bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of diagnosis and health service codes in identifying frailty in Medicare data
Authors: Festa Natalia , Shi Sandra M. , Kim Dae Hyun
Published: September 2020

Background

Capturing frailty within administrative claims data may help to identify high-risk patients and inform population health management strategies. Although it is common to ascertain frailty status utilizing claims-based surrogates (e.g. diagnosis and health service codes) selected according to clinical knowledge, the accuracy of this approach has not yet been examined. We evaluated the accuracy of claims-based surrogates against two clinical definitions of frailty.

Methods

This cross-sectional study was conducted in a Health and Retirement Study subsample of 3097 participants, aged 65 years or older and with at least 12-months of continuous fee-for-service Medicare enrollment. We defined 18 previously utilized claims-based surrogates of frailty from Medicare data and evaluated each against clinical reference standards, ascertained from a direct examination: a deficit accumulation frailty index (FI) (range: 0–1) and frailty phenotype. We also compared the accuracy of the total count of 18 claims-based surrogates with that of a validated claims-based FI model, comprised of 93 claims-based variables.

Results

19% of participants met clinical criteria for the clinical frailty phenotype. The mean clinical FI for our sample was 0.20 (standard deviation 0.13). Hospital Beds and associated supplies was the claims-based surrogate associated with the highest clinical FI (mean FI 0.49). Claims-based surrogates had low sensitivity ranging from 0.01 (cachexia, adult failure to thrive, anorexia) to 0.38 (malaise and fatigue) and high specificity ranging from 0.79 (malaise and fatigue) to 0.99 (cachexia, adult failure to thrive, anorexia) in discriminating the clinical frailty phenotype. Compared with a validated claims-based FI, the total count of claims-based surrogates demonstrated lower Spearman correlation with the clinical FI (0.41 [95% CI 0.38–0.44] versus 0.59 [95% CI, 0.56–0.61]) and poorer discrimination of the frailty phenotype (C-statistics 0.68 [95% CI, 0.66–0.70] versus 0.75 [95% CI, 0.73–0.77]).

Conclusions

Claims-based surrogates, selected according to clinical knowledge, do not accurately capture frailty in Medicare claims data. A simple count of claims-based surrogates improves accuracy but remains inferior to a claims-based FI model.
Patients’ perceptions of frequent hospital admissions: a qualitative interview study with older people above 65 years of age
Authors: Huang Miaolin , van der Borght Carolien , Leithaus Merel , Flamaing Johan , Goderis Geert
Published: September 2020

Background

Although ‘frequent flyer’ hospital admissions represent barely 3 to 8% of the total patient population in a hospital, they are responsible for a disproportionately high percentage (12 to 28%) of all admissions. Moreover, hospital admissions are an important contributor to health care costs and overpopulation in various hospitals. The aim of this research is to obtain a deeper insight into the phenomenon of frequent flyer hospital admissions. Our objectives were to understand the patients’ perspectives on the cause of their frequent hospital admissions and to identify the perceived consequences of the frequent flyer status.

Methods

This qualitative study took place at the University Hospital of Leuven. The COREQ guidelines were followed to provide rigor to the study. Patients were included when they had at least four overnight admissions in the past 12 months, an age above 65 years and hospital admission at the time of the study. Data were collected via semi-structured interviews and encoded in NVivo.

Results

Thirteen interviews were collected. A total of 17 perceived causes for frequent hospital admission were identified, which could be divided into the following six themes: patient, drugs, primary care, secondary care, home and family. Most of the causes were preventable or modifiable. The perceived consequences of being a frequent flyer were divided into the following six themes: body, daily life functioning, social participation, mental status and spiritual dimension. Negative experiences were linked to frequent flying and could be situated mainly in the categories of social participation, mental status and spiritual dimensions.

Conclusions

Frequent hospital admissions may be conceived as an indicator, i.e., a ‘red flag’, of patients’ situations characterized by physical, mental, spiritual and social deprivation in their home situation.
Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017)
Authors: Scheibe Andrew , Young Katherine , Versfeld Anna , Spearman C. Wendy , Sonderup Mark W. , Prabdial-Sing Nishi , Puren Adrian , Hausler Harry
Published: September 2020

Background

People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses.

Methods

We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested.

Results

Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%).

Conclusions

HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.
Comparative efficacy of placebos in short-term antidepressant trials for major depression: a secondary meta-analysis of placebo-controlled trials
Authors: Holper Lisa , Hengartner Michael P.
Published: September 2020

Background

The issue of unblinded outcome-assessors and patients has repeatedly been stressed as a flaw in allegedly double-blind antidepressant trials. Unblinding bias can for example result from a drug‘s marked side effects. If such unblinding bias is present for a given drug, then it might be expected that the placebos of that drug are rated significantly less effective than that of other antidepressants.

Methods

To test this hypothesis, the present exploratory analysis conducted a Bayesian network meta-analysis (NMA) comparing the efficacy of 19 different placebos in placebo-controlled trials provided in the dataset by Cipriani et al. (Lancet 2018; 391: 1357–66). Primary outcome was efficacy (continuous) estimated on the standardized mean difference (SMD) scale and defined as the pre-post change on the Hamilton Depression scale (HAMD-17), on which information was available in N = 258 trials.

Results

Comparative placebo ranking suggested mirtazapine-placebo (SMD -2.0 [− 5.0–1.0 95% CrI]) to be the most, and amitriptyline- (SMD 1.2 [− 1.6–3.9 95% CrI]) and trazodone- (SMD 2.1 [− 0.9–5.2 95% CrI]) placebos to be the least effective placebos. Other placebos suggested to be more effective than amitriptyline- and trazodone-placebos (based on 95% CrIs excluding zero) were citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine placebos. These NMA results were corroborated by the observation that the relative efficacy between drug and placebo was considerably larger for amitriptyline and trazodone than for instance mirtazapine, duloxetine, and venlafaxine, supported by a small and insignificant correlation between drug-efficacy and placebo-efficacy (r = − 0.202, p = 0.408).

Discussion

The present exploratory NMA indicates that distinguishable side effects of older drugs may unblind outcome-assessors thus resulting in overestimation of the average drug-placebo difference and underrating bias in placebo-arms, particularly for the older antidepressant drugs amitriptyline and trazodone. If confirmed in prospective studies, these findings suggest that efficacy rankings for antidepressants are susceptible to bias and should be considered unreliable or misleading. The analysis is limited by the focus on the single-comparison placebos (76%, i.e., placebos assessed in two-arm trials), since double-comparison placebos (25%, i.e., placebos assessed in three-arm trials) are hard to interpret and therefore not included in the present interpretation. Another limitation is the problem of multiplicity, which was only approximately accounted for in the Bayesian NMA by modelling treatment effects as exchangeable.
The role of tobacco and alcohol use in the interaction of social determinants of non-communicable diseases in Nepal: a systems perspective
Authors: Sharma Sudesh Raj , Matheson Anna , Lambrick Danielle , Faulkner James , Lounsbury David W. , Vaidya Abhinav , Page Rachel
Published: September 2020

Background

Tobacco and alcohol use are major behavioural risks in developing countries like Nepal, which are contributing to a rapid increase in non-communicable diseases (NCDs). This causal relationship is further complicated by the multi-level social determinants such as socio-political context, socio-economic factors and health systems. The systems approach has potential to facilitate understanding of such complex causal mechanisms. The objective of this paper is to describe the role of tobacco and alcohol use in the interaction of social determinants of NCDs in Nepal.

Method

The study adopted a qualitative study design guided by theSystemic Interventionmethodology. The study involved key informant interviews (n = 63) and focus group discussions (n = 12) at different levels (national, district and/or community) and was informed by the adaptedSocial Determinants of Health Framework. The data analysis involved case study-based thematic analysis using framework approach and development of causal loop diagrams. The study also involved three sense-making sessions with key stakeholders.

Results

Three key themes and causal loop diagrams emerged from the data analysis. Widespread availability of tobacco and alcohol products contributed to the use and addiction of tobacco and alcohol. Low focus on primary prevention by health systems and political influence of tobacco and alcohol industries were the major contributors to the problem. Gender and socio-economic status of families/communities were identified as key social determinants of tobacco and alcohol use.

Conclusion

Tobacco and alcohol use facilitated interaction of the social determinants of NCDs in the context of Nepal. Socio-economic status of families was both driver and outcome of tobacco and alcohol use. Health system actions to prevent NCDs were delayed mainly due to lack of system insights and commercial influence. A multi-sectoral response led by the health system is urgently needed.
Comparison of oral health behaviour between dental and non-dental undergraduates in a university in southwestern China——exploring the future priority for oral health education
Authors: Li Mingming , Wu Zhiwu , Zhang Rui , Lei Lei , Ye Siqi , Cheng Ran , Hu Tao
Published: September 2020

Background

Based on a national survey in 2015, people’s oral health behaviour (OHB) has not kept up with the pace of knowledge and attitudes in China after decades of oral health education (OHE). Thus, we need to improve OHE to strengthen people’s OHB. Undergraduates are regarded as the best candidates for the improvement of OHE. The objective of this study is to determine undergraduates’ oral health status and existing problems in OHB by comparing dental and non-dental students at Sichuan University. We hope to provide some suggestions for future OHE to improve people’s OHB.

Methods

A quasi-experimental study designed with a pre-test and post-test group was conducted. A total of 217 dental students and 135 non-dental students were enrolled. They were administered an OHE course focused on OHB. A survey about oral health behaviour and knowledge was conducted before and after the course.

Results

According to the pre-course survey, dental students surpassed non-dental students in terms of toothbrushing frequency, method, and time, but unfortunately, flossing was overlooked by all the students. After the course, both dental and non-dental students showed strong willingness to improve their OHB. More non-dental students than dental students were willing to use toothpicks and Chinese herbal toothpaste before and after the course.

Conclusions

OHE focused on behaviour has a positive effect on university students. Future OHE and interventions should focus on flossing, toothbrushing methods, toothpicks, Chinese herbal toothpaste and modifications to adopt new media.
Development, implementation, and prospective validation of a model to predict 60-day end-of-life in hospitalized adults upon admission at three sites
Authors: Major Vincent J. , Aphinyanaphongs Yindalon
Published: September 2020

Background

Automated systems that use machine learning to estimate a patient’s risk of death are being developed to influence care. There remains sparse transparent reporting of model generalizability in different subpopulations especially for implemented systems.

Methods

A prognostic study included adult admissions at a multi-site, academic medical center between 2015 and 2017. A predictive model for all-cause mortality (including initiation of hospice care) within 60 days of admission was developed. Model generalizability is assessed in temporal validation in the context of potential demographic bias. A subsequent prospective cohort study was conducted at the same sites between October 2018 and June 2019. Model performance during prospective validation was quantified with areas under the receiver operating characteristic and precision recall curves stratified by site. Prospective results include timeliness, positive predictive value, and the number of actionable predictions.

Results

Three years of development data included 128,941 inpatient admissions (94,733 unique patients) across sites where patients are mostly white (61%) and female (60%) and 4.2% led to death within 60 days. A random forest model incorporating 9614 predictors produced areas under the receiver operating characteristic and precision recall curves of 87.2 (95% CI, 86.1–88.2) and 28.0 (95% CI, 25.0–31.0) in temporal validation. Performance marginally diverges within sites as the patient mix shifts from development to validation (patients of one site increases from 10 to 38%). Applied prospectively for nine months, 41,728 predictions were generated in real-time (median [IQR], 1.3 [0.9, 32] minutes). An operating criterion of 75% positive predictive value identified 104 predictions at very high risk (0.25%) where 65% (50 from 77 well-timed predictions) led to death within 60 days.

Conclusion

Temporal validation demonstrates good model discrimination for 60-day mortality. Slight performance variations are observed across demographic subpopulations. The model was implemented prospectively and successfully produced meaningful estimates of risk within minutes of admission.
Trends in the use of computerized physician order entry by health-system affiliated ambulatory clinics in the United States, 2014–2016
Authors: Fischer Shira H. , Rudin Robert S. , Shi Yunfeng , Shekelle Paul , Amill-Rosario Alejandro , Scanlon Dennis , Damberg Cheryl L.
Published: September 2020

Background

Computerized provider order entry (CPOE) can help providers deliver better quality care. We aimed to understand recent trends in use of CPOE by health system-affiliated ambulatory clinics.

Methods

We analyzed longitudinal data (2014–2016) for 19,109 ambulatory clinics that participated in all 3 years of the Healthcare Information and Management Systems Society Analytics survey to assess use of CPOE and identify characteristics of clinics associated with CPOE use.

We calculated descriptive statistics to examine overall trends in use, location of order entry (bedside vs. clinical station), and system-level use CPOE across all clinics. We used linear probability models to explore the association between clinic characteristics (practice size, practice type, and health system type) and two outcomes of interest: CPOE use at any point between 2014 and 2016, and CPOE use beginning in 2015 or 2016.

Results

Between 2014 and 2016, use of CPOE increased more than 9 percentage points from 58 to 67%. Larger clinics and those affiliated with multi-hospital health systems were more likely to have reported use of CPOE. We found no difference in CPOE use by primary care versus specialty care clinics. When used, most clinics reported using CPOE for most or all of their orders. Health systems that used CPOE usually did so for all system-affiliated clinics.

Conclusions

Small practice size or not being part of a multi-hospital system are associated with lower use of CPOE between 2014 and 2016. Less than optimal use in these environments may be harming patient outcomes.
Correction to: Activation and enhancement of caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies
Authors: Xie Yunchang , Chen Jiawen , Wang Bo , Chen Tai , Chen Junyu , Zhang Yuan , Liu Xiaoying , Chen Qi
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
MiR-1231 decrease the risk of cancer-related mortality in patients combined with non-small cell lung cancer and diabetes mellitus
Authors: Li Jing , Xu Jialiang , Cao Zhijun , Du Shouzuo , Zhang Luyu
Published: September 2020

Background

Non-small cell lung cancer (NSCLC) is a deadly human malignancy, and previous studies support the contribution of microRNAs (miRNAs) to cancer assessment. It has been reported that miR-1231 can be used as a biomarker to assess prognosis in different cancers. However, the prognostic value of miR-1231 in NSCLC patients with comorbid diabetes mellitus (DM) remains unclear. The present study evaluated the risk factors for NSCLC with DM and developed a predictive model for it.

Methods

A real-world study was conducted, including data from 108 patients with NSCLC combined with DM from April 1, 2010, to June 1, 2015. MiR-1231 was recorded during hospital admission. Cox-proportional hazards model was applied for survival analysis of risk factors for cancer-related mortality and to create nomograms for prediction. The accuracy of the model was evaluated by C-index and calibration curves.

Results

The mortality rate in the high miR-1231 level (≥ 1.775) group was 57.4%. On the basis of univariate analysis, we put factors (P < 0.05) into multivariate regression models, and high miR-1231 levels (P < 0.001, HR = 0.57), surgery (P < 0.001, HR = 0.37) and KPS score > 80 (P = 0.01, HR = 0.47) had a better prognosis and were considered as independent protective factors. These independently relevant factors were used to create nomograms to predict long-term patient survival. Nomogram showed good accuracy in risk estimation with a guide-corrected C-index of 0.691.

Conclusion

MiR-1231 reduced the risk of cancer-related death in patients with combined NSCLC and DM. Nomogram based on multivariate analysis showed good accuracy in estimating the overall risk of death.
Beliefs, perceptions and practices of chiropractors and patients about mitigation strategies for benign adverse events after spinal manipulation therapy
Authors: Funabashi Martha , Pohlman Katherine A. , Goldsworthy Rachel , Lee Alex , Tibbles Anthony , Mior Silvano , Kawchuk Greg
Published: September 2020

Background

Approximately 50% of patients who receive spinal manipulative therapy (SMT) experience some kind of adverse event (AE), typically benign and transient in nature. Regardless of their severity, mitigating benign AEs is important to improve patient experience and quality of care. The aim of this study was to identify beliefs, perceptions and practices of chiropractors and patients regarding benign AEs post-SMT and potential strategies to mitigate them.

Methods

Clinicians and patients from two chiropractic teaching clinics were invited to respond to an 11-question survey exploring their beliefs, perceptions and practices regarding benign AEs post-SMT and strategies to mitigate them. Responses were analyzed using descriptive statistics.

Results

A total of 39 clinicians (67% response rate) and 203 patients (82.9% response rate) completed the survey. Most clinicians (97%) believed benign AEs occur, and 82% reported their own patients have experienced one. For patients, 55% reported experiencing benign AEs post-SMT, with the most common symptoms being pain/soreness, headache and stiffness. While most clinicians (61.5%) reported trying a mitigation strategy with their patients, only 21.2% of patients perceived their clinicians had tried any mitigation strategy. Clinicians perceived that patient education is most likely to mitigate benign AEs, followed by soft tissue therapy and/or icing after SMT. Patients perceived stretching was most likely to mitigate benign AEs, followed by education and/or massage.

Conclusions

This is the first study comparing beliefs, perceptions and practices from clinicians and patients regarding benign AEs post-SMT and strategies to mitigate them. This study provides an important step towards identifying the best strategies to improve patient safety and improve quality of care.
Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia
Authors: Gu Runxia , Liu Fang , Zou Dehui , Xu Yingxi , Lu Yang , Liu Bingcheng , Liu Wei , Chen Xiaojuan , Liu Kaiqi , Guo Ye , Gong Xiaoyuan , Lv Rui , Chen Xia , Zhou Chunlin , Zhong Mengjun , Wang Huijun , Wei Hui , Mi Yingchang , Qiu Lugui , Lv Lulu , Wang Min , Wang Ying , Zhu Xiaofan , Wang Jianxiang
Published: September 2020

Background

Recent evidence suggests that resistance to CD19 chimeric antigen receptor (CAR)-modified T cell therapy may be due to the presence of CD19 isoforms that lose binding to the single-chain variable fragment (scFv) in current use. As such, further investigation of CARs recognize different epitopes of CD19 antigen may be necessary.

Methods

We generated a new CD19 CAR T (HI19α-4-1BB-ζ CAR T, or CNCT19) that includes an scFv that interacts with an epitope of the human CD19 antigen that can be distinguished from that recognized by the current FMC63 clone. A pilot study was undertaken to assess the safety and feasibility of CNCT19-based therapy in both pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).

Results

Data from our study suggested that 90% of the 20 patients treated with infusions of CNCT19 cells reached complete remission or complete remission with incomplete count recovery (CR/CRi) within 28 days. The CR/CRi rate was 82% when we took into account the fully enrolled 22 patients in an intention-to-treat analysis. Of note, extramedullary leukemia disease of two relapsed patients disappeared completely after CNCT19 cell infusion. After a median follow-up of 10.09 months (range, 0.49–24.02 months), the median overall survival and relapse-free survival for the 20 patients treated with CNCT19 cells was 12.91 months (95% confidence interval [CI], 7.74–18.08 months) and 6.93 months (95% CI, 3.13–10.73 months), respectively. Differences with respect to immune profiles associated with a long-term response following CAR T cell therapy were also addressed. Our results revealed that a relatively low percentage of CD8+ naïve T cells was an independent factor associated with a shorter period of relapse-free survival (p = 0.012, 95% CI, 0.017–0.601).

Conclusions

The results presented in this study indicate that CNCT19 cells have potent anti-leukemic activities in patients with R/R B-ALL. Furthermore, our findings suggest that the percentage of CD8+ naïve T cells may be a useful biomarker to predict the long-term prognosis for patients undergoing CAR T cell therapy.

Trial registration

ClinicalTrials.gov: NCT02975687; registered 29 November, 2016. https://clinicaltrials.gov/ct2/keydates/NCT02975687
Severe haemophilia a in a preterm girl with turner syndrome - a case report from the prenatal period to early infancy (part I)
Authors: Berendt Agnieszka , Wójtowicz-Marzec Monika , Wysokińska Barbara , Kwaśniewska Anna
Published: September 2020

Background

Bleedings are more frequent in the population of preterm children than among those born at term, much less in older children. The reasons for such bleedings in preterms include plasma factor deficiencies, immaturity of small vessels in the germinal matrix region, prenatal hypoxia or sepsis. They affect the brain tissue, the gastrointestinal tract and the respiratory system, or are manifested by prolonged bleedings from injection sites. Haemophilia is a rare cause of haemorrhages in the neonatal period, and in the female population it is even seen as an extremely rare disorder. Its aetiology in girls is diverse: inheriting defective genes from their parents, skewed X inactivation or a single X chromosome.

Case presentation

The article presents a case of a preterm girl born in the 28th week of pregnancy, who was diagnosed with severe haemophilia A stemming from the absence of the X chromosome. The girl’s father is healthy, but her mother’s brother suffers from haemophilia.

On the second day of the child’s life, a prolonged bleeding from the injection site was observed. A coagulation profile revealed prolonged APTT which pointed to haemophilia A diagnosis. Moreover, a marked clinical dysmorphy, female sex and a negative family history on the father’s side led the treating team to extend the diagnostic procedures to encompass karyotype evaluation. The girl was diagnosed with Turner syndrome. No bleeding to the central nervous system was observed during her hospital stay.

Conclusions

Preterm children belong to the risk group of bleeding into the central nervous system or haemorrhages in the course of sepsis. Rare causes of such bleedings should also be borne in mind, including haemophilia.

The initial symptoms of haemophilia in preterm children occur in the first days of their lives, which is connected with a number of invasive procedures required in that period.

Genetic conditions may coexist with one another. Arriving at one diagnosis does not mean one should abandon further diagnostic procedures in cases where additional atypical symptoms are present which do not match the clinical image of a primary disease.
Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance
Authors: Martínez-Valladares María , Valderas-García Elora , Gandasegui Javier , Skuce Philip , Morrison Alison , Castilla Gómez de Agüero Verónica , Cambra-Pellejà Maria , Balaña-Fouce Rafael , Rojo-Vázquez Francisco A.
Published: September 2020

Background

Benzimidazole resistance is associated with isotype-1 β-tubulin gene F200Y, E198A and F167Y SNPs. In this study, the recently described polymorphism E198L was reported and analysed in Teladorsagia circumcincta.

Methods

The benzimidazole phenotypic resistance was measured by the faecal egg count reduction test (FECRT) and the egg hatch test (EHT) using a discriminating dose (DD) in 39 sheep flocks. Around 1000 larvae collected before and after treatment were used for DNA extraction. The resistant species identified in all flocks was T. circumcincta. The resistance alleles frequencies were measured for F200Y and E198A. A 371-bp fragment of the isotype-1 β-tubulin gene was analysed, including the three codons of interest, and a new pyrosequencing assay was designed for testing E198L.

Results

The percentage of resistant flocks was 35% by FECRT or 26% by EHT; however, F200Y and E198A SNPs were absent in T. circumcincta. The amplification of a 371-bp fragment confirmed the absence of F167Y and F200Y in 6 resistant flocks. Regarding codon 198, all samples after treatment carried a leucine (CTA). A pyrosequencing assay analysed the allele frequencies for the first two bases at codon 198 independently, G/C and A/T. The correlation between C and T frequencies was almost 1 (r = 0.929, P < 0.0001) and the mean value of both was calculated to measure the leucine frequency; this value ranged between 10.4–80.7% before treatment, and 82.3–92.8% after treatment. High and similar correlations were reported between the genotypic variables (C frequency, T frequency or mean of both frequencies) and phenotypic resistance (r > 0.720, P < 0.0001), although negatively associated with the FECRT and positively with the EHT. According to multivariate linear regression analysis, the T frequency was the most significant variable influencing the phenotypic resistance (FECRT or EHT; P < 0.0001). In the EHT, 67.1% of the phenotypic variability is associated with the T frequency but in the FECRT only 33.4%; therefore, the EHT using a DD seems to detect the genotypic resistance more accurately than the FECRT.

Conclusions

The E198L polymorphism can confer BZ resistance on its own in T. circumcincta.
Associations of maternal early-pregnancy blood glucose and insulin concentrations with DNA methylation in newborns
Authors: Geurtsen Madelon L. , Jaddoe Vincent W. V. , Gaillard Romy , Felix Janine F.
Published: September 2020

Background

Intrauterine exposure to a disturbed maternal glucose metabolism is associated with adverse offspring outcomes. DNA methylation is a potential mechanism underlying these associations. We examined whether maternal early-pregnancy glucose and insulin concentrations are associated with newborn DNA methylation. In a population-based prospective cohort study among 935 pregnant women, maternal plasma concentrations of non-fasting glucose and insulin were measured at a median of 13.1 weeks of gestation (95% range 9.4–17.4). DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Ilumina). We analyzed associations of maternal early-pregnancy glucose and insulin concentrations with single-CpG DNA methylation using robust linear regression models. Differentially methylated regions were analyzed using the dmrff package in R. We stratified the analyses on normal weight versus overweight or obese women. We also performed a look-up of CpGs and differently methylated regions from previous studies to be associated with maternal gestational diabetes, hyperglycemia or hyperinsulinemia, or with type 2 diabetes in adults.

Results

Maternal early-pregnancy glucose and insulin concentrations were not associated with DNA methylation at single CpGs nor with differentially methylated regions in the total group. In analyses stratified on maternal BMI, maternal early-pregnancy glucose concentrations were associated with DNA methylation at one CpG (cg03617420,XKR6) among normal weight women and at another (cg12081946,IL17D) among overweight or obese women. No stratum-specific associations were found for maternal early-pregnancy insulin concentrations. The two CpGs were not associated with birth weight or childhood glycemic measures (pvalues > 0.1). Maternal early-pregnancy insulin concentrations were associated with one CpG known to be related to adult type 2 diabetes. Enrichment among nominally significant findings in our maternal early-pregnancy glucose concentrations was found for CpGs identified in a previous study on adult type 2 diabetes.

Conclusions

Maternal early-pregnancy glucose concentrations, but not insulin concentrations, were associated with DNA methylation at one CpG each in the subgroups of normal weight and of overweight or obese women. No associations were present in the full group. The role of these CpGs in mechanisms underlying offspring health outcomes needs further study. Future studies should replicate our results in larger samples with early-pregnancy information on maternal fasting glucose metabolism.
hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β1/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats
Authors: Cui Linlu , Bao Hongchu , Liu Zhongfeng , Man Xuejing , Liu Hongyuan , Hou Yun , Luo Qianqian , Wang Siyuan , Fu Qiang , Zhang Hongqin
Published: September 2020

Objective

The basic pathological changes of primary ovarian insufficiency (POI) include ovarian tissue fibrosis and follicular development disorders. The human umbilical cord mesenchymal stem cell (hUMSC) transplantation has been shown an effective method to improve the ovarian function in POI rat model; however, the exact mechanisms are still unclear. The purpose of this study is to investigate whether the recovery of ovarian function in POI rats is related to the inhibition of tissue fibrosis following hUMSC transplantation. Furthermore, the transforming growth factor-β1(TGF-β1) signaling pathway is explored to determine the mechanisms of ovarian function recovery through its inhibition of tissue fibrosis.

Methods

The primary ovarian insufficiency (POI) rat model was established by intraperitoneal injection of chemotherapy drug cisplatin (CDDP) for 7 days. The levels of serum sex hormones were measured using enzyme-linked immunosorbent assay (ELISA). The tissue fibrosis in the ovary was examined using Masson staining and Sirius red staining. The collagen fibers in the ovarian tissues were detected by Western blot analysis. To investigate the mechanisms of ovarian function recovery following hUMSC transplantation, ovarian stromal cells were isolated from the ovarian cortex of immature rats. The expression of Cytochrome P450 17A1 (Cyp17a1) and fibrosis marker of alpha smooth muscle actin (α-SMA) in ovarian stromal cells was examined using immunofluorescence analysis. Also, the protein levels of Cyp17a1 and α-SMA in ovarian stromal cells were examined by Western blot analysis. The expression of TGF-β1and Smad3 signals was measured by Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.

Results

The results show that the function of the ovary in POI rats was significantly improved after hUMSC transplantation. The expression of fibrosis markers (α-SMA) and production of Collagen Type I (Collagen I) and Collagen Type III (Collagen III) in POI rats were significantly inhibited in POI rats following hUMSC transplantation. In the cultured ovarian stromal cells, the decrease of TGF-β1and p-Smad3 protein expression was observed in hUMSC-treated POI rats. The treatment with TGF-β1inhibitor of SB431542 further confirmed this signal pathway was involved in the process.

Conclusion

Our study demonstrated that the TGF-β1/Smad3 signaling pathway was involved in the inhibition of ovarian tissue fibrosis, which contributed to the restoration of ovarian function in POI rats following hUMSC transplantation.
Regeneration of a full-thickness defect of rotator cuff tendon with freshly thawed umbilical cord-derived mesenchymal stem cells in a rat model
Authors: Yea Ji-Hye , Park Jin-Kyung , Kim In Ja , Sym Gayoung , Bae Tae-Soo , Jo Chris Hyunchul
Published: September 2020

Background

It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model.

Methods

We evaluated morphology, viability, and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs, respectively. Two and 4 weeks later, macroscopic, histological, biomechanical, and cell trafficking were evaluated. T test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant.

Results

T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was more recovered at 2 and 4 weeks such as inflammation, defect size, neighboring tendon, swelling/redness, the connecting surrounding tissue and slidability. Histologically, the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization, and fiber coherence were improved by 33.33%, 42.75%, 1.86-fold, and 1.99-fold at 4 weeks, and GAG-rich area decreased by 88.13% and 94.70% at 2 and 4 weeks respectively. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both 2 and 4 weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Moreover, T-UC MSCs remained 8.77% at 4 weeks after injury, and there was no significant difference between C-UC MSCs and T-UC MSCs.

Conclusions

The morphology, viability, and proliferation of T-UC MSCs were comparable to those of C-UC MSCs. Treatment with T-UC MSCs could induce tendon regeneration of FTD at the macroscopic, histological, and biomechanical levels comparable to treatment with C-UC MSCs.
Multipotent adult progenitor cells grown under xenobiotic-free conditions support vascularization during wound healing
Authors: Vaes Bart , Van Houtven Ellen , Caluwé Ellen , Luttun Aernout
Published: September 2020

Background

Cell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. Here, the potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated.

Methods

The potential of XF-hMAPC cells to support blood vessel formation was first scored in an in vivo Matrigel assay in mice. Next, a dose-response study was performed with XF-hMAPC cells in which they were tested for their ability to support vascularization and (epi) dermal healing in a physiologically relevant splinted wound mouse model.

Results

XF-hMAPC cells supported blood vessel formation in Matrigel by promoting the formation of mature (smooth muscle cell-coated) vessels. Furthermore, XF-hMAPC cells dose-dependently improved wound vascularization associated with increasing wound closure and re-epithelialization, granulation tissue formation, and dermal collagen organization.

Conclusions

Here, we demonstrated that the administration of clinical-grade XF-hMAPC cells in mice represents an effective approach for improving wound vascularization and healing that is readily applicable for translation in humans.
Bacillus velezensis 83 a bacterial strain from mango phyllosphere, useful for biological control and plant growth promotion
Authors: Balderas-Ruíz Karina A. , Bustos Patricia , Santamaria Rosa I. , González Víctor , Cristiano-Fajardo Sergio Andrés , Barrera-Ortíz Salvador , Mezo-Villalobos Miriam , Aranda-Ocampo Sergio , Guevara-García Ángel Arturo , Galindo Enrique , Serrano-Carreón Leobardo
Published: September 2020

Bacillus velezensis 83 was isolated from mango tree phyllosphere of orchards located in El Rosario, Sinaloa, México. The assessment of this strain as BCA (biological control agent), as well as PGPB (plant growth-promoting bacteria), were demonstrated through in vivo and in vitro assays. In vivo assays showed that B. velezensis 83 was able to control anthracnose (Kent mangoes) as efficiently as chemical treatment with Captan 50 PH™ or Cupravit hidro™. The inoculation of B. velezensis 83 to the roots of maize seedlings yielded an increase of 12% in height and 45% of root biomass, as compared with uninoculated seedlings. In vitro co-culture assays showed that B. velezensis 83 promoted Arabidopsis thaliana growth (root and shoot biomass) while, under the same experimental conditions, B. velezensis FZB42 (reference strain) had a suppressive effect on plant growth. In order to characterize the isolated strain, the complete genome sequence of B. velezensis 83 is reported. Its circular genome consists of 3,997,902 bp coding to 3949 predicted genes. The assembly and annotation of this genome revealed gene clusters related with plant-bacteria interaction and sporulation, as well as ten secondary metabolites biosynthetic gene clusters implicated in the biological control of phytopathogens. Despite the high genomic identity (> 98%) between B. velezensis 83 and B. velezensis FZB42, they are phenotypically different. Indeed, in vitro production of compounds such as surfactin and bacillomycin D (biocontrol activity) and γ-PGA (biofilm component) is significantly different between both strains.
Technical and environmental characterization of dual-purpose cattle farms and ways of improving production: A case study in Colombia
Authors: González-Quintero Ricardo , Barahona-Rosales Rolando , Bolívar-Vergara Diana María , Chirinda Ngonidzashe , Arango Jacobo , Pantévez Heiber Alexander , Correa-Londoño Guillermo , Sánchez-Pinzón María Solange
Published: September 2020

There are few reports on dual-purpose cattle systems characterization in Latin America and Colombia based on large datasets. This limits our understanding of their dynamics, and the establishment of public policies and government programs to improve their productive performance, promotion and rural development. This study aimed to characterize very small, small, medium, and large dual-purpose farms in Colombia from technical and environmental perspectives. The data analysed were obtained from the Ganadería Colombiana Sostenible and the LivestockPlus projects, which gathered information from a total of 1313 dual-purpose farms in Colombia. Farms were classified as being either very small (1 to 30 bovines), small (31 to 50 bovines), medium (51 to 250 bovines), or large farms (more than 251 bovines). Numerical and categorical variables were distributed into five components: (1) General Farm Information, (2) Herd Composition and Management, (3) Pasture Management, (4) Production Information, and (5) Environmental Information. Each component was analysed using the factorial analysis of mixed data (FAMD) method. According to FAMD, for the components General Farm Information, Herd Composition and Management, Pasture Management, and Production Information, the distribution of variables led to a spatial separation of the centroid from each category of producers. For the component Environmental Information, there was no separation of the centroid. In general, medium-sized and large farms showed better infrastructure, better machinery and equipment, and better reproductive practices; however, this was not reflected in a significant improvement of productive parameters, except for a lower mortality rate. Larger livestock producers need to plan their livestock husbandry activities properly, based on their better available infrastructure and livestock management practices, with the purpose of increasing productivity. The main features identified for each livestock producer category can be the basis to guide and establish policies and programmes for their technological development. The development of better livestock management practices and the implementation of technology, as well as technical assistance, should focus on small- and medium-sized livestock producers, which could lead to reaching a better productive and reproductive performance of dual-purpose systems.
The need for post-operative vasopressor infusions after major gynae-oncologic surgery within an ERAS (Enhanced Recovery After Surgery) pathway
Authors: Bossy Michèle , Nyman Molly , Madhuri Thumuluru Kavitha , Tailor Anil , Chatterjee Jayanta , Butler-Manuel Simon , Ellis Patricia , Feldheiser Aarne , Creagh-Brown Ben
Published: September 2020

Background

Hypotension following major abdominal surgery is common, and once hypovolaemia has been optimally treated, is often due to vasodilation which can be treated with vasopressor infusions. There is unpredictability in the dose and duration of post-operative vasopressor infusions, and factors associated with this have not been determined.

Methods

We present a case series of consecutive patients who received major gynae-oncology surgery delivered within an Enhanced Recovery After Surgery (ERAS) pathway at a single institution. Patients were electively admitted from theatre directly to the intensive care unit (ICU). Data was collected prospectively into electronic databases (Philips ICCA, Wardwatcher) and then retrospectively collated and appropriate statistical analyses were performed. In the absence of a consensus definition of vasoplegia, we, necessarily arbitrarily, chose a noradrenaline dose of > 0.1 mcg/kg/min at 08:00 on the first post-operative day. The rationale is that this would be more than would typically be expected to counteract the vasodilatory effects of epidural analgesia, which is commonly used at our institution.

Results

Data was collected from 324 patients, all treated between February 2014 and July 2016. The average age was 67 years and 39% received neoadjuvant chemotherapy. The commonest tumour type was ovarian (58%). The median estimated blood loss was 800 ml and epidural analgesia was used in 71%. Fifty per cent received post-operative vasopressor infusions: factors associated with this included epidural use and estimated blood loss. Nineteen per cent met our criteria for vasoplegia: factors associated with this included CRP on post-operative day 1 and P-POSSUM morbidity score. Hospital and ICU length of stay was prolonged in those who had vasoplegia.

Conclusions

Patients commonly receive vasopressors following major gynae-oncologic surgery, and this can be at relatively high doses. Clinical factors only accounted for a minority of the variability in vasopressor usage—suggesting considerable biological variability. Optimal care of patients having major abdomino-pelvic surgery may include advanced haemodynamic monitoring and ready availability of infused vasopressors, in a suitable environment.