both physical activity and fruit/vegetable intake at month 24, with body satisfaction also a significant predictor of physical activity. From these data, mediation analyses found that the predictions of long‐term weight loss by scores of self‐regulation, self‐efficacy, body satisfaction, and mood at month 24 were significantly mediated by fruit/vegetable intake and physical activity in separate equations. Findings indicated both psychosocial and behavioral targets, and timing for those targets, most indicative of long‐term success with weight loss.
The Personal Sources of Responsiveness. Introduction to a Special Section
Authors: Campbell Rosie , Zittel Thomas
Published: February 2020

Responsiveness is a core value in democratic politics. Individual legislators are important mechanisms for implementing this concern in real‐world settings and thus facilitating responsive government. This introduction to the special section on this topic starts out by highlighting the special relevance of individual legislators in this regard and by sketching important theoretical considerations that emerge from the political science literature on this issue. In its main part, it summarizes the key findings of the contributions in relation to its main theme, namely the personal sources of responsiveness. We end with a short conclusion that reflects on possible tensions between responsiveness and the personalization of representative systems.
Political or Financial Benefits? Ideology, Tenure, and Parliamentarians’ Choice of Interest Group Ties
Authors: Huwyler Oliver , Turner‐Zwinkels Tomas
Published: February 2020

This article develops and tests a parliamentarian‐centred decision model of the collaboration between interest groups (IGs) and parliamentarians. We posit that parliamentarians face a trade‐off when deciding on IG ties that offer them either political (policy support and votes) or financial benefits (additional income). We theorise the balance in this trade‐off to be moderated by ideology and tenure because both introduce variations in IG ties’ utility across politicians. Using Swiss longitudinal data from 1985 to 2015 on 743 parliamentarians and their 5,431 IG board positions, we show that parliamentarians become more financial benefit‐seeking over time. This holds in particular if they belong to right‐leaning parties. We also find self‐imposed restrictions for new and left‐leaning parliamentarians on seeking financial benefits. This highlights that parliamentarians are responsive to their partisan constituents when building their IG tie portfolio.
When Do Men Represent Women’s Interests in Parliament? How the Presence of Women in Parliament Affects the Legislative Behavior of Male Politicians
Authors: Höhmann Daniel
Published: February 2020

This paper analyzes the conditions affecting male Members of Parliaments’ (MPs) proclivity for representing women’s interests. It particularly explores whether the presence of female MPs has an effect on men’s parliamentary behavior. Three contrasting effects are discussed in the literature: (1) A spillover effect which postulates that men will become more likely to act on behalf of women if the number of female MPs increases, (2) a group‐threat effect which creates a hostile backlash among male MPs, or (3) a specialization effect which makes male MPs less likely to represent women because this is typically seen as a function that should be fulfilled by female MPs. Empirically, this paper analyzes the representation of women’s issues in parliamentary questions tabled in the German Bundestag (1998‐2013) by using automated content analysis. The results support the specialization hypothesis and show that male MPs reduce their intensity of women’s representation if the proportion of female MPs is high.
A plastid‐localized bona fide geranylgeranyl diphosphate synthase plays a necessary role in monoterpene indole alkaloid biosynthesis in Catharanthus roseus
Authors: Kumar Sarma Rajeev , Rai Avanish , Bomzan Dikki Pedenla , Kumar Krishna , Hemmerlin Andréa , Dwivedi Varun , Godbole Rucha C. , Barvkar Vitthal , Shanker Karuna , Shilpashree H. B. , Bhattacharya Ankita , Smitha Attibele Ramamurthy , Hegde Namratha , Nagegowda Dinesh A.
Published: February 2020

In plants, geranylgeranyl diphosphate (GGPP, C20) synthesized by GGPP synthase (GGPPS) serves as precursor for vital metabolic branches including specialized metabolites. Here, we report the characterization of a GGPPS (CrGGPPS2) from the Madagascar periwinkle (Catharanthus roseus) and demonstrate its role in monoterpene (C10)‐indole alkaloids (MIA) biosynthesis. The expression of CrGGPPS2 was not induced in response to methyl jasmonate (MeJA), and was similar to the gene encoding type‐I protein geranylgeranyltransferase_β subunit (CrPGGT‐I_β), which modulates MIA formation in C. roseus cell cultures. Recombinant CrGGPPS2 exhibited a bona fide GGPPS activity by catalyzing the formation of GGPP as the sole product. Co‐localization of fluorescent protein fusions clearly showed CrGGPPS2 was targeted to plastids. Downregulation of CrGGPPS2 by virus‐induced gene silencing (VIGS) significantly decreased the expression of transcription factors and pathway genes related to MIA biosynthesis, resulting in reduced MIA. Chemical complementation of CrGGPPS2‐vigs leaves with geranylgeraniol (GGol, alcoholic form of GGPP) restored the negative effects of CrGGPPS2 silencing on MIA biosynthesis. In contrast to VIGS, transient and stable overexpression of CrGGPPS2 enhanced the MIA biosynthesis. Interestingly, VIGS and transgenic‐overexpression of CrGGPPS2 had no effect on the main GGPP‐derived metabolites, cholorophylls and carotenoids in C. roseus leaves. Moreover, silencing of CrPGGT‐I_β, similar to CrGGPPS2‐vigs, negatively affected the genes related to MIA biosynthesis resulting in reduced MIA. Overall, this study demonstrated that plastidial CrGGPPS2 plays an indirect but necessary role in MIA biosynthesis. We propose that CrGGPPS2 might be involved in providing GGPP for modifying proteins of the signaling pathway involved in MIA biosynthesis.
Ferroportin inhibition attenuates plasma iron, oxidant stress, and renal injury following red blood cell transfusion in guinea pigs
Authors: Baek Jin Hyen , Shin Hye Kyung H. , Gao Yamei , Buehler Paul W.
Published: February 2020

BACKGROUND

Red blood cell (RBC) transfusions result in the sequestration and metabolism of storage‐damaged RBCs within the spleen and liver. These events are followed by increased plasma iron concentrations that can contribute to oxidant stress and cellular injury. We hypothesized that administration of a ferroportin inhibitor (FPN‐INH) immediately after acute RBC exchange transfusion could attenuate posttransfusion circulatory compartment iron exposure, by retaining iron in spleen and hepatic macrophages.

STUDY DESIGN AND METHODS

Donor guinea pig blood was leukoreduced, and RBCs were preserved at 4°C. Recipient guinea pigs (n = 5/group) were exchange transfused with donor RBCs after refrigerator preservation and dosed intravenously with a small‐molecule FPN‐INH. Groups included transfusion with vehicle (saline), 5 mg/kg or 25 mg/kg FPN‐INH. A time course of RBC morphology, plasma non–transferrin‐bound iron (NTBI) and plasma hemoglobin (Hb) were evaluated. End‐study spleen, liver, and kidney organ iron levels, as well as renal tissue oxidation and injury, were measured acutely (24‐hr after transfusion).

RESULTS

RBC transfusion increased plasma NTBI, with maximal concentrations occurring 8 hours after transfusion. Posttransfusion iron accumulation resulted in tubule oxidation and acute kidney injury. FPN inhibition increased spleen and liver parenchymal/macrophage iron accumulation, but attenuated plasma NTBI, and subsequent renal tissue oxidation/injury.

CONCLUSION

In situations of acute RBC transfusion, minimizing circulatory NTBI exposure by FPN inhibition may attenuate organ‐specific adverse consequences of iron exposure.
An animal model of transfusion‐related acute lung injury and the role of soluble CD40 ligand
Authors: Hu Ai , Chen Weiyun , Wu Shubin , Pan Boju , Zhu Afang , Yu Xuerong , Huang Yuguang
Published: February 2020

Background and objectives

Transfusion‐related acute lung injury (TRALI) is a life‐threatening complication of transfusion and is one of leading causes of transfusion‐associated fatalities. However, the pathogenesis of TRALI is still unclear. Soluble CD40 ligand (sCD40L) is a proinflammatory cytokine that accumulates during blood component storage and is involved in transfusion reactions. The objective of this study was to establish a clinically relevant TRALI animal model and to evaluate the role of sCD40L in TRALI.

Materials and methods

Rats’ red‐blood‐cell (RBC) suspensions were prepared, and the quality of RBC was evaluated. A trauma–haemorrhage–transfusion strategy was applied to build the animal model. Lung oedema was evaluated by histopathology examination, total bronchoalveolar lavage fluid (BALF) protein concentration, Evans blue dye (EBD) leakage and inflammatory cytokines. The sCD40L concentrations were measured.

Results

Storage lesions of RBCs gradually increased over time. Obvious histological evidence of lung injury of rats transfused with a 35‐day RBC was observed. The total BALF protein concentration, EBD leakage, inflammatory cytokines concentration were increased significantly in the Day 35 group. The sCD40L concentration increased significantly in the storage RBC suspension over time but was slightly elevated in rat plasma.

Conclusions

These findings indicated successful establishment of a TRALI animal model with trauma–haemorrhage–transfusion, in which sCD40L may play a minor role in the development of TRALI.
Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir
Authors: Rabie Helena , Tikiso Tjokosela , Lee Janice , Fairlie Lee , Strehlau Renate , Bobat Raziya , Liberty Afaaf , McIlleron Helen , Andrieux-Meyer Isabelle , Cotton Mark , Lallemant Marc , Denti Paolo
Published: February 2020

In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1.
Pharmacy-Based Infectious Disease Management Programs Incorporating CLIA-Waived Point-of-Care Tests
Authors: Herbin S. R. , Klepser D. G. , Klepser M. E.
Published: February 2020

There are roughly 48,000 deaths caused by influenza annually and an estimated 200,000 people who have undiagnosed human immunodeficiency virus (HIV). These are examples of acute and chronic illnesses that can be identified by employing a CLIA-waived test. Pharmacies across the country have been incorporating CLIA-waived point-of-care tests (POCT) into disease screening and management programs offered in the pharmacy. The rationale behind these programs is discussed. Additionally, a summary of clinical data for some of these programs in the infectious disease arena is provided.
Evaluation of a Novel Multiplex PCR Panel Compared to Quantitative Bacterial Culture for Diagnosis of Lower Respiratory Tract Infections
Authors: Collins Mackenzie E. , Popowitch Elena B. , Miller Melissa B.
Published: February 2020

Quantitative bacterial culture of bronchoalveolar lavage fluids (BALF) is labor-intensive, and the delay involved in performing culture, definitive identification, and susceptibility testing often results in prolonged use of broad-spectrum antibiotics. The Unyvero lower respiratory tract (LRT) panel (Curetis, Holzgerlingen, Germany) allows the multiplexed rapid detection and identification of 20 potential etiologic agents of pneumonia within 5 h of collection. In addition, the assay includes detection of gene sequences that confer antimicrobial resistance.
The Carboxyl Terminus of the Porcine Circovirus Type 2 Capsid Protein Is Critical to Virus-Like Particle Assembly, Cell Entry, and Propagation
Authors: Zhan Yang , Yu Wanting , Cai Xiong , Lei Xinnuo , Lei Hongyu , Wang Aibing , Sun Yujie , Wang Naidong , Deng Zhibang , Yang Yi
Published: February 2020

The carboxyl terminus (CT) of porcine circovirus type 2 (PCV2) capsid protein (Cap) was previously reported to be associated with immunorecognition, alterations of viral titer in swine sera, and pathogenicity. However, the molecular mechanisms underlying these effects remain unknown. In this study, roles of the critical residues and motifs of the CT are investigated with respect to virus-like particle (VLP) assembly, cell entry, and viral proliferation. The results revealed that the positively charged
227
K of the CT is essential for both cell entry of PCV2 VLPs and virus proliferation. Our findings, therefore, suggest that the CT should be considered one of the key epitopes, recognized by neutralizing antibodies, for vaccine design and a target for drug development to prevent PCV2-associated diseases (PCVADs). Furthermore, it is important to respect the function of
227
K for its role in cell entry if using either PCV2 VLPs for nanoscale DNA/drug cell delivery or using PCV2 VLPs to display a variety of foreign epitopes for immunization.
Pseudorabies Virus Infection Accelerates Degradation of the Kinesin-3 Motor KIF1A
Authors: Huang Hao , Koyuncu Orkide O. , Enquist Lynn W.
Published: February 2020

Pseudorabies virus (PRV) is an alphaherpesvirus related to human pathogens herpes simplex viruses 1 and 2 and varicella-zoster virus. Alphaherpesviruses are neuroinvasive pathogens that establish lifelong latent infections in the host peripheral nervous system (PNS). Following reactivation from latency, infection spreads from the PNS back via axons to the peripheral mucosal tissues, a process mediated by kinesin motors. Here, we unveil and characterize the underlying mechanisms for a PRV-induced, accelerated degradation of KIF1A, a kinesin-3 motor promoting the sorting and transport of PRV virions in axons. We show that PRV infection disrupts the synthesis of KIF1A and simultaneously promotes the degradation of intrinsically unstable KIF1A proteins by proteasomes in axons. Our work implies that the timing of motor reduction after reactivation would be critical because progeny particles would have a limited time window for sorting into and transport in axons for further host-to-host spread.
Mitochondrial and Innate Immunity Transcriptomes from Spodoptera frugiperda Larvae Infected with the Spodoptera frugiperda Ascovirus
Authors: Zaghloul Heba A. H. , Hice Robert , Bideshi Dennis K. , Arensburger Peter , Federici Brian A.
Published: February 2020

Ascoviruses are large DNA viruses that infect insects, inducing a cellular pathology that resembles apoptosis but which differs by causing enormous cellular hypertrophy followed by cleavage of the cell into numerous viral vesicles for replication. Previous EM studies suggest that mitochondria are important for vesicle formation. Transcriptome analyses of
Spodoptera frugiperda
larvae infected with SfAV-1a showed that mitochondrial transcripts were similar to those from uninfected controls or increased slightly during vesicle formation, especially for ATP6, ATP8 synthase, and NADH dehydrogenase subunits. This pattern resembles that for chronic disease-inducing viruses, which conserve mitochondria, differing markedly from viruses causing short-term viral diseases, which degrade mitochondrial DNA. Though mitochondrial transcript increases were low, our results demonstrate that SfAV-1a alters host mitochondrial expression more than any other virus. Regarding innate immunity, although SfAV-1a destroys most fat body cells, certain immunity genes were highly upregulated (greater than 20-fold), suggesting that these transcripts may originate from other tissues.
Plant Virus Genome Is Shaped by Specific Dinucleotide Restrictions That Influence Viral Infection
Authors: González de Prádena Alfonso , Sánchez Jimenez Adrián , San León David , Simmonds Peter , García Juan Antonio , Valli Adrián A.
Published: February 2020

Dinucleotides (combinations of two consecutive nucleotides) are not randomly present in RNA viruses; in fact, the presence of CpG and UpA is significantly repressed in their genomes. Although the meaning of this phenomenon remains obscure, recent studies with animal-infecting viruses have revealed that their low CpG/UpA frequency prevents virus restriction via a host antiviral system that recognizes, and promotes the degradation of, CpG/UpA-rich RNAs. Whether similar systems act in organisms from other life kingdoms has been unknown. To fill this gap in our knowledge, we built several synthetic variants of a plant RNA virus with deoptimized dinucleotide frequencies and analyzed their viral fitness and genome adaptation. In brief, our results inform us for the first time about an effective dinucleotide-based system that acts in plants against viruses. Remarkably, this viral restriction in plants is reminiscent of, but not identical to, the equivalent antiviral response in animals.
Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis
Authors: Kim Minsuk , Vogtmann Emily , Ahlquist David A. , Devens Mary E. , Kisiel John B. , Taylor William R. , White Bryan A. , Hale Vanessa L. , Sung Jaeyun , Chia Nicholas , Sinha Rashmi , Chen Jun
Published: February 2020

Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., the collection of microbes residing in our gut, has been recognized as a key player in CRC development. There have been a number of gut microbiota profiling studies for colorectal adenoma and CRC; however, fewer studies have considered the gut metabolome, which serves as the chemical interface between the host and gut microbiota. Here, we conducted a gut metabolome profiling study of colorectal adenoma and CRC and analyzed the metabolomic profiles together with paired microbiota composition profiles. We found several chemical signatures of colorectal adenoma that were associated with some gut microbes and potentially indicative of future CRC. This study highlights potential early-driver metabolites in CRC pathogenesis and guides further targeted experiments and thus provides an important stepping stone toward developing better CRC prevention strategies.
Dynamic Membrane Localization of RNase Y in Bacillus subtilis
Authors: Hamouche Lina , Billaudeau Cyrille , Rocca Anna , Chastanet Arnaud , Ngo Saravuth , Laalami Soumaya , Putzer Harald
Published: February 2020

All living organisms must degrade mRNA to adapt gene expression to changing environments. In bacteria, initiation of mRNA decay generally occurs through an endonucleolytic cleavage. In the Gram-positive model organism
Bacillus subtilis
and probably many other bacteria, the key enzyme for this task is RNase Y, which is anchored at the inner cell membrane. While this pseudocompartmentalization appears coherent with translation occurring primarily at the cell periphery, our knowledge on the distribution and dynamics of RNase Y in living cells is very scarce. Here, we show that RNase Y moves rapidly along the membrane in the form of dynamic short-lived foci. These foci become more abundant and increase in size following transcription arrest, suggesting that they do not constitute the most active form of the nuclease. This contrasts with RNase E, the major decay-initiating RNase in
E. coli
, where it was shown that formation of foci is dependent on the presence of RNA substrates. We also show that a protein complex (Y-complex) known to influence the specificity of RNase Y activity
in vivo
is capable of shifting the assembly status of RNase Y toward fewer and smaller complexes. This highlights fundamental differences between RNase E- and RNase Y-based degradation machineries.
An Advanced Human Intestinal Coculture Model Reveals Compartmentalized Host and Pathogen Strategies during
Salmonella
Infection
Authors: Schulte Leon N. , Schweinlin Matthias , Westermann Alexander J. , Janga Harshavardhan , Santos Sara C. , Appenzeller Silke , Walles Heike , Vogel Jörg , Metzger Marco
Published: February 2020

Infection research routinely employs
in vitro
cell cultures or
in vivo
mouse models as surrogates of human hosts. Differences between murine and human immunity and the low level of complexity of traditional cell cultures, however, highlight the demand for alternative models that combine the
in vivo
-like properties of the human system with straightforward experimental perturbation. Here, we introduce a 3D tissue model comprising multiple cell types of the human intestinal barrier, a primary site of pathogen attack. During infection with the foodborne pathogen
Salmonella enterica
serovar Typhimurium, our model recapitulates human disease aspects, including pathogen restriction to the epithelial compartment, thereby deviating from the systemic infection in mice. Combination of our model with state-of-the-art genetics revealed
Salmonella
-mediated local manipulations of human immune responses, likely contributing to the establishment of the pathogen’s infection niche. We propose the adoption of similar 3D tissue models to infection biology, to advance our understanding of molecular infection strategies employed by bacterial pathogens in their human host.
Comparative Analysis of Root Microbiomes of Rice Cultivars with High and Low Methane Emissions Reveals Differences in Abundance of Methanogenic Archaea and Putative Upstream Fermenters
Authors: Liechty Zachary , Santos-Medellín Christian , Edwards Joseph , Nguyen Bao , Mikhail David , Eason Shane , Phillips Gregory , Sundaresan Venkatesan
Published: February 2020

Rice cultivation is a major source of anthropogenic emissions of methane, a greenhouse gas with a potentially severe impact on climate change. Emission variation between rice cultivars suggests the feasibility of breeding low-emission rice, but there is a limited understanding of how genotypes affect the microbiota involved in methane cycling. Here, we show that the root microbiome of the high-emitting cultivar is enriched both in methanogens and in taxa associated with fermentation, iron, and sulfate reduction and acetogenesis, processes that support methanogenesis. Understanding how cultivars affect microbes with methanogenesis-related functions is vital for understanding the genetic basis for methane emission in rice and can aid in the development of breeding programs that reduce the environmental impact of rice cultivation.
manta: a Clustering Algorithm for Weighted Ecological Networks
Authors: Röttjers Lisa , Faust Karoline
Published: February 2020

manta comes with unique strengths, such as the abilities to identify nodes that represent an intermediate between clusters, to exploit negative edges, and to assess the robustness of cluster membership. manta does not require parameter tuning, is straightforward to install and run, and can be easily combined with existing microbial network inference tools.
Metagenome Mining Reveals Hidden Genomic Diversity of Pelagimyophages in Aquatic Environments
Authors: Zaragoza-Solas Asier , Rodriguez-Valera Francisco , López-Pérez Mario
Published: February 2020

SAR11 clade members are among the most abundant bacteria on Earth. Their study is complicated by their great diversity and difficulties in being grown and manipulated in the laboratory. On the other hand, and due to their extraordinary abundance, metagenomic data sets provide enormous richness of information about these microbes. Given the major role played by phages in the lifestyle and evolution of prokaryotic cells, the contribution of several new bacteriophage genomes preying on this clade opens windows into the infection strategies and life cycle of its viruses. Such strategies could provide models of attack of large-genome phages preying on streamlined aquatic microbes.
Rasmussen’s aneurysm masquerading as mass lesion
Authors: Sahoo Satyajeet , Panigrahi Manoj Kumar , Naik Suprava , Mohapatra Prasanta Raghab
Published: February 2020

Haemoptysis is an often encountered respiratory symptom. The amount of haemoptysis varies from mild to life-threatening severity and may indicate the underlying pulmonary disorder. Herein, we report a 50-year-old male smoker who presented with occasional streaky to mild haemoptysis for last 1 year. He had pulmonary tuberculosis 10 years ago and had received adequate treatment. Chest radiograph was suspicious of a mass lesion in left upper lung. Contrast-enhanced CT scan of thorax revealed pulmonary artery pseudoaneurysm suggestive of Rasmussen’s aneurysm. Unlike this case, Rasmussen’s aneurysm usually manifests as life-threatening haemoptysis and portends a high mortality.
Long-term visual outcomes of the Boston type I keratoprosthesis in Canada
Authors: Szigiato Andrei-Alexandru , Bostan Cristina , Nayman Taylor , Harissi-Dagher Mona
Published: February 2020

Background/aims

To evaluate long-term visual outcomes of Boston type I keratoprosthesis (KPro) surgery and identify risk factors for visual failure.

Methods

Single surgeon retrospective cohort study including 85 eyes of 74 patients who underwent KPro implantation to treat severe ocular surface disease, including limbal stem cell deficiency, postinfectious keratitis, aniridia and chemical burns. Procedures were performed at the Centre hospitalier de l'Université de Montréal from October 2008 to May 2012. All patients with at least 5 years of follow-up were included in the analysis, including eyes with repeated KPro. Main outcome measures were visual acuity (VA), visual failure, defined as a sustained worse than preoperative VA, postoperative complications, and device retention.

Results

Mean follow-up was 7.2±1.3 years (±SD). Mean VA was 2.1±0.7 (logarithm of minimal angle resolution) preoperatively and 1.9±1.2 at last follow-up. There were 2.4% of patients with VA better than 20/200 preoperatively and 36.5% at last follow-up. Maintenance of improved postoperative VA was seen in 61.8% of eyes at 7 years. Preoperative factors associated with visual failure were known history of glaucoma (HR=2.7 (1.2 to 5.9), p=0.02) and Stevens-Johnson syndrome (HR=7.3 (2.5 to 21.4) p<0.01). Cumulative 8-year complication rates were 38.8% retroprosthetic membrane formation, 25.9% hypotony, 23.5% new onset glaucoma, 17.6% retinal detachment, 8.2% device extrusion and 5.9% endophthalmitis. The majority (91.8%) of eyes retained the device 8 years after implantation.

Conclusion

Almost two-thirds of patients had improved VA 7 years after KPro implantation. Preoperative risk factors for visual failure were known glaucoma and Stevens-Johnson syndrome.
Multicentre randomised controlled trial to evaluate the efficacy of pre-emptive inferior mesenteric artery embolisation during endovascular aortic aneurysm repair on aneurysm sac change: protocol of Clarify IMA study
Authors: Ichihashi Shigeo , Takahara Mitsuyoshi , Fujimura Naoki , Nagatomi Satoru , Iwakoshi Shinichi , Bolstad Francesco , Kichikawa Kimihiko
Published: February 2020

Introduction

Type II endoleak (EL) is frequently seen after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) and is often considered responsible for aneurysm sac enlargement if it persists. In order to reduce type II EL and consequent sac enlargement, pre-emptive embolisation of the inferior mesenteric artery (IMA), which is a main source for persistent type II EL, has been introduced in many vascular centres. At present, there is a lack of robust evidence to support the efficacy of pre-emptive embolisation of IMA on reduction of persistent type II EL with subsequent sac shrinkage.

Method and analysis

This multicentre, randomised controlled trial will recruit 200 patients who have fusiform AAA ≥50 mm/rapidly enlarging fusiform AAA, with patent IMA, and randomly allocate them either to a pre-emptive IMA embolisation group or non-embolisation control group in a ratio of 1:1. The primary endpoint is the difference of aneurysm sac volume change assessed by CT scans between the pre-emptive IMA embolisation group and the control group at 12 months after EVAR. The secondary endpoints are defined as change of aneurysm sac volume in both groups at 6 and 24 months, freedom from sac enlargement at 12 and 24 months after EVAR, prevalence of type II EL at 1, 6, 12 and 24 months evaluated by contrast-enhanced CT, reintervention rate, aneurysm related mortality, overall survival, perioperative morbidity, volume of contrast media used during EVAR and dosage of radiation.

Ethics and dissemination

The protocol has been reviewed and approved by the ethics committee of Nara Medical University (No. 2113). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry home page.

Trial registration number

UMIN000035502.