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2.
Ann Lab Med ; 42(1): 79-88, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374352

RESUMO

Background: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are genomic imprinting disorders that are mainly caused by a deletion on 15q11-q13, the uniparental disomy of chromosome 15, or an imprinting defect. We evaluated the utility of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a diagnostic tool and for demonstrating the relationship between molecular mechanisms and clinical presentation. Methods: We performed MS-MLPA using DNA samples from 93 subjects (45 PWS, 24 AS, and 24 non-PWS/AS controls) who had previously undergone MS-PCR for the diagnosis of PWS/AS. We compared the results of both assays, and patients' clinical phenotypes were reviewed retrospectively. Results: MS-MLPA showed a 100% concordance rate with MS-PCR. Among the 45 PWS patients, 26 (57.8%) had a deletion of 15q11-q13, and the others (42.2%) had uniparental disomy 15 or an imprinting defect. Among the 24 AS patients, 16 (66.7%) had a deletion of 15q11-q13, 7 AS patients (29.2%) had uniparental disomy 15 or an imprinting defect, and one AS patient (4.2%) showed an imprinting center deletion. Conclusions: MS-MLPA has clinical utility for the diagnosis of PWS/AS, and it is superior to MS-PCR in that it can identify the molecular mechanism underlying the disease.


Assuntos
Síndrome de Angelman , Síndrome de Prader-Willi , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/genética , Cromossomos Humanos Par 15/genética , Metilação de DNA , Humanos , Metilação , Reação em Cadeia da Polimerase Multiplex , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Estudos Retrospectivos
3.
Ann Lab Med ; 42(2): 213-248, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635615

RESUMO

Background: Sequence-based identification is one of the most effective methods for species-level identification of nontuberculous mycobacteria (NTM). However, it is time-consuming because of the bioinformatics processes involved, including sequence trimming, consensus sequence generation, and public database searches. We developed a simple and fully automated software that enabled species-level identification of NTM from trace files, SnackNTM (https://github.com/Young-gonKim/SnackNTM). Methods: JAVA programing language was used for software development. The SnackNTM diagnostic algorithm utilized 16S rRNA gene sequences, according to the Clinical & Laboratory Standards Institute guidelines, and an rpoB gene region was adjunctively utilized to narrow down the species. The software performance was validated using trace files of 234 clinical cases, comprising 217 consecutive cases and 17 additionally selected cases of unique species. Results: SnackNTM could analyze multiple cases at once, and all the bioinformatics processes required for sequence-based NTM identification were automatically performed with a single mouse click. SnackNTM successfully identified 95.9% (208/217) of consecutive clinical cases, and the results showed 99.0% (206/208) agreement with manual classification results. SnackNTM successfully identified all 17 cases of unique species. In a processing time comparison test, the analysis and reporting of 30 cases, which took 150 minutes manually, took only 40 minutes with SnackNTM. Conclusions: SnackNTM is expected to reduce the workload for NTM identification, especially in clinical laboratories that process large numbers of cases.


Assuntos
Micobactérias não Tuberculosas , Software , Micobactérias não Tuberculosas/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
4.
J Glaucoma ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34628426

RESUMO

PRCIS: A decrease in Bruch's membrane opening-minimum rim area, which represents the optic nerve head, preceded a decrease in the peripapillary retinal nerve fiber layer thickness and the visual field index. PURPOSE: This study aimed to investigate the relative comparison between a decrease in Bruch's membrane opening-minimum rim area (BMO-MRA), the peripapillary retinal nerve fiber layer thickness (RNFLT), and the visual field index (VFI), according to the severity of glaucoma. METHODS: This retrospective cross-sectional study included 121 eyes (73 with open-angle glaucoma and 48 normal eyes). The optic nerve head (ONH) and retinal nerve fiber layer were analyzed using spectral domain optical coherence tomography, and VFI was obtained using the Humphrey Field Analyzer. The tipping points of RNFLT for VFI and BMO-MRA were estimated using broken-stick regression models. Polynomial regression analysis was performed, and the changes in the three parameters were expressed as a graph. RESULTS: The tipping point of the RNFLT for the VFI was 88.62▒µm (95% confidence interval (CI), 79.59 to 97.65; P=0.001). The tipping point of the RNFLT for BMO-MRA was 60.00▒µm (95% CI, 48.28 to 71.72; P=0.220). Above the tipping point, BMO-MRA decreased with a decrease in the RNFLT (slope=0.0135 [95% CI, 0.0115 to 0.0155]; P<0.001); below the tipping point, BMO-MRA did not decrease significantly (slope=0.0002 [95% CI, -0.0177 to 0.0181]; P=0.983). Polynomial regression analysis showed that with the progression of glaucoma, BMO-MRA decreased more rapidly, and this preceded a decrease in the RNFLT followed by a decrease in the VFI. CONCLUSION: The ONH parameter, BMO-MRA, showed a faster decrease than RNFLT and VFI in early glaucoma. BMO-MRA may help detect early glaucomatous damage and its progression.

5.
J Phys Chem A ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34628860

RESUMO

Conformers have similar vibrational structures both in neutral (S0) and cationic (D0) states owing to the comparable force fields between their nuclei. Nevertheless, there is a continuous development of vibrational spectroscopic techniques to rigorously identify individual conformers in the designated molecule but only in the S0 state. We developed an inventive conformer-specific vibrational spectroscopic technique to measure identifiable vibrational spectra of individual conformers in both S0 and D0 states. We measured isomer-specific vibrational spectra in both states for gas-phase acetone and oxetane isomers from a solution with azeotropic composition to verify the proposed techniques that are based on infrared (IR) resonant vacuum ultraviolet mass-analyzed threshold ionization (VUV-MATI) spectroscopy. The measured IR dip VUV-MATI and IR hole-burn VUV-MATI spectra for each isomer, which correspond to isomer-specific vibrational spectra in both states, can be represented by IR-resonant VUV photoionization and one-photon VUV-MATI spectra of the binary mixture, respectively, under supersonic expansion conditions. The partial pressures of the individual isomers in the binary mixture with different mole fractions estimated according to the relative peak intensities in the measured spectra provide insights on solute-solvent interactions. We suggest that the verified IR-resonant VUV-MATI spectroscopy can form the basis of effective schemes toward conformational chemistry.

6.
Adv Mater ; : e2106215, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632653

RESUMO

Color-selective multi-functional and multiplexed photodetectors have attracted considerable interest with the increasing demand for color filter free optoelectronics which can simultaneously process multispectral signal via minimized system complexity. The low efficiency of color-filter technology and conventional laterally pixelated photodetector array structures often limit opportunities for widespread realization of high-density photodetectors. Here, we develop low-temperature solution-processed vertically stacked full color quantum dot (QD) phototransistor arrays on plastic substrates for high-resolution color-selective photosensor applications. Particularly, the three different-sized/color (RGB) QDs were vertically stacked and pixelated via direct photo-patterning using a unique chelating chalcometallate ligand functioning both as solubilizing component and, after photoexposure, a semiconducting cement creating robust, insoluble, and charge-efficient QD layers localized in the a-IGZO transistor region, resulting in efficient wavelength-dependent photo-induced charge transfer. Thus, high-resolution vertically stacked full color QD photodetector arrays were successfully implemented with the density of 5,500 devices cm-2 on ultrathin flexible polymeric substrates with highly photosensitive characteristics such as photoresponsivity (1.1×104 AW-1 ) and photodetectivity (1.1×1018 Jones) as well as wide dynamic-ranges (> 150 dB). This article is protected by copyright. All rights reserved.

7.
Ann Coloproctol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34610653

RESUMO

Purpose: Local excision (LE) is an alternative initial treatment for clinical T1 rectal cancer, and has avoided potential morbidity. This study aimed to evaluate the clinical outcomes of LE compared with total mesorectal excision (TME) for clinical T1 rectal cancer. Methods: Between January 2000 and December 2011, we retrospectively reviewed from multicenter data in patients with clinically suspected T1 rectal cancer treated with either LE or TME. Of 1,071 patients, 106 were treated with LE and 965 were treated with TME. The data were analyzed using propensity score matching, with each group comprising 91 patients. Results: After propensity score matching, the median follow-up time was 60.8 months (range, 0.6-150.6 months). After adjustment for the necessary variables, patients who underwent LE showed a significantly higher local recurrence rate than did those who underwent TME; however, there were no differences in disease-free survival and overall survival. In the multivariate analysis, age (hazard ratio [HR], 9.620; 95% confidence interval [CI], 3.415-27.098; P<0.001) and angiolymphatic invasion (HR, 3.63; 95% confidence interval, 1.33-9.89; P=0.012) were independently associated with overall survival. However, LE was neither associated with overall survival nor disease-free survival. Conclusion: LE for clinical T1 rectal cancer yielded a higher local recurrence rate than did TME. Nevertheless, LE provided comparable overall survival rate and can be proposed as an optional treatment in terms of organ-preserving strategies.

9.
Anal Bioanal Chem ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617153

RESUMO

Sensitive and selective determination of protein biomarkers with high accuracy often remains a great challenge due to their existence in the human body at an exceptionally low concentration level. Therefore, sensing mechanisms that are easy to use, simple, and capable of accurate quantification of analyte are still in development to detect biomarkers at a low concentration level. To meet this end, we demonstrated a methodology to detect thrombin in serum at low concentration levels using polypyrrole (PPy)-palladium (Pd)nanoparticle-based hybrid transducers using liposomes encapsulated redox marker as a label. The morphology of Ppy-Pd composites was characterized by scanning electron microscopy, and the hybrid structure provided excellent binding and detection platform for thrombin detection in both buffer and serum solutions. For quantitative measurement of thrombin in PBS and serum, the change in current was monitored using differential pulse voltammetry, and the calculated limit of quantification (LOQ) and limit of detection (LOD) for the linear segment (0.1-1000 nM of thrombin) were 1.1 pM and 0.3 pM, in serum, respectively. The sensors also exhibited good stability and excellent selectivity towards the detection of thrombin, and thus make it a strong candidate for adopting its sensing applications in biomarker detection technologies.

10.
Int J Hematol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34617186

RESUMO

Isolated extramedullary relapse (EMR) without bone marrow relapse (BMR) after allogeneic hematopoietic cell transplantation (allo-HCT) is a rare condition in patients with acute lymphoblastic leukemia (ALL), and the role of immunotherapeutic agents for these patients remains unclear. We analyzed treatment outcomes of blinatumomab or inotuzumab ozogamicin (INO) as first- or second-line salvage therapy in nine patients with Philadelphia chromosome-negative B-cell precursor ALL presenting with isolated EMR after previous allo-HCT. In seven patients receiving blinatumomab as first-line salvage therapy, 4 (57.1%) achieved complete remission (CR). Among the three patients without remission after blinatumomab, two switched to INO and subsequently showed responses {one CR and one partial response [PR]}, and one switched to multiagent chemotherapy that led to CR. In the two patients receiving first-line salvage therapy with INO, one showed PR and the other achieved CR. Overall, 6 (66.7%) of nine patients achieved CR, and five of them proceeded to allo-HCT in CR. The median overall survival after relapse was 27.8 months. In conclusion, both blinatumomab and INO showed good response rates and a safe bridging role to second allo-HCT in patients with isolated EMR. However, clinical differences between isolated EMR and EMR with BMR remain to be elucidated.

11.
Sci Rep ; 11(1): 19886, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615979

RESUMO

This study aims to quantitatively investigate the optical coherence tomographic angiography (OCTA) findings of capillary congestion and its association with macular edema (ME) recurrence in chronic branch retinal vein occlusion (BRVO). We retrospectively reviewed the medical records of 115 consecutive patients with major ischemic BRVO who reached stable macula (without ME for two consecutive visits) at baseline (the first visit within the stable period). All patients were classified into a recurrence or non-recurrence groups depending on ME recurrence. Capillary congestion of deep capillary plexuses (DCP-C) and other abnormal capillary lesions were segmented, and their areas, vascular densities, and mean retinal thicknesses (MRT) were calculated. The main outcomes were differences between the two groups and risk factors for recurrence among baseline and OCTA parameters. A total of 76 eyes were included, of which 22 (28.9%) recurred. DCP-C existed in all eyes at baseline. MRT of DCP-C (p = 0.006) was greater in the recurrence group. Greater MRT of DCP-C (OR: 1.044; p = 0.002) and more frequent intravitreal injections (OR: 1.803; p < 0.001) were associated with a higher risk of relapsing ME. DCP-C may contribute to the anatomical stability of chronic BRVO and simultaneously be the source of ME.

12.
Medicine (Baltimore) ; 100(37): e27263, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664878

RESUMO

ABSTRACT: Evaluating various parameters, including preoperative cardiorespiratory fitness markers, is critical for patients with morbid obesity. Also, clinicians should prescribe suitable exercise and lifestyle guideline based on the tested parameters. Therefore, we investigated cardiorespiratory fitness and its correlation with preoperative evaluation in patients with morbid obesity scheduled for laparoscopic sleeve gastrectomy.A retrospective cross-sectional study was conducted with 38 patients (13 men and 25 women; mean age, 34.9 ±â€Š10.9 years) scheduled for laparoscopic sleeve gastrectomy. Cardiopulmonary exercise stress tests were also performed. Measured cardiopulmonary responses included peak values of oxygen consumption (VO2), metabolic equivalents (METs), respiratory exchange ratio, heart rate (HR), and rate pressure product. Body composition variables were analyzed using bioimpedance analysis, laboratory parameters (hemoglobin A1c, lipid profile, inflammatory markers), and comorbidities. In addition, self-reported questionnaires were administered, including the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), Short-Form Health Survey (SF-36), and Moorehead-Ardelt Quality of Life Questionnaire (MAQOL).The average body mass index (BMI) and percent body fat were 39.8 ±â€Š5.7 kg/m-2 and 46.2 ±â€Š6.1%, respectively. The VO2peak/kg, METs, RERpeak, HRpeak, RPPpeak, age-predicted HR percentage, and VO2peak percentage were 18.6 ±â€Š3.8 mL/min-1/kg-1, 5.3 ±â€Š1.1, 1.1 ±â€Š0.1, 158.5 ±â€Š19.8, 32,414.4 ±â€Š6,695.8 mm Hg/min-1, 85.2 ±â€Š8.8%, and 76.1 ±â€Š14.8%, respectively. BMI (P = .026), percent body fat (P = .001), HRpeak (P = .018), erythrocyte sedimentation rate (P = .007), total BDI (P = .043), HDRS (P = .025), SF-36 (P = .006), and MAQOL (P = .007) scores were significantly associated with VO2peak/kg. Body fat percentage (P < .001) and total SF-36 score (P < .001) remained significant in the multiple linear regression analysis.Various cardiorespiratory fitness markers were investigated in patients with morbid obesity who underwent the sleeve gastrectomy. Peak aerobic exercise capacity was significantly associated with preoperative parameters such as body fat composition and self-reported quality of life in these patients. These results could be utilized for preoperative and/or postoperative exercise strategies in patients with morbid obesity scheduled for laparoscopic sleeve gastrectomy.

13.
Nat Med ; 27(10): 1725-1734, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34642494

RESUMO

Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low with current treatment options (nucleos(t)ide analogs (NAs) and pegylated interferons). Bepirovirsen is an antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture and animal models, bepirovirsen leads to reductions in HBV-derived RNAs, HBV DNA and viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial is the first evaluation of the safety and activity of an antisense oligonucleotide targeting HBV RNA in both treatment-naïve and virally suppressed individuals with chronic HBV infection. The primary objective was to assess the safety and tolerability of bepirovirsen in individuals with chronic hepatitis B (CHB) (NCT02981602). The secondary objective was to assess antiviral activity, including the change from baseline to day 29 in serum hepatitis B surface antigen (HBsAg) concentration. Participants with CHB infection ≥6 months and serum HBsAg ≥50 IU ml-1 were enrolled from seven centers across Hong Kong and the Republic of Korea and randomized (3:1 within each dose cohort) to receive bepirovirsen or placebo via subcutaneous injection twice weekly during weeks 1 and 2 (days 1, 4, 8 and 11) and once weekly during weeks 3 and 4 (days 15 and 22). Participants were then followed for 26 weeks. Twenty-four participants were treatment-naïve and seven were receiving stable NA therapy. Treatment-emergent adverse events were mostly mild/moderate (most commonly injection site reactions). Eleven (61.1%) and three (50.0%) treatment-naïve participants experienced one or more treatment-emergent adverse event in the bepirovirsen and placebo groups, respectively. In participants receiving NA therapy, the corresponding numbers were three (60.0%) and one (50.0%). Transient, self-resolving alanine aminotransferase flares (≥2× upper limit of normal) were observed in eight treatment-naïve participants and three participants on stable NA regimens in the bepirovirsen treatment arms. HBsAg reductions were observed and were significant versus placebo for treatment-naïve participants receiving bepirovirsen 300 mg (P = 0.001), but not for the bepirovirsen 150 mg group (P = 0.245) or participants receiving stable NA therapy (P = 0.762). Two participants in each of the 300 mg dose groups achieved HBsAg levels below the lower limit of quantitation by day 29 (n = 3) or day 36 (n = 1). Bepirovirsen had a favorable safety profile. These preliminary observations warrant further investigation of the safety and activity of bepirovirsen in a larger CHB patient population.

14.
PLoS One ; 16(10): e0257241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648499

RESUMO

Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.

15.
Comput Methods Programs Biomed ; 211: 106424, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34598081

RESUMO

BACKGROUND: The accurate prediction of blood glucose (BG) level is still a challenge for diabetes management. This is due to various factors such as diet, personal physiological characteristics, stress, and activities influence changes in BG level. To develop an accurate BG level predictive model, we propose a personalized model based on a convolutional neural network (CNN) with a fine-tuning strategy. METHODS: We utilized continuous glucose monitoring (CGM) datasets from 1052 professional CGM sessions and split them into three groups according to type 1, type 2, and gestational diabetes mellitus (T1DM, T2DM, and GDM, respectively). During the preprocessing, only CGM data points were utilized, and future BG levels of four different prediction horizons (PHs, 15, 30, 45, and 60 min) were used as output. In training, we trained a general CNN and a multi-output random forest regressor using a hold-out method for each group. Next, we developed two personalized models: (1) by fine-tuning the general CNN on partial sample points of each CGM dataset, and (2) by learning a CNN from scratch on the points. RESULTS: For all groups, the fine-tuned CNN showed the lowest average root mean squared error, average mean absolute percentage error, highest average time gain (PH = 15 and 60 min in T1DM) and highest percentage in region A of Clarke error grid analysis at all PHs. In the performance comparison between the fine-tuned CNN and other models, we found that the fine-tuned CNN improved the performance of the general CNN in most cases and outperformed the scratch CNN at all PHs in all groups, making the fine-tuning strategy was useful for accurate BG level prediction. We analyzed all cases of four predictive patterns in each group, and found that the input BG level trend and the BG level at the time of prediction were related to the future BG level trend. CONCLUSIONS: We demonstrated the efficacy of the fine-tuning method in a large number of CGM datasets and analyzed the four predictive patterns. Therefore, we believe that the proposed method will significantly contribute to the development of an accurate personalized model and the analysis for its predictions.

16.
Front Immunol ; 12: 704526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497607

RESUMO

Objective: Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine model. Methods: To investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib. Results: Baricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway. Conclusions: The present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE.

17.
Eur Radiol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34505194

RESUMO

OBJECTIVES: To investigate transcholecystic management of extrahepatic duct (EHD) stones using balloon ampulloplasty in patients who are poor candidates for endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) and assess its efficacy and safety. METHODS: Forty-one patients who were unable to undergo ERCP or had failed ERCP with non-dilated intrahepatic ducts (IHD) between February 2019 and October 2020 were retrospectively enrolled. After clinical improvement with percutaneous cholecystostomy (PC), EHD stones were managed through cystic duct passage, guidewire unwinding, sheath insertion, and EHD stone removal using balloon ampulloplasty. If the transcholecystic route failed, a transhepatic approach was used according to the pre-existing cholangiogram obtained via PC. We evaluated the technical success rate and complications of each step. RESULTS: The technical success rate for the transcholecystic-only approach was 80.5%. The remaining cases were successfully managed with transhepatic conversion. Multiple stone removal sessions were required in 22% of the cases. One patient with combined IHD stones was initially converted to a transhepatic approach without any transcholecystic removal trial. The technical success rates for each step were as follows: cystic duct passage (38/40, 95%), guidewire unwinding (36/38, 94.7%), sheath insertion (36/36, 100%), and stone removal using balloon ampulloplasty (33/36, 91.7%). The overall clinical success was 97.6% (40/41) without major procedure-related complications. Thereafter, cholecystectomy was successfully performed in patients with concomitant gallstones (n = 20). No postprocedural complications occurred during the follow-up (1-70 days). CONCLUSIONS: Percutaneous EHD stone removal through transcholecystic and transhepatic routes after PC is effective and safe in poor candidates for PTBD or ERCP. KEY POINTS: • This study shows the safety and efficacy of extrahepatic duct (EHD) stones in patients who are poor candidates for initial percutaneous transhepatic biliary drainage and endoscopic retrograde cholangiopancreatography. • The overall technical success for the transcholecystic-only approach was 80.5% (33/41). Including transhepatic conversions, it was 100% (41/41). Stone removal was successful in one session in 78% (32/41) of the patients and in multiple sessions in 28.1% (9/41) of the patients. • Balloon ampulloplasty with stone expulsion using an occlusion balloon catheter is also a safe and effective method for removing EHD stones.

18.
Brain Pathol ; : e13020, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506076

RESUMO

We report a case of spinal ependymoma with ZFTA-YAP1 fusion, occurring in a 5-year-old boy who complained of back pain. It was high-grade ependymoma, developed in the spinal cord at the level of T9-12. Since ZFTA-YAP1 fusion-positive ependymoma has never been reported in the spinal cord, this case is exceptional and worth reporting because the anatomical location, genetics, and epigenetics are important parameters in the classification of the ependymal tumor. This is the first case of spinal ependymoma harboring ZFTA-fusion to be diagnosed by NGS and Sanger studies to the best of our knowledge.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34495634

RESUMO

The individual moiety-functionalized organosilane single molecule, that is, 1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]-3-vinyltrisiloxane (TMSV), is investigated as an electrolyte additive for a less charge-consuming and viscoelastic solid electrolyte interphase (SEI) forming agent, finally accomplishing extremely quick (6 min) rechargeable SiO/NCM811 lithium-ion batteries. The moiety of the vinyl group serves with a poly(ethylene oxide)-like viscoelastic SEI film on the SiO electrode, which provides a physicochemically stable interphase during long-term cycling. The increase of DC-iR due to electrolyte decomposition on the continuously exposed SiO surface with cycling is inhibited by the alternated SEI composition. Degradation of bulk electrolyte solution caused by thermal decomposition of the LiPF6 salt is also suppressed by the trimethylsilyl moiety in the TMSV additive, which scavenges HF. Owing to the multifunctionality of TMSV, the cycle performance of laminated pouch full cells comprising high-nickel-contented NCM811 positive electrode and SiO-enriched negative electrode is significantly improved at both room and elevated temperatures. Furthermore, the 6 min quick recharging cycle performance is also enhanced by the TMSV additive.

20.
Sci Rep ; 11(1): 17604, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475505

RESUMO

Apolipoprotein E (ApoE) plays multiple roles in lipid transport, neuronal signaling, glucose metabolism, mitochondrial function, and inflammation in the brain. It is also associated with neurodegenerative diseases, and its influence differs depending on the isoform. In particular, the ε4 allele of APOE is the highest genetic risk factor for developing late-onset Alzheimer's disease (AD). However, the mechanism by which ApoE4 contributes to the pathogenesis of AD remains unclear. We investigated the effect of ApoE4 on autophagy in the human brains of ApoE4 carriers. Compared to non-carriers, the expression of FoxO3a regulating autophagy-related genes was significantly reduced in ApoE4 carriers, and the phosphorylation level of FoxO3a at Ser253 increased in ApoE4 carriers, indicating that FoxO3a is considerably repressed in ApoE4 carriers. As a result, the protein expression of FoxO3a downstream genes, such as Atg12, Beclin-1, BNIP3, and PINK1, was significantly decreased, likely leading to dysfunction of both autophagy and mitophagy in ApoE4 carriers. In addition, phosphorylated tau accumulated more in ApoE4 carriers than in non-carriers. Taken together, our results suggest that ApoE4 might attenuate autophagy via the repression of FoxO3a in AD pathogenesis. The regulation of the ApoE4-FoxO3a axis may provide a novel therapeutic target for the prevention and treatment of AD with the APOE4 allele.

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