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Cureus May 2024This case report introduces a rare occurrence of transverse colon volvulus associated with persistent descending mesocolon (PDM), a congenital anomaly characterized by...
This case report introduces a rare occurrence of transverse colon volvulus associated with persistent descending mesocolon (PDM), a congenital anomaly characterized by the medial positioning of the descending colon due to a failed fusion with the dorsal abdominal wall. We detail the case of an 18-year-old female, with a medical history of surgically corrected coarctation of the aorta and anal atresia, who presented with recurrent transverse colon volvulus despite having undergone a laparoscopic colopexy three years earlier. Physical examination revealed abdominal distension and metallic colic sounds while imaging studies confirmed the recurrence of the volvulus. Laparoscopic partial resection of the transverse colon was performed, which revealed a medially positioned descending colon due to PDM. Postoperative complications included anastomotic failure, necessitating a second operation. The patient was successfully discharged without further complications after seven days. This case underscores the clinical significance of recognizing PDM, highlighting its potential role in causing transverse colon volvulus and increasing the risk of anastomotic failure. It emphasizes the need for surgeons to remain vigilant regarding this congenital anomaly to mitigate unexpected outcomes such as recurrent volvulus and postoperative complications.
PubMed: 38947618
DOI: 10.7759/cureus.61272 -
IScience Jun 2024Mechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for brain development. Hyperactive mTORC1...
Mechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for brain development. Hyperactive mTORC1 is found in autism spectrum disorder (ASD) characterized by atypical reactivity to sensory stimuli, among other symptoms. In Tuberous sclerosis complex (TSC) inactivating mutations in the or genes result in hyperactivation of the mTORC1 pathway and ASD. Here, we show that lack of light preference of the TSC zebrafish model, is caused by aberrant processing of light stimuli in the left dorsal habenula and fish have impaired function of the left dorsal habenula, in which neurons exhibited higher activity and lacked habituation to the light stimuli. These characteristics were rescued by rapamycin. We thus discovered that hyperactive mTorC1 caused aberrant habenula function resulting in lack of light preference. Our results suggest that mTORC1 hyperactivity contributes to atypical reactivity to sensory stimuli in ASD.
PubMed: 38947496
DOI: 10.1016/j.isci.2024.110149 -
World Journal of Orthopedics Jun 2024Cheilectomy of the 1 metatarsophalangeal joint (MTPJ) is one of the most common procedures for the management of hallux rigidus. However, there is no consensus regarding...
BACKGROUND
Cheilectomy of the 1 metatarsophalangeal joint (MTPJ) is one of the most common procedures for the management of hallux rigidus. However, there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy (MIDC) for the management of hallux rigidus.
AIM
To evaluate outcomes following MIDC for the management of hallux rigidus.
METHODS
During November 2023, the PubMed, EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux rigidus.
RESULTS
Six studies were included. In total, 348 patients (370 feet) underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9 ± 16.5 months. The distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows: I (58 patients, 27.1%), II (112 patients, 52.3%), III (44 patients, 20.6%). Three studies performed an additional 1 MTPJ arthroscopy and debridement following MIDC. Retained intra-articular bone debris was observed in 100% of patients in 1 study. The weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9 ± 3.2 to a postoperative score of 87.1. The complication rate was 8.4%, the most common of which was persistent joint pain and stiffness. Thirty-two failures (8.7%) were observed. Thirty-three secondary procedures (8.9%) were performed at a weighted mean time of 8.6 ± 3.2 months following the index procedure.
CONCLUSION
This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up. A moderate re-operation rate at short-term follow-up was recorded. The marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.
PubMed: 38947256
DOI: 10.5312/wjo.v15.i6.585 -
The Korean Journal of Pain Jul 2024Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine...
BACKGROUND
Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats.
METHODS
This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG.
RESULTS
After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance ( < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS ( < 0.001), while simultaneously causing a decrease in TAS levels ( < 0.001).
CONCLUSIONS
The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.
PubMed: 38946696
DOI: 10.3344/kjp.24042 -
Advanced Science (Weinheim,... Jul 2024Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity....
Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
PubMed: 38946582
DOI: 10.1002/advs.202402086 -
Nihon Yakurigaku Zasshi. Folia... 2024Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed...
Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed patients fail to respond to multiple antidepressant medications and are considered treatment-resistant). Conversely, ketamine, an N-methyl-D-aspartate receptor antagonist, exhibits rapid and sustained antidepressant actions in patients with treatment-resistant depression. However, clinical use of ketamine is limited due to its serious side effects. Thus, there is a significant need to develop novel ketamine-like antidepressants with fewer side effects. We previously demonstrated that intracerebroventricular infusion of resolvins (RvD1, RvD2, RvE1, RvE2, and RvE3), specialized pro-resolving lipid mediators derived from docosahexaenoic and eicosapentaenoic acids, produce antidepressant-like effects in mouse models of depression. Among resolvins, RvE1 produces the most potent antidepressant-like effects likely via ChemR23 in several mouse models of depression. Local infusion of RvE1 into the medial prefrontal cortex (mPFC) or dorsal hippocampal dentate gyrus (DG) also produces antidepressant-like effects, suggesting that these brain regions are sites of action of RvE1. Additionally, intranasal (i.n.) administration of RvE1 produces antidepressant-like effects through mechanisms similar to ketamine: activity-dependent release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and subsequent mechanistic target of rapamycin complex 1 (mTORC1) activation in the mPFC play a crucial role in the rapid and sustained antidepressant-like actions of i.n. RvE1. Moreover, the antidepressant-like effects of i.n. RvE1 require BDNF and VEGF release, but not mTORC1 activation, in the dorsal DG. These findings suggest that RvE1 can be a promising lead for a novel rapid-acting antidepressant.
Topics: Animals; Humans; Mice; Antidepressive Agents; Depression; Eicosapentaenoic Acid
PubMed: 38945902
DOI: 10.1254/fpj.23008 -
The Journal of Investigative Dermatology Jun 2024Pruritus is the leading symptom of dermatophytosis. Microsporium canis is one of the predominant dermatophytes causing dermatophytosis. However, the pruritogenic agents...
Pruritus is the leading symptom of dermatophytosis. Microsporium canis is one of the predominant dermatophytes causing dermatophytosis. However, the pruritogenic agents and the related molecular mechanisms of the dermatophyte M. canis remain poorly understood. Here, the secretion of the dermatophyte M. canis was found to dose-dependently evoke itch in mice. The fungal peptide micasin secreted from M. canis was then identified to elicit mouse significant scratching and itching responses. The peptide micasin was further revealed to directly activate mouse dorsal root ganglia (DRG) neurons to mediate the non-histaminergic itch. Knockout and antagonistic experiments demonstrated that MRGPRX1/C11/A1 rather than MRGPRX2/b2 activated by micasin contributed to pruritus. The chimera and mutation of MRGPRX1 showed that three domains (ECL3, TMH3 and TMH6) and four hydrophobic residues (Y99, F237, L240 and W241) of MRGPRX1 played the key role in micasin-triggered MRGPRX1 activation. Our study sheds light on the dermatophytosis-associated pruritus and may provide potential therapeutic targets and strategies against pruritus caused by dermatophytes.
PubMed: 38945438
DOI: 10.1016/j.jid.2024.05.031 -
World Neurosurgery Jun 2024This systematic review aims to determine the effectiveness of Dorsal Root Ganglion Stimulation (DRGS) in chronic pain management. (Review)
Review
OBJECTIVE
This systematic review aims to determine the effectiveness of Dorsal Root Ganglion Stimulation (DRGS) in chronic pain management.
MATERIALS AND METHODS
In 2023, a comprehensive systematic review was undertaken utilizing various electronic databases, employing MeSH terms and free search terms tailored to the study's aims. This review included primary research such as cohorts, case-control studies, and clinical trials, all focusing on the efficacy of DRGS in treating various chronic pain conditions. Non-human or animal studies were omitted from the selection process. A review of study quality was conducted, followed by meticulous analysis of the findings to synthesize the evidence. This review represents the most current research, with updates extending to 2024. A total of 400 articles were reviewed. 29 articles were included in our review after meticulous screening.
RESULTS
Twenty-nine articles published in the last five years meeting selection criteria were identified, encompassing patients with various diagnoses warranting the use of DRGS beyond CRPS. Additionally, the analysis includes different outcome measurement tools, emphasizing improvements in pain management, functionality, and quality of life. Finally, common complications such as surgical site infection and issues with electrodes are highlighted.
CONCLUSIONS
This systematic review affirms the effectiveness of DRGS therapy in managing diverse chronic pain conditions, highlighting improvements in quality of life, functionality, and mood states, making it a viable alternative for patients unresponsive to traditional treatments.
PubMed: 38945208
DOI: 10.1016/j.wneu.2024.06.138 -
Journal of the Mechanical Behavior of... Jun 2024Micro finite-element (μFE) simulations serve as a crucial research tool to assist laboratory experiments in the biomechanical assessment of screw anchorage in bone....
Micro finite-element (μFE) simulations serve as a crucial research tool to assist laboratory experiments in the biomechanical assessment of screw anchorage in bone. However, accurately modelling the interface between bone and screw threads at the microscale poses a significant challenge. Currently, the gold-standard approach involves employing computationally intensive physical contact models to simulate this interface. This study compared nonlinear μFE predictions of deformations, whole-construct stiffness, maximum force and damage patterns of three different computationally efficient simplified interface approaches to the general contact interface in Abaqus Explicit, which was defined as gold-standard and reference model. The μCT images (resolution: 32.8 μm) of two human radii with varying bone volume fractions were utilized and a screw was virtually inserted up to 50% and 100% of the volar-dorsal cortex distance. Materially nonlinear μFE models were generated and loaded in tension, compression and shear. In a first step, the common simplification of using a fully-bonded interface was compared to the general contact interface, revealing overestimations of whole-construct stiffness (19% on average) and maximum force (26% on average), along with inaccurate damage pattern replications. To enhance predictions, two additional simplified interface models were compared: tensionally strained element deletion (TED) and a novel modification of TED (TED-M). TED deletes interface elements strained in tension based on a linear-elastic simulation before the actual simulation. TED-M extends the remaining contact interface of TED by incorporating neighboring elements to the contact area. Both TED and TED-M reduced the errors in whole-construct stiffness and maximum force and improved the replication of the damage distributions in comparison to the fully-bonded approach. TED was better in predicting whole-construct stiffness (average error of 1%), while TED-M showed lowest errors in maximum force (1% on average). In conclusion, both TED and TED-M offer computationally efficient alternatives to physical contact modelling, although the fully-bonded interface may deliver sufficiently accurate predictions for many applications.
PubMed: 38945119
DOI: 10.1016/j.jmbbm.2024.106634 -
Journal of Electromyography and... Jun 2024This study aimed to develop an insertion technique for intramuscular EMG recording of the oblique head of adductor hallucis (AddH) and first dorsal interosseous (FDI)...
This study aimed to develop an insertion technique for intramuscular EMG recording of the oblique head of adductor hallucis (AddH) and first dorsal interosseous (FDI) muscles in humans via the dorsum of the foot, and report feasibility of intramuscular EMG data acquisition during walking in shoes. In eight individuals without musculoskeletal pain or injury (5 males; 32 ± 8 years), intramuscular electrodes were inserted into AddH (oblique head) and FDI through the right foot's dorsum (between metatarsals I-II) with ultrasound guidance. The ultrasound transducer was positioned on the plantar surface. Intramuscular EMG was also recorded from abductor hallucis, tibialis posterior, flexor digitorum longus and peroneus longus. Participants performed six overground walking trials wearing modified shoes, and rated pain associated with the intramuscular electrodes during walking (numerical rating scale, 0-10). High-quality EMG recordings were obtained from intrinsic and extrinsic foot muscles. Analyses of power spectral densities indicated that movement artefacts commonly observed during gait were removed by filtering. Pain associated with AddH/FDI electrodes during walking was low (median[IQR] 1[2]; range 0-4) and similar to other sites. Findings demonstrate that intramuscular EMG recording from AddH (oblique head) and FDI using this insertion technique is feasible and associated with minimal pain when walking in shoes.
PubMed: 38945047
DOI: 10.1016/j.jelekin.2024.102914