bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding why patients request euthanasia when it is illegal: a qualitative study in palliative care units on the personal and practical impact of euthanasia requests
Authors: Leboul Danièle , Bousquet Anne , Chassagne Aline , Mathieu-Nicot Florence , Ridley Ashley , Cretin Elodie , Guirimand Frédéric , Aubry Régis
Published: January 2022

Context:

Some patients in palliative care units request euthanasia regardless of legislation. Although studies have explored the reasons for these requests, little is known about the subjective, relational, and contextual repercussions for the patient.

Objectives:

The aim of this study is to understand the purpose of euthanasia requests from the patient’s viewpoint and their personal and practical impact.

Methods:

We conducted in-depth interviews with patients requesting euthanasia, their family members, and health care providers in 11 French palliative care units. A thematic analysis of the data was performed.

Results:

In total, 18 patients were interviewed within 48 h of the request being made; 1 week later, 9 patients were interviewed again. Five main themes emerged: assuming the possibility of transgressing the forbidden, a call for unbearable suffering to be recognized, encouragement to change clinical practice, reclaiming a sense of freedom over medical constraints, and imagining a desirable future for oneself.

Conclusions:

A request for euthanasia appears to be a willful means to remove oneself from the impasse of an existence paralyzed by suffering. It creates a space for discussion, which promotes negotiation with patients on care practices and therapeutics, and strengthens patients’ sense of autonomy. Investigating the relationship between the evolution of euthanasia requests within the palliative care setting could be beneficial. It is important to encourage health care professionals to adopt a readiness to listen by interacting with patients in a way that is not momentarily action-oriented but rather focused on proactive discussion.
NSAID-exacerbated respiratory disease: a population study
Authors: Andersén Heidi , Ilmarinen Pinja , Honkamäki Jasmin , Tuomisto Leena E. , Hisinger-Mölkänen Hanna , Backman Helena , Lundbäck Bo , Rönmark Eva , Haahtela Tari , Sovijärvi Anssi , Lehtimäki Lauri , Piirilä Päivi , Kankaanranta Hannu
Published: January 2022

Background

Nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate respiratory symptoms. A recent European Academy of Allergy and Clinical Immunology position paper recommended the use of an acronym, N-ERD (NSAID-exacerbated respiratory disease), for this hypersensitivity associated with asthma or chronic rhinosinusitis with or without nasal polyposis. Our aim was to estimate the prevalence of N-ERD and identify factors associated with N-ERD.

Methods

In 2016, a cross-sectional questionnaire survey of a random adult population of 16 000 subjects aged 20–69 years was performed in Helsinki and Western Finland. The response rate was 51.5%.

Results

The prevalence was 1.4% for N-ERD, and 0.7% for aspirin-exacerbated respiratory disease (AERD). The prevalence of N-ERD was 6.9% among subjects with asthma and 2.7% among subjects with rhinitis. The risk factors for N-ERD were older age, family history of asthma or allergic rhinitis, long-term smoking and exposure to environmental pollutants. Asthmatic subjects with N-ERD had a higher risk of respiratory symptoms, severe hypersensitivity reactions and hospitalisations than asthmatic subjects without N-ERD. The subphenotype of N-ERD with asthma was most symptomatic. Subjects with rhinitis associated with N-ERD, which would not be included in AERD, had the fewest symptoms.

Conclusion

We conclude that the prevalence of N-ERD was 1.4% in a representative Finnish adult population sample. Older age, family history of asthma or allergic rhinitis, cumulative exposure to tobacco smoke, secondhand smoke, and occupational exposures increased odds of N-ERD. N-ERD was associated with significant morbidity.
Computed tomography lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with lung disease
Authors: Dwivedi Krit , Condliffe Robin , Sharkey Michael , Lewis Robert , Alabed Samer , Rajaram Smitha , Hill Catherine , Saunders Laura , Metherall Peter , Alandejani Faisal , Alkhanfar Dheyaa , Wild Jim M. , Lu Haiping , Kiely David G. , Swift Andrew J.
Published: January 2022

Background

Patients with pulmonary hypertension (PH) and lung disease may pose a diagnostic dilemma between idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-CLD). The prognostic impact of common computed tomography (CT) parenchymal features is unknown.

Methods

660 IPAH and PH-CLD patients assessed between 2001 and 2019 were included. Reports for all CT scans 1 year prior to diagnosis were analysed for common lung parenchymal patterns. Cox regression and Kaplan–Meier analysis were performed.

Results

At univariate analysis of the whole cohort, centrilobular ground-glass (CGG) changes (hazard ratio, HR 0.29) and ground-glass opacification (HR 0.53) predicted improved survival, while honeycombing (HR 2.79), emphysema (HR 2.09) and fibrosis (HR 2.38) predicted worse survival (all p<0.001). Fibrosis was an independent predictor after adjusting for baseline demographics, PH severity and diffusing capacity of the lung for carbon monoxide (HR 1.37, p<0.05). Patients with a clinical diagnosis of IPAH who had an absence of reported parenchymal lung disease (IPAH-noLD) demonstrated superior survival to patients diagnosed with either IPAH who had coexistent CT lung disease or PH-CLD (2-year survival of 85%, 60% and 46%, respectively, p<0.05). CGG changes were present in 23.3% of IPAH-noLD and 5.8% of PH-CLD patients. There was no significant difference in survival between IPAH-noLD patients with or without CGG changes. PH-CLD patients with fibrosis had worse survival than those with emphysema.

Interpretation

Routine clinical reports of CT lung parenchymal disease identify groups of patients with IPAH and PH-CLD with significantly different prognoses. Isolated CGG changes are not uncommon in IPAH but are not associated with worse survival.
Monogenic gene variants in lung transplant recipients with usual interstitial pneumonia
Authors: Stark Christoffer , Koskenvuo Juha W. , Nykänen Antti , Seppälä Eija H. , Myllykangas Samuel , Lemström Karl , Raivio Peter
Published: January 2022

Aim

The prevalence of monogenic disease-causing gene variants in lung transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.

Patients and methods

We retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.

Results

15 patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. 11 patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.

Conclusion

Genetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.
ERS International Congress 2021: highlights from the Interstitial Lung Diseases Assembly
Authors: Guler Sabina A. , Cuevas-Ocaña Sara , Nasser Mouhamad , Wuyts Wim A. , Wijsenbeek Marlies S. , Froidure Antoine , Bargagli Elena , Renzoni Elisabetta A. , Veltkamp Marcel , Spagnolo Paolo , Nunes Hilario , McCarthy Cormac , Molina-Molina Maria , Bonella Francesco , Poletti Venerino , Kreuter Michael , Antoniou Katerina M. , Moor Catharina C.
Published: January 2022

This article provides an overview of scientific highlights in the field of interstitial lung disease (ILD), presented at the virtual European Respiratory Society Congress 2021. A broad range of topics was discussed this year, ranging from translational and genetic aspects to novel innovations with the potential to improve the patient pathway. Early Career Members summarise a selection of interesting findings from different congress sessions, together with the leadership of Assembly 12 – Interstitial Lung Disease.
Evaluation of adverse effects/events of genetically modified food consumption: a systematic review of animal and human studies
Authors: Shen Chen , Yin Xiang-Chang , Jiao Bo-Yang , Li Jing , Jia Peng , Zhang Xiao-Wen , Cheng Xue-Hao , Ren Jian-Xin , Lan Hui-Di , Hou Wen-Bin , Fang Min , Li Xun , Fei Yu-Tong , Robinson Nicola , Liu Jian-Ping
Published: January 2022

Objective

A systematic review of animal and human studies was conducted on genetically modified (GM) food consumption to assess its safety in terms of adverse effects/events to inform public concerns and future research.

Methods

Seven electronic databases were searched from January 1st 1983 till July 11th 2020 for in vivo, animal and human studies on the incidence of adverse effects/events of GM products consumption. Two authors independently identified eligible studies, assessed the study quality, and extracted data on the name of the periodical, author and affiliation, literature type, the theme of the study, publication year, funding, sample size, target population characteristics, type of the intervention/exposure, outcomes and outcome measures, and details of adverse effects/events. We used the Chi-square test to compare the adverse event reporting rates in articles funded by industry funding, government funding or unfunded articles.

Results

One crossover trial in humans and 203 animal studies from 179 articles met the inclusion criteria. The study quality was all assessed as being unclear or having a high risk of bias. Minor illnesses were reported in the human trial. Among the 204 studies, 59.46% of adverse events (22 of 37) were serious adverse events from 16 animal studies (7.84%). No significant differences were found in the adverse event reporting rates either between industry and government funding (χ2 = 2.286, P = 0.131), industry and non-industry funding (χ2 = 1.761, P = 0.185) or funded and non-funded articles (χ2 = 0.491, P = 0.483). We finally identified 21 GM food-related adverse events involving 7 GM events (NK603 × MON810 maize, GTS 40-3-2 soybean, NK603 maize, MON863 maize, MON810 maize, MON863 × MON810 × NK603 maize and GM Shanyou 63 rice), which had all been on regulatory approval in some countries/regions.

Conclusion

Serious adverse events of GM consumption include mortality, tumour or cancer, significant low fertility, decreased learning and reaction abilities, and some organ abnormalities. Further clinical trials and long-term cohort studies in human populations, especially on GM food-related adverse events and the corresponding GM events, are still warranted. It suggests the necessity of labelling GM food so that consumers can make their own choice.
Ear microbiota and middle ear disease: a longitudinal pilot study of Aboriginal children in a remote south Australian setting
Authors: Taylor Steven L. , Papanicolas Lito E. , Richards Alyson , Ababor Furdosa , Kang Wan Xian , Choo Jocelyn M. , Woods Charmaine , Wesselingh Steve L. , Ooi Eng H. , MacFarlane Patricia , Rogers Geraint B.
Published: January 2022

Background

Otitis media (OM) is a major disease burden in Australian Aboriginal children, contributing to serious long-term health outcomes. We report a pilot analysis of OM in children attending an outreach ear and hearing clinic in a remote south Australian community over a two-year period. Our study focuses on longitudinal relationships between ear canal microbiota characteristics with nasopharyngeal microbiota, and clinical and treatment variables.

Results

Middle ear health status were assessed in 19 children (aged 3 months to 8 years) presenting in remote western South Australia and medical interventions were recorded. Over the two-year study period, chronic suppurative OM was diagnosed at least once in 7 children (37%), acute OM with perforation in 4 children (21%), OM with effusion in 11 children (58%), while only 1 child had no ear disease. Microbiota analysis of 19 children (51 sets of left and right ear canal swabs and nasopharyngeal swabs) revealed a core group of bacterial taxa that included Corynebacterium, Alloiococcus, Staphylococcus, Haemophilus, Turicella, Streptococcus, and Pseudomonas. Within-subject microbiota similarity (between ears) was significantly greater than inter-subject similarity, regardless of differences in ear disease (p = 0.0006). Longitudinal analysis revealed changes in diagnosis to be associated with more pronounced changes in microbiota characteristics, irrespective of time interval. Ear microbiota characteristics differed significantly according to diagnosis (P (perm) = 0.0001). Diagnoses featuring inflammation with tympanic membrane perforation clustering separately to those in which the tympanic membrane was intact, and characterised by increased Proteobacteria, particularly Haemophilus influenzae, Moraxella catarrhalis, and Oligella. While nasopharyngeal microbiota differed significantly in composition to ear microbiota (P (perm) = 0.0001), inter-site similarity was significantly greater in subjects with perforated tympanic membranes, a relationship that was associated with the relative abundance of H. influenzae in ear samples (rs = − 0.71, p = 0.0003). Longitudinal changes in ear microbiology reflected changes in clinical signs and treatment.

Conclusions

Children attending the ear and hearing clinic in a remote Aboriginal community present with a broad spectrum of OM conditions and severities, consistent with other remote Aboriginal communities. Ear microbiota characteristics align with OM diagnosis and change with disease course. Nasopharyngeal microbiota characteristics are consistent with the contribution of acute upper respiratory infection to OM aetiology.
Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible with clinical-pathologic grounds) during the COVID-19 pandemic: an observational case-control study
Authors: Bickel Amitai , Ganam Samer , Abu Shakra Ibrahim , Farkash Inbal , Francis Rola , Karra Nour , Merei Fahed , Cohen Isaac , Kakiashvili Eli
Published: January 2022

Background

During a global crisis like the current COVID-19 pandemic, delayed admission to hospital in cases of emergent medical illness may lead to serious adverse consequences. We aimed to determine whether such delayed admission affected the severity of an inflammatory process regarding acute appendicitis, and its convalescence.

Methods

In a retrospective observational cohort case-control study, we analyzed the medical data of 60 patients who were emergently and consecutively admitted to our hospital due to acute appendicitis as established by clinical presentation and imaging modalities, during the period of the COVID-19 pandemic (our study group). We matched a statistically control group consisting of 97 patients who were admitted during a previous 12-month period for the same etiology. All underwent laparoscopic appendectomy. The main study parameters included intraoperative findings (validated by histopathology), duration of abdominal pain prior to admission, hospital stay and postoperative convalescence (reflecting the consequences of delay in diagnosis and surgery).

Results

The mean duration of abdominal pain until surgery was significantly longer in the study group. The rate of advanced appendicitis (suppurative and gangrenous appendicitis as well as peri-appendicular abscess) was greater in the study than in the control group (38.3 vs. 21.6%, 23.3 vs. 16.5%, and 5 vs. 1% respectively), as well as mean hospital stay.

Conclusions

A global crisis like the current viral pandemic may significantly affect emergent admissions to hospital (as in case of acute appendicitis), leading to delayed surgical interventions and its consequences.
Mild renal insufficiency and attributable risk of adverse In-hospital outcomes in patients with Acute Coronary Syndrome from the improving care for Cardiovascular Disease in China (CCC) project
Authors: Xu Fengbo , Wang Guoqin , Ye Nan , Bian Weijing , Yang Lijiao , Ma Changsheng , Zhao Dong , Liu Jing , Hao Yongchen , Liu Jun , Yang Na , Cheng Hong
Published: January 2022

Background

Renal insufficiency (RI) is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate the attributable risk associated with mild RI for the in-hospital outcomes in patients with ACS.

Methods

The Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 92,509 inpatients with a discharge diagnosis of ACS were included. The attributable risk was calculated to investigate the effect of mild RI (eGFR 60-89 ml / min · 1.73 m2) on major adverse cardiovascular events (MACEs) during hospitalization.

Results

The average age of these ACS patients was 63 years, and 73.9% were men. The proportion of patients with mild RI was 36.17%. After adjusting for other possible risk factors, mild RI was still an independent risk factor for MACEs in ACS patients. In the ACS patients, the attributable risk of eGFR 60-89ml/min·1.73m2to MACEs was 7.78%, 4.69% of eGFR 45-59 ml/min·1.73m2, 4.46% of eGFR 30-44 ml/min·1.73m2, and 3.36% of eGFR<30 ml/min·1.73m2.

Conclusion

Compared with moderate to severe RI, mild RI has higher attributable risk to MACEs during hospitalization in Chinese ACS population.
Association between county-level risk groups and COVID-19 outcomes in the United States: a socioecological study
Authors: Khan Sadiya S. , Krefman Amy E. , McCabe Megan E. , Petito Lucia C. , Yang Xiaoyun , Kershaw Kiarri N. , Pool Lindsay R. , Allen Norrina B.
Published: January 2022

Background

Geographic heterogeneity in COVID-19 outcomes in the United States is well-documented and has been linked with factors at the county level, including sociodemographic and health factors. Whether an integrated measure of place-based risk can classify counties at high risk for COVID-19 outcomes is not known.

Methods

We conducted an ecological nationwide analysis of 2,701 US counties from 1/21/20 to 2/17/21. County-level characteristics across multiple domains, including demographic, socioeconomic, healthcare access, physical environment, and health factor prevalence were harmonized and linked from a variety of sources. We performed latent class analysis to identify distinct groups of counties based on multiple sociodemographic, health, and environmental domains and examined the association with COVID-19 cases and deaths per 100,000 population.

Results

Analysis of 25.9 million COVID-19 cases and 481,238 COVID-19 deaths revealed large between-county differences with widespread geographic dispersion, with the gap in cumulative cases and death rates between counties in the 90th and 10th percentile of 6,581 and 291 per 100,000, respectively. Counties from rural areas tended to cluster together compared with urban areas and were further stratified by social determinants of health factors that reflected high and low social vulnerability. Highest rates of cumulative COVID-19 cases (9,557 [2,520]) and deaths (210 [97]) per 100,000 occurred in the cluster comprised of rural disadvantaged counties.

Conclusions

County-level COVID-19 cases and deaths had substantial disparities with heterogeneous geographic spread across the US. The approach to county-level risk characterization used in this study has the potential to provide novel insights into communicable disease patterns and disparities at the local level.
Quantitative comparison of SARS-CoV-2 nucleic acid amplification test and antigen testing algorithms: a decision analysis simulation model
Authors: Salvatore Phillip P. , Shah Melisa M. , Ford Laura , Delaney Augustina , Hsu Christopher H. , Tate Jacqueline E. , Kirking Hannah L.
Published: January 2022

Background

Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations recommend different strategies for utilizing NAATs and antigen tests. We sought to create a framework for the quantitative comparison of these recommended strategies based on their expected performance.

Methods

We utilized a decision analysis approach to simulate the expected outcomes of six testing algorithms analogous to strategies recommended by public health organizations. Each algorithm was simulated 50,000 times in a population of 100,000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported.

Results

Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case compared to exclusive use of antigen tests.

Conclusions

No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and resource constraints.
Validation of the family health scale among heterosexual couples: a dyadic analysis
Authors: Crandall AliceAnn , Barlow Melissa
Published: January 2022

Background

The Family Health Scale (FHS) is a recently validated comprehensive measure of family health for use in survey research with the potential to also be used as a clinical measure. However, previous research has only validated the FHS among one member of the family rather than multiple family members. The objective of the study was to examine the psychometric properties of the FHS long- and short-form among married and cohabitating partners (dyads).

Method

The sample for this study was comprised of 482 married or cohabitating heterosexual couples (dyads) who were parents of a child between the ages of 3–13, heterosexual, and living in the United States. Each member of the dyad completed a survey about his or her perception of family health, personal health, childhood experiences, and demographic characteristics. Confirmatory factor analyses (CFA) were conducted to examine the factor structure. Unidimensional, correlational, and second-order factor structures were examined using responses from both partners. The relationships between family health with individual health and demographic covariates were also examined.

Results

Women and men reported their family health similarly. The unidimensional factor structure had the best fit for the FHS short-form while either the unidimensional model or the second-order model would be appropriate for the FHS long-form. Household income, individual member mental health, and childhood experiences were associated with family health in the expected direction.

Conclusion

The results demonstrate that the FHS is a valid and reliable family measure when examining family health among dyads including married and cohabitating heterosexual couples who have children.
GLP2-GLP2R signal affects the viability and EGFR-TKIs sensitivity of PC9 and HCC827 cells
Authors: Song Bin , Ge Hong , Pu Chenwei , Li Ning
Published: January 2022

Background

The resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs) therapy is currently the major clinical challenge in the treatment of lung cancer. This study aims to reveal the role of glucagon-like peptide (GLP) 2 and GLP-2 receptor (GLP2R) signaling on the EGFR-TKIs and cisplatin resistance of lung cancer cells.

Methods

The common differentially expressed genes in PC9 and HCC827 cells that were individually resistant to one of the three EGFR-TKIs (dacomitinib, osimertinib and afatinib) were screened. The data were from GSE168043 and GSE163913. The expression of GLP2R in drug-resistant cells was detected by western blot. The effect of GLP2R expression down- or up-regulation on resistance to dacomitinib, osimertinib, afatinib or cisplatin was measured by CCK-8 and flow cytometry assays. The long-acting analog of GLP-2, teduglutide, treated the parental cells.

Results

A total of 143 common differentially expressed genes were identified. Compared with the parent cells, the GLP2R expression in drug-resistant cell lines was significantly up-regulated. The exogenous expression of GLP2R in parental cells enhanced cell viability, while knockdown of GLP2R levels in drug-resistant cell lines inhibited cell viability. In addition, teduglutide treatment also enhanced the viability of lung cancer cells.

Conclusion

GLP2-GLP2R signal may change the sensitivity of cells to EGFR-TKIs and cisplatin. The development of GLP-2 or GLP2R inhibitors may be beneficial to the clinical treatment of lung cancer.
An anti-inflammatory diet intervention for knee osteoarthritis: a feasibility study
Authors: Cooper Indiana , Brukner Peter , Devlin Brooke L. , Reddy Anjana J. , Fulton Melanie , Kemp Joanne L. , Culvenor Adam G.
Published: January 2022

Background

Knee osteoarthritis has an inflammatory component that is linked to pain and joint pathology, yet common non-surgical and non-pharmacological interventions (e.g., exercise, calorie restricting diets) do not typically target inflammation. We aimed to evaluate the feasibility of a telehealth delivered anti-inflammatory diet intervention for knee osteoarthritis.

Methods

This 9-week single-arm feasibility study recruited participants aged 40–85 years with symptomatic knee osteoarthritis (inclusion criteria: average pain ≥4/10 or maximal pain ≥5/10 during past week). All participants received a telehealth-delivered anti-inflammatory dietary education intervention involving 1:1 consultations at baseline, 3- and 6-week follow-up. The diet emphasised nutrient-dense wholefoods and minimally processed anti-inflammatory foods and discouraged processed foods considered to be pro-inflammatory. The primary outcome of feasibility was assessed via: i) eligibility, recruitment and retention rates; ii) self-reported dietary adherence; iii) adverse events; and iv) treatment satisfaction. Post-intervention interviews evaluated the acceptability of the dietary intervention delivered via telehealth. Secondary outcomes included changes in self-reported body mass, Knee injury and Osteoarthritis Outcome Score (KOOS), health-related quality of life (EuroQoL-5D), analgesic use and global rating of change. Worthwhile effects were determined by the minimal detectable change (MDC) for all five KOOS-subscales (pain, symptoms, activities of daily living, sport/recreation, quality of life) being contained within the 95% confidence interval.

Results

Forty-eight of seventy-three (66%) individuals screened were eligible and 28 enrolled over 2 months (82% female, mean age 66 ± 8 years, body mass index 30.7 ± 4.8 kg.m−2). Six participants withdrew prior to final follow-up (21% drop-out). Of those with final follow-up data, attendance at scheduled telehealth consultations was 99%. Self-reported adherence to diet during the 9-week intervention period: everyday = 27%, most of time = 68% and some of time = 5%. Two minor adverse events were reported. Change scores contained the MDC within the 95% confidence interval for all five KOOS subscales. Suggestions to improve study design and limit drop-out included an initial face-to-face consultation and more comprehensive habitual dietary intake data collection.

Conclusion

This study supports the feasibility of a full-scale randomised controlled trial to determine the efficacy of a primarily telehealth-delivered anti-inflammatory dietary education intervention in adults with symptomatic knee osteoarthritis.

Trial registration

ACTRN12620000229976 prospectively on 25/2/2020.
The effect of Kappaphycus alvarezii active fraction on oxidative stress and inflammation in streptozotocin and nicotinamide-induced diabetic rats
Authors: Yulianti Evy , Sunarti  , Wahyuningsih Mae Sri Hartati
Published: January 2022

Background

High glucose concentration increases the glycation process which leads to oxidative stress and inflammation, that can cause complications in diabetes. Several medicinal plants have been used in the treatment of diabetes and its complications. One of them is Kappaphycus alvarezii, an algae that has known antidiabetic abilities. This study aimed to examine the effect of K. alvarezii active fraction on plasma hydrogen peroxide (H2O2) and Tumor Necrosis Factor α (TNFα) levels, renal NADPH oxidase 4 (NOX4) and Nuclear Factor κ B (NFκB) gene expressions.

Methods

Active fraction was obtained from bioassay-guided fractionation with antiglycation ability. In vivo study was performed on twenty Wistar male rats. The level of H2O2 was measured using H2O2 Assay Kit, the Optical Density value measured using spectrophotometer at a wavelength of 405 nm. Plasma TNFα level was measured using ELISA. Renal NOX4 and NFκB gene expression was analyzed using qPCR.

Results

Active fraction significantly reduced plasma H2O2 but not TNFα levels. Furthermore, renal NOX4 gene expression was lower in the diabetic rat group treated with active fraction compared to the untreated group but not NFκB gene expression.

Conclusions

K. alvarezii active fraction has an activity to reduce plasma H2O2 as well as renal NOX4 gene expression. Therefore, this fraction could be developed as a potential candidate for diabetes treatment through oxidative stress mechanisms.
Student usage of open educational resources and social media at a Sri Lanka Medical School
Authors: Hettige Samankumara , Dasanayaka Eshani , Ediriweera Dileepa Senajith
Published: January 2022

Background

The use of Open Educational Resources (OER) and Social Media (SM) for academic information seeking is common among undergraduates nowadays. There is limited data on OER and SM use for education in Sri Lanka. This study was aimed at evaluating the OER and SM use for education among the medical students at the Faculty of Medicine, University of Kelaniya, Sri Lanka.

Methods

A cross-sectional study was conducted at the Faculty of Medicine, University of Kelaniya. Stratified random sampling was used to select students from the first year to the final year. A self-administrated questionnaire was used to collect data.

Results

The study included 257 responses (response rate: 89.5%), of which 185 (72.0%) were females. The OER and SM use for educational purposes at least once a month among students was 96.1% (95%CI: 93.7–98.5%) and 88.3% (95%CI: 84.4–92.3%) respectively. There was no gender difference in OER and SM use. The main reasons for accessing OER were the availability of information at any time (36.1%) and ease of information access (31.5%). Wiki sites (84.4%) and Facebook (79.8%) were the highest accessed OER and SM platforms. The majority of students were in view that the information on wiki sites (51.4%) and results of general non-specific web searches (56.0%) were reliable. Only 33.9% of students searched information from educational and government-related sources and 18.7% had accessed e-journals. Through SM, 79.0% joined educational groups and 77.0% followed the medical-related sites, pages and people. More than one-third of students (35.8%) could not find academic information from SM due to the information overload and 31.1% mentioned that SM distracted their education.

Conclusion

The majority of the students used OER and SM for education; however, only a minority accessed reliable information. Students accepted information available in wiki sites and general non-specific web searchers without considering the credibility of sources. The majority of the students did not refer to e-journals. Distractions to academic work and the difficulty to access accurate information were major concerns of using SM. This study highlights the importance of improving information literacy among medical students.
Cost-savings and potential cost-savings through the distribution of generic antiretroviral drugs within the statutory health insurance market of Germany between January 2017 and June 2019
Authors: Lottes Matthäus , Bremer Viviane , Prugger Christof , Kollan Christian , Schmidt Daniel
Published: January 2022

Background

Recent patent losses for antiretroviral drugs (ARV) have led to the debate of cost-saving through the replacement of patented drugs with generic drugs. The split of recommended single-tablet regimens (STR) into their single substance partners is one of the considerations mentioned in said debate. Particularly, generic tenofovir disoproxil/emtricitabine (TDF/FTC) is expected to hold untapped cost-saving potential, which may curb increasing overall expenditures for combined antiretroviral therapy (cART) within the statutory health insurance (SHI) of Germany.

Methods

Data of ARV reimbursed by the SHI were used to describe the trends of defined daily doses (DDD) as well as the revenue within the German ARV market. They were also used to determine the cost-savings of moving to generic drugs. The time period observed was between January 2017 and June 2019. The potential cost-savings were determined with following assumption in mind: the maximum possible use of generic ARV, including 1) the split of STR and replacing all substance partners with generic ones, and 2) replacing patented tenofovir alafenamide/emtricitabine (TAF/FTC) with generic TDF/FTC.

Results

Throughout the observation period, the DDD of generic ARV increased nearly five-fold while their revenue increased more than four-fold. Total cost-saving showed a sharp increase over the same period, with generic TDF/FTC accounting for a share of around 70%. The largest potential cost-saving could have been achieved through replacing patented TAF/FTC with generic TDF/FTC, peaking at nearly 10% of total revenue, but showing decreasing trends in general.

Conclusion

The progressive distribution of generic ARV ensured increasing cost-savings, but consequently curbed the potential cost-savings. Unique price reductions of generic TDF/FTC have played a pivotal role for these effects. In any case, substituting with generic ARV should not fail to adhere to the treatment guidelines and continue to consider the medical requirements for the treatment.
Conventional laboratory housing increases morbidity and mortality in research rodents: results of a meta-analysis
Authors: Cait Jessica , Cait Alissa , Scott R. Wilder , Winder Charlotte B. , Mason Georgia J.
Published: January 2022

Background

Over 120 million mice and rats are used annually in research, conventionally housed in shoebox-sized cages that restrict natural behaviours (e.g. nesting and burrowing). This can reduce physical fitness, impair thermoregulation and reduce welfare (e.g. inducing abnormal stereotypic behaviours). In humans, chronic stress has biological costs, increasing disease risks and potentially shortening life. Using a pre-registered protocol (https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17955), this meta-analysis therefore tested the hypothesis that, compared to rodents in ‘enriched’ housing that better meets their needs, conventional housing increases stress-related morbidity and all-cause mortality.

Results

Comprehensive searches (via Ovid, CABI, Web of Science, Proquest and SCOPUS on May 24 2020) yielded 10,094 publications. Screening for inclusion criteria (published in English, using mice or rats and providing ‘enrichments’ in long-term housing) yielded 214 studies (within 165 articles, using 6495 animals: 59.1% mice; 68.2% male; 31.8% isolation-housed), and data on all-cause mortality plus five experimentally induced stress-sensitive diseases: anxiety, cancer, cardiovascular disease, depression and stroke. The Systematic Review Center for Laboratory animal Experimentation (SYRCLE) tool assessed individual studies’ risks of bias. Random-effects meta-analyses supported the hypothesis: conventional housing significantly exacerbated disease severity with medium to large effect sizes: cancer (SMD = 0.71, 95% CI = 0.54–0.88); cardiovascular disease (SMD = 0.72, 95% CI = 0.35–1.09); stroke (SMD = 0.87, 95% CI = 0.59–1.15); signs of anxiety (SMD = 0.91, 95% CI = 0.56–1.25); signs of depression (SMD = 1.24, 95% CI = 0.98–1.49). It also increased mortality rates (hazard ratio = 1.48, 95% CI = 1.25–1.74; relative median survival = 0.91, 95% CI = 0.89–0.94). Meta-regressions indicated that such housing effects were ubiquitous across species and sexes, but could not identify the most impactful improvements to conventional housing. Data variability (assessed via coefficient of variation) was also not increased by ‘enriched’ housing.

Conclusions

Conventional housing appears sufficiently distressing to compromise rodent health, raising ethical concerns. Results also add to previous work to show that research rodents are typically CRAMPED (cold, rotund, abnormal, male-biased, poorly surviving, enclosed and distressed), raising questions about the validity and generalisability of the data they generate. This research was funded by NSERC, Canada.
Modular evolution of secretion systems and virulence plasmids in a bacterial species complex
Authors: Chou Lin , Lin Yu-Chen , Haryono Mindia , Santos Mary Nia M. , Cho Shu-Ting , Weisberg Alexandra J. , Wu Chih-Feng , Chang Jeff H. , Lai Erh-Min , Kuo Chih-Horng
Published: January 2022

Background

Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobacterium tumefaciens species complex (a.k.a. Agrobacterium biovar 1), a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes.

Results

We utilized 35 genome assemblies, including 14 newly generated ones, to achieve a phylogenetically balanced sampling of A. tumefaciens. Our genomic analysis suggested that the 10 genomospecies described previously are distinct biological species and supported a quantitative guideline for species delineation. Furthermore, our inference of gene content and core-genome phylogeny allowed for investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins.

Conclusions

We demonstrate that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. We show that the T6SS VgrG proteins involved in specific effector binding and delivery can be classified into distinct types based on domain organization. The co-occurrence patterns of VgrG-associated domains and the neighboring genes that encode different chaperones/effectors can be used to infer possible interacting partners. Similarly, the associations between plant host preference and the pTi type among these strains can be used to infer phenotype-genotype correspondence. Our strategies for multi-level investigations at scales that range from whole genomes to intragenic domains and phylogenetic depths from between- to within-species are applicable to other bacteria. Furthermore, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works.
Modelling upper respiratory viral load dynamics of SARS-CoV-2
Authors: Challenger Joseph D. , Foo Cher Y. , Wu Yue , Yan Ada W. C. , Marjaneh Mahdi Moradi , Liew Felicity , Thwaites Ryan S. , Okell Lucy C. , Cunnington Aubrey J.
Published: January 2022

Relationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.
Chicken hepatomegaly and splenomegaly associated with novel subgroup J avian leukosis virus infection
Authors: Xu Moru , Hang Fusen , Qian Kun , Shao Hongxia , Ye Jianqiang , Qin Aijian
Published: January 2022

Background

Subgroup J avian leukosis virus (ALV-J) is an oncovirus which can induce multiple types of tumors in chicken. In this report, we found novel ALV-J infection is closely associated with serious hepatomegaly and splenomegaly in chicken.

Case presentation

The layer chickens from six flocks in Jiangsu province, China, showed serious hemoperitoneum, hepatomegaly and splenomegaly. Histopathological results indicated focal lymphocytic infiltration, cell edema and congestion in the liver, atrophy and depletion of lymphocyte in the spleen. Tumor cells were not detected in all the organs. avian hepatitis E virus (aHEV), which is thought to be the cause of a very similar disease, big liver and spleen disease (BLS), was not detected. Other viruses causing tumors or liver damage including Marek’s disease virus (MDV), reticuloendotheliosis virus (REV), fowl adenovirus (FAdV) and chicken infectious anemia virus (CIAV) were also proved negative by either PCR or RT-PCR. However, we did detect ALV-J in those chickens using PCR. Only novel ALV-J strains were efficiently isolated from these chicken livers.

Conclusions

This is the first report that chicken hepatomegaly and splenomegaly disease was closely associated with novel ALV-J, highlighting the importance of ALV-J eradication program in China.
Enhanced production of ectoine from methane using metabolically engineered Methylomicrobium alcaliphilum 20Z
Authors: Cho Sukhyeong , Lee Yun Seo , Chai Hanyu , Lim Sang Eun , Na Jeong Geol , Lee Jinwon
Published: January 2022

Background

Ectoine (1,3,4,5-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) is an attractive compatible solute because of its wide industrial applications. Previous studies on the microbial production of ectoine have focused on sugar fermentation. Alternatively, methane can be used as an inexpensive and abundant resource for ectoine production by using the halophilic methanotroph, Methylomicrobium alcaliphilum 20Z. However, there are some limitations, including the low production of ectoine from methane and the limited tools for the genetic manipulation of methanotrophs to facilitate their use as industrial strains.

Results

We constructed M. alcaliphilum 20ZDP with a high conjugation efficiency and stability of the episomal plasmid by the removal of its native plasmid. To improve the ectoine production in M. alcaliphilum 20Z from methane, the ectD (encoding ectoine hydroxylase) and ectR (transcription repressor of the ectABC-ask operon) were deleted to reduce the formation of by-products (such as hydroxyectoine) and induce ectoine production. When the double mutant was batch cultured with methane, ectoine production was enhanced 1.6-fold compared to that obtained with M. alcaliphilum 20ZDP (45.58 mg/L vs. 27.26 mg/L) without growth inhibition. Notably, a maximum titer of 142.32 mg/L was reached by the use of an optimized medium for ectoine production containing 6% NaCl and 0.05 μM of tungsten without hydroxyectoine production. This result demonstrates the highest ectoine production from methane to date.

Conclusions

Ectoine production was significantly enhanced by the disruption of the ectD and ectR genes in M. alcaliphilum 20Z under optimized conditions favoring ectoine accumulation. We demonstrated effective genetic engineering in a methanotrophic bacterium, with enhanced production of ectoine from methane as the sole carbon source. This study suggests a potentially transformational path to commercial sugar-based ectoine production.

Graphical Abstract
Six-sigma and quality planning of TORCH tests in the Peruvian population: a single-center cross-sectional study
Authors: Moya-Salazar Jeel , SantaMaria Bianca M. , Moya-Salazar Marcia M. , Rojas-Zumaran Víctor , Chicoma-Flores Karina , Contreras-Pulache Hans
Published: January 2022

Objective

To ensure the health of newborns, it is necessary to perform high-quality diagnostic tests. The TORCH panel is a set of tests that identifies infectious pathogens such as Toxoplasma (Toxo) and Cytomegalovirus (CMV) that are common in low-setting populations. We performed TORCH panel quality planning using six sigma in a reference laboratory at Peru.

Results

This was a cross-sectional study. TORCH tests include Toxo, Rubella, CMV, and Herpes. We processed all samples by fourth-generation ELISA on the GEMINI XCR200 analyzer (Diatron, Budapest, Hungary). We obtained the imprecision from the annual data of the external quality assessment plan and we used the CLSI EP12-A3 guideline. In a total of 44,788 analyses, the average imprecision was 3.69 ± 1.47%, and CMV had lower imprecision (2.3 and 2.6% for IgM and IgG, respectively). Quality planning of the TORCH panel allowed estimating the sigma value that ranged from 4 to 10 (average 7 ± 2 sigma), where rubella had the highest values (10 for IgM and 8 for IgG) while HSV2 had the lowest values (4 for IgM and 5 for IgG). Our results suggest the optimal performance of half of the markers including Toxoplasma, Rubella, and CMV in the Peruvian population.