High mobility group box 1 in the central nervous system: regeneration hidden beneath inflammation.

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields, including neurology and neuroscience. High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern, which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, epilepsy, and traumatic brain injury. Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern, such as glycyrrhizin, ethyl pyruvate, and neutralizing anti-high-mobility group box 1 antibodies, are commonly used to target high-mobility group box 1 activity in central nervous system disorders. Although it is commonly known for its detrimental inflammatory effect, high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders. In this narrative review, we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern, its downstream receptors, and intracellular signaling pathways, how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system, and clues on how to differentiate the pro-regenerative from the pro-inflammatory role. Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

Analysis of the spatial and morphological characteristics of oligodendrocytes from images of in vitro culture.

Oligodendrocytes (OLs) are glial cells responsible for the formation of myelin sheaths in the central nervous system. The characteristic features of the oligodendrocyte lineage, ranging from proliferative and migratory oligodendrocyte progenitor cells (OPC) to myelinating mature OLs, can be observed in vitro cultures of OL lineage cells. Here, we introduce a method for analyzing the spatial distribution of OPCs, which reflects their capacity for proliferation and migration, and the morphological complexity of mature OLs, which reflects their capacity for myelin formation, from immunostaining images of in vitro OL cultures. Through the methods described, we have demonstrated the tendency for OPCs to cluster in an environment with epidermal growth factor (EGF), and the differing morphological complexity of mature OLs according to culture medium and duration of differentiation.•The proliferative and migratory characteristics of OPCs can be evaluated by analyzing their spatial distribution.•The myelin-forming capacity of mature OLs can be measured by analyzing their morphological complexity.•Image-based analyses may be a substitute for more convoluted experiments to assess OL function.

Joint preserving procedures for Takakura stage IIIB varus ankle osteoarthritis.

A man in his early 70s with right Takakura stage IIIB varus ankle osteoarthritis underwent medial opening wedge supramalleolar osteotomy with inframalleolar correction as joint preserving procedure. We also performed anteroinferior tibiofibular ligament (AITFL) resection with fibular shortening valgisation osteotomy to enhance the talar tilt correction. Postoperative decrease in talar tilt with dramatic symptom improvement was achieved. Performing the AITFL resection with fibular shortening valgisation osteotomy plus concomitant supramalleolar osteotomy and inframalleolar correction for Takakura stage IIIB varus ankle osteoarthritis resulted in successful improvement in talar tilt by making room for the valgus deviation of the talus.

Outcome comparison of minimally invasive proximal and distal chevron Akin osteotomies in patients with severe hallux valgus deformity: A randomized prospective study.

PURPOSE: To date, the surgical treatment of severe hallux valgus deformity remains challenging despite the various methods presented. This study aimed to compare the effectiveness of minimally invasive distal chevron Akin osteotomies (d-MICA) and minimally invasive proximal chevron Akin osteotomies (p-MICA) in correcting severe hallux valgus deformities. METHODS: This prospective follow-up study included patients randomly assigned to undergo p-MICA or d-MICA for hallux valgus deformities with a preoperative hallux valgus angle (HVA) ≥ 40° and/or a first to second intermetatarsal angle (IMA) ≥ 16°. After a minimum follow-up period of two years, we compared various clinico-radiographic parameters of patients whose HVA exceeded 15° at the final follow-up. RESULTS: In the p-MICA and d-MICA groups, seven of 40 cases (17.5%) and 16 of 41 cases (39.0%), respectively, exhibited HVA > 15° at the final follow-up (P = 0.048). The preoperative parameters showed no significant differences. However, at the first weight-bearing assessment, the HVA, IMA, and relative second metatarsal length were significantly smaller, and the distal metatarsal articular angle (DMAA) was greater in the p-MICA group (all P < 0.05) compared with the d-MICA group. Postoperatively, both groups exhibited significant decreases in HVA and IMA at the final follow-up (P < 0.001 for all parameters). The p-MICA group showed no significant changes in DMAA and the relative length of the second metatarsal (P = 0.253 and 0.185, respectively). However, the d-MICA group showed a significant decrease in DMAA (P < 0.001) and an increase in the relative length of the second metatarsal at the final follow-up (P = 0.01). CONCLUSIONS: p-MICA and d-MICA procedures demonstrated effective correction potential for severe hallux valgus deformities; however, the d-MICA procedure exhibited a notably higher incidence of unsatisfactory correction at the final follow-up than p-MICA. Therefore, d-MICA may be less predictable in achieving successful outcomes than p-MICA in treating severe hallux valgus deformities.

A primary culture method for the easy, efficient, and effective acquisition of oligodendrocyte lineage cells from neonatal rodent brains.

Oligodendrocytes (OL) are myelin-forming glial cells in the central nervous system. In vitro primary OL culture models offer the benefit of a more readily controlled environment that facilitates the examination of diverse OL stages and their intricate dynamics. Although conventional methods for primary OL culture exist, their performance in terms of simplicity and efficiency can be improved. Here, we introduce a novel method for primary OL culture, namely the E3 (easy, efficient, and effective) method, which greatly improves the simplicity and efficiency of the primary OL culture procedure using neonatal rodent brains. We also provided the optimal media composition for the augmentation of oligodendrocyte progenitor cell (OPC) proliferation and more robust maturation into myelin-forming OLs. Overall, E3 offers an undemanding method for obtaining primary OLs with high yield and quality. Alongside its value as a practical tool, in vitro characteristics of the OL lineage additionally identified during the development of the E3 method have implications for advancing research on OL physiology and pathophysiology.

Lateral Deviation of the Hyoid Bone and Thyroid Cartilage Influences Prevertebral Soft-Tissue Swelling and Dysphagia After Anterior Cervical Diskectomy and Fusion.

BACKGROUND AND OBJECTIVES: Prevertebral soft-tissue swelling (PSTS) after anterior cervical diskectomy and fusion (ACDF) is known to be influenced by several factors. We considered the effect of lateral deviation on the traction force and attempted to find a relationship with the PSTS. This study was designed to evaluate the preoperative lateral deviation of the hyoid bone and thyroid cartilage and its effect on PSTS, airway collapse, and clinical outcomes after ACDF. METHODS: Preoperative lateral deviations of the hyoid bone and thyroid cartilage at the superior cornu and inferior cornu were measured. To assess the effect of lateral deviation, patients who underwent 1 or 2 level ACDF with the left-sided approach were divided into a deviation group (left-sided deviation >5 mm or >10 mm) and a nondeviation group (left-sided deviation <5 mm or <10 mm). Difference of preoperative and postoperative PSTS (dPSTS), airway collapse, dysphagia score, and Neck Disability Index were compared between the 2 groups. RESULTS: Lateral deviation was measured in 290 patients, and 145 were enrolled to assess the effect of lateral deviation. Left-sided deviation was more common than right-sided deviation in all 3 structures (the hyoid bone, superior cornu, and inferior cornu of the thyroid cartilage). The deviation group demonstrated a significantly larger dPSTS at the C3 and C4 levels, more airway collapse at the C4 level, and a higher dysphagia score. There was no significant difference in the Neck Disability Index between the 2 groups. Lateral deviation significantly correlated with dPSTS (C3, C4, C5, and C6 levels) and airway collapse (C3 and C4 levels). CONCLUSION: A left-sided deviation of more than 5 mm of the hyoid bone or thyroid cartilage discouraged the left-sided approach for ACDF because of the aggravation of dPSTS, airway collapse, and dysphagia postoperatively.

Reoperation Rates According to Surgical Approach After Operation for Degenerative Cervical Pathology in Patients With Athetoid Cerebral Palsy: A Nationwide Cohort Study.

STUDY DESIGN: National population-based cohort study. OBJECTIVE: The overall complication rate for patients with athetoid cerebral palsy (CP) undergoing cervical surgery is significantly higher than that of patients without CP. The study was conducted to compare the reoperation and complication rates of anterior fusion, posterior fusion, combined fusion, and laminoplasty for degenerative cervical myelopathy/radiculopathy in patients with athetoid cerebral palsy. METHODS: The Korean Health Insurance Review and Assessment Service national database was used for analysis. Data from patients diagnosed with athetoid CP who underwent cervical spine operations for degenerative causes between 2002 and 2020 were reviewed. Patients were categorized into four groups for comparison: anterior fusion, posterior fusion, combined fusion, and laminoplasty. RESULTS: A total of 672 patients were included in the study. The overall revision rate was 21.0% (141/672). The revision rate was highest in the anterior fusion group (42.7%). The revision rates of combined fusion (11.1%; hazard ratio [HR], .335; P = .002), posterior fusion (13.8%; HR, .533; P = .030) were significantly lower than that of anterior fusion. Revision rate of laminoplasty (13.1%; HR, .541; P = .240) was also lower than anterior fusion although the result did not demonstrate statistical significance. CONCLUSION: Anterior fusion presented the highest reoperation risk after cervical spine surgery reaching 42.7% in patients with athetoid CP. Therefore, anterior-only fusion in patients with athetoid CP should be avoided or reserved for strictly selected patients. Combined fusion, with the lowest revision risk at 11.1%, could be safely applied to patients with athetoid CP.

Phase Change Heterostructure Memory with Oxygen-Doped Sb2Te3 Layers for Improved Durability and Reliability through Nano crystalline Island Formation.

Phase-change random access memory represents a notable advancement in nonvolatile memory technology; however, it faces challenges in terms of thermal stability and reliability, hindering its broader application. To mitigate these issues, doping and structural modification techniques such as phase-change heterostructures (PCH) are widely studied. Although doping typically enhances thermal stability, it can adversely affect the switching speed. Structural modifications such as PCH have struggled to sustain stable performance under high atmospheric conditions. In this study, these challenges are addressed by synergizing oxygen-doped Sb2Te3 (OST) with PCH technology. This study presents a novel approach in which OST significantly improves the crystallization temperature, power efficiency, and cyclability. Subsequently, the integration of the PCH technology bolsters the switching speed and further amplifies the device's reliability and endurance by refining the grain size (≈7 nm). The resultant OST-PCH devices exhibit exceptional performance metrics, including a drift coefficient of 0.003 in the RESET state, endurance of ≈4 × 108 cycles, an switching speed of 300 ns, and 67.6 pJ of RESET energy. These findings suggest that the OST-PCH devices show promise for integration into embedded systems, such as those found in automotive applications and Internet of Things devices.

Corrigendum to "The Association of Body Mass Index and Waist Circumference with the Risk of Achilles Tendon Problems: A Nationwide Population-Based Longitudinal Cohort Study".

[This corrects the article on p. 488 in vol. 15, PMID: 37274500.].

Association between pre-diagnostic serum uric acid levels in patients with newly diagnosed epilepsy and conversion rate to drug-resistant epilepsy within 5 years: A common data model analysis.

PURPOSE: Drug-resistant epilepsy (DRE) poses a significant challenge in epilepsy management, and reliable biomarkers for identifying patients at risk of DRE are lacking. This study aimed to investigate the association between serum uric acid (UA) levels and the conversion rate to DRE. METHODS: A retrospective cohort study was conducted using a common data model database. The study included patients newly diagnosed with epilepsy, with prediagnostic serum UA levels within a six-month window. Patients were categorized into hyperUA (≥7.0 mg/dL), normoUA (<7.0 and >2.0 mg/dL), and hypoUA (≤2.0 mg/dL) groups based on their prediagnostic UA levels. The outcome was the conversion rate to DRE within five years of epilepsy diagnosis. RESULTS: The study included 5,672 patients with epilepsy and overall conversion rate to DRE was 19.4%. The hyperUA group had a lower DRE conversion rate compared to the normoUA group (HR: 0.81 [95% CI: 0.69-0.96]), while the hypoUA group had a higher conversion rate (HR: 1.88 [95% CI: 1.38-2.55]). CONCLUSIONS: Serum UA levels have the potential to serve as a biomarker for identifying patients at risk of DRE, indicating a potential avenue for novel therapeutic strategies aimed at preventing DRE conversion.

Transpedicular injection of rhBMP-2 with ß-tricalcium phosphate to reduce the proximal junctional kyphosis after adult spinal deformity correction: preliminary study.

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.

A Novel Technique of Medial Displacement Calcaneal Osteotomy Using the Intramedullary Fixation of a Conventional Low-Profile Locking Wedge Plate.

BACKGROUND: Postoperative heel pain arising from prominent screw heads is a common complication following medial displacement calcaneal osteotomy (MDCO). This study aims to present the clinicoradiographic outcomes of a novel MDCO technique, wherein intramedullary fixation of a conventional low-profile locking wedge plate is employed. METHODS: A retrospective analysis, involving a comparison of clinical and radiographic parameters among consecutive patients who underwent MDCO was conducted. The patients were subjected to either intramedullary wedge plate fixation through the osteotomy site (IWPF group, n = 45 cases) or conventional cannulated screw fixation from the heel (CCSF group, n = 51 cases). Radiographic evaluation included measurement of hindfoot alignment angle, alignment ratio, and moment arm. Clinical outcomes were measured with the American Orthopaedic Foot & Ankle Society ankle-hindfoot score, and the Foot and Ankle Ability Measure (FAAM) activities of daily living and sports subscales, before and at 6, 12, and ≥24 months postoperatively. The presence of heel pain was evaluated at the postoperative 6 and 12 months in both groups. RESULTS: For both groups, a marked enhancement in all 3 radiographic parameters was observed. The extent of correction for all clinicoradiographic parameters demonstrated no statistically significant divergence between the 2 groups. However, the FAAM-Sports scores at the 6-month postoperative juncture exhibited a significant elevation in the IWPF group relative to the CCSF group. Importantly, no patient reported heel pain at postoperative 6 and 12 months in the IWPF group whereas the rates of patients having heel pain at postoperative 6 and 12 months were 56.8% (29 cases) and 33.3% (17 cases), respectively, in the CCSF group. CONCLUSION: Both techniques yield analogous postoperative clinical and radiographic enhancements. However, the utilization of IWPF promotes a swifter clinical improvement with respect to sports activities when juxtaposed with the CCSF from the calcaneal tuberosity. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Comparison of supramalleolar and inframalleolar correction for Takakura stage IIIB ankle arthritis in a single patient.

A man in his early 60s with bilateral Takakura stage IIIB varus ankle arthritis underwent calcaneal osteotomy on the right side and supramalleolar osteotomy (SMO) with fibular osteotomy on the left side. Both sides underwent identical procedures, including multiple drilling of the denuded talar dome and gutter, deltoid ligament release, anterior talofibular ligament (ATFL) reconstruction and posterior tibial tendon (PTT) lengthening. This aimed to minimise patient-related factors when assessing correction efficacy. Both procedures demonstrated a similar degree of improvement in talar tilt. Supramalleolar correction contributed more significantly to lateralising the talar centre, while greater improvement in preoperative hindfoot varus was achieved through inframalleolar correction.

Prediction of Intracranial Atherosclerotic Disease-Related Large-Vessel Occlusion Stroke on the Basis of Novel Cerebral Blood Volume Parameters.

BACKGROUND: Mechanical thrombectomy is an effective treatment method for large-vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)-related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT). METHODS AND RESULTS: We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia-only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P<0.001). Regarding the estimated infarct patterns on the CBV, ICAD was most frequently observed in the normal CBV group (territorial, 14.9%; cortical wedge, 10.0%; basal ganglia-only, 43.8%; subcortical, 35.7%; normal, 61.7%). CBV parameters, including "an increase in CBV," "normal CBV infarct pattern," and "an increase in CBV or normal CBV infarct pattern composite," were independently associated with ICAD. CONCLUSIONS: An increased CBV or normal CBV pattern may be associated with ICAD LVOS on the pretreatment perfusion imaging.

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). METHODS: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. RESULTS: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC. CONCLUSIONS: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.

The association between refractory plantar fasciitis and insertional Achilles tendinopathy and peripheral spondyloarthritis: a report of human leukocyte antigen B-27 investigation and treatment outcome.

PURPOSE: This study aimed to determine the presence of peripheral spondyloarthritis and investigate the clinical characteristics of patients with concurrent peripheral spondyloarthritis in those presenting with refractory plantar fasciitis and Achilles tendinopathy by conducting human leukocyte antigen B-27 (HLA-B27) testing. METHODS: This retrospective study aimed to investigate patients who complained of persistent pain and significant limitations in daily activities due to their respective foot pain, despite receiving conservative treatment for over one year under the diagnosis of plantar fasciitis or insertional Achilles tendinopathy. The study included 63 patients who underwent HLA-B27 testing. The patients were classified into two groups based on the presence or absence of HLA-B27 positivity. The Mann-Whitney U test assessed significant relationships between continuous variables, and the chi-square test was used to compare categorical variables. RESULTS: Among the 63 included patients, HLA-B27 positivity was confirmed in 11 patients (17.5%), which was significantly associated with a lower average age (22.8 years versus 31.7 years, P = 0.01) and a substantially lower proportion of females compared to HLA-B27-negative patients (9.1% vs. 25.0%, P = 0.001). Ten of the 11 patients initiated treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) combined with oral steroids as the first-line medication after being diagnosed as HLA-B27 positive. Six patients experienced pain relief with the first-line medication (60%). Four patients who did not achieve pain control with the first-line medication received tumour necrosis factor-alpha inhibitors as the second-line medication. Two patients experienced pain relief, while two experienced reduced but persistent pain. CONCLUSIONS: Among the patients with "refractory" plantar fasciitis and insertional Achilles tendinopathy, 17.5% were diagnosed with peripheral spondyloarthritis. Patients diagnosed with peripheral spondyloarthritis had a higher proportion of men and relatively younger mean age compared to those without the diagnosis. Approximately 70% of these patients achieved symptom improvement in foot and ankle joints by taking conventional synthetic DMARDs, TNF-α inhibitors, or both appropriate for spondyloarthritis.

Combination of Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 attenuates fat accumulation and alters the metabolome and gut microbiota in mice with high-fat diet-induced obesity.

This study evaluated the effects of formulations with Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 on adiposity, the alteration of microbiota, and the metabolome in high-fat diet-fed mice. The strains were selected based on their fat and glucose absorption inhibitory activities and potential metabolic interactions. The optimal ratio of the two strains in the probiotic formulation was determined based on their adipocyte differentiation inhibitory activities. Treatment of formulations with BEPC22 and BELP53 for 10 weeks decreased body weight gain at 6 weeks; it also decreased the food efficiency ratio, white adipose tissue volume, and adipocyte size. Moreover, it decreased the expression of the lipogenic gene Ppar-γ in the liver, while significantly increasing the expression of the fat oxidation gene Ppar-α in the white adipose tissue. Notably, treatment with a combination of the two strains significantly reduced the plasma levels of the obesity hormone leptin and altered the microbiota and metabolome. The omics data also indicated the alteration of anti-obesity microbes and metabolites such as Akkermansia and indolelactic acid, respectively. These findings suggest that treatment with a combination of BEPC22 and BELP53 exerts synergistic beneficial effects against obesity.

Conservative treatment outcome for Achilles tendon re-rupture occurring in the subacute phase after primary repair.

INTRODUCTION: Until now, a treatment protocol for Achilles tendon re-rupture (ATRR) occurring in the postoperative period 5-12 weeks following primary Achilles tendon repair has not been established. We refer to this time frame as the subacute postoperative phase, and the objective of this study was to assess the efficacy of conservative treatment for subacute ATRR in this phase. MATERIALS AND METHODS: We conducted a retrospective review of 390 cases (385 patients) who had undergone primary Achilles tendon repair using the 4-strand Krachow method between January 2010 and August 2021. All patients were subjected to more than 12 months of follow-up and were categorized into two groups based on the presence of subacute ATRR: Group 1 comprised 370 cases without ATRR, while Group 2 comprised 20 cases with ATRR. Following confirmation of ATRR, we immediately applied a below-knee cast in an ankle plantar flexed position (25°-30°), followed by bracing according to the same rehabilitation plan used for the primary repair. After administering conservative treatment to the patients with ATRR, we compared several outcome parameters between the two groups, including isokinetic plantar flexion power measured using a dynamometer, time required for a single heel raise (t-SHR), time needed for ten repetitive SHRs (t-SHR10), Achilles Tendon Total Rupture Score (ATRS), and Foot and Ankle Ability Measure (FAAM) scores. The baseline timepoints for Groups 1 and 2 were the dates of the primary repair and the re-injury event. RESULTS: After primary Achilles tendon repair, subacute ATRR occurred in 5.1% of patients. There were no significant differences between the groups in terms of t-SHR and t-SHR10 (P = 0.281, 0.486). Similarly, the isokinetic dynamometer measurements revealed no significant differences in peak torque for plantar flexion at angular velocities of 30°/s and 120°/s, both in absolute values and as a percentage of the contralateral side, between the groups (P > 0.05 for each). However, ATRSs were significantly lower in Group 2 compared to Group 1 before 6 months (P < 0.05), as were FAAM-Activities of Daily Living scores at 6 months (P < 0.05). After 12 months, there were no significant differences in these scores between the two groups (both P > 0.05). CONCLUSION: Conservative treatment for subacute ATRR following primary Achilles tendon repair yields clinical outcomes comparable to those without ATRR. Therefore, we recommend that surgeons consider relying on the patient's natural healing capabilities rather than opting for aggressive surgical interventions, as expediting such operations may be unnecessary for subacute injuries.

Visualizing mast cell migration to tumor sites using sodium iodide symporter of nuclear medicine reporter gene.

PURPOSE: Owing to the close relationship between mast cells and cancer progression, an imaging technique that can be applied in a clinical setting to explore the biological behavior of mast cells in the tumor microenvironment is needed. In this study, we visualized mast cell migration to lung tumor lesions in live mice using sodium iodide symporter (NIS) as a nuclear medicine reporter gene. EXPERIMENTAL DESIGN: The murine mast cell line MC-9 was infected with retrovirus including NIS, luciferase (as a surrogate marker for NIS), and Thy1.1 to generate MC-9/NFT cells. Radioiodine uptake was measured in MC-9/NFT cells, and an inhibition assay of radioiodine uptake using KCLO4 was also performed. Cell proliferation and FcεRI expression was examined in MC-9 and MC-9/NFT cells. The effect of mast cell-conditioned media (CM) on the proliferation of Lewis lung cancer (LLC) cells was examined. The migration level of MC-9/NFT cells was confirmed in the presence of serum-free media (SFM) and CM of cancer cells. After intravenous injection of MC-9/NFT cells into mice with an LLC tumor, I-124 PET/CT and biodistribution analysis was performed. RESULTS: MC-9/NFT cells exhibited higher radioiodine avidity compared to parental MC-9 cells; this increased radioiodine avidity in MC-9/NFT cells was reduced to basal level by KCLO4. Levels of FcεRI expression and cell proliferation were not different in parental MC-9 cell and MC-9/ NFT cells. The CM of MC-9/NFT cells increased cancer cell proliferation relative to that of the SFM. The migration level of MC-9/NFT cells was higher in the CM than the SFM of LLC cells. PET/CT imaging with I-124 clearly showed infiltration of reporter mast cells in lung tumor at 24 h after transfer, which was consistent with the findings of the biodistribution examination. CONCLUSION: These findings suggest that the sodium iodide symporter can serve as a reliable nuclear medicine reporter gene for non-invasively imaging the biological activity of mast cells in mice with lung tumors. Visualizing mast cells in the tumor microenvironment via a nuclear medicine reporter gene would provide valuable insights into their biological functions.

Post-Vaccination Delivery of CpG ODNs Enhances the Th2-Associated Protective Immunity of the Smallpox DNA Vaccine.

Potential threat of smallpox bioterrorism and concerns related to the adverse effects of currently licensed live-virus vaccines suggest the need to develop novel vaccines with better efficacy against smallpox. Use of DNA vaccines containing specific antigen-encoding plasmids prevents the risks associated with live-virus vaccines, offering a promising alternative to conventional smallpox vaccines. In this study, we investigated the efficiency of toll-like receptor (TLR) ligands in enhancing the immunogenicity of smallpox DNA vaccines. BALB/c mice were immunized with a DNA vaccine encoding the vaccinia virus L1R protein, along with the cytosine-phosphate-guanine (CpG) motif as a vaccine adjuvant, and their immune response was analyzed. Administration of B-type CpG oligodeoxynucleotides (ODNs) as TLR9 ligands 24 h after DNA vaccination enhanced the Th2-biased L1R-specific antibody immunity in mice. Moreover, B-type CpG ODNs improved the protective effects of the DNA vaccine against the lethal Orthopoxvirus challenge. Therefore, use of L1R DNA vaccines with CpG ODNs as adjuvants is a promising approach to achieve effective immunogenicity against smallpox infection.