RESUMEN
Age-related hearing loss (ARHL) is characterized by an age-dependent decline of auditory function characterized by with loss of sensory hair cells, spiral ganglion neurons, and stria vascularis (SV) cells in the cochlea of the inner ear. Aging and age-related diseases result from accumulated oxidative damage caused by reactive oxygen species (ROS) generated by mitochondria. The isocitrate dehydrogenase (IDH) family includes three enzymes in human cells: IDH1, IDH2, and IDH3. Although all three enzymes catalyze the same enzymatic reaction, that is, oxidative decarboxylation of isocitrate to produce α-ketoglutarate, each IDH enzyme has unique features. We identified and characterized IDH expression in the cochlea and vestibule of the murine inner ear. We examined the mRNA expression levels of Idh family members in the cochlea and vestibule using reverse transcription-PCR (RT-PCR) and detected expression of IDH family members in both tissues. We also used immunohistochemistry to localize IDH family members within the cochlea and vestibule of the adult mouse inner ear. IDH1 was detected throughout the cochlea. IDH2 was expressed specifically in the hair cells, spiral ganglion, and stria vascularis. IDH3α was found in the cell bodies of neurons of the spiral ganglion, the stria vascularis, and in types II, IV, and V cells of the spiral ligament in a pattern that resembled the location of the Na+, K+-ATPase ion channel. We postulate that the IDH family participates in transporting K+ ions in the cochlea. In the vestibule, all IDH family members were detected in both hair cells and the vestibular ganglion. We hypothesize that IDH1, IDH2, and IDH3 function to protect proteins in the inner ear from oxidative stress during K+ recycling.
Asunto(s)
Oído Interno , Isocitrato Deshidrogenasa/metabolismo , Animales , Oído Interno/enzimología , Oído Interno/metabolismo , Femenino , Humanos , Inmunohistoquímica , Isocitrato Deshidrogenasa/genética , Masculino , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Bancos de Muestras Biológicas , Línea Celular , Células Madre Pluripotentes , Guías de Práctica Clínica como Asunto , Bancos de Muestras Biológicas/ética , Pruebas de Carcinogenicidad , Inestabilidad Genómica , Humanos , Cooperación Internacional , Medición de Riesgo , Seguridad , Donantes de Tejidos , Conservación de Tejido/métodosRESUMEN
The aim of this study was to determine the clinical characteristics of patients with resistant hypertension (RH) and predictors among elderly Korean hypertensives. This prospective, multi-center, observational study evaluated 2439 elderly hypertensive patients between December 2008 and November 2011, who visited secondary hypertension clinics for high blood pressure (BP). Patients were categorized as resistant if their BP was ≥140/90 mm Hg and if they reported using antihypertensive medications from three different drug classes, including a diuretic or drugs from ≥4 antihypertensive drug classes, regardless of BP. Characteristics of patients with RH were compared with those of patients who were controlled with one or two antihypertensive medications after 6-month antihypertensive treatment. In comparison with 837 patients with non-RH, 404 patients with RH were more likely to be aware of their status of high BP before enrollment and have a high baseline systolic BP ≥160 mm Hg, microalbuminuria, high body mass index (BMI) ≥24 kg m(-2) and diabetes mellitus (DM). In drug-naive patients, awareness of hypertension at baseline was the only independent predictor for RH. In elderly Korean hypertensives, BMI (≥24 kg m(-2)), baseline systolic BP (≥160 mm Hg), microalbuminuria, DM and awareness of hypertension showed an association with RH.
Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Sistema de Registros , República de Corea/epidemiología , Factores de RiesgoRESUMEN
This study examined the effect of electron-beam (E-beam) irradiation on the AIGaN/GaN HEMTs for the reduction of gate leakage. After E-beam irradiation, the gate leakage current significantly decreased from 2.68 x 10(-8) A to 4.69 x 10(-9) A at a drain voltage of 10 V. The maximum drain current density of the AIGaN/GaN HEMTs with E-beam irradiation increased 14%, and the threshold voltage exhibited a negative shift, when compared to that of the AIGaN/GaN HEMTs before E-beam irradiation. These results strongly suggest that the reduction of gate leakage current resulted from neutralization nitrogen vacancies and removing of oxygen impurities.
RESUMEN
We have investigated the high-temperature degradation of optical power as well as electrical properties of InGaN/GaN light-emitting diodes (LEDs) fabricated with ITO transparent p-electrode during accelerated electro-thermal stress. As the thermal stress increased from 150 degrees C to 250 degrees C at a electrical stress of 200 mA, the optical power of the LEDs was significantly reduced. Degradation of the optical power was thermally activated, with the activation of 0.9 eV. In addition, the activation energy of the degradation of optical power was fairly similar to that of the degradation of series resistance of the LEDs, 1.0 eV, which implies that the increase in the series resistance may result in the severe degradation of optical power. We also showed that the increase in the series resistance of the LEDs during the accelerated electro-thermal stress can be attributed to reduction of the active acceptor concentration in the p-type semiconductor layers and local joule heating due to the current crowding.
RESUMEN
Understanding the interaction between the magnetic domain wall and the various artificial defects in ferromagnetic nanowires has been of utmost importance for the future realization of the spintronic devices based on the magnetic domain wall motion in nanowires. In this work, the chirality filter effect of the magnetic domain wall in T-shaped ferromagnetic nanowires with a stray field filter was investigated via micromagnetic simulation. A tapered wire was attached to the flat nanowires to form a potential barrier or well for the domain wall propagating along them. For the domain wall passing through the potential barrier or the potential well, the spin structure of the domain wall and the interaction between the domain wall and the potential barrier/well were investigated in detail. The chirality-dependent translational positioning of the domain wall was intensively examined for the potential barrier and potential well cases. The domain wall chirality transmission on relatively long length scales using a series of potential wells was explored.
RESUMEN
The interaction of antiparallel transverse domain walls in ferromagnetic nanowires was investigated via micromagnetic simulation with systematic variations of the external field strength as well as the wire thickness. The interaction of antiparallel transverse walls after domain wall collision exhibited damped multiple collisions due to the rigid structure of the antiparallel transverse walls. The detailed process during the multiple collisions was analyzed via the Fast Fourier Transform technique, along with a careful examination of the inner spin structures of the colliding domain walls. It was found that a frequency peak of multiple collisions shifted to a higher peak position as the external field strength increases. With a stronger field strength of around a few hundred mT, it was found that two antiparallel transverse walls were finally annihilated with formation of complex antivortex structures.
RESUMEN
We have systematically investigated three-dimensional spin configurations in ferromagnetic nanocubes using micromagnetic simulation with variation of cube geometry. For thin cuboids, a spin configuration exhibits a four-domain Landau state with a magnetic vortex structure at the center as in the case of a thin film square. For a thick cube, a complex spin configuration with an S-type cylindrically asymmetric vortex having two cores on a pair of surfaces while a leaf-like and a C-type states are observed on the other two pairs of cube surfaces. Competition between the geometrical symmetry and magnetic energy minimization condition in ferromagnetic nanocubes leads to the complex spin structure with a spontaneously broken symmetry.
RESUMEN
Si(100)/CoFe/AlO(x)/CoFe/FeMn/Cu/Ta magnetic tunnelling transistors (MTTs) with differing base thicknesses (W) were investigated. The magneto-transport properties of the MTTs were measured at 77 K and room temperature (RT). We obtained magneto-current ratios of 48.3% and 55.9% for emitter-base bias voltages of 1.45 and 2.0 V, respectively, at 77 K. The transfer ratios are 2.83 x 10(-5) and 1.52 x 10(-4), respectively, corresponding to bias voltages of 1.45 and 2.0 V. Moreover, the highest tunnel magneto-resistance (TMR) ratios turned out to be 12% and 20% for a base thickness of 30 A at RT and 77 K, respectively. These properties raise not only some fundamental questions regarding the phenomenon of spin-independent tunnelling at low and room temperatures, but also show some promising aspect for magneto-electronic applications. In addition, we attempted to elucidate the reason behind the outstanding TMR effect at low and room temperatures. Finally, the origin of the decrease in the mean free path asymmetry ([Formula: see text]) was clarified by using x-ray photoelectron spectroscopy profile analysis of the elements existing in the interface between Si and the CoFe base (Co, Fe, Al, Si, O).
RESUMEN
Nitric oxide is produced enzymatically by the nitric oxide synthase (NOS), which converts L-arginine in the presence of oxygen to L-citrulline and NO. Moreover, it has been reported that asymmetric dimethylarginine (ADMA) acts as is an endogenous inhibitor of endothelial NOS (eNOS) by competing with the enzyme for L-arginine. In this study, we measured L-arginine and ADMA in normal and preeclamptic women, and also investigated the association between the Glu298Asp eNOS gene polymorphism and preeclampsia. Finally, we assessed eNOS expression levels in the placentas of both normal and preeclamptic patients, using Western blot and immunohistochemistry. L-arginine levels were found to be significantly lower in the preeclamptic women than in the normal pregnant women (p=0.02) but there were no significant differences in ADMA levels between the normal and preeclamptic women. We also determined there to be no association between the Glu298Asp eNOS gene and preeclampsia. With regard to placental eNOS expression, we detected a lower degree of eNOS expression in the preeclamptic syncytiotrophoblasts than in the normal syncytiotrophoblasts. We suggest that reduced L-arginine levels, rather than increased ADMA levels, contribute to the development of preeclampsia, and also that decreased placental eNOS expression constitutes a characteristic finding in preeclamptic placentas.
Asunto(s)
Arginina/análogos & derivados , Arginina/sangre , Óxido Nítrico Sintasa de Tipo III/genética , Placenta/metabolismo , Preeclampsia/metabolismo , Adulto , Arginina/metabolismo , Western Blotting , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Óxido Nítrico Sintasa de Tipo III/metabolismo , Polimorfismo Genético , Preeclampsia/genética , Embarazo , Estudios RetrospectivosRESUMEN
A single high dose of apomorphine (10 mg x kg(-1)) produced not only contextual sensitization to and conditioning of climbing behavior, but also context-independent tolerance to hypothermia. MK-801 (0.15 and 0.3 mg x kg(-1)) inhibited contextual sensitization to and conditioning of climbing behavior. Development of tolerance to hypothermia was also inhibited by MK-801. Dopamine D1 antagonist, SCH23390 (0.5 mg x kg(-1)), but not D2 antagonist, sulpiride, inhibited sensitization to and conditioning of climbing behavior. D2 antagonist, sulpiride (50 mg x kg(-1)), but not D1 antagonist, SCH23390, inhibited development of tolerance to hypothermia. These results suggest that MK-801 inhibited contextual sensitization to climbing behavior and development of tolerance to hypothermia through glutamatergic modulation of dopaminergic functions at dopamine receptors.
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Apomorfina , Condicionamiento Psicológico/efectos de los fármacos , Maleato de Dizocilpina/farmacología , Agonistas de Dopamina , Antagonistas de Aminoácidos Excitadores/farmacología , Hipotermia/metabolismo , Actividad Motora/efectos de los fármacos , Animales , Apomorfina/farmacología , Benzazepinas/farmacología , Depresión Química , Dopamina/metabolismo , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Hipotermia/inducido químicamente , Masculino , Ratones , Ratones Endogámicos ICR , Receptores de Dopamina D1/efectos de los fármacos , Receptores de Dopamina D2/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Sulpirida/farmacologíaRESUMEN
Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive imaging technique capable of identifying primary tumors and metastases with high sensitivity and accuracy. The aim of this study was to evaluate the diagnostic accuracy of whole-body FDG-PET imaging for the detection of recurrent or metastatic breast cancer after surgery. Whole-body FDG-PET imaging was performed on 27 patients with suspected recurrent breast carcinoma. PET images were evaluated qualitatively for each patient and lesion. FDG-PET scans showed that there were 61 reference sites of malignant or benign lesions in 27 patients. In a patient-based analysis, FDG-PET scans correctly identified 16 of 17 patients with recurrent or metastatic disease and 8 of 10 without recurrence, resulting in a sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively. In a lesion-based analysis, FDG-PET scans correctly identified 46 of 48 lesion sites with recurrent or metastatic disease and 11 of 13 without recurrence. The overall sensitivity, specificity, and accuracy for all lesion sites were 96%, 85%, and 93%, respectively. FDG-PET scans revealed unsuspected recurrent or metastatic diseases in 8 of 27 (30%) of patients and 11 of 20 (55%) distant metastatic lesions. In 13 patients treatment was altered by the outcome of the PET scan. We concluded that whole-body FDG-PET scan is a useful diagnostic imaging modality for detecting recurrent or metastatic breast carcinoma in patients suspected of having recurrent disease after primary surgery.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Metástasis de la Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Radiofármacos , Tomografía Computarizada de Emisión , Adulto , Neoplasias de la Mama/cirugía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
The effects of baclofen on the development of reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine were examined in mice. A single administration of morphine induced hyperactivity and the morphine-induced hyperactivity was inhibited dose dependently by the administration of a GABA(B)receptor agonist, baclofen (1.25, 2.5 and 5 mg kg(-1), i.p.). Daily repeated administration of morphine developed reverse tolerance to the hyperactivity of morphine. The concomitant administration of baclofen inhibited the morphine-induced hyperactivity and the baclofen administration prior to and during the chronic administration of morphine in mice inhibited the development of reverse tolerance to the hyperactivity of morphine (10 mg kg(-1), s.c.). Postsynaptic dopamine receptor supersensitivity was also developed in reverse-tolerant mice that had received the same morphine. The development of postsynaptic dopamine receptor supersensitivity was evidenced by the enhanced ambulatory activity of apomorphine (2 mg kg(-1), s.c.). Baclofen also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine may be modulated via the activation of GABA(B)receptors induced by baclofen.
Asunto(s)
Baclofeno/farmacología , Hipercinesia/inducido químicamente , Morfina/antagonistas & inhibidores , Morfina/farmacología , Receptores Dopaminérgicos/metabolismo , Sinapsis/metabolismo , Animales , Apomorfina/farmacología , Baclofeno/uso terapéutico , Tolerancia a Medicamentos , Agonistas del GABA/farmacología , Agonistas del GABA/uso terapéutico , Hipercinesia/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos ICR , Monitoreo Fisiológico , Actividad Motora/efectos de los fármacos , Factores de TiempoRESUMEN
Glutamate receptors-mediated excitotoxicity is believed to play a role in the pathophysiology of neurodegenerative diseases. The present study was performed to evaluate the inhibitory effect of fangchinoline, a bis-benzylisoquinoline alkaloid, which has a characteristic as a Ca2+ channel blocker, on excitatory amino acids (EAAs)-induced neurotoxicity in cultured rat cerebellar granule neuron. Fangchinoline (1 and 5 microM) inhibited glutamate (1 mM), N-methyl-D-aspartate (NMDA; 1 mM) and kainate (100 microM)-induced neuronal cell death which was measured by trypan blue exclusion test. Fangchinoline (1 and 5 microM) inhibited glutamate release into medium induced by NMDA (1 mM) and kainate (100 microM), which was measured by HPLC. And fangchinoline (5 microM) inhibited glutamate (1 mM)-induced elevation of intracellular calcium concentration. These results suggest that inhibition of Ca2+ influx by fangchinoline may contribute to the beneficial effects on neurodegenerative effect of glutamate in pathophysiological conditions.
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Alcaloides/farmacología , Bencilisoquinolinas , Cerebelo/citología , Aminoácidos Excitadores/antagonistas & inhibidores , Aminoácidos Excitadores/toxicidad , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Cerebelo/efectos de los fármacos , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Ácido Glutámico/metabolismo , Plantas Medicinales/química , Ratas , Ratas Sprague-DawleyRESUMEN
Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from one which is indolent to one which rapidly progresses. Although it is the metastasis rather than the primary tumor that ultimately overwhelms the patients, studies concerning the DNA pattern have focused on the primary tumors. This study was undertaken to identify heterogeneities between primary tumors and metastases, and to evaluate the prognostic significance of the ploidy pattern and the S-phase fraction (SPF) of metastatic nodes in axillary node positive patients. Seventy-four frozen specimens of the primary and corresponding metastatic nodes from 37 patients have been analyzed by flow cytometry and the SPF calculated. The results of ploidy pattern analysis in primaries revealed 25 diploidy (67.6%) and 12 aneuploidy (32.4%), while those in metastasis showed 17 diploidy (46.0%) and 20 aneuploidy (54.0%). The aneuploidy group in metastatic nodes had the poorer histological grade (85.0% vs. 15.0%, p = 0.02), and more mean metastatic nodes (5.75 +/- 2.10 vs. 3.05 +/- 1.56, p = 0.018), and more frequent lymphatic vessel invasion (65.0% vs. 11.8%, p = 0.031) than its counterpart. Decreased expression of ER (70.6% vs. 25.0% p = 0.006) and increased expression of c-erbB2 (65.0% vs. 23.5%, p = 0.012) were observed in the aneuploidy of metastatic nodes. The group with higher SPF in metastatic nodes had more metastatic nodes (5.47 +/- 2.31 vs. 4.00 +/- 1.78, p = 0.042), and the higher incidence of lymphatic vessel invasion (57.9% vs. 22.2%, p = 0.027), and poor histological grade (71.4% vs. 37.5%, p = 0.039). In conclusion, the cell populations in metastatic nodes revealed DNA pattern which differed from that of primary tumors. The ploidy pattern and SPF in metastatic nodes might be considered as discriminate measure for risk factors in breast cancer patients with positive axillary node.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Citometría de Flujo , Metástasis Linfática/genética , Ploidias , Fase S/genética , Adulto , Anciano , Axila/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ganglios Linfáticos/patología , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Receptores de Estrógenos/biosíntesis , Factores de RiesgoRESUMEN
OBJECTIVES: We report the development of a fully automated, random access, chemiluminescent immunoassay, for the detection of human cardiac Troponin I (cTnI) in serum and plasma for use on the ACS:180(R) System. DESIGN AND METHODS: This assay format uses a combination of two monoclonal antibodies covalently coupled to paramagnetic (PMP) particles as a solid phase and an affinity purified polyclonal antibody, specific to the N-terminal domain of cTnI (peptide-3 region) labeled with a chemiluminescent compound as the detector antibody. The assay offers excellent low-end sensitivity and precision. RESULTS: No interferences are observed from by blood components such as HAMA and drugs used in cardiac therapy. Patient samples tested on the ACS:180 cTnI assay showed good correlation with the Stratus cTnI assay (ACS: cTnI = 1. 02*Stratus + 0.05 g/L, r = 0.96, n = 1170). CONCLUSION: Paired with the other ACS:180 cardiac assays, myoglobin and CKMBII, the ACS:180 system now offers an excellent panel of cardiac assay for use in rapid and accurate diagnosis of a myocardial event.
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Inmunoensayo/métodos , Miocardio/química , Troponina I/sangre , Anticuerpos Monoclonales , Especificidad de Anticuerpos , Biomarcadores/sangre , Pruebas de Química Clínica , Femenino , Humanos , Mediciones Luminiscentes , Masculino , Infarto del Miocardio/diagnóstico , Análisis de Regresión , Sensibilidad y Especificidad , Troponina I/inmunologíaRESUMEN
cis-Prenyltransferase catalyzes the sequential condensation of isopentenyl diphosphate with allylic diphosphate to synthesize polyprenyl diphosphates that play vital roles in cellular activity. Despite potential significance of cis-prenyltransferase in plant growth and development, no gene of the enzyme has been cloned from higher plants. Using sequence information of the conserved region of cis-prenyltransferase cloned recently from Escherichia coli, Micrococcus luteus, and yeast, we have isolated and characterized the first plant cis-prenyltransferase from Arabidopsis thaliana. Sequence analysis revealed that the protein is highly homologous in several conserved regions to cis-prenyltransferases from M. luteus, E. coli, and yeast. In vitro analyses using the recombinant protein overexpressed in E. coli revealed that the enzyme catalyzed the formation of polyprenyl diphosphates ranging in carbon number from 100 to 130 with a predominance of C(120). The enzyme exhibited a higher affinity for farnesyl diphosphate than for geranylgeranyl diphosphate, with the K(m) values being 0.13 and 3.62 micrometer, respectively, but a lower affinity for isopentenyl diphosphate, with a K(m) value of 23 micrometer. In vitro rubber biosynthesis analysis indicated that the Arabidopsis cis-prenyltransferase itself could not catalyze the formation of higher molecular weight polyprenyl diphosphates similar to natural rubber. A reverse transcriptase-polymerase chain reaction analysis showed that the gene was expressed at low levels in Arabidopsis plant, in which expression of the cis-prenyltransferase in leaf and root was higher than that in stem, flower, and silique. These results indicate the tissue-specific expression of cis-prenyltransferase and suggest a potential role and significance of the enzyme in the polyisoprenoid biosynthesis in plants.
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Arabidopsis/enzimología , Goma , Transferasas/fisiología , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Biblioteca de Genes , Magnesio/farmacología , Datos de Secuencia Molecular , Octoxinol/farmacología , Reacción en Cadena de la Polimerasa , Especificidad por Sustrato , Transferasas/genéticaRESUMEN
Recent clinical trials have demonstrated the significant cancer preventive potential of vitamin E in many different cancer sites, ranging from oral and pharyngeal cancer to prostate cancer. There is an extensive experimental basis for this clinical cancer inhibition. The experimental background includes animal studies (experimental pathology, immunology and molecular biology, synergism, selectivity and safety), in vitro biochemical studies, and human studies (epidemiology and biomarkers, prevention of many pathologic entities other than cancer).
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Neoplasias/prevención & control , Vitamina E/farmacología , Animales , Biomarcadores de Tumor , Modelos Animales de Enfermedad , Estudios Epidemiológicos , Humanos , Neoplasias Experimentales/prevención & control , Vitamina E/uso terapéuticoRESUMEN
OBJECTIVE: To assess the diagnostic efficiency of positron emission tomography with 18-fluorine fluorodeoxyglucose in detecting breast cancer in augmented breasts. DESIGN: Retrospective study. SETTING: University hospital, Korea. SUBJECT: 9 cases or 8 patients with breasts augmented with paraffin or silicone. INTERVENTION: FDG-PET, mammography, and ultrasonography RESULTS: The mammogram detected the breast cancer in only 1 of 3 patients, and ultrasonography gave a false positive result in 1 patient with an augmented breast. In contrast, PET predicted all the cancers and 5/6 benign lesions. 2/3 breast cancers had axillary FDG uptake interpreted as showing metastatic involvement, and in 1 case with cancer with no axillary lymph node involvement there was no FDG uptake in the axilla, which correlated with the pathological finding. CONCLUSIONS: Although the high cost of PET makes its use as a screening test for all patients with augmented breasts unrealistic, it would be the best diagnostic choice if other methods failed.