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.

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.

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.

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.

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.

High Mobility Group Box 1 as an Autocrine Chemoattractant for Oligodendrocyte Lineage Cells in White Matter Stroke.

BACKGROUND: The migration of oligodendrocyte precursor cells (OPC) is a key process of remyelination, which is essential for the treatment of white matter stroke. This study aimed to investigate the role of HMGB1 (high mobility group box 1), a damage-associated molecular pattern released from dying oligodendrocytes, as an autocrine chemoattractant that promotes OPC migration. METHODS: The migratory capacity of primary cultured OPCs was measured using the Boyden chamber assay. The downstream pathway of HMGB1-mediated OPC migration was specified by siRNA-induced knockdown or pharmacological blockade of TLR2 (toll-like receptor 2), RAGE (receptor for advanced glycation end product), Src, ERK1/2 (extracellular signal-regulated kinase1/2), and FAK (focal adhesion kinase). Conditioned media were collected from oxygen-glucose deprivation-treated oligodendrocytes, and the impact on OPC migration was assessed. Lesion size and number of intralesional Olig2(+) cells were analyzed in an in vivo model of white matter stroke with N5-(1-iminoethyl)-L-ornithine (L-NIO). RESULTS: HMGB1 treatment promoted OPC migration. HMGB1 antagonism reversed such effects to untreated levels. Among the candidates for the downstream signal of HMGB1-mediated migration, the knockdown of TLR2 rather than that of RAGE attenuated the migration-promoting effect of HMGB1. Further specification of the HMGB1-TLR2 axis revealed that the phosphorylation of ERK1/2 and its downstream molecule FAK, rather than of Src, was decreased in TLR2-knockdown OPCs, and pharmacological inhibition of ERK1/2 and FAK led to decreased OPC migration. Oxygen-glucose deprivation-conditioned media promoted OPC migration, suggesting the autocrine chemoattractant function of HMGB1. In vivo, TLR2(-/-)-mice showed lesser intralesional Olig2(+) cells compared to wild-type controls in response to L-NIO induced ischemic injury regardless of HMGB1 administration. CONCLUSIONS: HMGB1, through the TLR2-ERK1/2-FAK axis, functions as an autocrine chemoattractant to promote OPC migration, which is an initial and indispensable step in remyelination. Thus, a novel treatment strategy for white matter stroke based on the HMGB1-TLR2 axis in the oligodendrocyte lineage could be feasible.

Effect of Transition Metal Dichalcogenide Based Confinement Layers on the Performance of Phase-Change Heterostructure Memory.

Phase-change random-access memory is a promising non-volatile memory technology. However repeated phase-change operations can cause durability issues owing to defects formed by long-distance atom diffusion. To mitigate these issues, phase-change heterostructure (PCH) devices with confinement material (CM) layers based on transition metal dichalcogenides (TMDs) such as TiTe2 have been proposed. This study implements PCH devices with additional TMDs, including NiTe2 and MoTe2 , alongside TiTe2 , and analyzes their characteristics by examining the differences in the CM layers. The results show that the NiTe2 -based PCH device demonstrates a RESET current of 1.4 mA, 38% lower than that of the TiTe2 -based device, enabling low-power operation. Furthermore, the MoTe2 -based PCH device exhibits a cycling endurance exceeding 107 cycles, a five-fold improvement in durability compare with the TiTe2 -based device. The performance differences observe in each PCH device can be attributed to the variation in the material properties, such as the cohesive energy and electrical conductivity, of the TMDs used as the CM layer. These results provide critical clues to improve the performance and reliability of conventional PCH memory devices.

Pretreatment of rhesus monkeys with transdermal patches containing physostigmine and procyclidine: implications of the delivery system for the potential application against VX nerve agent intoxication in humans.

Physostigmine (Phs) is a reversible inhibitor of acetylcholinesterase (AChE) that penetrates the blood-brain barrier (BBB) and could be used to protect the central nervous system (CNS) against the effects of nerve agents. For prophylactic effectiveness, long, steady, and adequate inhibition of AChE activity by Phs is needed to broadly protect against the CNS effects of nerve agents. Here, we evaluated the efficacy of transdermal patches containing Phs and procyclidine (PC) as prophylactic agents. Patches (25 cm2) containing 4.4 mg Phs and 17.8 mg PC had a protective ratio of approximately 78.6-fold in rhesus monkeys challenged with VX nerve agent and given an antidote. Physiologically based pharmacokinetic model in conjunction with an indirect pharmacodynamic (PBPK/PD) was developed for Phs and scaled to rhesus monkeys. The model was able to reproduce the concentration profile and inhibitory effect on AChE of Phs in monkeys, as evidenced by correlation coefficients of 0.994 and 0.992 for 25 cm2 and 49 cm2 patches, respectively (i.e., kinetic data), and 0.989 and 0.968 for 25 cm2 and 49 cm2 patches, respectively (i.e., dynamic data). By extending the monkey PBPK/ PD model to humans, the effective human dose was predicted to be five applications of a 25 cm2 patch (i.e., 22 mg Phs), and two applications of a 49 cm2 patch (i.e., 17.4 mg Phs). Therefore, given that patch application of Phs in rhesus monkeys has a prolonged effect (namely, AChE inhibition of 19.6% for the 25 cm2 patch and 23.0% for the 49 cm2 patch) for up to 216 h, patch formulation of Phs may provide similar protection against nerve agent intoxication in humans.

Biportal endoscopic discectomy versus tubular microscopic discectomy for treating single-level lumbar disc herniation in obese patients: a multicenter, retrospective analysis.

PURPOSE: In microscopic lumbar discectomy in obese patients, a correlation is found between the operation time and increase in estimated blood loss according to the increase in body mass index; however, no studies have investigated the outcomes of biportal endoscopic lumbar discectomy in obese patients. Therefore, this study aimed to compare the clinical and radiographic outcomes of microscopic and endoscopic discectomy in obese patients with lumbar herniated discs. METHODS: In this multicenter, retrospective study, clinical and radiological data were compared and analyzed in 73 obese patients with a body mass index of > 30 kg/m2 who underwent microscopic or biportal endoscopic lumbar discectomy. Clinical data on the visual analog scale (VAS), Oswestry disability index (ODI), and EuroQol-5D (EQ-5D) scores were measured, and radiological data were obtained using magnetic resonance imaging (MRI). RESULTS: This study enrolled 43 patients who underwent microscopic discectomy and 30 who underwent biportal endoscopic discectomy. The VAS, ODI, and EQ-5D scores in both groups improved after surgery compared with those before surgery, although there was no difference between the two groups. Although there was a difference in the incidence of recurrent disc herniation confirmed by MRI after surgery, no difference was found in the number of patients requiring surgery between the two groups. CONCLUSION: In obese patients with lumbar disc herniation that was not improved with conservative treatment, no significant clinical or radiological differences in outcomes were noted between microscopic and biportal endoscopic surgery methods. In contrast, minor complications were less common in the biportal group.

Does ankle arthrodesis induce satisfactory changes in the medial longitudinal arch height of the foot for severe varus ankle arthritis?

PURPOSE: We designed this study to determine how changes in coronal ankle alignment affect sagittal alignment of the foot. Specifically, we focused on the changes in medial longitudinal arch height, which could be reflected by the medial cuneiform height (MCH), Meary's angle, and calcaneal pitch angle (CPA). METHODS: We retrospectively analyzed the radiographic findings of 37 patients who underwent open ankle arthrodesis without inframalleolar correction (such as first metatarsal dorsal closing wedge osteotomy, calcaneal osteotomies, tendon transfers, or tarsal joint arthrodesis) of severe varus ankle arthritis. The inclusion criterion was a pre-operative tibial axis to talar dome angle of 80 degrees or less. The enrolled patients were divided into two groups according to the post-operative decrease in MCH (≥ 2 mm or < 2 mm). RESULTS: A post-operative MCH decrease of ≥ 2 mm was observed in 43.2% (16 patients). Although the degree of coronal ankle varus correction was similar, the decrease in the Meary's angle was significantly greater in the group with a post-operative MCH decrease of ≥ 2 mm than in those with < 2 mm (- 4.1 degrees vs. - 1.3 degrees, P = 0.01). The changes in CPA were not significantly different (P = 0.172). CONCLUSION: Correction of ankle varus deformity via ankle arthrodesis could lead to a decrease in the medial longitudinal arch height in less than half of the enrolled patients. In these patients, a cavus component of the foot might be an important factor in determining a successful sagittal foot alignment change, while the CPA was maintained post-operatively.

A comparison of characteristics and outcomes of operative treatment for Achilles tendon sleeve avulsion in older versus younger patients.

INTRODUCTION: Achilles tendon sleeve avulsion (ATSA) is a rare injury that often results from pre-existing insertional Achilles tendinopathy and occurs when a tendon avulses from the insertion as a continuous sleeve. To date, outcomes of operative treatment for ATSA in older patients have not been reported. Therefore, this study aims to compare the characteristics and outcomes of Achilles tendon (AT) reattachment with or without tendon lengthening for ATSA between older and younger patients. MATERIALS AND METHODS: This study enrolled 25 consecutive patients who underwent operative treatment following a diagnosis of ATSA between January 2006 and June 2020. The inclusion criterion was a minimum follow-up duration of one year. The enrolled patients were divided into two groups according to their age at operation: ≥ 65 years (group 1, 13 patients) and < 65 years (group 2, 12 patients). AT reattachment was performed in all patients using two 5.0-mm suture anchors after an inflamed distal stump resection in the 30° plantar-flexed ankle position. RESULTS: The degree of active dorsiflexion and plantar flexion, mean visual analog scale score, and Victorian Institute of Sports Assessment-Achilles scores at the final follow-up were not significantly different between the two groups (P > 0.05 each). The rate of satisfactory clinical outcomes (defined as fair or greater) was 84.6% and 91.7% in groups 1 and 2, respectively. CONCLUSION: We observed that comparable clinical outcomes could be achieved after AT reattachment with or without lengthening for ATSA between older and younger patients.

Operative outcome of mucous cyst of lesser toes: A comparison between cyst excision with osteophytectomy and distal interphalangeal fusion.

BACKGROUND: To date, the optimal operative treatment for mucous cysts of the lesser toes (MCLT) has not been discussed in detail, although many previous studies have focused on treating finger lesions. Therefore, we evaluated the operative outcomes of two different procedures for MCLT: cyst excision with osteophytectomy and cyst excision with distal interphalangeal (DIP) fusion. METHODS: We retrospectively reviewed and compared the clinico-radiographic outcomes of patients who underwent cyst excision with osteophytectomy (group 1, 22 cases) or cyst excision with DIP fusion (group 2, 16 cases) for MCLT between January 2010 and August 2021. The minimum follow-up duration for inclusion in the study was 12 months. Clinical outcomes were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) lesser toes metatarsophalangeal-interphalangeal scale and the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) subscale. We also collected information on postoperative recurrence and operation-related complications. RESULTS: The preoperative and postoperative AOFAS and FAAM-ADL scores were not significantly different between the two groups (P > 0.05, each). However, the postoperative recurrence rate was 31.8 % in group 1 (7 of 22 cases), whereas no recurrence was observed in group 2. Every recurrence occurred within 8 postoperative weeks (mean, 4.8 weeks; range, 3-8 weeks). Nonunion of the fusion site was observed in one patient (6.3 %). CONCLUSION: We confirmed that postoperative recurrence was significantly lower in the case of cyst excision with DIP fusion than in cyst excision with osteophytectomy for the treatment of MCLT. Clinical outcomes were not significantly different between the two procedures. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Operative outcomes of a high-grade talar neck fracture - Lessons from 20 years' clinical experience in a single, tertiary hospital.

BACKGROUND: The operative treatment of high-grade talar neck fractures remains challenging, despite numerous previous reports. Our goal was to determine long-term outcomes and to establish a plan for management of postoperative complications (especially, avascular necrosis [AVN] of talar body) after high-grade talar neck fractures. We hypothesized that not every case with AVN of talar body require secondary surgical interventions. METHODS: We retrospectively reviewed the radiographic and clinical findings of 14 patients who underwent operative treatment for high-grade talar neck fractures (modified Hawkins type III and IV) between January 2000 and December 2017. The minimum follow-up duration for inclusion was 3 years. Using radiographs during follow-up, we assessed the development of AVN of the talar body, malunion, nonunion, and posttraumatic osteoarthritis. Information about the secondary operations and their outcomes were also investigated using visual analogue scale (VAS) and American orthopaedic foot and ankle society (AOFAS) ankle-hindfoot scale at the final follow-up. RESULTS: In 10 of 14 patients (71.4 %), talar body AVN developed during follow-up. However, secondary operation was required in only 30.0 % (3 of 10 patients). In the remaining 7 patients who did not undergo secondary operation, the symptoms were tolerable with a maximum of 89 months follow-up; although the talar body presented sclerotic changes, but without talar dome collapse. The rates of malunion and post-traumatic subtalar osteoarthritis were 21.4 % and 14.3 %, respectively. No patients presented with fracture site nonunion. After a mean of 55.86 ± 14.45 months (range, 37-89) follow-up, the final mean VAS and AOFAS scores were 3.07 ± 0.73 (range, 2-4) and 80.43 ± 3.11 (range, 75-85), respectively. CONCLUSION: We recommend leaving talar body AVN untouched, unless the patient's symptoms become intolerable. In our clinical practice, postoperative AVN could be stably maintained without talar dome collapse for more than 7 years, although the sclerotic change persisted. Despite the small number of patients, our clinical experience may benefit patients with high-grade talar neck fractures and surgeons who treat such rare, serious, and challenging foot injuries. LEVEL OF EVIDENCE: Level IV, Case series.

Melanin biopolymer synthesis using a new melanogenic strain of Flavobacterium kingsejongi and a recombinant strain of Escherichia coli expressing 4-hydroxyphenylpyruvate dioxygenase from F. kingsejongi.

BACKGROUND: Melanins are a heterologous group of biopolymeric pigments synthesized by diverse prokaryotes and eukaryotes and are widely utilized as bioactive materials and functional polymers in the biotechnology industry. Here, we report the high-level melanin production using a new melanogenic Flavobacterium kingsejongi strain and a recombinant Escherichia coli overexpressing F. kingsejongi 4-hydroxyphenylpyruvate dioxygenase (HPPD). RESULTS: Melanin synthesis of F. kingsejongi strain was confirmed via melanin synthesis inhibition test, melanin solubility test, genome analysis, and structural analysis of purified melanin from both wild-type F. kingsejongi and recombinant E. coli expressing F. kingsejongi HPPD. The activity of F. kingsejongi HPPD was demonstrated via in vitro assays with 6 × His-tagged and native forms of HPPD. The specific activity of F. kingsejongi HPPD was 1.2 ± 0.03 µmol homogentisate/min/mg-protein. Bioreactor fermentation of F. kingsejongi produced a large amount of melanin with a titer of 6.07 ± 0.32 g/L, a conversion yield of 60% (0.6 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.03 g/L·h, indicating its potential for industrial melanin production. Additionally, bioreactor fermentation of recombinant E. coli expressing F. kingsejongi HPPD produced melanin at a titer of 3.76 ± 0.30 g/L, a conversion yield of 38% (0.38 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.04 g/L·h. CONCLUSIONS: Both strains showed sufficiently high fermentation capability to indicate their potential as platform strains for large-scale bacterial melanin production. Furthermore, F. kingsejongi strain could serve as a model to elucidate the regulation of melanin biosynthesis pathway and its networks with other cellular pathways, and to understand the cellular responses of melanin-producing bacteria to environmental changes, including nutrient starvation and other stresses.

Encephalitis with status epilepticus and stroke as complications of non-severe COVID-19 in a young female patient: a case report.

BACKGROUND: Neurological manifestations of COVID-19 are thought to be associated with the disease severity of COVID-19 and poor clinical outcomes. Dysregulated immune responses are considered to be mediating such complications. Our case illustrates multiple critical neurological complications simultaneously developed in a patient with non-severe COVID-19 and successful recovery with a multifaceted therapeutic approach. The cerebrospinal fluid (CSF) interleukin-6 (IL-6) level was temporally correlated with the clinical severity of the status epilepticus in our patient, suggesting a causal relationship. CASE PRESENTATION: A previously healthy 20-year-old female patient presented with a first-onset seizure. Concomitant non-severe COVID-19 pneumonia was diagnosed. CSF study showed lymphocytic pleocytosis with elevated IL-6 levels in CSF. During hospitalization under the diagnosis of autoimmune encephalitis, status epilepticus developed, and the seizure frequency was temporally correlated with the CSF IL-6 level. Furthermore, a new embolic stroke developed without a significant cardioembolic source. Contrary to the exacerbated COVID-19-associated neurological complications, COVID-19 pneumonia was cleared entirely. After treatment with antiseizure medications, antithrombotics, antiviral agents, and immunotherapy, the patient was discharged with near-complete recovery. CONCLUSION: Active serological, and radiological evaluation can be helpful even in non-severe COVID-19, and multidimensional treatment strategies, including immunotherapy, can successfully reverse the neurological complication.

A multipathogen DNA vaccine elicits protective immune responses against two class A bioterrorism agents, anthrax and botulism.

The potential use of biological agents has become a major public health concern worldwide. According to the CDC classification, Bacillus anthracis and Clostridium botulinum, the bacterial pathogens that cause anthrax and botulism, respectively, are considered to be the most dangerous potential biological agents. Currently, there is no licensed vaccine that is well suited for mass immunization in the event of an anthrax or botulism epidemic. In the present study, we developed a dual-expression system-based multipathogen DNA vaccine that encodes the PA-D4 gene of B. anthracis and the HCt gene of C. botulinum. When the multipathogen DNA vaccine was administered to mice and guinea pigs, high level antibody responses were elicited against both PA-D4 and HCt. Analysis of the serum IgG subtype implied a combined Th1/Th2 response to both antigens, but one that was Th2 skewed. In addition, immunization with the multipathogen DNA vaccine induced effective neutralizing antibody activity against both PA-D4 and HCt. Finally, the protection efficiency of the multipathogen DNA vaccine was determined by sequential challenge with 10 LD50 of B. anthracis spores and 10 LD50 of botulinum toxin, or vice versa, and the multipathogen DNA vaccine provided higher than 50% protection against lethal challenge with both high-risk biothreat agents. Our studies suggest the strategy used for this anthrax-botulinum multipathogen DNA vaccine as a prospective approach for developing emergency vaccines that can be immediately distributed on a massive scale in response to a biothreat emergency or infectious disease outbreak. Key points • A novel multipathogen DNA vaccine was constructed against anthrax and botulism. • Robust immune responses were induced following vaccination. • Suggests a potential vaccine development strategy against biothreat agents.

Clinical and radiologic outcomes of biportal endoscopic lumbar discectomy in obese patients: a retrospective case-control study.

BACKGROUND: Obese patients have a higher risk of complications during spinal surgery than non-obese patients. To the best of our knowledge, no studies have examined the differences in clinical and radiological outcomes after biportal endoscopic lumbar discectomy (BELD) between obese and non-obese patients. The study evaluated the association between obesity and outcomes after BELD in patients with lumbar disc herniation. METHODS: This was a retrospective case-control study conducted from March 2017 to March 2021 at two hospitals with 360 patients who underwent BELD after showing no improvement with conservative treatment. Clinical and radiologic outcomes were retrospectively analyzed after BELD in the non-obese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) groups. Demographic data and surgery-related factors were compared between the two groups. Clinical outcomes were followed up for 12 months after surgery and analyzed for differences. RESULTS: A total of 211 patients were enrolled in this study, and through case-control matching, the data of 115 patients (29, obese group; 86, non-obese group) were analyzed. The two groups showed no significant differences in Oswestry Disability Index, European Quality of Life-5 Dimensions (EQ-5D), and visual analog scale scores measured immediately after BELD and 12 months after surgery. After surgery, back pain, radiating leg pain, and EQ-5D scores improved. However, there was no significant difference in improvement, residual herniated disc, hematoma, or recurrence between the groups. CONCLUSIONS: Obese patients who underwent BELD for lumbar disc herniation showed no significant difference in clinical and radiologic outcomes compared with non-obese patients.

Operative strategy for tri-malleolar ankle fractures with posteromedial plafond involvement: a review of sixty six cases.

PURPOSE: We aimed to summarize the radiographic and clinical outcomes in various conditions of tri-malleolar ankle fractures (TMFs) with posteromedial (PM) plafond involvement (TMF + PM) and determine the factors affecting their subjective clinical outcomes. METHODS: Radiographic and clinical findings of 66 patients who underwent operative treatment for TMF + PM were retrospectively reviewed. The patients were classified into three groups according to the PM fracture line location. Type I fractures were defined when the PM fracture line extended medially beyond the PM corner of the distal tibia while type II fractures were those in which the PM fracture line was located laterally to the PM corner. Type III fractures were defined as medial malleolar avulsion fractures when the PM fracture integrated into the medial malleolus. Clinical outcomes were evaluated using a subjective rating scale (excellent, good, fair, poor, and bad). Satisfactory results were defined as excellent, good, and fair. Factors affecting satisfactory clinical outcomes were assessed using a binary logistic regression analysis. Independent variables included demographic, fracture-related, and operation-related factors and radiographic measurements at the final follow-up. RESULTS: Satisfactory clinical outcomes were observed in 74.2% of the total patients; of these patients, 75.7% (28/37), 76.5% (13/17), and 66.7% (8/12) had type I, type II, and type III fractures, respectively. The binary logistic regression analysis revealed that age at the time of operation, number of incarcerated fragments (IFs), type of IFs, and postoperative articular step-offs (mm) were related to subjective clinical outcomes (all P < 0.05). A positive value for post-operative articular step-offs represented distal migration of the posterior malleolar fragments. The odds ratios for older age, increased numbers of IFs, rotated IFs, and positive articular step-offs were 0.936, 0.116, 0.020, and 0.295, respectively. CONCLUSION: Because TMF + PM is highly unstable, a delicate approach is needed according to each patient's fracture condition. Although it is best to reduce the fractured articular surface, a negative step-off, rather than a positive step-off, would be more likely recommended if accurate reduction is impossible. This could be applied to manage IFs, especially when the IFs are rotated. Dimpling of the articular surface induced by the removal of a small IF was not related to unsatisfactory clinical outcomes.

Factors influencing postoperative residual diastasis after the operative treatment of acute Lisfranc fracture dislocation.

INTRODUCTION: Clinically, surgeons may frequently encounter residual diastasis between the medial cuneiform and 2nd metatarsal base after the operative treatment of acute Lisfranc fracture dislocations. The purpose of this study was to identify factors influencing postoperative residual diastasis. We specifically focused on the preoperative fracture pattern using 3-dimensional computed tomography (3D-CT). MATERIALS AND METHODS: Radiographic and clinical findings of 66 patients who underwent operative treatment for acute Lisfranc fracture dislocation were reviewed. Patients were grouped according to residual diastasis evaluated by weight-bearing anteroposterior radiograph of the foot at the final follow-up. Residual diastasis was defined as distance between the medial cuneiform and 2nd metatarsal base greater than the distance on the contralateral side by 2 mm or more. Demographic parameters and fracture patterns based on preoperative foot 3D-CT were compared. A paired t test was used to compare continuous numeric parameters, while a Chi-square test was used for the proportional parameters. Statistical significance was set at P value less than 0.05 for all analyses. RESULTS: The mean age at operation, sex, body mass index, and the rate of underlying diabetes were not significantly different between the two groups (P > 0.05 each). Preoperative foot 3D-CT evaluation showed that the rate of large (> 25% of 2nd tarsometatarsal joint involvement), displaced (> 2 mm) fracture fragments on the plantar side of the 2nd metatarsal base was more pronounced in the group with residual diastasis (P = 0.001), while medial wall avulsion of the 2nd metatarsal base was more frequent in the group without residual diastasis (P = 0.001). CONCLUSIONS: While treating acute Lisfranc injuries, surgeons should be aware of the presence of a 2nd metatarsal base plantar fracture. A dorsoplantar inter-fragmentary fixation can be considered if the fragment is large and displaced.

Accuracy of the Tibial Component Alignment by Extramedullary System Using Simple Radiographic References in Total Knee Arthroplasty.

Background and Objectives: The tibial component alignment is an important issue for the longevity of total knee arthroplasty (TKA). The purpose of our study was to investigate the usefulness of proximal tibial references determined by pre-operative radiography and intraoperative C-arm-guided hip and ankle center marking for the extramedullary guided tibial cut in mild (<10°) and severe (≥10°) varus knee TKA. Materials and Methods: A total of 150 consecutive patients (220 cases) who underwent total knee arthroplasty who were recruited from July 2011 to April 2017 were reviewed retrospectively. Before surgery, the proximal tibial reference point and medio-lateral cut thickness difference were identified. Then, hip and ankle centers were checked using a C-arm intensifier intraoperatively. The hip−knee−ankle (HKA) alignment and medial proximal tibial angle (MPTA) were assessed pre-operatively and post-operatively. More than 3° varus or valgus of HKA alignment or tibial component angle was defined as an outlier. Results: Mean follow-up duration was 26.9 months. Among 220 cases, 111 cases are classified as mild varus group and 109 cases are classified as severe varus group. The HKA alignment is significantly improved (p < 0.001). The average tibial component angle after surgery is 90.1°. A total of 21 cases (9.5%) and 3 cases (1.4%) are classified as outliers of HKA alignment and MPTA, respectively. Among MPTA outliers, one case is in the mild varus group and two cases are in the in severe varus group (p = 0.62). Conclusion: Measurement of proximal tibial radiographic references and checking the C-arm-guided intraoperative hip and ankle center could be helpful to obtain the favorable coronal position of the tibial component in the extramedullary guided tibial cut.