Rejected

The goal of this study was to elucidate the anti-pruritic and anti-inflammatory efficacy of ruxolitinib cream in experimentally-induced dermatitis. Atopic dermatitis (AD), the most common chronic relapsing inflammatory skin disease, significantly impairs patients' quality of life, with pruritus being a common complaint. The sensation of itch results from the interplay between epidermal barrier dysfunction, upregulated immune signaling and the activation of the central nervous system. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a central role in pro-inflammatory cytokine signaling in AD. Ruxolitinib cream is a potent and selective JAK1/2 inhibitor currently undergoing clinical evaluation in adults with mild-to-moderate AD (NCT03745638, NCT03920852 and NCT03745651). The efficacy of ruxolitinib cream was tested in murine models of acute and chronic dermatitis and was also characterized in an human skin dermatitis model. Ruxolitinib cream was highly effective at ameliorating disease symptoms in multiple murine dermatitis models through downregulation of T helper (Th)2-driven inflammation, resulting in reduced skin thickening and decreased itch. Pathway analysis of mouse ear tissue and human skin explants underscored the role for ruxolitinib in ameliorating inflammation and reducing itch modulation of the JAK-STAT pathway. Together, the data offer a strong rationale for the use of ruxolitinib cream as a potent therapeutic agent for the clinical management of atopic dermatitis.

Dementia is one the major problems of aging societies, and, novel and effective non-drug therapies are required as interventions in the oldest-old to prevent cognitive decline. This study aims to examine the efficacy and safety of reminiscence using immersive virtual reality (iVR reminiscence) focusing on anxiety that often appears with cognitive decline. The secondary objective is to reveal the preference for VR image types for reminiscence: live-action (LA) or computer graphics (CG). This was a pilot, open-label, and randomized crossover study which was conducted on January 2020 at a single nursing home. The subjects were randomly divided into two groups (A or B) in equal numbers, and they alternately viewed two types of VR images (LA and CG) themed on the mid- to late Showa era (A.D. 1955-1980) in Japan. In group A, the CG images were viewed first, and then the LA images were viewed (CG→ LA). In group B, the images were viewed in the opposite order (LA→ CG). Before VR viewing, subjects responded to Mini-Mental State Examination (MMSE) Japanese version and State-Trait Anxiety Inventory (STAI) Japanese version. After viewing the first and second VR, subjects responded to STAI and the numerical rating scale (NRS) for satisfaction and side effects (nausea, dizziness, headache, and tiredness). Ten subjects participated in this study. The values of analyses are presented in the mean (SD). The age was 87.1 years (4.2), and the MMSE was 28.5 (1.8). The total STAI score before VR viewing was 36.1 (7.2), but it significantly decreased to 26.8 (4.9) after the first VR viewing ( = 0.0010), and further decreased to 23.4 (2.8) after the second VR viewing ( < 0.001). The NRS score for satisfaction tended to be higher after viewing LA in group A (CG→ LA) (CG vs. LA; 7.0 (2.3) vs. 8.6 (1.5), = 0.0993), while in group B (LA→ CG), the score after CG was slightly lower than that after LA. There were no serious side effects. This study suggests that iVR reminiscence can reduce anxiety in the oldest-old without causing serious side effects. Furthermore, the impacts might be better with LA images.

Charcot spine arthropathy (CSA), a result of reduced afferent innervation, is an occurrence of Charcot joint, a progressive, degenerative disorder in vertebral joints, related mostly to spinal cord injury. The repeated microtrauma is a result of a lack of muscle protection and destroys cartilage, ligaments, and disc spaces, leading to vertebrae destruction, joint instability, subluxation, and dislocation. Joint destruction compresses nerve roots, resulting in pain, paresthesia, sensory loss, dysautonomia, and spasticity. CSA presents with back pain, spinal deformity and instability, and audible spine noises during movement. Autonomic dysfunction includes bowel and bladder dysfunction. It is slowly progressive and usually diagnosed at a late stage, usually, on average, 20 years after the first initial insult. Diagnosis is rarely clinical related to the nature of nonspecific symptoms and requires imaging with computed tomography (CT) and magnetic resonance imaging (MRI). Conservative management focuses on the prevention of fractures and the progression of deformities. This includes bed rest, orthoses, and braces. These could be useful in elderly or frail patients who are not candidates for surgical treatment, or in minimally symptomatic patients, such as patients with spontaneous fusion leading to a stable spine. Symptomatic treatment is offered for autonomic dysfunction, such as anticholinergics for bladder control. Most patients require surgical treatment. Spinal fusion is achieved with open, minimally-open (MOA) or minimally-invasive (MIS) approaches. The gold standard is open circumferential fusion; data is lacking to determine the superiority of open or MIS approaches. Patients usually improve after surgery; however, the rarity of the condition makes it difficult to estimate outcomes. This is a review of the latest and seminal literature about the treatment and chronic management of Charcot spine. The review includes the background of the syndrome, clinical presentation, and diagnosis, and compares the different treatment options that are currently available.

The treatment of symptomatic uncomplicated colonic diverticular disease (SUDD) is still under debate, and new data show a pathogenic role of dysbiosis and low-grade inflammation in intestinal mucosa. Recent research has highlighted the anti-inflammatory effects of botanical extracts such as L. and Roxb. ex Colebr. The aim of this work is to investigate the potential role of a new delivery formulation of the association of curcumin and boswellia phytosome extracts (CBP) in SUDD.

Corydalis Rhizoma (CR) is a commonly used traditional Chinese medicine for its potency in activating blood circulation and analgesia. In clinic, CR extracts or components are commonly used in the treatment of myocardial ischemia, rheumatism, and dysmenorrhea with different types of inflammation. However, due to different mechanism of pain and inflammation, the anti-inflammatory property of CR has not been fully revealed. Here, the major chromatographic peaks of CR extracts in different extracting solvents were identified, and the anti-inflammatory activities of CR extracts and its major alkaloids were evaluated in LPS-treated macrophages by determining expressions of proinflammatory cytokines, IB and NF-B. The most abundant alkaloid in CR extract was dehydrocorydaline, having >50% of total alkaloids. Besides, the anti-inflammatory activities of dehydrocorydaline and its related analogues were demonstrated. The anti-inflammatory roles were revealed in LPS-treated cultured macrophages, including (i) inhibiting proinflammatory cytokines release, for example, TNF-, IL-6; (ii) suppressing mRNA expressions of proinflammatory cytokines; (iii) promoting IB expression and suppressing activation of NF-B transcriptional element; and (iv) reducing the nuclear translocation of NF-B. The results supported that dehydrocorydaline was the major alkaloid in CR extract, which, together with its analogous, accounted the anti-inflammatory property of CR.

An opioid-sparing anesthetic involves a multi-modal technique with non-opioid medications targeting different analgesic pathways. Such techniques may decrease adverse effects related to opioids. These techniques may be considered in patients at higher risk for opioid-related adverse effects including obstructive sleep apnea or sleep disordered breathing.

CircRNAs are noncoding RNA molecules that have recently been described and shown to regulate miRNA functionality. While recent studies have suggested such circRNAs to be associated with pain related diseases in humans, no comprehensive migraine-related circRNA profiles have been generated, and there is currently no clear understanding of whether they can serve as regulators of migraine pathology.

Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by hypertrabeculations and intertrabecular recesses most often seen in the left ventricle (LV). The patient may be asymptomatic or present with heart failure, arrhythmia, and sudden death. We discuss a previously healthy 7-year-old male who presented to the Emergency Department (ED) multiple times over a three-week period. His complaints evolved over the course of his illness, initially presenting with fatigue and suicidal ideation, followed by diffuse abdominal pain. Prior to his ICU admission, he had been discharged from the ED twice, due to well appearance and reassuring lab findings. He returned to the ED a final time with severe venous congestion and cardiogenic shock with acute hepatic injury. Echocardiogram revealed LV apical hypertrabeculation with a severe dilated cardiomyopathy and biventricular failure along with a large thrombus in the left ventricular cavity. Congestive heart failure and anticoagulation therapy was initiated, and the patient went on to biventricular assist device (BiVAD) placement and cardiac transplant. Although LVNC is rare, pediatric heart failure does present to the general pediatrician and has high morbidity and mortality. The presenting symptoms can be obscure and pose a challenge to pediatricians. This case report and review will assist in familiarizing the general pediatrician with pediatric heart failure presentation, treatment, and course.

Autoimmune hypophysitis (AH) is a primary autoimmune inflammatory disorder of the pituitary gland, which usually presents as a mass in the sella turcica. Systemic lupus erythematosus (SLE) is another inflammatory disorder in which the immune system attacks healthy cells and tissues throughout the body. Although both diseases are autoimmune disorders, they rarely coexist, and the relationship between them is unclear.

Vitamin B12 (cobalamin) deficiency is a frequent cause of megaloblastic anemia, manifested through various symptoms. Screening for this deficiency can be justified in case of patients with one or more risk factors present from the following: gastric resections, inflammatory bowel disease, use of metformin over a prolonged period of time, administration of proton pump inhibitors or H2 histamine receptor blockers for more than 12 months and in case of adults over 75 years of age. One method of determining vitamin B12 deficiency is measuring its serum levels, as well as performing measurements of serum levels of methylmalonic acid and homocysteine levels, which experience an increase in the early stages of vitamin B12 deficiency.