bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated triglycerides and reduced high-density lipoprotein cholesterol are independently associated with the onset of advanced chronic kidney disease: a cohort study of 911,360 individuals from the United Kingdom
Authors: Weldegiorgis Misghina , Woodward Mark
Published: September 2022

Background

Increased total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) concentrations, are established risk factors for cardiovascular morbidity and mortality; but their impact on the risk of advanced chronic kidney disease (CKD) is unclear. This study evaluates the association between the different lipid profiles and the onset of advanced CKD using a general population sample.

Methods

This observational study used records of 911,360 individuals from the English Clinical Practice Research Datalink (from 2000 to 2014), linked to coded hospital discharges and mortality registrations. Cox models were used to examine the independent association between the equal quarters of TC, TG, LDL-C, and HDL-C and the risk of advanced CKD, after adjustment for sex and age, and potential effect mediators.

Results

During a median follow-up of 7.5 years, 11,825 individuals developed CKD stages 4–5. After adjustment for sex and age, the hazard ratios (HRs) and confidence intervals (CIs) for CKD stages 4–5 comparing the 4th vs. 1st quarters of TG and 1st vs. 4th quarters of HDL-C were 2.69 (95% CI, 2.49–2.90) and 2.61 (95% CI, 2.42–2.80), respectively. Additional adjustment for potential effect mediators reduced the HRs to 1.28 (95% CI, 1.15–1.43), and 1.27 (95% CI, 1.14–1.41), respectively. There was no evidence of fully adjusted associations with CKD stages 4–5 for levels of either TC or LDL-C.

Conclusions

Elevated TG and reduced HDL-C levels are independently associated with the onset of advanced CKD. Future studies, such as in basic science and randomized trials, are needed to understand whether associations between TG and HDL-C and the development of CKD are causal.
In-hospital clinical outcomes in diffusion weighted imaging-negative stroke treated with intravenous thrombolysis
Authors: Li Guangshuo , Feng Xueyan , Wang Chuanying , Hao Yahui , Wang Shang , Xiong Yunyun , Zhao Xingquan
Published: September 2022

Objective

We aimed to investigate whether negative diffusion weighted imaging (DWI) is related to the in-hospital clinical outcomes for ischemic stroke patients with intravenous tissues plasminogen activator (IV tPA).

Methods

We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. The classification of DWI-positive or negative was based on post-IV tPA MR scan. Demographic factors, stroke characteristics, imaging information, and the in-hospital clinical outcomes including early neurological improvement (ENI) and favourable functional outcome were collected. Multivariable logistic regression and sensitivity analyses were conducted to test whether negative DWI imaging was an independent predictor of the in-hospital clinical outcomes.

Results

In the final study population, 437 patients treated with IV tPA were included and 12.36% of them had negative DWI imaging at the first MR scan post IV tPA. In the DWI-negative group, 51.9% (28/54) of the patients achieved ENI at 24 hours and 74.1% (40/54) of the patients achieved favourable clinical outcome at discharge. DWI-negative was not related to ENI (adjusted odds ratio 0.93, 95% confidence interval 0.17–4.91) or favourable clinical outcome (adjusted odds ratio 2.40, 95% confidence interval 0.48–11.95). Additional sensitivity analyses yielded similar results.

Conclusion

DWI-negative is not associated with ENI or favourable functional outcome at discharge.
Flagellin synergistically enhances anti-tumor effect of EGFRvIII peptide in a glioblastoma-bearing mouse brain tumor model
Authors: Choi Jin Myung , Lim Sa-Hoe , Liu Zhi-Peng , Lee Tae Kyu , Rhee Joon Haeng , Yoon Mee Sun , Min Jung-Joon , Jung Shin
Published: September 2022

Background

Glioblastoma (GBM) is the most aggressive type of brain tumor with heterogeneity and strong invasive ability. Treatment of GBM has not improved significantly despite the progress of immunotherapy and classical therapy. Epidermal growth factor receptor variant III (EGFRvIII), one of GBM-associated mutants, is regarded as an ideal therapeutic target in EGFRvIII-expressed GBM patients because it is a tumor-specific receptor expressed only in tumors. Flagellin B (FlaB) originated from Vibrio vulnificus, is known as a strong adjuvant that enhances innate and adaptive immunity in various vaccine models. This study investigated whether FlaB synergistically could enhance the anti-tumor effect of EGFRvIII peptide (PEGFRvIII).

Methods

EGFRvIII-GL261/Fluc cells were used for glioblastoma-bearing mouse brain model. Cell-bearing mice were inoculated with PBS, FlaB alone, PEGFRvIII alone, and PEGFRvIII plus FlaB. Tumor growth based on MRI and the survival rate was investigated. T cell population was examined by flow cytometry analysis. Both cleaved caspase-3 and CD8 + lymphocytes were shown by immunohistochemistry (IHC) staining.

Results

The PEGFRvIII plus FlaB group showed delayed tumor growth and increased survival rate when compared to other treatment groups. As evidence of apoptosis, cleaved caspase-3 expression and DNA disruption were more increased in the PEGFRvIII plus FlaB group than in other groups. In addition, the PEGFRvIII plus FlaB group showed more increased CD8 + T cells and decreased Treg cells than other treatment groups in the brain.

Conclusions

FlaB can enhance the anti-tumor effect of PEGFRvIII by increasing CD8 + T cell response in a mouse brain GBM model.
How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak
Authors: Cesca Laura , Conversano Ester , Vianello Federica Alessandra , Martelli Laura , Gualeni Chiara , Bassani Francesca , Brugnara Milena , Rubin Giulia , Parolin Mattia , Anselmi Mauro , Marchiori Mara , Vergine Gianluca , Miorin Elisabetta , Vidal Enrico , Milocco Cristina , Orsi Cecilia , Puccio Giuseppe , Peruzzi Licia , Montini Giovanni , Dall’Amico Roberto ,   on the behalf of the Italian Society of Pediatric Nephrology (SINePe)
Published: September 2022

Background

The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts.

Methods

This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0–18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected.

Results

The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02).

Conclusions

The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered.
European birth cohorts: a consideration of what they have addressed so far
Authors: Pandolfini Chiara , Campi Rita , Bonati Maurizio
Published: September 2022

Background

Knowing the research issues addressed by other cohorts when setting up new cohorts allows researchers to avoid unnecessary duplication of efforts, while permitting collaborations, including data merging data, to better tackle knowledge gaps. This study describes the topics addressed by European birth cohorts, the interaction between these cohort interests and aims, and describes the scientific publications deriving from the cohorts.

Methods

A previous study found 66 pregnancy and 45 birth cohorts in Europe. In this study, between August and October 2020, the predominant key areas addressed by the 45 birth cohorts identified in the previous study were evaluated, as were the publications found in PubMed that were associated with the 45 cohorts. A network analysis was performed to show the connections between the 13 key areas identified. A focus on a topic in common between two areas was provided, describing the related publications.

Results

A total of 1512 references were found in PubMed (148 publications per cohort). Thirteen predominant key areas were identified, the most common of which was “Environmental” (addressed by 20 cohorts). The Environmental, Genes, and Lifestyle exposure areas were the prevalent topics characterizing the network figure. The Environmental area had the largest number of interactions with the other areas, while the Prematurity area (4 cohorts) the least. The focus provided on smoking led to the comparison of 35 publications from the Environmental group of cohorts and 22 from the Prematurity group, but their objectives did not overlap.

Conclusions

The results of this descriptive study show that the environment is a priority research area for cohorts in Europe and that cohorts with different research areas may have study issues in common, but may approach them from different viewpoints. Birth cohorts have wide-ranging aims and it would be almost impossible, and undesirable, to have perfectly overlapping and comparable objectives, but joining efforts would permit maximum use of available resources.
Brain connectomes in youth at risk for serious mental illness: an exploratory analysis
Authors: Metzak Paul D. , Shakeel Mohammed K. , Long Xiangyu , Lasby Mike , Souza Roberto , Bray Signe , Goldstein Benjamin I. , MacQueen Glenda , Wang JianLi , Kennedy Sidney H. , Addington Jean , Lebel Catherine
Published: September 2022

Background

Identifying early biomarkers of serious mental illness (SMI)—such as changes in brain structure and function—can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI.

Methods

Participants were classified as healthy controls (HC; n = 33), familial risk for serious mental illness (stage 0; n = 31), mild symptoms (stage 1a; n = 37), attenuated syndromes (stage 1b; n = 61), or discrete disorder (transition; n = 9) based on clinical assessments. Imaging data was collected from two sites. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers derived from constrained spherical deconvolution of the diffusion tensor imaging (DTI) scans, and from the correlations between brain regions measured with resting state functional magnetic resonance imaging (fMRI) data.

Results

Linear mixed effects analysis and analysis of covariance revealed no significant differences between groups in global or nodal metrics after correction for multiple comparisons. A follow up machine learning analysis broadly supported the findings. Several non-overlapping frontal and temporal network differences were identified in the structural and functional connectomes before corrections.

Conclusions

Results suggest significant brain connectome changes in youth at transdiagnostic risk may not be evident before illness onset.
Personality traits and hardiness as risk- and protective factors for mental distress during the COVID-19 pandemic: a Norwegian two-wave study
Authors: Lassen Espen Rasmussen , Hagen Kristen , Kvale Gerd , Eid Jarle , Le Hellard Stephanie , Solem Stian
Published: September 2022

Background

Several risk factors for anxious-depressive symptomatology during the COVID-19 pandemic have been established. However, few studies have examined the relationship between personality traits, hardiness, and such symptomatology during the pandemic. These constructs might serve as risk- and/or protective factors for such mental distress through the pandemic.

Methods

A sample of 5783 Norwegians responded to a survey at two time points within the first year of the pandemic. The first data collection was in April 2020 (T1) and the second in December 2020 (T2). Measures included the Ten-Item Personality-Inventory, the Revised Norwegian Dispositional Resilience Scale, and the Patient Health Questionnaire Anxiety and Depression Scale. Analyses were performed using Pearson’s correlations, multiple linear regression, and a moderation analysis.

Results

Anxious-depressive symptomatology in early phases (T1) of the pandemic was the strongest predictor for the presence of such symptomatology 9 months after the outbreak (T2). Personality and hardiness correlated significantly with mental distress at T1 and T2. Personality traits explained 5% variance in symptoms when controlling for age, gender, solitary living, negative economic impact, and mental distress at baseline. Higher neuroticism predicted higher mental distress, whereas higher conscientiousness and extraversion predicted less mental distress. Hardiness did not explain variance in outcome beyond personality traits. Hardiness did not significantly moderate the relationship between neuroticism and mental distress.

Conclusion

Individuals with high levels of neuroticism had greater difficulties adapting to the circumstances of the COVID-19 pandemic and were more prone to mental distress. Contrastingly, higher conscientiousness and extraversion may have served as protective factors for mental distress during the pandemic. The current findings might aid identification of vulnerable individuals and groups. Consequently, preventive interventions could be offered to those who need it the most.
Guiding organisational decision-making about COVID-19 asymptomatic testing in workplaces: mixed-method study to inform an ethical framework
Authors: van der Scheer Jan W. , Ansari Akbar , McLaughlin Meredith , Cox Caitríona , Liddell Kathleen , Burt Jenni , George Jenny , Kenny Rebecca , Cousens Ruth , Leach Brandi , McGowan James , Morley Katherine , Willars Janet , Dixon-Woods Mary
Published: September 2022

Background

Workplace programmes to test staff for asymptomatic COVID-19 infection have become common, but raise a number of ethical challenges. In this article, we report the findings of a consultation that informed the development of an ethical framework for organisational decision-making about such programmes.

Methods

We conducted a mixed-method consultation – a survey and semi-structured interviews during November–December 2020 in a UK case study organisation that had introduced asymptomatic testing for all staff working on-site in its buildings. Analysis of closed-ended survey data was conducted descriptively. An analysis approach based on the Framework Method was used for the open-ended survey responses and interview data. The analyses were then integrated to facilitate systematic analysis across themes. Inferences were based on the integrated findings and combined with other inputs (literature review, ethical analysis, legal and public health guidance, expert discussions) to develop an ethical framework.

Results

The consultation involved 61 staff members from the case study organisation (50 survey respondents and 11 interview participants). There was strong support for the asymptomatic testing programme: 90% of the survey respondents viewed it as helpful or very helpful. Open-ended survey responses and interviews gave insight into participants’ concerns, including those relating to goal drift, risk of false negatives, and potential negative impacts for household members and people whose roles lacked contractual and financial stability. Integration of the consultation findings and the other inputs identified the importance of a whole-system approach with appropriate support for the key control measure of isolation following positive tests. The need to build trust in the testing programme, for example through effective communication from leaders, was also emphasised.

Conclusions

The consultation, together with other inputs, informed an ethical framework intended to support employers. The framework may support organisational decision-making in areas ranging from design and operation of the programme through to choices about participation. The framework is likely to benefit from further consultation and refinement in new settings.
Interaction of sleep duration and depression on cardiovascular disease: a retrospective cohort study
Authors: Jin Bowen , Zhang Hang , Song Fuchun , Wu Guangjun , Yang Hui
Published: September 2022

Background

To assess the interaction of sleep duration and depression on the risk of cardiovascular disease (CVD).

Methods

A total of 13,488 eligible participants were enrolled in this retrospective cohort study eventually. Baseline characteristics were extracted from the China Health and Retirement Longitudinal Study (CHARLS) database, including age, sex, diabetes, high-density lipoprotein (HDL), blood glucose (GLU), glycosylated hemoglobin (GHB) etc. Univariate and multivariate negative binomial regression models were carried out to assess the statistical correlation of sleep duration and depression on CVD separately. Additionally, multivariate negative binomial regression model was used to estimate the interaction of sleep duration and depression on CVD risk.

Results

After adjusting for age, sex, educational background, hypertension, diabetes, dyslipidemia, the use of hypnotics, disability, nap, drinking, deposit, sleep disturbance, HDL, triglyceride, total cholesterol, GLU and GHB, the risk of CVD in participants with the short sleep duration was increased in comparison with the normal sleep duration [relative risk (RR)=1.02, 95% confidence interval (CI):1.01-1.03]; compared to the participants with non-depression, participants suffered from depression had an increased risk of CVD (RR=1.05, 95%CI:1.04-1.06). Additionally, the result also suggested that the interaction between short sleep duration and depression on the risk of CVD was statistically significant in these patients with diabetes and was a multiplicative interaction.

Conclusion

An interaction between short sleep duration and depression in relation to an increased risk of CVD among Chinese middle-aged and elderly individuals was noticed, which may provide a reference that people with diabetes should focus on their sleep duration and the occurrence of depression, and coexisting short sleep duration and depression may expose them to a higher risk of CVD.
Launching an innovative educational model addressing substance use disorders and dental pain management (Project ECHO® in dentistry)
Authors: Kohli Richie , Replogle Karan , Gough-Goldman Andrea , Taylor Barry , Maughan Brandon , Sehgal Harjit Singh , Herink Megan C. , Hemmings Rosemarie , Mahoney Sean , McDonnell Margaret McLain , McLemore Kenneth , Schwarz Eli
Published: September 2022

Background

Uninformed opioid prescribing by dentists has contributed to the current opioid crisis. This report describes the development and implementation of an innovative, interactive, multidisciplinary, and participant-centric telementoring program “Pain Management and Substance Use Disorders Dental ECHO (Extension for Community Health Care Outcomes)”. We disseminated information to dentists about appropriate opioid prescribing practices and engaged them with a focus on pain management and substance use disorders. The objective of this study was to assess the effectiveness of this program for self-reported: (1) change in knowledge and confidence related to clinical skills for dental pain management of patients with substance use disorders; (2) change in clinical behavior of dentists for safe opioids prescribing; and (3) change in clinic policies regarding safe opioids prescribing.

Methods

An interdisciplinary panel of experts in medicine, pharmacy, social work, and dentistry designed and led the “Pain Management and Substance Use Disorders Dental ECHO” for invited dental care providers and dental students. Six cohorts each consisting of six, 1-h-long sessions were conducted via the Zoom videoconference platform in years 2020 and 2021. Each session included a didactic expert presentation, a participant-presented patient case and discussion. Each participant completed pre- and post-program surveys to assess the program’s influence on participant knowledge, clinical confidence and behavior change.

Results

The participants (N = 151) were dentists (n = 109), dental faculty (n = 15), dental residents (n = 6), dental hygienists/assistants (n = 13) and nurses and clinic administrators (n = 8). Self-reported perceived medication knowledge, confidence in identification, treatment and willingness to engage with substance use disorders patients, and reported compliance with Prescription Drug Monitoring Program (PDMP) checks increased significantly from before to after the sessions (p < 0.001). Overall, participants expressed high levels of satisfaction with the content and reported that the sessions provided high benefit.

Conclusion

The Project ECHO model is effective in rapidly disseminating evidence-based information. Dentists viewed this model as having a high degree of benefit for the optimal management of dental pain and the recognition and treatment of substance use disorders.
Effects of cottonseed meal on growth performance, liver redox status, and serum biochemical parameters in goslings at 1 to 28 days of age
Authors: Yu Jun , Yang Zhengfeng , Yang Haiming , Wang Zhiyue
Published: September 2022

Background

Cottonseed meal (CSM), a relatively rich source of protein and amino acids, is used as an inexpensive alternative to soybean meal (SBM) in poultry diets. However, the toxicity of free gossypol in CSM has been a primary concern. The present study was conducted to investigate the effects of CSM on growth performance, serum biochemical parameters, and liver redox status in goslings at 1 to 28 days of age. Three hundred 1-day-old male goslings were randomly divided into 5 groups (10 goslings/pen, 6 replicate pens/group) and subjected to a 28-day experiment. Five isonitrogenous and isoenergetic diets were formulated such that 0% (control), 25% (CSM25), 50% (CSM50), 75% (CSM75), and 100% (CSM100) of protein from SBM was replaced by protein from CSM. The free gossypol contents in the five diets were 0, 56, 109, 166, and 222 mg/kg, respectively.

Results

The results showed that dietary CSM was associated with linear decreases in body weight, average daily feed intake and average daily gain and linear increases in the feed-to-gain ratio from 1 to 28 days of age (P < 0.001). As the dietary CSM concentration increased, a numerical increase was found in the mortality of goslings. According to a single-slope broken-line model, the breakpoints for the average daily gain of dietary free gossypol concentration on days 1 to 14, 15 to 28, and 1 to 28 occurred at 23.63, 14.78, and 18.53 mg/kg, respectively. As the dietary CSM concentration increased, serum albumin (P < 0.001) concentrations decreased linearly and serum uric acid (P = 0.011) increased linearly. The hydroxyl radical scavenging ability (P = 0.002) and catalase (P < 0.001) and glutathione peroxidase (P = 0.001) activities of the liver decreased linearly with increasing dietary CSM. However, dietary CSM did not affect the concentrations of reactive oxygen metabolites, malondialdehyde, or protein carbonyl in the liver.

Conclusions

The increasing dietary CSM increased the concentration of free gossypol and altered the composition of some amino acids in the diet. A high concentration of CSM reduced the growth performance of goslings aged 1 to 28 days by decreasing feed intake, liver metabolism, and antioxidant capacity. From the primary concern of free gossypol in CSM, the tolerance of goslings to free gossypol from CSM is low, and the toxicity of free gossypol has a cumulative effect over time.
Temporal dynamics of Plasmodium falciparum population in Metehara, east-central Ethiopia
Authors: Reda Abeba Gebretsadik , Messele Alebachew , Mohammed Hussein , Assefa Ashenafi , Golassa Lemu , Mamo Hassen
Published: September 2022

Background

Plasmodium falciparum is the most serious, genetically most complex and fastest-evolving malaria parasite. Information on genetic diversity of this parasite would guide policy decision and malaria elimination endeavors. This study explored the temporal dynamics of P. falciparum population in two time points in Metehara, east-central Ethiopia.

Methods

The participants were quantitative real-time polymerase chain reaction-confirmed patients who were recruited for uncomplicated falciparum malaria therapeutic efficacy test in 2015 and 2019. Dry blood spot samples were analysed by the nested PCR to genotype P. falciparum merozoite surface protein (msp1, msp2) and glutamate-rich protein (glurp) genes.

Results

While msp1, msp2 and glurp genotypes were successfully detected in 26(89.7%), 24(82.8%) and 14(48.3%) of 2015 samples (n = 29); the respective figures for 2019 (n = 41) were 31(68.3%), 39(95.1%), 25(61.0%). In 2015, the frequencies of K1, MAD20 and RO33 allelic families of msp1, and FC27 and IC/3D7 of msp2 were 19(73.1%), 8(30.6%), 14(53.8%), 21(87.5%), 12(50.5%); and in 2019 it was 15(48.4%), 19(61.3%), 15(48.4%), 30(76.9%), 27(69.2%) respectively. MAD20 has shown dominance over both K1 and RO33 in 2019 compared to the proportion in 2015. Similarly, although FC27 remained dominant, there was shifting trend in the frequency of IC/3D7 from 50.5% in 2015 to 69.2% in 2019. The multiplicity of infection (MOI) and expected heterozygosity index (He) in 2015 and 2019 were respectively [1.43 ± 0.84] and [1.15 ± 0.91], 0.3 and 0.03 for msp1. However, there was no significant association between MOI and age or parasitaemia in both time points.

Conclusion

The lower genetic diversity in P. falciparum population in the two time points and overall declining trend as demonstrated by the lower MOI and He may suggest better progress in malaria control in Metehara. But, the driving force and selective advantage of switching to MAD20 dominance over the other two msp1 allelic families, and the dynamics within msp2 alleles needs further investigation.
Repositioning of drugs for Parkinson’s disease and pharmaceutical nanotechnology tools for their optimization
Authors: Hernández-Parra Héctor , Cortés Hernán , Avalos-Fuentes José Arturo , Del Prado-Audelo María , Florán Benjamín , Leyva-Gómez Gerardo , Sharifi-Rad Javad , Cho William C.
Published: September 2022

Parkinson’s disease (PD) significantly affects patients’ quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science, and Scopus from January 2015 at the end of 2021, with the descriptors “Parkinson’s disease” and “drug repositioning” or “drug repurposing”. We identified 28 drugs as potential candidates, and six of them were found in repositioning clinical trials for PD. However, a limitation of many of these drugs to achieve therapeutic success is their inability to cross the blood–brain barrier (BBB), as is the case with nilotinib, which has shown promising outcomes in clinical trials. We suggest reformulating these drugs in biodegradable nanoparticles (NPs) based on lipids and polymers to perform future trials. As a complementary strategy, we propose functionalizing the NPs surface by adding materials to the surface layer. Among other advantages, functionalization can promote efficient crossing through the BBB and improve the affinity of NPs towards certain brain regions. The main parameters to consider for the design of NPs targeting the central nervous system are highlighted, such as size, PDI, morphology, drug load, and Z potential. Finally, current advances in the use of NPs for Parkinson's disease are cited.
Application of nanotechnology in the early diagnosis and comprehensive treatment of gastrointestinal cancer
Authors: Deng Shenghe , Gu Junnan , Jiang Zhenxing , Cao Yinghao , Mao Fuwei , Xue Yifan , Wang Jun , Dai Kun , Qin Le , Liu Ke , Wu Ke , He Qianyuan , Cai Kailin
Published: September 2022

Gastrointestinal cancer (GIC) is a common malignant tumour of the digestive system that seriously threatens human health. Due to the unique organ structure of the gastrointestinal tract, endoscopic and MRI diagnoses of GIC in the clinic share the problem of low sensitivity. The ineffectiveness of drugs and high recurrence rates in surgical and drug therapies are the main factors that impact the curative effect in GIC patients. Therefore, there is an urgent need to improve diagnostic accuracies and treatment efficiencies. Nanotechnology is widely used in the diagnosis and treatment of GIC by virtue of its unique size advantages and extensive modifiability. In the diagnosis and treatment of clinical GIC, surface-enhanced Raman scattering (SERS) nanoparticles, electrochemical nanobiosensors and magnetic nanoparticles, intraoperative imaging nanoparticles, drug delivery systems and other multifunctional nanoparticles have successfully improved the diagnosis and treatment of GIC. It is important to further improve the coordinated development of nanotechnology and GIC diagnosis and treatment. Herein, starting from the clinical diagnosis and treatment of GIC, this review summarizes which nanotechnologies have been applied in clinical diagnosis and treatment of GIC in recent years, and which cannot be applied in clinical practice. We also point out which challenges must be overcome by nanotechnology in the development of the clinical diagnosis and treatment of GIC and discuss how to quickly and safely combine the latest nanotechnology developed in the laboratory with clinical applications. Finally, we hope that this review can provide valuable reference information for researchers who are conducting cross-research on GIC and nanotechnology.

Graphical Abstract
The roles of physician associates and advanced nurse practitioners in the National Health Service in the UK: a scoping review and narrative synthesis
Authors: Wang Hanyu , English Mike , Chakma Samprita , Namedre Mesulame , Hill Elaine , Nagraj Shobhana
Published: September 2022

Background

Mid-level practitioners (MLPs), including physician associates (PAs) and advanced nurse practitioners (ANPs), have emerged to address workforce shortages in the UK and perform specific roles in relation to population needs. This has resulted in new ways of working and changes to established professional hierarchies. We conducted a study to investigate the career development, competencies, effectiveness, perceptions, and regulation of PAs and ANPs, with the aim of understanding ways to effectively integrate MLPs into the NHS workforce.

Methods

We conducted a systematic scoping review following PRISMA guidelines. Embase, Medline, the Cochrane database, Pubmed, and CINAHL databases were searched, using terms relating to PAs and ANPs in the UK. A total of 128 studies (60 on PAs and 68 on ANPs) were included in the final analysis. A narrative synthesis, guided by the pre-defined themes and emerging themes, was conducted to bring together the findings.

Results

PAs are educated on a medical model with basic medical skills but lack formal professional regulation and do not have prescribing rights. ANPs are educated on a nurse model with enhanced skills that depend on roles within specific specialities, and their governance is mostly employer-led. PAs are primarily employed in secondary care. ANPs are employed widely in both primary and secondary care. No defined career progression exists for PAs. In contrast, becoming an ANP is a form of career progression within nursing. Both roles were regarded as cost-effective in comparison to doctors performing simple tasks. PAs were less understood compared to ANPs and received a mixed reception from colleagues, which sometimes undermined their professional identity, whereas ANPs were mostly welcomed by colleagues.

Conclusions

Potential ways to better integrate PAs and ANPs into the NHS workforce include further initiatives by regulatory bodies and the NHS to create more awareness and clearer role definitions for MLPs, outline potential for career progression, offer transparency with regard to remuneration, and introduction of prescribing rights. Future research might include more cadres of MLPs and explore the international literature.
Epidemiology and clinical features of PFAPA: a retrospective cohort study of 336 patients in western Sweden
Authors: Rydenman Karin , Fjeld Hanna , Hätting Josefine , Berg Stefan , Fasth Anders , Wekell Per
Published: September 2022

Background

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is generally regarded as the most common autoinflammatory disease, but the epidemiology of the disease is largely unknown. The objectives of this study were to estimate the annual incidence and describe the clinical features of PFAPA in a large cohort from western Sweden.

Methods

The study retrospectively included children < 18 years of age diagnosed with PFAPA between 2006 and 2017 at three hospitals: NU Hospital Group, Skaraborg Hospital and Queen Silvia Children’s Hospital. Patients were identified by searching for relevant diagnostic ICD-10 codes in the comprehensive electronic medical records and data were retrieved by reviewing case records. To estimate incidence, patients with symptom onset from January 1, 2006, to December 31, 2016, were included. Population data for the study area during this period were retrieved from Statistics Sweden.

Results

In this study, 336 patients with PFAPA were identified. Of these, 156 (46%) were girls and 180 (54%) were boys. Almost 90% of the children with PFAPA (291 patients) experienced their first symptoms before the age of 5 years and fewer than 3% presented at ages above 10 years. Pharyngitis was the most common symptom during febrile episodes, followed by cervical adenitis and aphthous stomatitis. Fourteen percent of the patients displayed atypical features, of which skin rash was the most common.

To calculate incidence, 251 patients with symptom onset during the study period were identified. The mean annual incidence was estimated at 0.86/10,000 for children < 18 years of age and 2.6/10,000 for children < 5 years of age.

Conclusions

This study adds to the understanding of the epidemiology of PFAPA syndrome by presenting incidence rates based on a large cohort and in different age groups in a population-based setting. It also shows the distribution of age of onset of PFAPA, with a peak in 1-year-olds and waning at older ages. Signs and symptoms of PFAPA syndrome were similar in children with symptom onset before vs. after 5 years of age.
Serum urea acid and urea nitrogen levels are risk factors for maternal and fetal outcomes of pregnancy: a retrospective cohort study
Authors: Wu Lanlan , Liu Yao , Liu Zengyou , Chen Hengying , Shen Siwen , Wei Yuanhuan , Sun Ruifang , Deng Guifang
Published: September 2022

Background

In recent years, results on the association between serum uric acid (UA) and pregnancy outcomes have been inconsistent, and the association between urea nitrogen (UN) and adverse pregnancy outcomes in normal pregnant women has not been reported. Thus, we examined the association of UA and UN levels during gestation with the risk of adverse pregnancy outcomes in a relatively large population.

Methods

A total of 1602 singleton mothers from Union Shenzhen Hospital of Huazhong University of Science and Technology at January 2015 to December 2018 were included. Both UA and UN levels were collected and measured during the second (16–18th week) and third (28–30th week) trimesters of gestation respectively. Statistical analysis was performed using multivariate logistic regression.

Results

After adjustment, the highest quartile of UA in the third trimester increased the risk of premature rupture of membranes (PROM) and small for gestational age infants (SGA) by 48% (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.04–2.10) and 99% (95% CI: 1.01–3.89) compared to those in the lowest quartile. The adjusted OR (95% CI) in the highest quartile of UN for the risk of SGA was 2.18 (95% CI: 1.16–4.13) and 2.29 (95% CI: 1.20–4.36) in the second and third trimester, respectively. In the second trimester, when UA and UN levels were both in the highest quartile, the adjusted OR (95% CI) for the risk of SGA was 2.51 (95% CI: 1.23–5.10). In the third trimester, when the group 1 (both indicators are in the first quartile) was compared, the adjusted ORs (95% CI) for the risk of SGA were 1.98 (95% CI: 1.22–3.23) and 2.31 (95% CI: 1.16–4.61) for group 2 (UA or UN is in the second or third quartile) and group 3 (both indicators are in the fourth quartile), respectively.

Conclusions

Higher UA and UN levels increased the risk of maternal and fetal outcomes. The simultaneous elevation of UA and UN levels was a high-risk factors for the development of SGA, regardless of whether they were in the second or third trimester.
Quality of care in abortion in the era of technological and medical advancements and self-care
Authors: Shukla Ankita , Vazquez-Quesada Lucía , Vieitez Isabel , Acharya Rajib , RamaRao Saumya
Published: September 2022

Background

Discussions around quality of abortion care have been focused mainly on service-delivery aspects inside healthcare facilities. More recently, with availability of medical abortion (MA), increase in its self-use, and emergence of other delivery platforms such as telemedicine, the responsibility of quality care has broadened to actors outside of facilities.

Body of text

This commentary discusses the meaning of quality of abortion care with the paradigm shift brought by medical and technological advancement in abortions, and raises questions on the role of the state in ensuring quality in abortion management—especially in settings where abortion is decriminalized, but also in countries where abortion is permitted under certain circumstances. It consolidates the experience gained thus far in the provision of safe abortion services and also serves as a forward-thinking tool to keep pace with the uptake of newer health technologies (e.g., availability of medical abortion drugs), service delivery platforms (e.g., telemedicine, online pharmacies), and abortion care providers (e.g., community based pharmacists).

Conclusions

This commentary provides context and rationale, and identifies areas for action that different stakeholders, including health advocates, policymakers, program managers, and women themselves, can adopt to fit into an alternative regime of abortion care.
Effect of hydroalcoholic seed extract of Nigella sativa on hepatic and pancreatic factors of Nrf2 and FGF21 in the regulation of insulin transcription factors of MafA and PDX-1 in streptozotocin-treated diabetic rats
Authors: Soleimani-Dodran Mahsa , Alipanah-Moghadam Reza , Jeddi Farhad , Babaei Mohammad , Salimnejad Ramin , Bahreini Elham
Published: September 2022

Introduction

Nigella sativa (N. sativa), one of the most commonly used medicinal herbs with antioxidant properties, increases blood insulin levels and lowers fasting blood sugar. Nuclear Erythroid Factor-Related Factor 2 (Nrf2) and Fibroblast Growth Factor 21 (FGF21) are two antioxidant factors that are increased by oxidative stress and hyperglycemia. The present study investigated how hydroalcoholic extract of N. sativa seed (HENS) increases blood insulin levels, taking into account changes in antioxidant factors and expression of insulin transcription factors.

Materials and methods

Two groups of male diabetic wistar rats were treated orally with HESN at doses of 200 and 400 mg/kg-body weight for one month. Fasting blood sugar (FBS) and insulin were measured using standard kits by photometric and ELISA methods, respectively. The expression levels of the Nrf2, FGF21 and β-Klotho genes as well as the insulin gene-stimulating transcription factors of MafA and PDX-1 were evaluated using real-time PCR. Oxidative stress was assessed by assessing serum total oxidation status (TOS), malondialdehyde (MDA), and total antioxidant capacity (TAC).

Results

HSEN showed a significant reducing effect on FBS and oxidative biomarkers and an increasing effect on serum insulin levels in treated diabetic rats compared to untreated diabetics (P < 0.05). The elevated levels of NRF2 and FGF21 in the liver and pancreas of the diabetic control group were significantly reduced after treatment with both HESN doses (P < 0.05). Following the ameliorative effects of HENS on pancreatic tissue and the reduction of oxidative stress, the expression level of MafA and PDX1 genes approached the level of these factors in healthy rats (P < 0.05).

Conclusion

This study showed the therapeutic effects of HENS on diabetic pancreas by reducing oxidative stress and tissue damage, modifying the expression levels of PDX-1 and MafA genes, and regulating insulin secretion and blood glucose levels.
The “whole ingredients extract” of Astragali Radix improves the symptoms of dextran sulfate sodium-induced ulcerative colitis in mice through systemic immunomodulation
Authors: Linghu Ke-Gang , Ma Qiushuo , Xiong Shi-Hang , Zhao Mingming , Chen Qiling , Xu Wen , Chen Meiwan , Zhang Jian-Ye , Hu Yuanjia , Xu Wei , Yu Hua
Published: September 2022

Background

Ulcerative colitis (UC) is a common inflammatory intestinal disease. Astragali Radix (AR) is one of the traditional Chinese medicines used in clinic for UC treatment. In our previous study, the whole ingredient extract (WIE) from AR have been proved to possess better immunomodulatory effects on immunosuppressed mice compared with the conventional water extraction (WAE). In the present study, we further evaluated the therapeutic effects of WIE against dextran sodium sulfate (DSS)-induced UC in mice through systemic immune regulation.

Methods

Gradient solvent extraction has been used to prepare the WIE of AR. The HPLC–MS analysis approach has been employed to analyze and compare the chemical differences between WAE and WIE. UC model was reproduced in 3% DSS-induced C57BL/6 mice for 6 days. Flow cytometric analysis for splenic lymphocyte subset. ELISA kits were used to determine the cytokines in the serum and colon tissues. The histopathological characteristics of colon were evaluated by hematoxylin–eosin staining and immunohistochemistry.

Results

The chemical compositions and the contents of main active ingredients were more abundant and higher in WIE than those in WAE. The WIE treatment altered a better action on reducing colitis disease activity index (DAI) and histological scores, as well as the recovered body weight and increased colon length in mice compared to the WAE group. Additionally, WIE showed better effects in recovering the levels of peripheral white blood cells in blood and cytokines (IL-2, IL-6 and MCP-1) in serum or colon tissues, improving the percentage of CD3+ and the ratio of CD4+/CD8+ in the spleen, and inhibiting the spleen enlargement in DSS-induced UC mice.

Conclusions

WIE has a more complete chemical composition than WAE. Meanwhile, WIE possesses better therapeutic effects on UC through resuming dysfunctional immunity in mice.
A scoping review of FGM in humanitarian settings: an overlooked phenomenon with lifelong consequences
Authors: Elnakib Shatha , Metzler Janna
Published: September 2022

Background

Female genital mutilation (FGM) is widely recognized as a human rights violation. Little is known about FGM rates and practices in humanitarian settings, and about the impact of crisis on the drivers and consequences of FGM. This scoping review set out to investigate the current research landscape on FGM in humanitarian settings.

Methods

We conducted a search of electronic databases and gray literature published between 1990 and 2021. This was coupled with backward citation tracking on eligible studies and reviews. We analyzed studies that met our eligibility criteria using thematic analysis.

Results

We found 13 peer-reviewed and four grey literature articles. Most studies were published in the last decade between 2010 and 2021, signaling growing attention to the issue. Five of the 17 articles provided estimates of incidence based on primary data collection amongst crisis-affected populations, ten focused on drivers, ten on consequences and five on interventions. The limited studies that have examined FGM in humanitarian settings indicate that the impact of crisis on FGM is multifaceted and context-specific, depending in part on interactions with host and other displaced communities and their social norms and practices. There is evidence that the acquisition and transfer of harmful social norms may take place during migration flows, but also that social norms underlying FGM may weaken in contexts of displacement, causing the practice to decrease. The incidence of FGM may also remain unchanged, but the type of FGM practiced may shift from more harmfully perceived forms to less radical forms. We found that drivers of FGM may be exacerbated, attenuated, or unchanged by crisis and displacement. Overall, there was predominant focus on medical consequences of FGM, and limited research on the social, economic, and psychological consequences of the practice. There was also a dearth of research into intervention effectiveness.

Conclusions

Despite an increase in research on FGM in humanitarian settings, there is still a notable dearth of studies investigating the impact of emergencies on FGM and the factors that propel it. More research and documentation of evidence are needed to inform interventions and policies.