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Musculoskeletal Care Sep 2024Advanced practice physiotherapy (APP) models of care are promising to alleviate pressure in emergency departments (EDs) where physiotherapists' new roles include being a... (Randomized Controlled Trial)
Randomized Controlled Trial
Patients presenting with musculoskeletal disorders in the emergency department: A qualitative study of their experiences when cared by advanced practice physiotherapists in the province of Québec.
BACKGROUND
Advanced practice physiotherapy (APP) models of care are promising to alleviate pressure in emergency departments (EDs) where physiotherapists' new roles include being a first-contact practitioner and leading the overall care and management of patients with minor musculoskeletal disorders (MSKDs) to alleviate ED physicians' caseload.
PURPOSE
To explore patients' acceptability, experience, satisfaction, and perception of a new APP-led model of care in the ED.
METHODS
Patients presenting to the ED with a minor MSKD and who agreed to participate in a multicenter, pan-Canadian randomized controlled trial assessing the efficacy and costs of an APP model of care were invited to participate in this qualitative study. Semi-structured interviews were performed to identify themes related to their experiences with this model. Verbatim transcripts were coded and analysed using an inductive thematic analysis.
RESULTS
11 patients participated and three themes were identified: 1- They were satisfied with the care received within the model; 2- They found APPs to have the appropriate skill set to manage MSKDs and to assume medical-delegated tasks; 3- Timely access to care was a key factor in the acceptability of this model and participants believed physiotherapists were appropriate first-contact practitioners. One participant proposed that the APP model of care should also offer follow-up care.
CONCLUSION
Participants had a positive experience of care in this new model. These results support the implementation of APP models of care in EDs as the participants appear receptive to new roles for APPs.
Topics: Humans; Emergency Service, Hospital; Musculoskeletal Diseases; Male; Female; Middle Aged; Adult; Physical Therapists; Quebec; Patient Satisfaction; Qualitative Research; Aged
PubMed: 38943044
DOI: 10.1002/msc.1914 -
Internal and Emergency Medicine Jun 2024It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation...
It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15-29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings.
PubMed: 38943034
DOI: 10.1007/s11739-024-03658-9 -
Cellular and Molecular Life Sciences :... Jun 2024Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes...
Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.
Topics: Humans; MicroRNAs; Cetuximab; Drug Resistance, Neoplasm; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Jumonji Domain-Containing Histone Demethylases; Argonaute Proteins; Animals; Mice; Cell Nucleus; Female; Mice, Nude
PubMed: 38943031
DOI: 10.1007/s00018-024-05324-x -
International Ophthalmology Jun 2024To investigate the clinical significance of the correlation between optical densitometry and both biomechanical and morphological parameters in keratoconus (KC) and to...
PURPOSE
To investigate the clinical significance of the correlation between optical densitometry and both biomechanical and morphological parameters in keratoconus (KC) and to verify the diagnostic value of optical densitometry in KC.
METHOD
This cross-sectional study included 436 eyes of 295 patients with KC. Corneal optical densitometry, morphological parameters and biomechanical parameters were measured. Spearman's correlation analysis was employed to investigate the association between optical densitometry and both biomechanical and morphological parameters.
RESULT
Optical densitometry of the anterior (0-2 mm and 2-6 mm), central (0-2 mm), posterior (2-6 mm) and total (2-6 mm) layers correlated positively with SPA1, while the posterior layer (0-2 mm) correlated negatively. Optical densitometry of the anterior layers 2-6 mm, 6-10 mm, and the central layer 6-10 mm negatively affected AL1, while the posterior layer 0-2 mm positively affected it. Optical densitometry of the anterior, central, and posterior layers 0-2 mm and 2-6 mm positively influenced the morphological parameters K, K, K and the absolute values of K, K, K. Optical densitometry of the center (0-2 mm) and posterior (2-6 mm) layers negatively influenced TCT. Optical densitometry of the anterior (0-2 mm and 2-6 mm), center (0-2 mm), posterior (2-6 mm) and total (2-6 mm) layers correlated positively with ACE and PCE, whereas the posterior layer (0-2 mm) correlated negatively.
CONCLUSION
Optical densitometry was correlated with biomechanical and morphological parameters in keratoconus, suggesting its potential as a diagnostic indicator for assessing keratoconus progression and treatment efficacy.
Topics: Humans; Keratoconus; Cross-Sectional Studies; Female; Densitometry; Male; Cornea; Adult; Corneal Topography; Young Adult; Adolescent; Middle Aged; Biomechanical Phenomena
PubMed: 38943020
DOI: 10.1007/s10792-024-03212-8 -
Microbial Ecology Jun 2024Plastic pollution poses a worldwide environmental challenge, affecting wildlife and human health. Assessing the biodegradation capabilities of natural microbiomes in...
Plastic pollution poses a worldwide environmental challenge, affecting wildlife and human health. Assessing the biodegradation capabilities of natural microbiomes in environments contaminated with microplastics is crucial for mitigating the effects of plastic pollution. In this work, we evaluated the potential of landfill leachate (LL) and estuarine sediments (ES) to biodegrade polyethylene (PE), polyethylene terephthalate (PET), and polycaprolactone (PCL), under aerobic, anaerobic, thermophilic, and mesophilic conditions. PCL underwent extensive aerobic biodegradation with LL (99 ± 7%) and ES (78 ± 3%) within 50-60 days. Under anaerobic conditions, LL degraded 87 ± 19% of PCL in 60 days, whereas ES showed minimal biodegradation (3 ± 0.3%). PE and PET showed no notable degradation. Metataxonomics results (16S rRNA sequencing) revealed the presence of highly abundant thermophilic microorganisms assigned to Coprothermobacter sp. (6.8% and 28% relative abundance in anaerobic and aerobic incubations, respectively). Coprothermobacter spp. contain genes encoding two enzymes, an esterase and a thermostable monoacylglycerol lipase, that can potentially catalyze PCL hydrolysis. These results suggest that Coprothermobacter sp. may be pivotal in landfill leachate microbiomes for thermophilic PCL biodegradation across varying conditions. The anaerobic microbial community was dominated by hydrogenotrophic methanogens assigned to Methanothermobacter sp. (21%), pointing at possible syntrophic interactions with Coprothermobacter sp. (a H-producer) during PCL biodegradation. In the aerobic experiments, fungi dominated the eukaryotic microbial community (e.g., Exophiala (41%), Penicillium (17%), and Mucor (18%)), suggesting that aerobic PCL biodegradation by LL involves collaboration between fungi and bacteria. Our findings bring insights on the microbial communities and microbial interactions mediating plastic biodegradation, offering valuable perspectives for plastic pollution mitigation.
Topics: Biodegradation, Environmental; Microbiota; Microplastics; Waste Disposal Facilities; Bacteria; Water Pollutants, Chemical; Polyesters; Geologic Sediments; RNA, Ribosomal, 16S; Estuaries; Polyethylene; Polyethylene Terephthalates
PubMed: 38943017
DOI: 10.1007/s00248-024-02399-8 -
Cell Biochemistry and Biophysics Jun 2024Chronic arsenic-exposure causes neuromuscular disorders and other health anomalies. Damage to DNA and cytoskeletal/extracellular matrix is brought on by...
Arsenic Induced Oxidative Neural-Damages in Rat are Mitigated by Tea-Leave Extract via MMPs and AChE Inactivation, Shown by Molecular Docking and in Vitro Studies with Pure Theaflavin and AChE.
BACKGROUND
Chronic arsenic-exposure causes neuromuscular disorders and other health anomalies. Damage to DNA and cytoskeletal/extracellular matrix is brought on by reactive-oxygen-species (ROS)-induced intrinsic antioxidant depletion (thiols/urate). Therapeutic chelating-agents have multiple side-effects.
OBJECTIVES
The protection of (Camellia sinensis) tea-extract and role of uric-acid (UA) or allopurinol (urate-depletor) on arsenic-toxicity were verified in rat model.
METHODS
Camellia sinensis (CS dry-leaves), UA or allopurinol was supplemented to arsenic-intoxicated rats for 4-weeks. Purified theaflavins and their galloyl-ester were tested in-vitro on pure AChE (acetylcholinesterase) and their PDB/PubChem 3-D structures were utilized for in-silico binding studies. The primary chemical components were evaluated from CS-extracts. Biochemical analysis, PAGE-zymogram, DNA-stability comet analysis, HE-staining was performed in arsenic-exposed rat brain tissues.
RESULTS
Animals exposed to arsenic showed symptoms of erratic locomotion, decreased intrinsic antioxidants (catalase/SOD1/uric acid), increased AChE, and malondialdehyde. Cerebellar and cerebrum tissue damages were shown with increased levels of matrix-metalloprotease (MMP2/9) and DNA damage (comets). Allopurinol- supplemented group demonstrated somewhat similar biochemical responses. In the CS-group brain tissues especially cerebellum is considerably protected which is evident from endogenous antioxidant and DNA and cytoskeleton protection with concomitant inactivation of MMPs and AChE. Present study indicates theaflavin-digallate (TFDG) demonstrated the highest inhibition of purified AChE (IC = 2.19 µg/ml with the lowest binding free-energy; -369.87 kcal/mol) followed by TFMG (IC = 3.86 µg/ml, -347.06 kcal/mol) suggesting their possible restoring effects of cholinergic response.
CONCLUSIONS
Favorable responses in UA-group and adverse outcome in allo-group justify the neuro-protective effects of UA as an endogenous antioxidant. Role of flavon-gallate in neuro protection mechanism may be further studied.
PubMed: 38943009
DOI: 10.1007/s12013-024-01369-8 -
GeroScience Jun 2024A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive... (Review)
Review
A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive disorders, dementia, and depression. This is especially true in cases of changes in diet, malnutrition, loss of muscular endurance, and abnormal systemic inflammatory response. Our study aimed to determine the extent of these associations to better target the multi-level healthy aging challenge investigating the impact of periodontal disease on cognitive disorders (cognitive impairment and cognitive decline), dementia, and depression. We conducted a comprehensive literature search up to November 2023 using six different electronic databases. Two independent researchers assessed the eligibility of 7363 records against the inclusion criteria and found only 46 records that met the requirements. The study is registered on PROSPERO (CRD42023485688). We generated random effects pooled estimates and 95% confidence intervals (CI) to evaluate whether periodontal disease increased the risk of the investigated outcomes. The quality assessment revealed moderate quality of evidence and risk of bias. Periodontal disease was found to be associated with both cognitive disorders (relative risk (RR) 1.25, 95% CI 1.11-1.40, in the analysis of cross-sectional studies); cognitive impairment (RR 3.01, 95% CI 1.52-5.95 for longitudinal studies, cognitive decline); and dementia (RR 1.22, 95% CI 1.10-1.36). However, no significant increased risk of depression among subjects with periodontal disease was found (RR 1.07, 95% CI 0.95-1.21). Despite the association with two of the three explored outcomes, the available evidence on periodontal diseases and dementia, cognitive disorders, and depression is controversial due to several limitations. Therefore, further investigations involving validated and standardized tools are required.
PubMed: 38943006
DOI: 10.1007/s11357-024-01243-8 -
EMBO Reports Jun 2024Centrosomes are the canonical microtubule organizing centers (MTOCs) of most mammalian cells, including spermatocytes. Centrosomes comprise a centriole pair within a...
Centrosomes are the canonical microtubule organizing centers (MTOCs) of most mammalian cells, including spermatocytes. Centrosomes comprise a centriole pair within a structurally ordered and dynamic pericentriolar matrix (PCM). Unlike in mitosis, where centrioles duplicate once per cycle, centrioles undergo two rounds of duplication during spermatogenesis. The first duplication is during early meiotic prophase I, and the second is during interkinesis. Using mouse mutants and chemical inhibition, we have blocked centriole duplication during spermatogenesis and determined that non-centrosomal MTOCs (ncMTOCs) can mediate chromosome segregation. This mechanism is different from the acentriolar MTOCs that form bipolar spindles in oocytes, which require PCM components, including gamma-tubulin and CEP192. From an in-depth analysis, we identified six microtubule-associated proteins, TPX2, KIF11, NuMA, and CAMSAP1-3, that localized to the non-centrosomal MTOC. These factors contribute to a mechanism that ensures bipolar MTOC formation and chromosome segregation during spermatogenesis when centriole duplication fails. However, despite the successful completion of meiosis and round spermatid formation, centriole inheritance and PLK4 function are required for normal spermiogenesis and flagella assembly, which are critical to ensure fertility.
PubMed: 38943004
DOI: 10.1038/s44319-024-00187-6 -
Environmental Science and Pollution... Jun 2024Indoor air quality (IAQ) in the built environment is significantly influenced by particulate matter, volatile organic compounds, and air temperature. Recently, the... (Review)
Review
Indoor air quality (IAQ) in the built environment is significantly influenced by particulate matter, volatile organic compounds, and air temperature. Recently, the Internet of Things (IoT) has been integrated to improve IAQ and safeguard human health, comfort, and productivity. This review seeks to highlight the potential of IoT integration for monitoring IAQ. Additionally, the paper details progress by researchers in developing IoT/mobile applications for IAQ monitoring, and their transformative impact in smart building, healthcare, predictive maintenance, and real-time data analysis systems. It also outlines the persistent challenges (e.g., data privacy, security, and user acceptability), hampering effective IoT implementation for IAQ monitoring. Lastly, the global developments and research landscape on IoT for IAQ monitoring were examined through bibliometric analysis (BA) of 106 publications indexed in Web of Science from 2015 to 2022. BA revealed the most significant contributing countries are India and Portugal, while the top productive institutions and researchers are Instituto Politecnico da Guarda (10.37% of TP) and Marques Goncalo (15.09% of TP), respectively. Keyword analysis revealed four major research themes: IoT, pollution, monitoring, and health. Overall, this paper provides significant insights for identifying prospective collaborators, benchmark publications, strategic funding, and institutions for future IoT-IAQ researchers.
PubMed: 38943001
DOI: 10.1007/s11356-024-34075-2 -
Nature Medicine Jun 2024As artificial intelligence (AI) rapidly approaches human-level performance in medical imaging, it is crucial that it does not exacerbate or propagate healthcare...
As artificial intelligence (AI) rapidly approaches human-level performance in medical imaging, it is crucial that it does not exacerbate or propagate healthcare disparities. Previous research established AI's capacity to infer demographic data from chest X-rays, leading to a key concern: do models using demographic shortcuts have unfair predictions across subpopulations? In this study, we conducted a thorough investigation into the extent to which medical AI uses demographic encodings, focusing on potential fairness discrepancies within both in-distribution training sets and external test sets. Our analysis covers three key medical imaging disciplines-radiology, dermatology and ophthalmology-and incorporates data from six global chest X-ray datasets. We confirm that medical imaging AI leverages demographic shortcuts in disease classification. Although correcting shortcuts algorithmically effectively addresses fairness gaps to create 'locally optimal' models within the original data distribution, this optimality is not true in new test settings. Surprisingly, we found that models with less encoding of demographic attributes are often most 'globally optimal', exhibiting better fairness during model evaluation in new test environments. Our work establishes best practices for medical imaging models that maintain their performance and fairness in deployments beyond their initial training contexts, underscoring critical considerations for AI clinical deployments across populations and sites.
PubMed: 38942996
DOI: 10.1038/s41591-024-03113-4