Lysine-homologue substitution: Impact on antimicrobial activity and proteolytic stability of cationic stapled heptapeptides.

Numerous natural antimicrobial peptides (AMPs) exhibit a cationic amphipathic helical conformation, wherein cationic amino acids, such as lysine and arginine, play pivotal roles in antimicrobial activity by aiding initial attraction to negatively charged bacterial membranes. Expanding on our previous work, which introduced a de novo design of amphipathic helices within cationic heptapeptides using an 'all-hydrocarbon peptide stapling' approach, we investigated the impact of lysine-homologue substitution on helix formation, antimicrobial activity, hemolytic activity, and proteolytic stability of these novel AMPs. Our results demonstrate that substituting lysine with ornithine enhances both the antimicrobial activity and proteolytic stability of the stapled heptapeptide AMP series, while maintaining low hemolytic activity. This finding underscores lysine-homologue substitution as a valuable strategy for optimizing the therapeutic potential of diverse cationic AMPs.

Real-world Nationwide Outcomes of Minimally Invasive Surgery for Advanced Gastric Cancer Based on Korean Gastric Cancer Association-Led Survey.

PURPOSE: The study aimed to investigate real-world surgical outcomes of minimally invasive surgery (MIS) for advanced gastric cancer using Korean Gastric Cancer Association (KGCA)-led nationwide data. MATERIALS AND METHODS: A nationwide survey of patients who underwent surgical treatment for gastric cancer in 2019 was conducted by the KGCA. A total of 14,076 patients from 68 institutions underwent surgery, and 4,953 patients diagnosed with pathological stages IB-III gastric cancer were included. Among them, 1,689 patients who underwent MIS (MIS group) and 1,689 who underwent the open approach (open group) were matched using propensity score in a 1:1 ratio. Surgical outcomes were compared, and multivariate analysis was performed to identify the independent factors for overall morbidity. RESULTS: The MIS group had a lower proportion of D2 lymphadenectomy, total omentectomy, and combined resection. However, the number of harvested lymph nodes was higher in the MIS group. Better surgical outcomes, including less blood loss and shorter hospital stay, were observed in the MIS group, and the overall morbidity rate was significantly lower in the MIS group (17.5% vs. 21.9%, P=0.001). The mortality rates did not differ significantly between the 2 groups. In the multivariate analysis, the minimally invasive approach was a significant protective factor against overall morbidity (odds ratio, 0.799; P=0.006). CONCLUSIONS: Based on the Korean nationwide data, MIS for stage IB-III gastric cancer had better short-term outcomes than the open approach, including lower rates of wound complications, intra-abdominal abscesses, and cardiac problems.

Comparative Short-Term Outcomes of Femoral Neck System (FNS) and Cannulated Screw Fixation in Patients with Femoral Neck Fractures: A Multicenter Study.

Background: Femoral neck fractures need to be treated in their early stages with accurate reduction and stable fixation to reduce complications. The authors compared the early radiologic outcomes of femoral neck fractures treated with the recently introduced Femoral Neck System (FNS, Depuy-Synthes) with conventional cannulated screws (CS) in a multicenter design. Furthermore, the factors associated with early failure after FNS were analyzed. Methods: The FNS group included 40 patients treated between June 2019 and January 2020, and the CS group included 65 patients treated between January 2015 and May 2019. The operation was performed in 3 university hospitals. Patient demographics, fracture classification, postoperative reduction quality, sliding distance of FNS or CS, union and time to union, and complication rates were examined. Logistic regression analysis was performed on candidate factors for early failure of the FNS group. Results: The FNS group had a 90% union rate and a mean time to union of 4.4 months, while the CS group had similar results with an 83.1% union rate and a mean time to union of 5.1 months. In the subgroup analysis of Pauwels type III fractures, the union rates were 75.0% and 58.8% in the FNS and CS groups, respectively, and the time to union was significantly shorter in the FNS group with 4.8 months compared to 6.8 months in the CS group. Early failure rate within 6 months of FNS fixation was observed to be 10%, which included 3 reduction failures and 1 excessive sliding with a broken implant. Risk factors for early failure after FNS were identified as displaced fractures (Garden classification type III or IV), poor reduction quality, longer tip-apex distance, greater sliding distance, and 1-hole implants, of which sliding distance was the only significant risk factor in multivariate analysis. Conclusions: In femoral neck fractures, FNS and CS did not show significant differences for short-term radiologic results. FNS resulted in shorter operative time than cannulated screw fixation and favorable outcomes in Pauwels type III femoral neck fractures. The FNS could be considered a reliable and safe alternative to CS when treating femoral neck fractures.

Comparative study of retrograde intramedullary nailing versus locking extramedullary plating in complete articular fractures with metaphyseal comminution of the distal femur.

INTRODUCTION: Fractures of the distal femur with metaphyseal comminution and complete intra-articular involvement (AO/OTA classifications 33C2 and 33C3) present challenges for reduction and fixation. However, an optimal fixation method remains unknown. This study aimed to compare the clinical and radiographic outcomes of locking extramedullary plating (LEP) and retrograde intramedullary nailing (RIN) for complete distal femoral intra-articular fractures with metaphyseal comminution. MATERIALS AND METHODS: Between January 2016 and May 2022, 80 patients (45 men and 35 women; average age, 56.7 years) diagnosed with AO/OTA 33C2 and 33C3 were treated with either LEP or RIN and followed up for at least one year. Post-operative evaluations included radiographic assessments of bone union rate, timing, and alignment. Clinically, the knee joint range of motion (ROM), lower extremity functional scale (LEFS), and Kellgren and Lawrence (KL) grade were analyzed. The complications were also compared. RESULTS: 36 underwent LEP and 44 underwent RIN. Bone union was observed in 69.4% and 63.6% of the patients in the LEP and RIN groups, respectively (p = 0.64). The average union time was 6.9 months for the LEP group and 6.6 months for the RIN group (p = 0.51). A tendency toward varus deformity was observed in the RIN group, although the difference was not statistically significant. No significant differences were observed in knee ROM, LEFS, or KL grade. Complications included non-union (33.8%; RIN, 11; LEP, 16), varus deformity (5%; RIN, 4; LEP, 0), infection (1.3%; RIN, 0; LEP, 1), heterotrophic ossification (1.3%; RIN, 0; LEP, 1), and wound dehiscence (2.5%; RIN, 2; LEP, 0). CONCLUSIONS: The surgical fixation methods, RIN and LEP, for complete distal femoral intra-articular fractures with metaphyseal comminution showed similar clinical and radiological outcomes. However, regardless of the type of fixation device used, there was a reduced rate of bone union owing to high energy and a less favorable prognosis.

Streptomyces tagetis sp. nov., a chromomycin producing bacteria isolated from the roots of Tagetes patula.

A novel halotolerant actinobacterium, designated as RG38T, capable of producing black extracellular melanin pigment on SP2 agar, was isolated from the roots of Tagetes patula. Comparative analysis of the 16S rRNA gene sequence revealed the highest similarity to Streptomyces collinus NBRC 12759T (99.3%). Phylogenetic analysis showed that strain RG38T clustered within the genus Streptomyces forming a monophyletic cluster with its close relatives. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and amino-acid identity (AAI) values between strain RG38T and related species within the genus Streptomyces were below the standard threshold for prokaryotic species delineation. The DNA G + C content of the strain RG38T was determined to be 73.3%. The genome size measured 7,150,598 bp comprising 17 contigs and encompassed 6,053 protein coding genes. AntiSMASH analysis of the whole genome revealed 35 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites. Among these clusters, two gene clusters exhibited 100% similarity to the chromomycin A3, albaflavenone, and anthracimycin, respectively. These compounds were reported to possess significant anticancer and antibacterial activities. LC-MS-based analysis, coupled with further isolation studies, confirmed the production of chromomycins A2 (1), A3 (2), and their derivatives, along with their antibiotic activities. These findings underscore the potential of this novel strain as a novel resource for the discovery of diverse antimicrobial compounds. This study is the first to report an antimicrobial compound producing Streptomyces species isolated from medicinal plant T. patula. Based on a polyphasic study, the strain RG38T isolated from an unexplored habitat with a high potential for new natural products represents a novel species within the genus Streptomyces. Accordingly, we propose the name Streptomyces tagetis sp. nov. for this novel species, with the type strain is RG38T (=KCTC 49624T = TBRC 15113T).

Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb-antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan- 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang-1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san-1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang-1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.

Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial.

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

The relationship between spino-pelvic-hip mobility and quality of life before and after total hip arthroplasty.

INTRODUCTION: Total hip arthroplasty (THA) can significantly improve quality of life (QOL) in patients with hip osteoarthritis. A relationship exists between activity levels and postoperative QOL, but its determinants are not well known. The aim of this work was to investigate the relationship between hip, pelvis and lumbar spine mobility and alignment before and after THA with QOL. MATERIAL AND METHODS: Consecutive patients with hip arthrosis and an indication for THA were included prospectively between July 2019 and December 2020, and they underwent lateral radiographs in free-standing, extension, relaxed- and flexed-seated position. Spinopelvic and hip parameters were measured, as well as their changes between positions to assess hip, pelvis and lumbar spine mobility. Patients were also administered QOL questionnaires. Data were collected preoperatively and 6 and 12 months postoperatively. RESULTS: Seventy patients were included; QOL significantly increased 6 months after THA (from 18 [10; 27] to 61 [48; 72], p < 0.001). QOL further increased by 10 points or more after 6 months in 18% of patients, while it decreased in 16%. The latter showed higher pelvic range of motion (between flexion and extension) than the former. CONCLUSIONS: This study confirmed that QOL is significantly improved by THA, and that spinopelvic alignment and function can play a role. Future work should elucidate how to better predict postoperative QOL from preoperative patient characteristics to improve patient treatment and establish early postoperative physical therapy for patients who could benefit from postoperative improvement of activity-related QOL.

An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Real-World Compliance of Surgical Treatment According to the Korean Gastric Cancer Guideline 2018: Evaluation From the Nationwide Survey Data 2019 in Korea.

PURPOSE: This study evaluated real-world compliance with surgical treatment according to Korea's gastric cancer treatment guidelines. MATERIALS AND METHODS: The 2018 Korean Gastric Cancer Treatment Guidelines were evaluated using the 2019 national survey data for surgically treated gastric cancer based on postoperative pathological results in Korea. In addition, the changes in surgical treatments in 2019 were compared with those in the 2014 national survey data implemented before the publication of the guidelines in 2018. The compliance rate was evaluated according to the algorithm recommended in the 2018 Korean guidelines. RESULTS: The overall compliance rates in 2019 were 83% for gastric resection extent, 87% for lymph node dissection, 100% for surgical approach, and 83% for adjuvant chemotherapy, similar to 2014. Among patients with pathologic stages IB, II, and III disease who underwent total gastrectomy, the incidence of splenectomy was 8.08%, a practice not recommended by the guidelines. The survey findings revealed that 48.66% of the patients who underwent gastrectomy had pathological stage IV disease, which was not recommended by the 2019 guidelines. Compared to that in 2014, the rate of gastrectomy in stage IV patients was 54.53% in 2014. Compliance rates were similar across all regions of Korea, except for gastrectomy in patients with stage IV disease. CONCLUSIONS: Real-world compliance with gastric cancer treatment guidelines was relatively high in Korea.

Long-term Functional and Patient-reported Outcomes Between Intra-corporeal Delta-shaped Gastroduodenostomy and Gastrojejunostomy After Laparoscopic Distal Gastrectomy.

PURPOSE: This study aimed to compare the long-term functional and patient-reported outcomes between intra-corporeal delta-shaped gastroduodenostomy and gastrojejunostomy after laparoscopic distal gastrectomy for gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data from 616 patients who had undergone laparoscopic distal gastrectomy for stage I gastric cancer between January 2015 and September 2020. Among them, 232 patients who had undergone delta-shaped anastomosis and another 232 who had undergone Billroth II anastomosis were matched using propensity scores. Confounding variables included age, sex, body mass index, physical status classification, tumor location, and T classification. Postoperative complications, nutritional outcomes, endoscopic findings, and quality of life (QoL) were compared between the 2 groups. RESULTS: No significant differences in postoperative complications or nutritional parameters between the two groups were observed. Annual endoscopic findings revealed more residual food and less bile reflux in the delta group (P<0.001) than in the Billroth II group. Changes of QoL were significantly different regarding emotional function, insomnia, diarrhea, reflux symptoms, and dry mouth (P=0.007, P=0.002, P=0.013, P=0.001, and P=0.03, respectively). Among them, the delta group had worse insomnia, reflux symptoms, and dry mouth within three months postoperatively. CONCLUSIONS: Long-term nutritional outcomes and QoL were comparable between the delta and Billroth II groups. However, more residual food and worse short-term QoL regarding insomnia, reflux symptoms, and dry mouth were observed in the delta group. Longer fasting time before endoscopic evaluation and short-term symptom management would have been helpful for the delta group.

Effect of Vitamin B12 Replacement Intervals on Clinical Symptoms and Laboratory Findings in Gastric Cancer Patients after Total Gastrectomy.

The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients.

Electrical Performance Analysis of High-Speed Interconnection and Power Delivery Network (PDN) in Low-Loss Glass Substrate-Based Interposers.

In this article, electrical performance analysis of high-speed interconnection and power delivery network (PDN) in low-loss glass substrate-based interposers is conducted considering signal integrity (SI) and power integrity (PI). The low-loss glass substrate is a superior alternative to silicon substrate in terms of high-speed signaling and fabrication yield. However, the low-loss of the substrate is vulnerable to power/ground noise in the PDN since the low-loss property of the substrate cannot suppress the noise naturally. In this article, an in-depth electrical performance analysis is conducted based on various measurements and simulations to fully benefit the advantages of the low-loss glass substrate. First, the fabrication process and test vehicles for the analysis are explained. Using the test vehicles, the electrical performance of the glass interposer's high-speed interconnection is compared with those of silicon and organic interposers. The insertion loss, eye-diagrams, and signal bandwidths of three interposer channels are compared and analyzed based on electromagnetic (EM) and circuit simulations. Also, the electrical performance of the through glass via (TGV) channel is measured and compared with through silicon via (TSV) channel. The high-speed interconnection of the glass interposer showed better performance for most of the parameters which is more suitable for maintaining the SI. Even though the low-loss of the glass substrate ensured the SI, power/ground noise issues in the PDN must be analyzed and solved. In this article, various cases inducing the power/ground noise in the PDN are considered, simulated, and measured. To solve the issues, ground TGV design and electromagnetic bandgap (EBG) design are proposed for an efficient broadband suppression of the noise generated in the glass interposer PDN.

Fibular Fixation in Same-Level Distal Third Tibiofibular Fractures: Is Fibular Fracture Regarded as a Secondary Importance?

Background: Although most studies focused on the alignment or union of the tibia in same-level distal third tibiofibular fractures, the outcome of a concomitant fibular fracture is generally regarded as being of secondary importance in the literature. This study aimed to assess the outcomes of fibular fractures in same-level distal third tibiofibular fractures. Methods: In this retrospective study, we enrolled 111 patients with same-level distal third tibiofibular fractures treated at our institute between January 2016 and August 2020. Tibial fractures were stabilized with intramedullary nailing, and the cases were divided into two groups based on whether they additionally underwent fibular fixation (group 1, 57 cases) or not (group 2, 54 cases). Clinical and radiographic outcomes were used for the evaluation of tibial and fibular alignments, union of the tibia and fibula, number of interlocking screws in the distal tibial fragment, range of motion of the ankle joint, and complications. Results: No statistically significant differences in the tibial union rate or mean tibial alignment were observed between the two groups on either the immediate postoperative or final radiographs. The fibular union rate in group 1 was significantly higher than that in group 2 (fibular nonunion, 0 vs. 15; p < 0.001). Statistically significant differences in fibular displacement were observed on immediate postoperative radiographs between patients with fibular union and those without it. At the final follow-up, the mean range of ankle motion and lower extremity functional scale scores did not differ between the two groups. Conclusions: Regardless of whether fibular fixation was performed, the overall tibial alignment with intramedullary nailing was well restored and the union rate of the tibia was comparable in the two groups. Fibular nonunion is not uncommon in unfixed fibula fractures. Displacement of the fibula as seen on immediate postoperative radiographs was related to fibular nonunion.

Clinical and radiographic outcomes of negative pressure wound therapy combined with polymethylmethacrylate sealant for wound management of Gustilo type III open tibia fractures.

OBJECTIVE: This study aimed to introduce a new wound management method combining negative pressure wound therapy and polymethylmethacrylate sealant for Gustilo type III open tibia fractures and to evaluate its clinical outcomes. METHODS: Among 186 patients who visited our institution for the treatment of open tibia fractures between January 2016 and December 2019, 20 male patients who sustained Gustilo type III open tibia fractures and were compelled to undergo delayed flap coverage using negative pressure wound therapy combined with polymethylmethacrylate sealant due to initial critical condition were enrolled in this study. We retrospectively investigated patients' demographics, interval between the injury and flap coverage, number of negative pressure wound therapy changes, flap survival, bone union time, and infection-induced complications. RESULTS: The mean interval from injury until flap coverage was 27.8 (range, 8-63) days. Most soft-tissue defects were reconstructed using free flaps (14/20, 70%); the anterolateral thigh flap was the most frequently used flap (12/20, 60%) in this study. Among 20 flaps trans- ferred, 16 flaps (80%) survived uneventfully, 1 flap (5%) developed partial necrosis, and 3 flaps (15%) failed. The mean follow-up period was 22.7 (range, 12- 43) months. A total of 17 patients (85%) achieved tibia fracture union. The mean bone union time was 31 (range, 12-81) weeks. With regard to infection-induced complications, 3 patients (15%) developed osteomyelitis and no patient showed superficial surgical site infection. CONCLUSION: Combination therapy using negative pressure wound therapy and polymethylmethacrylate sealant serves as a useful and reliable therapeutic strategy for wound management of Gustilo type III open tibia fractures, especially when delayed soft-tissue recon- struction is unavoidable. Corresponding author: Yoo Joon Sur yoojoon@catholic.ac.kr Content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

A Statistical Approach for Signal and Power Integrity Co-Design in High-Speed Interconnects Considering Non-Linear Power/Ground Noise and Bit-Patterns.

In this article, a novel statistical approach is proposed and applied to co-design signal and power integrity (SI/PI) in high-speed interconnects considering the non-linear power/ground noise generated by parallel buffers and bit-patterns. With increased data rates and decreased operating voltages, the allowed noise margin in high-speed interconnects is continuously reduced, and this trend requires SI/PI co-design. Specifically, non-linear power/ground noise associated with simultaneous switching circuits sharing a power delivery network (PDN) and bit-patterns must be carefully considered during the interconnects' design and analysis phase. In many cases, conventional electromagnetic (EM) and transient circuit simulators require heavy computational resources or even fail to deliver an accurate result. The proposed statistical method estimates the statistical eye-diagram in the high-speed interconnect considering power/ground noise and bit-patterns such as data bus inversion (DBI) coding. The accuracy and computational efficiency of the proposed method are validated by comparing the result with HSPICE transient simulation result. The proposed method is also compared with conventional statistical methods, such as peak distortion analysis (PDA) and statistical channel simulation in the transient simulator. Lastly, the proposed method is applied to the SI/PI co-design and co-analysis in the high bandwidth memory (HBM) interposer channel. Impacts of decoupling capacitors on hierarchical PDN impedance, statistical eye-diagram of the HBM channel, and bit error rate (BER) Bathtub curves are summarized. Finally, the BER eye-diagram is derived from the estimated statistical eye-diagram for timing and voltage analysis. The impacts of hierarchical PDN design and bit-patterns on SI/PI are discussed.

Efficacy of ferric carboxymaltose in iron deficiency anemia patients scheduled for pancreaticoduodenectomy.

Purpose: Perioperative transfusion is reported to be an independent risk factor not only for postoperative complications but also for early recurrence of periampullary carcinoma after pancreaticoduodenectomy (PD). The purpose of this study was to evaluate the safety and efficacy of ferric carboxymaltose (FCM) in reducing the need for perioperative transfusion in iron deficiency anemia patients scheduled for PD. Methods: Twenty-two male patients (hemoglobin [Hb] 7 to <13 g/dL) and 18 female patients (Hb 7 to <12 g/dL) were enrolled in the study group and administered FCM 1-3 weeks before PD. The perioperative transfusion rate was the primary endpoint; morbidity, length of postoperative hospital stay, change in hematological parameters after FCM injection, and adverse effects of FCM were also investigated. Results: The perioperative transfusion rate of the study group was 22.5% (9 of 40). Hb level was significantly higher on the day of the operation compared to baseline (P < 0.001). Levels of Hb, transferrin saturation, and ferritin were higher at the follow-up compared to baseline (P = 0.008, P = 0.033, and P < 0.001, respectively). Conclusions: FCM administration was associated with a reduced need for perioperative transfusion and can safely stabilize hematological parameters.

Estimation of Cooling Rate of High-Strength Thick Plate Steel during Water Quenching Based on a Dilatometric Experiment.

The microstructure and hardness along the thickness direction of a water-quenched, high-strength thick plate with a thickness of 40 mm were investigated with three specimens from the thick plate: surface, 1/4t, and 1/2t (center) thickness, and the phase transformation behavior of the thick plate according to the cooling rate was analyzed through dilatometric experiments. Finally, the cooling rate for each thickness of the thick plate was estimated by comparing the microstructure and hardness of the thick plate along with the thickness with those of the dilatometric specimens. Martensite microstructure was observed on the surface of the water-quenched thick plate due to the fast cooling rate. On the other hand, an inhomogeneous microstructure was transformed inside the thick plate due to the relatively slow cooling rate and central segregation of Mn. A small fraction of bainite was shown at 1/4t thickness. A banded microstructure with martensite and bainite resulting from Mn segregation was developed at 1/2t; that is, the full martensite microstructure was transformed in the Mn-enriched area even at a slow cooling rate due to high hardenability, but a bainite microstructure was formed in the Mn-depleted area owing to relatively low hardenability. A portion of martensite with fine cementite at the surface and 1/4t was identified as auto-tempered martensite with a Bagaryatskii orientation relationship between the ferrite matrix and cementite. The microstructure and hardness as well as dilatation were investigated at various cooling rates through a dilatometric experiment, and a continuous cooling transformation (CCT) diagram was finally presented for the thick plate. Comparing the microstructure and hardness at the surface, 1/4t, and 1/2t of the thick plate with those of dilatometric specimens cooled at various cooling rates, it was estimated that the surface of the thick plate was cooled at more than 20 °C/s, whereas the 1/4t region was cooled at approximately 5~10 °C/s during water quenching. Despite the difficulty in estimation of the cooling rate of 1/2t due to the banded structure, the cooling rate of 1/2t was estimated between 3 and 5 °C/s based on the results of an Mn-depleted zone.

Development of a Novel ATP Bioluminescence Assay Based on Engineered Probiotic Saccharomyces boulardii Expressing Firefly Luciferase.

Quantitative analysis of adenosine triphosphate (ATP) has been widely used as a diagnostic tool in the food and medical industries. Particularly, the pathogenesis of a few diseases including inflammatory bowel disease (IBD) is closely related to high ATP concentrations. A bioluminescent D-luciferin/luciferase system, which includes a luciferase (FLuc) from the firefly Photinus pyralis as a key component, is the most commonly used method for the detection and quantification of ATP. Here, instead of isolating FLuc produced in recombinant Escherichia coli, we aimed to develop a whole-cell biocatalyst system that does not require extraction and purification of FLuc. To this end, the gene coding for FLuc was introduced into the genome of probiotic Saccharomyces boulardii using the CRISPR/Cas9-based genome editing system. The linear relationship (r2 = 0.9561) between ATP levels and bioluminescence generated from the engineered S. boulardii expressing FLuc was observed in vitro. To explore the feasibility of using the engineered S. boulardii expressing FLuc as a whole-cell biosensor to detect inflammation biomarker (i.e., ATP) in the gut, a colitis mouse model was established using dextran sodium sulfate as a colitogenic compound. Our findings demonstrated that the whole-cell biosensor can detect elevated ATP levels during gut inflammation in mice. Therefore, the simple and powerful method developed herein could be applied for non-invasive IBD diagnosis.