bluuebunny/crossref_metadata_2025 huggingface dataset:
Von Willebrand factor, ADAMTS13 and mortality in dialysis patients
Authors: Ocak Gurbey , Roest Mark , Verhaar Marianne C. , Rookmaaker Maarten B. , Blankestijn Peter J. , Bos Willem Jan W. , Fijnheer Rob , Péquériaux Nathalie C. , Dekker Friedo W.
Published: June 2021

Background

Von Willebrand Factor (VWF) multimers are cleaved into smaller and less coagulant forms by the metalloprotease ADAMTS13. The aim of this study was to investigate the association between VWF and ADAMTS13 and mortality in dialysis patients.

Methods

We prospectively followed 956 dialysis patients. VWF levels and ADAMTS13 activity were measured. Cox proportional hazard analyses were used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) to investigate the association between quartiles of VWF levels and ADAMTS13 activity and all-cause mortality. HRs were adjusted for age, sex, body mass index, cardiovascular disease, dialysis modality, primary kidney disease, use of antithrombotic medication, systolic blood pressure, albumin, C-reactive protein and residual GFR.

Results

Of the 956 dialysis patients, 288 dialysis patients died within three years (mortality rate 151 per 1000 person-years). The highest quartile of VWF as compared with lower levels of VWF was associated with a 1.4-fold (95 %CI 1.1–1.8) increased mortality risk after adjustment. The lowest quartile of ADAMTS13 activity as compared with other quartiles was associated with a 1.3-fold (95 %CI 1.0-1.7) increased mortality risk after adjustment. The combination of the highest VWF quartile and lowest ADAMTS13 quartile was associated with a 2.0-fold (95 %CI 1.3-3.0) increased mortality risk as compared with the combination of the lowest VWF quartile and highest ADAMTS13 quartile.

Conclusions

High VWF levels and low ADAMTS13 activity were associated with increased mortality risks in dialysis patients.
Euglycaemic ketoacidosis in pregnant women with COVID-19: two case reports
Authors: Pikovsky Margaret , Tan Min Yi , Ahmed Amanda , Sykes Lynne , Agha-Jaffar Rochan , Yu Christina K. H.
Published: June 2021

Background

Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis. COVID-19 is associated with worse clinical outcomes in patients with diabetes and is an independent risk factor for ketoacidosis in normoglycaemic individuals.

Case presentations

We describe two cases of SARS-CoV-2 positive pregnant women presenting with normoglycaemic metabolic ketoacidosis. Both cases were associated with maternal and fetal compromise, requiring aggressive fluid and insulin resuscitation and early delivery.

Conclusion

We discuss possible physiology and propose a management strategy for euglycaemic ketoacidosis in pregnancy.
Acceptability and feasibility of strategies to shield the vulnerable during the COVID-19 outbreak: a qualitative study in six Sudanese communities
Authors: Abdelmagid Nada , Ahmed Salma A. E. , Nurelhuda Nazik , Zainalabdeen Israa , Ahmed Aljaile , Fadlallah Mahmoud Ali , Dahab Maysoon
Published: June 2021

Background

Shielding of high-risk groups from coronavirus disease (COVID-19) has been suggested as a realistic alternative to severe movement restrictions during the COVID-19 epidemic in low-income countries. The intervention entails the establishment of ‘green zones’ for high-risk persons to live in, either within their homes or in communal structures, in a safe and dignified manner, for extended periods of time during the epidemic. To our knowledge, this concept has not been tested or evaluated in resource-poor settings. This study aimed to explore the acceptability and feasibility of strategies to shield persons at higher risk of severe COVID-19 outcomes, during the COVID-19 epidemic in six communities in Sudan.

Methods

We purposively sampled participants from six communities, illustrative of urban, rural and forcibly-displaced settings. In-depth telephone interviews were held with 59 members of households with one or more members at higher risk of severe COVID-19 outcomes. Follow-up interviews were held with 30 community members after movement restrictions were eased across the country. All interviews were audio-recorded, transcribed verbatim, and analysed using a two-stage deductive and inductive thematic analysis.

Results

Most participants were aware that some people are at higher risk of severe COVID-19 outcomes but were unaware of the concept of shielding. Most participants found shielding acceptable and consistent with cultural inclinations to respect elders and protect the vulnerable. However, extra-household shielding arrangements were mostly seen as socially unacceptable. Participants reported feasibility concerns related to the reduced socialisation of shielded persons and loss of income for shielding families. The acceptability and feasibility of shielding strategies were reduced after movement restrictions were eased, as participants reported lower perception of risk in their communities and increased pressure to comply with social commitments outside the house.

Conclusion

Shielding is generally acceptable in the study communities. Acceptability is influenced by feasibility, and by contextual changes in the epidemic and associated policy response. The promotion of shielding should capitalise on the cultural and moral sense of duty towards elders and vulnerable groups. Communities and households should be provided with practical guidance to implement feasible shielding options. Households must be socially, psychologically and financially supported to adopt and sustain shielding effectively.
Socioeconomic inequalities in 29 childhood diseases: evidence from a 1,500,000 children population retrospective study
Authors: Carrilero Neus , Dalmau-Bueno Albert , García-Altés Anna
Published: June 2021

Background

Socioeconomic position (SEP) powerfully affects health status in the childhood population. However, the knowledge of which diseases are more affected by SEP and whose outcomes could be improved by having a more equitable society remains uncertain on a population basis.

Methods

We measured socioeconomic and gender inequalities in the pre-COVID-19 era for 29 diseases in the entire childhood population in Catalonia to identify which diseases are most impacted by inequalities. This population-based study included 1,449,816 children under 15 years old from 2014 to 2017 (48.52% girls) and each of their registered diagnoses within the Catalonia National Health System. We calculated frequency measures by SEP and their sex ratios for each disease. We estimated four regression-based inequality measures: slope index of inequality, relative index of inequality (RII), absolute population-attributable fraction, and population-attributable fraction.

Results

Twenty-five of the 29 diseases examined showed SEP inequalities. The diseases with the greatest inequalities in both sexes were tuberculosis, obesity, adjustment and anxiety disorders, essential hypertension, poisoning, short gestation, low birth weight, foetal growth retardation and intrauterine hypoxia and birth asphyxia and trauma (RII ≥ 2.0); only food allergy showed the opposite pattern (RII < 1.0). Overall, 80,188 (7.80%) of the disease events in boys and 74,921 (8.88%) in girls would be avoided if all children had the same disease rate as those in the medium-high SEP group, with tuberculosis, intrauterine hypoxia and birth asphyxia and trauma, obesity, and short gestation, low birth weight, foetal growth retardation being those that could be reduced the most in relative terms, and dermatitis, injuries, acute bronquitis, and being overweight those that could be reduced the most in absolute terms. Girls present higher RII than boys for respiratory allergy, asthma, dermatitis, being overweight, and obesity (p < 0.05). In contrast, boys showed higher RII compared to girls only in congenital anomalies (p < 0.05).

Conclusions

Socioeconomic and gender inequalities are widely present in childhood health. This indicates that SEP plays a common role in their development although it varies in magnitude according to each disease. It is also a phenomenon that comprises all SEP groups in society. Action needs to be taken to ensure a fairer start in life in terms of health.
The potential impacts of community drug checking within the overdose crisis: qualitative study exploring the perspective of prospective service users
Authors: Wallace Bruce , van Roode Thea , Pagan Flora , Hore Dennis , Pauly Bernadette
Published: June 2021

Background

As drug checking becomes more integrated within public health responses to the overdose crisis, and potentially more institutionalized, there is value in critically questioning the impacts of drug checking as a harm reduction response.

Methods

As part of a pilot project to implement community drug checking in Victoria, BC, Canada, in-depth interviews (N = 27) were held with people who use or have used substances, family or friends of people who use substances, and/or people who make or distribute substances. Critical harm reduction and social justice perspectives and a socioecological model guided our analysis to understand the potential role of drug checking within the overdose crisis, from the perspective of prospective service users.

Results

Participants provided insight into who might benefit from community drug checking and potential benefits. They indicated drug checking addresses a “shared need” that could benefit people who use substances, people who care for people who use substances, and people who sell substances. Using a socioecological model, we identified four overarching themes corresponding to benefits at each level: “drug checking to improve health and wellbeing of people who use substances”, “drug checking to increase quality control in an unregulated market”, “drug checking to create healthier environments”, and “drug checking to mediate policies around substance use”.

Conclusions

Drug checking requires a universal approach to meet the needs of diverse populations who use substances, and must not be focused on abstinence based outcomes. As a harm reduction response, community drug checking has potential impacts beyond the individual level. These include increasing power and accountability within the illicit drug market, improving the health of communities, supporting safer supply initiatives and regulation of substances, and mitigating harms of criminalization. Evaluation of drug checking should consider potential impacts that extend beyond individual behaviour change and recognize lived realities and structural conditions.
Early detection and intervention for acute perforated peptic ulcer after elective spine surgeries: a review of 13 cases from 24,026 patients
Authors: Lin Tung-Yi , Chuang Yu-Chun , Kao Fu-Cheng , Ping-Yeh Chiu , Tsai Tsung-Ting , Fu Tsai-Sheng , Lai Po-Liang
Published: June 2021

Background

To determine how perforated peptic ulcers be diagnosed earlier after patients undergoing an elective spine surgery.

Methods

Patients who underwent elective spine surgeries at our hospital between January 2000 and April 2018 and experienced an acute perforated peptic ulcer were included. An age-and gender-matched control group was comprised of 26 patients without a postoperative acute perforated peptic ulcer who received spine surgery during the same period. Medical records and imaging studies were thoroughly reviewed.

Results

Thirteen patients were enrolled in the study group, including eight females and five males. Three patients, two females and one male, died of uncontrolled peritonitis during the hospital stay. All patients in the study group experienced the sudden onset of abdominal pain, which was continuous and progressively worsening. Patients with elevated serum amylase, a peptic ulcer history and increased intraoperative blood loss had a tendency to develop a postoperative perforated peptic ulcer.

Conclusion

Spine surgeons should be highly alert to these risk factors of postoperative perforated peptic ulcers inpatients who has history of peptic ulcer, large amount ofintraoperative blood loss and abnormal high serum amylase level after elective spine surgery. Early diagnosis and emergent surgical intervention promote better outcomes.
Development of a method for phycocyanin recovery from filamentous cyanobacteria and evaluation of its stability and antioxidant capacity
Authors: Aoki Jinichi , Sasaki Daisaku , Asayama Munehiko
Published: June 2021

Background

Most commercial phycocyanins are extracted from a filamentous cyanobacterium, Arthrospira (Spirulina) platensis. Owing to the expenses of culture and complexities of the physical and chemical methods of phycocyanin purification, a more effective and simple method is required.

Results

We developed a new method for efficiently recovering the blue pigment protein, phycocyanin, from unique filamentous cyanobacteria, Pseudanabaena sp. ABRG5-3 and Limnothrix sp. SK1-2-1. The cells were cultivated in economy medium BG11 and lysed by adding water in a 1:16 ratio of wet cells to water. After extraction and purification, 28–30% dry cell weight of phycocyanin was obtained and its purity was confirmed. The stabilities of the phycocyanins at different pH in the presence of high temperature and light conditions and their antioxidant abilities were assessed. Results indicated that the phycocyanins were stable and possessed antioxidant properties. Interestingly, the Pseudanabaena phycocyanin was less likely to deteriorate under acidic conditions.

Conclusions

Overall, we developed a promising and novel method for producing high functional phycocyanin concentrations at a low cost. The possibilities of adapting this new phycocyanin biorefinery to unique bioreactor utilization have also been discussed.
The association of glycemic level and prevalence of tuberculosis: a meta-analysis
Authors: Chen Zhifei , Liu Qi , Song Ranran , Zhang Wenxin , Wang Tingping , Lian Zhan , Sun Xuezhi , Liu Yanli
Published: June 2021

Background

Diabetes is a well-known risk factor for tuberculosis and poorly glycemic control may increase the risk of tuberculosis. We performed a meta-analysis to explore the association of glycemic control in diabetic patients and their tuberculosis prevalence.

Methods

We included observational studies that investigated the prevalence of tuberculosis associated with glycemic control. The markers of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose were used to evaluate the exposure of interest in the study. We searched related articles in PubMed, EMBASE and Web of Science through 14 December 2019. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies.

Results

Seventeen studies (four cohort studies, five case-control studies and eight cross-sectional studies) were included, involving 1,027,074 participants. The meta-analysis found the pooled odds ratio of prevalent tuberculosis increased a 2.05-fold (95%CI: 1.65, 2.55) for the patients with HbA1c ≥7.0% compared to those with HbA1c concentration < 7.0%. Furthermore, we found the mean of HbA1c was higher in the diabetes mellitus with tuberculosis group than the diabetes-only group (P = 0.002). In the sensitivity analysis, the finding remains consistent.

Conclusion

Our study provides the evidence that poorly controlled diabetes in diabetics may be associated with increased prevalence of tuberculosis. More efforts should focus on screening tuberculosis in uncontrolled diabetes.
Residential exposure to fast-food restaurants and its association with diet quality, overweight and obesity in the Netherlands: a cross-sectional analysis in the EPIC-NL cohort
Authors: Harbers Marjolein C. , Beulens Joline W.J. , Boer Jolanda MA , Karssenberg Derek , Mackenbach Joreintje D. , Rutters Femke , Vaartjes Ilonca , Verschuren WM Monique , van der Schouw Yvonne T.
Published: June 2021

Background

Unhealthy food environments may contribute to unhealthy diets and risk of overweight and obesity through increased consumption of fast-food. Therefore, we aimed to study the association of relative exposure to fast-food restaurants (FFR) with overall diet quality and risk of overweight and obesity in a sample of older adults.

Methods

We analyzed cross-sectional data of the EPIC-NL cohort (n = 8,231). Data on relative FFR exposure was obtained through linkage of home address in 2015 with a retail outlet database. We calculated relative exposure to FFR by dividing the densities of FFR in street-network buffers of 400, 1000, and 1500 m around the home of residence by the density of all food retailers in the corresponding buffer. We calculated scores on the Dutch Healthy Diet 2015 (DHD15) index using data from a validated food-frequency questionnaire. BMI was categorized into normal weight (BMI < 25), overweight (25 ≤ BMI < 30), and obesity (BMI ≥ 30). We used multivariable linear regression (DHD15-index) and multinomial logistic regression (weight status), using quartiles of relative FFR exposure as independent variable, adjusting for lifestyle and environmental characteristics.

Results

Relative FFR exposure was not significantly associated with DHD15-index scores in the 400, 1000, and 1500 m buffers (βQ4vsQ1= -0.21 [95 %CI: -1.12; 0.70]; βQ4vsQ1= -0.12 [95 %CI: -1.10; 0.87]; βQ4vsQ1 = 0.37 [95 %CI: -0.67; 1.42], respectively). Relative FFR exposure was also not related to overweight in consecutive buffers (ORQ4vsQ1=1.10 [95 %CI: 0.97; 1.25]; ORQ4vsQ1=0.97 [95 %CI: 0.84; 1.11]; ORQ4vsQ1= 1.04 [95 %CI: 0.90–1.20]); estimates for obesity were similar to those of overweight.

Conclusions

A high proportion of FFR around the home of residence was not associated with diet quality or overweight and obesity in this large Dutch cohort of older adults. We conclude that although the food environment may be a determinant of food choice, this may not directly translate into effects on diet quality and weight status. Methodological improvements are warranted to provide more conclusive evidence.
Sociodemographic inequities in dental care utilisation among governmental welfare recipients in Japan: a retrospective cohort study
Authors: Nishioka Daisuke , Ueno Keiko , Kino Shiho , Aida Jun , Kondo Naoki
Published: June 2021

Background

Maintaining oral health is one of the global public health challenges. Income and out-of-pocket payments for dental care services are predictors of dental care utilisation. Although public assistance programmes guarantee income security for impoverished people, access barriers other than financial costs may cause unmet dental care needs. We aimed to explore the potential sociodemographic factors determining dental care utilisation among recipients of public assistance in Japan using linkage data of public assistance database and medical assistance claim data administered by municipalities.

Methods

This was a retrospective cohort study involving a sample of public assistance recipients. We extracted the recipients’ sociodemographic data (age, sex, household number, employment status, nationality, disability certificates, and long-term care status) in January 2016 and observed them until December 2016 to identify incidences of dental care utilisation as outcomes. We performed a multivariable modified Poisson regression analysis with a robust standard error estimator to calculate the incidence ratio (IR) of dental care utilisation in each variable.

Results

We identified a total of 4497 recipients at risk. Among them, 839 recipients used dental care services. Younger age was associated with a higher incidence of dental care utilisation. The female recipients had a higher incidence of dental care utilisation when compared to the male ones (adjusted IR, 1.22; 95% confidence interval [CI], 1.08–1.38). Immigrant recipients had a higher incidence of dental care utilisation than the Japanese ones (IR, 1.53; 95% CI, 1.16–2.01). Recipients with mental disabilities had higher incidences than those without disability certificates (IR, 1.30; 95% CI, 1.08–1.56).

Conclusions

Non-financial sociodemographic inequities in dental care utilisation stemming from age, sex, nationality, and presence of mental disability were found despite minimum income protection and equitable financial dental service access amongst public assistance recipients in Japan. Providing targeted preventive care and treatments for dental care among underserved populations is required to tackle oral health inequities.
Histiocytic pleural effusion: the strong clue to malignancy
Authors: Chae Ganghee , Jun Jae-Bum , Jung Hwa Sik , Park Chui Yong , Kim Jin Hyoung , Kang Byung Ju , Kang Hyeon Hui , Ra Seung Won , Seo Kwang Won , Jegal Yangjin , Ahn Jong Joon , Park Sang Hyuk , Lee Taehoon
Published: June 2021

Background

There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE.

Methods

In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed.

Results

Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology.

Conclusions

The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.
Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany
Authors: Bühler Klaus F. , Fischer Robert , Verpillat Patrice , Allignol Arthur , Guedes Sandra , Boutmy Emmanuelle , Bilger Wilma , Richter Emilia , D’Hooghe Thomas
Published: June 2021

Background

This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany.

Methods

Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle).

Results

Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP.

Conclusions

This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.
Advancing our understanding of HIV co-infections and neurological disease using the humanized mouse
Authors: Endsley Janice J. , Huante Matthew B. , Naqvi Kubra F. , Gelman Benjamin B. , Endsley Mark A.
Published: June 2021

Humanized mice have become an important workhorse model for HIV research. Advances that enabled development of a human immune system in immune deficient mouse strains have aided new basic research in HIV pathogenesis and immune dysfunction. The small animal features facilitate development of clinical interventions that are difficult to study in clinical cohorts, and avoid the high cost and regulatory burdens of using non-human primates. The model also overcomes the host restriction of HIV for human immune cells which limits discovery and translational research related to important co-infections of people living with HIV. In this review we emphasize recent advances in modeling bacterial and viral co-infections in the setting of HIV in humanized mice, especially neurological disease, andMycobacterium tuberculosisand HIV co-infections. Applications of current and future co-infection models to address important clinical and research questions are further discussed.
Repeated oral administration of low doses of silver in mice: tissue distribution and effects on central nervous system
Authors: Recordati Camilla , De Maglie Marcella , Cella Claudia , Argentiere Simona , Paltrinieri Saverio , Bianchessi Silvia , Losa Marco , Fiordaliso Fabio , Corbelli Alessandro , Milite Gianpaolo , Aureli Federica , D’Amato Marilena , Raggi Andrea , Cubadda Francesco , Soldati Sabina , Lenardi Cristina , Scanziani Eugenio
Published: June 2021

Background

Widespread use of silver in its different forms raises concerns about potential adverse effects after ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4 weeks of recovery.

Results

There were no treatment-related clinical signs and mortality, and no significant effects on body and organ weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No histopathological changes and absence of silver staining by autometallography were observed in the organs of treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgAc-treated mice at the EoT.

Conclusions

Our study revealed accumulation and slow clearance of silver in the brain after oral administration of 10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of the Blood-Brain Barrier.
How to deal with the consent of adults with cognitive impairment involved in European geriatric living labs?
Authors: Sacco Guillaume , Noublanche Frédéric , Blazek Frédéric , Hue Catherine , Carballido Loïc , Asfar Marine , Allain Philippe , Annweiler Cédric
Published: June 2021

Background

Living labs are realistic environments designed to create links between technology developers and end-users (i.e. mostly older adults). Research in LLH (Living labs in health) covers a wide range of studies from non-interventional studies to CT (clinical trials) and should involve patients with neurocognitive disorders. However, the ethical issues raised by the design, development, and implementation of research and development projects in LLH have been the subject of only little interest thus far.

Objective

Our aim was to determine a pragmatic, ethical and regulatory correct approach to seek the informed consent of patients with neurocognitive disorders according to the different types of studies carried out in European LLH, with a focus on the French context.

Methods

A narrative review of regulatory texts and clinical articles was conducted, and a pragmatic procedure to determine the decision-making capacity of older adults in LLH was proposed.

Results

Individuals must be adequately informed and freely agree to participate in CT. The capacity to consent should be assessed in CT including cognitively impaired older adults. We propose the following steps: first to assess for delirium using the 4 ‘A’s Test (4AT) or the 3-min Diagnostic interview for Confusion Assessment Method (3D-CAM), second to search for medical history of major neurocognitive disorder, and third to assess the decision capacity using the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC).

Conclusions

Including individuals with neurocognitive disorders in research implies using an efficient and pragmatic strategy to inform participants and obtain their consent. The tool we offer here may be useful in the routine operation of LLH but can also be extended to all CT with this population.
Increased acromiohumeral distance in a double-row arthroscopic rotator cuff surgery compared to a single-row surgery after 12 months
Authors: Turan Kaya , Çabuk Haluk , Köroğlu Cenk , Öztürk Çağatay
Published: June 2021

Background

Arthroscopic rotator cuff surgery is an effective treatment for rotator cuff tears with the considered use of double-row repair techniques becoming popular in the last decade. We aim to compare the effects of double- and single-row arthroscopic rotator cuff repairs (ARCR) on repair integrity (RI) and acromiohumeral distance (AHD).

Methods

In this observational study, we retrospectively identified 98 patients with degenerative rotator cuff tear treated with arthroscopic rotator cuff repair between 2016 and 2019. We excluded 22 patients with partial-thickness tears, 15 with associated subscapularis or SLAP tears, 13 with massive tears, and 5 patients lost to follow-up; we included 43 patients who had ARCR for full-thickness cuff tear and clinical, radiologic follow-up. Of these 43 patients, 23 are grouped as double-row repair group (DRG) and 20 as single-row repair group (SRG). A minimum of 12 months after the surgery, bilateral shoulder MRIs were obtained. Contralateral shoulders without asymptomatic rotator cuff tears served as a control group (CG). The operating surgeon and two other surgeons experienced in arthroscopy blindly measured the AHD and determined the RI at the control MRIs in all groups. Functional assessments relied on UCLA and qDASH Scores.

Results

The mean age was 57.89 (45–78) years, and the mean follow-up time was 28,65 (21–43) months. The mean AHD of the CG was 9.7 ± 0.96 mm, the preoperative AHD of DRG was 8.62 ± 1.45 mm, and SRG was 9.71 ± 0.95 mm. The postoperative mean AHD of DRG 9.61 ± 1.83 mm and SRG was 10.21 ± 1.97 mm. AHD differences between the preoperative and postoperative groups were significant (P=0.009). The increase of the AHD in the double-row group was significantly higher than the single-row group (P=0.004). There was a high correlation between the RI and DASH scores (P=0.005). RI did not correlate with the repair method (P=0.580).

Conclusion

Although double-row repairs can maintain greater AHD than single-row repairs in the clinical setting, this difference did not affect functional results. Regardless of the surgical intervention, functional results are favourable if RI is achieved.

Level of evidence

Level III, Retrospective Cohort Study
The comparison between anterior and posterior approaches for removal of infected lumbar interbody cages and a proposal regarding the use of endoscope-assisted technique
Authors: Li Yun-Da , Chi Jia-En , Chiu Ping-Yeh , Kao Fu-Cheng , Lai Po-Liang , Tsai Tsung-Ting
Published: June 2021

Background

In cases of postoperative deep wound infection after interbody fusion with cages, it is often difficult to decide whether to preserve or remove the cages, and there is no consensus on the optimal approach for removing cages. The aim of this study was to investigate the surgical management of cage infection after lumbar interbody fusion.

Methods

A retrospective study was conducted between January 2012 and August 2018. Patients were included if they had postoperative deep wound infection and required cage removal. Clinical outcomes, including operative parameters, visual analog scale, neurologic status, and fusion status, were assessed and compared between anterior and posterior approaches for cage removal.

Results

Of 130 patients who developed postoperative infection and required surgical debridement, 25 (27 levels) were diagnosed with cage infection. Twelve underwent an anterior approach, while 13 underwent cage removal with a posterior approach. Significant differences were observed between the anterior and posterior approaches in elapsed time to the diagnosis of cage infection, operative time, and hospital stay. All patients had better or stationary American Spinal Injury Association impairment scale, but one case of recurrence in adjacent disc 3 months after the surgery.

Conclusions

Both anterior and posterior approaches for cage removal, followed by interbody debridement and fusion with bone grafts, were feasible methods and offered promising results. An anterior approach often requires an additional extension of posterior instrumentation due to the high incidence of concurrent pedicle screw loosening. The use of an endoscope-assisted technique is suggested to facilitate safe removal of cages.
Circulating tumor DNA tracking through driver mutations as a liquid biopsy-based biomarker for uveal melanoma
Authors: Bustamante Prisca , Tsering Thupten , Coblentz Jacqueline , Mastromonaco Christina , Abdouh Mohamed , Fonseca Cristina , Proença Rita P. , Blanchard Nadya , Dugé Claude Laure , Andujar Rafaella Atherino Schmidt , Youhnovska Emma , Burnier Miguel N. , Callejo Sonia A. , Burnier Julia V.
Published: June 2021

Background

Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations.

Methods

We used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15).

Results

The in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors.

Conclusions

We report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.
Two Fusarium copper radical oxidases with high activity on aryl alcohols
Authors: Cleveland Maria , Lafond Mickael , Xia Fan Roderick , Chung Ryan , Mulyk Paul , Hein Jason E. , Brumer Harry
Published: June 2021

Background

Biomass valorization has been suggested as a sustainable alternative to petroleum-based energy and commodities. In this context, the copper radical oxidases (CROs) from Auxiliary Activity Family 5/Subfamily 2 (AA5_2) are attractive biocatalysts for the selective oxidation of primary alcohols to aldehydes. Originally defined by the archetypal galactose 6-oxidase fromFusarium graminearum, fungal AA5_2 members have recently been shown to comprise a wide range of specificities for aromatic, aliphatic and furan-based alcohols. This suggests a broader substrate scope of native CROs for applications. However, only 10% of the annotated AA5_2 members have been characterized to date.

Results

Here, we define two homologues from the filamentous fungiFusarium graminearumandF. oxysporumas predominant aryl alcohol oxidases (AAOs) through recombinant production inPichia pastoris, detailed kinetic characterization, and enzyme product analysis. Despite possessing generally similar active-site architectures to the archetypalFgrGalOx,FgrAAO andFoxAAO have weak activity on carbohydrates, but instead efficiently oxidize specific aryl alcohols. Notably, bothFgrAAO andFoxAAO oxidize hydroxymethyl furfural (HMF) directly to 5-formyl-2-furoic acid (FFCA), and desymmetrize the bioproduct glycerol to the uncommon L-isomer of glyceraldehyde.

Conclusions

This work expands understanding of the catalytic diversity of CRO from AA5_2 to include unique representatives fromFusariumspecies that depart from the well-known galactose 6-oxidase activity of this family. Detailed enzymological analysis highlights the potential biotechnological applications of these orthologs in the production of renewable plastic polymer precursors and other chemicals.
Correction to: A point-of-care thoracic ultrasound protocol for hospital medical emergency teams (METUS) improves diagnostic accuracy
Authors: Blans M. J. , Bousie E. , van der Hoeven J. G. , Bosch F. H.
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Enriched gardens improve cognition and independence of nursing home residents with dementia: a pilot controlled trial
Authors: Bourdon Etienne , Belmin Joël
Published: June 2021

Background

Dementia is a major issue worldwide, and considerable efforts were made to design therapeutic mediation tools and evaluate their benefits on the health of patients.

Methods

Design: Multi-center cluster-controlled pilot trial.

Settings and participants: Four nursing homes that offered separated access to one conventional sensory garden (CSG) and one enriched garden (EG). The participants were residents with dementia, independent for walking and with no severe dementia or behavioural troubles. Eligible residents were divided into three groups according to the proximity of their room: close to the CSG or EG gardens for the first two groups and further from the gardens for the third (control) group.

Interventions: We asked staff members to frequently invite residents to visit the EG or the CSG depending on their group allocation. No invitation to gardens was made to the control group. We installed 12 enrichment modules in the EG that stimulated cognitive, independence and walking/balance functions.

Measures: Cognitive function (MMSE), independence for activities of daily living (ADL) and risk of falls (unipodal stance and timed up and go – (TUG)) were assessed at baseline and after 6 months.

Results

The 120 participants were 81·0 ± 3·5 years old and comprised of 83 women. Their MMSE score was 17·5 ± 2·9. Patients’ characteristics were not significantly different between the three groups. Among the participants invited to visit the EG group, 6-month changes in MMSE showed improvement compared to other groups (+ 0·93 ± 0·65 vs −0·25 ± 0·71 and −0·24 ± 0·73 in the EG vs CSG and control groups, respectively, P < 0·0001). Changes in ADL, TUG and unipodal stance were significantly improved in the group visiting the EG as compared to other groups, which indicates better functioning.

Conclusions

EGs offer a new approach to therapeutic mediation for residents of nursing homes with dementia.
Differential diagnosis of uncommon prostate diseases: combining mpMRI and clinical information
Authors: Han Chao , Zhu Lina , Liu Xiang , Ma Shuai , Liu Yi , Wang Xiaoying
Published: June 2021

The differential diagnosis of abnormalities in the prostate is broad, covering common (acinar adenocarcinoma, benign prostatic hyperplasia, chronic prostatitis, hemorrhage, cysts, calcifications, atrophy and fibrosis) and less common conditions (tumors other than acinar adenocarcinoma, granulomatous prostatitis containing tuberculosis, abscesses and other conditions, and idiopathic disorders such as amyloidosis and exophytic benign prostatic hyperplasia). Recent advances in magnetic resonance imaging (MRI) of the prostate gland and imaging guidelines, such as the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1), have dramatically improved the ability to distinguish common abnormalities, especially the ability to detect clinically significant prostate cancer (csPCa). Overlap can exist in the clinical history and imaging features associated with various common/uncommon prostate abnormalities, and biopsy is often required but is invasive. Prostate abnormalities can be divided into two categories: category 1, diseases for which PI-RADS scores are suitable for use, and category 2, diseases for which PI-RADS scores are unsuitable for use. Radiologists must have an intimate knowledge of other diseases, especially uncommon conditions. Past relevant history, symptoms, age, serum prostate-specific antigen (PSA) levels, MRI manifestations, and the applicability of the PI-RADS assessment should be considered when diagnosing prostate abnormalities.
RETRACTED ARTICLE: Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
Authors: Zhang Ruijie , Li Peng , Lv Heli , Li Nana , Ren Suliang , Xu Wentao
Published: June 2021

Background

Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy.

Methods

Long non-coding RNA (lncRNA) SNHG16 expression level was measured by microarray and qRT-PCR assay; ISH was used to identify the location of SNHG16. Cancer stem cells (CSCs) were separated from glioma tissues and identified using immunofluorescence. Exosomes were isolated from CSCs and cancer cells and identified by TEM and western blot. MTT, wound healing, transwell, and colony formation assay were performed to explore the role of SNHG16 or si-SNHG16 from CSCs on progression of glioma cells. RIP was used to verify the interaction between SNHG16 and TLR7. The experiment of Xenograft used for exploring the function of SNHG16/ TLR7/MyD88/NFκB/c-Myc on growth on glioma in vivo.

Results

Microarray assay showed long non-coding RNA (lncRNA) SNHG16 was upregulated in glioma. Followed qRT-PCR also showed an increase of SNHG16 in glioma tissues; high expression of SNHG16 indicated a poor prognosis in glioma patients. Interestingly, SNHG16 was packaged into exosomes and derived from CSCs. Functional analysis showed exo-SNHG16 secreted by CSCs promoted the progression of glioma cell lines SHG44 and U251. Furthermore, SNHG16 interacted with TLR7 and activated NFκB/c-Myc signaling in glioma cells. And the silencing of TLR7 inhibited the progression of SHG44 and U251 cells by exo-SNHG16 from CSCs. In vivo tumorigenesis experiments showed that exo-SNHG16 induced glioma progression by activating TLR7/MyD88/NFκB/c-Myc signaling.

Conclusion

Our study suggested CSC-derived exo-SNHG16 promoted cancer progression by activating TLR7/MyD88/NFκB/c-Myc signaling pathway.