Koenigcochran1330

Background Contrary to the belief that patients with diabetes-related foot ulcers (DRFU) do not experience wound related pain due to the presence of peripheral neuropathy there is increasing evidence that pain can be present. Subsequently, wound-related pain is often underestimated and undertreated. The aim of this study is to describe what influences pain assessment of DRFU. Methods A qualitative exploratory study was conducted with podiatrists who managed DRFU. Eight podiatrists were recruited through a professional organisation to participate in a focus group. A thematic analysis was conducted to identify themes that explored the barriers and enablers to pain assessment and management of DRFU. Results Three themes emerged. Observational and non-verbal cues were the preferred approaches used to assess wound pain. Assumptions and value judgments of the pain patients experienced and the relationships between podiatrists, patients and other health care practitioners were important influencers on the assessment and management of pain. Conclusion The perceived barriers to the assessment and management of wound related pain in DRFU were attitudes and beliefs about pain, lack of DRFU-specific validated assessment tools and lack of knowledge and skills to manage the pain.Background Human papillomavirus (HPV)-positive oral squamous cell carcinoma (OSCC) is increasing worldwide with typically higher grade and stage, while better prognosis. microRNAs (miRNAs) has been shown to play a critical role in cancer, however, their role in HPV-positive OSCC progression remains unclear. Methods miRNA microarray was performed to identify differentially expressed miRNAs. qRT-PCR and FISH were performed to determine the relative expression of miR-550a-3-5p. CCK-8, Flow cytometry, Wound healing, Cell invasion assays and xenograft experiments were conducted to analyze the biological roles of miR-550a-3-5p. Tumor-associated macrophages (TAMs) generation, co-culturing of cancer cells with TAMs, Western blot, Dual-luciferase reporter gene assay, Immunohistochemistry and animal studies were performed to explore the mechanisms underlying the functions of miR-550a-3-5p. Results We identified 19 miRNAs differentially expressed in HPV-positive OSCC specimens and miR-550a-3-5p was down-regulated. The low expression of miR-550a-3-5p correlated with higher tumor size and nodal metastasis of HPV-positive OSCC patients. Then, we found that miR-550a-3-5p suppressed the migration, invasion and EMT of HPV-positive OSCC cells dependent on decreasing M2 macrophages polarization. Moreover, miR-550a-3-5p, down-regulated by E6 oncoprotein, inhibited M2 macrophages polarization by YAP/CCL2 signaling, which in turn abrogating EMT program in HPV-positive OSCC cells. In addition, in both xenografts and clinical HPV-positive OSCC samples, miR-550a-3-5p levels were inversely associated with YAP, CCL2 expressions and the number of M2 macrophages. Conclusions E6/miR-550a-3-5p/YAP/CCL2 signaling induces M2 macrophages polarization to enhance EMT and progression, revealing a novel crosstalk between cancer cells and immune cells in HPV-positive OSCC microenvironment.Treatment with small-molecule inhibitors, guided by precision medicine has improved patient outcomes in multiple cancer types. However, these compounds are often not effective against central nervous system (CNS) tumors. selleck screening library The failure of precision medicine approaches for CNS tumors is frequently attributed to the inability of these compounds to cross the blood-brain barrier (BBB), which impedes intratumoral target engagement. This is complicated by the fact that information on CNS penetration in CNS-tumor patients is still very limited. Herein, we evaluated cerebrospinal fluid (CSF) drug penetration, a well-established surrogate for CNS-penetration, in pediatric brain tumor patients. We analyzed 7 different oral anti-cancer drugs and their metabolites by high performance liquid chromatography mass spectrometry (HPLC-MS) in 42 CSF samples obtained via Ommaya reservoirs of 9 different patients. Moreover, we related the resulting data to commonly applied predictors of BBB-penetration including ABCB1 substrate-charce for physicochemical and biological factors favoring CNS-penetration.Background Occipital neuralgia is one of the main causes of occipital pain. This systematic review aims to assess the level of evidence in randomized controlled trials (RCTs) on the effects of acupuncture on occipital neuralgia. Methods We searched 11 databases and a journal archive from their inception up to December 2019 for relevant RCTs. We did not place any specific restrictions on patients diagnosed with occipital neuralgia, such as age or gender. We included studies that used an acupuncture intervention group, with or without the control group treatment, and that set a control group receiving active, interventional treatment such as medication. For outcomes, we used visual analogue scale (VAS) and effective rate. Results We included a total of 11 RCTs. All VAS scores (mean difference [MD] -2.35, 95% confidence interval [CI] -2.84, - 1.86) and effective rate values (odds ratio [OR] 4.96, 95% CI 2.24, 10.96) showed significant differences in effect between acupuncture treatment alone and the control group treatment. Similarly, combined acupuncture treatment with control group treatment also showed significant effects in effective rate (OR 6.68, 95% CI 1.11, 40.37). We performed a subgroup analysis on studies that used acupuncture only as the intervention and reported the effective rate, and found that all acupuncture subgroups showed significant effects compared to the control group treatments. None of the studies reported severe adverse effects. Conclusions Although acupuncture only and combined acupuncture treatments showed significant effects compared to medication, the results of this study are inconclusive. Studies with rigorous study design and larger sample sizes are needed to confirm the role of acupuncture in this field. Trial registration International prospective register for systematic review (PROSPERO) number CRD42019128050.Synaptojanin 1 (SYNJ1) is a brain-enriched lipid phosphatase critically involved in autophagosomal/endosomal trafficking, synaptic vesicle recycling and metabolism of phosphoinositides. Previous studies suggest that SYNJ1 polymorphisms have significant impact on the age of onset of Alzheimer's disease (AD) and that SYNJ1 is involved in amyloid-induced toxicity. Yet SYNJ1 protein level and cellular localization in post-mortem human AD brain tissues have remained elusive. This study aimed to examine whether SYNJ1 localization and expression are altered in post-mortem AD brains. We found that SYNJ1 is accumulated in Hirano bodies, plaque-associated dystrophic neurites and some neurofibrillary tangles (NFTs). SYNJ1 immunoreactivity was higher in neurons and in the senile plaques in AD patients carrying one or two ApolipoproteinE (APOE) ε4 allele(s). In two large cohorts of APOE-genotyped controls and AD patients, SYNJ1 transcripts were significantly increased in AD temporal isocortex compared to control. There was a significant increase in SYNJ1 transcript in APOEε4 carriers compared to non-carriers in AD cohort.