Role of noradrenergic and dopaminergic systems in the antinociceptive effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide in mice.

Pain has a negative impact on public health, reducing quality of life. Unfortunately, current treatments are not fully effective and have adverse effects. Therefore, there is a need to develop new analgesic compounds. Due to promising results regarding the antinociceptive effect of N-(3-(phenylselanyl)prop-2-in-1-yl)benzamide (SePB), this study aimed to evaluate the participation of the dopaminergic and noradrenergic systems in this effect in mice, as well as its toxicity. To this, the antagonists sulpiride (D2/D3 receptor antagonist, 5 mg/kg), SCH-23390 (D1 receptor antagonist, 0.05 mg/kg), prazosin (α1 adrenergic receptor antagonist, 0.15 mg/kg), yohimbine (α2-adrenergic receptors, 0.15 mg/kg) and propranolol (non-selective ß-adrenergic antagonist, 10 mg/kg) were administered intraperitoneally to mice 15 min before SePB (10 mg/kg, intragastrically), except for propranolol (20 min). After 26 min of SePB administration, the open field test was performed for 4 min to assess locomotor activity, followed by the tail immersion test to measure the nociceptive response. For the toxicity test, animals received a high dose of 300 mg/kg of SePB. SePB showed an increase in the latency for nociceptive response in the tail immersion test, and this effect was prevented by SCH-23390, yohimbine and propranolol, indicating the involvement of D1, α2 and ß-adrenergic receptors in the antinociceptive mechanism of the SePB effect. No changes were observed in the open field test, and the toxicity assessment suggested that SePB has low potential to induce toxicity. These findings contribute to understanding SePB's mechanism of action, with a focus on the development of new alternatives for pain treatment.

Minimally invasive hallux valgus surgery using 3D printed patient specific instrumentation.

In this technical report study, we describe technique for performing the osteotomy and screw passage in minimally invasive fourth-generation hallux valgus surgery with transverse and akin extra-articular metaphyseal osteotomy (META) using a 3D-printed patient-specific surgical instrumentation guide. In an effort to minimize the learning curve and address the variability associated with technical corrections and screw placement, we have initiated the creation of personalized patient-specific instrumentation guides using 3D printing. Our hypothesis is that this approach will enhance safety, precision, decrease surgical time, and reduce exposure to radiation. Level of Evidence: Level V, expert opinion.

Biomechanical consequences of Zadek osteotomy in insertional achilles tendinopathy: A virtual surgical simulation study.

BACKGROUND: The Zadek osteotomy modified by Taylor (ZO) is a surgical technique used to treat insertional Achilles tendinopathy (IAT) by reducing the heel's prominence and elevating the Achilles tendon insertion. This study aims to analyze the biomechanical consequences of IAT after ZO using a virtual surgical simulation with a specific software. METHODS: A retrospective analysis of 20 wtbearing computed tomography (WBCT) scans of IAT patients was conducted. Using Disior's BonelogicTM software, 3D models were created from WBCT images. Virtual ZO was performed on these models, and various biomechanical parameters were measured before and after the virtual osteotomy. RESULTS: The virtual ZO showed significant statistical differences in the average of the calcaneal length (p < 0.001), Fowler Philips angle (p < 0.001), calcaneal pitch (p < 0.001), and the sagittal talocalcaneal angle (p < 0.001). CONCLUSIONS: The virtual ZO analysis suggests that this procedure can decrease the Fowler Philips angle, shorten the calcaneus, modifying specifically the sagittal alignment. LEVEL OF EVIDENCE: IV; case series.

Minimally invasive Chevron-Akin (MICA) osteotomies without Akin fixation in hallux valgus correction: a case series with 2-year follow-up.

PURPOSE: The minimally invasive Chevron-Akin (MICA) is considered the third generation of minimally invasive hallux valgus (HV) surgery, and its original description included fixation of the Akin osteotomy with a screw. The aim of this study is to evaluate a series of patients undergoing HV correction using the MICA technique without screw fixation of the Akin osteotomy. METHODS: We retrospectively evaluated 58 consecutive patients who underwent surgical correction for HV between August 2018 and March 2020. A total of 69 feet were evaluated with a minimum follow-up of 2 years. Clinical outcomes such as pain (VAS), function (AOFAS), range of movement, criteria personal satisfaction and complications were evaluated. RESULTS: The AOFAS score (mean ± standard deviation) significantly improved from 57.0 ± 8.6 preoperatively to 93.9 ± 8.7 postoperatively (p < .001) with a minimum follow-up of 2 years. The VAS score improved from 6.0 ± 1.8 preoperatively to 0.6 ± 1.4 at 2-year follow-up (p < .001), and the hallux valgus angle reduced from 39.7 ± 6.9 to 8.9 ± 9.0 (p < .001). The majority of patients (95.6%) reported the result as excellent or good, and the most common complication was the need to remove the screw (7.2%). CONCLUSIONS: The use of MICA without Akin osteotomy fixation resulted in successful correction of hallux valgus with improvements in clinical and radiographic parameters. LEVEL OF EVIDENCE: IV, case series.

Precision and reliability study of hospital infusion pumps: a systematic review.

BACKGROUND: Infusion Pumps (IP) are medical devices that were developed in the 1960s and generate fluid flow at pressures higher than that of normal blood pressure. Various hospital sectors make use of them, and they have become indispensable in therapies requiring continuity and precision in the administration of medication and/or food. As they are classified Class III (high risk) equipment, their maintenance is crucial for proper performance of the device, as well as patient and operator safety. The principal consideration of the pump is the volume infused, and the device demands great attention to detail when being calibrated. A lack of necessary care with this equipment can lead to uncertainty in volume and precision during the administration of substances. Because of this, it is essential to evaluate its reliability, to prevent possible failures at time of execution. This control aims at the quality of the intended infusion result, becoming an indication of quality. METHODS: This systematic review summarizes studies done over the last 10 years (2011 to December 2021) that address the reliability and accuracy of hospital infusion pumps, in order to identify planning of maintenance and/or other techniques used in management of the equipment. The Prisma method was applied and the databases utilized were Embase, MEDLINE/Pubmed, Web of Science, Scopus, IEEE Xplore, and Science Direct. In addition, similar reviews were studied in Prospero and the Cochrane Library. For data analysis, softwares such as Mendeley, Excel, RStudio, and VOSviewer were used, and Robvis helped in plotting risk of bias results for studies performed with Cochrane tools. RESULTS: The six databases selected produced 824 studies. After applying eligibility criteria (inclusion and exclusion), removing duplicates, and applying filters 1 and 2, 15 studies were included in the present review. It was found that the most relevant sources came from the Institute of Electrical and Electronics Engineers (IEEE) and that the most relevant keywords revolved around the terms ("device failure", "infusion pumps", "adverse effects", "complications", etc.). These results made clear that there remains substantial room for improvement as it relates to the study of accuracy and reliability of infusion. CONCLUSIONS: We verified that the reliability and precision analysis of hospital infusion pumps need to be performed in a more detailed and consistent way. New developments, considering the model and IP specification, are intended, clearly explaining the adopted methodology.

High body mass index is not a contraindication for an arthroscopic ligament repair with biological augmentation in case of chronic ankle instability.

PURPOSE: Obesity remains frequently mentioned as a contraindication for lateral ankle ligament repair. The aim of the study was to compare the clinical results of an arthroscopic lateral ligament repair with biological augmentation between patients with a body mass index (BMI) of more than 30 and less than 30. METHODS: Sixty-nine patients with an isolated lateral ankle instability were treated with an arthroscopic anterior talofibular ligament (ATFL) repair with biological augmentation using the inferior extensor retinaculum (IER). Patients were divided into two groups according to their BMI: ≥ 30 (Group A; n = 26) and < 30 (Group B; n = 43). Patients were pre-and post-operatively evaluated, with a minimum of 2 years follow-up, and using the Karlsson Score. Characteristics of the patients, complications, ankle instability symptoms recurrence, and satisfaction score were recorded. RESULTS: In group A, the median Karlsson Score increased from 43.5 (Range 22-72) to 85 (Range 37-100) at follow-up. Complications were observed in seven patients (27%). Nineteen patients (73%) reported that they were "very satisfied". One patient (4%) described persistent ankle instability symptoms. In group B, the median Karlsson Score increased from 65 (Range 42-80) to 95 (Range 50-100) at follow-up. Complications were observed in four patients (9%). Thirty-three patients (77%) reported that they were "very satisfied". Two patients (5%) described persistent ankle instability symptoms. Pre-operative and at last follow-up Karlsson Score, results were significantly different between the two groups. There was no significant statistical difference in favour of satisfaction score, complications and recurrence of ankle instability between the two groups. CONCLUSION: ATFL repair with biological augmentation using IER gives excellent results for patients with BMI ≥ 30. Compared to patients with BMI < 30, they present a slightly lower preoperative and postoperative Karlsson score, however, with a similar satisfaction rate, but are at higher risk of transient superficial peroneal nerve dysesthesia. LEVEL OF EVIDENCE: Level III.

The ATFL inferior fascicle, the CFL and the PTFL have a continuous footprint at the medial side of the fibula.

PURPOSE: Knowledge of the complex anatomy of the lateral ankle ligaments is essential to understand its function, pathophysiology and treatment options. This study aimed to assess the lateral ligaments and their relationships through a 3D view achieved by digitally marking their footprints. METHODS: Eleven fresh-frozen ankle specimens were dissected. The calcaneus, talus and fibula were separated, maintaining the lateral ligament footprints. Subsequently, each bone was assessed by a light scanner machine. Finally, all the scans were converted to 3D polygonal models. The footprint areas of the talus, calcaneus and fibula were selected, analysed and the surface area was quantified in cm2. RESULTS: After scanning the bones, the anterior talofibular ligament inferior fascicle (ATFLif), calcaneofibular ligament (CFL) and posterior talofibular ligament (PTFL) footprints were continuous at the medial side of the fibula, corresponding to a continuous footprint with a mean area of 4.8 cm2 (± 0.7). The anterior talofibular ligament (ATFL) footprint on the talus consisted of 2 parts in 9 of the 11 feet, whilst there was a continuous insertion in the other 2 feet. The CFL insertion on the calcaneus was one single footprint in all cases. CONCLUSION: The tridimensional analysis of the lateral ligaments of the ankle demonstrates that the ATFLif, CFL and PTFL have a continuous footprint at the medial side of the fibula in all analysed specimens. These data can assist the surgeon in interpreting the ligament injuries, improving the imaging assessment and guiding the surgeon to repair and reconstruct the ligaments in an anatomical position.

Minimally invasive Chevron Akin (MICA) osteotomy for severe hallux valgus.

INTRODUCTION: The minimally invasive Chevron Akin (MICA) osteotomy has been widely used to treat hallux valgus (HV). The purpose of this study was to present a case series of patients with severe HV undergoing surgical treatment using the MICA procedure and to evaluate the clinical and radiographic outcomes. MATERIALS AND METHODS: Retrospective study including 60 consecutive feet (52 patients) undergoing MICA for severe HV. The data were collected pre- and post-operatively at the last follow-up. Patients were clinically evaluated by the visual analog pain scale (VAS) and AOFAS hallux MTP-IP score. Radiographic assessments included measurements of hallux valgus angle (HVA), intermetatarsal angle (IMA), metatarsal (MT) length, distal metatarsal articular angle (DMAA), and plantar translation of MT head. The complications were recorded during the follow-up. RESULTS: The mean age was 59.9 years, and the mean follow-up was 20.5 months. The average AOFAS increased from 41.2 to 90.9 points, and the VAS from 8.1 to 1.3 at the last follow-up. The average HVA decreased from 41.2º to 11.6º, the IMA from 17.1º to 6.9º, and the DMAA from 17.9º to 7.8º. The average shortening of the first metatarsal and the plantar translation of the MT head was 5.1 mm and 2.8 mm, respectively. The most observed complication was hardware discomfort, observed in 5 feet (8.3%). There were two cases of recurrence (3.3%). CONCLUSION: MICA technique was demonstrated in this series of cases to be an effective procedure for severe HV, with a low rate of recurrence and an acceptable rate of complications. LEVEL OF EVIDENCE: IV; case series.

Treatment of hallux rigidus with percutaneous metatarsophalangeal arthrodesis: a case series with a minimum follow-up of 2 years.

BACKGROUND: Percutaneous metatarsophalangeal arthrodesis is an option for the treatment of hallux rigidus in more advanced cases. The aim of this study was to investigate the clinical and radiographic results at least 2 years after percutaneous metatarsophalangeal arthrodesis in patients with hallux rigidus. METHODS: This is a case series of consecutive patients undergoing percutaneous metatarsophalangeal arthrodesis in patients with hallux rigidus grades III and IV with a minimum of 24 months of clinical and radiographic follow-up. The primary outcome was clinical assessment using the Visual Analog Scale for Pain (VAS). Secondary outcomes included American Orthopedic Foot & Ankle Society (AOFAS) score, patient satisfaction, complications, and bone healing (radiographic analysis). RESULTS: Between August 2017 and February 2020, 29 feet (24 patients) underwent percutaneous metatarsophalangeal arthrodesis. The mean follow-up was 38.4 (range 24-54) months. There was an improvement in the pain (VAS) from 7.8 to 0.6 (p < 0.001) and in the AOFAS score from 49.9 to 83.6 (p < 0.001). There was a rate of bone union of 82.8% and screw removal of 13.8%. All patients considered the result to be excellent or good. CONCLUSION: The treatment of grade III and IV hallux rigidus with percutaneous metatarsophalangeal arthrodesis demonstrated high patient satisfaction and significantly improves in clinical outcomes but the nonunion rate was higher than reported outcomes for open 1st metatarsophalangeal joint arthrodesis. LEVEL OF EVIDENCE: IV, case series.

All-inside arthroscopic repair of the anterior talofibular ligament: a case series.

INTRODUCTION: The all-inside arthroscopic repair of the anterior talofibular ligament (ATFL) is a technically challenging and still-recent procedure to treat chronic ankle instability (CAI). Favourable clinical outcomes have been shown from originator centers, but this is one of the first series from a non-originator centre. The purpose of the present study is to present the clinical and functional results of patients with CAI underwent arthroscopic all-inside ATFL repair. METHODS: This is a series of cases of 18 consecutive patients who underwent the all-inside arthroscopic ATFL repair, for CAI, after the failure of conservative treatment performed for six months. The evaluation was made using the American Orthopaedic Foot and Ankle Score (AOFAS), visual analog pain scale (VAS), anterior drawer, and talar tilt tests. RESULTS: All 18 patients were evaluated for a mean follow-up period of 12 months. There was an improvement in the AOFAS (p < 0.001), with the mean improving from 69.6 points to 98.1, standard deviation (SD) = 11.09, and in the mean VAS score (p < 0.001), from 5.0 to 0.5 points (SD = 0.78). All ankles were stable, as assessed by the anterior drawer test and talar tilt test. The only complication found was neurapraxia of the superficial fibular nerve in one patient (5%). All of the patients classified the treatment as good or excellent and returned to sports activities without limitations. CONCLUSION: Treatment of CAI by the all-inside arthroscopic ATFL repair was able to restore ankle stability and showed good clinical results and high satisfaction rates.

Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.

Technique Tip: Medial prominence bone spur resection in the third-generation percutaneous Chevron-Akin Osteotomy Technique (PECA) for hallux valgus correction.

The third-generation percutaneous chevron and Akin osteotomy (PECA) technique for surgical management of hallux valgus has shown improvement in clinical and radiographic outcomes. During this procedure, lateral translation and fixation of the first metatarsal head results in the formation of a bony prominence on the medial side of the distal aspect of the first metatarsal which can cause pain and discomfort to the patient. We describe two techniques to address this bony prominence; either i) excision osteotomy and removal of the fragment or ii) a dorsal closing wedge osteotomy retaining the bony fragment. LEVEL OF EVIDENCE: Level V, expert opinion.

Connecting fibers between ATFL's inferior fascicle and CFL transmit tension between both ligaments.

PURPOSE: The lateral ligament complex of the ankle has been extensively studied. Recently an anatomical study described a connection between anterior talofibular ligament inferior fascicle (ATFLif) and calcaneofibular ligament (CFL). The applicability and the mechanical role of these connections have not yet been studied and need to be clarified. The purpose of this study is to evaluate the connection between ATFLif and CFL through a dynamic measurement analysis. METHODS: An anatomical study was performed in 13 fresh-frozen below-the-knee ankle specimens. Each specimen was dissected in a protocolized manner until the lateral ligaments were exposed. A complete injury to both ATFL's fascicles was created in the proximal third of the ligament. A displacement transducer specifically design was inserted in the CFL and in the lateral part of the calcaneus to test its lengthening. A traction of 1 kg weight (9.8 N) was applied to ATFLif while the transducer measured the lengthening that this force created in the CFL. RESULTS: A total of 13 ankle specimens were carefully dissected. One specimen with signals of a prior traumatic injury of the ATFLif was excluded. A total of 12 specimens were included, 7 females and 5 males with an average age of 74 years (52-88 years). The right ankle was dissected in 6 specimens. ATFL was identified as a two-fascicled ligament in all cases. The fibers connecting the ATFLif and CFL were observed in all specimens. The displacement transducer showed lengthening in the CFL in all measurements with a median of 0.59 mm (SD ± 0.34). CONCLUSION: Connecting fibers between ATFLif and CFL are robust enough to transmit tension from one structure to the other. In the case of associated proximal lesions of the ATFLif and CFL, ligaments repair with a single suture may be considered. This can be applied in surgical procedures in patients with lateral ankle instability.

Reduced CD4 T Lymphocytes in Lymph Nodes of the Mouse Model of Autism Induced by Valproic Acid.

OBJECTIVE: Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal model of autism induced by valproic acid (VPA). Pregnant Swiss mice received a single intraperitoneal injection of 600 mg/kg of VPA (VPA group) or saline (control group) on day 11 of gestation. Male offspring were euthanized on postnatal day 60 for removal of thy-muses, spleens, and a pool of inguinal, axillary and brachial lymph nodes. Cellularity was evaluated, and flow cytometry analysis was performed on cell suspensions incubated with the mouse antibodies anti-CD3-FITC, anti-CD4-PE, and anti-CD8-PE-Cy7. We observed that the prenatal exposure to VPA induced a reduction in the numbers of CD3+CD4+ T cells in their lymph nodes when compared to the control animals. This was specific since it was not seen in the thymus or spleen. The consistent decrease in the number of CD4+ T cells in subcutaneous lymph nodes of mice from the animal model of autism may be related to the allergic symptoms frequently observed in ASD. Further research is necessary to characterize the immunological patterns in ASD and the connection with the pathophysiology of this disorder.

Acetyl-CoA production from pyruvate is not necessary for preservation of myelin.

Oligodendrocytes and Schwann cells not only form myelin in the central and peripheral nervous system, but also provide metabolic and trophic support to the axons they ensheathe. Acetyl-CoA is potentially a key molecule in Schwann cells and oligodendrocytes because it is at the crossroads of cellular lipid biosynthesis and energy generation. The main route for acetyl-CoA production is the oxidation of pyruvate by the pyruvate dehydrogenase complex (PDC). PDC deficiency in humans results in neurodegeneration and developmental impairments in both white and gray matter structures. To address the importance of PDC in myelinating glia, we deleted Pdha1 gene specifically in oligodendrocytes and Schwann cells. Surprisingly, sciatic and optic nerve morphology and the motor performance of Pdha1f/Y; CnpCre/+ mice are undistinguishable from those of controls at 1 month of age. In addition, myelin is stably maintained for at least 10 months. However, Pdha1f/Y; CnpCre/+ mice showed reduced fiber density and signs of axonal degeneration in both sciatic and optic nerves from 6 months of age. In contrast, 10 month-old mice bearing a floxed Pdha1 gene with either P0-Cre (expressed only by Schwann cells) or NG2-CreER (expressed in oligodendrocyte precursor cells) do not show any sign of axonal pathology or alterations in myelin structure or thickness. This indicates that the axonopathy is specific to the Pdha1f/Y; CnpCre/+ mice. Taken together, these results suggest that acetyl-CoA derived from pyruvate is not necessary for myelin maintenance and, thus, myelin-forming cells are not likely to contribute to the pathophysiology of PDC deficiency.

Impact of Sesamoid Coverage on Clinical Foot Function Following Fourth-Generation Percutaneous Hallux Valgus Surgery.

Background: The impact of pronation and sesamoid coverage on clinical outcomes following percutaneous hallux valgus surgery are not currently known. The aim of this study was to investigate if sesamoid coverage was associated with worse clinical outcomes at 12-month follow-up following percutaneous hallux valgus surgery. Methods: Retrospective comparative observational study of clinical and radiographic outcomes based on a previously published prospective dataset. Patients were stratified into 3 cohorts based on the degree of sesamoid coverage (normal, mild, or moderate) on 12-month weightbearing radiographs following fourth-generation percutaneous hallux valgus surgery. Primary outcome was a validated patient-reported outcome measure (PROM), the Manchester-Oxford Foot Questionnaire (MOXFQ). Secondary outcomes included Euroqol-5D, VAS Pain, and radiographic deformity correction. Results: Forty-seven feet underwent primary fourth-generation HV surgery and were stratified into 3 cohorts. There were 19, 16, and 12 feet in the normal, mild, and moderate cohorts respectively. There was no significant difference in either pre- or postoperative foot function (all MOXFQ domains, P > .05) or health-related quality of life (EQ-5D Index or VAS, P > .05). The MOXFQ Index preoperatively was as follows: normal cohort, 56.1 ± 26.9; mild cohort, 54.1 ± 17.9; and severe cohort, 49.6 ± 23.8; and postoperatively was as follows: normal cohort, 15.6 ± 21.5; mild cohort, 11.4 ± 15.5; and severe cohort, 11.4 ± 13.6 (P = .737-.908). There was significantly worse hallux valgus angle (HVA) and intermetatarsal angle (IMA) between the cohorts (P < .01). Although HVA and IMA were corrected to normal parameters following surgery in all cohorts, there was a significantly worse postoperative HVA in the moderate sesamoid coverage (5.3 ± 3.9 vs 7.9 ± 5.3 vs 11.4 ± 3.7, P < .01); however, IMA was not significantly different (3.4 ± 2.2 vs 4.1 ± 2.7 vs 5.2 ± 2.9, P = .168). Conclusion: This study found that cases where the sesamoids were not reduced had a poorer correction and had worse preoperative deformity. Clinical outcomes and foot function following fourth-generation percutaneous hallux valgus surgery were not affected by sesamoid coverage at the 12-month follow-up. The long-term implications in the difference in radiographic deformity between the 3 cohorts are not known, and further work should explore the relationship of first ray pronation and sesamoid position, particularly with regard to recurrence. Level of evidence: Level III, retrospective comparative study of prospectively collected data.

MRI Assessment of Tendon Graft After Lateral Ankle Ligament Reconstruction: Does Ligamentization Exist?

BACKGROUND: No description exists in the literature about the normal evolution of tendon graft after a lateral ankle ligament (LAL) reconstruction. PURPOSE: To assess the magnetic resonance imaging (MRI) characteristics and the evolution of the tendon graft during different moments in the follow-up after an endoscopic reconstruction of the LAL. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This prospective study included 37 consecutive patients who underwent an endoscopic reconstruction of the LAL with an autograft using the gracilis tendon to treat chronic ankle instability (CAI) resistant to nonoperative treatment (CAI group) and 16 patients without ankle instability (control group). All patients in the CAI group underwent a postoperative assessment at 6, 12, and 24 months using the Karlsson score and MRI examination. Only patients with good and excellent results were included in the study. Graft assessment consisted of qualitative measurements and quantitative evaluations of the reconstructed anterior talofibular ligament (RATFL) and reconstructed calcaneofibular ligament (RCFL), including signal-to-noise quotient (SNQ) and contrast-to-noise quotient (CNQ) measurements in proton density-fat suppressed (PD-FS) and T1-weighted sequences. The analysis of variance test was used to compare the SNQ and the CNQ at different time points for each sequence. RESULTS: The MRI signal at 6 months was increased compared with that of the control group. Next, a significant signal decrease from 6 to 24 months was noted on PD-FS and T1-weighted images. SNQ measurements on PD-FS weighted images for both the RATFL and the RCFL demonstrated a significantly higher signal (P < .01 and P = .01, respectively) at 6 months compared with that of the control group. Subsequently, the signal decreased from 6 to 24 months. Similarly, CNQ measurements on PD-FS weighted images for both the RATFL and the RCFL demonstrated a significantly higher signal (P < .01 and P < .01, respectively) at 6 months compared with that of the control group. Subsequently, the signal decreased from 6 to 24 months. CONCLUSION: The present study demonstrated an evolution of the MRI characteristics, suggesting a process of graft maturation toward ligamentization. This is important for clinical practice, as it suggests an evolution in graft properties and supports the possibility of creating a viable ligament.

Minimally Invasive Chevron Akin Osteotomy: Preoperative Planning Using the Radiographic First-Ray Squeeze Test.

Background: Recognizing preoperative first-ray hypermobility is important to planning hallux valgus (HV) surgery. A recent study showed the minimally invasive chevron Akin (MICA) osteotomy increased varus displacement of the proximal fragment of the first metatarsal osteotomy. The present study aims to evaluate the ability of the radiographic first-ray squeeze test to predict the varus displacement of the proximal fragment of the first metatarsal osteotomy when performing the MICA procedure. Methods: A prospective case series of patients with moderate to severe HV who underwent MICA was performed. The HV deformity correction was analyzed by comparing the preoperative and 12-week postoperative hallux valgus angle (HVA) and the intermetatarsal angle between the first and second rays (1-2 IMA). The ability of the radiographic first-ray squeeze test to predict the varus displacement of the first metatarsal was done by comparing the preoperative 1-2 IMA measured in the AP radiographic first-ray squeeze test (IMA-ST) with the intermetatarsal angle between the second metatarsal and the axis of the first metatarsal osteotomy proximal fragment (IAPF) taken 12 weeks postoperatively. Results: Between July 2022 and May 2023, a total of 39 feet in 28 patients underwent MICA. The mean IMA improved from 13.8 (SD = 2.2) to 3.8 degrees (SD = 1.5) (P < .001), and the mean HVA improved from 27.8 (SD = 6.1) to 4.9 degrees (SD = 2.5) (P < .001). A linear regression analysis revealed that IMA-ST is highly associated with the 12 week assessed IAPF (P < .001). Conclusion: The preoperative radiographic first-ray squeeze test appears to predict with high fidelity the varus displacement of the proximal fragment of the first metatarsal that can occur after the MICA procedure.Level of Evidence: Level III, prospective cohort study.

Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination.

Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this work, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in early and severe defects in peripheral nerve development. Using a proteomic approach in vitro, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on the presence of axonal signals. Furthermore, we show in vivo that loss of Phb2 in mouse Schwann cells causes ineffective proliferation and dysregulation of transcription factors EGR2 (KROX20), POU3F1 (OCT6) and POU3F2 (BRN2) that are necessary for proper Schwann cell maturation. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the development defect seen in mice lacking Schwann cell Phb2. This work develops our understanding of Schwann cell biology, revealing that Phb2 may directly or indirectly modulate the timely expression of transcription factors necessary for proper peripheral nervous system development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.

1-(Phenylselanyl)-2-(p-tolyl)indolizine: A selenoindolizine with potential antidepressant-like activity in mice mediated by the modulation of dopaminergic and noradrenergic systems.

1-(Phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) is a selenoindolizine with an antidepressant-like effect in mice by regulation of the serotonergic system. This study investigated the involvement of dopaminergic and noradrenergic systems in the antidepressant-like action of MeSeI. For this purpose, Swiss male mice were pretreated with different antagonists, after 15 min, the MeSeI was administrated by intragastric (i.g.) via; after 30 min, the mouse behavior was assessed in the forced swimming test (FST). The action of MeSeI on the activity of monoamine oxidase (MAO) was determined. The pretreatment of mice with haloperidol (0.05 mg/kg, intraperitoneally, i.p.; non-selective dopamine receptor antagonist), sulpiride (50 mg/kg, i.p.; D2 receptor antagonist), yohimbine (1 mg/kg, i.p.; α2 receptor antagonist), and propranolol (2 mg/kg, i.p.; non-selective ß receptor antagonist), inhibited the anti-immobility action of MeSeI (50 mg/kg, i.g.) in the FST. This blocking effect was not observed when SCH23390 (0.01 mg/kg, i.p.; D1 receptor antagonist), and prazosin (1 mg/kg, i.p.; α1 receptor antagonist) were administered. The coadministration of subeffective doses of bupropion (3 mg/kg. i.g.; dopamine and noradrenaline reuptake inhibitor) and MeSeI (0.5 mg/kg. i.g.) reduced the immobility time in the FST. Furthermore, MeSeI inhibited MAO-A and B activities in vitro and ex vivo tests. These results suggest that MeSeI exerts its antidepressant-like effect via regulation of the D2, α2, and ß1 receptors and the inhibition of MAO-A and B activities. Molecular docking investigations corroborated these results. This study provides comprehensive insights into the antidepressant-like mechanism of MeSeI in mice, suggesting its potential as a novel antidepressant candidate.