bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Corticosteroids on the Respiratory Microbiome: A Systematic Review
Authors: Hartmann Julia E. , Albrich Werner C. , Dmitrijeva Marija , Kahlert Christian R.
Published: March 2021

Background: Since its discovery, the respiratory microbiome has been implicated in the pathogenesis of multiple pulmonary diseases. Even though corticosteroid treatments are widely prescribed for pulmonary diseases, their effects on the respiratory microbiome are still poorly understood. This systematic review summarizes the current understanding of the effects of corticosteroids on the microbiome of the airways.

Research Question: How does treatment with corticosteroids impact the respiratory microbiome?

Study Design and Methods: According to the PRISMA guidelines, Embase, Medline, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for all observational or randomized-controlled studies comparing the microbiome parameters of patients receiving corticosteroids to those of controls. The primary outcomes of interest were changes in the diversity, composition and total burden of the respiratory microbiome as assessed by culture-independent molecular methods.

Results: Out of 1,943 identified reports, five studies could be included: two on patients with asthma, two on patients with chronic obstructive pulmonary disease and one on patients with chronic rhinosinusitis. The studies were highly heterogeneous with regards to the methods used and the populations investigated. Microbiome diversity increased with corticosteroids at least transiently in three studies and decreased in one study. The effects of corticosteroids on the composition of the respiratory microbiome were significant but without a clear shared direction. A significant increase in microbial burden after corticosteroids was seen in one study.

Interpretation: Data on the effect of corticosteroids on the respiratory microbiome are still limited, with considerable heterogeneity between studies. However, available data suggest that corticosteroid treatment may have significant effects on the composition and possibly the diversity of the respiratory microbiome. Further research is needed to better understand the influence of corticosteroids on the respiratory microbiome and thus better target its widespread therapeutic use.
Dynamic Chronological Changes in Serum Triglycerides Are Associated With the Time Point for Non-alcoholic Fatty Liver Disease Development in the Nationwide Korean Population Cohort
Authors: Rim John Hoon , Youk Taemi , Gee Heon Yung , Cho Jooyoung , Yoo Jongha
Published: March 2021

Background: We investigated the effects of anthropometric, laboratory, and lifestyle factors on the development of non-alcoholic fatty liver disease (NAFLD) in a nationwide, population-based, 4-year retrospective cohort.

Methods: The propensity score-matched study and control groups contained 1,474 subjects who had data in the Korean National Health Insurance Service-National Sample Cohort in 2009, 2011, and 2013. NAFLD was defined using medical records of a diagnosis confirmed by primary clinicians and meeting two previously validated fatty liver prediction models. Chronological changes in anthropometric variables, laboratory results, and lifestyle factors during two periods were compared between patient and control groups in order to find out parameters with consistent dynamics in pre-NAFLD stage which was defined as period just before the NAFLD development.

Results: Among the 5 anthropometric, 10 laboratory, and 3 lifestyle factors, prominent chronological decremental changes in serum triglycerides were consistently observed during the pre-NAFLD stage, although the degrees of changes were more predominant in men (−9.46 mg/dL) than women (−5.98 mg/dL). Furthermore, weight and waist circumference changes during the pre-NAFLD stage were noticeable only in women (+0.36 kg and +0.9 cm for weight and waist circumference, respectively), which suggest gender difference in NAFLD.

Conclusion: Early screening strategies for people with abrupt chronological changes in serum triglycerides to predict NAFLD development before the progression is recommended.
Biotransformation of Methane and Carbon Dioxide Into High-Value Products by Methanotrophs: Current State of Art and Future Prospects
Authors: Sahoo Krishna Kalyani , Goswami Gargi , Das Debasish
Published: March 2021

Conventional chemical methods to transform methane and carbon dioxide into useful chemicals are plagued by the requirement for extreme operating conditions and expensive catalysts. Exploitation of microorganisms as biocatalysts is an attractive alternative to sequester these C1 compounds and convert them into value-added chemicals through their inherent metabolic pathways. Microbial biocatalysts are advantageous over chemical processes as they require mild-operating conditions and do not release any toxic by-products. Methanotrophs are potential cell-factories for synthesizing a wide range of high-value products via utilizing methane as the sole source of carbon and energy, and hence, serve as excellent candidate for methane sequestration. Besides, methanotrophs are capable of capturing carbon dioxide and enzymatically hydrogenating it into methanol, and hence qualify to be suitable candidates for carbon dioxide sequestration. However, large-scale production of value-added products from methanotrophs still presents an overwhelming challenge, due to gas-liquid mass transfer limitations, low solubility of gases in liquid medium and low titer of products. This requires design and engineering of efficient reactors for scale-up of the process. The present review offers an overview of the metabolic architecture of methanotrophs and the range of product portfolio they can offer. Special emphasis is given on methanol biosynthesis as a potential biofuel molecule, through utilization of methane and alternate pathway of carbon dioxide sequestration. In view of the gas-liquid mass transfer and low solubility of gases, the key rate-limiting step in gas fermentation, emphasis is given toward reactor design consideration essential to achieve better process performance.
Gait Assessment Using Three-Dimensional Acceleration of the Trunk in Idiopathic Normal Pressure Hydrocephalus
Authors: Yamada Shigeki , Aoyagi Yukihiko , Ishikawa Masatsune , Yamaguchi Makoto , Yamamoto Kazuo , Nozaki Kazuhiko
Published: March 2021

Background: The subjective evaluation of pathological gait exhibits a low inter-rater reliability. Therefore, we developed a three-dimensional acceleration of the trunk during walking to assess the pathological gait quantitatively.

Methods: We evaluated 97 patients who underwent the cerebrospinal tap test and were diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and 68 healthy elderlies. The gait features of all patients were evaluated and classified as one of the following: freezing of gait, wide-based gait, short-stepped gait, shuffling gait, instability, gait festination, difficulty in changing direction, and balance disorder in standing up. All gait features of 68 healthy elderlies were treated as normal. Trunk acceleration was recorded automatically by a smartphone placed on the umbilicus during a 15-foot walking test. Two novel indices were created. The first index was a trunk acceleration index, which was defined as (forward acceleration fluctuation) + (vertical acceleration fluctuation) – (lateral acceleration fluctuation) based on the multivariate logistics regression model, and the second index was created by multiplying the forward acceleration with the vertical acceleration. Additionally, 95% confidence ellipsoid volume of the three-dimensional accelerations was assessed.

Results: Forward and vertical acceleration fluctuations were significantly associated with the probability of an iNPH-specific pathological gait. The trunk acceleration index demonstrated the strongest association with the probability of an iNPH-specific pathological gait. The areas under the receiver-operating characteristic curves for detecting 100% probability of an iNPH-specific pathological gait were 86.9% for forward acceleration fluctuation, 88.0% for vertical acceleration fluctuation, 82.8% for lateral acceleration fluctuation, 89.0% for trunk acceleration index, 88.8% for forward × vertical acceleration fluctuation, and 87.8% for 95% confidence ellipsoid volume of the three-dimensional accelerations.

Conclusions: The probability of a pathological gait specific to iNPH is high at the trunk acceleration fluctuation, reduced in the forward and vertical directions, and increased in the lateral direction.
Lymphocyte Activation Gene 3 (Lag3) Contributes to α-Synucleinopathy in α-Synuclein Transgenic Mice
Authors: Gu Hao , Yang Xiuli , Mao Xiaobo , Xu Enquan , Qi Chen , Wang Haibo , Brahmachari Saurav , York Bethany , Sriparna Manjari , Li Amanda , Chang Michael , Patel Pavan , Dawson Valina L. , Dawson Ted M.
Published: March 2021

Aggregation of misfolded α-synuclein (α-syn) is the major component of Lewy bodies and neurites in Parkinson’s disease (PD) and related α-synucleinopathies. Some α-syn mutations (e.g., A53T) in familial PD recapitulate the α-syn pathology in transgenic mice, which supports the importance of pathologic α-syn in driving the pathogenesis of α-synucleinopathies. Lymphocyte activation gene 3 (Lag3) is a receptor of α-syn fibrils facilitating pathologic α-syn spread; however, the role of Lag3 in mediating the pathogenesis in α-syn transgenic mice is not clear. Here, we report that depletion of Lag3 in human α-syn A53T transgenic (hA53T) mice significantly reduces the level of detergent-insoluble α-syn aggregates and phosphorylated ser129 α-syn, and inhibits activation of microglia and astrocytes. The absence of Lag3 significantly delays disease progression and reduces the behavioral deficits in hA53T transgenic mice leading to prolonged survival. Taken together, these results show that Lag3 contributes to the pathogenesis in the α-syn A53T transgenic mouse model.
A Case Report of Central Nervous System Graft-Versus-Host Disease and Literature Review
Authors: Li Mingming , Zhang Yue , Guan Yujia , Zhang Zunwei , Dong Hanbing , Zhao Yang , Deng Hui
Published: March 2021

As an adverse immune phenomenon, graft-versus-host disease often occurs after allogeneic hematopoietic stem cell transplantation. The incidence of acute and chronic graft-versus-host disease is about 40–60% and the mortality rate can reach 15%, which is a potentially fatal disease. There are rare GvHD cases involving the central nervous system. We reported a rare case of diffuse white matter changes after haploid bone marrow transplantation, summarizing its clinical manifestations and diagnosis and treatment in conjunction with the literature.
Cognitive Impairment After Resolution of Hepatic Encephalopathy: A Systematic Review and Meta-Analysis
Authors: López-Franco Óscar , Morin Jean-Pascal , Cortés-Sol Albertina , Molina-Jiménez Tania , Del Moral Diana I. , Flores-Muñoz Mónica , Roldán-Roldán Gabriel , Juárez-Portilla Claudia , Zepeda Rossana C.
Published: March 2021

Hepatic encephalopathy (HE) is one of the most disabling metabolic diseases. It consists of a complication of liver disease through the action of neurotoxins, such as excessive production of ammonia from liver, resulting in impaired brain function. Its prevalence and incidence are not well known, although it has been established that up to 40% of cirrhotic patients may develop HE. Patients with HE episodes display a wide range of neurological disturbances, from subclinical alterations to coma. Recent evidence suggests that the resolution of hepatic encephalopathy does not fully restore cognitive functioning in cirrhotic patients. Therefore, the aim of this review was to evaluate the evidence supporting the presence of lingering cognitive deficits in patients with a history of HE compared to patients without HE history and how liver transplant affects such outcome in these patients. We performed two distinct meta-analysis of continuous outcomes. In both cases the results were pooled using random-effects models. Our results indicate that cirrhotic patients with a history of HE show clear cognitive deficits compared to control cirrhotic patients (Std. Mean Difference (in SDs) = −0.72 [CI 95%: −0.94, −0.50]) and that these differences are not fully restored after liver transplant (Std. Mean Difference (in SDs) = −0.48 [CI 95%: −0.77, −0.19]).
Dietary Fibers (Gum Arabic) Supplementation Modulates Hepatic and Renal Profile Among Rheumatoid Arthritis Patients, Phase II Trial
Authors: Kamal Ebtihal , Kaddam Lamis AbdelGadir , Alagib Alnour , Saeed Amal
Published: March 2021

Background: Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects the synovial joints with systemic manifestations. RA has a major impact on liver and kidney functions as part of the disease pathogenesis or as a sequel of disease medications or, mostly, both of them. The kidney and liver involvement increases the RA morbidity and mortality. Nowadays, dietary interventions are proposed as potential modifiers for disease severity. Gum Arabic (GA) is acacia senegal exudates; it is soluble fiber with prebiotic properties. GA has been discovered to be protective against experimental nephrotoxicity and hepatotoxicity, with comparable findings in human studies. This article addresses the effect of GA on hepatic and renal profile among RA patients.

Methods: Forty patients aged 18–70 received GA daily for 12 weeks as a single dose of 30 g. The liver enzymes, total protein level, serum albumin, serum globulin level, urea, creatinine, and serum electrolytes have been measured as a baseline after 4 weeks and by the end of the study. Cobas C311 (Roche, Germany) automated chemistry analyzer directly determined the values for total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine. The study ethically has been approved by the Ethical Committee of the National Medicines and Poisons Board. Trial Registration Identifier: NCT02804581.

Results: Regarding the liver enzymes, GA has significantly decreased the liver enzymes apart from alkaline phosphatase, which showed no significant change. In contrast, GA has increased the serum albumin level with a minor impact on the serum globulin level. Furthermore, GA has also significantly decreased the level of urea (P = 0.0001) and level of Sodium (P = 0.002) with nonsignificant change on creatinine and potassium concentrations.

Conclusion: GA presents hepatic and renal protective effects among RA patients, evidenced by the significant reduction of urea and liver enzymes. Thus, it can be recommended as a dietary supplement for RA patients. Nonetheless, we recommend further investigation to support our findings.
Integrin Alpha V in Urine: A Novel Noninvasive Marker for Prostate Cancer Detection
Authors: Zemskova Marina Y. , Marinets Maria V. , Sivkov Andrey V. , Pavlova Julia V. , Shibaev Andrey N. , Sorokin Konstantin S.
Published: March 2021

Prostate cancer (PCa) diagnosis based on patient urine analysis provides non-invasive and promising method as compared to biopsy and a prostate-specific antigen (PSA) test. This study was conceived to investigate whether Integrin alpha V (ITGAV) protein is present in urine and assess the urinary ITGAV diagnostic potential for PCa. Materials and Methods: Urinary ITGAV expression was determined by Western blot analysis and quantified by ELISA in urine from men with PCa (n = 47), benign prostate hyperplasia (n = 42) and age-matched controls (n = 22). Results: The level of ITGAV protein was significantly lower in PCa urine samples as compared to those in the control group (p < 0.00001). The decrease of ITGAV in urine was highly predictive of PCa with 91.5% sensitivity, 91.4% specificity, 0.93 area under the ROC curve, and its specificity was better than that of serum PSA. Conclusion: Urinary ITGAV provides a novel noninvasive biomarker with high specificity.
Cause-Specific Mortality Among Survivors From T1N0M0 Renal Cell Carcinoma: A Registry-Based Cohort Study
Authors: Wang Zhixian , Wang Jing , Zhu Yunpeng , Liu Chang , Li Xing , Zeng Xiaoyong
Published: March 2021

Objective

More T1N0M0 renal cell carcinoma (RCC) is detected and the prognosis has improved, but, the current focus on non-RCC-related mortality is superficial. We investigated cause-specific mortality and its temporal patterns after an RCC diagnosis.

Methods

In the Surveillance, Epidemiology, and End Results-18 database, patients with T1N0M0 RCC treated with partial nephrectomy (PN) or radical nephrectomy (RN) during 2000–15 were identified. Standardized mortality ratios (SMRs) for cause of death were calculated. Risk predictors for each cause-specific mortality were investigated using the Fine and Gray sub-distribution model.

Results

In all, 68,612 eligible patients were pooled. A total of 14,047 (20.5%) patients had died (cardiovascular disease [CVD], 28.3%; other non-cancer-related diseases, 20.3%; RCC, 18.7%; other cancer types, 16.3%; non-disease events, 16.1%) during follow-up. Heart disease, diabetes mellitus, and cerebrovascular disease were the primary causes of non-RCC-related mortality within 1 year after the diagnosis. The greatest proportion of death (39.0%) occurred within 1–5 years after the diagnosis, mostly due to RCC itself, followed by heart disease. However, >5 years after the diagnosis, heart disease became the leading cause of death. Compared with the general US population, a 21% (SMR, 1.21; 95%CI 1.19–1.23) increased risk of all-mortality was observed; RCC patients had a higher risk of heart disease-related death within 5–10 years (SMR, 1.10; 95%CI 1.04–1.17) and >10 years (1.12; 1.02–1.22) after the diagnosis. Older age and RN increased the death risk of CVD and RCC-specific mortality. Although a larger tumor diameter increased the risk of RCC-specific death, this was not a significant predictor for CVD. Moreover, for T1N0M0 RCC tumors of diameter >4 cm, there was no significant difference in CVD incidence for RN vs. PN.

Conclusions

RCC-specific mortality is a common challenge for the prognosis. Importantly, a large proportion and higher SMRs of other non-RCC-related diseases (especially CVD) should not be disregarded for the better holistic management of survivors of local RCC. Targeted prevention strategies for non-RCC-related death could lead to significant reductions in mortality for RCC survivors.
Prediction of Post-hepatectomy Liver Failure in Patients With Hepatocellular Carcinoma Based on Radiomics Using Gd-EOB-DTPA-Enhanced MRI: The Liver Failure Model
Authors: Chen Yuyan , Liu Zelong , Mo Yunxian , Li Bin , Zhou Qian , Peng Sui , Li Shaoqiang , Kuang Ming
Published: March 2021

Objectives: Preoperative prediction of post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) is significant for developing appropriate treatment strategies. We aimed to establish a radiomics-based clinical model for preoperative prediction of PHLF in HCC patients using gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI).

Methods: A total of 144 HCC patients from two medical centers were included, with 111 patients as the training cohort and 33 patients as the test cohort, respectively. Radiomics features and clinical variables were selected to construct a radiomics model and a clinical model, respectively. A combined logistic regression model, the liver failure (LF) model that incorporated the developed radiomics signature and clinical risk factors was then constructed. The performance of these models was evaluated and compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) with 95% confidence interval (CI).

Results: The radiomics model showed a higher AUC than the clinical model in the training cohort and the test cohort for predicting PHLF in HCC patients. Moreover, the LF model had the highest AUCs in both cohorts [0.956 (95% CI: 0.955–0.962) and 0.844 (95% CI: 0.833–0.886), respectively], compared with the radiomics model and the clinical model.

Conclusions: We evaluated quantitative radiomics features from MRI images and presented an externally validated radiomics-based clinical model, the LF model for the prediction of PHLF in HCC patients, which could assist clinicians in making treatment strategies before surgery.
Initial Clinical Experience of MR-Guided Radiotherapy for Non-Small Cell Lung Cancer
Authors: Crockett Cathryn B. , Samson Pamela , Chuter Robert , Dubec Michael , Faivre-Finn Corinne , Green Olga L. , Hackett Sara L. , McDonald Fiona , Robinson Clifford , Shiarli Anna-Maria , Straza Michael W. , Verhoeff Joost J. C. , Werner-Wasik Maria , Vlacich Gregory , Cobben David
Published: March 2021

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and Elekta Unity. The challenges and potential solutions associated with MRgRT in lung cancer will also be highlighted.
Clinical and Psychological Factors to Consider in Achieving Treatment-Free Remission in Patients With Chronic Myeloid Leukemia
Authors: Breccia Massimo , Abruzzese Elisabetta , Annunziata Mario , Luciano Luigia , Sica Simona
Published: March 2021

Treatment of chronic myeloid leukemia (CML) has evolved dramatically in recent years. In this regard, the introduction of second-generation tyrosine kinase inhibitors (TKI) has revolutionized therapeutic goals, and it is now desirable to obtain treatment-free remission (TFR), i.e. when a patient who has stopped TKI therapy maintains a major molecular response and does not need to restart treatment. This report summarizes the main findings from a group of expert hematologists in Italy who met to discuss treatment and management of patients with CML with focus on broad-ranging aspects of TFR. A survey was used to obtain information about the clinicians’ experience with TFR and to better understand the clinical and psychological issues that patients and physicians face when considering TFR. The overall goal was to explore the possibility of discontinuing treatment from multiple points of view, considering both clinical aspects of TFR as well as psychological management of patients. Practical information is provided on aspects associated with initiating TFR, clinical data supporting it, the role of monitoring, and management of discontinuation-related adverse events. This publication outlines many of the shortcomings and highlights proposed solutions for routine clinical practice, and provides an overview of the literature relative to TFR.
Early Robotic-Assisted Laparoscopic Pyeloplasty for Infants Under 3 Months With Severe Ureteropelvic Junction Obstruction
Authors: Li Pin , Zhou Huixia , Cao Hualin , Guo Tao , Zhu Weiwei , Zhao Yang , Tao Tian , Zhou Xiaoguang , Ma Lifei , Yang Yunjie , Feng Zhichun
Published: March 2021

Objective: To present our primary experience of robotic-assisted laparoscopic pyeloplasty (RALP) for severe ureteropelvis junction obstruction (UPJO) infants under 3 months.

Methods: We performed a retrospective study of 9 infants under 3 months who underwent RALP for severe UPJO between April 2017 and March 2019 in our center. The severe UPJO was defined as infants with severe hydronephrosis (Society of Fetal Urology grades III or IV, anteroposterior diameter >3 cm or split renal function <40% or T 1/2 >20 min) involving bilateral, solitary kidney, or contralateral renal hypoplasia UPJO at the same time. All clinical, perioperative, and postoperative information was collected.

Results: There were four bilateral UPJO cases, two solitary kidney UPJO cases and three unilateral UPJO with contralateral renal hypoplasia cases included. One single surgeon performed RALP on all of the infants. The mean age of the infants was 1.62 ± 0.54 months. The mean operative time was 109.55 ± 10.47 min. The mean estimated blood loss was 19.29 ± 3.19 ml, and the mean length of hospital stay was 5.57 ± 0.73 days. According to the ultrasonography results, all patients had a significant recovery of renal function at 12 months after the operation.

Conclusions: To maximize the protection of renal function, early RALP is a safe and feasible option for the treatment of severe UPJO in infants under 3 months.
Evaluation of a Multidisciplinary Antimicrobial Stewardship Program in a Saudi Critical Care Unit: A Quasi-Experimental Study
Authors: Haseeb Abdul , Faidah Hani Saleh , Al-Gethamy Manal , Iqbal Muhammad Shahid , Barnawi Abrar Mohammed , Elahe Shuruq S. , Bukhari Duha Nabeel , Noor Al-Sulaimani Turki Mohammad , Fadaaq Mohammad , Alghamdi Saad , Almalki Waleed Hassan , Saleem Zikria , Elrggal Mahmoud Essam , Khan Amer Hayat , Algarni Mohammed A , Ashgar Sami S. , Hassali Mohamed Azmi
Published: March 2021

Background: Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. With regard to critically ill patients, appropriate antimicrobial usage is of significance, and any delay in therapy increases their risk of mortality. Therefore, the implementation of structured multidisciplinary ASPs in critical care settings is of the utmost importance to promote the judicious use of antimicrobials.

Methods: This quasi-experimental study evaluating a multidisciplinary ASP in a 20-bed critical care setting was conducted from January 1, 2016 to July 31, 2017. Outcomes were compared nine months before and after ASP implementation. The national antimicrobial stewardship toolkit by Ministry of health was reviewed and the hospital antibiotic prescribing policy was accordingly modified. The antimicrobial stewardship algorithm (Start Smart and Then Focus) and an ASP toolkit were distributed to all intensive care unit staff. Prospective audit and feedback, in addition to prescribing forms for common infectious diseases and education, were the primary antimicrobial strategies.

Results: We found that the mean total monthly antimicrobial consumption measured as defined daily dose per 100 bed days was reduced by 25% (742.86 vs. 555.33; p = 0.110) compared to 7% in the control condition (tracer medications) (35.35 vs. 38.10; p = 0.735). Interestingly, there was a negative impact on cost in the post-intervention phase. Interestingly, the use of intravenous ceftriaxone measured as defined daily dose per 100 bed days was decreased by 82% (94.32 vs. 16.68; p = 0.008), whereas oral levofloxacin use was increased by 84% (26.75 vs. 172.29; p = 0.008) in the intensive care unit.

Conclusion: Overall, involvement of higher administration in multidisciplinary ASP committees, daily audit and feedback by clinical pharmacists and physicians with infectious disease training, continuous educational activities about antimicrobial use and resistance, use of local antimicrobial prescribing guidelines based on up-to-date antibiogram, and support from the intensive care team can optimize antibiotic use in Saudi healthcare institutions.
The Bioequivalence of Emulsified Isoflurane With a New Formulation of Emulsion: A Single-Center, Single-Dose, Double-Blinded, Randomized, Two-Period Crossover Study
Authors: Yang Hui , Yin Qinqin , Huang Luying , Zhang Min , Zhang Xinxin , Sun Qirong , Liu Xuewei , Wang Qi , Yang Xi , Tan Lingcan , Ye Mao , Liu Jin
Published: March 2021

Background: Emulsified isoflurane is a novel intravenous general anesthetic obtained by encapsulating isoflurane molecules into emulsion. The formulation of emulsion has been improved according to the latest regulations of the China Food and Drug Administration. This study was designed to compare the bioequivalence of the new and previous formulation emulsion of isoflurane.

Methods: In a single-center, single-dose, double-blinded, randomized, two-period crossover study, healthy volunteers received intravenous injection of 30 mg/kg of isoflurane with either previous formulation of emulsion isoflurane (PFEI) or new formulation of emulsion isoflurane (NFEI). Arterial and venous blood samples were obtained for geometric mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞, as well as their 90% confidence interval (CI90) as the primary outcome. The secondary outcomes were safety measurements such as vital signs, 12-lead electrocardiography, adverse effects, and laboratory tests; and anesthesia efficacy was assessed by Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score, bispectral index (BIS), and loss/recovery of eyelash reflex.

Results: 24 subjects were eligible, of which 21 completed the whole experiment (NFEI n = 21, PFEI n = 23). Arterial geometric mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 104.50% (CI90 92.81%–117.65%), 108.23% (94.51%–123.96%), and 106.53% (93.94%∼120.80%), respectively. The most commonly seen adverse effects for NFEI and PFEI were injection pain (38.1% vs. 34.8%), hypotension (19.0% vs. 13.0%), apnea (14.3% vs. 17.4%), and upper airway obstruction (14.3% vs. 13.0%). No severe adverse effect was observed. The effectiveness of general anesthesia was similar between the two formulations.

Conclusion: The CI90 of Cmax, AUC0-t, AUC0-∞, NFEI, and PFEI were within the range of 80%–125%, suggesting bioequivalence between NFEI and PFEI. The safety and anesthesia effectiveness were also similar.
Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease
Authors: Zhou Yiwen , Wu Meifei , Xu Lei , Cheng Jieling , Shen Jie , Yang Tianyu , Zhang Lei
Published: March 2021

Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. In vitro, blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What’s more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD.
Neurodegenerative Disease and the NLRP3 Inflammasome
Authors: Holbrook Jonathan A. , Jarosz-Griffiths Heledd H. , Caseley Emily , Lara-Reyna Samuel , Poulter James A. , Williams-Gray Caroline H. , Peckham Daniel , McDermott Michael F.
Published: March 2021

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by a progressive neuronal loss in the brain or peripheral nervous system, and generally involve protein aggregation, as well as metabolic abnormalities and immune dysregulation. Although the vast majority of neurodegeneration is idiopathic, there are many known genetic and environmental triggers. In the past decade, research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease or is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, a crucial component of the innate immune system, is usually activated in response to infection or tissue damage. Dysregulation of the NLRP3 inflammasome has been implicated in the progression of several neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. This review aims to summarise current literature on the role of the NLRP3 inflammasome in the pathogenesis of neurodegenerative diseases, and recent work investigating NLRP3 inflammasome inhibition as a potential future therapy.
Simultaneous Two-Photon Fluorescence Microscopy of NADH and FAD Using Pixel-to-Pixel Wavelength-Switching
Authors: Qin Yifan , Xia Yuanqin
Published: March 2021

Two-photon fluorescence (TPF) microscopy of intrinsic fluorophores provides physiological and pathological information from biological tissues. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are two endogenous fluorescent coenzymes existing on the intracellular scale. Autofluorescence images of NADH and FAD have been applied to noninvasively record changes during metabolism, according to their distributions and concentrations. However, the widely used sequential (non-simultaneous) excitation scheme results in artifacts caused by sample motion or laser power fluctuation. The single-wavelength illumination scheme suffers from low excitation efficiency and spectral bleed-through. In this paper, we demonstrate a new imaging system simultaneously capturing autofluorescence images from NADH and FAD, with high excitation efficiency and negligible spectral bleed-through. Two temporally multiplexed and spatially overlapped excitation beams were achieved with fast-switching light paths based on an electro-optic modulator. The switching beams were centered at 750 and 860 nm, enabling independent excitations of NADH and FAD. Autofluorescence images of NADH and FAD were acquired at the wavelength ranges of 415–455 nm and 500–550 nm, respectively. The electro-optic modulator was synchronized with the pixel clock from the microscope, achieving pixel-to-pixel wavelength-switching. The capability of the system was demonstrated by performing TPF imaging of freshly excised mouse colon tissues. The microenvironment of the colon wall was depicted by the distributions of colonocytes, goblet cells, and crypts of Lieberkühn, and the relative concentrations of NADH and FAD were estimated. The experimental results show that the system can effectively perform simultaneous imaging of NADH and FAD, and is considered a promising tool for investigations into metabolism-associated processes and diseases.
Different Waterlogging Depths Affect Spatial Distribution of Fine Root Growth for Pinus thunbergii Seedlings
Authors: Fujita Saki , Noguchi Kyotaro , Tange Takeshi
Published: March 2021

The increase of waterlogged environments at forests and urban greenery is of recent concern with the progress of climate change. Under waterlogging, plant roots are exposed to hypoxic conditions, which strongly affect root growth and function. However, its impact is dependent on various factors, such as waterlogging depth. Therefore, our objective is to elucidate effects of different waterlogging depths on Pinus thunbergii Parl., which is widely used for afforestation, especially at coastal forests. We conducted an experiment to examine growth and morphology of fine roots and transpiration using 2-year-old seedlings under three treatments, (1) control (no waterlogging), (2) partial waterlogging (partial-WL, waterlogging depth = 15 cm from the bottom), and (3) full waterlogging (full-WL, waterlogging depth = from the bottom to the soil surface, 26 cm). As a result, fine root growth and transpiration were both significantly decreased at full-WL. However, for partial-WL, fine root growth was significantly increased compared to control and full-WL at the top soil, where it was not waterlogged. Additionally, transpiration which had decreased after 4 weeks of waterlogging showed no significant difference compared to control after 8 weeks of waterlogging. This recovery is to be attributed to the increase in fine root growth at non-waterlogged top soil, which compensated for the damaged roots at the waterlogged bottom soil. In conclusion, this study suggests that P. thunbergii is sensitive to waterlogging; however, it can adapt to waterlogging by plastically changing the distribution of fine root growth.
Nitrogen Levels Regulate Sugar Metabolism and Transport in the Shoot Tips of Crabapple Plants
Authors: Zhang Lihua , Sun Simin , Liang Yonghui , Li Baiyun , Ma Songya , Wang Zhengyang , Ma Baiquan , Li Mingjun
Published: March 2021

To comprehensively understand the responses of carbohydrate metabolism and transport to different levels of nitrogen supply in growing shoot tips of crabapple (Malus hupehensis Rehd), enzyme activities and related genes involved in the sugar metabolism pathway were investigated. The nitrogen and chlorophyll content of plants increased with increasing nitrogen supply. High nitrogen application increased the net photosynthesis rate and the growth rate of shoot tips but decreased the synthesis capability of sucrose and sorbitol in mature leaves. However, the shoot tips of plants under high-nitrogen treatment had higher contents of sucrose and sorbitol than did those under low-nitrogen treatment, while the activity of sucrose phosphate synthase and aldose-6-phosphate was increased and the transporters MdSOT and MdSUT were up-regulated. Moreover, the activities of enzymes involved in sucrose and hexose metabolism (including sucrose synthase, fructokinase, and hexokinase) were enhanced in the shoot tips of plants under high-nitrogen conditions, and the expression levels of MdSUSY3 and MdHK1 were significantly up-regulated. These findings indicate that a high nitrogen supply increases the metabolic capacity of assimilatory substances in shoot tips, accelerates the efficiency of sugar utilization and eventually leads to a rapid increase in the growth of shoot tips. Our results highlight that high nitrogen increases the capacity of sugar unloading and metabolic utilization in growing shoot tissues.
Unraveling Interactions of the Necrotrophic Fungal Species Botrytis cinerea With 1-Methylcyclopropene or Ozone-Treated Apple Fruit Using Proteomic Analysis
Authors: Testempasis Stefanos , Tanou Georgia , Minas Ioannis , Samiotaki Martina , Molassiotis Athanassios , Karaoglanidis Georgios
Published: March 2021

Gray mold caused by the necrotrophic fungus Botrytis cinerea is one of the major postharvest diseases of apple fruit. The exogenous application of 1-methylcyclopropene (1-MCP) and gaseous ozone (O 3) is commonly used to ensure postharvest fruit quality. However, the effect of these treatments on the susceptibility of apple fruit to postharvest pathogens remains largely unknown. Herein, the effect of O 3 and 1-MCP treatments on the development of gray mold on apple fruit (cv. “Granny Smith”) was investigated. Artificially inoculated apple fruits, treated or not with 1-MCP, were subjected for 2 months to cold storage [0°C, relative humidity (RH) 95%] either in an O3-enriched atmosphere or in a conventional cold chamber. Minor differences between 1-MCP-treated and control fruits were found in terms of disease expression; however, exposure to ozone resulted in a decrease of disease severity by more than 50% compared with 1-MCP-treated and untreated fruits. Proteomic analysis was conducted to determine proteome changes in the mesocarp tissue of control and 1-MCP- or O3-treated fruits in the absence or in the presence of inoculation with B. cinerea. In the non-inoculated fruits, 26 proteins were affected by 1-MCP, while 51 proteins were altered by ozone. Dynamic changes in fruit proteome were also observed in response to B. cinerea. In O3-treated fruits, a significant number of disease/defense-related proteins were increased in comparison with control fruit. Among these proteins, higher accumulation levels were observed for allergen, major allergen, ACC oxidase, putative NBS-LRR disease resistance protein, major latex protein (MLP)-like protein, or 2-Cys peroxiredoxin. In contrast, most of these proteins were down-accumulated in 1-MCP-treated fruits that were challenged with B. cinerea. These results suggest that ozone exposure may contribute to the reduction of gray mold in apple fruits, while 1-MCP was not effective in affecting this disease. This is the first study deciphering differential regulations of apple fruit proteome upon B. cinerea infection and postharvest storage treatments, underlying aspects of host response related to the gray mold disease.
Need-Supportive and Need-Thwarting Teacher Behavior: Their Importance to Boys’ and Girls’ Academic Engagement and Procrastination Behavior
Authors: Opdenakker Marie-Christine
Published: March 2021

Motivation plays an important role in students’ school behavior, and research has established that students’ learning environment experiences such as teachers’ behavior toward them contribute to their motivation and behavior at school. Self-determination theory (SDT) offers an interesting frame of reference in the study of the relationship between students’ learning experiences at school and their school behavior. Considering three basic psychological needs (the need for autonomy, competence, and relatedness), the SDT points to the importance of nutriments and support in the social environment in order to allow growth in motivation, engagement, and (psychological) well-functioning. In addition, thwarting these needs is supposed to contribute to maladaptive functioning. Teachers can play an important role in the fulfillment of students’ basic psychological needs by delivering support (autonomy support, structure, and involvement); however, controlling instructional behavior, chaos in the classroom, and teacher rejection and neglect are supposed to be a treat to the fulfillment of students’ basic psychological needs. In the current innovative longitudinal study, teachers’ need-supportive behavior as well as teachers’ thwarting of these needs are considered and their relationship with students’ academic engagement (adaptive functioning) and procrastination behavior (maladaptive functioning) is studied. In addition, attention is paid to differential effects of teachers’ behavior with regard to boys and girls. Participants were 566 students belonging to 20 mathematics/English grade 1 secondary education classes in the Netherlands. Multilevel analyses revealed evidence for the importance of both teachers’ need-supportive and need-thwarting behaviors in relation to students’ academic engagement and procrastination behavior. In addition, the findings revealed that teachers’ need-supportive behavior is more important for students’ academic engagement (adaptive functioning), while teachers’ need-thwarting behavior has larger effects on students’ procrastination behavior (maladaptive functioning). Furthermore, evidence was found that boys often seemed to be more sensitive to their teachers’ behavior than girls. The findings highlight the importance of both teachers’ need-supportive and need-thwarting behaviors in daily classrooms and contribute to deepen our insight into and understanding of factors leading to adaptive and maladaptive functioning of boys and girls in relation to learning tasks at school.
Understanding Older Adults' Memory Distortion in the Light of Stereotype Threat
Authors: Mazerolle Marie , Smith Amy M. , Torrance McKinzey , Thomas Ayanna K.
Published: March 2021

Numerous studies have documented the detrimental impact of age-based stereotype threat (ABST) on older adults' cognitive performance and especially on veridical memory. However, far fewer studies have investigated the impact of ABST on older adults' memory distortion. Here, we review the subset of research examining memory distortion and provide evidence for the role of stereotype threat as a powerful socio-emotional factor that impacts age-related susceptibility to memory distortion. In this review we define memory distortion as errors in memory that are associated with gist-based errors or source misattributions. Whereas, some of the reviewed experiments support the conclusion that ABST should be considered in the context of age-related differences in memory distortion, others reported little or no impact of stereotype threat. These discrepancies suggest that the role of ABST, and socio-emotional processes generally, in age-related changes in memory distortion are less clear. In this review, we argue that ABST does play an important role in age-related changes in memory distortion. We present evidence suggesting that discrepancies in the reviewed literature may be reconciled when evaluated in the context of the leading theories about stereotype threat: the Executive Resource Depletion hypothesis and the Regulatory Focus theory. We also discuss how differences in methodology and participant characteristics can account for a priori contradictory results in the literature. Finally, we propose some recommendations for researchers and practitioners when assessing memory in older adults.
Psychometric Properties and Rasch Validation of the Teachers’ Version of the Perception of Resources Questionnaire
Authors: Alnahdi Ghaleb H. , Goldan Janka , Schwab Susanne
Published: March 2021

Research indicates that the perception of available resources is a key factor for the implementation of inclusive education. Regarding the teachers, a relatively high level of perceived personnel and physical resources is associated with more positive attitudes toward inclusive education and experiencing a higher level of self-efficacy. Thus, this study aims to examine the psychometric properties of the teacher version of the Perceptions of Resources Questionnaire (PRQ-T). Data were collected from a sample of 1,078 in-service teachers in Austria. Different statistical analyses were used, including Rasch analysis and confirmatory factor analysis. The results indicated good psychometric properties of the PRQ-T regarding internal consistency measured by person separation index (PSI) and construct validity by both confirmatory factor analysis and the Rasch analysis. Moreover, the findings supported that the PRQ-T is a two-factor scale to measure teachers’ perceptions of personnel and physical resources in inclusive education. Further studies with different samples are necessary to confirm the findings.