Search Results (11)

Appropriate suture tension is a key factor in successful meniscal repair. This study aimed to clarify the appropriate value of meniscal stabilization with suture repair based on a probing procedure for healthy porcine menisci and a novel meniscal scaffold. After evaluating the reliability of the probing sensor, meniscal vertical tear and partial meniscectomy models were developed, in which suture repair and meniscal scaffold implantation were performed at suture intervals ranging between 20 and 2.5 mm. The residence forces at each interval were evaluated using a probing sensor. Moreover, a tensile test was conducted to evaluate the displacement and presence or absence of gaps. We found that normal and meniscal scaffolds should be fixed within 5 mm of suture interval. The probing residence forces required were at least 1.0 N for vertical tears and 3.0 N for meniscal scaffolds. These findings may be taken into consideration to reduce suture failure following meniscal tear repair and stabilizing meniscal scaffold fixation. Full article

With only four classes of antifungal drugs available for the treatment of invasive systemic fungal infections, the number of resistant fungi is increasing, highlighting the urgent need for novel antifungal drugs. Ergosterol, an essential component of cell membranes, and its synthetic pathway have been targeted for antifungal drug development. Sterol-C4-methyl monooxygenase (Erg25p), which is a greater essential target than that of existing drugs, represents a promising drug target. However, the development of antifungal drugs must consider potential side effects, emphasizing the importance of evaluating their selective toxicity against fungi. In this study, we knocked in ERG25 of Candida glabrata and its human ortholog, SC4MOL, in ERG25-deleted Saccharomyces cerevisiae. Utilizing these strains, we evaluated 1181-0519, an Erg25p inhibitor, that exhibited selective toxicity against the C. glabrata ERG25 knock-in strain. Furthermore, 1181-0519 demonstrated broad-spectrum antifungal activity against pathogenic Candida species, including Candida auris. The approach of utilizing a gene that is functionally conserved between yeast and humans and subsequently screening for molecular target drugs enables the identification of selective inhibitors for both species. Full article

It has been reported that high intensity in the hepatobiliary (HB) phase of Gd-EOB-DTPA-enhanced MRI (EOB-MRI) is associated with an immune-cold microenvironment in HCC. The aim of this study is to reveal whether non-high-intensity HCCs are homogeneous with respect to the immune microenvironment and to investigate the predictive ability of EOB-MRI for the response to atezolizumab + bevacizumab therapy (Atezo/Bev). The association between differences in stepwise signal intensity of HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment was investigated in 65 HCC patients (cohort 1). The association between EOB-MRI and the therapeutic effect of Atezo/Bev was evaluated in the Atezo/Bev cohort (60 patients in cohort 2). The proportion of HCCs having CTNNB1 mutations and classified as Chiang CTNNB1 and Hoshida S3 was high in the high-intensity HB-phase group. Infiltration of tumor-associated macrophages (TAM) and regulatory T-lymphocytes (Treg) was characteristic of the high-intensity and low-intensity groups, respectively. Although EOB-MRI could not predict the response to Atezo/Bev treatment, our results demonstrate that EOB-MRI could serve as a surrogate marker predicting the immune microenvironment. This suggests that Atezo/Bev treatment can be selected regardless of signal intensity in the EOB-MRI HB phase. Full article

Mitochondrial dysfunction or morphological abnormalities in human pathogenic fungi are known to contribute to azole resistance; however, the underlying molecular mechanisms are unknown. In this study, we investigated the link between mitochondrial morphology and azole resistance in Candida glabrata, which is the second most common cause of human candidiasis worldwide. The ER-mitochondrial encounter structure (ERMES) complex is thought to play an important role in the mitochondrial dynamics necessary for mitochondria to maintain their function. Of the five components of the ERMES complex, deletion of GEM1 increased azole resistance. Gem1 is a GTPase that regulates the ERMES complex activity. Point mutations in GEM1 GTPase domains were sufficient to confer azole resistance. The cells lacking GEM1 displayed abnormalities in mitochondrial morphology, increased mtROS levels, and increased expression of azole drug efflux pumps encoded by CDR1 and CDR2. Interestingly, treatment with N-acetylcysteine (NAC), an antioxidant, reduced ROS production and the expression of CDR1 in Δgem1 cells. Altogether, the absence of Gem1 activity caused an increase in mitochondrial ROS concentration, leading to Pdr1-dependent upregulation of the drug efflux pump Cdr1, resulting in azole resistance. Full article

Upper extremity dysfunction after stroke affects quality of life. Focusing on the shoulder joint, we investigated the safety and effectiveness of rehabilitation using a shoulder joint hybrid assistive limb (HAL). Eight patients with chronic stroke and upper extremity functional disability were enrolled and used a shoulder joint HAL, which assisted shoulder movement based on the user’s intention, through myoelectric activation of the shoulder flexor. Ten training sessions of 30–40 min each were performed to assist voluntary movement of upper limb elevation on the affected side through triggering the deltoid muscle. All patients completed the interventions without shoulder pain. Surface electromyography evaluation indicated post-intervention improvement in coordinated movement of the affected upper extremity. Significant improvements in voluntary and passive shoulder joint range of motion were obtained after the intervention, suggesting improvement in shoulder muscle strength. A significant decrease in the modified Ashworth scale and improvements in functional scores in the upper limb were also observed. Along with safe use for our study patients, the shoulder HAL provided appropriate motor learning benefits. Improvements in shoulder joint function and whole upper limb function were observed, suggesting that HAL could be an optimal treatment method. Full article

Mobile magnetic resonance imaging (MRI) using a car is a recent advancement in imaging technology. Specifically, a car-mounted mobile MRI system is expected to be used for medical check-ups; however, this is still in the research stage. This study demonstrated the practicality of a small car-mounted mobile MRI in on-field screening for osteochondritis dissecans (OCD) of the humeral capitellum. In the primary check-up, we screened the throwing elbows of 151 young baseball players using mobile MRI and ultrasonography. We definitively diagnosed OCD at the secondary check-up using X-ray photography and computed tomography or MRI. We investigated the sensitivity and specificity of mobile MRI and ultrasonography for OCD. Six patients were diagnosed with OCD. The sensitivity was 83.3% for mobile MRI and 66.7% for ultrasonography, with specificity of 99.3% vs. 100%, respectively. One patient was detected using ultrasonography but was missed by mobile MRI due to poor imaging quality at the first medical check-up. Following this false-negative case, we replaced a damaged radio frequency coil to improve the image quality, and the mobile MRI could detect all subsequent OCD cases. Two patients were diagnosed by mobile MRI only; ultrasonography missed cases lacking subchondral bone irregularity, such as a healing case, and an early-stage case. Mobile MRI could screen for OCD from the very early stages through the healing process and is therefore a practical tool for on-field screening. Full article

Background Relevant criteria for total hip arthroplasty (THA) planning have been introduced in the literature which include the hip range of motion, bony coverage, anterior cup overhang, leg length discrepancy, edge loading risk, and wear. The optimal implant design and alignment depends on the patient’s anatomy and patient-specific functional parameters such as the pelvic tilt. The approaches proposed in literature often consider one or more criteria for THA planning. but to the best of our knowledge none of them follow an integrated approach including all criteria for the definition of a patient-specific combined target zone (PSCTZ). Questions/purposes (1) How can we calculate suitable THA implant and implantation parameters for a specific patient considering all relevant criteria? (2) Are the resulting target zones in the range of conventional safe zones? (3) Do patients who fulfil these combined criteria have a better outcome score? Methods A method is presented that calculates individual target zones based on the morphology, range of motion and load acting on the hip joint and merges them into the PSCTZ. In a retrospective analysis of 198 THA patients, it was calculated whether the patients were inside or outside the Lewinnek safe zone, Dorr combined anteversion range and PSCTZ. The postoperative Harris Hip Scores (HHS) between insiders and outsiders were compared. Results 11 patients were inside the PSCTZ. Patients inside and outside the PSCTZ showed no significant difference in the HHS. However, a significant higher HHS was observed for the insiders of two of the three sub-target zones incorporated in the PSCTZ. By combining the sub-target zones in the PSCTZ, all PSCTZ insiders except one had an HHS higher than 90. Conclusions The results might suggest that, for a prosthesis implanted in the PSCTZ a low outcome score of the patient is less likely than using the conventional safe zones by Lewinnek and Dorr. For future studies, a larger cohort of patients inside the PSCTZ is needed which can only be achieved if the cases are planned prospectively with the method introduced in this paper. Clinical Relevance The method presented in this paper could help the surgeon combining multiple different criteria during THA planning and find the suitable implant design and alignment for a specific patient. Full article

Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism. Full article

Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts. Full article

Photoaffinity labeling is a reliable analytical method for biological functional analysis. Three major photophores—aryl azide, benzophenone and trifluoromethyldiazirine—are utilized in analysis. Photophore-bearing l-phenylalanine derivatives, which are used for biological functional analysis, were inoculated into a Klebsiella sp. isolated from the rhizosphere of a wild dipterocarp sapling in Central Kalimantan, Indonesia, under nitrogen-limiting conditions. The proportions of metabolites were quite distinct for each photophore. These results indicated that photophores affected substrate recognition in rhizobacterial metabolic pathways, and differential photoaffinity labeling could be achieved using different photophore-containing l-phenylalanine derivatives. Full article