Rejected

Several types of sensory perception have circadian rhythms. The spinal cord can be considered a center for controlling circadian rhythms by changing clock gene expression. However, to date, it is not known if mechanonociception itself has a circadian rhythm. The hypothalamic A11 area represents the primary source of dopamine (DA) in the spinal cord and has been found to be involved in clock gene expression and circadian rhythmicity. Here, we investigate if the paw withdrawal threshold (PWT) has a circadian rhythm, as well as the role of the dopaminergic A11 nucleus, DA, and DA receptors (DR) in the PWT circadian rhythm and if they modify clock gene expression in the lumbar spinal cord. Naïve rats showed a circadian rhythm of the PWT of almost 24 h, beginning during the night-day interphase and peaking at 14.63 h. Similarly, DA and DOPAC's spinal contents increased at dusk and reached their maximum contents at noon. The injection of 6-hydroxydopamine (6-OHDA) into the A11 nucleus completely abolished the circadian rhythm of the PWT, reduced DA tissue content in the lumbar spinal cord, and induced tactile allodynia. Likewise, the repeated intrathecal administration of D1-like and D2-like DA receptor antagonists blunted the circadian rhythm of PWT. 6-OHDA reduced the expression of and and increased gene expression during the day. In contrast, 6-OHDA diminished , , , , , , and at night. The repeated intrathecal administration of the D1-like antagonist (SCH-23390) reduced clock genes throughout the day ( and ) and throughout the night (, and ) whereas it increased and throughout the day. In contrast, the intrathecal injection of the D2 receptor antagonists (L-741,626) increased the clock genes , , and and decreased throughout the day. This study provides evidence that the circadian rhythm of the PWT results from the descending dopaminergic modulation of spinal clock genes induced by the differential activation of spinal DR.

Nephron-sparing surgery is a well-established treatment in patients with T1a renal cell carcinoma; however, the complex suturing process prolongs warm ischaemia time, affects the preservation of normal renal parenchymal function, and causes avoidable postoperative tissue adhesion complications, including chronic abdominal pain, intestinal obstruction, and female infertility. Hence, the design of multifunctional biomaterials with haemostasis, postoperative wound management, and postoperative tissue adhesion prevention properties for nephron-sparing surgeries is urgently needed. In this study, a series of injectable adhesive multifunctional biocompatible hydrogels were designed based on the free-radical polymerisation of monomers acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG), and the ionic coordination between Ca and the abundant carboxyl groups in AA and NAG. AA/NAG/Ca (AA, NAG, and Ca refer to acryloyl-6-aminocaproic acid, N-acryloyl 2-glycine and calcium chloride, respectively) hydrogel exhibited good mechanical properties, swelling and adhesion properties, flexibility, in vitro blood-clotting ability, and cytocompatibility. In vivo experiments on liver injury models and rat/rabbit nephron-sparing surgery models elucidated that the AA/NAG/Ca hydrogel had haemostasis performance and wound healing properties that led to short bleeding time, reduced bleeding volume, and well-organised nephron structures. An abdomen-caecum adhesion model indicated that the AA/NAG/Ca hydrogel showed excellent anti-adhesion properties. In summary, this multifunctional hydrogel exhibited potential for improving haemostasis and wound management in nephron-sparing surgeries, showing potential for clinical application. STATEMENT OF SIGNIFICANCE: Extended warm ischemia time during nephron sparing surgery negatively affected postoperative renal function due to the need for hemostasis at the wound with abundant blood supply, and postoperative wound healing and additional adhesions caused by the surgical procedure deserve attention. Based on the efficient and stable adhesion properties of hydrogels and the ability to promote wound healing. Herein, a series of adhesive self-healing biocompatible hydrogels were prepared based on free-radical polymerization of acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG) and the ionic coordination between Ca with the abundant carboxyl groups in AA and NAG. AA/NAG/Ca hydrogel showed hemostasis property in nephron sparing surgery model, promote kidney wound healing, and could perform anti-postoperative adhesion efficacy in an abdomen-caecum adhesion model.

Regenerative medicine through interventional pain procedures is evolving with data demonstrating efficacy for a number of pain states in recent years. Platelet-rich plasma (PRP), defined as a sample of plasma with a platelet concentration 3 to 5 times greater than the physiologic platelet concentration found in healthy whole blood, releases bioactive proteins which can restore anatomical function in degenerative states. PRP is dense in growth factors, such as platelet-derived growth factor, transforming growth factor-beta1, basic fibroblastic growth factor, vascular endothelial growth factor, and epidermal growth factors.

Molnupiravir is an oral antiviral drug that received Emergency Use Authorization in three countries for the treatment of mild COVID-19. The aim of this systematic review was to find out the safety and efficacy of Molnupiravir in SARS-COV-2 infections.

People with kidney failure treated with dialysis are at increased risk of SARS-CoV-2 infection, and severe COVID-19 outcomes such as hospitalization and death. Though there are well-defined sex differences in outcomes for the general population with COVID-19, we do not know whether this translates into kidney failure populations. We aimed to estimate the differences in COVID-19 symptoms and clinical outcomes between males and females treated with maintenance dialysis.

This study aims to assess the effectiveness of Microfragmented Autologous Fat Tissue (MFAT) treatment for knee osteoarthritis and to investigate whether patients' pre-treatment clinical condition, such as synovitis, correlates with clinical outcomes, to identify potential predicting factors for the success or failure of the treatment.

Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019 and October 1, 2021 at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (IQR 2-8 months.) At the end of the study period, 9 of 17 patients (52.9%) were still on letermovir and 4 of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy. This article is protected by copyright. All rights reserved.

To explore the pathological characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A) with cutaneous lichen amyloidosis (CLA).

Pediatric umbilical hernia repair could cause considerable postoperative discomfort. This study aimed to compare the analgesia between rectus sheath block and local anesthetic infiltration in child pediatric umbilical hernia repair.