bluuebunny/crossref_metadata_2025 huggingface dataset:
Albumin/fibrinogen ratio, a predictor of chemotherapy resistance and prognostic factor for advanced gastric cancer patients following radical gastrectomy
Authors: Zhao Guojun
Published: May 2022

Background

The objective of this study was to investigate potential predictors of chemotherapy resistance in patients with advanced gastric cancer (GC) following radical gastrectomy.

Methods

Eligible stage II/III GC patients with adjuvant chemotherapy after radical gastrectomy were enrolled in this study. A receiver operating characteristic (ROC) curve analysis was performed to assess the predictive and optimal cut-off values of continuous variables for chemotherapy resistance. Potential risk factors for chemotherapy resistance were determined with binary univariate and multivariate analyses. Potential prognostic factors for overall survival (OS) were determined by COX regression analysis. The association between survival and AFR level was examined using the Kaplan–Meier curve analysis.

Results

A total of 160 patients were included in the data analysis, and 41 patients achieved chemotherapeutic resistance with an incidence of 25.6%. Pretreatment albumin/fibrinogen ratio (AFR) (cut-off value: 10.85, AUC: 0.713, P < 0.001) was a predictor for chemotherapeutic resistance by ROC curve analysis. Low AFR (< 10.85) was an independent risk factor of chemotherapeutic resistance as determined by the univariate and multivariate logistic regression analyses (OR: 2.55, 95%CI: 1.21–4.95, P = 0.005). Multivariate COX regression analyses indicated low AFR as a prognostic factor for 5-year OS (HR: 0.36, 95%CI: 0.15–0.73, P = 0.011). Low AFR was associated with poorer 5-year disease-free survival and overall survival.

Conclusions

This study indicated that a low level of pretreatment AFR could serve as an independent predictor of chemotherapy resistance and postoperative prognosis in GC patients following radical gastrectomy.
Regeneration of meniscal avascular zone using autogenous meniscal fragments in a rabbit model
Authors: Deng Yan , Tong Zuo-Ming , Dai Zhu , Chen Zhi-Wei
Published: May 2022

Background

To investigate the effects of autologous meniscus fragment (AMF) implantation on injury in the meniscal avascular zone in mature rabbits.

Methods

Adult New Zealand white rabbits were randomly divided into two groups. Massive one-piece meniscus tissue was implanted in situ as control. In the experimental group, AMF was used to repair the meniscal injury in the avascular zone. Meniscal damage was assessed by gross observation of the degree of healing and histological semi-quantitative evaluation within 12 weeks postoperatively. The healing of meniscus interface was assessed by gross observation semiquantitative scoring and microscopic examination hematoxylin and eosin (H&E) staining at 2, 4, 8, and 12 weeks after surgery. The expressions of proliferating cell nuclear antigen (PCNA), collagen type I (COL1A1), and collagen type II (COL2) were detected by immunohistochemical staining.

Results

The degree of healing in the AMF group showed a significant increase over time (P < 0.05); the AMF group showed higher gross scores than the control group at 4, 8, and 12 weeks after surgery (P < 0.05). The histological scores in the AMF group were significantly higher than those in the control group at 4, 8, and 12 weeks after surgery (P < 0.05). The protein expression of PCNA in the AMF group was greater than that in the control group at 2, 4, and 8 weeks after surgery (P < 0.05). In addition, compared with the control group, the protein levels of COL1A1 and COL2 were significantly upregulated at each time-point. At 2 and 4 weeks after surgery, the expression level of COL1A1 increased in both groups followed by a gradual decrease after 8 weeks (P < 0.05). At 2, 4, 8, and 12 weeks after surgery, the expression levels of COL2 showed a gradual decrease in both groups (P < 0.05).

Conclusions

Our study demonstrated that the AMF method can promote the repair of rabbit meniscal injury in the avascular zone, and this method may potentially be used for clinical application.
Levothyroxine treatment for congenital hypothyroidism based on thyroid function: a 10-year clinical retrospective study
Authors: He Shan , Ma Xiaolin , Yang Jinghui , Li Li
Published: May 2022

Objective

To explore the appropriate dosage of levothyroxine treatment for congenital hypothyroidism patients with different thyroid stimulating hormone (TSH) levels.

Methods

A total of 116 patients, who were regularly followed-up in our endocrine clinic from January 2010 to December 2020, were divided into four groups based on their thyroid function (group A: TSH ≥ 100 mIU/L, group B: TSH ≥ 20, and < 100, group C: TSH > 4.6 mIU/L and < 20 mIU/L with free thyroxine (FT4) < 6.6 pmol/L, and group D: TSH > 4.6 mIU/L and < 20 mIU/L with FT4 > 6.6 pmol/L). The initial dosage of levothyroxine was individualized for each patient based on their TSH level and then adjusted according to their thyroid function at every follow-up time point. The levothyroxine dosage at each time point was compared between the groups, and thyroid function and physical and neurological development after treatment were also compared.

Results

After individualized dosage adjustment, all patients achieved normal thyroid function. Although there were statistical differences in neurological development between the four groups (p < 0.05), development was within the normal range for all groups.

Conclusion

An individualized levothyroxine dosage can provide the same therapeutic effect compared to the recommended dosage. This strategy may also reduce the risk of a drug overdose.
Primary school teachers’ contributions to oral health promotion in urban and rural areas of the Gulu District, Northern Uganda: a qualitative study
Authors: Akera Peter , Kennedy Sean E. , Obwolo Mark J. , Schutte Aletta E. , Lingam Raghu , Richmond Robyn
Published: May 2022

Background

Dental caries remains the most prevalent non-communicable disease globally affecting 60–90% of children. The World Health Organisation’s (WHO) health-promoting school program offers a framework for dental intervention in low- and middle-income countries (LMICs). This study explored teacher contributions to children’s oral health in relation to the WHO health-promoting school framework in rural Uganda.

Methods

Semi structured interviews were conducted with a purposive sample of 18 teachers. All interviews were transcribed verbatim and analysed thematically.

Results

Many teachers reported preparing children to practise proper oral hygiene care through skills training and demonstrations around proper teeth brushing. Teachers’ roles included raising health awareness by providing information on oral health topics using different educational methods. Many teachers mentioned performing oral health examinations on children at the school, first aid, referral for dental treatments and engaging parents, students and health workers in oral health promotion.

Conclusions

Teachers play an essential role in oral health promotion in countries like Uganda. Teachers are implementing key principles of the WHO’s health-promoting school framework on the ground and need to be considered as a key public health resource. If improvements in oral health are to be attained in Sub-Saharan Africa and other LMICs, government interventions need to harness teachers’ contributions in delivering oral health promotion.
Progression and postoperative complications of osteoradionecrosis of the jaw: a 20-year retrospective study of 124 non-nasopharyngeal cancer cases and meta-analysis
Authors: Kang Ziqin , Jin Tingting , Li Xueer , Wang Yuepeng , Xu Tianshu , Wang Yan , Huang Zixian , Huang Zhiquan
Published: May 2022

Background

To assess the contributing risk factors for the progression of, and the postoperative poor prognosis associated with, osteoradionecrosis of jaw (ORNJ) following non-nasopharyngeal cancer treatment in head and neck.

Methods

A retrospective study of 124 non-nasopharyngeal carcinoma patients in head and neck treated at one institution between 2001 and 2020 was conducted. A cumulative meta-analysis was conducted according to PRISMA protocol and the electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. After assessing surgery with jaw lesions as a risk factor for the occurrence of ORNJ, 124 cases were categorized into two groups according to the “BS” classification, after which jaw lesions, chemotherapy, flap reconstruction and onset time of ORNJ were analyzed through the chi-square test and t-test to demonstrate the potential association between them and the progression of ORNJ. Postoperative outcomes of wound healing, occlusal disorders, and nerve injury were statistically analyzed.

Results

With the statistically significant results of the meta-analysis (odds ratio = 3.07, 95% CI: 1.84–5.13,p < 0.0001), the chi-square test and t-test were used to validate our hypotheses and identified that surgery with jaw lesions could aggravate the progression and accelerate the appearance of ORNJ. Patients who underwent chemotherapy tended to suffer from severe-to-advanced osteonecrosis but did not shorten the onset time of ORNJ. Flap reconstruction presented obvious advantages in wound healing (p < 0.001) and disordered occlusion (p < 0.005). The mean onset time of ORNJ in non-nasopharyngeal cancer patients (4.5 years) was less than that in patients with nasopharyngeal cancer (NPC) (6.8 years).

Conclusions

Iatrogenic jaw lesions are evaluated as a significant risk factor in the occurrence and progression of ORNJ in non-nasopharyngeal carcinoma patients who tend to have more severe and earlier osteonecrosis after radiotherapy than NPC patients. Flap reconstruction is a better choice for protecting the remaining bone tissue and reducing postoperative complications of ORNJ.
Validation of a Spanish-language scale for evaluating perceived quality of care of medical abortions before 9 weeks gestation
Authors: Cabedo-Ferreiro Rosa , Vicente-Hernández Maria-Mercedes , Manresa-Domínguez Josep-Maria , Gómez-Masvidal Miriam , Montero-Pons Laura , Reyes-Lacalle Azahara , Falguera-Puig Gemma
Published: May 2022

Background

Spanish Organic Law 2/2010 legalizes abortion within 14 weeks of gestation. Medical abortion with mifepristone and misoprostol is around 97% effective and is offered at primary care centers during the first 9 weeks of gestation. It consists of the administration of 200 mg of mifepristone by a healthcare professional and of the self-administration 800 mg of misoprostol by the patient at home, along with prescribed analgesics. However, the quality of this process as perceived by patients has never been assessed. This study aims to validate a scale designed to assess the perceived quality of the entire process, structure and results of at-home medical abortion.

Methods

Validation study of a Spanish adaptation of the SERVPERF scale. In total, 289 patients completed a self-administered questionnaire consisting of 26 items previously evaluated by a group of experts. A re-test was performed on 53 of these patients 15 days later to assess interobserver consistency.

Results

The highest non-response rate for any single item was 2.1%. The floor effect was 26% and the ceiling effect did not surpass 83%. The linearly weighted Kappa coefficient was good to excellent, in general. An exploratory factor analysis was performed with Varimax rotation, obtaining a total of 7 dimensions that explain 65.9% of the variability. The internal consistency (Cronbach's alpha) for all items was 0.862.

Conclusion

This psychometric instrument is valid and reliable for assessing the quality of care of medical abortion. Medical abortion is efficient, effective and eliminates the need for hospital care, anesthesia and surgical risk. However, user satisfaction has yet to be determined. This study offers a validated scale to assess perceived quality of care, their quality experience and person-centered care for abortion as a fundamental part of overall service quality as a fundamental part of overall service quality.
Gao-Zi-Yao improves learning and memory function in old spontaneous hypertensive rats
Authors: Han Meng-Xiao , Jiang Wen-Yi , Jiang Yan , Wang Lin-Hui , Xue Rong , Zhang Guo-Xing , Chen Jing-Wei
Published: May 2022

Aims

Gao-Zi-Yao has long been a unique way for treating various diseases. The present study is to explore the effect of Gao-Zi-Yao on learning and memory function in old spontaneous hypertensive rats (SHR) and its possible mechanism.

Method

Male old SHR were received different doses of Gao-Zi-Yao for 4 weeks. Systolic blood pressure (SBP) and heart rate were monitored. Serum levels of nitric oxide (NO), interleukin (IL)-1β, IL-2, and tumor necrotic factor (TNF)-α were measured. Morris water maze was performed to test the learning and memory function of the rats. Number of neurons in hippocampus was counted by Nissl staining. Western blot was applied to detect the expressions of learning and memory function related proteins, N-methyl-d-aspartate receptor 2B (NMDAR 2B), glutamate receptor 1 (GluR1), phosphorylated-calmodulin-dependent protein kinase II (p-CaMK II), and phosphorylated-cAMP responsive element-binding protein (p-CREB) in rat hippocampus.

Results

Data showed that Gao-Zi-Yao reduced SBP in old SHR, elevated NO level, and suppressed levels of IL-1β, IL-2, TNF-α. The results of Morris water maze experiment showed that Gao-Zi-Yao dose-dependently improved learning and memory function. Number of neurons in the hippocampal dentate gyrus (DG) region of the old SHR was increased by Gao-Zi-Yao treatment. In addition, Gao-Zi-Yao elevated the protein expressions of NMDAR 2B, GluR1, p-CaMK II, and p-CREB in hippocampus.

Conclusion

Gao-Zi-Yao decreases SBP and improves the learning and memory function of the old SHR by regulation of oxidative stress, inflammatory factors and neuron number in hippocampal DG area and the expression of learning and memory function related proteins.
Shaping the right conditions in programmatic assessment: how quality of narrative information affects the quality of high-stakes decision-making
Authors: de Jong Lubberta H. , Bok Harold G. J. , Schellekens Lonneke H. , Kremer Wim D. J. , Jonker F. Herman , van der Vleuten Cees P. M.
Published: May 2022

Background

Programmatic assessment is increasingly being implemented within competency-based health professions education. In this approach a multitude of low-stakes assessment activities are aggregated into a holistic high-stakes decision on the student’s performance. High-stakes decisions need to be of high quality. Part of this quality is whether an examiner perceives saturation of information when making a holistic decision. The purpose of this study was to explore the influence of narrative information in perceiving saturation of information during the interpretative process of high-stakes decision-making.

Methods

In this mixed-method intervention study the quality of the recorded narrative information was manipulated within multiple portfolios (i.e., feedback and reflection) to investigate its influence on 1) the perception of saturation of information and 2) the examiner’s interpretative approach in making a high-stakes decision. Data were collected through surveys, screen recordings of the portfolio assessments, and semi-structured interviews. Descriptive statistics and template analysis were applied to analyze the data.

Results

The examiners perceived less frequently saturation of information in the portfolios with low quality of narrative feedback. Additionally, they mentioned consistency of information as a factor that influenced their perception of saturation of information. Even though in general they had their idiosyncratic approach to assessing a portfolio, variations were present caused by certain triggers, such as noticeable deviations in the student’s performance and quality of narrative feedback.

Conclusion

The perception of saturation of information seemed to be influenced by the quality of the narrative feedback and, to a lesser extent, by the quality of reflection. These results emphasize the importance of high-quality narrative feedback in making robust decisions within portfolios that are expected to be more difficult to assess. Furthermore, within these “difficult” portfolios, examiners adapted their interpretative process reacting on the intervention and other triggers by means of an iterative and responsive approach.
An algorithm to identify cases of pulmonary arterial hypertension from the electronic medical record
Authors: Schuler Kyle P. , Hemnes Anna R. , Annis Jeffrey , Farber-Eger Eric , Lowery Brandon D. , Halliday Stephen J. , Brittain Evan L.
Published: May 2022

Background

Study of pulmonary arterial hypertension (PAH) in claims-based (CB) cohorts may facilitate understanding of disease epidemiology, however previous CB algorithms to identify PAH have had limited test characteristics. We hypothesized that machine learning algorithms (MLA) could accurately identify PAH in an CB cohort.

Methods

ICD-9/10 codes, CPT codes or PAH medications were used to screen an electronic medical record (EMR) for possible PAH. A subset (Development Cohort) was manually reviewed and adjudicated as PAH or “not PAH” and used to train and test MLAs. A second subset (Refinement Cohort) was manually reviewed and combined with the Development Cohort to make The Final Cohort, again divided into training and testing sets, with MLA characteristics defined on test set. The MLA was validated using an independent EMR cohort.

Results

194 PAH and 786 “not PAH” in the Development Cohort trained and tested the initial MLA. In the Final Cohort test set, the final MLA sensitivity was 0.88, specificity was 0.93, positive predictive value was 0.89, and negative predictive value was 0.92. Persistence and strength of PAH medication use and CPT code for right heart catheterization were principal MLA features. Applying the MLA to the EMR cohort using a split cohort internal validation approach, we found 265 additional non-confirmed cases of suspected PAH that exhibited typical PAH demographics, comorbidities, hemodynamics.

Conclusions

We developed and validated a MLA using only CB features that identified PAH in the EMR with strong test characteristics. When deployed across an entire EMR, the MLA identified cases with known features of PAH.
Imbalanced prostanoid release mediates cigarette smoke-induced human pulmonary artery cell proliferation
Authors: Alqarni Abdullah A. , Brand Oliver J. , Pasini Alice , Alahmari Mushabbab , Alghamdi Abdulrhman , Pang Linhua
Published: May 2022

Background

Pulmonary hypertension is a common and serious complication of chronic obstructive pulmonary disease (COPD). Studies suggest that cigarette smoke can initiate pulmonary vascular remodelling by stimulating cell proliferation; however, the underlying cause, particularly the role of vasoactive prostanoids, is unclear. We hypothesize that cigarette smoke extract (CSE) can induce imbalanced vasoactive prostanoid release by differentially modulating the expression of respective synthase genes in human pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs), thereby contributing to cell proliferation.

Methods

Aqueous CSE was prepared from 3R4F research-grade cigarettes. Human PASMCs and PAECs were treated with or without CSE. Quantitative real-time RT-PCR and Western blotting were used to analyse the mRNA and protein expression of vasoactive prostanoid syhthases. Prostanoid concentration in the medium was measured using ELISA kits. Cell proliferation was assessed using the cell proliferation reagent WST-1.

Results

We demonstrated that CSE induced the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostanoid synthesis, in both cell types. In PASMCs, CSE reduced the downstream prostaglandin (PG) I synthase (PGIS) mRNA and protein expression and PGI2production, whereas in PAECs, CSE downregulated PGIS mRNA expression, but PGIS protein was undetectable and CSE had no effect on PGI2production. CSE increased thromboxane (TX) A synthase (TXAS) mRNA expression and TXA2production, despite undetectable TXAS protein in both cell types. CSE also reduced microsomal PGE synthase-1 (mPGES-1) protein expression and PGE2production in PASMCs, but increased PGE2production despite unchanged mPGES-1 protein expression in PAECs. Furthermore, CSE stimulated proliferation of both cell types, which was significantly inhibited by the selective COX-2 inhibitor celecoxib, the PGI2analogue beraprost and the TXA2receptor antagonist daltroban.

Conclusions

These findings provide the first evidence that cigarette smoke can induce imbalanced prostanoid mediator release characterized by the reduced PGI2/TXA2ratio and contribute to pulmonary vascular remodelling and suggest that TXA2may represent a novel therapeutic target for pulmonary hypertension in COPD.
Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study
Authors: Xiong Xiao-feng , Zhu Min , Wu Hong-xia , Fan Li-li , Cheng De-yun
Published: May 2022

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD).

Methods

A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated.

Results

A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = − 0.367, P = 0.009) and proportion of Th2 cells (r = − 0.655, P < 0.0001).

Conclusions

The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity.

Trial registration: China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://www.chictr.org.cn/index.aspx.
Association of ambulatory blood pressure with coronary microvascular and cardiac dysfunction in asymptomatic type 2 diabetes
Authors: Yeo Jian L. , Gulsin Gaurav S. , Brady Emer M. , Dattani Abhishek , Bilak Joanna M. , Marsh Anna-Marie , Sian Manjit , Athithan Lavanya , Parke Kelly S. , Wormleighton Joanne , Graham-Brown Matthew P. M. , Singh Anvesha , Arnold J. Ranjit , Lawson Claire , Davies Melanie J. , Xue Hui , Kellman Peter , McCann Gerry P.
Published: May 2022

Background

Type 2 diabetes (T2D) and hypertension commonly coexist and are associated with subclinical myocardial structural and functional changes. We sought to determine the association between blood pressure (BP) and left ventricular (LV) remodeling, systolic/diastolic function, and coronary microvascular function, among individuals with T2D without prevalent cardiovascular disease.

Methods

Participants with T2D and age-, sex-, and ethnicity-matched controls underwent comprehensive cardiovascular phenotyping including fasting bloods, transthoracic echocardiography, cardiovascular magnetic resonance imaging with quantitative adenosine stress/rest perfusion, and office and 24-h ambulatory BP monitoring. Multivariable linear regression was performed to determine independent associations between BP and imaging markers of remodeling and function in T2D.

Results

Individuals with T2D (n = 205, mean age 63 ± 7 years) and controls (n = 40, mean age 61 ± 8 years) were recruited. Mean 24-h systolic BP, but not office BP, was significantly greater among those with T2D compared to controls (128.8 ± 11.7 vs 123.0 ± 13.1 mmHg, p = 0.006). Those with T2D had concentric LV remodeling (mass/volume 0.91 ± 0.15 vs 0.82 ± 0.11 g/mL, p < 0.001), decreased myocardial perfusion reserve (2.82 ± 0.83 vs 3.18 ± 0.82, p = 0.020), systolic dysfunction (global longitudinal strain 16.0 ± 2.3 vs 17.2 ± 2.1%, p = 0.004) and diastolic dysfunction (E/e’ 9.30 ± 2.43 vs 8.47 ± 1.53, p = 0.044) compared to controls. In multivariable regression models adjusted for 14 clinical variables, mean 24-h systolic BP was independently associated with concentric LV remodeling (β = 0.165, p = 0.031), diastolic dysfunction (β = 0.273, p < 0.001) and myocardial perfusion reserve (β = − 0.218, p = 0.016). Mean 24-h diastolic BP was associated with LV concentric remodeling (β = 0.201, p = 0.016).

Conclusion

24-h ambulatory systolic BP, but not office BP, is independently associated with cardiac remodeling, coronary microvascular dysfunction, and diastolic dysfunction among asymptomatic individuals with T2D. (Clinical trial registration. URL: https://clinicaltrials.gov/ct2/show/NCT03132129 Unique identifier: NCT03132129).
Display of a novel carboxylesterase CarCby on Escherichia coli cell surface for carbaryl pesticide bioremediation
Authors: Liu Yan , Wang Xiaoliang , Nong Sujin , Bai Zehui , Han Nanyu , Wu Qian , Huang Zunxi , Ding Junmei
Published: May 2022

Background

Carbamate pesticides have been widely used in agricultural and forestry pest control. The large-scale use of carbamates has caused severe toxicity in various systems because of their toxic environmental residues. Carbaryl is a representative carbamate pesticide and hydrolase/carboxylesterase is the initial and critical enzyme for its degradation. Whole-cell biocatalysts have become a powerful tool for environmental bioremediation. Here, a whole cell biocatalyst was constructed by displaying a novel carboxylesterase/hydrolase on the surface of Escherichia coli cells for carbaryl bioremediation.

Results

The carCby gene, encoding a protein with carbaryl hydrolysis activity was cloned and characterized. Subsequently, CarCby was displayed on the outer membrane of E. coli BL21(DE3) cells using the N-terminus of ice nucleation protein as an anchor. The surface localization of CarCby was confirmed by SDS–PAGE and fluorescence microscopy. The optimal temperature and pH of the engineered E. coli cells were 30 °C and 7.5, respectively, using pNPC4 as a substrate. The whole cell biocatalyst exhibited better stability and maintained approximately 8-fold higher specific enzymatic activity than purified CarCby when incubated at 30 °C for 120 h. In addition, ~ 100% and 50% of the original activity was retained when incubated with the whole cell biocatalyst at 4 ℃ and 30 °C for 35 days, respectively. However, the purified CarCby lost almost 100% of its activity when incubated at 30 °C for 134 h or 37 °C for 96 h, respectively. Finally, approximately 30 mg/L of carbaryl was hydrolyzed by 200 U of the engineered E. coli cells in 12 h.

Conclusions

Here, a carbaryl hydrolase-containing surface-displayed system was first constructed, and the whole cell biocatalyst displayed better stability and maintained its catalytic activity. This surface-displayed strategy provides a new solution for the cost-efficient bioremediation of carbaryl and could also have the potential to be used to treat other carbamates in environmental bioremediation.
Heterologous expression of pediocin/papA in Bacillus subtilis
Authors: Wang Genyu , Guo Zhijun , Zhang Xueqian , Wu Hao , Bai XiuMei , Zhang Hailiang , Hu Richa , Han Shaoliang , Pang Yuanxiang , Gao Zi’ang , Yan Lili , Huang Cuiying , Zhang Le , Pan Chunli , Liu Xuelian
Published: May 2022

Listeria monocytogenes is a food-borne pathogen. Pediocin is a group IIα bacteriocin with anti-listeria activity that is naturally produced by Pediococcus acidilactic and Lactobacillus plantarum. The pedA/papA gene encodes pediocin/plantaricin. In native hosts, the expression and secretion of active PedA/PapA protein rely on the accessory protein PedC/PapC and ABC transporter PedD/PapD on the same operon. The excretion machines were also necessary for pediocin protein expression in heterologous hosts of E. coli, Lactobacillus lactis, and Corynebacterium glutamicum. In this study, two vectors carrying the codon sequence of the mature PapA peptide were constructed, one with and one without a His tag. Both fragments were inserted into the plasmid pHT43 and transformed into Bacillus subtilis WB800N. The strains were induced with IPTG to secrete the fused proteins PA1 and PA2. Supernatants from both recombinant strains can inhibit Listeria monocytogenes ATCC54003 directly. The fused protein possesses inhibition activity as a whole dispense with removal of the leading peptide. This is the first report of active pediocin/PapA expression without the assistance of PedCD/PapCD in heterogeneous hosts. In addition, the PA1 protein can be purified by nickel-nitrilotriacetic acid (Ni-NTA) metal affinity chromatography.
Engineering a carbohydrate-binding module to increase the expression level of glucoamylase in Pichia pastoris
Authors: Tong Lige , Huang Huoqing , Zheng Jie , Wang Xiao , Bai Yingguo , Wang Xiaolu , Wang Yuan , Tu Tao , Yao Bin , Qin Xing , Luo Huiying
Published: May 2022

Background

Glucoamylase is an important industrial enzyme for the saccharification of starch during sugar production, but the production cost of glucoamylase is a major limiting factor for the growth of the starch-based sugar market. Therefore, seeking strategies for high-level expression of glucoamylase in heterologous hosts are considered as the main way to reduce the enzyme cost.

Results

ReGa15A from Rasamsonia emersonii and TlGa15B-GA2 from Talaromyces leycettanus have similar properties. However, the secretion level of ReGa15A was significantly higher than TlGa15B-GA2 in Pichia pastoris. To explore the underlying mechanisms affecting the differential expression levels of glucoamylase in P. pastoris, the amino acid sequences and three-dimensional structures of them were compared and analyzed. First, the CBM region was identified by fragment replacement as the key region affecting the expression levels of ReGa15A and TlGa15B-GA2. Then, through the substitution and site-directed mutation of the motifs in the CBM region, three mutants with significantly increased expression levels were obtained. The eight-point mutant TlGA-M4 (S589D/Q599A/G600Y/V603Q/T607I/V608L/N609D/R613Q), the three-point mutant TlGA-M6 (Q599A/G600Y/V603Q) and the five-point mutant TlGA-M7 (S589D/T607I/V608L/N609D/R613Q) have the same specific activity with the wild-type, and the enzyme activity and secretion level have increased by 4–5 times, respectively. At the same time, the expression levels were 5.8-, 2.0- and 2.4-fold higher than that of wild type, respectively. Meanwhile, the expression of genes related to the unfolded protein responses (UPR) in the endoplasmic reticulum (ER) did not differ significantly between the mutants and wild type. In addition, the most highly expressed mutant, TlGA-M7 exhibits rapidly and effectively hydrolyze raw corn starch.

Conclusions

Our results constitute the first demonstration of improved expression and secretion of a glucoamylase in P. pastoris by introducing mutations within the non-catalytic CBM. This provides a novel and effective strategy for improving the expression of recombinant proteins in heterologous host expression systems.
Conversion of banana peel into diverse valuable metabolites using an autochthonous Rhodotorula mucilaginosa strain
Authors: Torres-Alvarez Dagoberto , León-Buitimea Angel , Albalate-Ramírez Alonso , Rivas-García Pasiano , Hernández-Núñez Emanuel , Morones-Ramírez José Rubén
Published: May 2022

Low-cost substrates are an exciting alternative for bioprocesses; however, their complexity can affect microorganism metabolism with non-desirable outcomes. This work evaluated banana peel extract (BPE) as a growth medium compared to commercial Yeast-Malt (YM) broth in the native and non-conventional yeast Rhodotorula mucilaginosa UANL-001L. The production of carotenoids, fatty acids, and exopolysaccharides (EPS) was also analyzed. Biomass concentration (3.9 g/L) and growth rate (0.069 g/h) of Rhodotorula mucilaginosa UANL-001L were obtained at 200 g/L of BPE. Yields per gram of dry biomass for carotenoids (317 µg/g) and fatty acids (0.55 g/g) showed the best results in 150 g/L of BPE, while 298 µg/g and 0.46 mg/g, respectively, were obtained in the YM broth. The highest yield of EPS was observed in 50 g/L of BPE, a two-fold increase (160.1 mg/g) compared to the YM broth (76.3 mg/g). The fatty acid characterization showed that 100 g/L of BPE produced 400% more unsaturated compounds (e.g., oleic and ricinoleic acid) than the YM broth. Altogether, these results indicate that BPE is a suitable medium for producing high-value products with potential industrial applications.
Measures of high-density lipoprotein function in men and women with severe aortic stenosis
Authors: Hafiane Anouar , Favari Elda , Bortnick Anna E.
Published: May 2022

Background

Calcification of the aortic valve is a common heart valve disorder, in some cases leading to clinically impactful severe aortic stenosis (AS). Sex-specific differences in aortic valve calcification (ACV) exist, with women having a lower burden of calcification than men as measured by computed tomography; however, the pathophysiological mechanism that leads to these differences remains unclear.

Methods

Using cultured human Tamm-Horsfall protein 1 (THP-1) macrophages and human aortic valve interstitial cells, the effects of high-density lipoprotein (HDL) particles isolated from the plasma of men and women with severe AS were studied for cholesterol efflux capacity (CEC).

Results

HDL-CEC was assessed in 46 patients with severe AS, n = 30 men, n = 16 women. ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC was measured from human cultured THP-1 macrophages to plasma HDL samples. Women with severe AS had more ABCA1-mediated HDL-CEC, as compared to men (8.50 ± 3.90% cpm vs. 6.80 ± 1.50% cpm, P = 0.04). HDL pre-β1 and α-particles were higher in woman than in men by spectral density, (pre-β1 HDL, 20298.29 ± 1076.15 vs. 15,661.74 ± 789.00, P = 0.002, and α-HDL, 63006.35 ± 756.81 vs. 50,447.00 ± 546.52, P = 0.03). Lecithin-cholesterol acyltransferase conversion of free cholesterol into cholesteryl esters was higher in women than men (16.44 ± 9.11%/h vs. 12.00 ± 8.07%/h, P = 0.03).

Conclusions

Sex-specific changes in various parameters of HDL-CEC were found in patients with severe AS. Sex-based modifications in HDL functionality by HDL-CEC might account for the reduced burden of calcification in women vs. men with severe AS. Therefore, future studies should target sex-related pathways in AS to help to improve understanding and treatment of AS.

Graphical abstract

Sex specifc differences in AVC and differences associated with HDL function in men and women with severe AS. When compared to men, women had higher preβ-HDL and α-HDL migrating particles, higher cholesterol efflux to HDL, and higher lecithin cholesterol acyl transferase (LCAT) activity, possibly indicating that improved reverse cholesterol transport may be protective against worsened calcification.
High-density lipoprotein cholesterol efflux capacity and incidence of coronary artery disease and cardiovascular mortality: a systematic review and meta-analysis
Authors: Cheng Wenke , Rosolowski Maciej , Boettner Julia , Desch Steffen , Jobs Alexander , Thiele Holger , Buettner Petra
Published: May 2022

Background

The preventive effect of cholesterol efflux capacity (CEC) on the progression of atherosclerotic lesions has been confirmed in animal models, but findings in the population are inconsistent. Therefore, this meta-analysis aimed to systematically investigate the relationship of CEC with coronary artery disease (CAD) and cardiovascular mortality in a general population.

Methods

Four electronic databases (PubMed, Embase database, Cochrane Library, Web of Science) were searched from inception to February 1st, 2022 for relevant studies, without any language restriction. For continuous variables, the mean and standard deviation (SD), maximum adjusted odds ratios (ORs), relative risks (RRs), or hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. The random-effects model was adopted to calculate the pooled results, and dose-response analyses were conducted. All pooled results were expressed by standardized mean difference (SMD) and ORs.

Results

Finally, 18 observational studies were included. Compared with the non-CAD group, the CAD group (SMD -0.48, 95% CI − 0.66 to − 0.30; I2 88.9%) had significantly lower CEC. In the high-CEC population, the risks of CAD (OR 0.52, 95% CI 0.37 to 0.71; I2 81%) significantly decreased, and a linear negative dose-response was detected. However, an association between CEC and the risk of cardiovascular mortality was not found (OR 0.44, 95% CI 0.18 to 1.06; I2 83.2%).

Conclusions

This meta-analysis suggests that decreased CEC is strongly associated with the risk of CAD, independent of HDL-C level. However, a decreased CEC seems not to be related to cardiovascular mortality. Meanwhile, CEC is linearly negatively correlated with the risk of CAD.
Best practices for community-based overdose education and naloxone distribution programs: results from using the Delphi approach
Authors: Wenger Lynn D. , Doe-Simkins Maya , Wheeler Eliza , Ongais Lee , Morris Terry , Bluthenthal Ricky N. , Kral Alex H. , Lambdin Barrot H.
Published: May 2022

Background

Opioid-related overdose deaths have surged in the USA over the last two decades. Overdose fatalities are preventable with the timely administration of naloxone. Syringe service programs (SSP) have pioneered community-based naloxone distribution through overdose prevention and naloxone distribution (OEND) programs. There is a dearth of information with regards to best practices for community-based OEND.

Methods

We utilized a modified Delphi approach to develop a set of best practices for OEND delivery. Starting with an initial list of best practices, we engaged 27 experts, in the field of OEND programming who reviewed, made recommendations for changes, and assigned a priority to each best practice.

Results

Two rounds of input resulted in a final list of 20 best practices organized into four categories. The mean priority scores ranged from 1.17 to 2.17 (range 1 to 3). The top 5 ranked best practices were ensuring that SSP participants have low barrier, consistent, needs-based access to naloxone and that there is ample naloxone available within communities. While the remaining fifteen best practices were deemed important, they had more to do with organizational culture and implementation climate.

Conclusions

Increasing community-based OEND delivery is essential to reduce opioid overdose deaths; however, it will be insufficient to add programs without an eye toward quality of implementation and fidelity to the model upon which the evidence is based. This list of best practices summarizes the consensus among OEND experts and can serve as a tool for SSPs providing OEND programming to improve services.
Partners matter: The psychosocial well-being of couples when dealing with endometriosis
Authors: Schick Maren , Germeyer Ariane , Böttcher Bettina , Hecht Stephanie , Geiser Magdalena , Rösner Sabine , Eckstein Monika , Vomstein Kilian , Toth Bettina , Strowitzki Thomas , Wischmann Tewes , Ditzen Beate
Published: May 2022

Background

Endometriosis is often associated with severe dysmenorrhea, pelvic pain and dyspareunia and has a high impact on daily life as well as sexuality. Quality of partnership positively influences the course of various diseases and ability to cope with emotional and physical distress. However, studies focusing on the male partners of endometriosis patients are rare, and even less is known about the reciprocal relationship in these couples. Therefore, this study aims to explore the interrelations in couples with endometriosis in matters of psychological distress, sexual and partnership satisfaction and social support.

Methods

The cross-sectional study was conducted in two university-affiliated fertility centres in Germany and Austria with n = 104 female/male couples affected by endometriosis. Participants completed a questionnaire regarding endometriosis, partnership, sexuality, stress, anxiety, depression and social support. Both women and men were asked about the impact of women’s endometriosis-related pain (IEP) on their everyday life (e.g. leisure time). Data were analysed using the Actor-Partner-Interdependence Model.

Results

Significant partner effects were evident: High depression, anxiety and stress scores in women were associated with a higher IEP in men (all p ≤ 0.01), reciprocally high stress and depression scores in men were correlated with a higher IEP in women (all p ≤ 0.05). Less sexual satisfaction in women was associated with a higher IEP in men (p = 0.040). There was a significant reciprocal association between the perceived lack of understanding from the social environment and a higher IEP, for both women (p = 0.022) and men (p = 0.027).

Conclusions

The male partner should be taken into account when counselling or treating women with endometriosis. Our study shows a high interdependence and reciprocal influence from both partners—positively and negatively—concerning psychological distress and sexual satisfaction. Furthermore, there ought to be more awareness for the psychosocial impact of endometriosis, especially in regard to social support and understanding. Talking about and improving sexual satisfaction as well as enhancing stress reducing techniques may hold great benefits for dealing with endometriosis.

Registration number The study is registered with the German Clinical Trials Register (DRKS), number DRKS00014362.
Proximal femur versus acetabular extra-articular resection of the hip joint for primary malignant bone tumors: a retrospective comparative review of 33 cases
Authors: Housset Victor , Anract Philippe , Babinet Antoine , Auberger Guillaume , Biau David
Published: May 2022

Introduction

Extra-articular resection (EAR) of the hip joint is prone to significant complications and morbidity. Thus, this study evaluates the cumulative incidences and main reasons of reoperation following EAR of primary malignant bone tumors (PMBT) of the hip to determine whether the outcomes are different between EAR of the pelvis and that of the proximal femur.

Patients and methods

Thirty-three patients presented with a PMBT of the proximal femur or pelvis were included in this study. Among all PMBTs, 58% originated from the pelvis and 42% were from the proximal femur. Twenty patients had chondrosarcomas (61%), 10 had osteosarcomas (30%), and 3 had sarcomas of another histological subtype (9%).

Results

The mean follow-up was of 76 months (range: 24–220 months). The cumulative probabilities of revision for any reason were 52% (95% confidence interval [CI] 30–70%) 5 years after surgery. The 5-year cumulative probabilities of revision were 13% (95% CI 4–27%), 24% (95% CI 10–42%), and 34% (95% CI 14–56%) for mechanical, infectious, and tumoral reasons, respectively. The 5-year cumulative probabilities of revision for any reason were 78% (95% CI 37–94%) and 14% (95% CI 2–38%) for the pelvis and proximal femur, respectively (p = 0.004). Posterior column preservation was significantly associated with more mechanical complications even after adjusting for the resection site (p = 0.043).

Conclusion

Half of patients undergoing EAR of the hip joint for PMBT of the proximal femur or acetabulum will require another operation. EAR of the pelvis is associated with significantly worse outcome than EAR of the proximal femur.
Systemic and central nervous system neuroinflammatory signatures of neuropsychiatric symptoms and related cognitive decline in older people
Authors: Clark Christopher , Richiardi Jonas , Maréchal Bénédicte , Bowman Gene L. , Dayon Loïc , Popp Julius
Published: May 2022

Background

Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer’s disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression.

Methods

We quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) samples in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits.

Results

NPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10-kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1.

Conclusions

Distinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression.
Doctors’ experiences providing sexual and reproductive health care at Catholic Hospitals in the conflict-affected North-West region of Cameroon: a qualitative study
Authors: Awasom-Fru Adama , Sop Sop Maturin Désiré , Larsson Elin Charlotte , Herzig van Wees Sibylle
Published: May 2022

Background

Sexual and reproductive health (SRH) care services are essential to improving the lives of women and achieving the Sustainable Development Goals. In Cameroon, the Catholic Church is one the largest non-governmental suppliers of health care, but its role in providing SRH care is restricted by religious norms.

Methods

This study explored doctors’ experiences and perceptions of providing SRH care at Catholic hospitals in a conflict-affected area in Cameroon by using 10 in-depth interviews with doctors from three Catholic hospitals in the North-West region. Qualitative coding was done with NVivo, and data were analysed using thematic analysis.

Results

Three themes and seven categories were identified. The respondents described strict rules and a broad range of challenges to providing comprehensive sexual and reproductive health care services. Nonetheless, there is evidence of doctors overcoming obstacles to providing SRH care despite the religious and political climate. However, whilst attempting to overcome challenges, participants described numerous examples of poor SRH care and health outcomes.

Conclusion

The study highlights the importance of understanding the intersect between religion and women’s health, particularly in improving access to SRH for vulnerable populations in conflict-affected areas. It further provides insight into doctors’ motivations in practicing medicine and how doctors cope and make efforts to provide care and minimize harm.