bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipose tissue specific CCL18 associates with cardiometabolic diseases in non-obese individuals implicating CD4+ T cells
Authors: Subramanian Narmadha , Hofwimmer Kaisa , Tavira Beatriz , Massier Lucas , Andersson Daniel P , Arner Peter , Laurencikiene Jurga
Published: April 2023

Aim

Obesity is linked to cardiometabolic diseases, however non-obese individuals are also at risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). White adipose tissue (WAT) is known to play a role in both T2D and CVD, but the contribution of WAT inflammatory status especially in non-obese patients with cardiometabolic diseases is less understood. Therefore, we aimed to find associations between WAT inflammatory status and cardiometabolic diseases in non-obese individuals.

Methods

In a population-based cohort containing non-obese healthy (n = 17), T2D (n = 16), CVD (n = 18), T2D + CVD (n = 19) individuals, seventeen different cytokines were measured in WAT and in circulation. In addition, 13-color flow cytometry profiling was employed to phenotype the immune cells. Human T cell line (Jurkat T cells) was stimulated by rCCL18, and conditioned media (CM) was added to the in vitro cultures of human adipocytes. Lipolysis was measured by glycerol release. Blocking antibodies against IFN-γ and TGF-β were used in vitro to prove a role for these cytokines in CCL18-T-cell-adipocyte lipolysis regulation axis.

Results

In CVD, T2D and CVD + T2D groups, CCL18 and CD4+ T cells were upregulated significantly compared to healthy controls. WAT CCL18 secretion correlated with the amounts of WAT CD4+ T cells, which also highly expressed CCL18 receptors suggesting that WAT CD4+ T cells are responders to this chemokine. While direct addition of rCCL18 to mature adipocytes did not alter the adipocyte lipolysis, CM from CCL18-treated T cells increased glycerol release in in vitro cultures of adipocytes. IFN-γ and TGF-β secretion was significantly induced in CM obtained from T cells treated with CCL18. Blocking these cytokines in CM, prevented CM-induced upregulation of adipocyte lipolysis.

Conclusion

We suggest that in T2D and CVD, increased production of CCL18 recruits and activates CD4+ T cells to secrete IFN-γ and TGF-β. This, in turn, promotes adipocyte lipolysis – a possible risk factor for cardiometabolic diseases.
Engineering osmolysis susceptibility in Cupriavidus necator and Escherichia coli for recovery of intracellular products
Authors: Adams Jeremy David , Sander Kyle B. , Criddle Craig S. , Arkin Adam P. , Clark Douglas S.
Published: April 2023

Background

Intracellular biomacromolecules, such as industrial enzymes and biopolymers, represent an important class of bio-derived products obtained from bacterial hosts. A common key step in the downstream separation of these biomolecules is lysis of the bacterial cell wall to effect release of cytoplasmic contents. Cell lysis is typically achieved either through mechanical disruption or reagent-based methods, which introduce issues of energy demand, material needs, high costs, and scaling problems. Osmolysis, a cell lysis method that relies on hypoosmotic downshock upon resuspension of cells in distilled water, has been applied for bioseparation of intracellular products from extreme halophiles and mammalian cells. However, most industrial bacterial strains are non-halotolerant and relatively resistant to hypoosmotic cell lysis.

Results

To overcome this limitation, we developed two strategies to increase the susceptibility of non-halotolerant hosts to osmolysis using Cupriavidus necator, a strain often used in electromicrobial production, as a prototypical strain. In one strategy, C. necator was evolved to increase its halotolerance from 1.5% to 3.25% (w/v) NaCl through adaptive laboratory evolution, and genes potentially responsible for this phenotypic change were identified by whole genome sequencing. The evolved halotolerant strain experienced an osmolytic efficiency of 47% in distilled water following growth in 3% (w/v) NaCl. In a second strategy, the cells were made susceptible to osmolysis by knocking out the large-conductance mechanosensitive channel (mscL) gene in C. necator. When these strategies were combined by knocking out the mscL gene from the evolved halotolerant strain, greater than 90% osmolytic efficiency was observed upon osmotic downshock. A modified version of this strategy was applied to E. coli BL21 by deleting the mscL and mscS (small-conductance mechanosensitive channel) genes. When grown in medium with 4% NaCl and subsequently resuspended in distilled water, this engineered strain experienced 75% cell lysis, although decreases in cell growth rate due to higher salt concentrations were observed.

Conclusions

Our strategy is shown to be a simple and effective way to lyse cells for the purification of intracellular biomacromolecules and may be applicable in many bacteria used for bioproduction.
Assessing feasibility of a modified same-day test-and-treat model for hepatitis C among rural people who inject drugs
Authors: Hassan Muhammad Radzi Abu , Chan Huan-Keat , Nordin Mahani , Yahya Ranimah , Sulaiman Wan Ruzilasalwa Wan , Merican Siti Aminah Akbar , Lah Darisah , Sem Xiaohui , Shilton Sonjelle
Published: April 2023

Background

Despite advancements in hepatitis C virus (HCV) treatment, low uptake among hard-to-reach populations remains a global issue. The current study aimed to assess the feasibility of a modified same-day test-and-treat model in improving HCV care for people who inject drugs (PWID) living in resource-constrained rural areas.

Methods

A pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).

Results

A total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.

Conclusions

The modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.
P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction
Authors: Chen Qi , Li Yilan , Bie Bike , Zhao Bin , Zhang Yanxiu , Fang Shaohong , Li Shuijie , Zhang Yao
Published: April 2023

Background

Heart failure (HF) after myocardial infarction (MI) is a prevalent disease with a poor prognosis. Relieving pathological cardiac remodeling and preserving cardiac function is a critical link in the treatment of post-MI HF. Thus, more new therapeutic targets are urgently needed. The expression of ADAM17 is increased in patients with acute MI, but its functional role in post-MI HF remains unclear.

Methods

To address this question, we examined the effects of ADAM17 on the severity and prognosis of HF within 1 year of MI in 152 MI patients with or without HF. In mechanistic studies, the effects of ADAM17 on ventricular remodeling and systolic function were extensively assessed at the tissue and cellular levels by establishing animal model of post-MI HF and in vitro hypoxic cell model.

Results

High levels of ADAM17 predicted a higher incidence of post-MI HF, poorer cardiac function and higher mortality. Animal studies demonstrated that ADAM17 promoted the occurrence of post-MI HF, as indicated by increased infarct size, cardiomyocyte hypertrophy, myocardial interstitial collagen deposition and cardiac failure. ADAM17 knock down significantly improved pathological cardiac remodeling and cardiac function in mice with MI. Mechanistically, activated ADAM17 inhibited the cardioprotective effects of ACE2 by promoting hydrolytic shedding of the transmembrane protein ACE2 in cardiomyocytes, which subsequently mediated the occurrence of cardiac remodeling and the progression of heart failure. Moreover, the activation of ADAM17 in hypoxic cardiomyocytes was dependent on p38 MAPK phosphorylation at threonine 735.

Conclusions

These data highlight a novel and important mechanism for ADAM17 to cause post-MI HF, which will hopefully be a new potential target for early prediction or intervention of post-MI HF.
Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression
Authors: Yu Huangfei , Qu Tianyin , Yang Jinlan , Dai Qing
Published: April 2023

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a key messenger that mediates several central and peripheral functions in the human body. Emerging evidence indicates that serotonin is critical in tumorigenesis, but its role in colorectal cancer remains elusive. Herein, we report that serotonin transporter (SERT) transports serotonin into colorectal cancer cells, enhancing Yes-associated protein (YAP) expression and promoting in vitro and in vivo colon cancer cell growth. Once within the cells, transglutaminase 2 (TG2) mediates RhoA serotonylated and activates RhoA-ROCK1/2 signalling to upregulate YAP expression in SW480 and SW1116 cells. Blocking SERT with citalopram reversed the serotonin-induced YAP expression and cell proliferation, inhibiting serotonin’s effects on tumour formation in mice. Moreover, SERT expression was correlated with YAP in pathological human colorectal cancer samples and the levels of 5-HT were highly significant in the serum of patients with colorectal cancer. Together, our findings suggested that serotonin enters cells via SERT to activate RhoA/ROCK/YAP signalling to promote colon cancer carcinogenesis. Consequently, targeting serotonin-SERT-YAP axis may be a potential therapeutic strategy for colorectal cancer.
Distinct phenotypes of multisystem inflammatory syndrome in children: a cohort study
Authors: Renson Thomas , Forkert Nils D. , Amador Kimberly , Miettunen Paivi , Parsons Simon J. , Dhalla Muhammed , Johnson Nicole A. , Luca Nadia , Schmeling Heinrike , Stevenson Rebeka , Twilt Marinka , Hamiwka Lorraine , Benseler Susanne
Published: April 2023

Background

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease with an unpredictable course and a substantial risk of cardiogenic shock. Our objectives were to (a) compare MIS-C phenotypes across the COVID-19 pandemic, (b) identify features associated with intensive care need and treatment with biologic agents.

Methods

Youth aged 0–18 years, fulfilling the World Health Organization case definition of MIS-C, and admitted to the Alberta Children’s Hospital during the first four waves of the COVID-19 pandemic (May 2020-December 2021) were included in this cohort study. Demographic, clinical, biochemical, imaging, and treatment data were captured.

Results

Fifty-seven MIS-C patients (median age 6 years, range 0–17) were included. Thirty patients (53%) required intensive care. Patients in the third or fourth wave (indicated as phase 2 of the pandemic) presented with higher peak ferritin (µg/l, median (IQR) = 1134 (409–1806) vs. 370 (249–629), P = 0.001), NT-proBNP (ng/l, median (IQR) = 12,217 (3013–27,161) vs. 3213 (1216–8483), P = 0.02) and D-dimer (mg/l, median (IQR) = 4.81 (2.24–5.37) vs. 2.01 (1.27–3.34), P = 0.004) levels, and higher prevalence of liver enzyme abnormalities (n(%) = 17 (68) vs. 11 (34), P = 0.02), hypoalbuminemia (n(%) = 24 (100) vs. 25 (81), P = 0.03) and thrombocytopenia (n(%) 18 (72) vs. 11 (34), P = 0.007) compared to patients in the first two waves (phase 1). These patients had a higher need of non-invasive/mechanical ventilation (n(%) 4 (16) vs. 0 (0), P = 0.03). Unsupervised clustering analyses classified 47% of the patients in the correct wave and 74% in the correct phase of the pandemic. NT-proBNP was the only significant contributor to the need for intensive care in all applied multivariate regression models. Treatment with biologic agents was significantly associated with peak CRP (mg/l (median, IQR = 240.9 (132.9-319.4) vs. 155.8 (101.0-200.7), P = 0.02) and ferritin levels (µg/l, median (IQR) = 1380 (509–1753) vs. 473 (280–296)).

Conclusions

MIS-C patients in a later stage of the pandemic displayed a more severe phenotype, reflecting the impact of distinct SARS-CoV-2 variants. NT-proBNP emerged as the most crucial feature associated with intensive care need, underscoring the importance of monitoring.
Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions
Authors: Müller Ludmila , Di Benedetto Svetlana
Published: April 2023

Advanced age is one of the significant risk determinants for coronavirus disease 2019 (COVID-19)-related mortality and for long COVID complications. The contributing factors may include the age-related dynamical remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. Both of these factors may induce an inflammatory milieu in the aged brain and drive the changes in the microenvironment of neurons and microglia, which are characterized by a general condition of chronic inflammation, so-called neuroinflammation. Emerging evidence reveals that the immune privilege in the aging brain may be compromised. Resident brain cells, such as astrocytes, neurons, oligodendrocytes and microglia, but also infiltrating immune cells, such as monocytes, T cells and macrophages participate in the complex intercellular networks and multiple reciprocal interactions. Especially changes in microglia playing a regulatory role in inflammation, contribute to disturbing of the brain homeostasis and to impairments of the neuroimmune responses. Neuroinflammation may trigger structural damage, diminish regeneration, induce neuronal cell death, modulate synaptic remodeling and in this manner negatively interfere with the brain functions.

In this review article, we give insights into neuroimmune interactions in the aged brain and highlight the impact of COVID-19 on the functional systems already modulated by immunosenescence and neuroinflammation. We discuss the potential ways of these interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and review proposed neuroimmune mechanisms and biological factors that may contribute to the development of persisting long COVID conditions. We summarize the potential mechanisms responsible for long COVID, including inflammation, autoimmunity, direct virus-mediated cytotoxicity, hypercoagulation, mitochondrial failure, dysbiosis, and the reactivation of other persisting viruses, such as the Cytomegalovirus (CMV). Finally, we discuss the effects of various interventional options that can decrease the propagation of biological, physiological, and psychosocial stressors that are responsible for neuroimmune activation and which may inhibit the triggering of unbalanced inflammatory responses. We highlight the modulatory effects of bioactive nutritional compounds along with the multimodal benefits of behavioral interventions and moderate exercise, which can be applied as postinfectious interventions in order to improve brain health.
Screening and identification of cyprinid herpesvirus 2 (CyHV-2) ORF55-interacting proteins by phage display
Authors: Qian Min , Xiao Simin , Yang Yapeng , Yu Fei , Wen Jinxuan , Lu Liqun , Wang Hao
Published: April 2023

Background

Cyprinid herpesvirus 2 (CyHV-2) is a pathogenic fish virus belonging to family Alloherpesviridae. The CyHV-2 gene encoding thymidine kinase (TK) is an important virulence-associated factor. Therefore, we aimed to investigate the biological function of open reading frame 55 (ORF55) in viral replication.

Methods

Purified CyHV-2 ORF55 protein was obtained by prokaryotic expression, and the interacting peptide was screened out using phage display. Host interacting proteins were then predicted and validated.

Results

ORF55 was efficiently expressed in the prokaryotic expression system. Protein and peptide interaction prediction and dot-blot overlay assay confirmed that peptides identified by phage display could interact with the ORF55 protein. Comparing the peptides to the National Center for Biotechnology Information database revealed four potential interacting proteins. Reverse transcription quantitative PCR results demonstrated high expression of an actin-binding Rho-activating protein in the latter stages of virus-infected cells, and molecular docking, cell transfection and coimmunoprecipitation experiments confirmed that it interacted with the ORF55 protein.

Conclusion

During viral infection, the ORF55 protein exerts its biological function through interactions with host proteins. The specific mechanisms remain to be further explored.
Mobile homes in the land of illness: the hospitality and hostility of language in doctor-patient relations
Authors: Milford Stephen R.
Published: April 2023

Illness has a way of disorientating us, as if we are cast adrift in a foreign land. Like strangers in a dessert we seek oasis to recollect ourselves, find refuge and learn to build our own shelters. Using the philosophy of Levinas and Derrida, we can interpret health care providers (HCP), and the sites from which they act (e.g. hospitals), as dwelling hosts that offer hospitality to strangers in this foreign land. While often the dwellings are physical (e.g. hospitals), this is not always the case. Language represents a mobile home of refuge to the sick. Using language the HCP has built a shelter so as to dwell in the land of illness. However, while hospitality is an inviting concept, it also implies hostility. The door that opens may also be slammed shut. This article explores the paradox of the linguistic mobile home offered to patients. It highlights the power of language to construct a safe place in a strange land, but also explores the inherent violence. It ends with an exploration of the ways language can be used by HCP to assist patients to construct their own mobile shelters.
Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
Authors: Talaverón-Rey Marta , Álvarez-Córdoba Mónica , Villalón-García Irene , Povea-Cabello Suleva , Suárez-Rivero Juan M. , Gómez-Fernández David , Romero-González Ana , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Cilleros-Holgado Paula , Reche-López Diana , Piñero-Pérez Rocío , Sánchez-Alcázar José A.
Published: April 2023

Background

Neurodegeneration with brain iron accumulation (NBIA) disorders are a group of neurodegenerative diseases that have in common the accumulation of iron in the basal nuclei of the brain which are essential components of the extrapyramidal system. Frequent symptoms are progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. One of the most prevalent subtypes of NBIA is Pantothenate kinase-associated neurodegeneration (PKAN). It is caused by pathogenic variants in the gene of pantothenate kinase 2 (PANK2) which encodes the enzyme responsible for the first reaction on the coenzyme A (CoA) biosynthesis pathway. Thus, deficient PANK2 activity induces CoA deficiency as well as low expression levels of 4′-phosphopantetheinyl proteins which are essential for mitochondrial metabolism.

Methods

This study is aimed at evaluating the role of alpha-lipoic acid (α-LA) in reversing the pathological alterations in fibroblasts and induced neurons derived from PKAN patients. Iron accumulation, lipid peroxidation, transcript and protein expression levels of PANK2, mitochondrial ACP (mtACP), 4′′-phosphopantetheinyl and lipoylated proteins, as well as pyruvate dehydrogenase (PDH) and Complex I activity were examined.

Results

Treatment with α-LA was able to correct all pathological alterations in responsive mutant fibroblasts with residual PANK2 enzyme expression. However, α-LA had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of α-LA in particular pathogenic variants was also confirmed in induced neurons derived from mutant fibroblasts.

Conclusions

Our results suggest that α-LA treatment can increase the expression levels of PANK2 and reverse the mutant phenotype in PANK2 responsive pathogenic variants. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of α-LA.
Androgen-induced exosomal miR-379-5p release determines granulosa cell fate: cellular mechanism involved in polycystic ovaries
Authors: Salehi Reza , Wyse Brandon A. , Asare-Werehene Meshach , Esfandiarinezhad Fereshteh , Abedini Atefeh , Pan Bo , Urata Yoko , Gutsol Alex , Vinas Jose L. , Jahangiri Sahar , Xue Kai , Xue Yunping , Burns Kevin D. , Vanderhyden Barbara , Li Julang , Osuga Yutaka , Burger Dylan , Tan Seang-Lin , Librach Clifford L. , Tsang Benjamin K.
Published: April 2023

Polycystic ovarian syndrome (PCOS) is a complex multi-factorial syndrome associated with androgen excess and anovulatory infertility. In the current study, we investigated the role of dihydrotestosterone-induced exosomal miR-379-5p release in determining the destiny of the developing follicles. Our hypothesis was that androgen regulates granulosa cell miR-379-5p content by facilitating its exosomal release in a follicular-stage dependent manner, a process which determines granulosa cell fate. Compared to human non-PCOS subjects, individuals with PCOS exhibit higher follicular fluid free testosterone levels, lower exosomal miR-379-5p content and granulosa cell proliferation. Androgenized rats exhibited lower granulosa cell miR-379-5p but higher phosphoinositide-dependent kinase-1 (PDK1; a miR-379-5p target) content and proliferation. Androgen reduced granulosa cell miR-379-5p content by increasing its exosomal release in preantral follicles, but not in antral follicles in vitro. Studies with an exosomal release inhibitor confirmed that androgen-induced exosomal miR-379-5p release decreased granulosa cell miR-379-5p content and proliferation. Ovarian overexpression of miR-379-5p suppressed granulosa cell proliferation, and basal and androgen-induced preantral follicle growth in vivo. These findings suggest that increased exosomal miR-379-5p release in granulosa cells is a proliferative response to androgenic stimulation specific for the preantral stage of follicle development and that dysregulation of this response at the antral stage is associated with follicular growth arrest, as observed in human PCOS.
Effects of prebiotic supplement on gut microbiota, drug bioavailability, and adverse effects in patients with colorectal cancer at different primary tumor locations receiving chemotherapy: study protocol for a randomized clinical trial
Authors: Chen Ya , Liao Xiaowei , Li Yanmin , Cao Hong , Zhang Feng , Fei Bojian , Bao Chuanqing , Cao Huaxiang , Mao Yong , Chen Xiaoping , Gao Xiang , Zhao Wei , Xu Jianmin
Published: April 2023

Background

The prevalence of colorectal cancer (CRC) worldwide is a huge challenge to human health. Primary tumor locations found to impact prognosis and response to therapy. The important role of gut microbiota in the progression and treatment of CRC has led to many attempts of alleviating chemotherapy-induced adverse effects using microecologics. However, the underlying mechanism of the difference in the prognosis of different primary tumor locations and the synergistic effect of prebiotics on chemotherapy need to be further elucidated. This study aims to explore the differences in tumor microbiota and examine the effectiveness of xylooligosaccharides (XOS) on gut microbiota, adverse effects, and bioavailability of chemotherapy drugs in CRC patients at different primary tumor locations.

Methods

This is a double-blinded, randomized, parallel controlled clinical trial. Participants with left-sided CRC (LSCRC, n = 50) and right-sided CC (RSCC, n = 50) will randomly allocated to prebiotic group (n = 25) or control group (n = 25) and will receive either a daily XOS (3 g/day) or placebo, respectively, for 12 weeks. The primary outcomes will be the differences in the mucosa microbiota composition at different tumor locations and differences in gut microbiota composition, adverse effects, and blood concentration of capecitabine posttreatment. The secondary outcomes will include other blood indicators, short-chain fatty acids (SCFAs) concentration, quality of life, and mental health.

Discussion

This study will reveal the potential benefits of prebiotic for improving the gut microbiota composition, alleviating the adverse effects, and improving the efficacy of chemotherapy in patients with CRC. In addition, this study will provide data on the different distribution of tumor microbiota and the different changes of gut microbiota during treatment in LSCRC and RSCC, which may provide novel insights into personalized cancer treatment strategies based on primary tumor locations and gut microbiota in the future.

Trial registration

Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR2100046237. Registered on 12 May 2021.
Re-thinking osteoarthritis pathogenesis: what can we learn (and what do we need to unlearn) from mouse models about the mechanisms involved in disease development
Authors: Poulsen Raewyn C. , Jain Lekha , Dalbeth Nicola
Published: April 2023

Efforts to develop effective disease-modifying drugs to treat osteoarthritis have so far proved unsuccessful with a number of promising drug candidates from pre-clinical studies failing to show efficacy in clinical trials. It is therefore timely to re-evaluate our current understanding of osteoarthritis pathogenesis and the similarities and differences in disease development between commonly used pre-clinical mouse models and human patients. There is substantial heterogeneity between patients presenting with osteoarthritis and mounting evidence that the pathways involved in osteoarthritis (e.g. Wnt signalling) differ between patient sub-groups. There is also emerging evidence that the pathways involved in osteoarthritis differ between the STR/ort mouse model (the most extensively studied mouse model of spontaneously occurring osteoarthritis) and injury-induced osteoarthritis mouse models. For instance, while canonical Wnt signalling is upregulated in the synovium and cartilage at an early stage of disease in injury-induced osteoarthritis mouse models, this does not appear to be the case in the STR/ort mouse. Such findings may prove insightful for understanding the heterogeneity in mechanisms involved in osteoarthritis pathogenesis in human disease. However, it is important to recognise that there are differences between mice and humans in osteoarthritis pathogenesis. A much more extensive array of pathological changes are evident in osteoarthritic joints in individual mice with osteoarthritis compared to individual patients. There are also specified differences in the pathways involved in disease development. For instance, although increased TGF-β signalling is implicated in osteoarthritis development in both mouse models of osteoarthritis and human disease, in mice, this is mainly mediated through TGF-β3 whereas in humans, it is through TGF-β1. Studies in other tissues have shown TGF-β1 is more potent than TGF-β3 in inducing the switch to SMAD1/5 signalling that occurs in osteoarthritic cartilage and that TGF-β1 and TGF-β3 have opposing effects on fibrosis. It is therefore possible that the relative contribution of TGF-β signalling to joint pathology in osteoarthritis differs between murine models and humans. Understanding the similarities and differences in osteoarthritis pathogenesis between mouse models and humans is critical for understanding the translational potential of findings from pre-clinical studies.
Vibrio cholerae O1 associated with recent endemic cholera shows temporal changes in serotype, genotype, and drug-resistance patterns in Bangladesh
Authors: Jubyda Fatema Tuz , Nahar Kazi Sumaita , Barman Indrajeet , Johura Fatema-Tuz , Islam Mohammad Tarequl , Sultana Marzia , Ullah Wali , Tasnim Jarin , Biswas Sahitya Ranjan , Monir Md Mamun , George Christine Marie , Camilli Andrew , Ahmed Niyaz , Ross Allen G. , Clemens John D. , Alam Munirul
Published: April 2023

Background

Despite the advancement in our understanding of cholera and its etiological agent, Vibrio cholerae, the prevention and treatment of the disease are often hindered due to rapid changes in drug response pattern, serotype, and the major genomic islands namely, the CTX-prophage, and related genetic characteristics. In the present study, V. cholerae (n = 172) associated with endemic cholera in Dhaka during the years 2015–2021 were analyzed for major phenotypic and genetic characteristics, including drug resistance patterns.

Results

Results revealed that the V. cholerae strains belonged to serogroup O1 biotype El Tor carrying El Tor -specific genes rtxC, tcpA El Tor, and hlyA El Tor, but possessed classical-biotype cholera toxin. Serotypes of V. cholerae strains differed temporally in predominance with Inaba during 2015–2017, and again in 2020–2021, while Ogawa was the predominant serotype in 2018–2019. Also, ctxB1 was predominant in V. cholerae associated with cholera during 2015–2017, while ctxB7 was predominant in 2018, and in the subsequent years, as observed until 2021. V. cholerae strains differed in their antibiotic resistance pattern with a majority (97%) being multi-drug resistant (MDR) and belonging to six sub-groups. Notably, one of these MDR strains was resistant to eleven of the eighteen antibiotics tested, with resistance to fourth-generation cephalosporin (cefepime), and aztreonam. This extreme drug resistant (XDR) strain carried resistance-related genes namely, extended-spectrum β-lactamases (ESBL), blaOXA-1 and blaPER-3.

Conclusion

The observed temporal switching of serotypes, as well as the ctxB genotype, and the emergence of MDR/XDR V. cholerae and their association with endemic cholera in Dhaka underscore the need for routine monitoring of the pathogen for proper patient management.
Pathological mechanisms of neuroimmune response and multitarget disease-modifying therapies of mesenchymal stem cells in Parkinson’s disease
Authors: Zhuo Yi , Li Xuan , He Zhengwen , Lu Ming
Published: April 2023

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN); the etiology and pathological mechanism of the disease are still unclear. Recent studies have shown that the activation of a neuroimmune response plays a key role in the development of PD. Alpha-synuclein (α-Syn), the primary pathological marker of PD, can gather in the SN and trigger a neuroinflammatory response by activating microglia which can further activate the dopaminergic neuron’s neuroimmune response mediated by reactive T cells through antigen presentation. It has been shown that adaptive immunity and antigen presentation processes are involved in the process of PD and further research on the neuroimmune response mechanism may open new methods for its prevention and therapy. While current therapeutic regimens are still focused on controlling clinical symptoms, applications such as immunoregulatory strategies can delay the symptoms and the process of neurodegeneration. In this review, we summarized the progression of the neuroimmune response in PD based on recent studies and focused on the use of mesenchymal stem cell (MSC) therapy and challenges as a strategy of disease-modifying therapy with multiple targets.
Feasibility of implementing an innovative manual handling risk assessment training program for staff working in long-term care
Authors: Brusco Natasha K , Graven Christine , Boyd Leanne , Kugler Helen , Dawes Helen , Rawson Helen , Clayton Lynne , Tan Suzanna , Goodwin Victoria A , Hall Abi J , Taylor Nicholas F
Published: April 2023

Background

The Risk Assessment for moving Individuals SafEly (RAISE) program is a hospital-based manual handling nursing training program. RAISE involves upskilling on continual risk assessment during patient-assisted movements. RAISE aims to optimise staff and patient safety while providing the patient with movement and rehabilitation opportunities. Implementation of RAISE in the hospital setting has been established. The aim of this study was to explore the feasibility of implementing RAISE in the long-term care setting.

Methods

We examined three feasibility domains: acceptability, practicality, and limited efficacy (observed nursing behaviour change which has the potential to reduce nursing injuries), using a prospective pilot pre-post design in the long-term care setting. Staff completed a 4-hour training session on RAISE delivered by two physiotherapists, followed by 8 h of supported behaviour change in the workplace. Staff acceptability and practicality of incorporating risk assessment strategies into manual handling approaches were explored through pre- and post-training staff surveys and a semi-structured interview. Resident acceptability of manual handling practices was explored via survey data collected after the RAISE training. Pre to post-training changes in staff knowledge and behaviour were examined through the pre- and post-training staff survey, and observation of staff assisting resident movement.

Results

Two enrolled nurses and five residents participated. Staff reported the RAISE program was acceptable and practical to implement in the long-term care setting. There were no adverse events or safety concerns. Staff reported the RAISE program provided guidance and enhanced staff empowerment to make decisions during assisted resident movement. There were 26 observed resident-staff manual handling interactions recorded, with 13 pre-training and 13 post-training. Post-training, RAISE skills had improved and were completed 100% of the time, except for completing a physical risk assessment which improved from 46 to 85%, demonstrating limited efficacy. Residents reported it’s important for staff to be trained on how to assist them to mobilise and they found the concept of the RAISE program acceptable.

Conclusions

This pilot study supports the feasibility of long-term care facilities participating in future studies testing the effectiveness and cost-effectiveness of the Risk Assessment for moving Individuals SafEly (RAISE) patient and resident manual handling program.
Systematic literature review of the techniques for household electrical appliance anomaly detections and knowledge extractions
Authors: Rauf Seidu Agbor Abdul , Adekoya Adebayo F.
Published: April 2023

The demand for electricity at home has increased in recent times globally, this high demand for continuous, stable and affordable power can be attributed to the demand for comfortable lifestyle of consumers but the quality and efficiency of the appliances being used remain questionable. Malfunctioning appliances usually show a power signature statistically different from their normal behavior, which can lead to higher energy consumption or more serious damages. As a result, numerous studies in recent times have been conducted on the household electrical appliance anomaly behaviors to find the root-cause of these anomalies using machine learning techniques and algorithms. This study attempted to undertake a systematic and critical review of ninety-two (92) research works reported in academic journals over fifteen (15) years (2006–2021) in the area of household electrical appliance anomaly detections and knowledge extraction using machine learning. The various techniques used in these reports were clustered based on machine learning-based techniques, statistical techniques and physical based approach techniques and the parameters adopted, such as machine learning algorithms, feature extraction approaches, anomaly detection levels, computing platforms and application scenarios. This clustering was done based on the following criteria: the nature of a dataset and the number of data sources used, the data timeframe, the machine learning algorithms used, machine learning task, used accuracy and error metrics and software packages used for modeling. For the number of data source used, the results revealed that 81.2% of documents reviewed used single sources and Autoregressive integrated moving average (ARIMA) was the highest implemented regression model (60.9%), the probability model that was mostly implemented was the Bayesian network. Furthermore, the study revealed that, root-mean-square error (RMSE) accounted 35% was the most used error metric among household appliance abnormal behaviors, followed by mean absolute percentage error MAPE which accounted 32%. The study further revealed that 46% of appliance abnormal detections was based on weather parameters, and historical energy consumption. Finally, we recap the challenges and limitations for further research in electrical appliance anomaly detections locally and globally.
Patients’ experiences of clinical team meetings (ward rounds) at an adult in-patient eating disorders ward: mixed-method service improvement project
Authors: Yim See Heng , Jones Roshan , Cooper Myra , Roberts Lyn , Viljoen David
Published: April 2023

Aims

Ward rounds are key to treatment-related decision-making, but are often stressful. This project aimed to explore and improve patients’ experiences of the clinical team meeting (CTM; historically known as ward round) in an adult in-patient eating disorders unit. A mixed-method approach was adopted with in vivo observations, two focus groups and an interview. Six patients participated. Two former patients contributed to data analysis, co-production of service improvement initiatives and write-up.

Results

The mean CTM duration was 14.3 min. Patients spoke half of the time, followed by psychiatry colleagues. ‘Request’ was the most discussed category. Three themes were identified: CTMs are important but impersonal, a sense of palpable anxiety was generated and staff and patients had divergent views regarding CTM goals.

Clinical implications

The co-produced changes to CTMs were implemented and improved patient's experiences despite COVID-19 challenges. Factors beyond CTMs, including the ward's power hierarchy, culture and language, need addressing to facilitate shared decision-making.
Experiences and support needs of consultant psychiatrists following a patient-perpetrated homicide
Authors: Hussain Qamar , Killaspy Helen , McPherson Peter , Gibbons Rachel
Published: April 2023

Aims and method

To investigate the experiences and support needs of consultant psychiatrists following a patient-perpetrated homicide, an anonymous online survey was sent to all consultant psychiatrists registered as members of the UK's Royal College of Psychiatrists.

Results

Of the 497 psychiatrists who responded, 165 (33%) had experienced a homicide by a patient under their consultant care. Most respondents reported negative impacts on their clinical work (83%), mental and/or physical health (78%) or personal relationships (59%), and for some (9–12%) these were severe and long lasting. Formal processes such as serious incident inquiries were commonly experienced as distressing. Support was mainly provided by friends, family and colleagues rather than the employing organisation.

Clinical implications

Mental health service providers need to provide support and guidance to psychiatrists following a patient-perpetrated homicide to help them manage the personal and professional impact. Further research into the needs of other mental health professionals is needed.
Children with autism in the Greek educational system: ongoing challenges during the COVID-19 pandemic
Authors: Mitroulaki Sotiria , Samakouri Maria , Serdari Aspasia
Published: April 2023

The inclusion of children with autism spectrum disorder (ASD) in typical educational settings has only recently gained momentum in Greece, responding to the recommendations of the international conventions. Reform of special education legislation spotlights the inclusion of children with autism in mainstream schools. The principal goal is to accept the diversity and heterogeneity of all students. This paper presents the educational policy for children with ASD in Greece and comments on teachers’ perceptions of inclusion. School closures due to the COVID-19 pandemic had an adverse impact on children's lives and created a new environment with different demands for educational inclusion.
Investigating the potential association of temporary employment and job dissatisfaction with alcohol use disorder and depressive symptoms: a 13-wave longitudinal analysis
Authors: Baek Seong-Uk , Yoon Jin-Ha , Won Jong-Uk
Published: April 2023

Background

There has been growing interest in protecting workers’ mental health. Identifying social determinants that affect workers’ mental health could play an important role in preventing psychiatric diseases.

Aims

We investigated the effects of temporary employment and job dissatisfaction on alcohol use disorder and depressive symptoms.

Method

The Korea Welfare Panel Study data-set (2009–2021) was used, and 9611 participants with 52 639 observations were included. Generalised linear mixed models were employed to estimate odds ratios and 95% confidence intervals. The relative excess risk due to interaction (RERI) was calculated to assess supra-additive interactions between temporary employment and job dissatisfaction.

Results

Increased risks for depressive symptoms were observed among fixed-term workers (odds ratio 1.12, 95% CI 1.00–1.26) and daily labourers (odds ratio 1.68, 95% CI 1.44–1.95). Daily labourers were associated with an increased risk of alcohol use disorder (odds ratio 1.54, 95% CI 1.22–1.95). Job dissatisfaction was associated with alcohol use disorder (odds ratio 1.78, 95% CI 1.52–2.08) and depressive symptoms (odds ratio 4.88, 95% CI 4.36–5.46). This effect became stronger when workers were concurrently exposed to temporary employment and job dissatisfaction. Daily labourers with job dissatisfaction showed the highest risks for alcohol use disorder (odds ratio 2.99, 95% CI 2.21–4.03) and depressive symptoms (odds ratio 9.00, 95% CI 7.36–11.02). RERIs between daily employment and job dissatisfaction were >0 for alcohol use disorder (0.91, 95% CI 0.06–1.76) and depressive symptoms (3.47, 95% CI 1.80–5.14), indicating a supra-additive interaction.

Conclusions

We revealed that temporary employment and job dissatisfaction had detrimental effects on alcohol use disorder and depressive symptoms.
Cancer Survivors' Experiences With and Preferences for Medical Information Disclosure and Advance Care Planning: An Online Survey Among Indonesian Cancer Support Groups
Authors: Martina Diah , Angka Rebecca Noerjani , Putranto Rudi , Shatri Hamzah , Sudoyo Aru Wisaksono , van der Heide Agnes , van der Rijt Carin C.D. , Rietjens Judith A.C.
Published: April 2023

PURPOSE

To understand the experiences and preferences of Indonesian cancer survivors regarding medical information disclosure and advance care planning.

METHODS

On the basis of systematic reviews of the scientific literature, qualitative studies, and expert-panel input, we developed an online survey that was distributed to nine cancer survivor support groups in Indonesia.

RESULTS

A total of 1,030 valid responses were received. Most participants were younger than 60 years (92%), female (91%), married (78%), Muslim (75%), diagnosed with breast cancer (68%), highly educated (64%), and more than one year beyond diagnosis of their cancer. If diagnosed with a life-limiting illness, participants wished to be informed about their diagnosis (74%), disease severity (61%), estimated curability (81%), expected disease trajectory (66%), and estimated life expectancy (37%). Between 46%-69% of the participants wished to discuss four topics of advance care planning (end-of-life treatments, resuscitation, health care proxies, and what matters at the end of life); 21%-42% had done so. Of those who wished to discuss these topics, 36%-79% preferred to do so with their family members. The most important reasons for not being willing to engage in advance care planning were the desire to surrender to God's will and to focus on here and now.

CONCLUSION

In a group of cancer survivors, most of them were highly educated, young, female, and diagnosed with breast cancer. Their preferences for medical information and advance care planning varied, with the majority wishing for information and involvement in advance care planning. Culturally sensitive advance care planning involves health care professionals eliciting individuals' preferences for medical information disclosure and discussing different topics in advance care planning conversations.
Disorder-induced mode coupling and symmetry breaking in amorphous solids
Authors: Kumar Avanish , Procaccia Itamar , Singh Murari
Published: April 2023

Applying very small purely radial strains on amorphous solids in radial geometry one observes elastic responses that break the radial symmetry. Without any plasticity involved, the responses indicate mode coupling contributions even for minute strains. We show that these symmetry-breaking responses are due to disorder, typical to amorphous configurations. The symmetry-breaking responses are quantitatively explained using the classical Michell solutions which are excited by mode coupling.
Diagnosis and Incidence of Congenital Combined Pituitary Hormone Deficiency in Denmark—A National Observational Study
Authors: Jakobsen Louise Kjersgaard , Jensen Rikke Beck , Birkebæk Niels Holtum , Hansen Dorte , Christensen Ann-Margrethe Rønholt , Bjerrum Maja Carsting , Christesen Henrik Thybo
Published: April 2023

Context

Congenital combined pituitary hormone deficiency (cCPHD) is the loss of ≥2 pituitary hormones caused by congenital factors.

Objective

We aimed to estimate the national incidence of cCPHD diagnosed before age 18 years and in subgroups.

Methods

Patients with cCPHD were identified in the Danish National Patient Registry and Danish hospital registries in the period 1996-2020. Hospital files were reviewed and incidences calculated using background population data. Incidence was the main outcome measure.

Results

We identified 128 patients with cCPHD; 88 (68.8%) were males. The median (range) age at diagnosis was 6.2 (0.01-19.0) years. The median (25th;75th percentile) number of hormone deficiencies at diagnosis was 3 (3; 4) at <1 year vs 2 (2; 2) at 1-17 years, P < .0001. Abnormal pituitary magnetic resonance imaging findings were seen in 70.3% (83/118). For those born in Denmark aged <18 years at diagnosis (n = 116/128) the estimated national incidence (95% CI) of cCPHD was 10.34 (7.79-13.72) per 100 000 births, with an annual incidence rate of 5.74 (4.33-7.62) per million. In subgroup analysis (diagnosis <1 vs 1-17 years), the incidence was highest in the 1-17 years subgroup, 7.97 (5.77-11.00) vs 1.98 (1.39-2.84) per 100 000 births, whereas the annual incidence rate was highest at <1 year, 19.8 (13.9-28.4) vs 4.69 (3.39-6.47) per million births.

Conclusion

cCPHD had the highest incidence rate and the most hormone deficiencies in those diagnosed at <1 year. The incidence was highest in the 1-17 years age group, underscoring the need for multiple pituitary hormone investigations throughout childhood and adolescence in children with only 1 hormone deficiency.