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1.
Neuron ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31668484

RESUMO

Anatomical and behavioral data suggest that the ventrolateral orbitofrontal cortex (VLO), which exhibits extensive connectivity and supports diverse sensory and cognitive processes, may exert global influence over brain activity. However, this hypothesis has never been tested directly. We applied optogenetic fMRI to drive various elements of VLO circuitry while visualizing the whole-brain response. Surprisingly, driving excitatory thalamocortical projections to VLO at low frequencies (5-10 Hz) evoked widespread, bilateral decreases in brain activity spanning multiple cortical and subcortical structures. This pattern was unique to thalamocortical projections, with direct stimulations of neither VLO nor thalamus eliciting such a response. High-frequency stimulations (25-40 Hz) of thalamocortical projections evoked dramatically different-though still far-reaching-responses, in the form of widespread ipsilateral activation. Importantly, decreases in brain activity evoked by low-frequency thalamocortical input were mediated by GABA and activity in zona incerta. These findings identify specific circuit mechanisms underlying VLO control of brain-wide neural activities.

2.
Dig Dis Sci ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31776862

RESUMO

BACKGROUND AND AIMS: Colitis-associated cancer (CAC) is one of the most serious complications in patients with inflammatory bowel disease. Sphingosine kinase 1 (Sphk1) is a key enzyme in the sphingolipid pathway and has oncogene potential for inducing both initiation and progression of tumors. The aim of this work is to characterize the role of epithelial Sphk1 in mouse colitis and CAC models. METHODS: We investigated the roles of Sphk1 in CAC by conditional deletion of Sphk1 in intestinal epithelial cells (IECs). RESULTS: CAC was induced in both Sphk1ΔIEC/ApcMin/+ and Sphk1IEC/ApcMin/+ mice by administration of 2% dextran sodium sulfate (DSS) for 7 days. Genetic deletion of Sphk1 significantly reduced the number and size of tumors in ApcMin/+ mice. Histologic grade was more severe in Sphk1ΔIEC/ApcMin/+ mice compared with Sphk1IEC/ApcMin/+ mice (invasive carcinoma, 71% versus 13%, p < 0.05). Deletion of Sphk1 decreased mucosal proliferation and inhibited STAT3 activation and genetic expression of cyclin D1 and cMyc in tumor cells. Conditional deletion of Sphk1 using CRISPR-Cas9 in HCT 116 cells inhibited interleukin (IL)-6-mediated STAT3 activation. CONCLUSIONS: Epithelial conditional deletion of Sphk1 inhibits CAC in ApcMin/+-DSS models in mice by inhibiting STAT3 activation and its target signaling pathways.

3.
Medicine (Baltimore) ; 98(41): e17565, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593140

RESUMO

RATIONALE: Invasive moles occur in the fertile period, with about 95% occurring after previous mole removal and the remaining 5% occurring after several other pregnancies. PATIENT CONCERNS: A 27-year-old patient developed a rare invasive mole two months after a missed abortion. DIAGNOSES: A transvaginal ultrasound scan revealed a 3.6 × 2.9 × 2.4 cm sized lesion with cystic vascular areas within it, within the myometrium of the right fundal posterior region of the uterus. There was no metastasis to other organs. INTERVENTIONS: After administration of methotrexate, the level of beta-human chorionic gonadotropin (ß-hCG) was elevated and liver enzymes were also markedly elevated. She wanted to retain fertility for future pregnancies. After laparoscopic removal of the myometrial invasive mole, the incision site was sutured with a 3-0 V-Loc. OUTCOMES: One year later, a natural pregnancy occurred and a cesarean section was performed at 36 weeks. LESSONS: This is the first reported case of its type. Our case demonstrated that pelviscopic removal of an invasive mole is possible if there are no other metastases, and that future pregnancy and childbirth are still feasible in women of reproductive age.


Assuntos
Mola Hidatiforme Invasiva/cirurgia , Miométrio/cirurgia , Pelve/diagnóstico por imagem , Neoplasias Uterinas/cirurgia , Adulto , Gonadotropina Coriônica/análise , Feminino , Humanos , Mola Hidatiforme Invasiva/diagnóstico por imagem , Mola Hidatiforme Invasiva/patologia , Laparoscopia/métodos , Metotrexato/administração & dosagem , Miométrio/patologia , Gravidez , Resultado do Tratamento , Ultrassonografia/métodos , Neoplasias Uterinas/patologia
4.
Regul Toxicol Pharmacol ; 109: 104487, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31585136

RESUMO

Cassia tora Linn. is an annual or perennial plant of the Fabaceae/Leguminosae family. It is used in traditional medicine for various biological activities including anti-constipation, anti-inflammatory, visual acuity, and hepato-protective activities. The present study was carried out to investigate the potential toxicity of C. tora L. seed ethanol extract (CTSEE) following a 13-week repeated oral administration to Sprague-Dawley rats. CTSEE was administered orally to male and female rats for 13 weeks at 0 (control), 500, 1000, and 2000 mg/kg/day (n = 10, for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 4-week recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples collected. There were no treatment-related adverse effects in clinical signs, body weight, food consumption, estrous cycle, sperm parameters, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any doses tested. Under the present experimental conditions, the no-observed-adverse-effect level of the CTSEE was >2000 mg/kg/day in both genders, and no target organs were identified.

5.
Orthop Surg ; 11(5): 845-849, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663284

RESUMO

OBJECTIVE: To define risk factors of having persistent shoulder pain following cervical spine surgery. METHODS: From April 1995 to May 2012, 862 patients underwent cervical spine surgery in a tertiary referral university hospital. Ninety-six patients were referred to a shoulder surgeon for persistent shoulder pain over 3 months after cervical spine surgery. Thirty-five were excluded from the study due to failure to follow-up or lack of radiographic data. We analyzed a total of 61 patients as patient group (PG) compared to age, sex, and surgeon matched control group (CG) with no shoulder pain after surgery. Medical records were reviewed for age, sex, level of cervical surgery, approach of cervical surgery, underlying medical problems, final diagnosis of the shoulder pathology, and shoulder visual analog scale (VAS) score. The pre- and post-operative variables for level of cervical surgery, approach of cervical surgery, underlying medical history, and shoulder VAS were compared and analyzed in this study. RESULTS: The number of patients with lower cervical level surgery was significantly higher (91 patients, 74.6%) compared to upper cervical level surgery (31 patients, 25.4%) (P = 0.005). Anterior approach was more frequently used (70 patients, 57.3%) compared to posterior approach (52 patients, 42.7%) (P < 0.001). The final diagnosis of shoulder pathology in PG were rotator cuff disease in 31 patients, adhesive capsulitis in 18 patients, and calcific tendinitis in 10 patients respectively. No significant difference for preoperative shoulder VAS score was found in both groups. A lower level of cervical spine pathology in patients (C4 -T1 level) and posterior approach surgery were factors that significantly presented with more shoulder pain. Subgroup analysis revealed no statistical difference for level of cervical surgery and approach of cervical surgery among groups with different shoulder pathology. CONCLUSIONS: The current study includes patients with persistent shoulder pain following cervical surgery without having evidence of concurrent preexisting shoulder pathology documented previously. We suggest that posterior approach and lower level of cervical surgery patients could be clinically relevant risk factors for persistent shoulder pain following cervical spine surgery.

6.
Yonsei Med J ; 60(10): 992-997, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31538435

RESUMO

PURPOSE: We investigated the characteristics of lung allocation and outcomes of lung transplant (LTx) according to the Korean urgency status. MATERIALS AND METHODS: LTx registration in the Korean Organ Transplantation Registry (KOTRY) began in 2015. From 2015 to June 2017, 86 patients who received LTx were enrolled in KOTRY. After excluding one patient who received a heart-lung transplant, 85 were included. Subjects were analyzed according to the Korean urgency status. RESULTS: Except for Status 0, urgency status was classified based on partial pressure of oxygen in arterial blood gas analysis and functional status in 52 patients (93%). The wait time for lung allograft was well-stratified by urgency (Status 0, 46.5±59.2 days; Status 1, 104.4±98.2 days; Status 2 or 3, 132.2±118.4 days, p=0.009). Status 0 was associated with increased operative times and higher intraoperative blood transfusion. Status 0 was associated with prolonged extracorporeal membrane oxygenation use, postoperative bleeding, and longer mechanical ventilation after operation. Survival of Status 0 patients seemed worse than that of non-Status 0 patients, although differences were not significant. CONCLUSION: The Korean urgency classification for LTx is determined by using very limited parameters and may not be a true reflection of urgency. Status 0 patients seem to have poor outcomes compared to the other urgency status patients, despite having the highest priority for donor lungs. Further multi-center and nationwide studies are needed to revise the lung allocation system to reflect true urgency and provide the best benefit of lung transplantation.


Assuntos
Transplante de Pulmão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Sistema de Registros , República da Coreia , Análise de Sobrevida , Resultado do Tratamento
7.
Anticancer Res ; 39(9): 5123-5133, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519624

RESUMO

BACKGROUND/AIM: We investigated the role of esophagectomy after clinical complete response (cCR) to chemoradiotherapy for esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Patients with resectable cT3-T4a/anyN/M0 or anyT/N+/M0 thoracic ESCC received two cycles of induction chemotherapy and then chemoradiotherapy (50.4 Gy/28 fractions). Patients with cCR were randomized to surgery or observation. RESULTS: Among 86 patients, 38 (44.2%) achieved cCR after chemoradiotherapy; 37 were randomized to surgery (n=19) or observation (n=18). Although there were trends of better disease-free survival (DFS) toward the surgery arm in the intent-to-treat analysis (2-year DFS, 66.7% vs. 42.7%; p=0.262) or as-treated analysis (66.7% vs. 50.2%; p=0.273), overall survival was not different between the two arms in the intent-to-treat (HR=1.48; p=0.560) or as-treated analysis (HR=1.09; p=0.903). Among the 11 patients having recurrence during observation, 8 underwent surgery (n=7) or endoscopic dissection (n=1). CONCLUSION: Close observation with salvage surgery might be a reasonable option in resectable ESCC patients achieving cCR after chemoradiation.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Terapia Combinada , Progressão da Doença , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Resultado do Tratamento , Adulto Jovem
8.
J Mol Biol ; 431(22): 4475-4496, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31473157

RESUMO

Aminoacyl-tRNA synthetases (AARSs) ligate amino acids to their cognate tRNAs during protein synthesis. In humans, eight AARSs and three non-enzymatic AARS-interacting multifunctional proteins (AIMP1-3), which are involved in various biological processes, form a multi-tRNA synthetase complex (MSC). Elucidation of the structures and multiple functions of individual AARSs and AIMPs has aided current understanding of the structural arrangement of MSC components and their assembly processes. Here, we report the crystal structure of a complex comprising a motif from aspartyl-tRNA synthetase (DRS) and the glutathione transferase (GST)-homology domains of methionyl-tRNA synthetase (MRS), glutamyl-prolyl-tRNA synthetase (EPRS), AIMP2, and AIMP3. In the crystal structure, the four GST domains are assembled in the order of MRS-AIMP3-EPRS-AIMP2, and the GST domain of AIMP2 binds DRS through the ß-sheet in the GST domain. The C-terminus of AIMP3 enhances the binding of DRS to the tetrameric GST complex. A DRS dimer and two GST tetramers binding to the dimer with 2-fold symmetry complete a decameric complex. The formation of this complex enhances the stability of DRS and enables it to retain its reaction intermediate, aspartyl adenylate. Since the catalytic domains of MRS and EPRS are connected to the decameric complex through their flexible linker peptides, and lysyl-tRNA synthetase and AIMP1 are also linked to the complex via the N-terminal region of AIMP2, the DRS-GST tetramer complex functions as a frame in the MSC.

9.
IEEE Int Conf Rehabil Robot ; 2019: 861-867, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31374738

RESUMO

This paper presents a novel robotic finger prosthesis for partially amputated patients who have lost a thumb and index finger. The challenging issues were to design i) a three-degree-of-freedom (DOF) underactuated mechanism that mimics intact finger movements including motion profiles and self-adaptation for unknown constraints, ii) an attachment socket for everyday life that allows ease of donning and doffing, and comfortable wearability, and iii) a shape to pack the selected components including an actuator, linkages, and sensors into a limited space avoiding motion interference with other intact fingers and wrist. This paper reports our effort to solve the challenging issues. The proposed three-DOF prosthetic finger can generate 4.6N pinch force and 99.4°/s angular velocity at the MCP joints. For command signals, surface-electromyogram (sEMG) sensors were used. This enables users to operate the fingers with certain configuration and grasping force. The performance of the proposed design was verified through the box-and-block test and bottle opening test with a patient who has a partially amputated hand.

10.
Oral Oncol ; 96: 34-41, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31422211

RESUMO

OBJECTIVES: Signaling between cancer stem cells (CSC) and their extracellular matrix has a crucial role in CSC progression and maintenance. However, mediators of this signaling pathway in head and neck squamous cell carcinoma (HNSCC) are largely unknown. Here, we explored whether integrin ß1, which is one of the key regulators of the communication between cells and their microenvironment, affected the stemness of HNSCC cells. MATERIALS AND METHODS: We examined self-renewal capacity, chemoresistance, and xenograft tumorigenicity after knockdown of integrin ß1 in primary HNSCC cells. In addition, we studied the role of focal adhesion kinase (FAK), an intracellular downstream molecule of integrin signaling, in influencing stemness of HNSCC. The relevance of Notch1 and integrin ß1 interactions in HNSCC cells was also examined. Finally, immunohistochemical analysis was carried out to test whether the coexpression of integrin ß1 and Notch1 in the samples from HNSCC patients correlated with their survival. RESULTS: Targeting integrin ß1 in HNSCC cells inhibited self-renewal, chemoresistance, and in vivo tumor-forming capacity. Treatment with an inhibitor of FAK decreased self-renewal capacities and expression of various putative stem cell markers (Oct4, Sox2, and Nanog) in a dose-dependent manner. Moreover, knockdown of integrin ß1 decreased the expression of Notch1 and its target genes (Hey1 and Hes1). Notably, HNSCC patients demonstrating simultaneous expression of integrin ß1 and Notch1 in their tissue samples had significantly worse survival rate. CONCLUSION: Integrin ß1/Notch1 axis has a significant role in the regulation of stemness in HNSCC.

11.
BMJ Open ; 9(7): e026605, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340958

RESUMO

OBJECTIVES: Clinical practice guidelines for the management of pain and sedation in critically ill patients have been developed and applied; however, there is limited data on medication use among elderly patients. This study identifies current practice patterns for analgo-sedative use in mechanically ventilated elderly patients in Korea using a national claims database. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Ventilated elderly patients aged 65 years or older in intensive care units (ICUs) from an aged patients' national claims database in Korea PRIMARY OUTCOME MEASURES: Use of sedatives including benzodiazepines, opioids and non-opioid analgesics, neuromuscular blocking agents (NMBAs) and antipsychotic drugs were analysed by the duration of mechanical ventilation (MV), age and time. RESULTS: From 2012 to 2016, 22 677 elderly patients underwent MV in 267 general or tertiary ICUs. Mean age was 77.2 (±6.9) years and the median duration of MV was 4.1 days; 77.2% of patients received sedatives, 65.0% analgesics, 29.1% NMBAs and 19.6% antipsychotics. Midazolam (62.0%) was the most commonly prescribed medication. The proportions of sedatives, analgesics and NMBAs increased, whereas the percentages of person-days decreased with longer MV duration (p<0.01). With advanced age, the prevalence and duration of sedative, analgesic and NMBA use decreased (adjusted OR (95% CI) 0.98 (0.97 to 0.98) in all three classes) while antipsychotic did not (adjusted OR 1.00 (1.00-1.01)). Annually, benzodiazepines showed reduced administration (76.2% in 2012 and 71.4% in 2016, p<0.01), while daily opioid dose increased (21.6 in 2012 vs 30.0 mg in 2016, p<0.01). CONCLUSIONS: The prevalence of sedative, analgesic and NMBAs use and daily opioid doses were lower, whereas antipsychotic use was higher compared with those in previous studies in adult patients. The findings warrant further studies investigating appropriateness and safety of medication use that consider clinical severity scores with a focus on elderly patients in ICUs.

12.
J Shoulder Elbow Surg ; 28(10): 1861-1868, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279717

RESUMO

BACKGROUND: The correlation between shoulder strength deficits and function in rotator cuff tears remains uncertain. This study aimed to determine the correlation between shoulder strength deficits and shoulder function evaluated by various clinical scoring systems. METHODS: A total of 262 patients (mean age, 59.67 years [standard deviation, 8.06 years]) who underwent full-thickness rotator cuff repair were included. Patients in group I (n = 188) had small to large rotator cuff tears, whereas those in group II (n = 74) had massive rotator cuff tears. Demographic factors, isokinetic test results, and shoulder function evaluated using various scoring systems were obtained. Correlation differences according to severity of the rotator cuff tear were evaluated. RESULTS: We found weak correlations between shoulder strength deficits (peak torque and total work) and clinical outcomes in patients with rotator cuff tears (r = -0.288). For patients in group I (nonmassive tears), we found a weaker correlation (r = -0.242) according to the tear pattern. However, shoulder strength deficits in group II patients (massive tears) were strongly correlated with American Shoulder and Elbow Surgeons (r = -0.598), Constant (r = -0.582), and Short Form 36 (r = -0.511) scores, especially regarding internal rotator strength deficits. CONCLUSIONS: Shoulder strength deficits measured via isokinetic testing and shoulder function were weakly correlated in patients with rotator cuff tears. However, shoulder strength deficits in patients with massive tears considerably worsened shoulder function and systemic disability, but not regional disability. In particular, internal rotator strength deficits were strongly correlated with poor shoulder function.

13.
Chem Biol Interact ; 311: 108755, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31319077

RESUMO

Effective control of white adipose tissue accumulation would provide a therapeutic strategy for obesity, which poses a growing global problem. The plant chemical mangiferin stimulates adenosine monophosphate-activated protein kinase (AMPK), which inhibits adipogenesis and has therefore been considered a therapeutic target for obesity and related diseases. We previously reported the anti-inflammatory properties of 6'-O-acetyl mangiferin (OAM). In this study, we evaluated the potential of OAM as an AMPK activator in vitro in 3T3-L1 preadipocytes. OAM inhibited adipogenesis as indicated by lower intracellular lipid and triglyceride accumulation as well as reduced adipogenic gene and protein expression upon treatment. OAM-treated 3T3-L1 cells excreted more glycerol, indicating increased lipolysis, which was supported by increased expression of lipolysis-related genes, including adipose triglyceride lipase and hormone-sensitive lipase. We determined that OAM upregulates lipolysis via phosphorylation-dependent activation of AMPK. Further, OAM upregulated the ß-oxidation pathway as indicated by enhanced expression of phosphorylated acetyl-CoA-carboxylase and long-chain acyl-CoA synthetase 1. In conclusion, OAM markedly decreased intracellular lipid accumulation by enhancing lipolysis via AMPK activation and by upregulating ß-oxidation. Thus, OAM has potential as a drug for the prevention and/or improvement of obesity and related diseases and deserves further study.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Iris (Planta)/química , Lipólise/efeitos dos fármacos , Xantonas/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Iris (Planta)/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , PPAR gama/genética , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Triglicerídeos/metabolismo
14.
Orthop Traumatol Surg Res ; 105(5): 867-876, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331798

RESUMO

BACKGROUND: Indications for revision surgery are unclear in refractory cubital tunnel syndrome patients, and the optimal surgical method has not been determined. The systematic review evaluates the evidence of functional outcome for revision surgery in refractory cubital tunnel syndrome patients. HYPOTHESIS: We hypothesize that functional outcome of revision surgery in refractory cubital tunnel syndrome will be favorable. METHODS: We searched PubMed, Ovid/MEDLINE, Cochrane, Google Scholar, and EMBASE databases using the keywords "cubital tunnel syndrome" or "recurrent cubital tunnel syndrome" and "revision surgery" according to the MeSH index for English-language studies. We performed a systematic review using PRISMA guidelines. The review was registered in PROSPERO (CRD42018096622). RESULTS: Based on the Oxford Centre for Evidence-Based Medicine criteria, one level 3b study and nine level 4 studies were identified, including 195 elbows of 192 patients aged 15-75 years. The remission period for recurrent cubital tunnel syndrome was 6-21 months, and the follow-up period was 6-113 months. Transposition surgery was the primary surgery in 99 (51%) of 178 elbows. The most common intraoperative finding at revision surgery was perineural scarring (79%), with the most frequent entrapment site being the medial intermuscular septum (33%). The most common revision surgery was submuscular transposition of the ulnar nerve (75%). Most studies reported favorable outcomes, although outcomes varied widely among studies. CONCLUSION: This is the first study to summarize the functional outcomes of revision surgery for refractory cubital tunnel syndrome which showed to be favorable. Functional outcomes were averagely reported and varied widely. A consensus regarding the functional outcomes parameter after surgery for cubital tunnel syndrome is urgently needed. LEVEL OF EVIDENCE: III, systematic review.

15.
Clin Orthop Surg ; 11(2): 220-225, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31156775

RESUMO

Background: Fracture-dislocation of the proximal interphalangeal (PIP) joint of the finger is challenging due to the high risk of stiffness. The purpose of this study is to evaluate the clinical and radiological results of a modified transosseous wiring technique for the management of chronic fracture-dislocations of the PIP joint. Methods: Ten patients (nine men and one woman; mean age, 38.3 years; range, 21 to 69 years) with neglected fracture-dislocation of the PIP joint were included. The mean duration from injury to operation was 14.7 weeks (range, 3 to 66 weeks). The dorsolateral approach and extension block pinning were used to reduce dislocation. After thorough debridement of the scar tissues in the dorsal dead space and the fracture site, the reduction was maintained with transosseous wiring. Radiologic evaluations of bone union and arthritic changes and clinical evaluations (range of motion of the PIP joint and Disabilities of the Arm, Shoulder and Hand [DASH] score) were performed. The mean follow-up period was 12.9 months (range, 12 to 19 months). Results: All patients demonstrated evidence of radiographic healing within a mean healing time of 6 weeks (range, 4 to 10 weeks); however, one had a widened gap and one had an early arthritic change. The mean range of motion in the PIP joint was 81° (range, 50° to 105°). The mean DASH score was 21.6 (range, 7.5 to 35.8). Conclusions: For chronic fracture-dislocation of the PIP joint, transosseous wiring with direct curettage and optimal bone purchase can provide satisfying outcome.

16.
Int J Stem Cells ; 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31242717

RESUMO

Background and Objectives: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. Methods and Results: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory- cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. Conclusions: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs.

17.
J Korean Med Sci ; 34(14): e110, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30977312

RESUMO

BACKGROUND: The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS: In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS: The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6-10 days vs. 14 days; IQR, 12-21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION: PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02202941.


Assuntos
Antibacterianos/uso terapêutico , Pró-Calcitonina/análise , Sepse/tratamento farmacológico , Idoso , Antibacterianos/economia , Biomarcadores/análise , Efeitos Psicossociais da Doença , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sepse/mortalidade , Sepse/patologia , Método Simples-Cego
18.
Chem Biodivers ; 16(7): e1900033, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977279

RESUMO

Achillea alpina is widely distributed in Korea and is often used as a folk medicine for stomach disorders. Although a previous study isolated antioxidant compounds (flavonoid O-glucoside, sesquiterpene) from this plant, no systematic study of its chemical constituents had been reported. The present study aimed to identify the phytochemicals present in a methanol extract of A. alpina, assess their potential antioxidant activities in vitro, and determine their effects on melanogenesis in B16F10 melanoma cells. Column chromatographic separation of aqueous fractions of A. alpina led to the isolation of 17 compounds. The chemical structures of these compounds were determined using spectroscopic data from electrospray ionization-mass spectrometry and nuclear magnetic resonance. To the best of our knowledge, the present study is the first to identify compounds 2-10 and 12-17 in A. alpina. Furthermore, compound 6 possessed powerful antioxidant activity, while compound 15 suppressed intracellular tyrosinase activity and thus reduced melanogenesis in B16F10 cells. Therefore, our research suggested that these naturally occurring compounds have the potential to reduce oxidative stress and promote skin whitening. Further investigations will be required to elucidate the mechanisms underlying the antioxidant and antityrosinase activities of these compounds.


Assuntos
Achillea/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
19.
J Patient Saf ; 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30882616

RESUMO

OBJECTIVES: Teach-back methods are reported to improve patient outcomes by encouraging patient understanding and participation and are increasingly being used in various clinical settings. This study attempts to identify the effectiveness of discharge education using the teach-back method on 30-day readmission. METHODS: MEDLINE, CINAHL, Embase, The Cochrane Library, and Web of Science were used to search experimental studies. The search terms were "discharged patient," "teach-back," and "30-day readmission" published in English up until July 2017. Two trained reviewers performed a critical appraisal of retrieved studies using the Risk of Bias Assessment tool for Nonrandomized Studies. Data were analyzed using Cochrane Review Manager (Revman) software 5.2. RESULTS: A total of five studies were analyzed (3 studies on heart failure, 1 study on total joint replacement, and 1 study on a coronary artery bypass graft). The main content of the teach-back education was to confirm and reinforce the patients' comprehension of health-related information. Among the five studies, three studies were included in the meta-analysis. The odds ratio of 30-day readmission for discharge education with the teach-back method and usual care was 0.55 (95% confidence interval, 0.34-0.91; P = 0.02). The I score was 0%, which means that the analyzed studies are homogeneous. CONCLUSIONS: The results indicate that discharge education with the teach-back method resulted in a 45% reduction in 30-day readmission. However, only a few studies were included in the analysis, and they showed a high risk of selection bias. Therefore, we suggest that well-designed randomized controlled trials be conducted.

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