Rejected

Topical treatments are a potential therapeutic option for the therapy of osteoarthritis, with significant data supporting the effectiveness and safety of topical formulation. Topical gel formulations may offer an alternative to oral formulations to relieve osteoarthritis (OA) pain while decreasing systemic exposure. Topical capsaicin transemulgel may represent an effective and safe alternative. The transemulgel was prepared from aqueous gel and Carbopol 934 with capsaicin in clove oil emulsion. The optimized transemulgel of capsaicin showed a pH of 6.1 ± 0.1 and viscosity of 15263-998 cps. Data from in vitro diffusion demonstrated improved permeability properties. The formulation caused no skin irritation when applied topically. The optimal transemulgel spreadability was found to be 20.23 g·cm/s. In vitro and ex vivo studies of the optimized formulation were performed. The skin irritant test was performed on rat skin with an optimized and marketed formulation. Both showed no irritation on the skin. The transemulgel of the capsaicin with gel was proven to be effective for osteoarthritis therapy.

BACKGROUND We sought to further our understanding of the biological characteristics underlying severe COVID-19. MATERIAL AND METHODS RNA sequencing (RNA-Seq) analysis was used to evaluate peripheral blood mononuclear cells from 4 patients with severe COVID-19 and 4 healthy controls. We performed gene expression analyses to detect differentially expressed genes (DEGs). Enrichment analyses were performed to identify their molecular processes and signaling pathways, and the protein-protein interaction network was constructed to extract the core gene cluster. The investigation of protein-chemical interactions and regulatory signatures for specific regulatory checkpoints and powerful chemical agents was then conducted for these essential genes. Finally, we used single-cell RNA-Seq analysis from an online platform to show how these genes were expressed differently, depending on the kind of cell. RESULTS A total of 268 DEGs were found. The biological process of protein ubiquitination was later discovered to be highly influenced by the core gene cluster (ITCH, TRIM21, RNF130, FBXO11, UBE2J1, and ASB16) at the transcriptome level. Six transcription factors, FNIC, FOXA1, YY1, GATA2, MET2A, and FOXC1, as well as miRNAs hsa-miR-1-3p and hsa-miR-27a-3p were identified. We found a potent chemical agent, copper sulfate, may regulate protein ubiquitination genes cooperatively, and the genes regulating protein ubiquitination could be expressed highly on the macrophages. CONCLUSIONS Taken together, we suggest that protein ubiquitination is a crucial functional process in patients with severe COVID-19. This study will give a deeper insight into biological characteristics and progression of COVID-19 and facilitate development of novel therapeutics, leading to significant advancements in the COVID-19 pandemic.

Allogeneic hematopoietic stem cell transplant (HSCT) is the only established cure for sickle cell disease (SCD), a hemolytic disorder that arises due to a point mutation in the hemoglobin A gene. The result is an abnormal sickle hemoglobin (HbS) replacing hemoglobin A. Of the spectrum of sickle hemoglobinoapthies, homozygous (HbSS) and HbSβ thalassemia manifest severe forms of disease characterized by chronic endothelial injury/vasculopathy, ischemic pain, and vital organ damage that commence in childhood and escalate with age resulting in impaired quality of life, increased healthcare burden, and early mortality. HSCT has demonstrated durable disease control and regression of symptoms. Human leukocyte antigen (HLA) matched sibling donor (MSD) transplantation can achieve disease-free survival of > 90%. However, < 18% of SCD patients in the United States have a MSD. Familial mismatched and unrelated donors from registries provide alternate stem cell sources. Umbilical cord blood (UCB) from family or cord blood banks expand donor sources and are attractive due to donor-independent ease of use and availability. These naïve cells tolerate greater degrees of HLA-mismatch. The primary challenge with UCB is optimizing cell dose toward successful engraftment and timely immune reconstitution while minimizing graft-versus-host disease (GVHD). This review summarizes evidence that UCB remains a promising stem cell source where modern methods of graft expansion, conditioning, GVHD prophylaxis, and infection control can overcome these challenges and retain the value of this intervention.

This report seeks to highlight a pitfall that may be encountered in the management of patients with trigeminal neuralgia with imaging showing both neurovascular conflict as well as tumors.

To report the audiometric and surgical outcomes of a series of patients having undergone implantation of a novel transcutaneous bone conduction implant (t-BCI).

The main objective was to describe the nystagmus observed during benign paroxysmal vertigo (BPV) of childhood, which is one of the criteria included in the three versions of the International Classification of Headache Disorders that has never been specified. The secondary objectives were to emphasize the usefulness of a mobile phone to record nystagmus and discuss the physiopathology of this nystagmus.

Enhanced or accelerating recovery programs have significantly reduced hospital length stay after elective colorectal interventions. Our work aims at reporting an initial experience with ambulatory laparoscopic colectomy (ALC) to assess the criteria of discharge and outcomes. Between 2006 and 2016, data regarding patients having benefited from elective laparoscopic colorectal resections in two main centres in the United Kingdom have been analysed. Both benign and malignant pathologies were included. A standardised enhanced recovery program was performed for each patient, except epidural analgesia was replaced with single shot spinal infiltration. Patients were followed up through a telephone call system by a nurse. Short-term clinical outcomes were analysed. A total of 833 patients were included and 51 (6.1%) were discharged within 24 h following surgery. Of these, 4 out of 51 (7.8%) patients came back hospital within 30 days of discharge; 2 (3.9%) required reoperation (Small bowel obstruction and wound abscess drainage). This study highlights that a 24-h discharge following elective laparoscopic colorectal interventions seems safe and feasible in selected patients. Although challenging to achieve, a standardised approach to laparoscopic surgery in combination with strict adherence to an enhanced recovery protocol are the fundamental elements of this path.

Time-restricted eating (TRE) entails consuming energy intake within a 4- to 10-h window, with the remaining time spent fasting. Although studies have reported health benefits from TRE, little is known about the impact of TRE on common chronic diseases such as type 2 diabetes, cancer and cardiovascular disease. This review summarizes and critically evaluates the most recent TRE research findings relevant to managing and treating these chronic diseases.