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1.
Ann Surg ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994579

RESUMO

OBJECTIVE: To compare nutritional and postoperative outcomes between early oral feeding and late oral feeding with jejunostomy feeding support after esophagectomy. SUMMARY BACKGROUND DATA: Esophagectomy is associated with substantial body weight loss and malnutrition, impacting the prognosis of esophageal cancer patients. Despite many studies on post-esophagectomy nutritional support, optimal strategies remain elusive. This study investigates the impact of jejunostomy feeding with late oral feeding compared to conventional oral feeding on nutritional and postoperative outcomes. METHODS: We performed a single-center prospective open-labelled randomized controlled trial between 2020 and 2022. Patients aged 18 to 75 years with resectable esophageal cancer were randomly assigned to undergo either early oral feeding (early group) or late oral feeding with jejunostomy feeding support (late group) after esophagectomy. The primary endpoint was body weight loss from preoperative body weight at postoperative 4-5 weeks and 4 months. Other perioperative and nutritional outcomes were also evaluated. RESULTS: We randomly assigned 29 patients to the early group and 29 patients to the late group. The late group exhibited significantly less body weight loss at both postoperative 4-5 weeks (8.3% vs. 5.6%; P =0.002) and 4 months (15.0% vs. 10.5%; P =0.003). The total calorie intake and protein intake were higher in the late group for both postoperative 4-5 weeks (1800 kcal/day vs. 1100 kcal/day; P <0.001) and 4 months (1565 kcal/day vs. 1200 kcal/day; P =0.010). Sixty percentage of early group changed to malnutrition state, while 40% of the late group changed to malnutrition. The complication rate and length of hospital stays were similar. CONCLUSIONS: The late group demonstrated prevention of significant body weight loss, enhanced nutritional intake, and reduces malnutrition without compromising short-term surgical outcomes.

2.
Anal Chem ; 96(28): 11146-11154, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38917341

RESUMO

Here, we report an electrochemiluminescence (ECL)-based approach for imaging of local photoelectrochemical processes on hematite in a spatially and temporally controlled manner. The local processes were guided by flexible and dynamic light illumination, not requiring any prepatterned conductive features or photomasks, with a digital micromirror device (DMD). The imaging approach was based on light-addressable electrochemical reactions on hematite, resulting in photoinduced ECL emission for spatiotemporally resolved imaging of photoelectrochemical processes selectively guided by light illumination. After clarifying the capability of hematite as a photosensitive electrode, we validated that the illuminated hematite exhibited stable light-guided ECL emission in correspondence with the illuminated area, with a spatial resolution of 0.8 µm and a temporal resolution of 1 µs, even over a long period of 6 h. More importantly, this study exemplified the simple yet effective ECL-based approach for electrochemical visualization of local photoelectrochemical processes guided by flexible and dynamic adjustment of light illumination in a spatiotemporally controlled way.

3.
Dis Esophagus ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38964872

RESUMO

Robotic esophagectomy has improved early outcomes and enhanced the quality of lymphadenectomy for esophageal cancer surgery. This study aimed to determine risk factors for long-term survival following robotic esophagectomy and the causes of long-term mortality. We included patients who underwent robotic esophagectomy at our institute between 2010 and 2022. Robotic esophagectomy was defined as a surgical procedure performed robotically in both the abdomen and thorax. Robotic esophagectomy was performed in patients at all stages, including advanced stages, even in patients with stage IV and supraclavicular lymph node metastasis. A total of 340 patients underwent robotic esophagectomy during the study period. Ivor-Lewis operation and McKeown operation were performed on 153 (45.0%) and 187 (55.0%) patients, respectively. The five-year survival rates based on clinical stages were as follows: 85.2% in stage I, 62.0% in stage II, 54.5% in stage III, and 40.3% in stage IV. Risk factors for long-term survival included body mass index, Charlson comorbidity index, clinical stages, and postoperative complications of grade 4 or higher. Among the cases of long-term mortality, recurrence accounted for 42 patients (61.7%), while non-cancer-related death occurred in 26 patients (38.2%). The most common cause of non-cancer-related death was malnutrition and poor general condition, observed in 11 patients (16.2%). Robotic esophagectomy has demonstrated the ability to achieve acceptable long-term survival rates, even in patients with cervical lymph node metastasis. However, addressing high-grade postoperative complications and long-term malnutrition remains crucial for further improving the long-term survival outcomes of patients with esophageal cancer.

4.
J Med Internet Res ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978483

RESUMO

BACKGROUND: The adoption of immersive technology in simulation-based nursing education has grown significantly, offering a solution to resource limitations and enabling safe access to clinical environments. Despite its advantages, there are still diverse reports regarding the effectiveness of immersive technology. It is crucial to verify the effectiveness of immersive technology in nursing education to inform future educational programs. OBJECTIVE: This systematic review aimed to identify the contents of immersive technology-based education for undergraduate nursing students and evaluate the effectiveness of immersive technology compared to traditional teaching methods. METHODS: A literature search was performed using four databases: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and Web of Science, with the latest search completed on January 19, 2023. The inclusion criteria were as follows: participants were undergraduate nursing students; studies were published in Korean or English; designs included randomized controlled trials (RCTs) or non-randomized studies; and interventions involved virtual reality (VR), augmented reality (AR), mixed reality (MR), or extended reality (XR). Quality assessment was conducted using Version 2 of the Cochrane risk of bias tool (RoB 2) for RCTs and the Risk of Bias Assessment Tool for Non-Randomized Studies (RoBANS). The main outcomes of the included studies were classified according to the New World Kirkpatrick Model (NWKM), ranging from Level 1 (Reaction) to Level 4 (Results). Meta-analysis was conducted using RevMan 5.4 software, and subgroup analysis was conducted due to heterogeneity of the results of meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was adopted for assessing certainty and synthesizing results of the relevant literature. RESULTS: A total of 23 studies were included, with participants numbers ranging from 33 to 289. Nineteen studies adopted VR to simulate various nursing scenarios, including disaster training, resuscitation, health assessments, and home healthcare. Four studies utilized AR technologies. Fifteen studies involved virtual patients in their scenarios. Based on NWKM, the main outcome variables were classified as Level 1 (usability and satisfaction), Level 2 (knowledge, motivation, confidence, performance, attitude, and self-efficacy), and Level 3 (clinical reasoning). Level 4 outcomes were not found in selected studies. Results of the subgroup analysis of meta-analysis showed that immersive technology-based nursing education was more effective than traditional education on knowledge attainment (standard mean difference (SMD)=0.59, 95% confidence interval (CI)=0.28-0.90, P<.001, I2=49%). Additionally, there were significant difference differences between the experimental groups and the control groups in confidence (SMD=0.70, 95% CI= 0.05-1.35, P=.03, I2=82%), and self-efficacy (SMD=0.86, 95% CI= 0.42-1.30; P<.001, I2=63%). CONCLUSIONS: These findings support the effectiveness of immersive technology-based education for undergraduate nursing students, despite heterogeneity in methods and interventions. We suggest that long-term cohort studies should be conducted to evaluate the effects of immersive technology-based nursing education on the NWKM Level 4.

5.
Arthroscopy ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38311267

RESUMO

PURPOSE: To determine the effects of topical tranexamic acid (TXA) administration on tendon adhesions, shoulder range of motion (ROM), and tendon healing in an acute rotator cuff repair rat model. METHODS: A total of 20 Sprague Dawley rats were used. Tendon adhesion, ROM, and biomechanical and histological analysis of tendon-bone healing was conducted at 3 and 6 weeks after surgery. The rats underwent rotator cuff repair surgery on both shoulders and were administered TXA via subacromial injections. The tendon adhesion was evaluated macroscopically and histologically. Biomechanical tendon healing was measured using a universal testing machine, and histological analysis was quantified by H&E, Masson's trichrome, and picrosirius red staining. RESULTS: At 3 weeks after surgery, the adhesion score was significantly lower in the TXA group (2.10 ± 0.32) than in the control group (2.70 ± 0.48) (P = .005), but there was no significant difference between the 2 groups at 6 weeks. Regarding ROM, compared with the control group, the TXA group showed significantly higher external rotation (36.35° ± 4.52° vs 28.42° ± 4.66°, P < .001) and internal rotation (45.35° ± 9.36° vs 38.94° ± 5.23°, P = .013) 3 weeks after surgery. However, at 6 weeks, there were no significant differences in external and internal rotation between the 2 groups. In the biomechanical analysis, no significant differences in gross examination (3 weeks, P = .175, 6 weeks, P = .295), load to failure (3 weeks, P = .117, 6 weeks, P = .295), or ultimate stress (3 weeks, P = .602, 6 weeks, P = .917) were noted between the 2 groups 3 and 6 weeks after surgery. In the histological analysis of tendon healing, no significant differences in the total score (3 weeks, P = .323, 6 weeks, P = .572) were found between the 2 groups 3 and 6 weeks after surgery. CONCLUSIONS: Topical TXA administration showed a beneficial effect in reducing tendon adhesions and improving ROM 3 weeks postoperatively and had no effect at 6 weeks. This suggests that additional intervention with TXA may be useful in achieving long-term improvement in shoulder stiffness. Additionally, TXA may increase tissue ground substance accumulation in the late postoperative period but does not adversely affect tendon-bone interface healing. CLINICAL RELEVANCE: The use of TXA after rotator cuff repair has no effect on tendon-bone interface healing in clinical practice and can improve shoulder stiffness in the early postoperative period. Additional research on the long-term effects is needed.

6.
Arch Gynecol Obstet ; 310(1): 461-467, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38252305

RESUMO

PURPOSE: To investigate the effect of intravenous MgSO4 on maternal cerebral hemodynamics as well as the association between altered Doppler indices of the ophthalmic arteries and ocular lesions in patients with preeclampsia. METHODS: After each of the 15 included patients was diagnosed with preeclampsia, MgSO4 was infused followed by transcranial Doppler tests of the indices of the ophthalmic, anterior, middle, posterior cerebral, vertebral, and basilar arteries, followed by a second MgSO4 infusion. The peak, mean, diastolic velocity, and pulsatile and resistance indices of each artery were automatically measured during testing. Based on the emergent data, the cerebral perfusion pressure, resistance-area product, and cerebral flow index were calculated. RESULTS: The cerebral perfusion pressure of the posterior cerebral arteries significantly decreased following the infusion of MgSO4 (p < 0.05). Before the infusion of MgSO4, cerebral perfusion pressure and cerebral flow index of the ophthalmic arteries were significantly increased (p < 0.05) in the preeclamptic pregnant patients with ocular lesions compared those without ocular lesions. After the infusion of MgSO4, the cerebral perfusion pressure and cerebral flow index of both ophthalmic arteries were slightly decreased, but the difference was not significant. CONCLUSIONS: Altered Doppler indices following the infusion of MgSO4 suggest significant changes in the hemodynamics of the posterior cerebral and ophthalmic arteries that are particularly related to the neurological signs and symptoms of women with preeclampsia. These findings may improve the understanding of the mechanism of the cerebral complications of preeclampsia. Advancing comprehension of these underlying mechanisms is postulated to play a pivotal role in the mitigation of hypertensive encephalopathy associated with preeclampsia.


Assuntos
Circulação Cerebrovascular , Sulfato de Magnésio , Artéria Oftálmica , Pré-Eclâmpsia , Ultrassonografia Doppler Transcraniana , Humanos , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/tratamento farmacológico , Sulfato de Magnésio/administração & dosagem , Gravidez , Adulto , Artéria Oftálmica/diagnóstico por imagem , Circulação Cerebrovascular/efeitos dos fármacos , Adulto Jovem , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos
7.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612663

RESUMO

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.


Assuntos
Imunidade Inata , Pólipos Nasais , Humanos , Animais , Camundongos , Linfócitos , Inflamação/tratamento farmacológico , Citocinas , Poeira , Mucosa Nasal , Material Particulado/toxicidade
8.
Int J Mol Sci ; 25(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38339162

RESUMO

Globally, women have been adopting oocyte cryopreservation (OC) for fertility preservation for various reasons, such as inevitable gonadotoxic treatment for specific pathologic states and social preferences. While conventional vitrification (C-VIT) has improved the success rate of OC, challenges of possible toxicities of high-concentration cryoprotective agents and osmotic stress persist. To overcome these challenges, we evaluated the ultra-fast vitrification (UF-VIT) method, which reduces the equilibration solution stage exposure time compared to C-VIT by observing mouse oocyte intracellular organelles and embryonic development. Consequently, compared to fresh mouse oocytes, UF-VIT presented significant differences only in endoplasmic reticulum (ER) intensity and mitochondrial (MT) distribution. Meanwhile, C-VIT showed substantial differences in the survival rate, key ER and MT parameters, and embryonic development rate. UF-VIT exhibited considerably fewer negative effects on key MT parameters and resulted in a notably higher blastocyst formation rate than C-VIT. Meiotic spindle (spindle and chromosomes) morphology showed no significant changes between the groups during vitrification/warming (VW), suggesting that VW did not negatively affect the meiotic spindle of the oocytes. In conclusion, UF-VIT seems more effective in OC owing to efficient cytoplasmic water molecule extraction, osmotic stress reduction, and minimization of cell contraction and expansion amplitude, thus compensating for the drawbacks of C-VIT.


Assuntos
Crioprotetores , Vitrificação , Feminino , Animais , Camundongos , Humanos , Crioprotetores/farmacologia , Pressão Osmótica , Criopreservação/métodos , Oócitos
9.
Arch Orthop Trauma Surg ; 144(6): 2491-2500, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38698293

RESUMO

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.


Assuntos
Lesões do Manguito Rotador , Tendinopatia , Cicatrização , Humanos , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/fisiopatologia , Lesões do Manguito Rotador/complicações , Cicatrização/fisiologia , Tendinopatia/etiologia , Tendinopatia/fisiopatologia , Manguito Rotador/cirurgia , Manguito Rotador/fisiopatologia , Diabetes Mellitus , Animais
10.
BMC Immunol ; 24(1): 15, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391734

RESUMO

BACKGROUND: CD40L is primarily expressed on activated CD4+ T cells and binds to CD40 which is expressed by various cells including dendritic cells, macrophages and B lymphocytes. While CD40-CD40L interaction is known to be direct between B cells and CD4+ T cells which results in proliferation and immunoglobulin isotype switching, antigen presenting cells (APCs) were thought to be involved in the delivery of CD4+ help to CD8+ T cells by cross-talk between CD4+ and CD8+ T cells and APCs. However, subsequent study demonstrated that CD40L signal can be directly delivered to CD8+ T cells by CD40 expression on CD8+ T cells. Since most studies have been carried out in murine models, we aimed to investigate the direct effect of CD40L on human peripheral CD8+ T cells. RESULTS: Human peripheral CD8+ T cells were isolated to exclude the indirect effect of B cells or dendritic cells. Upon activation, CD40 expression on CD8+ T cells was transiently induced and stimulation with artificial APCs expressing CD40L (aAPC-CD40L) increased the number of total and central memory CD8+ T cells and also pp65 specific CD8+ T cells. Stimulation with aAPC-CD40L also resulted in higher proportion of central memory CD8+ T cells. CONCLUSIONS: Our study suggests that CD40L has an effect on the increased number of CD8+ T cells through CD40 expressed on activated CD8+ T cells and has influence on memory CD8+ T cell generation. Our results may provide a new perspective of the effect of CD40L on human peripheral CD8+ T cells, which differ according to the memory differentiation status of CD8+ T cells.


Assuntos
Ligante de CD40 , Linfócitos T CD8-Positivos , Humanos , Animais , Camundongos , Antígenos CD40 , Células Apresentadoras de Antígenos , Fenótipo
11.
Antimicrob Agents Chemother ; 67(11): e0100323, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37843254

RESUMO

This study retrospectively analyzed the treatment outcomes of 110 patients with non-cavitary nodular bronchiectatic-type Mycobacterium avium complex pulmonary disease who received intermittent or daily treatment with a three-drug oral antibiotic regimen (i.e., a macrolide, ethambutol, and rifampin) at a tertiary referral center in South Korea. Among these patients, 36 had sputum smear positivity. Of these 36 patients, intermittent treatment led to a lower culture conversion rate than daily treatment [50.0% (8/16) vs 85.0% (17/20), P = 0.034].


Assuntos
Bronquiectasia , Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Humanos , Complexo Mycobacterium avium , Estudos Retrospectivos , Escarro/microbiologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Antibacterianos/uso terapêutico , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Resultado do Tratamento
12.
J Autoimmun ; 137: 102997, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36737299

RESUMO

BACKGROUND: Escherichia coli (E.coli) infection has been proposed to play an important role as an initial trigger in the development of autoimmunity via molecular mimicry. However, there has been no preliminary cohort study to establish the association of E.coli infection with autoimmune diseases. Therefore, we conducted a large scale, population-matched cohort study to determine the risk of autoimmune disease among patients with exposure to E.coli. METHODS: Utilizing the National Health Insurance Service database, we retrospectively analyzed a total of 259,875 Korean children that consisted of 23,625 exposed and 236,250 unexposed persons from January 1, 2002 to December 31, 2017. The exposed cohort was defined as patients diagnosed with E.coli infection. Unexposed controls were matched by birth year and sex at a 1:10 ratio for each exposed patient, using incidence density sampling. The primary outcome was autoimmune disease development. We used the Cox model to estimate the risks of autoimmune diseases among patients diagnosed with E.coli infection. RESULTS: Over a mean follow-up of 10 years, there were 1455 autoimmune disease cases among exposed patients (incidence rate, 63.6 per 10,000 person-years) and 11,646 autoimmune disease cases among unexposed persons (incidence rate, 50.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.254 (95% CI 1.187-1.325). E.coli infection was associated with increased risks of autoimmune diseases; Reactive arthritis, HR 1.487, 95% CI 1.131-1.956; Henoch Schönlein purpura, HR 1.265, 95% CI 1.050-1.524; Systemic lupus erythematosus, HR 1.838, 95% CI 1.165-2.898; Sjögren's syndrome, HR 2.002, 95% CI 1.342-2.987; IgA nephropathy, HR 1.613, 95% CI 1.388-1.874. Kaplan-Meier cumulative incidence curves also showed a significant association between E.coli infection and incident autoimmune disease (p < 0.0001). This relationship was not only independent of demographic variables, but also remained consistent across various sensitivity analyses. On the other hand, patients with longer hospital stay for E.coli infection were at a higher risk of autoimmune disease (p = 0.0003), and the risk of autoimmune disease also tended to increase, as the frequency of E.coli infection was higher. Moreover, the relative risk of autoimmune disease seemed to be attenuated by use of antibiotics and a history of intestinal infectious disease, but elevated by coexistence of other autoimmune diseases. CONCLUSIONS: Our cohort study indicates that E.coli infection was significantly associated with increased susceptibility to autoimmune diseases, even after adjusting for different factors. Thus, among environmental factors, a previous history of E.coli infection could be a predisposing risk factor in the development of autoimmune diseases.


Assuntos
Doenças Autoimunes , Infecções por Escherichia coli , Humanos , Criança , Estudos Retrospectivos , Estudos de Coortes , Doenças Autoimunes/epidemiologia , Fatores de Risco , Infecções por Escherichia coli/epidemiologia , Incidência
13.
Gynecol Endocrinol ; 39(1): 2247094, 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37599578

RESUMO

OBJECTIVE: To evaluate the effects of various initiation time points and durations of hormone therapy (HT) on cardiovascular and metabolic parameters of premenarche, primary ovarian insufficiency (POI) mouse model, induced by 4-vinylcyclohexene diepoxide. METHODS: A total of 50 mice at 4 weeks of age were developed into POI mouse model, further randomly categorized into 5 groups: control group without any intervention; no HT group with only high-fat diet (NT); group 1 with delayed estradiol treatment (T1); group 2 with on-time, continuous estradiol treatment (T2); and group 3 with on-time estradiol treatment but early stop (T3). Cardiovascular risk and metabolic parameters were measured. RESULTS: Presenting with similar body weights, blood glucose levels of T1, T2, and T3 were all significantly lower than NT (p < .001). Serum total cholesterol and insulin were also significantly lower in all HT groups than in NT, especially in T2 (p < .001). For serum low-density lipoprotein-cholesterol, only T2 resulted in the statically lower level than those of NT, T1, and T3 (p < .001). Aortic thickness was significantly increased with aggravated fibrotic change of the intima in NT, and such consequence was significantly ameliorated in HT groups, mostly lowered in T2 (p < .05). Last, serum pro-inflammatory cytokines were significantly low in the HT groups than in NT, especially in T2 with the lowest level (p < .05). . CONCLUSIONS: On-time, continuous E2 treatment immediately after a biologic estrogen deprivation event significantly reduced metabolic and cardiovascular risks in young, pre-menarche female mouse models of POI, confirming decreased serum levels of pro-inflammatory cytokines.


Assuntos
Doenças Cardiovasculares , Insuficiência Ovariana Primária , Feminino , Animais , Camundongos , Humanos , Doenças Cardiovasculares/etiologia , Insuficiência Ovariana Primária/induzido quimicamente , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Citocinas , Modelos Animais de Doenças , Estradiol , Colesterol
14.
Nucleic Acids Res ; 49(11): 6549-6568, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34086935

RESUMO

In mammals, eight aminoacyl-tRNA synthetases (AARSs) and three AARS-interacting multifunctional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC). MSC components possess extension peptides for MSC assembly and specific functions. Human cytosolic methionyl-tRNA synthetase (MRS) has appended peptides at both termini of the catalytic main body. The N-terminal extension includes a glutathione transferase (GST) domain responsible for interacting with AIMP3, and a long linker peptide between the GST and catalytic domains. Herein, we determined crystal structures of the human MRS catalytic main body, and the complex of the GST domain and AIMP3. The structures reveal human-specific structural details of the MRS, and provide a dynamic model for MRS at the level of domain orientation. A movement of zinc knuckles inserted in the catalytic domain is required for MRS catalytic activity. Depending on the position of the GST domain relative to the catalytic main body, MRS can either block or present its tRNA binding site. Since MRS is part of a huge MSC, we propose a dynamic switching between two possible MRS conformations; a closed conformation in which the catalytic domain is compactly attached to the MSC, and an open conformation with a free catalytic domain dissociated from other MSC components.


Assuntos
Metionina tRNA Ligase/química , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Humanos , Modelos Moleculares , Fatores de Alongamento de Peptídeos/química , Peptídeos/química , Conformação Proteica , RNA de Transferência/química , Proteínas Supressoras de Tumor/química , Zinco/química
15.
J Korean Med Sci ; 38(3): e16, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647217

RESUMO

BACKGROUND: Although the "unclassifiable type" is categorized as one of the radiologic classifications in Mycobacterium avium complex (MAC) pulmonary disease (PD), there have been few studies of this type thus far. We aimed to investigate the radiologic subtypes and treatment outcome of unclassifiable type MAC-PD. METHODS: Ninety-six patients with unclassifiable type MAC-PD who initiated a macrolide-containing regimen from 2001 to 2020 were identified at a tertiary referral center in South Korea. Among these 96 patients, 1-year culture conversion rate was analyzed for 48 patients who received standard treatment (three-drug oral-antibiotic combination with or without an injectable agent) for ≥ 1 year. RESULTS: The mean age of the 96 patients was 65.4 ± 10.8 years, and 72.9% of them were male. These patients were classified into four major radiologic subtypes; the most common subtype was the focal cavity subtype (n = 31, 32.3%), followed by the focal mass or nodule (n = 23, 24.0%), consolidation upon emphysema (n = 21, 21.9%), and bronchiolitis (n = 21, 21.9%) subtypes. For the 48 patients who received standard treatment for ≥ 1 year, the overall rate of culture conversion at 1-year was 93.8%. All patients in the focal cavity subtype and focal mass or nodule subtype categories achieved 1-year culture conversion. Additionally, 1-year culture conversion rate was 92.9% in consolidation upon emphysema subtype and 75.0% in bronchiolitis subtype. CONCLUSION: Unclassifiable type MAC-PD can be radiologically further categorized into four major radiologic subtypes. The treatment outcome of all of these subtypes seems to be favorable.


Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Enfisema Pulmonar , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/diagnóstico por imagem , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Pneumopatias/diagnóstico por imagem , Pneumopatias/tratamento farmacológico , Resultado do Tratamento , Antibacterianos/uso terapêutico , Estudos Retrospectivos
16.
Neuroimage ; 263: 119640, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36176220

RESUMO

Primary motor cortex (M1) consists of a stack of interconnected but distinct layers (L1-L6) which affect motor control through large-scale networks. However, the brain-wide functional influence of each layer is poorly understood. We sought to expand our knowledge of these layers' circuitry by combining Cre-driver mouse lines, optogenetics, fMRI, and electrophysiology. Neuronal activities initiated in Drd3 neurons (within L2/3) were mainly confined within M1, while stimulation of Scnn1a, Rbp4, and Ntsr1 neurons (within L4, L5, and L6, respectively) evoked distinct responses in M1 and motor-related subcortical regions, including striatum and motor thalamus. We also found that fMRI responses from targeted stimulations correlated with both local field potentials (LFPs) and spike changes. This study represents a step forward in our understanding of how different layers of primary motor cortex are embedded in brain-wide circuitry.


Assuntos
Córtex Motor , Camundongos , Animais , Córtex Motor/fisiologia , Optogenética , Neurônios/fisiologia , Tálamo/fisiologia , Encéfalo
17.
Antimicrob Agents Chemother ; 66(12): e0052822, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36326247

RESUMO

In this retrospective analysis including 173 patients in a tertiary referral center in South Korea, compared with the standard therapeutic regimen, clofazimine or moxifloxacin plus standard treatment regimen potentially did not induce a higher 1-year culture conversion rate in patients with Mycobacterium avium complex pulmonary disease who present with cavitary lesions (fibrocavitary or cavitary nodular bronchiectatic type).


Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Humanos , Complexo Mycobacterium avium , Moxifloxacina/uso terapêutico , Clofazimina/uso terapêutico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Retrospectivos , Pneumopatias/microbiologia
18.
Antimicrob Agents Chemother ; 66(9): e0226121, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35950842

RESUMO

We investigated the treatment outcomes of patients with cavitary nodular bronchiectatic (C-NB)-type Mycobacterium avium complex (MAC) pulmonary disease (PD) via outcome comparisons between the fibrocavitary (FC) and C-NB types treated with guideline-based therapy (GBT) composed of daily three-drug oral antibiotics and injectable aminoglycoside. Additionally, we analyzed whether treatment with oral antibiotics alone would result in acceptable outcomes for the C-NB type. From 2002 to 2019, patients with cavitary MAC-PD who received three-drug oral antibiotics with or without an injectable aminoglycoside for ≥1 year were retrospectively enrolled at a tertiary referral center in South Korea. We compared the rates of culture conversion at 12 months according to the radiological type and treatment regimen. The overall culture conversion rate at 12 months of 154 patients with cavitary MAC-PD who received GBT was 75.3%. Among them, the culture conversion rates of 114 patients with the C-NB type were higher than that of 40 patients with the FC-type (80.7% versus 60.0%, respectively; P = 0.009). Of 166 patients with the C-NB-type treated with oral medications with or without an injectable drug, 83.7% achieved culture conversion at 12 months. The conversion rates of those who received oral medications alone and those treated with oral medications and an injectable aminoglycoside were similar (90.4% versus 80.7%, respectively; P = 0.117). In conclusion, the culture conversion rates of the patients with C-NB type treated with GBT were significantly higher than those of patients with the FC type. Additionally, the C-NB type could be treated with oral medications alone.


Assuntos
Bronquiectasia , Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Humanos , Pneumopatias/microbiologia , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/diagnóstico por imagem , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
19.
J Infect Chemother ; 28(8): 1112-1118, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35400550

RESUMO

BACKGROUND: We aimed to investigate treatment outcomes according to the presence or absence of cavitary lesions in patients with the interstitial lung disease (ILD) subtype of unclassifiable type Mycobacterium avium complex (MAC) pulmonary disease (PD). METHODS: Study subjects were enrolled at a tertiary referral center in South Korea from 2001 to 2020. Among patients with MAC-PD who had ILD as an underlying disease, 38 patients who were diagnosed with the ILD subtype of unclassifiable MAC-PD and who received treatment for ≥1 year were selected for this study. Treatment outcomes in terms of microbiological cure at 1 year were retrospectively analyzed for these patients. RESULTS: The mean age of the patients was 64.4 ± 12.9 years, and 63.2% were male. The presence of cavitary lesions was noted in 68.4% (26/38) patients. A usual interstitial pneumonia pattern was the predominant type of ILD, which was identified in 26 (68.4%) patients. The overall 1-year microbiological cure rate of the 38 patients was 65.8% (25/38). Of the 26 patients with cavitary lesions, microbiological cure at 1 year was achieved in 14 patients (53.8%), which is significantly lower than that in patients without cavitary lesions (91.7%, 11/12, p = 0.030). CONCLUSIONS: A clear difference in treatment outcomes was noted in the ILD subtype of MAC-PD according to the presence or absence of cavitary lesions.


Assuntos
Doenças Pulmonares Intersticiais , Infecção por Mycobacterium avium-intracellulare , Idoso , Feminino , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Pediatr Orthop ; 42(8): 439-442, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35818174

RESUMO

BACKGROUND: Preaxial or radial polydactyly is one of the most common hand congenital anomalies in newborns. Contemporary reconstruction methods include ligament reconstruction, excision of the polydactylous thumb, osteotomy, and other surgical techniques according to the type of polydactyly. The purpose of this study was to report mid-term to long-term reconstruction results for thumb (radial) polydactyly. METHODS: We retrospectively reviewed the medical records of patients who underwent reconstruction surgery for preaxial polydactyly. Clinical outcomes, including the range of motion (ROM), pain, and complications, were evaluated. We assessed the final radiographs of the reconstructed thumb to identify the potential development of arthritis or other remaining deformities. After excluding cases without a simple radiograph and cases with a short follow-up period of fewer than 5 years, 26 thumbs were included. The surgical technique followed including excision of polydactylout thumb was tailored to the type of polydactyly. If the nail size of the thumbs was similar, the Bilhaut-Cloquet method was preferred. RESULTS: The mean age of the patients at the surgery and final follow-up was 14.9 months (range: 8 to 30 mo) and 11.9 years (range: 5.8 to 19.3 y), respectively. The mean follow-up was 128.8 months years (range: 60 to 219 mo), and the mean ROM of the thumb was 32.7 and 57.5 degrees in the distal interphalangeal joint (DIP) and metacarpophalangeal (MP) joint, respectively. Ulnar or radial side instability was prominent in 7 patients in the involved joints (26.9%). One patient underwent interphalangeal (IP) fusion for extension lag with pain. The radiologic evaluation revealed that 2 patients developed radiographic evidence of IP joint arthritis (7.7%). Radial deviation of the MP or IP joint existed in 13 cases (range: 5 to 40 degrees) (50.0%), and ulnar deviation of the MP or IP joint existed in 2 cases (range: 19 to 20 degrees) (7.7%). CONCLUSIONS: In mid-term to long-term experience, sequelae such as joint instability, joint stiffness, and remaining deformity cannot be neglected. An unstable MP joint may result if the DIP joint remains stiff or has a lower ROM. LEVEL OF EVIDENCE: Level IV-therapeutic studies.


Assuntos
Artrite , Instabilidade Articular , Polidactilia , Pré-Escolar , Seguimentos , Humanos , Lactente , Recém-Nascido , Dor , Polidactilia/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Polegar/anormalidades , Polegar/cirurgia
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