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Experimental Drugs with the Potential to Treat Atopic Eczema.

Eczema or atopic dermatitis (AD) is a chronically relapsing dermatosis characterized by pruritus and a significant impact on the quality of life.

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Circular RNA ITCH Is a Tumor Suppressor in Clear Cell Renal Cell Carcinoma Metastasis through miR-106b-5p/PDCD4 Axis.

High metastasis of clear cell renal cell carcinoma (ccRCC) significantly influenced survival rate of ccRCC patients. Here, we intended to investigate the impacts of circular RNA ITCH (circ-ITCH) on the metastasis of ccRCC. The expression of circ-ITCH in ccRCC tissues and cells was evaluated utilizing qRT-PCR. Transwell assay and wound healing were applied to investigate migration and invasion of ccRCC cells. Target gene prediction and screening and luciferase reporter gene assays were utilized to assess downstream target genes of circ-ITCH. Western blot was utilized to detect metastasis-related protein expression. A xenograft tumor model was established to evaluate the role of circ-ITCH in vivo. Results showed that circ-ITCH was low expressed in ccRCC tissues and cells. Downregulation circ-ITCH promoted cell migration, but overexpressing circ-ITCH inhibited cell migration and invasion in OSRC-2 and SW839 cells. Mechanism investigations claimed that circ-ITCH exerted its metastasis-inhibitory activity via sponging miR-106b-5p and regulating the expression of PDCD4. Conclusively, circ-ITCH suppresses ccRCC metastasis by enforcing PDCD4 expression through binding miR-106b-5p. circ-ITCH may function as a novel diagnostic target to suppress ccRCC metastasis.

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LIFU Alleviates Neuropathic Pain by Improving the KCC Expression and Inhibiting the CaMKIV-KCC Pathway in the L4-L5 Section of the Spinal Cord.

Effective treatment remains lacking for neuropathic pain (NP), a type of intractable pain. Low-intensity focused ultrasound (LIFU), a noninvasive, cutting-edge neuromodulation technique, can effectively enhance inhibition of the central nervous system (CNS) and reduce neuronal excitability. We investigated the effect of LIFU on NP and on the expression of potassium chloride cotransporter 2 (KCC) in the spinal cords of rats with peripheral nerve injury (PNI) in the lumbar 4-lumbar 5 (L4-L5) section. In this study, rats received PNI surgery on their right lower legs followed by LIFU stimulation of the L4-L5 section of the spinal cord for 4 weeks, starting 3 days after surgery. We used the 50% paw withdraw threshold (PWT) to evaluate mechanical allodynia. Western blotting (WB) and immunofluorescence (IF) were used to calculate the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), and KCC in the L4-L5 portion of the spinal cord after the last behavioral tests. We found that PWT decreased ( < 0.05) 3 days post-PNI surgery in the LIFU and LIFU groups and increased ( < 0.05) after 4 weeks of LIFU stimulation. The expression of p-CREB and CaMKIV decreased ( < 0.05) and that of KCC increased ( < 0.05) after 4 weeks of LIFU stimulation, but that of p-ERK1/2 ( > 0.05) was unaffected. Our study showed that LIFU could effectively alleviate NP behavior in rats with PNI by increasing the expression of KCC on spinal dorsal corner neurons. A possible explanation is that LIFU could inhibit the activation of the CaMKIV-KCC pathway.

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Case Report: Virtual Reality Neurofeedback Therapy as a Novel Modality for Sustained Analgesia in Centralized Pain Syndromes.

Neurofeedback (NFB) Therapy is a form of biofeedback, using the electroencephalogram (EEG) that has been in use since the 1970s, serving as a non-pharmacological intervention for epilepsy and psychiatric conditions such as anxiety, depression, insomnia, PTSD, post-concussive syndrome, and now, centralized pain. Chronic pain can increase neuronal activity and eventually causes poor modulation of pain messages. With the emergence of Virtual Reality (VR) in acute pain management, and the contraindications of opioids in chronic pain, applying novel biotechnologies seems like the next frontier in multimodal pain management. In this study, the VR and NFB technologies were fused together (VR-NFB) and used as a novel treatment modality for a 55-year-old woman who suffered from chronic pain secondary to spondylolisthesis with cervical, thoracic, and lumbar disc herniations after a motor vehicle accident with comorbid depression, anxiety, sleep deprivation, and difficulty with activities of daily living, and inability to participate in physical therapy. Our case reports on the sustained analgesia achieved for 1 year after a trial of VR-NFB, and the usefulness of neuromodulation in centralized pain syndromes.

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Secondary Amyloidosis Presenting as Ischemic Proctitis.

A 49-year-old man presented with abdominal pain and rectal bleeding for two days associated with a 50-pound unintentional weight loss. History was notable for hypertension, chronic kidney disease, obesity, gout, and acute cholecystitis status post cholecystectomy. Computed tomography (CT) of the abdomen and pelvis showed rectal wall thickening. Colonoscopy showed proctitis with superficial ulcerations. In the setting of renal insufficiency, malabsorption, and low-voltage QRS complexes on electrocardiogram (ECG), amyloidosis was considered in the differential diagnosis. Rectal and renal biopsies with subsequent retrospective staining of gallbladder tissue confirmed amyloid deposition. Gastrointestinal involvement of amyloidosis is relatively uncommon. Particularly, amyloid deposition in the gallbladder and rectum is very rare. The development of AA amyloidosis in our patient may have been related to gout, obesity, and the presence of a heterozygous complex variant for the MEFV (familial Mediterranean fever) gene. Awareness of this atypical presentation of amyloidosis is important, as additional staining of biopsy samples is necessary, and diagnosis allows for directed treatment.

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Prevalence, characteristics, and impact of pain during the postpartum period.

To identify the prevalence of pain in puerperal women, describe the characteristics of pain and its impacts on the performance of daily life activities, and evaluate satisfaction with received analgesia.

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Theaflavin-3,3′-Digallate Promotes the Formation of Osteoblasts Under Inflammatory Environment and Increases the Bone Mass of Ovariectomized Mice.

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3'-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/β-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.

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Neurofibromatosis Type 1 with Highly Active Relapsing-Remitting Multiple Sclerosis (RRMS).

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disease which confers an increased risk of malignant tumour development. Relapsing remitting multiple sclerosis (RRMS) is an inflammatory demyelinating disease of the central nervous system. The coexistence of multiple sclerosis and NF1 is rare but has been reported. Here, we describe the case of a 31-year-old man with NF1 and subacute walking problems with proximal pain in the lower limbs who was successfully treated with natalizumab.

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Efficacy of Essential Oils in Pain: A Systematic Review and Meta-Analysis of Preclinical Evidence.

The demand for essential oils (EOs) has been steadily growing over the years. This is mirrored by a substantial increase in research concerned with EOs also in the field of inflammatory and neuropathic pain. The purpose of this present systematic review and meta-analysis is to investigate the preclinical evidence in favor of the working hypothesis of the analgesic properties of EOs, elucidating whether there is a consistent rational basis for translation into clinical settings. A literature search has been conducted on databases relevant for medical scientific literature, i.e., PubMed/MEDLINE, Scopus, and Web of Science from database inception until November 2, 2020, following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses. The search was conducted in order to answer the following PICOS (participants/population, interventions, comparisons, outcomes, and study design) question: are EOs efficacious in reducing acute nociceptive pain and/or neuropathic pain in mice experimental models? The search retrieved 2,491 records, leaving 954 studies to screen after the removal of duplicates. The title and abstract of all 954 studies were screened, which left 127 records to evaluate in full text. Of these, 30 articles were eligible for inclusion. Most studies (27) assessed the analgesic properties of EOs on acute nociceptive pain models, e.g. the acetic acid writhings test, the formalin test, and the hot plate test. Unfortunately, efficacy in neuropathic pain models, which are a more suitable model for human conditions of chronic pain, had fewer results (only three studies). Moreover, some methodologies raised concerns in terms of the risk of bias. Therefore, EOs with proven efficacy in both types of pain were corroborated by methodologically consistent studies, like the EO of bergamot, which should be studied in clinical trials to enhance the translational impact of preclinical modeling on clinical pain research.

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Age-Dependent Differences in the Rate and Symptoms of TIA Mimics in Patients Presenting With a Suspected TIA to a Neurological Emergency Room.

Transient ischemic attack (TIA) needs further diagnostic evaluation to prevent future ischemic stroke. However, prophylaxis can be harmful in elderly if the diagnosis is wrong. We aimed at characterizing differences in TIA mimics in younger and older patients to enhance diagnostic accuracy in elderly patients. In a dedicated neurological emergency room (nER) of a tertiary care University hospital, patients with transient neurological symptoms suspicious of TIA (<24 h) were retrospectively analyzed regarding their final diagnoses and their symptoms. These parameters were compared between patients aged 18-70 and >70 years using descriptive, univariable, and multivariable statistics. From November 2018 until August 2019, 386 consecutive patients were included. 271 (70%) had cardiovascular risk factors and all patients received cerebral imaging, mostly CT [376 (97%)]. There was no difference in the rate of diagnosed TIA between the age groups [85 (46%) vs. 58 (39%); = 0.213].TIA mimics in the elderly were more often internal medicine diseases [35 (19%) vs. 7 (5%); < 0.001] and epileptic seizures [48 (26%) vs. 24 (16%); = 0.032] but less often migraine [2 (1%) vs. 20 (13%); < 0.001]. The most frequent symptoms in all patients were aphasia and dysarthria [107 (28%) and 92 (24%)]. Sensory impairments were less frequent in elderly patients [23 (11%) vs. 54 (30%); < 0.001]. Impaired consciousness and orientation were independent predictors for TIA mimics ( < 0.001) whereas facial palsy ( < 0.001) motor weakness ( < 0.001), dysarthria ( = 0.022) and sensory impairment ( < 0.001) were independent predictors of TIA. TIA mimics in elderly patients are more likely to be internal medicine diseases and epilepsy compared to younger patients. Excluding internal medicine diseases seems to be important in elderly patients. Facial palsy, motor weakness, dysarthria and sensory impairment are associated with TIA.

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