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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent.
OBJECTIVE: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC).
METHODS: We used Wood\'s light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method.
RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood\'s light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L.
CONCLUSIONS: Use of Wood\'s light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.

BACKGROUND: Serotonin (5-hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor-mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic-targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin\'s role in cancer pathogenesis.
UNASSIGNED: Here, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment.
CONCLUSIONS: Primary synthesis and metabolic routes of peripheral 5-hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic-targeted drugs offer valuable clinical options for cancer therapy.

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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.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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 K1F, K2F, KmF and the absolute values of K1B, K2B, KmB. 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.
CONCLUSIONS: 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.

Systemic Immune Inflammatory Index (SII) is a novel indicator of inflammation. However, no studies have reported the effect of SII on the association between metals and total fat (TOFAT). We aim to investigate the mediated effect of SII on the relationship between urinary metals and TOFAT in a US adult population. This cross-sectional study was conducted among adults with complete information on SII, urine metal concentrations, and TOFAT from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression and restricted cubic splines were used to explore the association between urine metal levels and TOFAT. Furthermore, serial mediation analyses were used to investigate the mediating effect of SII on metals and TOFAT. A total of 3324 subjects were included in this study. After adjusting for confounders, arsenic (As), cadmium (Cd), cobalt (Co), cesium (Cs), inorganic mercury (Hg), molybdenum (Mo), manganese (Mn), lead (Pb), antimony (Sb), and thallium(Tl) had negative decreased trends of odds ratios for TOFAT (all P for trend < 0.05). In the total population, we found that Cd, Co, and Tu were positively associated with SII (β = 29.70, 79.37, and 31.08), whereas As and Hg had a negative association with SII. The mediation analysis showed that SII mediated the association of Co with TOFAT, with the β of the mediating effect being 0.9% (95%CI: 0.3%, 1.6%). Our findings suggested that exposure to As, Cd, and Hg would directly decrease the level of TOFAT. However, Co would increase TOFAT, completely mediated by SII, mainly exerted in females rather than males.

Humans can use prior information to optimize their haptic exploratory behavior. Here, we investigated the usage of visual priors, which mechanisms enable their usage, and how the usage is affected by information quality. Participants explored different grating textures and discriminated their spatial frequency. Visual priors on texture orientation were given each trial, with qualities randomly varying from high to no informational value. Adjustments of initial exploratory movement direction orthogonal to the textures\' orientation served as an indicator of prior usage. Participants indeed used visual priors; the more so the higher the priors\' quality (Experiment 1). Higher task demands did not increase the direct usage of visual priors (Experiment 2), but possibly fostered the establishment of adjustment behavior. In Experiment 3, we decreased the proportion of high-quality priors presented during the session, hereby reducing the contingency between high-quality priors and haptic information. In consequence, even priors of high quality ceased to evoke movement adjustments. We conclude that the establishment of adjustment behavior results from a rather implicit contingency learning. Overall, it became evident that humans can autonomously learn to use rather abstract visual priors to optimize haptic exploration, with the learning process and direct usage substantially depending on the priors\' quality.