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OBJECTIVE: This study aimed (1) to simulate pedicle screw pullout after intraoperative external wall perforation and (2) to assess restoration strength with different thread designs in the pedicle screw instrumentation for osteoporotic thoracic vertebrae. METHODS: Twenty fresh-frozen human cadaveric thoracic vertebra bodies were prepared and divided into 4 groups: group 1, 5.5 mm × 45 mm polyaxial single thread pedicle screws (PASTS); group 2, after wall injury 5.5 mm × 45 mm PASTS; group 3, 6.5 mm × 45 mm PASTS after wall injury; and group 4: 6.5 mm × 45 mm polyaxial mixed-threaded screws after wall injury. While group 1 was the control group, groups 2, 3, and 4 were used as study groups after the lateral wall breach. All prepared screw units were placed on a universal pullout measurement testing device. RESULTS: The mean bone mineral density for 20 thoracic vertebrae was 0.57 ± 0.12 g/cm2 (range 0.53-0.6 g/cm2 ). The mean pullout strength was 474.90 Newtons (N) for group 1, 412.85 N for group 2, 475.4 N for group 3, and 630.74N for group 4. The lateral wall breach caused a 14.1 % decrease in average pullout strength compared with the initial screw pullout. Mixed (double)-threaded screws increased pullout strength compared to 6.5 mm screws (P=.036) Conclusion: Using a 1 mm thicker polyaxial pedicle screw or mixed (double)-threaded pedicle screw seems to increase pullout strength; however, this was statistically significant only for group 4. In the thoracic spine, the redirection possibility of the pedicle screw is limited, and augmentation with cement will not be appropriate due to the risk of wall injury-related leakage. Therefore, care should be taken to avoid violating the lateral cortex by using appropriate pedicle entry points and trajectories.
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Tornillos Pediculares , Vértebras Torácicas , Humanos , Vértebras Torácicas/cirugía , Fenómenos Biomecánicos , Densidad Ósea , Cadáver , Vértebras Lumbares/cirugía , Ensayo de MaterialesRESUMEN
BACKGROUND: Although true splenic artery aneurysms (SAA) are rare, due to advancements in imaging techniques, they are seen more frequently. The aim of this study is to present our strategy of managing patients with SAA. METHODS: Retrospectively, 13 patients who were treated in a tertiary university care center between 2012 and 2020 were included. Their demographic, clinical information, and post-operative complications were analyzed. RESULTS: Seven male and six female patients were evaluated between the ages of 27 and 73. The mean age was 49.8±13.2. The diameter of the aneurysm was between 17 and 80 mm with a mean range of 31.5±16 mm. Seven patients were treated with endovascular interventions (EV). Two patients were referred to surgery with failed attempt of EV, but patients refused surgery and were followed up consequently. Patients who had larger aneurysms with an increased risk of rupture underwent aneurysmectomy and splenectomy. Conservative management was decided on two patients initially: A patient who was previously operated on for a sigmoid colon tumor, and had an aneurysm size of 15 mm and another patient with a surgical history of thoracic aortic dissection with an aneurysm size of 18 mm. One patient who underwent surgery had post-operative pancreatic fistula and was treated with percutaneous drainage. The treatment of the remaining 12 patients was completed without any further complications. CONCLUSION: Splenic artery aneurysm treatment should be individualized. Endovascular treatment can be considered for patients with stable aneurysms larger than 2 cm in the elective setting. Open surgical treatment should be considered in patients with ruptured SAA or hemodynamically unstable, complicated patients.
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Aneurisma , Embolización Terapéutica , Procedimientos Endovasculares , Enfermedades Gastrointestinales , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Arteria Esplénica/diagnóstico por imagen , Arteria Esplénica/cirugía , Estudios Retrospectivos , Procedimientos Endovasculares/efectos adversos , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Aneurisma/etiología , Embolización Terapéutica/efectos adversos , Resultado del TratamientoRESUMEN
AIM: CT-guided radiofrequency ablation (RFA) is among the thermal ablative procedures and provides great benefits with a minimally invasive procedure. In this prospective study, we aimed to reveal the significance of a multidisciplinary method in reducing the recurrence and complications in osteoid osteoma patients with CT-guided RFA performed by a team of experts in the field. MATERIALS AND METHODS: A total of consecutive 40 patients with osteoid osteoma were prospectively evaluated and treated with CT-guided RFA. Before and the post ablation the visual analog scale (VAS) and use of nonsteroidal anti-inflammatory drugs (NSAIDS) were compared. RESULTS: Post-ablation VAS of the patients at the 1st week and 3rd month after the procedure decreased significantly (p < 0.01) compared to the pre-ablation. The frequency of NSAID use after the ablation decreased significantly (p < 0.01) compared to the pre-ablation time. The pre-procedure NSAID use of our patients included in the study was average 6.93 per week, the NSAID use in the 3rd month post-procedure controls was average 0.53 per week. Recurrence was detected in 4 of our patients, 36 patients had complete recovery. CONCLUSION: Radiofrequency ablation is an effective treatment method in the management of osteoid osteomas. Radiofrequency ablation has low recurrence rates and provides rapid regression in patients' pain after treatment.
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Neoplasias Óseas , Ablación por Catéter , Osteoma Osteoide , Ablación por Radiofrecuencia , Humanos , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/cirugía , Estudios Prospectivos , Ablación por Catéter/métodos , Resultado del Tratamiento , Dolor/cirugía , Antiinflamatorios no Esteroideos/uso terapéutico , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugíaRESUMEN
BACKGROUND: In this case report, we present two chronic hemodialysis patients with upper extremity swelling due to central venous occlusions together with their clinical presentation, surgical management and brief review of the literature. METHODS: The first patient who was a 63-year-old female patient with a history of multiple bilateral arteriovenous fistulas (AVFs) was referred to our clinic. Physical examination demonstrated a functioning right brachio-cephalic AVF, with severe edema of the right arm, dilated venous collaterals, facial edema, and unilateral breast enlargement. In her history, multiple ipsilateral subclavian venous catheterizations were present for sustaining temporary hemodialysis access. The second patient was a 47-year-old male with a history of failed renal transplant, CABG surgery, multiple AV fistula procedures from both extremities, leg amputation caused by peripheral arterial disease, and decreased myocardial functions. He was receiving 3/7 hemodialysis and admitted to our clinic with right arm edema, accompanied by pain, stiffness, and skin hyperpigmentation symptoms ipsilateral to a functioning brachio-basilic AVF. He was not able to flex his arms, elbow, or wrist due to severe edema. RESULTS: Venography revealed right subclavian vein stenosis with patent contralateral central veins in the first patient. She underwent percutaneous transluminal angioplasty (PTA) twice with subsequent re-occlusions. After failed attempts of PTA, the patient was scheduled for axillo-axillary venous bypass in order to preserve the AV access function. In second patient, venography revealed right subclavian vein occlusion caused secondary to the subclavian venous catheters. Previous attempts for percutaneously crossing the chronic subclavian lesion failed multiple times by different centers. Hence, the patient was scheduled for axillo-axillary venous bypass surgery. CONCLUSION: In case of chronic venous occlusions, endovascular procedures may be ineffective. Since preserving the vascular access function is crucial in this particular patient population, venous bypass procedures should be kept in mind as an alternative for central venous reconstruction, before deciding on ligation and relocation of the AVF.
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Derivación Arteriovenosa Quirúrgica , Cateterismo Venoso Central , Procedimientos Endovasculares , Enfermedades Vasculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Vena Axilar/diagnóstico por imagen , Vena Axilar/cirugía , Vena Subclavia/diagnóstico por imagen , Vena Subclavia/cirugía , Vena Subclavia/patología , Diálisis Renal/efectos adversos , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/etiología , Enfermedades Vasculares/cirugía , Procedimientos Endovasculares/efectos adversos , Edema , Derivación Arteriovenosa Quirúrgica/efectos adversos , Cateterismo Venoso Central/efectos adversosRESUMEN
Objective: Patients with a C6 radiculopathy-mimicking complaint are always in the gray zone if the diagnosis is not clear. The aim of the study is to make the diagnosis clear if the neck and shoulder pain is caused by a dynamic stenosis of the neural foramen at the C5-C6 level. Methods: Patients with a C6 radiculopathy-mimicking complaint were included in the study. Patients had a cervical spine magnetic resonance imaging (MRI) at the normal limits, or a minimal protrusion at the C5-C6 level underwent a dynamic MRI procedure. We measured the foraminal area and spinal cord diameter (SCD) at the C5-C6 level by using the PACS system ROI irregular are determination integral embedded to PACS. Inter- and intraobserver reliability of measurements was evaluated. Results were analyzed statistically, and a p value< 0.05 was accepted as statistically meaningful. Results: A total of 23 patients between January 2019 and June 2019 were included in the study. There were 10 men and 13 women, and the mean age was 41.3 (range 33-53). Foraminal area decrease at C5-C6 in extension and increase in flexion when compared with the neutral position was statistically significant (p < 0.001). Foraminal area changes between the complaint side and the opposite side was not statistically different (p > 0.05). Interobserver and intraobserver reliability of measurements were classified as in almost perfect agreement. Conclusions: Our present work presented dynamic and positional foraminal changes in MRI with radiculopathy-mimicking patients. Soever, we did not find a difference between the clinical complaint side and the opposite side in radiculopathy-mimicking patients. Cervical radiculopathy pain should not be attributed only to foraminal sizes. PACS embedded irregular area measurement integral allows the easy measure of a big number of patients without additional set-up and digital work requirements.
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Radiculopatía , Estenosis Espinal , Adulto , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Estudios de Cohortes , Constricción Patológica/patología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Dolor de Cuello/patología , Estudios Prospectivos , Radiculopatía/diagnóstico por imagen , Reproducibilidad de los Resultados , Estenosis Espinal/patologíaRESUMEN
BACKGROUND: The Ottawa Ankle Rules (OARs) and Shetty test (ST), are assessment guidelines intended to minimize radiographs in patients with ankle trauma. The aim of this study is to determine and compare the effectiveness of OARs and ST in patients admitted to the emergency department (ED) with foot and ankle trauma. METHODS: This prospective cohort study was carried out in the ED of a tertiary care teaching hospital. OARs and ST were practiced by different doctors to patients, who were admitted with foot and ankle trauma. X-ray images were analyzed by a radiologist. Accuracy measures were covered such as sensitivity, specificity, positive predictive value, negative predictive value. RESULTS: The study was completed a total of 207 patients, after achieving the inclusion and exclusion criteria. The mean age of the patients was 33.1±16.3, and 96 (46.4%) were female. For OARs, it was determined that as sensitivity 97.22%, specificity 48.89%, positive predictive value 50.36%, negative predictive value 97.06%, positive likelihood ratio 1.9 and negative likelihood ratio 0.06. If the OARs had been used, there would have been a 32.8% reduction in the ankle X-ray system. For the ST, it was determined that as sensitivity 51.39%, specificity 85.93%, positive predictive value 66.07%, negative predictive value 76.82%, positive likelihood ratio 3.65 and negative likelihood ratio 0.57. DISCUSSION: The OARs can be used as a screening tool, due to causing the high sensitivity in foot and ankle traumas. The ST was found to be inefficient in this study. In addition, the significant reduction in the number of X-rays with the use of OARs is another major result of the study.
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Traumatismos del Tobillo , Traumatismos de los Pies , Fracturas Óseas , Tobillo , Traumatismos del Tobillo/diagnóstico por imagen , Servicio de Urgencia en Hospital , Femenino , Traumatismos de los Pies/diagnóstico por imagen , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Objectives: This study aimed to compare the metabolic parameters obtained from 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and gallium-68 (68Ga)-prostate-specific membrane antigen (PSMA) PET/CT and investigate the relationship between serum alpha-fetoprotein and PET scan parameters in patients with hepatocellular carcinoma. Methods: Fourteen patients were recruited after dynamic magnetic resonance imaging (MRI) of the upper abdomen, and 18F-FDG and 68Ga-PSMA PET/CT imaging studies were conducted. Regions of interest (ROIs) were drawn from lesion-free liver tissue, abdominal aorta (A), and right medial gluteal muscle (G) for the background activity. Maximum standard uptake value (SUVmax) of these regions were compared with the SUVmax of primary tumor (T). Results: On visual assessment, five patients (36%) experienced low 18F-FDG uptake in the primary lesion, three patients (21%) experienced moderate uptake, and six patients (43%) experienced high uptake. However, only one patient (7%) showed low 68Ga-PSMA uptake, two patients (14%) showed moderate uptake, and 11 patients (79%) showed high uptake. Four patients with a low 18F-FDG uptake showed high 68Ga-PSMA uptake, while one patient exhibited low uptake with both 18F-FDG and 68Ga-PSMA. The number of lesions on 68Ga-PSMA PET/CT and MRI was significantly higher than 18F-FDG PET/CT (p=0.042 and 0.026, respectively). T/A and T/G values were significantly higher in 68Ga-PSMA than 18F-FDG (p=0.002 and 0.002, respectively). Conclusion: 68Ga-PSMA PET/CT is superior to 18F-FDG PET/CT in the staging of hepatocellular carcinoma. High 68Ga-PSMA uptake could be promising for PSMA-targeted radionuclide treatments.
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OBJECTIVE: The aim of this retrospective study was to compare the diagnostic accuracies of conventional radiological imaging (CI) methods magnetic resonance imaging or computed tomography (MRI or CT) and intra venous (IV) contrast enhanced (CE) fluorine-18-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) for the staging of bladder cancer (BC). MATERIALS AND METHODS: The 18F-FDG CE-PET/CT results of 35 consecutive patients with BC were analyzed. Diagnostic value of CE-PET/CT and CI are compared for their accuracy in revealing primary tumors, nodal-distant metastasis, and the final tumor staging. The imaging results were compared with the gold standard, including of histopathology and clinical follow-up. We also investigated the effect of maximum standardize uptake value (SUVmax) and lymph node metastasis on survival. RESULTS: The CE-PET/CT had a diagnostic accuracy of 89% (31/35), compared to 57% (19/35) for CI. The results of CE-PET/CT imaging lead to upstaging in 37% (13/35) patients compared to CI staging. For primary tumor detection, the sensitivity of CE-PET/CT was 97% (34/35). Contrast enhanced-PET/CT detected nodal metastases in 19 (54%) patients, whereas CI detected in 9 (26%) patients. Contrast enhanced-PET/CT detected distant metastases in 14 (40%) patients, while conventional methods showed distant metastases in 9 (26%) patients. Maximum SUV of primary tumor does not have a significant effect on survival, whereas the median survival time of patients without lymph node metastasis is longer than patients who have lymph node metastasis (P=0.038). CONCLUSION: These data suggest that 18F-FDG CE-PET/CT had good diagnostic performance compared to conventional imaging for detecting primary tumor, nodal and distant metastasis in BC. Upstaging by CE-PET/CT changed the management of patients.
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Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Vejiga Urinaria , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
AIM: To examine the intra- and inter-observer variability for non-benign thyroid cytological subcategories according to the Bethesda classification system after the second review. METHODS: Between November 2018 and May 2019, thyroid fine needle aspiration biopsies of 381 nodules were retrospectively evaluated. Among them, 74 non-benign (category III-VI) thyroid biopsies, analyzed according to the Bethesda system (pathologist 1:40 vs pathologist 2:34) by two independent pathologists, were reassessed by the same pathologists and by a cytopathologist. In this observer-blinded study, weighted Cohen's kappa was used to assess the intra-observer agreement, and Krippendorff's alpha was used to assess the inter-observer agreement. RESULTS: At the first and second evaluations of pathologists 1 and 2, the percentage agreement was 62.5% for pathologist 1 and 58.8% for pathologist 2. The intra-observer agreement was substantial (κ = 0.705) for pathologist 1, and moderate (κ = 0.447) for pathologist 2. In the second evaluation of pathologist 1 and 2, which was compared with the cytopathologist, the agreement percentage of pathologist 1 with the cytopathologist was 50.0%, and that of pathologist 2 was 56.8%. The inter-observer agreement was below the lowest acceptable limit for an overall agreement (α = 0.634) among the three raters. The inter-observer agreement was only acceptable between the cytopathologist and the second pathologist, while it was low between the other raters. In the evaluation of the non-benign nodules, the mean category score of the cytopathologist was 3.22 and lower than both pathologists (3.73 and 3.58, respectively). CONCLUSIONS: The intra-observer agreement of pathologists was moderate-to-substantial in the evaluation of non-benign thyroid biopsies according to the Bethesda reporting system. However, the inter-observer agreement was below the lowest acceptable limit when the cytopathologist was taken as a reference.
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Citodiagnóstico/métodos , Patólogos , Nódulo Tiroideo/clasificación , Nódulo Tiroideo/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Femenino , Humanos , Biopsia Guiada por Imagen , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Nódulo Tiroideo/patología , Ultrasonografía IntervencionalRESUMEN
OBJECTIVES: This study evaluated the anatomical and functional results of 23-G transconjunctival sutureless vitrectomy (TSV) in diabetic retinopathy (DR) patients with a variety of vitreoretinal diseases. METHODS: Consecutive patients who underwent 23-G TSV for complications of DR were evaluated retrospectively. The primary outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and intraoperative and postoperative complications. RESULTS: A total of 42 eyes of 41 patients were included and followed up for a mean of 15.64±10.0 months. The mean patient age was 59.33±7.4 years. Indications for surgery were nonclearing vitreous hemorrhage (VH) (n=10), tractional retinal detachment (TRD) (n=8), TRD+VH (n=12), epiretinal membrane (n=5), diabetic macular edema (n=3), submacular hemorrhage (n=2), macular hole (n=1), or vitreomacular traction (n=1). There was a significant improvement in the BCVA at the postoperative first and third months, and at the last visit compared with the preoperative value (p<0.001). There was no significant change in the mean IOP measured on the postoperative first day, first week, first month, third month, or the last visit (p>0.05). In the postoperative period, the VH resolved spontaneously in 9 eyes. Repeat 23-G vitrectomy was performed in 6 eyes: 4 with recurrent retinal detachment and 2 with VH. CONCLUSION: The results indicate that 23-G TSV is an effective technique for vitreoretinal disease in patients with DR.
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BACKGROUND: G protein-coupled receptors (GPCR) are well-characterized regulators of a plethora of physiological functions among them the modulation of adipogenesis and adipocyte function. The class of Adhesion GPCR (aGPCR) and their role in adipose tissue, however, is poorly studied. With respect to the demand for novel targets in obesity treatment, we present a comprehensive study on the expression and function of this enigmatic GPCR class during adipogenesis and in mature adipocytes. METHODS: The expression of all aGPCR representatives was determined by reanalyzing RNA-Seq data and by performing qPCR in different mouse and human adipose tissues under low- and high-fat conditions. The impact of aGPCR expression on adipocyte differentiation and lipid accumulation was studied by siRNA-mediated knockdown of all expressed members of this receptor class. The biological characteristics and function of mature adipocytes lacking selected aGPCR were analyzed by mass spectrometry and biochemical methods (lipolysis, glucose uptake, adiponectin secretion). RESULTS: More than ten aGPCR are significantly expressed in visceral and subcutaneous adipose tissues and several aGPCR are differentially regulated under high-caloric conditions in human and mouse. Receptor knockdown of six receptors resulted in an impaired adipogenesis indicating their expression is essential for proper adipogenesis. The altered lipid composition was studied in more detail for two representatives, ADGRG2/GPR64 and ADGRG6/GPR126. While GPR126 is mainly involved in adipocyte differentiation, GPR64 has an additional role in mature adipocytes by regulating metabolic processes. CONCLUSIONS: Adhesion GPCR are significantly involved in qualitative and quantitative adipocyte lipid accumulation and can control lipolysis. Factors driving adipocyte formation and function are governed by signaling pathways induced by aGPCR yielding these receptors potential targets for treating obesity.
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Adipocitos/fisiología , Adipogénesis , Receptores Acoplados a Proteínas G/fisiología , Células 3T3-L1 , Animales , Humanos , Metabolismo de los Lípidos , Lipólisis , Masculino , Ratones , Ratones Endogámicos C57BL , RNA-SeqRESUMEN
Background/aim: In the recent years, videolaryngoscopes (VL) have emerged as alternative devices to direct laryngoscopes (DL) in difficult intubation situations. Therefore, we aimed to compare the Macintosh DL and McGrath VL in terms of the glottic image quality, intubation success, intubation time, hemodynamic response after intubation, and complications in bariatric surgery patients. Material and methods: After obtaining approval by the ethics committee and receiving informed consent, we recorded the demographic and physical data of patients undergoing bariatric surgery. Patients were divided into 2 groups: Group M was intubated with the Macintosh DL, and Group V was intubated with the McGrath VL. After intubation, we noted the CormackLehane score, the duration of intubation, the number of intubation interventions, and the hemodynamic data of patients. Results: A total of 62 patients (ASA II, body mass index of >35 kg/m2) were included in the study. All patients except 1 patient were intubated on the first attempt. Although there was a decrease in heart rate and blood pressure with induction, similar hemodynamic data were obtained between groups during the operation. In group V, we obtained a better glottic image (P = 0.011), but intubation success was similar between the study groups. We also measured the intubation time in group M as 45.9 ± 19.1 s and group V as 57.1 ± 15.8 s (P = 0.015). Discussion: Although we measured longer intubation times with the McGrath VL compared with the Macintosh DL, we obtained a better glottic image without causing hemodynamic changes. However, these findings did not make any difference in terms of intubation success.
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Cirugía Bariátrica/métodos , Hemodinámica/fisiología , Laringoscopía/instrumentación , Adulto , Cirugía Bariátrica/efectos adversos , Femenino , Glotis , Humanos , Laringoscopios , Masculino , Persona de Mediana Edad , Grabación en VideoRESUMEN
The phase change behavior of vanadium dioxide (VO2) has been widely explored in a variety of optical and photonic applications. Commonly, its optical parameters have been studied in two extreme regimes: hot (metallic) and cold (insulating) states. However, in the transition temperatures, VO2 acts like an inherent metamaterial with mixed metallic-insulating character. In this range, the portions of metallic and insulating inclusions are tuned by temperature, and therefore a gradual change of optical parameters can be achieved. In this paper, a universal hybrid modeling approach is developed to model VO2 in the intermediate region. For this aim, the measured reflectivity data, is analyzed and matched through the transfer matrix method (TMM) simulations where an effective medium theory (EMT) is employed. Based on the findings of this approach, not only the relative portions of inclusions are tailored but also their grain shapes are significantly altered in the transition range. Finally, the modeling approach is testified by experimental findings through dynamic device applications operating at short and mid infrared wavelengths. In addition, the hysteretic behaviors on electrical, optical, and structural parameters of the VO2 film along the heating and cooling cycles are demonstrated by the experiments and scrutinized by the simulations.
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Base excision repair (BER) defects and concomitant oxidative DNA damage accumulation play a role in the etiology and progression of late-onset Alzheimer's disease (LOAD). However, it is not known whether genetic variant(s) of specific BER genes contribute to reduced BER activity in LOAD patients and whether they are associated with risk, development and/or progression of LOAD. Therefore, we performed targeted next generation sequencing for three BER genes, uracil glycosylase (UNG), endonuclease VIII-like DNA glycosylase 1 (NEIL1) and polymerase ß (POLß) including promoter, exonic and intronic regions in peripheral blood samples and postmortem brain tissues (temporal cortex, TC and cerebellum, CE) from LOAD patients, high-pathology control and cognitively normal age-matched controls. In addition, the known LOAD risk factor, APOE was included in this study to test whether any BER gene variants associate with APOE variants, particularly APOE ε4. We show that UNG carry five significant variants (rs1610925, rs2268406, rs80001089, rs1018782 and rs1018783) in blood samples of Turkish LOAD patients compared to age-matched controls and one of them (UNG rs80001089) is also significant in TC from Brazilian LOAD patients (p<0.05). The significant variants present only in CE and TC from LOAD are UNG rs2569987 and POLß rs1012381950, respectively. There is also significant epistatic relationship (p = 0.0410) between UNG rs80001089 and NEIL1 rs7182283 in TC from LOAD subjects. Our results suggest that significant BER gene variants may be associated with the risk of LOAD in non-APOE ε4 carriers. On the other hand, there are no significant UNG, NEIL1 and POLß variants that could affect their protein level and function, suggesting that there may be other factors such as post-transcriptional or-translational modifications responsible for the reduced activities and protein levels of these genes in LOAD pathogenesis. Further studies with increased sample size are needed to confirm the relationship between BER variants and LOAD risk.
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Enfermedad de Alzheimer/genética , Apolipoproteínas E/metabolismo , Encéfalo , ADN Glicosilasas/genética , ADN Polimerasa beta/genética , Reparación del ADN , Polimorfismo Genético , Uracil-ADN Glicosidasa/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Apolipoproteínas E/genética , ADN Glicosilasas/metabolismo , ADN Polimerasa beta/metabolismo , Femenino , Humanos , Masculino , Factores de Riesgo , Uracil-ADN Glicosidasa/metabolismoRESUMEN
The enormous sizes of adhesion G protein-coupled receptors (aGPCRs) go along with complex genomic exon-intron architectures giving rise to multiple mRNA variants. There is a need for a comprehensive catalog of aGPCR variants for proper evaluation of the complex functions of aGPCRs found in structural, in vitro and animal model studies. We used an established bioinformatics pipeline to extract, quantify and visualize mRNA variants of aGPCRs from deeply sequenced transcriptomes. Data analysis showed that aGPCRs have multiple transcription start sites even within introns and that tissue-specific splicing is frequent. On average, 19 significantly expressed transcript variants are derived from a given aGPCR gene. The domain architecture of the N terminus encoded by transcript variants often differs and N termini without or with an incomplete seven-helix transmembrane anchor as well as separate seven-helix transmembrane domains are frequently derived from aGPCR genes. Experimental analyses of selected aGPCR transcript variants revealed marked functional differences. Our analysis has an impact on a rational design of aGPCR constructs for structural analyses and gene-deficient mouse lines and provides new support for independent functions of both, the large N terminus and the transmembrane domain of aGPCRs.
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Empalme del ARN , Receptores Acoplados a Proteínas G/genética , Animales , Células COS , Chlorocebus aethiops , Ratones , Especificidad de Órganos , Dominios Proteicos , ARN Mensajero/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
[This corrects the article DOI: 10.1371/journal.pgen.1008145.].
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The interplay of microbiota and the human host is physiologically crucial in health and diseases. The beneficial effects of lactic acid bacteria (LAB), permanently colonizing the human intestine or transiently obtained from food, have been extensively reported. However, the molecular understanding of how LAB modulate human physiology is still limited. G protein-coupled receptors for hydroxycarboxylic acids (HCAR) are regulators of immune functions and energy homeostasis under changing metabolic and dietary conditions. Most mammals have two HCAR (HCA1, HCA2) but humans and other hominids contain a third member (HCA3) in their genomes. A plausible hypothesis why HCA3 function was advantageous in hominid evolution was lacking. Here, we used a combination of evolutionary, analytical and functional methods to unravel the role of HCA3 in vitro and in vivo. The functional studies included different pharmacological assays, analyses of human monocytes and pharmacokinetic measurements in human. We report the discovery of the interaction of D-phenyllactic acid (D-PLA) and the human host through highly potent activation of HCA3. D-PLA is an anti-bacterial metabolite found in high concentrations in LAB-fermented food such as Sauerkraut. We demonstrate that D-PLA from such alimentary sources is well absorbed from the human gut leading to high plasma and urine levels and triggers pertussis toxin-sensitive migration of primary human monocytes in an HCA3-dependent manner. We provide evolutionary, analytical and functional evidence supporting the hypothesis that HCA3 was consolidated in hominids as a new signaling system for LAB-derived metabolites.
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Lactobacillales/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Dieta , Evolución Molecular , Alimentos Fermentados/microbiología , Humanos , Lactatos/metabolismo , Filogenia , Receptores Acoplados a Proteínas G/agonistas , Homología de Secuencia de Aminoácido , Transducción de SeñalRESUMEN
Bilhemia is very rare and serious complication of percutaneous transhepatic biliary drainage (PBD). Bile leakage occurs into the bloodstream through a fistula between the biliary tree and the hepatic venous system. We report a case of a 45-year-old woman with bilhemia complicated by PBD. She was successfully treated with primary coil embolization of biliovenous fistula tract. In the follow-up, bilirubin values dramatically regressed and returned to its normal limits. Rapid increase in total and direct bilirubin values after PBD without biliary tree dilatation almost always suggest biliovenous fistula. It is more likely that biliovenous fistulas will develop in catheters that are removed before the time of the tract maturation. Symptomatic bilhemia should be treated as soon as possible to prevent major complications like bile pulmonary embolism and biliary sepsis.
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INTRODUCTION: Pericatheter bleeding (PB) following tunneled hemodialysis catheter (THC) placement is a common phenomenon. In addition to complicating securement of the THC, the PB may loosen the adhesive catheter dressing and delay wound healing. The primary aim of this study was to determine whether epinephrine-containing local anesthetics rather than plain ones reduce superficial PB after THC placement. METHODS: The study was based on the retrospective analysis of the prospectively gathered data. Forty-six patients receiving local analgesia during THC placement were randomly assigned in a double-blind manner to two groups according to local anesthetic mixtures used (n =22 to prilocaine group [group 1]; n =24 to epinephrine-containing lidocaine group [group 2]). Presence or absence of PB after the THC placement was evaluated. Differences between groups with and without controlling other variables were statistically analyzed. FINDINGS: Epinephrine-containing lidocaine (group 2) significantly reduced PB in comparison with prilocaine, P = 0.003. Use of epinephrine-containing lidocaine (group 2) was associated with a reduction in the likelihood of PB (Odds ratio = 0.017). Meanwhile, use of prilocaine (group 1) had 59.7 times higher odds in the likelihood of PB after THC placement. Lower rate of systolic blood pressure (SBP) in group 2 patients after 5 minutes of injections was also noted, P = 0.008. Epinephrine-containing lidocaine was well tolerated and caused no significant cardiovascular disturbance. DISCUSSION: Local infiltration of epinephrine-containing lidocaine instead of plain local anesthetics during THC insertion may reduce superficial PB and improve patient comfort.
Asunto(s)
Anestésicos Locales/uso terapéutico , Cateterismo/efectos adversos , Epinefrina/uso terapéutico , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Lidocaína/uso terapéutico , Diálisis Renal/efectos adversos , Vasoconstrictores/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos Locales/farmacología , Cateterismo/métodos , Método Doble Ciego , Epinefrina/farmacología , Femenino , Humanos , Lidocaína/farmacología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal/métodos , Estudios Retrospectivos , Vasoconstrictores/farmacologíaRESUMEN
Atherosclerosis is a systemic disease, and multiarterial involvement is common. Involvement of all the supra-aortic arteries may occur in the same patient making cerebral revascularization challenging. In this report, we present complete supra-aortic revascularization, that is, revascularization of the bilateral common carotid and subclavian arteries in a 51-year-old male patient with occluded brachiocephalic trunk, left subclavian artery, and proximally stenotic left common carotid artery. A temporary ascending aorta to left external carotid artery bypass provided meticulous cerebral protection with pulsatile cerebral flow in the presence of a proximal arterial clamp; hence, a neurologically uneventful procedure during bilateral common carotid artery revascularization.