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1.
Nature ; 603(7902): 631-636, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35322249

RESUMO

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

2.
Clin Exp Nephrol ; 28(8): 803-810, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38478191

RESUMO

BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.


Assuntos
Estudos de Associação Genética , Síndrome de Gitelman , Membro 3 da Família 12 de Carreador de Soluto , Humanos , Síndrome de Gitelman/genética , Síndrome de Gitelman/diagnóstico , Membro 3 da Família 12 de Carreador de Soluto/genética , Criança , Masculino , Estudos Retrospectivos , Feminino , Adolescente , Fenótipo , República da Coreia , Pré-Escolar , Mutação , Potássio/sangue , Predisposição Genética para Doença , Cloretos/sangue
3.
Artigo em Inglês | MEDLINE | ID: mdl-39189118

RESUMO

PURPOSE: Anterior talofibular ligament (ATFL) insufficiency encompasses situations in which (i) frequent sprains cause ATFL loss, as evidenced by ATFL non-visualization on preoperative magnetic resonance imaging; or (ii) minimal healthy ATFL tissue for repair is left after the removal of the large os subfibulare. Suture tape implantation can be indicated for these cases rather than conventional ligament repair. This study was designed to investigate the incidence of post-operative re-sprain in patients who underwent suture tape implantation for ATFL insufficiency, and risk factors influencing the occurrence of post-operative re-sprain were identified. METHODS: A total of 68 patients who underwent suture tape implantation for ATFL insufficiency from January 2016 to December 2021 were retrospectively evaluated. The minimum follow-up duration for inclusion was 2 years after surgery. All included patients were divided into two groups according to the presence of post-operative re-sprain during the follow-up period. Multiple clinico-radiographic parameters were measured, and binary logistic regression analysis was performed to determine the factors influencing post-operative re-sprain. RESULTS: Post-operative re-sprain occurred in 19 of the 68 patients (27.9%), and multiple re-sprains persisted in 7 patients (10.3%). Post-operative re-sprain was more likely to occur in patients who smoked after surgery (odds ratio [OR], 3.510), had generalized ligament laxity (OR, 4.364) and engaged in occupations requiring high physical activity levels (OR, 4.421), including soldiers, professional athletes, student-athletes and mailmen. CONCLUSION: The incidence of multiple post-operative re-sprains was high after suture tape implantation for ATFL insufficiency. Caution is particularly warranted in patients with risk factors, necessitating meticulous attention to their care. Careful consideration of strategies to mitigate risks when performing the surgery is also recommended. LEVEL OF EVIDENCE: Level III.

4.
Int Orthop ; 48(3): 711-718, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37897545

RESUMO

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.


Assuntos
Tendão do Calcâneo , Antirreumáticos , Fasciíte Plantar , Espondilartrite , Tendinopatia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Antirreumáticos/uso terapêutico , Fasciíte Plantar/complicações , Fasciíte Plantar/diagnóstico , Fasciíte Plantar/terapia , Antígeno HLA-B27/análise , Antígeno HLA-B27/metabolismo , Dor/tratamento farmacológico , Estudos Retrospectivos , Espondilartrite/complicações , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Tendinopatia/complicações , Tendinopatia/diagnóstico , Tendinopatia/terapia , Resultado do Tratamento
5.
Int Orthop ; 48(8): 2153-2163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38705891

RESUMO

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.


Assuntos
Hallux Valgus , Procedimentos Cirúrgicos Minimamente Invasivos , Osteotomia , Humanos , Hallux Valgus/cirurgia , Hallux Valgus/diagnóstico por imagem , Osteotomia/métodos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Seguimentos , Radiografia/métodos , Idoso , Ossos do Metatarso/cirurgia
6.
Arch Orthop Trauma Surg ; 144(3): 1055-1063, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38114740

RESUMO

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.


Assuntos
Tendão do Calcâneo , Traumatismos do Tornozelo , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Atividades Cotidianas , Tratamento Conservador , Resultado do Tratamento , Articulação do Tornozelo , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/reabilitação , Ruptura/cirurgia
7.
Stem Cells ; 40(9): 818-830, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-35728620

RESUMO

Nerve growth factor (NGF) is the best-characterized neurotrophin and is primarily recognized for its key role in the embryonic development of the nervous system and neuronal cell survival/differentiation. Recently, unexpected actions of NGF in bone regeneration have emerged as NGF is able to enhance the osteogenic differentiation of mesenchymal stem cells. However, little is known regarding how NGF signaling regulates osteogenic differentiation through epigenetic mechanisms. In this study, using human dental mesenchymal stem cells (DMSCs), we demonstrated that NGF mediates osteogenic differentiation through p75NTR, a low-affinity NGF receptor. P75NTR-mediated NGF signaling activates the JNK cascade and the expression of KDM4B, an activating histone demethylase, by removing repressive H3K9me3 epigenetic marks. Mechanistically, NGF-activated c-Jun binds to the KDM4B promoter region and directly upregulates KDM4B expression. Subsequently, KDM4B directly and epigenetically activates DLX5, a master osteogenic gene, by demethylating H3K9me3 marks. Furthermore, we revealed that KDM4B and c-Jun from the JNK signaling pathway work in concert to regulate NGF-mediated osteogenic differentiation through simultaneous recruitment to the promoter region of DLX5. We identified KDM4B as a key epigenetic regulator during the NGF-mediated osteogenesis both in vitro and in vivo using the calvarial defect regeneration mouse model. In conclusion, our study thoroughly elucidated the molecular and epigenetic mechanisms during NGF-mediated osteogenesis.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Animais , Diferenciação Celular/genética , Epigênese Genética , Histona Desmetilases/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Osteogênese/genética , Receptor de Fator de Crescimento Neural/genética , Receptor de Fator de Crescimento Neural/metabolismo
8.
Pediatr Blood Cancer ; 70(4): e30233, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36751119

RESUMO

BACKGROUND: Patients with relapsed osteosarcoma have poor treatment outcomes. High-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) has been used in several high-risk malignant solid tumors; however, few studies have evaluated their role in treating osteosarcoma. We evaluated the effectiveness of HDCT/ASCT in relapsed pediatric osteosarcoma cases. PROCEDURE: We retrospectively reviewed the medical records of 40 patients diagnosed with and treated for relapsed osteosarcoma at Asan Medical Center and Samsung Medical Center from January 1996 to July 2019. RESULTS: The median age of this cohort was 13.4 years (range: 6.1-18.2). The cohort's 5-year overall survival (OS) was 51.0% ± 0.1% during a median follow-up period of 67.5 months. Twenty-five patients (62.5%) achieved complete remission (CR) with salvage treatment, and the 5-year OS was 82.4% ± 0.1%, whereas none of the remaining 15 patients who did not achieve CR survived (p < .0001). Of the 25 CR cases, 15 underwent subsequent HDCT/ASCT. We compared the effect of HDCT/ASCT among patients who achieved CR. There were no significant differences in the 5-year OS outcomes between patients who did and did not receive HDCT/ASCT (83.9% ± 0.1%, 13/15 vs. 80.0% ± 0.1%, 8/10, respectively; p = .923). CONCLUSION: To our knowledge, we report the first comparative cohort study that proved HDCT/ASCT does not significantly improve survival outcomes in relapsed osteosarcoma. Achievement of CR remains the most crucial factor for good survival outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Osteossarcoma , Humanos , Criança , Adolescente , Estudos Retrospectivos , Estudos de Coortes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo , Intervalo Livre de Doença , Transplante de Células-Tronco
9.
Epidemiol Infect ; 151: e180, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37814587

RESUMO

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18 years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriemia , COVID-19 , Adulto , Humanos , Adolescente , Estudos Retrospectivos , Carbapenêmicos/uso terapêutico , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico
10.
BMC Geriatr ; 23(1): 127, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36879198

RESUMO

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. RESULTS: Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. CONCLUSION: This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.


Assuntos
Regras de Decisão Clínica , Clostridioides difficile , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , Hospitais Universitários
11.
J Korean Med Sci ; 38(42): e330, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904655

RESUMO

BACKGROUND: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. METHODS: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. RESULTS: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). CONCLUSION: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.


Assuntos
Infecções Comunitárias Adquiridas , Infecções Pneumocócicas , Pneumonia Pneumocócica , Adulto , Masculino , Criança , Humanos , Feminino , Streptococcus pneumoniae , Sorogrupo , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Estudos Prospectivos , Estudos Soroepidemiológicos , Vacinas Conjugadas , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Infecções Comunitárias Adquiridas/epidemiologia , Vacinação
12.
Phytother Res ; 37(1): 7-14, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35916211

RESUMO

Though icariside E4 (IE4) is known to have anti-noceptive, anti-oxidant, anti-Alzheimer and anti-inflammatory effects, there was no evidence on the effect of IE4 on lipid metabolism so far. Hence, the hypolipogenic mechanism of IE4 was investigated in HepG2 hepatocellular carcinoma cells (HCCs) in association with MID1 Interacting Protein 1(MID1IP1) and AMPK signaling. Here, IE4 did not show any toxicity in HepG2 cells, but reduced lipid accumulation in HepG2 cells by Oil Red O staining. MID1IP1 depletion decreased the expression of SREBP-1c and fatty acid synthase (FASN) and induced phosphorylation of ACC in HepG2 cells. Indeed, IE4 activated phosphorylation of AMPK and ACC and inhibited the expression of MID1IP1 in HepG2 cells. Furthermore, IE4 suppressed the expression of SREBP-1c, liver X receptor-α (LXR), and FASN for de novo lipogenesis in HepG2 cells. Interestingly, AMPK inhibitor compound C reversed the ability of IE4 to reduce MID1IP1, SREBP-1c, and FASN and activate phosphorylation of AMPK/ACC in HepG2 cells, indicating the important role of AMPK/ACC signaling in IE4-induced hypolipogenic effect. Taken together, these findings suggest that IE4 has hypolipogenic potential in HepG2 cells via activation of AMPK and inhibition of MID1IP1 as a potent candidate for treatment of fatty liver disease.


Assuntos
Proteínas Quinases Ativadas por AMP , Metabolismo dos Lipídeos , Humanos , Células Hep G2 , Fosforilação , Proteínas Quinases Ativadas por AMP/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Lipogênese , Ácido Graxo Sintases/metabolismo , Fígado
13.
Int Orthop ; 47(1): 107-115, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36462088

RESUMO

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.


Assuntos
Tornozelo , Artrite , Humanos , Estudos Retrospectivos , , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Artrite/diagnóstico por imagem , Artrite/cirurgia , Artrodese/efeitos adversos
14.
Arch Orthop Trauma Surg ; 143(11): 6513-6520, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37341805

RESUMO

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.


Assuntos
Tendão do Calcâneo , Procedimentos Ortopédicos , Tendinopatia , Traumatismos dos Tendões , Humanos , Idoso , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Tendinopatia/cirurgia , Traumatismos dos Tendões/cirurgia , Ruptura/cirurgia , Técnicas de Sutura , Resultado do Tratamento
15.
Foot Ankle Surg ; 29(2): 118-127, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36526523

RESUMO

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.


Assuntos
Fraturas Ósseas , Fraturas não Consolidadas , Osteoartrite , Tálus , Humanos , Fixação Interna de Fraturas/efeitos adversos , Estudos Retrospectivos , Centros de Atenção Terciária , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Tálus/diagnóstico por imagem , Tálus/cirurgia , Tálus/lesões , Fraturas não Consolidadas/etiologia , Osteoartrite/diagnóstico por imagem , Osteoartrite/etiologia , Osteoartrite/cirurgia , Resultado do Tratamento
16.
Foot Ankle Surg ; 29(3): 256-260, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36806441

RESUMO

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.


Assuntos
Atividades Cotidianas , Cistos , Humanos , Estudos Retrospectivos , Dedos do Pé , Artrodese/métodos , Resultado do Tratamento
17.
HIV Med ; 23(7): 801-806, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35150183

RESUMO

OBJECTIVES: To describe a pharmacist-led campaign aimed at reducing the proportion of people with HIV with ongoing chronic hepatitis C virus (HCV) infection and delineating barriers to HCV care in this patient population. METHODS: An electronic report and retrospective chart review were used to identify patients who remained with HCV infections after a previous treatment initiative. A clinical pharmacist and pharmacy resident approached the remaining HCV patients during their routine visits for HIV care to offer and coordinate direct-acting antiviral (DAA) treatment. The primary end-point was to compare the prevalence of chronic HCV before and after the intervention period. Barriers to care were also evaluated, with logistic regression performed to identify predictors of sustained virologic response (SVR) attainment. RESULTS: Forty-six patients were included in the analysis (4.2% of clinic population), with HCV prevalence falling to 0.6% (six patients) by the end of the study (p < 0.0001). The HCV care cascade in the cohort was as follows: 70% agreed to and received DAA therapy, 63% initiated therapy, and 50% achieved SVR. The top barriers to care at baseline included recreational drug use (67%), poor engagement in care (61%), and mental health disorders (28%). Poor engagement in care and active recreational drug use were associated with decreased odds of achieving SVR in bivariate analysis. CONCLUSIONS: A coordinated effort can make strides towards reducing the overall burden of HCV in this challenging population. The HCV care cascade remains tied to the HIV continuum of care, with poor engagement in care remaining an important rate-limiting step impeding micro-elimination.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento
18.
Anal Biochem ; 641: 114560, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35065043

RESUMO

Rapid and simple spectrophotometric methods are required to detect various oligosaccharides produced by agar-hydrolysing enzymes. Herein, we present a quantitative agarose-iodine assay for agarase activity determination via the detection of the extent of agarose degradation. The agarose-iodine complex becomes reddish orange upon the addition of Lugol solution, and the enzymatic activity can be detected with ultraviolet-visible spectroscopy at 600 nm. The main advantages of this modified Lugol assay are high sensitivity, simple detection, and cost effectiveness. A novel definition of the unit to measure and compare the activities of agarases is also suggested.


Assuntos
Glicosídeo Hidrolases/análise , Iodo/química , Sefarose/química , Alteromonadaceae/enzimologia , Corantes Fluorescentes/química , Glicosídeo Hidrolases/metabolismo , Iodetos/química , Espectrofotometria Ultravioleta
19.
J Appl Clin Med Phys ; 23(1): e13483, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34854217

RESUMO

PURPOSE: The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer. MATERIALS AND METHODS: For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided with nonmagnetic components. Element values were optimized with an electromagnetic field simulation. Images were acquired on a GE 600 PET-computed tomography (CT) and GE 3.0 T MR system. For this study, we used the T1-weighted image (volunteer; repetition time (TR), 694 ms; echo time (TE), 9.6 ms) and T2-weighted image (phantom; TR, 8742 ms; TE, 104 ms) with the fast spin-echo sequence. RESULTS: The results of measuring image factors with the proposed radiofrequency (RF) coil and standard conventional RF coil were as follows: signal-to-noise ratio (breast; 207.7 vs. 175.2), percent image uniformity (phantom; 89.22%-91.27% vs. 94.63%-94.77%), and Hounsfield units (phantom; -4.51 vs. 2.38). CONCLUSIONS: Our study focused on the feasibility of proposed two-channel Helmholtz loops (by minimizing metallic components and soldering) for PET-MR imaging and found the comparable image quality to the standard conventional coil. We believe our work will help significantly to improve image quality with the development of a less metallic breast MR coil.


Assuntos
Artefatos , Mama , Mama/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons
20.
Int Orthop ; 46(11): 2637-2648, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35994065

RESUMO

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.


Assuntos
Fraturas do Tornozelo , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Humanos , Estudos Retrospectivos , Tíbia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
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