bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between physical activity and perceptions of ageing from the perspective of healthy ageing among older people with frailty with chronic disease: a cross-sectional study
Authors: Wang Yu-Rung , Lee Huan-Fang , Hsieh Pei-Lun , Chang Chia-Hsiu , Chen Ching-Min
Published: September 2023

Background

In Taiwan, the 2019 Elderly Frailty Assessment found that 11.2% of older people have frailty problems. Some researchers have found that older persons’ negative perspectives on ageing aggravate the progression of frailty, thereby increasing their risk of disability. This study aimed to investigate associations of physical activity and perceptions of ageing on perspectives of healthy ageing in older people with frailty and chronic diseases and to compare the differences in their frailty status.

Methods

This study used a descriptive cross-sectional design. Participants were recruited from community long-term care stations. The inclusion criteria were (1) no severe cognitive impairment and ability to communicate in Mandarin and Taiwanese; (2) over 65 years old; (3) at least one chronic disease; and (4) at least one debilitating item in the Study of Osteoporotic Fracture index. A total of 312 participants were recruited. The Brief Ageing Perceptions Questionnaire Chinese version, Healthy Ageing Perspectives Questionnaire, and Physical Activity Scale for the Elderly Chinese Version were used for measurement.

Results

The study results found that demographic variables, perceptions of ageing, and physical activity were significantly correlated with perspectives on healthy ageing, including age, Activities of Daily Living, education, all domains of perceptions of ageing, and household- and work-related physical activity. With regard to the frailty status level, prefrailty was better than frailty from the perspective of healthy ageing in older people with chronic disease (t = 5.35, p < 0.05). Hierarchical regression analysis was used to predict the healthy ageing perspectives of older persons with chronic disease involving a chronic time-line, positive control, health-related changes, and work-related activities. Those domains could predict 21% of the variance in healthy ageing perspectives.

Conclusion

It is suggested that in community long-term care stations, health care providers can arrange activities to improve the perception of ageing that are acceptable for older people with frailty and chronic diseases and encourage older people to participate in service activities to achieve a sense of social participation.
How is return on investment from quality improvement programmes conceptualised by mental healthcare leaders and why: a qualitative study
Authors: Thusini S’thembile , Soukup Tayana , Chua Kia-Chong , Henderson Claire
Published: September 2023

Background

Return on Investment (ROI), whereby the ratio of costs to benefits is assessed, is encouraged in-order to justify the value of Quality Improvement (QI) programmes. We previously performed a literature review to develop a ROI conceptual framework for QI programmes. We concluded that, QI-ROI is conceptualised as any monetary and non-monetary benefit. In the current study, we explored if this finding is shared by mental healthcare leaders. We also investigated the stability of this conceptualisation against influencing factors and potential for disinvestment.

Methods

We performed qualitative interviews with leaders in an NHS mental health organisation. There were 16 participants: nine board members and seven senior leaders. The interviews were held online via Microsoft Teams and lasted an hour on average. We performed deductive-inductive analysis to seek data from our initial ROI framework and any new data.

Results

We found that in mental healthcare, QI-ROI is also conceptualised as any valued monetary and non-monetary benefits. There was a strong emphasis on benefits to external partners and a de-emphasis of benefit monetisation. This conceptualisation was influenced by the 1) perceived mandates to improve quality and manage scarce resources, 2) expectations from QI, 3) health and social care values, 4) ambiguity over expectations, and 5) uncertainty over outcomes. Uncertainty, ambiguity, and potential for disinvestment posed a threat to the stability of this conceptualisation but did not ultimately change it. Health and social care values supported maintaining the QI-ROI as any benefit, with a focus on patients and staff outcomes. Socio-political desires to improve quality were strong drivers for QI investment.

Conclusion

Mental healthcare leaders primarily conceptualise QI-ROI as any valued benefit. The inclusion of externalised outcomes which are hard to attribute may be challenging. However, mental healthcare services do collaborate with external partners. The de-emphases of benefit monetisation may also be controversial due to the need for financial accountability. Mental healthcare leaders recognise the importance of efficiency savings. However, they raised concerns over the legitimacy and utility of traditional ROI as a tool for assessing QI value. Further research is needed to bring more clarity on these aspects of the QI-ROI concept.
Patient safety culture in home care settings in Sweden: a cross-sectional survey among home care professionals
Authors: Silverglow Anastasia , Wijk Helle , Lidén Eva , Johansson Lena
Published: September 2023

Background

The connection between a weak patient safety culture and adverse patient events is well known, but although most long-term care is provided outside of hospitals, the focus of patient safety culture is most commonly on inpatient care. In Sweden, more than a third of people who receive care at home have been affected by adverse events, with the majority judged to be preventable. The aim of this study was to investigate the patient safety culture among care professionals working in care at home with older people.

Methods

This cross-sectional study used a purposive sample of 66 municipal care workers, health care professionals, and rehabilitation staff from five municipal care units in two districts in western Sweden who provided care at home for older people and had been employed for at least six months. The participants completed the Hospital Survey on Patient Safety Culture (HSOPSC) self-report questionnaire, which assessed aspects of patient safety culture—norms, beliefs, and attitudes. Logistic regression analysis was used to test how the global ratings of Patient safety grade in the care units and Reporting of patient safety events were related to the dimensions of safety culture according to the staff’s professions and years of work experience.

Results

The most positively rated safety culture dimension was Teamwork within care units (82%), which indicates good cooperation with the closest co-workers. The least positively rated dimensions were Handoffs and transitions among care units (37%) and Management support (37%), which indicate weaknesses in the exchange of patient information across care units and limited support from top-level managers. The global rating of Patient safety grade was associated with Communication openness and Management support (p < 0.01 and p = 0.03, respectively). Staff with less work experience evaluated the Patient safety grade higher than those with more work experience.

Conclusions

This study suggests that improvements are needed in care transitions and in support from top-level managers and that awareness of patient safety should be improved in staff with less work experience. The results also highlight that an open communication climate within the care unit is important for patient safety.
High-intensity interval training induces lactylation of fatty acid synthase to inhibit lipid synthesis
Authors: Chen Xuefei , Huang Wenhua , Zhang Jingbo , Li Yanjun , Xing Zheng , Guo Lanlan , Jiang Hongfeng , Zhang Jing
Published: September 2023

Background

The aim of study was to observe the effect of increased lactate levels during high-intensity interval training (HIIT) on protein lactylation, identify the target protein, and investigate the regulatory effect of lactylation on the function of the protein.

Methods

C57B/L6 mice were divided into 3 groups: the control group, HIIT group, and dichloroacetate injection + HIIT group (DCA + HIIT). The HIIT and DCA + HIIT groups underwent 8 weeks of HIIT treatment, and the DCA + HIIT group was injected DCA before HIIT treatment. The expression of lipid metabolism-related genes was determined. Protein lactylation in subcutaneous adipose tissue was identified and analyzed using 4D label-free lactylation quantitative proteomics and bioinformatics analyses. The fatty acid synthase (FASN) lactylation and activity was determined.

Results

HIIT had a significant effect on fat loss; this effect was weakened when lactate production was inhibited. HIIT significantly upregulated the protein lactylation while lactate inhibition downregulated in iWAT. FASN had the most modification sites. Lactate treatment increased FASN lactylation levels, inhibited FASN activity, and reduced palmitate and triglyceride synthesis in 3T3-L1 cells.

Conclusions

This investigation revealed that lactate produced by HIIT increased protein pan-lactylation levels in iWAT. FASN lactylation inhibited de novo lipogenesis, which may be an important mechanism in HIIT-induced fat loss.
Small volume bone marrow aspirates with high progenitor cell concentrations maximize cell therapy dose manufacture and substantially reduce donor hemoglobin loss
Authors: Epah Jeremy , Spohn Gabriele , Preiß Kathrin , Müller Markus M. , Dörr Johanna , Bauer Rainer , Daqiq-Mirdad Shabnam , Schwäble Joachim , Bernas Stefanie N. , Schmidt Alexander H. , Seifried Erhard , Schäfer Richard
Published: September 2023

Background

Bone marrow (BM) transplantation is a life-saving therapy for hematological diseases, and the BM harbors also highly useful (progenitor) cell types for novel cell therapies manufacture. Yet, the BM collection technique is not standardized.

Methods

Benchmarking our collection efficiency to BM collections worldwide (N = 1248), we noted a great variability of total nucleated cell (TNC) yields in BM products (HPC-M) with superior performance of our center, where we have implemented a small volume aspirate policy. Thus, we next prospectively aimed to assess the impact of BM collection technique on HPC-M quality. For each BM collection (N = 20 donors), small volume (3 mL) and large volume (10 mL) BM aspirates were sampled at 3 time points and analyzed for cell composition.

Results

Compared to large volume aspirates, small volume aspirates concentrated more TNCs, immune cells, platelets, hematopoietic stem/progenitor cells, mesenchymal stromal cells (MSCs), and endothelial progenitors. Inversely, the hemoglobin concentration was higher in large volume aspirates indicating more hemoglobin loss. Manufacturing and dosing scenarios showed that small volume aspirates save up to 42% BM volume and 44% hemoglobin for HPC-M donors. Moreover, MSC production efficiency can be increased by more than 150%.

Conclusions

We propose to consider small volume BM aspiration as standard technique for BM collection.
Patient-reported reactogenicity and safety of COVID-19 vaccinations vs. comparator vaccinations: a comparative observational cohort study
Authors: Werner Felix , Zeschick Nikoletta , Kühlein Thomas , Steininger Philipp , Überla Klaus , Kaiser Isabelle , Sebastião Maria , Hueber Susann , Warkentin Lisette
Published: September 2023

Background

In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines.

Methods

A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors.

Results

In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations.

Conclusion

The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety.

Trial registration

DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.
Development of an amoxicillin-radix scutellaria extract formulation and evaluation of its pharmacokinetics in pigs
Authors: Yi Dandan , Wen Xuemei , Xu Wei , Xu Yangfeng , Deng Xin , Yan Guoqing , Wu Liqin , Liang Qiuling , Liang Zhengmin , Peng Jianbo , He Jiakang
Published: September 2023

Background

A new antibacterial compound powder of amoxicillin (AMO)/Radix Scutellaria extract (RSE) was developed, and its pharmacokinetics were determined in pigs following oral administration.

Results

The MIC ranges of AMO against Escherichia coli, Staphylococcus aureus and Streptococcus were 1–8 μg/mL, 0.5–4 μg/mL and 0.5–64 μg/mL, respectively. The MIC ranges of RSE against E. coli, S. aureus, and Streptococcus were greater than 2.5 mg/mL, 0.156–2.5 mg/mL, and greater than 2.5 mg/mL, respectively. For S. aureus, the combined drug susceptibility test showed that AMO and RSE had an additive or synergistic effect. The results of compatibility test, the excipient screening test and the drug quality control test showed that the formulation had stable quality and uniform properties under the test conditions. Two studies were conducted to investigate the pharmacokinetics of the compound product in pigs. First, the pharmacokinetics of the AMO-RSE powder were compared with those of their respective single products. The results showed no significant change in the main pharmacokinetic parameters when either component was removed from the compound formulation; thus, AMO and RSE have no pharmacokinetic interaction in pigs. Second, pigs were orally administered three different doses of AMO-RSE powder. The Cmax and AUC increased proportionally with increasing p.o. dose; thus, the λz, t1/2λ, MRT, and Tmax were unchanged for the doses of 10, 20, and 30 mg/kg AMO and the doses of 5, 10, and 15 mg/kg BCL, showing that AMO/baicalin in AMO-RSE powder showed linear pharmacokinetic characteristics in pigs.

Conclusions

The combined drug sensitivity test of AMO and RSE against S. aureus showed that the combination was additive or synergistic. Pharmacokinetic studies indicated that AMO and BCL do not interfere with each other in pigs when used in a compound formulation. The pharmacokinetic parameters remained unchanged regardless of the dose for p.o. administration, indicating linear pharmacokinetic properties over the tested dose range. The quality of the AMO-RSE powder was good and stable, providing a foundation for its clinical application in veterinary medicine. Further bioavailability, PK/PD and clinical trials are still needed to determine the final dosage regimen.
Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes
Authors: Rios Santiago , García-Gavilán Jesús F. , Babio Nancy , Paz-Graniel Indira , Ruiz-Canela Miguel , Liang Liming , Clish Clary B , Toledo Estefania , Corella Dolores , Estruch Ramón , Ros Emilio , Fitó Montserrat , Arós Fernando , Fiol Miquel , Guasch-Ferré Marta , Santos-Lozano José M , Li Jun , Razquin Cristina , Martínez-González Miguel Ángel , Hu Frank B , Salas-Salvadó Jordi
Published: September 2023

Background

A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk.

Methods

In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models.

Results

The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38–0.77 for dichotomous HL, and 0.22, 0.11–0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42–0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31–1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile.

Conclusions

In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD.

Trial registration

The PREDIMED trial was registered at ISRCTN (http://www.isrctn.com/, ISRCTN35739639).
Targeted therapy using engineered extracellular vesicles: principles and strategies for membrane modification
Authors: Liu Qisong , Li Defeng , Pan Xiaohua , Liang Yujie
Published: September 2023

Extracellular vesicles (EVs) are 30–150 nm membrane-bound vesicles naturally secreted by cells and play important roles in intercellular communication by delivering regulatory molecules such as proteins, lipids, nucleic acids and metabolites to recipient cells. As natural nano-carriers, EVs possess desirable properties such as high biocompatibility, biological barrier permeability, low toxicity, and low immunogenicity, making them potential therapeutic delivery vehicles. EVs derived from specific cells have inherent targeting capacity towards specific cell types, which is yet not satisfactory enough for targeted therapy development and needs to be improved. Surface modifications endow EVs with targeting abilities, significantly improving their therapeutic efficiency. Herein, we first briefly introduce the biogenesis, composition, uptake and function of EVs, and review the cargo loading approaches for EVs. Then, we summarize the recent advances in surface engineering strategies of EVs, focusing on the applications of engineered EVs for targeted therapy. Altogether, EVs hold great promise for targeted delivery of various cargos, and targeted modifications show promising effects on multiple diseases.

Graphical Abstract
Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway
Authors: Zhang PeiYao , Wu Panfeng , Khan Umar Zeb , Zhou Zekun , Sui Xinlei , Li Cheng , Dong Kangkang , Liu Yongjun , Qing Liming , Tang Juyu
Published: September 2023

Objectives

This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival.

Methods

The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry.

Results

LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1β signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells.

Conclusion

LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.
Cell-surface photochemistry mediated calcium overload for synergistic tumor therapy
Authors: Wang Jun , Wang Wei , Shen Qingmei , Lan Lan , Guan Cuiping , Xu Xinchang , Li Weishuo , Du Yongzhong
Published: September 2023

Calcium (Ca2+) is essential for mitochondrial homeostasis and function coordination, particularly in cancer cells that metabolize frequently to sustain their growth. Photochemistry mediated calcium overload has attracted lots of attention as an effective way to achieve tumor suppression. Herein, we developed a photonanomedicine to synergistically induce calcium overload via cell-surface photochemistry and thus tumor suppression. Specifically, the photosensitizer, protoporphyrin IX (PpIX) was loaded onto upconversion nanoparticles (UCNP), which was subsequently modified by a polymer bearing photo-crosslinking cinnamate (CA) groups. The resulting nanoparticle was further functionalized by anti-CD20 aptamers (Apt), to give photonanomedicine. The interaction between CD20 receptors and anti-CD20 aptamers allowed photonanomedicine to accurately attach onto the Raji cell surface after an intravenous injection. Following the local application of a 980 nm NIR laser, the photonanomedicine was able to capture the NIR light and convert it into ultraviolet (UV) light. On one hand, the converted UV light led the crosslinking of cinnamate groups in photonanomedicine, further stimulating the clustering of CD20 receptors and causing Ca2+ influx. On the other hand, the UV light could simultaneously excited PpIX to generate reactive oxygen species (ROS) in situ to break down the integrity of cell membrane and lead to an influx of Ca2+. The synergistic Ca2+ overload mediated by photonanomedicine exhibited an enhanced and superior anti-tumor efficacy. We believe this photonanomedicine expands the toolbox to manipulate intracellular Ca2+ concentration and holds a great potential as an anti-tumor therapy.
Implementation of a vascular access specialist team in a tertiary hospital: a cost-benefit analysis
Authors: Ricou Ríos Laura , Esposito Català Candela , Pons Calsapeu Arnau , Adroher Mas Cristina , Andrés Martínez Isabel , Nuño Ruiz Isaac , Castellà Creus Mònica , Castellà Fàbregas Laia , García Quesada Maria José , Estrada Cuxart Oriol , Ara del Rey Jordi , López Seguí Francesc
Published: September 2023

Background

The use of peripherally inserted central catheters and midline catheters is growing due to their potential benefits. These devices can increase patient safety and satisfaction while reducing the use of resources. As a result, many hospitals are establishing vascular access specialist teams staffed by nurses who are trained in the insertion and maintenance of these catheters. The objective of the study is to evaluate previously to the implementation whether the benefits of introducing ultrasound-guided peripheral venous catheters, midline catheters and peripherally inserted central catheters compared to current practice by a vascular access specialist team outweigh their costs.

Methods

Cost-benefit analysis from the perspective of the healthcare provider based on administrative data. The study estimates the reduction in resources used when changing the current practice for the use of ultrasound-guided midline and PICC catheters, as well as the additional resources required for their use.

Results

The use of an ultrasound-guided device on peripherally inserted central carheter, results in a measurable resource reduction of approximately €31. When 3 peripheral venous catheters are replaced by an ultrasound-guided peripherally inserted central catheter, the saving is €63. Similarly, the use of an ultrasound-guided device on a midline catheter, results in a reduction of €16, while each ultrasound-guided midline catheter replacing 3 peripheral venous catheters results in a reduction of €96.

Conclusion

The benefits of using ultrasound-guided midline and PICC catheters compared to current practice by introducing a vascular access specialist team trained in the implantation of ultrasound-guided catheters, outweigh its cost mainly because of the decrease in hospital stay due to the lowered risk of phebitis. These results motivate the implementation of the service, adding to previous experience suggesting that it is also preferable from the point of view of patient safety and satisfaction.
Rapid and sustained response to JAK inhibition in a child with severe MDA5 + juvenile dermatomyositis
Authors: Strauss Timmy , Günther Claudia , Schnabel Anja , Wolf Christine , Hahn Gabriele , Lee-Kirsch Min Ae , Brück Normi
Published: September 2023

Background

Juvenile dermatomyositis (jDM) is the most common idiopathic inflammatory myopathy of childhood. Amyopathic or hypomyopathic courses have been described.

Case presentation

We present the case of a 4-year-old patient with MDA5 antibody positive jDM and interstitial lung disease. In our patient, typical symptoms of jDM with classical skin lesions, arthritis, proximal muscle weakness, and ulcerative calcifications were observed. Due to the severity of the disease and the pulmonary changes, therapy with the Janus kinase (JAK) inhibitor ruxolitinib was added to the therapy with corticosteroids, intravenous immunoglobulins (IVIG) and hydroxychloroquine leading to a fast and sustained remission.

Conclusion

While there is growing evidence that JAK inhibition is a promising therapeutic option in jDM our case report shows that this approach may also be effective in MDA5-positive jDM with high risk features.
Influence of complement protein C1q or complement receptor C5aR1 on gut microbiota composition in wildtype and Alzheimer’s mouse models
Authors: Petrisko Tiffany J. , Gargus Matthew , Chu Shu-Hui , Selvan Purnika , Whiteson Katrine L. , Tenner Andrea J.
Published: September 2023

The contribution of the gut microbiome to neuroinflammation, cognition, and Alzheimer’s disease progression has been highlighted over the past few years. Additionally, inhibition of various components of the complement system has repeatedly been demonstrated to reduce neuroinflammation and improve cognitive performance in AD mouse models. Whether the deletion of these complement components is associated with distinct microbiome composition, which could impact neuroinflammation and cognitive performance in mouse models has not yet been examined. Here, we provide a comprehensive analysis of conditional and constitutive knockouts, pharmacological inhibitors, and various housing paradigms for the animal models and wild-type controls at various ages. We aimed to determine the impact of C1q or C5aR1 inhibition on the microbiome in the Arctic and Tg2576 mouse models of AD, which develop amyloid plaques at different ages and locations. Analysis of fecal samples from WT and Arctic mice following global deletion of C1q demonstrated significant alterations to the microbiomes of Arctic but not WT mice, with substantial differences in abundances of Erysipelotrichales, Clostridiales and Alistipes. While no differences in microbiome diversity were detected between cohoused wildtype and Arctic mice with or without the constitutive deletion of the downstream complement receptor, C5aR1, a difference was detected between the C5aR1 sufficient (WT and Arctic) and deficient (C5ar1KO and ArcticC5aR1KO) mice, when the mice were housed segregated by C5aR1 genotype. However, cohousing of C5aR1 sufficient and deficient wildtype and Arctic mice resulted in a convergence of the microbiomes and equalized abundances of each identified order and genus across all genotypes. Similarly, pharmacologic treatment with the C5aR1 antagonist, PMX205, beginning at the onset of beta-amyloid plaque deposition in the Arctic and Tg2576 mice, demonstrated no impact of C5aR1 inhibition on the microbiome. This study demonstrates the importance of C1q in microbiota homeostasis in neurodegenerative disease. In addition, while demonstrating that constitutive deletion of C5aR1 can significantly alter the composition of the fecal microbiome, these differences are not present when C5aR1-deficient mice are cohoused with C5aR1-sufficient animals with or without the AD phenotype and suggests limited if any contribution of the microbiome to the previously observed prevention of cognitive and neuronal loss in the C5aR1-deficient AD models.
A scoping review of implementation science theories, models, and frameworks — an appraisal of purpose, characteristics, usability, applicability, and testability
Authors: Wang Yingxuan , Wong Eliza Lai-Yi , Nilsen Per , Chung Vincent Chi-ho , Tian Yue , Yeoh Eng-Kiong
Published: September 2023

Background

A proliferation of theories, models, and frameworks (TMFs) have been developed in the implementation science field to facilitate the implementation process. The basic features of these TMFs have been identified by several reviews. However, systematic appraisals on the quality of these TMFs are inadequate. To fill this gap, this study aimed to assess the usability, applicability, and testability of the current TMFs in a structured way.

Methods

A scoping review method was employed. Electronic databases were searched to locate English and Chinese articles published between January 2000 and April 2022. Search terms were specific to implementation science. Additionally, hand searches were administered to identify articles from related reviews. Purpose and characteristics such as the type of TMF, analytical level, and observation unit were extracted. Structured appraisal criteria were adapted from Birken et al.’s Theory Comparison and Selection Tool (T-CaST) to conduct an in-depth analysis of the TMFs’ usability, applicability, and testability.

Results

A total of 143 TMFs were included in this analysis. Among them, the most common purpose was to identify barriers and facilitators. Most TMFs applied the descriptive method to summarize the included constructs or the prescriptive method to propose courses of implementation actions. TMFs were mainly mid-range theories built on existing conceptual frameworks or demonstrated grand theories. The usability of the TMFs needs to be improved in terms of the provision of conceptually matched strategies to barriers and facilitators and instructions on the TMFs usage. Regarding the applicability, little attention was paid to the constructs of macro-level context, stages of scale-up and sustainability, and implementation outcomes like feasibility, cost, and penetration. Also, fewer TMFs could propose recommended research and measurement methods to apply the TMFs. Lastly, explicit hypotheses or propositions were lacking in most of the TMFs, and empirical evidence was lacking to support the claimed mechanisms between framework elements in testability.

Conclusions

Common limitations were found in the usability, application, and testability of the current TMFs. The findings of this review could provide insights for developers of TMFs for future theoretical advancements.
Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis
Authors: Wang Lufei , Ye Shouxiu , Qin Jianliang , Tang Min , Dong Ming-You , Fang Jie
Published: September 2023

Background

Osteoarthritis (OA) is the most common chronic joint disease and how ferroptosis contributes to OA has garnered much attention recently. Bioinformatics promoted the discovery of ferroptosis-related biomarkers for OA. But since OA is a whole-joint disease, sensitive biomarkers for OA are still limited. We herein focused on subchondral bone, a joint component often-ignored by existing bioinformatic reports, to identify ferroptosis-related diagnostic biomarkers for OA.

Method

Microarray datasets GSE51588 and GSE55457 were downloaded from Gene Expression Omnibus database. Ferroptosis-related differential expression genes (Ferr-DEGs) between OA and normal samples were identified and their functional enrichment was analyzed. Common genes for OA diagnosis were selected from Ferr-DEGs using the combination of SVM-RFE, LASSO regression, and RandomForest machine learning algorithms. Common genes' diagnostic value was verified by receiver operating characteristic (ROC) curve and their association with immune infiltration was analyzed by CIBERSORT. Finally, candidate gene’s expression was verified in chondrocytes from OA patients and in an in vitro IL-1β-induced OA model, by RT-PCR.

Results

Two ferroptosis-related genes, LPCAT3 and PGD, were identified as OA diagnostic biomarkers and confirmed by ROC diagnostic test. The association of LPCAT3 and PGD with the infiltration of several types of immune cells was identified. The decreased expression of LPCAT3 and PGD was both confirmed in OA chondrocytes and IL-1β-induced OA condition.

Conclusions

We identified ferroptosis-related genes LPCAT3 and PGD as potential diagnostic biomarkers for OA, which may offer insight into the role of ferroptosis in OA and provides useful information for the diagnosis and treatment of OA.
Impact of ERAS compliance on the short-term outcomes for distal radius surgery: a single-center retrospective study
Authors: Mu Er Ti Zha Mi Er A. Li Mu , Sun Zhi Jian , Li Ting , Ai Mai Ti Re Zi Ya , Fu Gang , Yao Dong Chen , Yu Xiang
Published: September 2023

Background

Distal radius fractures (DRF) account for one in five bony injuries in both primary and secondary trauma care. Enhanced recovery after surgery (ERAS) has been adopted successfully to improve clinical outcomes in multiple surgical disciplines; however, no study has investigated the effect of different degrees of compliance with ERAS protocol on short-term outcomes following distal radius surgery. We aimed to analyze whether different degrees of compliance with the ERAS pathway are associated with clinical improvement following surgery for DRF.

Methods

We retrospectively analyzed all consecutive patients with ERAS who underwent surgery for DRF at our department between May 2019 and October 2022. Their pre-, peri-, and post-operative compliance with the 22 elements of the ERAS program were assessed. We compared parameters between low- (< 68.1%) and high-compliance (> 68.1%) groups, including patient complications, total length of hospitalization, discharge time after surgery, hospital costs, time taken to return to preinjury level performance level, number of visual analogue scale (VAS) pain scores > 3 points during hospitalization, disabilities of the arm, shoulder and hand (DASH) scores. We performed multiple linear regression analyses to assess the impact of ERAS compliance on the postoperative function level (DASH scores).

Results

No significant differences were detected between the high- and low-compliance groups with respect to demographics, including sex, age, body mass index (BMI), and comorbidities (P > 0.05). We observed significant differences between the high- and low-compliance groups in terms of the DASH score (32.25 ± 9.97 vs. 40.50 ± 15.65, p < 0.05) at 6 months postoperatively, the discharge time after surgery (2.45 ± 1.46 vs. 3.14 ± 1.50, p < 0.05), and number of times when the VAS pain score was > 3 points during hospitalization (0.88, [0.44, 1.31], p < 0.05). Our study demonstrated a significant negative association between ERAS compliance and the function level of patients postoperatively (DASH scores) when adjusted for age, comorbidity, sex, and BMI.

Conclusions

This study provided a realistic evaluation and comparison of the ERAS protocol among patients with DRF and can guide clinical decision making. The ERAS protocol may improve outcomes after surgery, with high postoperative function levels and reduced pain and discharge time after surgery, without increased complication rates or hospital costs.
Prevalence and quality of temporomandibular disorders, chronic pain and psychological distress in patients with classical and hypermobile Ehlers-Danlos syndrome: an exploratory study
Authors: Willich Leon , Bohner Lauren , Köppe Jeanette , Jackowski Jochen , Hanisch Marcel , Oelerich Ole
Published: September 2023

Background

The Ehlers-Danlos syndromes are a group of clinically and genetically heterogeneous hereditary diseases affecting the connective tissue. They are characterized by hypermobility of the joints, hyperextensible skin and friable tissue. According to current classification, 13 subtypes can be distinguished, of which the hypermobile and the classical subtype are the most prevalent. This study aimed to evaluate patients with classical (cEDS) and hypermobile (hEDS) Ehlers-Danlos syndrome regarding temporomandibular disorder (TMD), chronic pain, and psychological distress.

Methods

Support groups from Germany, Austria, and Switzerland were contacted, and social media were used to recruit participants. Free text questions, the German version of the Depression Anxiety and Stress Scale (DASS), and the German version of the Graded Chronic Pain Status (GCPS) were used.

Results

259 participants were included (230 hEDS/29 cEDS). At least 49.2% of the participants had painful or restricted jaw movements, and at least 84.9% had pain in the masticatory muscles, with 46.3% already having a diagnosed TMD. Multivariate analysis showed a significant correlation between TMJ involvement and chronic pain with a 2.5-fold higher risk of chronic pain with a diagnosed TMD. 22.8% of participants had a critical score for depression, 53.3% had a critical score for anxiety, and 34.0% had a critical score for stress.

Conclusion

There is a high prevalence of TMD problems and chronic pain in patients with cEDS and hEDS. The lack of knowledge about these problems can create psychological distress. More research is needed to provide adequate treatment for patients with EDS.
The major TMEM106B dementia risk allele affects TMEM106B protein levels, fibril formation, and myelin lipid homeostasis in the ageing human hippocampus
Authors: Lee Jun Yup , Harney Dylan J , Teo Jonathan D , Kwok John B , Sutherland Greg T. , Larance Mark , Don Anthony S
Published: September 2023

Background

The risk for dementia increases exponentially from the seventh decade of life. Identifying and understanding the biochemical changes that sensitize the ageing brain to neurodegeneration will provide new opportunities for dementia prevention and treatment. This study aimed to determine how ageing and major genetic risk factors for dementia affect the hippocampal proteome and lipidome of neurologically-normal humans over the age of 65. The hippocampus was chosen as it is highly susceptible to atrophy with ageing and in several neurodegenerative diseases.

Methods

Mass spectrometry-based proteomic and lipidomic analysis of CA1 hippocampus samples from 74 neurologically normal human donors, aged 66–104, was used in combination with multiple regression models and gene set enrichment analysis to identify age-dependent changes in the proteome and lipidome. ANOVA was used to test the effect of major dementia risk alleles in the TMEM106B and APOE genes on the hippocampal proteome and lipidome, adjusting for age, gender, and post-mortem interval. Fibrillar C-terminal TMEM106B fragments were isolated using sarkosyl fractionation and quantified by immunoblotting.

Results

Forty proteins were associated with age at false discovery rate-corrected P < 0.05, including proteins that regulate cell adhesion, the cytoskeleton, amino acid and lipid metabolism, and ribosomal subunits. TMEM106B, a regulator of lysosomal and oligodendrocyte function, was regulated with greatest effect size. The increase in TMEM106B levels with ageing was specific to carriers of the rs1990622-A allele in the TMEM106B gene that increases risk for frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, and hippocampal sclerosis with ageing. Rs1990622-A was also associated with higher TMEM106B fibril content. Hippocampal lipids were not significantly affected by APOE genotype, however levels of myelin-enriched sulfatides and hexosylceramides were significantly lower, and polyunsaturated phospholipids were higher, in rs1990622-A carriers after controlling for APOE genotype.

Conclusions

Our study demonstrates that TMEM106B protein abundance is increased with brain ageing in humans, establishes that dementia risk allele rs1990622-A predisposes to TMEM106B fibril formation in the hippocampus, and provides the first evidence that rs1990622-A affects brain lipid homeostasis, particularly myelin lipids. Our data suggests that TMEM106B is one of a growing list of major dementia risk genes that affect glial lipid metabolism.
Progress towards universal health coverage in the context of mental disorders in India: evidence from national sample survey data
Authors: Ranjan Alok , Crasta Jewel E
Published: September 2023

Background

Universal health coverage (UHC) has emerged as one of the important health policy discourses under the current sustainable development goals in the world. UHC in individual disease conditions is a must for attaining overall UHC. This study measures progress towards UHC in terms of access to health care and financial protection among individuals with mental disorders in India.

Methods

Data from the 75th Round National Sample Survey (NSS), 2017-18, was used, which is the latest round on health in India. Data collected from 555,115 individuals (rural: 325,232; urban: 229,232), from randomly selected 8077 villages and 6181 urban areas, included 283 outpatient and 374 hospitalization cases due to mental disorders in India. Logistic regression models were used for analyses.

Results

Self-reporting of mental disorders was considerably lower than the actual disease burden in India. However, self-reporting of ailment was 1.73 times higher (95% CI: 1.18–2.52, p < 0.05) among the richest income group population compared to the poorest in India. The private sector was a major service provider of mental health services with a larger share for outpatient (66.1%) than inpatient care (59.2%). Over 63% of individuals with a mental disorder who reported private sector hospitalization noted unavailability or poor service quality at public facilities. Only 23% of individuals hospitalized had health insurance coverage at All India level. However, health insurance coverage among poorest economic class was a meagre 3.4%. Average out-of-pocket expenditure during hospitalization (public: 123 USD; private: 576 USD) and outpatient care (public: 8 USD; private: 37 USD) was significantly higher in the private sector than in the public sector. Chances of facing catastrophic health expenditure at 10% threshold were 23.33 times (95% CI: 10.85–50.17; p < 0.001) higher under private sector than public sector during hospitalization. Expenditure on medicine, as the share of total medical expenditure, was highest for hospitalization (public: 45%, private:39.5%) and outpatient care (public: 74.1%, private:39.7%).

Conclusions

Social determinants play a vital role in access to healthcare and financial protection among individuals with mental disorders in India. For achieving UHC in mental disorders, India needs to address the gaps in access and financial protection for individuals with mental disorders.

Trial registration

Not applicable.