bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated decline in lung function in adults with a history of remitted childhood asthma
Authors: Miura Shinichiro , Iwamoto Hiroshi , Omori Keitaro , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Horimasu Yasushi , Masuda Takeshi , Miyamoto Shintaro , Nakashima Taku , Fujitaka Kazunori , Hamada Hironobu , Yokoyama Akihito , Hattori Noboru
Published: September 2021

Background

A significant number of children with asthma show remission in adulthood. Although these adults are often diagnosed with COPD in later life, the effect of clinically remitted childhood asthma on the decline in lung function during adulthood is uncertain. We examined whether clinical remission of childhood asthma was associated with an accelerated decline in lung function in apparently nonasthmatic adults.

Methods

3584 participants (mean (range) age 48.1 (35–65) years) who did not have adulthood asthma and other lung diseases and had normal lung function at the baseline visit were included. They were categorised as those with remitted childhood asthma (n=121) and healthy controls (n=3463) according to their self-reported childhood asthma history. Spirometry was performed at baseline and follow-up visits.

Results

The mean follow-up was 5.3 years. Multivariate regression analysis showed that remitted childhood asthma and smoking were independently associated with a rapid decline in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Smoking was an independent predictor of a rapid decline in FEV1/FVC. The annual decline in FEV1and FVC was significantly greater in participants with remitted childhood asthma than in healthy controls, and the differences remained significant after adjusting for the propensity score.

Conclusions

A history of clinically remitted childhood asthma is an independent risk factor for accelerated decline in lung function in adults. Remitted childhood asthma and smoking may additively accelerate the development of obstructive lung disease.
Rothia mucilaginosais an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease
Authors: Rigauts Charlotte , Aizawa Juliana , Taylor Steven L. , Rogers Geraint B. , Govaerts Matthias , Cos Paul , Ostyn Lisa , Sims Sarah , Vandeplassche Eva , Sze Mozes , Dondelinger Yves , Vereecke Lars , Van Acker Heleen , Simpson Jodie L. , Burr Lucy , Willems Anne , Tunney Michael M. , Cigana Cristina , Bragonzi Alessandra , Coenye Tom , Crabbé Aurélie
Published: September 2021

Background

Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases such as severe asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF) and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognised, the influence of other microbiota members is still poorly understood.

Methods

We hypothesised that the lung microbiota contains bacteria with immunomodulatory activity which modulate net levels of immune activation by key respiratory pathogens. Therefore, we assessed the immunomodulatory effect of several members of the lung microbiota frequently reported as present in CF lower respiratory tract samples.

Results

We show thatRothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- or lipopolysaccharide-induced pro-inflammatory responses,in vitro(three-dimensional cell culture model) andin vivo(mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance ofRothiaspecies was negatively correlated with pro-inflammatory markers (interleukin (IL)-8 and IL-1β) and matrix metalloproteinase (MMP)-1, MMP-8 and MMP-9 in sputum. Mechanistic studies revealed thatR. mucilaginosainhibits NF-κB pathway activation by reducing the phosphorylation of IκBα and consequently the expression of NF-κB target genes.

Conclusions

These findings indicate that the presence ofR. mucilaginosain the lower airways potentially mitigates inflammation, which could in turn influence the severity and progression of chronic respiratory disorders.
A systematic review of blood biomarkers with individual participant data meta-analysis of matrix metalloproteinase-7 in idiopathic pulmonary fibrosis
Authors: Khan Fasihul A. , Stewart Iain , Saini Gauri , Robinson Karen A. , Jenkins R. Gisli
Published: September 2021

Background

Blood-derived biomarkers have been described extensively as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of end-points, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood-derived biomarkers, sufficient studies with measurements of matrix metalloproteinase (MMP)-7 were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF.

Methods

Electronic databases were searched on 12 November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline, or change over 3 months. IPD were sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline forced vital capacity.

Results

IPD was available for nine studies out of 12 identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted hazard ratio 1.23, 95% CI 1.03–1.48; I2=64.3%) and disease progression (adjusted OR 1.27, 95% CI 1.11–1.46; I2=5.9%). In limited studies, 3-month change in MMP-7 was not associated with outcomes.

Conclusion

IPD meta-analysis demonstrated that greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, while short-term changes did not reflect disease progression.
Divergent patterns of selection on metabolite levels and gene expression
Authors: Kern Alexander F. , Yang Grace Xiaolu , Khosla Neil M. , Ang Roy Moh Lik , Snyder Michael P. , Fraser Hunter B.
Published: September 2021

Background

Natural selection can act on multiple genes in the same pathway, leading to polygenic adaptation. For example, adaptive changes were found to down-regulate six genes involved in ergosterol biosynthesis—an essential pathway targeted by many antifungal drugs—in some strains of the yeast Saccharomyces cerevisiae. However, the impact of this polygenic adaptation on metabolite levels was unknown. Here, we performed targeted mass spectrometry to measure the levels of eight metabolites in this pathway in 74 yeast strains from a genetic cross.

Results

Through quantitative trait locus (QTL) mapping we identified 19 loci affecting ergosterol pathway metabolite levels, many of which overlap loci that also impact gene expression within the pathway. We then used the recently developed v-test, which identified selection acting upon three metabolite levels within the pathway, none of which were predictable from the gene expression adaptation.

Conclusions

These data showed that effects of selection on metabolite levels were complex and not predictable from gene expression data. This suggests that a deeper understanding of metabolism is necessary before we can understand the impacts of even relatively straightforward gene expression adaptations on metabolic pathways.
Synergistic effects of silver ions and metformin against enterococcus faecalis under high-glucose conditions in vitro
Authors: Wu Xuying , Fan Wei , Fan Bing
Published: September 2021

Background

This study aimed to evaluate the synergistic antibacterial activities of silver ions (Ag+) and metformin hydrochloride (Met) against Enterococcus faecalis (E. faecalis) under normal or high-glucose conditions.

Results

The minimum inhibitory concentration, minimum bactericidal concentration, growth curves, and colony-forming units were used to evaluate the antibacterial effects of Ag+ and Met on planktonic E. faecalis in Brain Heart Infusion broth with or without additional glucose. The influences of Ag+ and Met on four weeks E. faecalis biofilm on human dentin slices was also tested. Cytotoxicity was tested on MC3T3-E1 osteoblastic cells using CCK-8 assays. The results indicated that E. faecalis showed higher resistance to drug treatment under high-glucose conditions. Ag+ (40 μg/mL) plus Met (3.2% or 6.4%) showed enhanced antibacterial activities against both planktonic E. faecalis and biofilm on dentin slices, with low cytotoxicity.

Conclusions

Met enhanced the bactericidal effects of Ag+ against both planktonic and biofilm E. faecalis under normal or high-glucose conditions with low cytotoxicity. Further molecular studies are needed to be conducted to understand the mechanisms underlying the synergistic activity between Met and Ag+.
Prevalence of methicillin resistance and superantigenic toxins in Staphylococcus aureus strains isolated from patients with cancer
Authors: Abbasi Montazeri Effat , Khosravi Azar Dokht , Khazaei Saeedeh , Sabbagh Ali
Published: September 2021

Background

This study aimed to determine the frequency of methicillin-resistant Staphylococcus aureus (MRSA), antibiotic resistance patterns, superantigenic toxins profile, and clonality of this pathogen in patients with cancer.

Results

In total, 79 (25.7%) isolates were confirmed as Staphylococcus species, from which 38 (48.1%) isolates were S. aureus, and 29 (76.3%) isolates were confirmed as MRSA. The highest resistance in MRSA strains was seen against ciprofloxacin (86.2%) and erythromycin (82.8%). Teicoplanin, and linezolid were the most effective antibiotics. From all MRSA isolates, 3 strains (10.3%) were resistant to vancomycin with minimum inhibitory concentration values of 128 μg/ml. The prevalence of superantigenic toxins genes was as follows: pvl (10.5%), tsst-1 (36.8%), etA (23.7%), and etB (23.7%). The t14870 spa type with frequency of 39.5% was the most prevalent clone type circulating in the cancer patients.

Conclusions

This study showed the circulating of spa t14870 as the most predominant MRSA clone in cancer patients of southwest Iran. Also, a diverse antibiotic resistance pattern and toxin profiles were seen among MRSA isolates.
Geographic distribution of the E1 family of genes and their effects on reproductive timing in soybean
Authors: Dietz Nicholas , Combs-Giroir Rachel , Cooper Grace , Stacey Minviluz , Miranda Carrie , Bilyeu Kristin
Published: September 2021

Background

Soybean is an economically important crop which flowers predominantly in response to photoperiod. Several major loci controlling the quantitative trait for reproductive timing have been identified, of which allelic combinations at three of these loci, E1, E2, and E3, are the dominant factors driving time to flower and reproductive period. However, functional genomics studies have identified additional loci which affect reproductive timing, many of which are less understood. A better characterization of these genes will enable fine-tuning of adaptation to various production environments. Two such genes, E1La and E1Lb, have been implicated in flowering by previous studies, but their effects have yet to be assessed under natural photoperiod regimes.

Results

Natural and induced variants of E1La and E1Lb were identified and introgressed into lines harboring either E1 or its early flowering variant, e1-as. Lines were evaluated for days to flower and maturity in a Maturity Group (MG) III production environment. These results revealed that variation in E1La and E1Lb promoted earlier flowering and maturity, with stronger effects in e1-as background than in an E1 background. The geographic distribution of E1La alleles among wild and cultivated soybean revealed that natural variation in E1La likely contributed to northern expansion of wild soybean, while breeding programs in North America exploited e1-as to develop cultivars adapted to northern latitudes.

Conclusion

This research identified novel alleles of the E1 paralogues, E1La and E1Lb, which promote flowering and maturity under natural photoperiods. These loci represent sources of genetic variation which have been under-utilized in North American breeding programs to control reproductive timing, and which can be valuable additions to a breeder’s molecular toolbox.
Predominant role of gut-vagus-brain neuronal pathway in postoperative nausea and vomiting: evidence from an observational cohort study
Authors: Li Nana , Liu Lu , Sun Menghan , Wang Ruiliang , Jin Wenjie , Liu Cunming , Hu Youli
Published: September 2021

Background

Postoperative nausea and vomiting (PONV) as a clinically most common postoperative complication requires multimodal antiemetic medications targeting at a wide range of neurotransmitter pathways. Lacking of neurobiological mechanism makes this ‘big little problem’ still unresolved. We aim to investigate whether gut-vagus-brain reflex generally considered as one of four typical emetic neuronal pathways might be the primary mediator of PONV.

Methods

Three thousand two hundred twenty-three patients who underwent vagus nerve trunk resection (esophagectomy and gastrectomy) and non-vagotomy surgery (hepatectomy, pulmonary lobectomy and colorectomy) from December 2016 to January 2019 were enrolled. Thirty cases of gastrectomy with selective resection on the gastric branch of vagus nerve were also recruited. Nausea and intensity of vomiting was recorded within 24 h after the operation.

Results

PONV occurred in 11.9% of 1187 patients who underwent vagus nerve trunk resection and 28.7% of 2036 non-vagotomy patients respectively. Propensity score matching showed that vagotomy surgeries accounted for 19.9% of the whole PONV incidence, much less than that observed in the non-PONV group (35.1%, P <  0.01). Multivariate logistic regression result revealed that vagotomy was one of underlying factor that significantly involved in PONV (OR = 0.302, 95% CI, 0.237-0.386). Nausea was reported in 5.9% ~ 8.6% vagotomy and 12 ~ 17% non-vagotomy patients. Most vomiting were mild, being approximately 3% in vagotomy and 8 ~ 13% in non-vagotomy patients, while sever vomiting was much less experienced. Furthermore, lower PONV occurrence (10%) was also observed in gastrectomy undergoing selective vagotomy.

Conclusion

Patients undergoing surgeries with vagotomy developed less PONV, suggesting that vagus nerve dependent gut-brain signaling might mainly contribute to PONV.
Application and evaluation of nucleic acid sequence-based amplification, PCR and cryptococcal antigen test for diagnosis of cryptococcosis
Authors: Wang Yanping , Yang Mi , Xia Yun , Yan Jia , Zou Jiaqi , Zhang Dawei
Published: September 2021

Background

Cryptococcosis is a major opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. In the early stages of cryptococcosis, limitations of the detection method may hinder the diagnosis. A molecular diagnostic technique based on nucleic acid sequence-based amplification (NASBA) method was developed to fulfil the need for efficient diagnosis of cryptococcosis.

Methods

We compared the diagnostic performance of NASBA, PCR and cryptococcal antigen (CrAg) test (colloidal gold method) in clinical samples from 25 cryptococcosis patients (including 8 cryptococcal meningoencephalitis and 17 pulmonary cryptococcosis) who were categorized as proven cases (n = 10) and probable cases (n = 15) according to the revised EORTC/MSG definitions. 10 patients with non-Cryptococcus infection and 30 healthy individuals were categorized as control group.

Results

The lowest detection limit of NASBA was 10 CFU/mL, and RNA of non-target bacteria or fungi was not amplified. The sensitivity of NASBA, PCR and colloidal gold method was 92.00% (95% CI 72.50–98.60%), 64.00% (95% CI 42.62–81.29%), 100.00% (95% CI 83.42–100.00%), and the specificity was 95.00% (95% CI 81.79–99.13%), 80.00% (95% CI 63.86–90.39%) and 82.50% (95% CI 66.64–92.11%) respectively. The highest specificity (97.50%), accuracy (95.38%) and k value (0.90) were achieved when both NASBA and colloidal gold results were positive.

Conclusions

NASBA is a new alternative detection method for cryptococcosis which is both accurate and rapid without expensive equipment and specialised personnel. It may be used as a tool for confirming current infection as well as monitoring the effectiveness of antifungal treatment. The use of NASBA to detect Cryptococcus RNA in blood samples is of great significance for the diagnosis of pulmonary cryptococcosis. The combination of NASBA and colloidal gold can improve the diagnostic accuracy of cryptococcosis.
Optical coherence tomography features and risk of macular hole formation in the fellow eye
Authors: Lindtjørn Birger , Krohn Jørgen , Forsaa Vegard A.
Published: September 2021

Background

To investigate the risk of primary macular hole (MH) in the fellow eye, and to evaluate baseline characteristics and optical coherence tomography (OCT) features that precede MH formation in the fellow eye.

Methods

A retrospective review of 229 patients treated for primary MH at Stavanger University Hospital, Norway, from January 2008 through December 2018. The patients were categorised into two groups according to subsequent development of MH in the fellow eye. The OCT findings of the two groups were compared, and associated risk factors for MH formation assessed.

Results

Twenty cases of bilateral MH were identified. The overall bilateral disease risk was 8.8% (95% CI, 5.8–13.2%). Two patients were previously operated in the fellow eye, six patients presented with bilateral MH, and 12 patients subsequently developed MH in the fellow eye. The risk of subsequent MH development was 5.7% (95% CI, 3.3–9.8%). Although the extent of posterior vitreous detachment (PVD) tended to be more progressed in the bilateral group compared with the unilateral group, the difference was not statistically significant. In the bilateral group, 41.7% had outer retinal defects vs 6.6% in the unilateral group (p = 0.001), and 33.3% in the bilateral group had intraretinal pseudocysts vs 10.2% in the unilateral group (p = 0.036, not significant after multiple testing correction).

Conclusion

Outer retinal defects and intraretinal pseudocysts are associated with an increased risk of MH formation in the fellow eye, and complete PVD indicates a decreased risk of MH formation.
Modeling mortality risk effects of cigarettes and smokeless tobacco: results from the National Health Interview Survey Linked Mortality File Data
Authors: Salazar Esther , Ren Chunfeng , Rostron Brian L. , Solomon Ghideon
Published: September 2021

Background

Cigarettes and smokeless tobacco (SLT) products are among a wide range of tobacco products that are addictive and pose a significant health risk. In this study, we estimated smoking- and SLT use-related mortality hazard ratios (HRs) among U.S. adults by sex, age group, and cause of death, for nine mutually exclusive categories of smoking and/or SLT use.

Methods

We used data from the public-use National Health Interview Survey Linked Mortality with mortality follow-up through 2015. We used Cox proportional hazard models to estimate mortality HRs, adjusted by race/ethnicity, education, poverty level, body mass index, and tobacco-use status.

Results

With never users as reference group, HRs for smoking-related diseases for male exclusive current smokers aged 35–64 and 65+ were 2.18 (95% confidence interval [CI]: 1.79–2.65), and 2.45 (95% CI: 2.14–2.79), respectively. Similar significant HR estimates were found for females and for all-cause mortality (ACM) and other-cause mortality (OCM) outcomes. HRs for exclusive current SLT users were only significant for males aged 35–64 for ACM (HR: 2.04, 95% CI: 1.27–3.27) and OCM (HR: 2.80, 95% CI: 1.50–5.25). HRs for users who switched from cigarettes to SLT products were significant for males aged 65+ for smoking-related diseases (HR: 2.06, 95% CI: 1.47–2.88), SLT-related diseases (HR: 1.99, 95% CI: 1.36–2.89), and ACM (HR: 1.63, 95% CI: 1.21–2.19).

Conclusions

Male exclusive current SLT users aged 35–64 had a significant HR for ACM and OCM outcomes, suggesting that deaths not attributed to SLT use could be contributing to the ACM elevated HR for exclusive current SLT users.
Minimum 10 years clinical and radiological outcomes of acetabular revisions of total hip arthroplasties with tricalcium phosphate/hydroxyapatite bone graft substitute
Authors: Gagala Jacek
Published: September 2021

Background

Aseptic loosening is the most frequent indication for revision of total hip arthroplasty. Revision arthroplasty of acetabular component is a challenge for every surgeon because they have to simultaneously deal with the reconstruction of bone defects, adequate implant geometry and stable fixation. Allografts are the most frequently used materials in reconstruction of bone loss during revision surgeries. Because of an increasing number of revision hip arthroplasties and poor availability of allografts, we decided to use bone graft substitutes in acetabular revisions.

Methods

Between September 2005 and January 2010, 44 revision arthroplasties in 43 patients were performed with the use of bone graft substitutes for acetabular defect reconstruction in revision of total hip arthroplasty. Acetabular bone defects were classified according to Paprosky. Seventeen hips were classified as IIA, 3 hips IIB, 3 hips IIC, 10 hips IIIA and 11 hips IIIB. Acetabular bone defects were reconstructed with tricalcium phosphate/hydroxyapatite bone graft substitute - BoneSave. Clinical and radiological examination was performed after 3 months, 1 year and then annually. Harris hip score was used for clinical evaluation. Survival analysis was performed with Kaplan-Meier method with aseptic loosening as the definition of endpoint.

Results

The average follow-up period is 12 (range from 10 to 15) years. During the follow-up, three patients died after 24 months because of causes not related to surgery. None of the patients was lost to follow-up. The evaluation of clinical results revealed an increase in pre-operative HHS from average 38.3 (range 25 to 55) points to average 86.3 (range 45 to 95) points at the most recent follow-up. Radiographic evaluation showed the migration of one revision cage 12 months after surgery. Revision arthroplasty performed after 14 months revealed the partial incorporation of bone graft substitute. There were not any cases of loosening of revision acetabular cup at the most recent follow up examination in the remaining 39 patients. Bone graft substitute was not absorbed in all of these patients. The survival after 10 years amounted to 97.56%.

Conclusion

Bone graft substitute Bone Save may be suitable for acetabular revision surgery, however preoperative bone defect is critical for success and determining of a surgical technique, so this is multifactorial in this challenge surgery.
Association between attitude towards death and spiritual care competence of Chinese oncology nurses: a cross-sectional study
Authors: Li Liujin , Lv Jingmin , Zhang Lingling , Song Yalan , Zhou Ying , Liu Jiaxian
Published: September 2021

Backgrounds

An understanding of the oncology nurse spiritual care competence would help nurse managers recognize weakness in spiritual practice and improve the quality of spiritual care. But the relationship between attitude towards death and spiritual care competence is unknown.

Methods

We recruited 326 nurses from hospitals in Guangzhou, China. The nurses completed the Chinese Spiritual Care Competence Scale and the Chinese Death Attitude Profile-Revised questionnaires.

Results

The total score of spiritual care competence was 61.62 ± 16.10. And the lowest score of attitude towards death was forescape acceptance, 2.64 ± 0.82. Factors associated with nurse spiritual care competence were work department, whether trained in spiritual care,approaching acceptance, andescaping acceptanceof attitude towards death.

Conclusion

Nurses need to perfect their spiritual care competence and establish positive attitudes towards death.
Feasibility and acceptability of virtually coaching residents on communication skills: a pilot study
Authors: Sasnal Marzena , Miller-Kuhlmann Rebecca , Merrell Sylvia Bereknyei , Beres Shannon , Kipp Lucas , Lee Sarah , Threlkeld Zachary , Nassar Aussama K. , Gold Carl A.
Published: September 2021

Background

Developing communication skills is a key competency for residents. Coaching, broadly accepted as a training modality in medical education, has been proven a successful tool for teaching communication skills. Little research is available thus far to investigate virtual coaching on communication skills for telemedicine encounters. The purpose of the study was to test the hypothesis that virtually coaching residents on communication skills is feasible and acceptable. We surveyed 21 resident-faculty pairs participating in a “fully virtual” coaching session (patient, coach, and resident were virtual).

Methods

We asked 50 neurology resident-faculty coach pairs to complete one “fully virtual” coaching session between May 20 and August 31, 2020. After each session, the resident and coach completed a 15-item survey, including Likert-style scale and open-ended questions, assessing feasibility and acceptability. Descriptive statistics and qualitative content and thematic analyses were performed.

Results

Forty-two percent (21/50) of all eligible residents completed “fully virtual” coaching sessions. The overall survey response rate was 91 % (38/42). The majority of respondents agreed that the direct observation and debriefing conversation were easy to schedule and occurred without technical difficulties and that debriefing elements (self-reflection, feedback, takeaways) were useful for residents. Ninety-five percent of respondents rated the coach’s virtual presence to be not at all disruptive to the resident-patient interaction. Virtual coaching alleviated resident stress associated with observation and was perceived as an opportunity for immediate feedback and a unique approach for resident education that will persist into the future.

Conclusions

In this pilot study, residents and faculty coaches found virtual coaching on communication skills feasible and acceptable for telemedicine encounters. Many elements of our intervention may be adoptable by other residency programs. For example, residents may share their communication goals with clinic faculty supervisors and then invite them to directly observe virtual encounters what could facilitate targeted feedback related to the resident’s goals. Moreover, virtual coaching on communication skills in both the in-person and telemedicine settings may particularly benefit residents in challenging encounters such as those with cognitively impaired patients or with surrogate decision-makers.
Estimating the health and economic effects of the voluntary sodium reduction targets in Brazil: microsimulation analysis
Authors: Nilson Eduardo Augusto Fernandes , Pearson-Stuttard Jonathan , Collins Brendan , Guzman-Castillo Maria , Capewell Simon , O’Flaherty Martin , Jaime Patrícia Constante , Kypridemos Chris
Published: September 2021

Background

Excessive sodium consumption is one of the leading dietary risk factors for non-communicable diseases, including cardiovascular disease (CVD), mediated by high blood pressure. Brazil has implemented voluntary sodium reduction targets with food industries since 2011. This study aimed to analyse the potential health and economic impact of these sodium reduction targets in Brazil from 2013 to 2032.

Methods

We developed a microsimulation of a close-to-reality synthetic population (IMPACTNCD-BR) to evaluate the potential health benefits of setting voluntary upper limits for sodium content as part of the Brazilian government strategy. The model estimates CVD deaths and cases prevented or postponed, and disease treatment costs. Model inputs were informed by the 2013 National Health Survey, the 2008–2009 Household Budget Survey, and high-quality meta-analyses, assuming that all individuals were exposed to the policy proportionally to their sodium intake from processed food. Costs included costs of the National Health System on CVD treatment and informal care costs. The primary outcome measures of the model are cardiovascular disease cases and deaths prevented or postponed over 20 years (2013–2032), stratified by age and sex.

Results

The study found that the application of the Brazilian voluntary sodium targets for packaged foods between 2013 and 2032 could prevent or postpone approximately 110,000 CVD cases (95% uncertainty intervals (UI): 28,000 to 260,000) among men and 70,000 cases among women (95% UI: 16,000 to 170,000), and also prevent or postpone approximately 2600 CVD deaths (95% UI: − 1000 to 11,000), 55% in men. The policy could also produce a net cost saving of approximately US$ 220 million (95% UI: US$ 54 to 520 million) in medical costs to the Brazilian National Health System for the treatment of CHD and stroke and save approximately US$ 71 million (95% UI: US$ 17 to170 million) in informal costs.

Conclusion

Brazilian voluntary sodium targets could generate substantial health and economic impacts. The reduction in sodium intake that was likely achieved from the voluntary targets indicates that sodium reduction in Brazil must go further and faster to achieve the national and World Health Organization goals for sodium intake.
Patient derived organoids in prostate cancer: improving therapeutic efficacy in precision medicine
Authors: Pamarthy Sahithi , Sabaawy Hatem E.
Published: September 2021

With advances in the discovery of the clinical and molecular landscapes of prostate cancer (PCa), implementation of precision medicine-guided therapeutic testing in the clinic has become a priority. Patient derived organoids (PDOs) are three-dimensional (3D) tissue cultures that promise to enable the validation of preclinical drug testing in precision medicine and coclinical trials by modeling PCa for predicting therapeutic responses with a reliable efficacy. We evaluate the advances in 3D culture and PDO use to model clonal heterogeneity and screen for effective targeted therapies, with a focus on the technological advances in generating PDOs. Recent innovations include the utilization of PDOs both in original research and/or correlative studies in clinical trials to examine drug effects within the PCa tumor microenvironment (TME). There has also been a significant improvement with the utilization of various extracellular matrices and single cell assays for the generation and long-term propagation of PDOs. Single cell derived PDOs could faithfully recapitulate the original tumor and reflect the heterogeneity features. While most PDO use for precision medicine understandably involved tissues derived from metastatic patients, we envision that the generation of PDOs from localized PCa along with the incorporation of cells of the TME in tissue models would fulfill the great potential of PDOs in predicting drug clinical benefits. We conclude that single cell derived PDOs reiterate the molecular features of the original tumor and represent a reliable pre-clinical PCa model to understand individual tumors and design tailored targeted therapies.
A prediction model based on platelet parameters, lipid levels, and angiographic characteristics to predict in-stent restenosis in coronary artery disease patients implanted with drug-eluting stents
Authors: Gai Min-Tao , Zhu Bing , Chen Xiao-Cui , Liu Fen , Xie Xiang , Gao Xiao-Ming , Ma Xiang , Fu Zhen-Yan , Ma Yi-Tong , Chen Bang-dang
Published: September 2021

Background

The present study was aimed to establish a prediction model for in-stent restenosis (ISR) in subjects who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DESs).

Materials and methods

A retrospective cohort study was conducted. From September 2010 to September 2013, we included 968 subjects who had received coronary follow-up angiography after primary PCI. The logistic regression analysis, receiver operator characteristic (ROC) analysis, nomogram analysis, Hosmer–Lemeshow χ2 statistic, and calibration curve were applied to build and evaluate the prediction model.

Results

Fifty-six patients (5.79%) occurred ISR. The platelet distribution width (PDW), total cholesterol (TC), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and lesion vessels had significant differences between ISR and non-ISR groups (all P < 0.05). And these variables were independently associated with ISR (all P < 0.05). Furthermore, they were identified as predictors (all AUC > 0.5 and P < 0.05) to establish a prediction model. The prediction model showed a good value of area under curve (AUC) (95%CI): 0.72 (0.64–0.80), and its optimized cut-off was 6.39 with 71% sensitivity and 65% specificity to predict ISR.

Conclusion

The incidence of ISR is 5.79% in CAD patients with DES implantation in the Xinjiang population, China. The prediction model based on PDW, SBP, TC, LDL-C, and lesion vessels was an effective model to predict ISR in CAD patients with DESs implantation.
Serum lipid levels in relation to clinical outcomes in pregnant women with gestational diabetes mellitus: an observational cohort study
Authors: Li Yuan , Wang Xiaoqian , Jiang Fengjuan , Chen Wenqing , Li Jie , Chen Xiaotian
Published: September 2021

Background

Research on dyslipidemia during pregnancy in women with gestational diabetes mellitus (GDM) has rarely been conducted in Asia. The present study aimed to evaluate maternal mid-trimester lipid profile in relation to GDM and clinical outcomes in these high-risk populations.

Methods

The medical records of 632 pregnant women in the second trimester were retrospectively analyzed. Maternal fasting serum lipids were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein A1 (Apo A1) and Apo B concentrations during the second trimester. The atherogenic index of plasma (AIP) was calculated as log (TG/HDL). The clinical outcomes were collected by evaluating delivery mode, postpartum hemorrhage, prematurity, macrosomia, birth weight, body length and neonatal Apgar 5 min score.

Results

Levels of TG and AIP were elevated while decreased HDL-C was observed in women with GDM compared with that of the control group. Significant differences were observed in gestational weeks at birth, cesarean section, postpartum hemorrhage, birth weight, body length, prematurity and macrosomia between the two groups. Compared with women with hyperlipidemia, the incidence of GDM and cesarean section was lower in normal lipid group. Women in the hyperlipidemia group had smaller gestational weeks at birth than those in the control group. According to the logistic regression analysis, each unit elevation in AIP increased the risk of GDM by 18.48 times (OR = 18.48, CI: 2.38–143.22). Besides, age (OR = 1.11, CI: 1.06–1.16) and pre-pregnancy BMI (OR = 1.15, CI: 1.07–1.24) were the risk factors of GDM.

Conclusions

These findings suggested that reasonable lipid control in the second trimester might reduce the incidence of GDM and be a potential strategy for improving clinical outcomes in these high-risk women.
Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease
Authors: Ruiz-Pérez Gonzalo , Ruiz de Martín Esteban Samuel , Marqués Sharai , Aparicio Noelia , Grande M. Teresa , Benito-Cuesta Irene , Martínez-Relimpio Ana M. , Arnanz M. Andrea , Tolón Rosa M. , Posada-Ayala María , Cravatt Benjamin F. , Esteban José A. , Romero Julián , Palenzuela Rocío
Published: September 2021

Background

The complex pathophysiology of Alzheimer’s disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit.

Methods

In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse− model.

Results

We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3–CA1 synapse, both basal synaptic transmission and long-term potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron–glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH−/− animals.

Conclusion

In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer’s disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the disease.
Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial
Authors: Payne Helen , Chan Man K. , Watters Sarah A. , Otwombe Kennedy , Hsiao Nei-Yuan , Babiker Abdel , Violari Avy , Cotton Mark F. , Gibb Diana M. , Klein Nigel J.
Published: September 2021

Background

Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial.

Methods

Infants with HIV  <  12 weeks old with CD4%  ≥  25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4%  <  25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received  ≥  24 weeks ART and two consecutive undetectable HIV-1 RNA 12–24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression.

Findings

Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0003) and 248 weeks (p  =  0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0225) and 248 weeks (p  =  0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p  =  0.0042).

Intepretation

Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure.

Funding

Wellcome Trust, National Institutes of Health, Medical Research Council.
Asymmetric cell division of mammary stem cells
Authors: Chhabra Shaan N. , Booth Brian W.
Published: September 2021

Somatic stem cells are distinguished by their capacity to regenerate themselves and also to produce daughter cells that will differentiate. Self-renewal is achieved through the process of asymmetric cell division which helps to sustain tissue morphogenesis as well as maintain homeostasis. Asymmetric cell division results in the development of two daughter cells with different fates after a single mitosis. Only one daughter cell maintains “stemness” while the other differentiates and achieves a non-stem cell fate. Stem cells also have the capacity to undergo symmetric division of cells that results in the development of two daughter cells which are identical. Symmetric division results in the expansion of the stem cell population. Imbalances and deregulations in these processes can result in diseases such as cancer. Adult mammary stem cells (MaSCs) are a group of cells that play a critical role in the expansion of the mammary gland during puberty and any subsequent pregnancies. Furthermore, given the relatively long lifespans and their capability to undergo self-renewal, adult stem cells have been suggested as ideal candidates for transformation events that lead to the development of cancer. With the possibility that MaSCs can act as the source cells for distinct breast cancer types; understanding their regulation is an important field of research. In this review, we discuss asymmetric cell division in breast/mammary stem cells and implications on further research. We focus on the background history of asymmetric cell division, asymmetric cell division monitoring techniques, identified molecular mechanisms of asymmetric stem cell division, and the role asymmetric cell division may play in breast cancer.
Self-regulation in Barth syndrome: a qualitative perspective of adolescents, adults and parents in the U.K
Authors: Searle Aidan , Herbert Georgia , Dabner Lucy , Steward Colin G. , Damin Michaela , Pieles Guido
Published: September 2021

Background

Barth syndrome (BS) is a life-threatening genetic disease caused by abnormal lipids in the mitochondria of cells and mostly affects young males. Those living with BS have severe exercise intolerance, lethargy and fatigue due to muscle disease which affect their daily life. Previous research suggests a need for qualitative exploration of self-regulation in BS and the inter-personal processes at play in family life. Therefore this study aimed to explore self-regulation and coping strategies and inter-personal responses in individuals and families affected by Barth syndrome. A multi-perspective qualitative study based on face to face, semi-structured, in-depth interviews with 11 participants (9–27 years, mean 15 years) with BS and/or their parents participating in a randomised double-blind clinical drug trial (CARDIOMAN). Interviews were transcribed verbatim and managed in NVivo prior to conducting a thematic analysis (AS and GH).

Results

Four key themes were identified: diagnosis and treatment, social support, identity and social integration, symptoms and self-regulation. The present findings suggest that self-regulation and coping in boys with BS was interpersonal and contingent on parental awareness such that parents were aware that their child had a limited energy reserve and that had to be managed due to the implications of fatigue for daily living.

Conclusion

The findings support previous quantitative work demonstrating that children and parents tend to share a coherent view of BS. However, there is a need for greater awareness from others within the wider context of social and employment networks to minimise adverse implications for future life choices.
Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms
Authors: Trelles M. Pilar , Levy Tess , Lerman Bonnie , Siper Paige , Lozano Reymundo , Halpern Danielle , Walker Hannah , Zweifach Jessica , Frank Yitzchak , Foss-Feig Jennifer , Kolevzon Alexander , Buxbaum Joseph
Published: September 2021

Background

FOXP1 syndrome is an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, speech and language delays, and externalizing behaviors. We previously evaluated nine children and adolescents with FOXP1 syndrome to better characterize its phenotype. We identified specific areas of interest to be further explored, namely autism spectrum disorder (ASD) and internalizing and externalizing behaviors.

Methods

Here, we assess a prospective cohort of additional 17 individuals to expand our initial analyses and focus on these areas of interest. An interdisciplinary group of clinicians evaluated neurodevelopmental, behavioral, and medical features in participants. We report results from this cohort both alone, and in combination with the previous cohort, where possible.

Results

Previous observations of intellectual disability, motor delays, and language deficits were confirmed. In addition, 24% of the cohort met criteria for ASD. Seventy-five percent of individuals met DSM-5 criteria for attention-deficit/hyperactivity disorder and 38% for an anxiety disorder. Repetitive behaviors were almost universally present (95%) even without a diagnosis of ASD. Sensory symptoms, in particular sensory seeking, were common.

Limitations

As FOXP1 syndrome is a rare disorder, sample size is limited.

Conclusions

These findings have important implications for the treatment and care of individuals with FOXP1 syndrome. Notably, standardized testing for ASD showed high sensitivity, but low specificity, when compared to expert consensus diagnosis. Furthermore, many individuals in our cohort who received diagnoses of attention-deficit/hyperactivity disorder or anxiety disorder were not being treated for these symptoms; therefore, our findings suggest that there may be immediate areas for improvements in treatment for some individuals.
Ulam stability for nonautonomous quantum equations
Authors: Anderson Douglas R. , Onitsuka Masakazu
Published: September 2021

We establish the Ulam stability of a first-order linear nonautonomous quantum equation with Cayley parameter in terms of the behavior of the nonautonomous coefficient function. We also provide details for some cases of Ulam instability.