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1.
J Orthop Res ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741241

RESUMO

Polymerase chain reaction (PCR)-based genetic diagnosis is a rapid and sensitive method to diagnose periprosthetic joint infection (PJI). DNA extraction using bead beating is an effective method for collecting bacterial genes in Gram-positive bacteria. We compared the detection accuracy between the conventional and bead-beating DNA extraction assay. The detection rate improved from 86.7% using the conventional method to 95.6% using the bead-beating. Our results suggest that bead-beating during DNA extraction can improve the accuracy of PCR-based genetic diagnosis of PJI.

2.
Regen Ther ; 25: 264-272, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38304617

RESUMO

Introduction: To ensure the sterility of cell products that cannot undergo conventional sterilization processes, it is imperative to establish and maintain a clean room environment, regulated through environmental monitoring, including particle counts. Nevertheless, the impact of particles generated by operators as potential contaminants remains uncertain. Thus, in this study, we conducted an accelerated test to assess the correlation between particles generated by operators and airborne bacteria, utilizing biosafety cabinets within a typical laboratory setting. These biosafety cabinets create a controlled environment with air conditioning and high-efficiency particulate air (HEPA) filters, offering fundamental data relevant to cell production. Materials and methods: We conducted a simulation followed by real-time experiments involving human operations to explore the quantity of particles, particle sizes, and the percentage of bacteria within these particles. This investigation focused on conditions with heightened particle generation from operators within a biosafety cabinet. The experiment was conducted on operators wearing textile and non-woven dustless clothing within biosafety cabinets. It entailed tapping the upper arms for a duration of 2 min. Results: Observations under biosafety cabinet-off conditions revealed the presence of various particles and falling bacteria in textile clothing. In contrast, no particles or falling bacteria were detected in operators wearing dustless clothing within biosafety cabinets. Notably, a correlation between 5 µm particles and colony-forming units in textile clothing was identified through this analysis. The ratio of falling bacteria to the total number of particles within the biosafety cabinet was 0.8 ± 0.5 % for textile clothing, while it was significantly lower at 0.04 ± 0.2 % for dustless clothing. Conclusion: This study demonstrated that the number of particles and falling bacteria varied depending on the type of clothing and that quantitative data could be used to identify risks and provide basic data for operator education and evidence-based control methods in aseptic manufacturing areas. Although, this study aims to serve as an accelerated test operating under worst-case conditions, the results need to make sure the study range in general research.

3.
JCI Insight ; 9(5)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38261406

RESUMO

Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages to promote allograft inflammation. However, factors that drive their differentiation to inflammatory macrophages are not understood. Here, we show that the receptor tyrosine kinase AXL was a key driver of early intragraft differentiation of recipient infiltrating monocytes to inflammatory macrophages in the presence of allogeneic stimulation and cell-to-cell contact. In this context, the differentiated inflammatory macrophages were capable of efficient alloantigen presentation and allostimulation of T cells of the indirect pathway. Consequently, early and transient AXL inhibition with the pharmacological inhibitor bemcentinib resulted in a profound reduction of initial allograft inflammation and a significant prolongation of allograft survival in a murine heart transplant model. Our results support further investigation of AXL inhibition as part of an induction regimen for transplantation.


Assuntos
Macrófagos , Monócitos , Camundongos , Animais , Transplante Homólogo , Aloenxertos , Inflamação
4.
J Orthop Sci ; 29(2): 675-680, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36732127

RESUMO

BACKGROUND: The Japanese Orthopedic Association launched the Japanese Orthopedic Association National Registry (JOANR), Japan's first large-scale nationwide musculoskeletal disease registry, in 2020. The World Health Organization released the International Classification of Health Interventions (ICHI) Beta-3 version in the same year. This concurrence served as an impetus to examine the relationship between domestic and international classification for orthopedic interventions. Our objective was to evaluate the possibility of utilizing JOANR for international comparison and the potential usage of ICHI in the domestic medical fee reimbursement system. This study is a novel attempt at mapping a domestic orthopedic scheme to the ICHI. METHODS: We mapped 149 codes out of 581 orthopedic surgical codes, on JOANR's registration form, to the ICHI, and then classified the nature of JOANR codes' relationship, to both ICHI single stem codes and stem codes accompanied by other additional stem codes, extension codes, and International Classification of Diseases for Mortality and Morbidity Statistics (ICD) codes, into five categories: Equivalent (exact match), Narrower (compared to ICHI; can be smoothly incorporated into ICHI), Broader (compared to ICHI), Slipped (combination of both Narrower and Broader), and None (no appropriate code). Finally, debatable issues that arose during the mapping operation were noted. RESULTS: The domestic codes' relationship to ICHI single stem code by category were Equivalent: 27 (18.1%) and Narrower: 65 (43.6%), respectively. Further, the rate of Equivalent rose to 120 (80.5%) on adding other stem codes, extension codes, and ICD codes. Additionally, certain domestic titles, which were unsuitable for classification as they included diagnostic information, and arthroscopic surgeries without corresponding ICHI codes, were recoded. CONCLUSIONS: JOANR can be converted to an international comparison standard via ICHI to a certain extent, and ICHI accompanied by ICD codes has potential for deployment in the domestic medical fee reimbursement system.


Assuntos
Doenças Musculoesqueléticas , Ortopedia , Humanos , Japão/epidemiologia , Classificação Internacional de Doenças , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/cirurgia , Sistema de Registros
5.
J Clin Med ; 12(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38137581

RESUMO

Periprosthetic joint infection (PJI) is one of the most intractable orthopedic diseases, partly because of the difficulty in differentiating septic from aseptic conditions. We aimed to evaluate and consolidate the diagnostic accuracy of the quantitative assessment of serum albumin (Alb), globulin (Glb), and albumin-globulin ratio (AGR), alone or in combination with the inflammatory marker, C-reactive protein (CRP), for PJI. We searched the PubMed, CINAHL, and Cochrane Library databases for studies that quantitatively measured Alb, Glb, or AGR for the diagnosis of PJI up until the 30 April 2023. A total of 2339 patients were included from 10 studies, including 845 patients with a definitive diagnosis of PJI and 1494 with non-PJI. The pooled sensitivity, specificity, and area under the curve (AUC) in the summary receiver-operating characteristic curve were as follows: 0.625, 0.732, and 0.715 for Alb; 0.815, 0.857, and 0.887 for Glb; 0.753, 0.757, and 0.875 for AGR; 0.788, 0.837, and 0.876 for CRP; 0.879, 0.890, and 0.917 for the CRP-Alb ratio; and 0.845, 0.855, and 0.908 for the CRP-AGR ratio. Serum Alb, Glb, and AGR levels are feasible and accurate diagnostic markers for PJI, and the combination of these markers with CRP levels may potentially improve preoperative serum diagnostic accuracy. Future prospective studies are required to verify these findings because of the small numbers of included studies.

6.
J Orthop Sci ; 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37985296

RESUMO

BACKGROUND: Osteoporosis is a global issue with a worldwide prevalence of 18.3%, and the presence of coexisting fragility fractures can reduce the survival rate by approximately 20%. In Japan, the prevalence of osteoporosis is estimated to be 12.8 million, and the annual occurrence of hip fractures is approximately 193,400. Remarkably, coexisting hip or spinal fragility fractures caused by slight external force meet the Japanese diagnostic criterion for osteoporosis regardless of bone mineral density. However, only 191 deaths due to osteoporosis were published in 2021 in Japan. With the concern that some cases of hip and spinal fragility fractures were assigned an underlying cause of death of traumatic fracture instead of osteoporosis, this study aimed to elucidate the actual number of deaths due to osteoporosis in Japan. METHODS: We used the data from Japan in 2018. First, the number of deaths due to osteoporosis and hip or spinal fractures was reviewed using published vital statistics. Second, we calculated the number of elderly deaths (age ≥80 years) resulting from hip or spinal fractures caused by falls on the same level using data from approximately 1.4 million annual individual death certificates. Combining the above data, the actual number of deaths due to osteoporosis was estimated. RESULTS: Only 190 deaths due to osteoporosis were reported in the published data. The individual certificate data revealed 3437 elderly deaths due to hip or spinal fractures caused by falls on the same level, which could meet the criteria of osteoporotic fragility fractures. Accordingly, the estimated number of deaths caused by osteoporosis was calculated as 3,627, approximately 19 times the published value. CONCLUSIONS: After researching the individual death certificate data focusing on the coexisting hip or spinal fragility fracture, it was implied that osteoporosis may have a higher mortality rate in Japan than what is published.

7.
Arthroplast Today ; 24: 101245, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38023642

RESUMO

Fungal periprosthetic joint infections are one of the most intractable orthopedic disorders. Continuous local antibiotic perfusion allows direct administration of the antifungal agent micafungin into the local infection area at biofilm-disruptive concentrations, while controlling the dead space in addition to conventional treatment. Although the appropriate use of continuous local antibiotic perfusion requires familiarity with the characteristics of local antibiotic perfusion, it is a versatile treatment modality that can improve the clinical outcomes of fungal periprosthetic joint infection in combination with conventional treatment methods.

8.
J Am Soc Nephrol ; 34(10): 1629-1646, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37545036

RESUMO

SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney protection. The current murine experiments show that IL-1R1 activation in the proximal tubule exacerbates toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorates AKI by restoring VEGFA-dependent endothelial cell viability. Using this information, future delivery strategies can maximize the protective effects of blocking IL-1R1 while mitigating unwanted actions of IL-1R1 manipulation. BACKGROUND: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. IL-1R1 is expressed on some myeloid cell populations and on multiple kidney cell lineages, including tubular and endothelial cells. Pharmacological inhibition of the IL-1R1 does not consistently protect the kidney from injury, suggesting there may be complex, cell-specific effects of IL-1R1 stimulation in AKI. METHODS: To examine expression of IL-1 and IL-1R1 in intrinsic renal versus infiltrating immune cell populations during AKI, we analyzed single-cell RNA sequencing (scRNA-seq) data from kidney tissues of humans with AKI and mice with acute aristolochic acid exposure. We then investigated cell-specific contributions of renal IL-1R1 signaling to AKI using scRNA-seq, RNA microarray, and pharmacological interventions in mice with IL-1R1 deletion restricted to the proximal tubule or endothelium. RESULTS: scRNA-seq analyses demonstrated robust IL-1 expression in myeloid cell populations and low-level IL-1R1 expression in kidney parenchymal cells during toxin-induced AKI. Our genetic studies showed that IL-1R1 activation in the proximal tubule exacerbated toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorated aristolochic acid-induced AKI by restoring VEGFA-dependent endothelial cell viability and density. CONCLUSIONS: These data highlight opposing cell-specific effects of IL-1 receptor signaling on AKI after toxin exposure. Disrupting pathways activated by IL-1R1 in the tubule, while preserving those triggered by IL-1R1 activation on endothelial cells, may afford renoprotection exceeding that of global IL-1R1 inhibition while mitigating unwanted actions of IL-1R1 blockade.


Assuntos
Injúria Renal Aguda , Receptores de Interleucina-1 , Humanos , Camundongos , Animais , Receptores de Interleucina-1/genética , Apolipoproteínas M , Células Endoteliais/metabolismo , Injúria Renal Aguda/patologia , Camundongos Knockout , Interleucina-1 , Endotélio/metabolismo , Camundongos Endogâmicos C57BL
9.
Regen Ther ; 24: 211-218, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37519908

RESUMO

Introduction: Cell processing operators (CPOs) use a variety of disinfectants that vaporize in the workspace environment. These disinfectants can induce allergic reactions in CPOs, due to their long working hours at cell processing facilities (CPFs). Ionic substances such as CH3COO- generated from peracetic acid, nitrogen oxides (NOx) and sulfur oxides (SOx) from outdoor environment are also known to pollute air. Therefore, our objective was to assess the air quality in CPFs and detect volatile organic compounds (VOCs) from disinfectants and building materials, and airborne ionic substances from outdoor air. Methods: Sampling was conducted at three CPFs: two located in medical institutions and one located at a different institution. Air samples were collected using a flow pump. Ion chromatographic analysis of the anionic and cationic compounds was performed. For VOC analysis, a thermal desorption analyzer coupled with capillary gas chromatograph and flame ionization detector was used. Results: Analysis of the ionic substances showed that Cl-, NOx, and SOx, which were detected in large amounts in the outdoor air, were relatively less in the CPFs. Ethanol was detected as the main component in the VOC analysis. Toluene was detected at all sampling points. As compared to the other environments, air in the incubator contained larger amounts of VOCs, that included siloxane, tetradecane, and aromatics. Conclusions: No VOCs or ionic substances of immediate concern to the health of the CPOs were detected during the non-operating period. However, new clinical trials of cell products are currently underway in Japan, and a variety of new cell products are expected to be approved. With an increase in cell processing, health risks to CPOs that have not been considered previously, may become apparent. We should continue to prepare for the future expansion of the industry using a scientific approach to collect various pieces of information and make it publicly available to build a database.

10.
J Clin Med ; 12(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37109208

RESUMO

BACKGROUND: Hip resurfacing arthroplasty (HRA) patients require subsequent annual screening for postoperative complications. Ultrasonography may be useful for this purpose but lacks a screening protocol for hips. The purpose of this study was to evaluate the accuracy of ultrasonography for detecting postoperative complications in HRA patients using a screening protocol that specifically targets periprosthetic muscles. METHODS: We enrolled 45 hips from 40 HRA patients with a mean follow-up period of 8.2 years. MRI and ultrasonography scans were simultaneously conducted at follow-up. The ultrasonography assessments were conducted on the anterior part of the hip that targets iliopsoas, sartorius, rectus femoris, lateral with anterior superior and inferior iliac spine (ASIS and AIIS) as bony landmarks, and the lateral and posterior parts that target fascia tensor, short rotators, and gluteus minimus, medius, and maximus with greater trochanter and ischial tuberosity as bony landmarks. The accuracy of diagnosing postoperative abnormalities and the visibility of periprosthetic muscles were compared between these two modalities. RESULTS: Both MRI and ultrasonography detected an abnormal region in eight cases comprising two infections, two pseudotumors, and four patients with greater trochanteric bursitis. Among these cases, four hips required implant removal. The increase in anterior space, measured as the distance between the iliopsoas and resurfacing head, was a good indicator for the abnormal mass in these four HRA cases. In the assessment of periprosthetic muscles, MRI showed a much lower visibility than ultrasonography in the iliopsoas (6.7% vs. 100%), gluteus minimus (6.7% vs. 88.9%), and short rotators (8.8% vs. 71.4%) due to implant halation. CONCLUSIONS: By targeting periprosthetic muscles, ultrasonography can detect postoperative complications as effectively as MRI assessments in HRA patients. Ultrasonography has superior visibility in the periprosthetic muscles of HRA patients, indicating its utility for the screening of small legions in these cases which may not be visible by MRI.

11.
Pain Ther ; 12(2): 461-473, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36645650

RESUMO

PURPOSE: We compared the clinical effects of Neurotropin, limaprost alfadex, and a combination of both drugs for lumbar spinal stenosis (LSS) with low back pain (LBP). METHODS: We conducted a multicenter, randomized, active-controlled, open-label trial from March 2021 to May 2022. Participants were patients diagnosed with LSS by MRI and were randomly assigned to three groups: Neurotropin/limaprost combination (NL group), Neurotropin (N group), and limaprost group (L group). Participants received the drugs administered orally for 12 weeks, and each examination and observation was performed before any drug administration and every 2 weeks thereafter. We recorded age, sex, height, weight, duration of symptoms, intermittent claudication distance, level of stenosis in MRI, and concomitant analgesics as examination items in the trial period. Items measured during the trial were visual analog scale (VAS) score (mm) for LBP, leg pain and numbness, walking activity (walking speed, stride length), standing balance (3 m Timed Up-and-Go (TUG) Test results, Five Times Sit-to-Stand Test (FTSST) results), LBP/Quality of Life (QOL)-related scores (Oswestry Disability Index (ODI), Euro QOL 5-Dimensions 5-Level (EQ-5D-5L), Roland-Morris Disability Questionnaire (RDQ)), psychological factors (Pain catastrophizing scale (PCS) and Pain Self-Efficacy Questionnaire (PSEQ) scores), and adverse events. Each item was evaluated using changes at each visit (weeks 2-12) from baseline value before drug administration (week 0), and changes were considered significant when p < 0.05. RESULTS: We included results from 64 patients in the present study; 24 were assigned to the NL group (mean age 71.2 years), 20 to the N group (mean age 76.2 years), and 20 to the L group (mean age 74.4 years). There were no significant differences between the three groups in patient characteristics, concomitant analgesics, or baseline VAS score, gait balance, or QOL-related scores (p ≥ 0.05). The VAS and leg pain scores were significantly improved in Group L, and LBP was improved significantly in Group N. QOL and ODI scores improved significantly in the NL and L groups, EQ-5D score improved significantly in the L group, and RDQ score improved significantly in all groups (p < 0.05). Psychological factor and PCS scores improved significantly in the NL and L groups (p < 0.05). Walking speed and stride length were improved significantly in the NL and N groups (p < 0.05). TUG/FTSST scores were improved significantly in all groups (p < 0.05). Leg pain VAS score was improved significantly (p < 0.05) in the L group compared with the NL group after 6 and 12 weeks of administration, and LBP VAS was improved significantly in the N group after 6 weeks compared with the NL group (p < 0.05). Walking speed was significantly improved in the NL group after 2 weeks compared with the N group and improved significantly in the NL group after 6 weeks (p < 0.05) compared with the L group. RDQ was decreased significantly in the L group compared with the NL group after 8 weeks (p < 0.05). CONCLUSIONS: Combined use of Neurotropin and limaprost showed an additional effect on walking speed compared with single drug administration. Neurotropin may contribute to the improvement of low back pain, walking speed/stride length, and standing balance. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031200282).

12.
J Org Chem ; 88(12): 7830-7838, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-36697373

RESUMO

An efficient enantioselective synthesis of γ-chiral α-spiro-γ-lactones, which are important building blocks for pharmaceuticals, was achieved via BINOL-derived chiral bifunctional sulfide-catalyzed bromolactonizations of α-allyl carboxylic acids containing either hetero- or carbocyclic structures. Transformations of the resultant α-spiro-type bromolactonization product were examined to obtain optically active γ-functionalized α-spiro-γ-lactones. The utility of this catalytic system was also demonstrated in the asymmetric synthesis of α,α-diaryl- and dialkyl-substituted γ-lactones.


Assuntos
Ácidos Carboxílicos , Lactonas , Catálise , Estereoisomerismo
13.
J Arthroplasty ; 38(3): 555-561, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36115535

RESUMO

BACKGROUND: Serum immune markers can be useful in the diagnosis of periprosthetic joint infection (PJI) by detecting long-lasting abnormal immunological conditions. The purpose of this study was to examine whether serum immune markers can improve the diagnostic accuracy of PJI. METHODS: We enrolled 51 PJI, 45 aseptic loosening, and 334 osteoarthritis patients for assessment of the discriminatory accuracy of serum markers including white blood cell count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer, total protein, albumin (Alb), globulin (Glb), neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, albumin-globulin ratio (AGR), CRP-albumin ratio (CAR), and CRP-AGR ratio (CAGR). These diagnostic accuracies for low-grade PJI were also calculated in patients who had serum CRP levels < 10 mg/L. RESULTS: Among serum markers, Alb, Glb, AGR, CRP, ESR, CAR, and CAGR had highly accurate diagnostic accuracy for PJI, with area under the curve of 0.92, 0.90, 0.96, 0.97, 0.92, 0.97, and 0.98, respectively. In low-grade PJI patients, area under the curve of CRP, ESR, CAR, and CAGR (0.69, 0.80, 0.65, and 0.82, respectively) was decreased but that of Alb, Glb, and AGR (0.90, 0.88, and 0.95, respectively) remained high, indicating the diagnostic utility of these immune markers. The sensitivity and specificity of AGR with cutoff value of 1.1 were demonstrated as 0.92 and 0.89, respectively, and with cutoff value of 1.2, 1.00, and 0.79, respectively, in the diagnosis of low-grade infection. CONCLUSION: Our results demonstrate the potential value of Alb, Glb, AGR, and combination indices of these immune makers with CRP in improving preoperative serum diagnosis for PJI, especially in low-grade PJI. LEVEL OF EVIDENCE: Diagnostic- Level II.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Globulinas , Infecções Relacionadas à Prótese , Humanos , Proteína C-Reativa/análise , Albumina Sérica , Infecções Relacionadas à Prótese/cirurgia , Biomarcadores , Artrite Infecciosa/cirurgia , Sensibilidade e Especificidade , Sedimentação Sanguínea , Estudos Retrospectivos
14.
Front Psychol ; 13: 952488, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467226

RESUMO

Music, and listening to music, has occurred throughout human history. However, it remains unclear why people prefer some types of music over others. To understand why we listen to a certain music, previous studies have focused on preferred tempo. These studies have reported that music components (external), as well as participants' spontaneous motor tempo (SMT; internal), determine tempo preference. In addition, individual familiarity with a piece of music has been suggested to affect the impact of its components on tempo preference. However, the relationships among participants' SMT, music components, and music familiarity as well as the influence of these variables on tempo preference have not been investigated. Moreover, the music components that contribute to tempo preference and their dependence on familiarity remain unclear. Here, we investigate how SMT, music components, and music familiarity simultaneously regulate tempo preference as well as which music components interact with familiarity to contribute to tempo preference. A total of 23 participants adjusted the tempo of music pieces according to their preferences and rated the familiarity of the music. In addition, they engaged in finger tapping at their preferred tempo. Music components, such as the original tempo and the number of notes, were also analyzed. Analysis of the collected data with a linear mixed model showed that the preferred tapping tempo of participants contributed to the preferred music tempo, regardless of music familiarity. In contrast, the contributions of music components differed depending on familiarity. These results suggested that tempo preference could be affected by both movement and memory.

15.
Cell Rep ; 41(6): 111610, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351395

RESUMO

In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. Using genetic and single-cell transcriptomic approaches in mice, we report that female sex confers striking protection against ferroptosis, which was experimentally induced in proximal tubular (PT) cells by deleting glutathione peroxidase 4 (Gpx4). Single-cell transcriptomic analyses further identify the NFE2-related factor 2 (NRF2) antioxidant protective pathway as a female resilience mechanism against ferroptosis. Genetic inhibition and pharmacological activation studies show that NRF2 controls PT cell fate and plasticity by regulating ferroptosis. Importantly, pharmacological NRF2 activation protects male PT cells from ferroptosis and improves cellular plasticity as in females. Our data highlight NRF2 as a potential therapeutic target to prevent failed renal repair after acute kidney injury in both sexes by modulating cellular plasticity.


Assuntos
Injúria Renal Aguda , Ferroptose , Humanos , Feminino , Masculino , Camundongos , Animais , Caracteres Sexuais , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Rim/metabolismo
17.
Comput Assist Surg (Abingdon) ; 27(1): 84-90, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35727185

RESUMO

Planning a three-dimensional (3D) osteotomy using computed tomography (CT) data is useful especially in cases with complex deformities. Furthermore, CT-based navigation system allows the preoperative virtual planning to be replicated in actual surgery. However, one disadvantage when using navigation systems is that when osteotomies are performed on tracker-attached bone, the bone fragments on the side that were cut away cannot be tracked. This is especially problematic when performing multiple osteotomies on bones with complex deformities. We solved this problem by creating a 3D printed bone model that can be referenced intraoperatively and used in combination with the navigation system. We applied these techniques to perform segmental corrective osteotomy for a complex tibial deformity with intramedullary nail (IMN) fixation case of hereditary vitamin D-resistant hypophosphatemic rickets (HVDRR) in an adult man. Due to the patient's history of multiple surgeries, the affected tibia had a narrow and partially closed medullary canal. Therefore, we planned to use an IMN for correction and fixation of tibial deformity to protect the thin and stretched skin around the deformed tibia. With the assistance of CT-based navigation, we could perform an accurate three-dimensional tibial osteotomy. Moreover, we could perform accurate preparation of closed medullary canal for the IMN placement by referring to the 3D printed bone models. Six months after the operation, the bone union at the osteotomy sites was confirmed and the patient was able to return to his normal life and work.


Assuntos
Raquitismo Hipofosfatêmico , Cirurgia Assistida por Computador , Adulto , Humanos , Masculino , Osteotomia/métodos , Impressão Tridimensional , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Vitamina D
18.
Chirality ; 34(7): 915-924, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35488466

RESUMO

Although the wide variety of heterocyclic compounds is common knowledge, chiral 2-oxazolidinones are recognized as some of the most important heterocycles in medicinal chemistry. Many important pharmaceutical molecules have been constructed based on the chiral 2-oxazolidinone backbone. Therefore, the development of even more efficient catalytic methods for the synthesis of chiral 2-oxazolidinones remains a very important pursuit in the field of synthetic organic chemistry. This review summarizes the coupling reactions of epoxides and isocyanates for the preparation of 2-oxazolidinones. Both metal catalysts and organocatalysts promote these reactions. Optically pure 2-oxazolidinones are prepared from optically pure epoxide substrates via these catalytic methods. A synthetic example of a commercially available pharmaceutical compound utilizing this method is also introduced.


Assuntos
Compostos Heterocíclicos , Oxazolidinonas , Catálise , Compostos de Epóxi/química , Compostos Heterocíclicos/química , Preparações Farmacêuticas , Estereoisomerismo
19.
Sci Rep ; 12(1): 3586, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246574

RESUMO

Preoperative diagnosis of infection is important for appropriate surgical treatment of patients with rapid hip destruction (RHD). We investigated whether test results, including inflammatory and nutritional markers, could be used to accurately differentiate infectious and non-infectious RHD. Fifty patients with RHD who underwent total hip arthroplasty within a year of onset were observed. Infectious RHD was defined as ≥ 2 positive serological inflammatory, microbiological, or pathological evaluations. The albumin to globulin ratio (AGR), C-reactive protein (CRP)/albumin ratio (CAR), Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and platelet to lymphocyte ratio (PLR) were calculated from the blood test results. In the infectious group, the white blood cell count, platelet count, CRP level, erythrocyte sedimentation rate, CAR, GPS, mGPS, and PLR were significantly higher, while the albumin level, AGR, PNI, and GNRI were significantly lower. The CRP and albumin levels showed the highest sensitivity (1.00 for both; specificity of 0.87 and 0.73, respectively) in diagnosing infectious RHD. Combining these measurements (CAR) increased the specificity to 0.92. The accuracy of other nutritional assessments was good. Thus, nutritional assessment as well as conventional assessment of the inflammatory response can improve the accuracy of preoperative diagnosis of infectious RHD.


Assuntos
Proteína C-Reativa , Inflamação , Idoso , Albuminas , Proteína C-Reativa/análise , Humanos , Inflamação/diagnóstico , Prognóstico , Estudos Retrospectivos
20.
Am J Sports Med ; 50(5): 1272-1280, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35238657

RESUMO

BACKGROUND: Precise osteochondroplasty is important in arthroscopic hip surgery for cam-type femoroacetabular impingement (FAI). Although computer-assisted surgery with a navigation system may enhance the accuracy of arthroscopic osteochondroplasty, few clinical studies have assessed its accuracy. PURPOSE: To evaluate the accuracy of arthroscopic osteochondroplasty by a computed tomography (CT)-based navigation system for cam-type FAI, using 3-dimensional (3D) reconstruction with more detail compared with previous methods. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty patients (14 men and 6 women) who underwent navigation-assisted arthroscopic surgery for cam-type FAI were included. The preoperative 3D model of the femur was constructed from each patient's CT data, and a planned model with virtual cam resection was generated. A femoral model was reconstructed from CT data postoperatively. The 3 models for each patient were overlaid using a 3D model registration method. Then, the contours of the bone resection area of each model were compared by measuring them. To measure the deviation between planned and actual bone resections, 4 cross-sectional images of the 3 femoral models were set at one-quarter intervals from the femoral head radius. All measurements were based on clockface lines set around the femoral neck axis at 30-minute intervals. Differences between the planned and postoperative contour lines were deemed resection deviations. RESULTS: All cam resections were performed in the anterior half of the region of interest. Therefore, only the anterior half (48 points) of the 96 points per case were analyzed. In 876 (91.3%) points of the total measurement points (960 points/20 cases), the error in resection depth was within 3 mm. Overresection was observed at 35 (3.6%) points and underresection at 49 (5.1%) points. The observed maximum deviations from the planned models were 6.3 mm overresection and -7.1 mm underresection. The alpha angles of the postoperative model at the posterior 9- to 3-o'clock position were <55° in all patients. CONCLUSION: Navigation-assisted arthroscopic osteochondroplasty showed favorable accuracy. Underresection was more frequent than overresection on the anterosuperior side of the femur, despite assistance of the navigation system.


Assuntos
Impacto Femoroacetabular , Artroscopia/métodos , Computadores , Feminino , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Cabeça do Fêmur/cirurgia , Colo do Fêmur/cirurgia , Articulação do Quadril/cirurgia , Humanos , Masculino
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