The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies.

Our newly developed menthyl esters of valine and isoleucine exhibit anti-inflammatory properties beyond those of the well-known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold-sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS-stimulated tumour necrosis factor-alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non-competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti-inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3-L1 adipocytes at the mitotic clonal expansion stage in an LXR-independent manner as well as in mice subjected to diet-induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications.

Peripheral nerve regeneration by bioabsorbable nerve conduits filled with platelet-rich fibrin.

PURPOSE: To repair peripheral nerve defects and seek alternatives for autografts, nerve conduits with various growth factors and cells have been invented. Few pieces of literature report the effect of nerve conduits plus platelet-rich fibrin (PRF). This study aimed to investigate the effectiveness of nerve conduits filled with PRF. METHODS: The model of a 10 mm sciatic nerve gap in a rat was used to evaluate peripheral nerve regeneration. The thirty rats were randomly divided into one of the following three groups (n = 10 per group). Autogenous nerve grafts (autograft group), conduits filled with phosphate-buffered saline (PBS) (PBS group), or conduits filled with PRF group (PRF group). We assessed motor and sensory functions for the three groups at 4, 8, and 12 weeks postoperatively. In addition, axon numbers were measured 12 weeks after repair of the peripheral nerve gaps. RESULTS: Significant differences in motor function were observed between the autograft group and the other two groups at 12 weeks postoperatively. In the test to evaluate the recovery of sensory function, there were significant differences between the PBS group and the other two groups at all time points. The most axon number was found in the autograft group. The axon number of the PRF group was significantly more extensive than that of the PBS group. CONCLUSIONS: The nerve conduit filled with PRF promoted the axon regeneration of the sciatic nerve and improved sensory function.

Nerve Grafting for Isolated Injury to the Intrinsic Motor Branch of the Ulnar Nerve due to a Stab Injury: A Case Report.

Isolated injury to the deep motor branch of the ulnar nerve caused by stabbing is sporadic, with only one reported case in the English-language literature. We report one such case treated successfully using nerve grafting. A 33-year-old patient had sustained a stab wound to the right hypothenar eminence and showed a claw hand deformity. Needle electromyography study revealed denervation potentials with no voluntary motor unit action potentials (MUAPs) in the first dorsal interosseous (FDI) muscles. Nerve exploration revealed a neuroma-in-continuity in the intrinsic motor branch of the ulnar nerve. Intraoperative nerve stimulation confirmed the absence of compound muscle action potentials in the FDI. The damaged scarred nerve was resected, and the 15-mm defects were reconstructed with cable autografting. Two years and 5 months after the surgery, voluntary MUAPs were observed in the FDI. The pinch strengths recovered. Laceration of the deep branch of the ulnar nerve caused by stabbing can sometimes remain hidden as the hand sensation remains intact. Pre- and intraoperative electrophysiological examination is essential to assess the severity of the injured nerve and determine an appropriate surgical option. Even nerve grafting can facilitate satisfactory results as target intrinsic muscles are quite close to the repair site.

Green leaf volatile sensory calcium transduction in Arabidopsis.

Plants perceive volatile organic compounds (VOCs) released by mechanically- or herbivore-damaged neighboring plants and induce various defense responses. Such interplant communication protects plants from environmental threats. However, the spatiotemporal dynamics of VOC sensory transduction in plants remain largely unknown. Using a wide-field real-time imaging method, we visualize an increase in cytosolic Ca2+ concentration ([Ca2+]cyt) in Arabidopsis leaves following exposure to VOCs emitted by injured plants. We identify two green leaf volatiles (GLVs), (Z)-3-hexenal (Z-3-HAL) and (E)-2-hexenal (E-2-HAL), which increase [Ca2+]cyt in Arabidopsis. These volatiles trigger the expression of biotic and abiotic stress-responsive genes in a Ca2+-dependent manner. Tissue-specific high-resolution Ca2+ imaging and stomatal mutant analysis reveal that [Ca2+]cyt increases instantly in guard cells and subsequently in mesophyll cells upon Z-3-HAL exposure. These results suggest that GLVs in the atmosphere are rapidly taken up by the inner tissues via stomata, leading to [Ca2+]cyt increases and subsequent defense responses in Arabidopsis leaves.

Long-duration upper extremity surgery under brachial plexus block combined with intravenous dexmedetomidine sedation without an anesthesiologist.

BACKGROUND: Dexmedetomidine (DEX) provides a unique conscious sedation without respiratory depression. We examined the usefulness of intravenous (IV) DEX sedation combined with brachial plexus block for long-duration upper extremity surgery without an anesthesiologist. METHODS: We retrospectively reviewed 90 limbs of 86 patients and measured the actual operative time course in detail. The adverse events and the patient-reported outcomes regarding intraoperative pain and depth of sedation were evaluated. RESULTS: The mean total time of the operation, tourniquet use, and the IV DEX sedation were 150 min, 132 min, and 117 min, respectively. The mean time between discontinuation of IV DEX sedation and completion of the operation was 51 min. The intraoperative adverse events involved bradycardia (21%), hypotension (18%), and oxygen desaturation (3%). The mean visual analog scale scores of pain during brachial plexus block, surgical site pain, tourniquet pain, and depth of the sedation were 23.4 mm, 0.14 mm, 4.2 mm, and 6.6 mm, respectively. Furthermore, 96% patients expressed a preference for receiving anesthesia as brachial plexus block with IV DEX sedation. CONCLUSIONS: Long-duration upper extremity surgery, even longer than 2 h, was feasible under brachial plexus block combined with IV DEX sedation without an anesthesiologist. For patients with low blood pressure and/or low heart rate, it is recommended to adjust the continuous infusion of IV DEX to less than 0.4 µg/kg/h. To ensure that the patients are able to promptly leave the operating room fully awake, IV DEX infusion should be stopped at least 30 min before finishing the operation.

Cytoplasmic Kinase Network Mediates Defense Response to Spodoptera litura in Arabidopsis.

Plants defend against folivores by responding to folivore-derived elicitors following activation of signaling cascade networks. In Arabidopsis, HAK1, a receptor-like kinase, responds to polysaccharide elicitors (Frα) that are present in oral secretions of Spodoptera litura larvae to upregulate defense genes (e.g., PDF1.2) mediated through downstream cytoplasmic kinase PBL27. Here, we explored whether other protein kinases, including CPKs and CRKs, function with PBL27 in the intracellular signaling network for anti-herbivore responses. We showed that CRK2 and CRK3 were found to interact with PBL27, but CPKs did not. Although transcripts of PDF1.2 were upregulated in leaves of wild-type Arabidopsis plants in response to mechanical damage with Frα, this failed in CRK2- and PBL27-deficient mutant plants, indicating that the CRK2/PBL27 system is predominantly responsible for the Frα-responsive transcription of PDF1.2 in S. litura-damaged plants. In addition to CRK2-phosphorylated ERF13, as shown previously, ethylene signaling in connection to CRK2-phosphorylated PBL27 was predicted to be responsible for transcriptional regulation of a gene for ethylene response factor 13 (ERF13). Taken together, these findings show that CRK2 regulates not only ERF13 phosphorylation but also PBL27-dependent de novo synthesis of ERF13, thus determining active defense traits against S. litura larvae via transcriptional regulation of PDF1.2.

Partial tibial nerve transfer for iatrogenic peroneal nerve palsy after endovenous laser ablation for varicose veins of the lower extremity: A case report.

Postprocedural peroneal nerve palsy after endovenous laser ablation (EVLA) for varicose veins is rare and is associated with poor functional recovery. There have been no reports using tibial nerve transfer for iatrogenic peroneal nerve palsy after EVLA. Herein, we present a case with peroneal nerve injury after EVLA, which was successfully treated by partial tibial nerve transfer for the first time. A 75-year-old female presented with a right foot drop immediately after EVLA of the lesser saphenous vein. The ankle and toe dorsiflexion had a muscle grade of M0 on the British Medical Research Council muscle scale, without voluntary motor unit action potentials (MUAP) in the tibialis anterior (TA) muscle on the needle electromyography. Three months after the injury, surgical nerve exploration revealed a damaged common peroneal nerve with discoloration and scarring at the fibular head. Intraoperative deep peroneal nerve stimulation confirmed the absence of compound muscle action potentials in the TA. The best functioning motor fascicles of the tibial nerve were transferred to the deep peroneal main trunk involving motor branches of the TA, extensor digitorum longus, and extensor hallucis longus (EHL) through the interosseous membrane. The postoperative course was uneventful, with no complications. After 3 months of surgery, nascent MUAP appeared in the TA. After 24 months, the patient regained the TA and EHL muscle function and ambulation without an ankle-foot orthosis and tibial nerve deficits. Thus, our procedure may serve as an alternative to nerve grafting, tendon transfer, and orthoses for better management of the major neural complications associated with EVLA.

Clinical Results of Surgical Treatment for Comminuted Radial Head and Neck Fracture: Headless Compression Screws Versus Plate Fixation.

Background: We surgically treated comminuted radial head and neck fractures using headless compression screws, including multiple screws for the radial head and a single oblique screw for the radial neck. This study aimed to compare the clinical and radiological results for comminuted radial head and neck fractures between surgery using headless compression screws with a single oblique screw for the radial neck, our new procedure, and a plate system precontoured to the proximal radius. Methods: This retrospective study included 23 patients (11 and 12 in the screw and plate groups, respectively). The fractures were type 3 according to the Mason-Johnston classification modified by Broberg and Morrey. Clinical outcomes analyzed included the motion range of the elbow and forearm, Mayo Elbow Performance Score, and radiological assessments. In addition, postoperative complications were also investigated. The average follow-up was 18 months. Results: The bone union was achieved in all the patients, and there were no significant differences in clinical outcomes and radiological assessments except forearm supination (p = 0.02). Furthermore, additional surgical procedures were performed in one and five patients in the screw and plate groups, respectively (p = 0.16). Posterior nerve palsy was observed in two patients in the plate group. Complications were observed in one and six patients in the screw and plate groups, respectively (p = 0.07). Conclusion: Both surgical procedures achieved good clinical and radiological outcomes with bone and ligament injury repair. The screw group had a greater range of forearm supination than the plate group.

Nerve-End Capping Treatment with a Polyglycolic Acid Conduit for Rat Sciatic Neuroma: A Preliminary Report.

BACKGROUND: The treatment of painful neuroma remains challenging. Recently, a nerve-end capping technique using a bioabsorbable nerve conduit was newly introduced to treat amputation neuroma. A collagen-coated polyglycolic acid (PGA) conduit has been commercially available for the reconstruction of peripheral nerve defects, yielding successful clinical outcomes. However, no experimental research has been conducted using this PGA nerve conduit as capping device for treating amputation neuroma. The purpose of this study was to investigate nerve-end capping treatment with the PGA conduit in the rat sciatic nerve amputation model, focusing on histological scar formation and neuroinflammation. METHODS: Forty-seven rats were divided into two groups: no capping (transected nerve stump without capping; n = 25) and capping (nerve-end capping with collagen-coated PGA nerve conduit; n = 22). Twelve weeks after sciatic neurectomy, neuropathic pain was evaluated using the autotomy score. Stump neuromas were histologically evaluated or perineural scar and neuroinflammation. RESULTS: While autotomy scores gradually exacerbated in both groups, they were consistently lower in the capping group at 4, 8, and 12 weeks postprocedure. Twelve weeks after surgery, the transected nerve stumps in the no-capping group had formed macroscopic bulbous neuromas strongly adhering to surrounding tissues, whereas they remained wrapped with the PGA nerve conduits loosely adhering to surrounding tissues in the capping group. Histologically, distal axonal fibers were expanded radially and formed neuromas in the no-capping group, while they were terminated within the PGA conduit in the capping group. Perineural scars and neuroinflammation were widely found surrounding the randomly sprouting nerve end in the no-capping group. In capped counterparts, scars and inflammation were limited to closely around the terminated nerve end. CONCLUSION: Nerve-end capping with a collagen-coated PGA conduit after rat sciatic neurectomy might prevent neuroma formation by suppressing perineural scar formation and neuroinflammation around the nerve stump, potentially relieving neuropathic pain.

Microvascular neural blood flow assessment for a chronic nerve compression neuropathy mouse model by fluorescein angiography.

BACKGROUND AND AIMS: Intraoperative fluorescence angiography with indocyanine green or fluorescein is used in ophthalmology and neurosurgery. However, there are few reports on the use of fluorescence angiography for peripheral neuropathy. This study aimed to assess the validity of fluorescein angiography (FAG) for peripheral nerve entrapment neuropathy. METHODS: We used an established model of chronic nerve compression (CNC) neuropathy in C57BL/6 mice by entrapping their left sciatic nerve with a silastic tube. Mice were assigned to the uninjured group (control), two-week CNC neuropathy group, four-week CNC neuropathy group, or six-week CNC neuropathy group. We then performed FAG to assess neural blood flow and quantified the peak of the luminance at the compression site with luminance analysis software. Following FAG, histological examinations using an anti-fluorescein antibody and Masson's trichrome staining were performed to evaluate the area of fluorescein distribution and epineural fibrosis. RESULTS: The luminance in the CNC neuropathy groups was significantly lower than that in the control group. Histological analysis revealed the fluorescein positive areas in the CNC neuropathy groups were significantly smaller than that in the control group, and the epineural fibrosis areas in the CNC neuropathy groups were significantly larger than that in the control group. CONCLUSION: We observed a significant decline of luminance in the CNC neuropathy groups, and the histological assessment was consistent with this result. FAG was found to be a valid method for assessing CNC neuropathy in mice.

Immune gene activation by NPR and TGA transcriptional regulators in the model monocot Brachypodium distachyon.

The nonexpressor of pathogenesis-related (NPR) gene family is well known to play a crucial role in transactivation of TGA transcription factors for salicylic acid (SA)-responsive genes, including pathogenesis-related protein 1 (PR1), during plants' immune response after pathogen attack in the model dicot Arabidopsis thaliana. However, little is known about NPR gene functions in monocots. We therefore explored the functions of NPRs in SA signaling in the model monocot Brachypodium distachyon. BdNPR1 and BdNPR2/3 share structural similarities with A. thaliana AtNPR1/2 and AtNPR3/4 subfamilies, respectively. The transcript level of BdNPR2 but not BdNPR1/3 appeared to be positively regulated in leaves in response to methyl salicylate. Reporter assays in protoplasts showed that BdNPR2 positively regulated BdTGA1-mediated activation of PR1. This transactivation occurred in an SA-dependent manner through SA binding at Arg468 of BdNPR2. In contrast, BdNPR1 functioned as a suppressor of BdNPR2/BdTGA1-mediated transcription of PR1. Collectively, our findings reveal that the TGA-promoted transcription of SA-inducible PR1 is orchestrated by the activator BdNPR2 and the repressor BdNPR1, which function competitively in B. distachyon.

Silicone Implant Arthroplasty for Severe Bony Ankylosis of the Proximal Interphalangeal Joints in Rheumatoid Arthritis.

Arthrodesis and prosthetic arthroplasty have been used to treat severe proximal interphalangeal (PIP) joint arthritis. Silicone implant arthroplasty is an established treatment for rheumatoid arthritis (RA) of the fingers. However, few studies have reported the application of silicone implant arthroplasty for the treatment of severe ankylosis of the PIP joint in RA patients. The authors report, for the first time, the case of a 46-year-old woman who presented with severe bony ankylosis of the right fourth and fifth PIP joints at greater than 90° of flexion. Proximal interphalangeal silicone arthroplasty in combination with reconstruction of the extensor mechanism was successfully performed in the affected joints. Four years after surgery, active flexion of the fourth and fifth PIP joints was 55° and 75°, respectively, with an extensor lag of only 5° without pain and joint instability. Proper repair of the extensor mechanism with shortening of the central slips and mobilization of the lateral bands dorsally was most important in maintaining the extended position of the PIP joints. Proximal interphalangeal silicone arthroplasty with intensive reconstruction of the extensor mechanism could become a potential treatment option to maintain joint mobility even in severe ankylosis of the PIP joints in RA patients. [Orthopedics. 2022;45(1):e53-e56.].

Pain and numbness one month after carpal tunnel release predict patient-reported outcome measures at sixth months.

A number of outcome predictors for carpal tunnel release (CTR) for carpal tunnel syndrome (CTS) have been reported. However, some predictors are controversial, and few studies have referred to the early postoperative outcome prognostic factors after CTR. The aim of this study was to investigate whether pain and numbness at 1 month post-CTR were early postoperative predictors of clinical outcomes 6 months after surgery. Pain and numbness were evaluated using the visual analog scale (VAS) preoperatively and at 1 month post-surgery. Patient-reported outcome measures (PROMs), including the Quick Disabilities of the Arm, Shoulder and Hand (QDASH) measure, the Hand20 questionnaire and the Boston Carpal Tunnel Questionnaire (BCTQ), were recorded for each patient 6 months after surgery. The BCTQ consisted of the Symptom Severity Scale (SSS) and Functional Status Scale (FSS). Multivariable linear regression analysis was performed to investigate the association between the VAS scores and PROMs. We retrospectively identified 93 patients who underwent open carpal tunnel release (OCTR) or endoscopic carpal tunnel release. The mean age of the patients was 67.5 years, and 67 patients (72.0%) were female. Sixty patients were treated by OCTR (65.0%). With multivariable linear regression analysis, we found that pain and numbness, evaluated with VAS 1 month post-surgery had significant correlations with QDASH, Hand20, SSS and FSS 6 months after surgery. In conclusion, pain and numbness 1 month after CTR predict PROMs at 6 months.

Nerve capping treatment using a bioabsorbable nerve conduit with open or closed end for rat sciatic neuroma.

BACKGROUND AND AIMS: Nerve capping treatment using bioabsorbable nerve conduits has recently been introduced for painful amputation neuroma. However, no clinical or experimental data are available for comparing nerve conduits with open distal ends and closed distal ends. Here, we investigated the nerve conduit with open or closed distal ends as the superior capping device, using a commercially available polyglycolic acid (PGA) nerve conduit in a rat sciatic nerve amputation model. METHODS: Ninety-one rats were assigned to three groups: no-capping (n = 30), capping the resected nerve stump with open ends (n = 31), and closed-end nerve conduits (n = 30). Twelve weeks after sciatic neurectomy, with or without capping, the evaluation of neuropathic pain using the autotomy score was performed. Stump neuromas with perineural scars and neuroinflammation were evaluated histologically. RESULTS: The mean autotomy scores in the closed-end nerve conduit group were significantly lower than those in the no-capping group. However, the difference between the open-end nerve conduit and the closed-end nerve conduit groups was insignificant. Histologically, distal axonal fibers expanded radially and formed neuromas in the no-capping group while they were terminated within the PGA conduit in both capping groups. In particular, the closed-end version of the PGA nerve conduit blocked scarring from intruding through the open end and protected the nerve stump with less neuroinflammation. Nerve capping with the closed-end version of the PGA nerve conduit most effectively suppressed perineural neuroinflammation and scar formation around the resected nerve stump. INTERPRETATION: Nerve capping with the PGA nerve conduit, particularly those with closed ends, after rat sciatic neurectomy prevented amputation neuroma and relieved neuropathic pain.

Wide-Field, Real-Time Imaging of Local and Systemic Wound Signals in Arabidopsis.

Plants respond to mechanical stresses such as wounding and herbivory by inducing defense responses both in the damaged and in the distal undamaged parts. Upon wounding of a leaf, an increase in cytosolic calcium ion concentration (Ca2+ signal) occurs at the wound site. This signal is rapidly transmitted to undamaged leaves, where defense responses are activated. Our recent research revealed that glutamate leaking from the wounded cells of the leaf into the apoplast around them serves as a wound signal. This glutamate activates glutamate receptor-like Ca2+ permeable channels, which then leads to long-distance Ca2+ signal propagation throughout the plant. The spatial and temporal characteristics of these events can be captured with real-time imaging of living plants expressing genetically encoded fluorescent biosensors. Here we introduce a plant-wide, real-time imaging method to monitor the dynamics of both the Ca2+ signals and changes in apoplastic glutamate that occur in response to wounding. This approach uses a wide-field fluorescence microscope and transgenic Arabidopsis plants expressing Green Fluorescent Protein (GFP)-based Ca2+ and glutamate biosensors. In addition, we present methodology to easily elicit wound-induced, glutamate-triggered rapid and long-distance Ca2+ signal propagation. This protocol can also be applied to studies on other plant stresses to help investigate how plant systemic signaling might be involved in their signaling and response networks.

Bone healing of distal radius nonunion treated with bridge plating with bone graft substitutes in combination with systemic romosozumab administration: A case report.

Romosozumab is a humanized, anti-sclerostin monoclonal antibody used to treat osteoporosis, which increases bone formation and decreases bone resorption. It enhances fracture healing and systemic romosozumab administration may have therapeutic potentials for accelerating bone healing of even nonunion. Herein, a 61-year-old heavy smoker male with distal radius nonunion who achieved successful bone union by combination therapy of romosozumab and spanning distraction plate fixation with bone graft substitutes was presented. Through the dorsal approach, atrophic comminuted nonunion of the distal radius was sufficiently debrided. Reduction of the distal radius was performed using indirect ligamentotaxis, and a 14-hole locking plate was fixed from the third metacarpal to the radial shaft. A beta (ß) tricalcium phosphate block was mainly packed into the substantial metaphyseal bone defect with additional bone graft from the resected ulnar head. Postoperatively, systemic administration of monthly romosozumab was continued for six months. Complete bone union was achieved 20 weeks postoperatively and the plate was, then, removed. Wrist extension and flexion improved to 75o and 55o, respectively, without pain, and grip strength increased 52 weeks postoperatively from 5.5 kg to 22.4 kg. During romosozumab treatment, bone formation marker levels increased rapidly and finally returned to baseline, and bone resorption marker levels remained low. In conclusion, combination of systemic romosozumab administration and grafting ß-tricalcium phosphate with bridge plating provides an effective treatment option for difficult cases of comminuted distal radius nonunion with risk factors such as smoking, diabetes, and fragility.

Phytohormone-dependent plant defense signaling orchestrated by oral bacteria of the herbivore Spodoptera litura.

A vast array of herbivorous arthropods live with symbiotic microorganisms. However, little is known about the nature and functional mechanism of bacterial effects on plant defense responses towards herbivores. We explored the role of microbes present in extracts of oral secretion (OS) isolated from larvae of Spodoptera litura, a generalist herbivore, in phytohormone signaling-dependent defense responses in Arabidopsis thaliana (Arabidopsis). In response to mechanical damage (MD) with application of bacteria-free OS (OS- ) prepared by sterilization or filtration of OS, Arabidopsis leaves exhibited enhanced de novo synthesis of oxylipins, and induction of transcript abundance of the responsible genes, in comparison to those in leaves with MD + nonsterilized OS (OS+ ), indicating that OS bacteria serve as suppressors of these genes. By contrast, de novo synthesis/signaling of salicylic acid and signaling of abscisic acid were enhanced by OS bacteria. These signaling networks were cross-regulated by each other. Meta-analysis of OS bacteria identified 70 bacterial strains. Among them was Staphylococcus epidermidis, an anaerobic staphylococcus that was shown to contribute to the suppression/manipulation of phytohormone-dependent plant defense signaling. The presence of OS bacteria was consequently beneficial for S. litura larvae hosted by Brassicaceae.