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1.
J Formos Med Assoc ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38710607

RESUMO

BACKGROUND/PURPOSE: Taiwan is one of the countries with the lowest birth rate in the world. We investigated factors associated with the time to diagnosis and treatment of infertility in Taiwan. METHODS: The study was conducted through an online questionnaire in December 2021. The questionnaire was adapted from a previously published multinational survey, and culture-specific questions were added. 91 infertile patients and 89 partners of patients in Taiwan, aged 20- to 45- year-old, were included. RESULTS: The average duration before diagnosis was 2.9 years, followed by 1.5 years before treatment. Older age at marriage (p = 0.0024), higher education level (P = 0.0001), and a higher gender equality score (p = 0.0031) were associated with earlier diagnosis. Conversely, folk therapy use was linked to later diagnosis (p < 0.0001) and treatment (p < 0.0001). Notably, in the female (p = 0.039) and patient (p = 0.0377) subgroups, a higher gender equality score was associated with a shorter duration of folk therapy. Subjectively, the most frequent factor influencing treatment decision was affordability or lack thereof. The government subsidy for in vitro fertilization led to increased treatment willingness for 46.3% of respondents, and 47.3% reported more likely to pursue earlier treatment. CONCLUSIONS: This study highlights the influence of education, gender equality, folk therapy, and government subsidy on fertility care decisions. To improve the timeliness of infertility healthcare in Taiwan, potential strategies include promoting education, fostering gender equality, providing financial support, and raising awareness on the association between folk therapy and delayed medical care.

2.
World J Urol ; 41(9): 2503-2509, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37491630

RESUMO

PURPOSE: Contemporary predictive tools for miniaturized percutaneous nephrolithotomy (mPCNL) mainly focus on stone clearance but not perioperative complications, especially infection and hemorrhage. This study aimed to evaluate whether the Mayo adhesive probability (MAP) score, an index of the perinephric fat characteristics, can predict postoperative fever and intraoperative hemorrhage in mPCNL. METHODS: This is a retrospective study recruiting 159 mPCNL patients from July 2018 to January 2022. MAP scores were recorded using preoperative computed tomography. Postoperative complications included postoperative fever and intraoperative bleeding, defined as hemoglobin drop. RESULTS: Over half patients had the MAP score ≧ 3. Men, elderly, chronic kidney disease, and diabetes were associated with a higher MAP score. The patients with a higher MAP score were more likely to have postoperative fever after mPCNL. On multivariate analysis, preoperative positive urine culture (OR 2.68) and a higher MAP score (OR 2.28) were both significantly associated with postoperative fever. ROC curves analysis of the combination of these two factors on predicting postoperative fever showed AUC values were 0.731 (0.652-0.810). Moreover, a higher MAP score (OR 2.30) and longer operative time (OR 2.16) were significantly associated with higher hemoglobin drop on multivariate analysis. CONCLUSION: A high MAP score was associated with postoperative fever and intraoperative hemorrhage in patients undergoing mPCNL. The MAP score can be a novel and easy predictive tool to help endourologists improve the awareness of mPCNL safety.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Masculino , Humanos , Idoso , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Estudos Retrospectivos , Cálculos Renais/cirurgia , Cálculos Renais/complicações , Resultado do Tratamento , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Perda Sanguínea Cirúrgica , Hemoglobinas , Probabilidade
3.
Acta Pharmacol Sin ; 43(10): 2651-2665, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35217814

RESUMO

Canagliflozin is an antidiabetic medicine that inhibits sodium-glucose cotransporter 2 (SGLT2) in proximal tubules. Recently, it was reported to have several noncanonical effects other than SGLT2 inhibiting. However, the effects of canagliflozin on skeletal muscle regeneration remain largely unexplored. Thus, in vivo muscle contractile properties recovery in mice ischemic lower limbs following gliflozins treatment was evaluated. The C2C12 myoblast differentiation after gliflozins treatment was also assessed in vitro. As a result, both in vivo and in vitro data indicate that canagliflozin impairs intrinsic myogenic regeneration, thus hindering ischemic limb muscle contractile properties, fatigue resistance recovery, and tissue regeneration. Mitochondrial structure and activity are both disrupted by canagliflozin in myoblasts. Single-cell RNA sequencing of ischemic tibialis anterior reveals a decrease in leucyl-tRNA synthetase 2 (LARS2) in muscle stem cells attributable to canagliflozin. Further investigation explicates the noncanonical function of LARS2, which plays pivotal roles in regulating myoblast differentiation and muscle regeneration by affecting mitochondrial structure and activity. Enhanced expression of LARS2 restores the differentiation of canagliflozin-treated myoblasts, and accelerates ischemic skeletal muscle regeneration in canagliflozin-treated mice. Our data suggest that canagliflozin directly impairs ischemic skeletal muscle recovery in mice by downregulating LARS2 expression in muscle stem cells, and that LARS2 may be a promising therapeutic target for injured skeletal muscle regeneration.


Assuntos
Aminoacil-tRNA Sintetases , Inibidores do Transportador 2 de Sódio-Glicose , Aminoacil-tRNA Sintetases/metabolismo , Aminoacil-tRNA Sintetases/farmacologia , Animais , Canagliflozina/metabolismo , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Diferenciação Celular , Glucose/metabolismo , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Sódio/metabolismo , Sódio/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
5.
J Obstet Gynaecol ; 37(2): 233-237, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27922289

RESUMO

The objective of this study was to identify clinical and pathologic factors that are significant to relapse in borderline ovarian tumours (BOT). All patients with BOTs from 1997 to 2012 in our institute were identified. 115 patients were included in the study. The Cox proportional hazards model was used to identify significant factors. The median age was 42 years (range 14-85 years). The majority of the patients were at FIGO stage I (88.7%), and most of the patients had mucinous histology (66.1%), reflecting the predominant distribution of mucinous BOTs in East Asia. The median follow-up was 3.3 years (range 0-4.1 years). Twelve patients (10.4%) relapsed and two died consequently. Advanced stage, invasive implants and restaging surgery were significant factors of recurrence. Serous tumours had slightly higher risk than mucinous tumours, but the difference was not significant. As the study was performed in an area where mucinous BOTs are predominant, the results may complement current literature on BOT management.


Assuntos
Adenocarcinoma Mucinoso/patologia , Recidiva Local de Neoplasia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Risco , Adenocarcinoma Mucinoso/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Adulto Jovem
6.
Inorg Chem ; 55(16): 7843-51, 2016 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-27479795

RESUMO

A series of novel nickel complexes 1-9 supported by NNO-tridentate Schiff-base derivatives have been synthesized and characterized. Treatment of the pro-ligands [L(1)-H = 2,4-di-tert-butyl-6-(((2-(dimethylamino)ethyl)imino)methyl)phenol, L(2)-H = 2-(((2-(dimethylamino)ethyl)imino)methyl)-4,6-bis(2-phenylpropan-2-yl)phenol, L(3)-H = 2-(((2-(dimethylamino)ethyl)imino)methyl)phenol] with Ni(OAc)2·4H2O in refluxing ethanol afforded mono- or bimetallic nickel complexes {[(L(1))Ni(OAc)] (1); (L(2))Ni(OAc)] (2); (L(3))2Ni2(OAc)2(H2O)] (3)}. Alcohol-solvated trimetallic nickel acetate complexes {[(L(3))2Ni3(OAc)4(MeOH)2] (4); (L(3))2Ni3(OAc)4(EtOH)2] (5)} could be generated from the reaction of L(3)-H and anhydrous nickel(II) acetate with a ratio of 2:3 in refluxing anhydrous MeOH or EtOH. The reaction of nickel acetate tetrahydrate and L(4)-H to L(6)-H [L(4)-H = 2-(((2-(dimethylamino)ethyl)imino)methyl)-5-methoxyphenol, L(5)-H = 2-(((2-(dimethylamino)ethyl)imino)methyl)-4-methoxy-phenol, L(6)-H = 2-(((2-(dimethylamino)ethyl)imino)(phenyl)methyl)phenol] produced, respectively, the alcohol-free trinuclear nickel complexes {[(L(4))2Ni3(OAc)4] (7); [(L(5))2Ni3(OAc)4] (8); [(L(6))2Ni3(OAc)4] (9)} with the same ratio in refluxing EtOH under the atmospheric environment. Interestingly, recrystallization of [(L(3))2Ni3(OAc)4(MeOH)] (4) or [(L(3))2Ni3(OAc)4(EtOH)] (5) in the mixed solvent of CH2Cl2/hexane gives [(L(3))2Ni3(OAc)4] (6), which is isostructural with analogues 7-9. All bi- and trimetallic nickel complexes exhibit efficient activity and good selectivity for copolymerization of CO2 with cyclohexene oxide, resulting in copolymers with a high alternating microstructure possessing ≥99% carbonate-linkage content. This is the first example to apply well-defined trinuclear nickel complexes as efficient catalysts for the production of perfectly alternating poly(cyclohexene carbonate).

7.
Ann Surg Oncol ; 22(12): 3976-80, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25777089

RESUMO

PURPOSE: To explore the risk factors in ovarian cancer with respects of time-varying effects on recurrence and survival. METHODS: Two hundred and ninety-eight patients with epithelial ovarian cancer in the Kaohsiung Veterans' General Hospital from January 1995 to the end of 2011 were included in the study. The assumption of the Cox proportional hazard model, i.e., the hazard ratio is a constant with time, was tested for available prognostic factors. An extended Cox model was then applied, and a statistical package was constructed to perform multivariate analysis in presence of both time-varying and time-independent factors. RESULTS: Most prognostic factors met the assumption of the Cox proportional hazard model (p > 0.05) except for cancer-associated antigen (CA) 125 nadir concentration during first-line chemotherapy (p = 0.02). Multivariate analysis, where CA125 nadir was allowed to change with time while other factors remained constant, showed that International Federation of Gynecology and Obstetrics (FIGO) stage, residual tumor, CA125 nadir, and age were independent risk factors for recurrence and death. CONCLUSIONS: The effect of CA125 nadir on recurrence and overall survival is not constant over time. It loses predictivity on recurrence and survival after 4.5 years. Awareness of the time-varying effects of the prognostic factors is beneficial to gynecologists in patient consultation and case evaluation.


Assuntos
Antígeno Ca-125/sangue , Recidiva Local de Neoplasia/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução , Técnicas de Apoio para a Decisão , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ovariectomia , Lavagem Peritoneal , Modelos de Riscos Proporcionais , Fatores de Risco , Salpingectomia , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
8.
Neurochem Res ; 40(1): 165-71, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25432463

RESUMO

Biochanin A, one of the major isoflavonoids in red clover or cabbage, has been reported to have anti-inflammatory effects. However, the molecular mechanism underlying the anti-inflammatory effects of biochanin A has not been completely elucidated. The aim of this study was to investigate the anti-inflammatory effect and mechanism on lipopolysaccharide (LPS)-stimulated BV2 microglia. The results showed that biochanin A suppressed LPS-induced inflammatory mediators nitric oxide, prostaglandin E2 and inflammatory cytokines TNF-α and IL-1ß production. LPS-induced NF-κB activation was also inhibited by biochanin A. In addition, biochanin A up-regulated the expression of PPAR-γ and the anti-inflammatory effects of biochanin A can be abolished by PPAR-γ antagonist GW9662. These results suggest that biochanin A exerts an anti-inflammatory property by activating PPAR-γ, thereby attenuating NF-κB activation and the release of pro-inflammatory mediators.


Assuntos
Citocinas/biossíntese , Genisteína/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Microglia/metabolismo , Animais , Linhagem Celular , Dinoprostona/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , PPAR gama/metabolismo
9.
iScience ; 27(6): 109895, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38827408

RESUMO

Digital divide and energy insecurity are pervasive issues among underserved communities, issues that become prounoued during the COVID-19 lockdowns. These disparities underscore the critical need to address them promptly to narrow socio-economic gaps. Our study, based on an online survey of 2,588 respondents in the United Kingdom, explores how concentrated socio-economic disadvantage exacerbates insecurities relating to energy and internet access. Our findings reveal that marginalized groups including low-income households, women, renters, ethnic minorities, and individuals with lower educational attainment are disproportionately affected. Our research extends beyond financial implications to explore the broader social and psychological effects such as trust in utility and internet providers. The study also demonstrates how heightened burdens from energy and internet costs adversely affect the quality of indoor environments, underscoring the interconnected nature of these challenges. Based on these insights, we advocate for policy interventions that adopt comprehensive social justice frameworks to tackle these intersecting inequalities effectively.

10.
Commun Chem ; 7(1): 91, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643239

RESUMO

Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (-)-diethyl D-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising ß-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 µM in recombinant human GCase activity in Gaucher cell lines.

11.
Medicine (Baltimore) ; 102(48): e36000, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050308

RESUMO

RATIONALE: Lumbar epidural analgesia is the gold standard for labor pain control. However, misplacement of epidural catheters into the subdural space may inadvertently happen. Unrecognized subdural administration of local anesthetics could result in serious consequences, including high spinal and brainstem blocks. This case report describes a case where subdural epidural catheter placement was recognized early but labor pain was adequately managed by dosage titration of subdural analgesia. PATIENT CONCERNS: This case report describes a 29-year-old primiparous pregnant woman who was admitted to our obstetric unit for labor induction at the gestational age of 38 weeks. An epidural catheter was inserted via the L2-3 intervertebral space using the standard loss of resistance to air technique. DIAGNOSES: The parturient experienced weakness in the lower extremities and numbness in the upper extremities within 15 minutes after administration of 5 mL of 2% v/v lidocaine as a loading dose and systolic blood pressure also dropped by 25%. INTERVENTIONS: The dose regimen (a mixture of 0.1% ropivacaine and 4 µg/mL fentanyl) for patient-controlled analgesia was given with bolus doses of 0.1 mL per demand and lockout intervals of 20 minutes. The analgesic effects were adequately maintained below the T8 dermatome for more than 12 hours without hypotensive episodes or obvious signs of neurological deficits. Computed tomographic myelography was performed by instillation of a nonionic iodinated contrast medium via the epidural catheter on postpartum day 2 for imaging confirmation of catheter placement in the extradural space. LESSONS: Early recognition that epidural catheters for neuraxial analgesia have been inserted into the subdural space is important for the prevention of high spinal blocks. Subdural analgesia could still be achieved by careful clinical assessment and titration of low analgesic doses. This report also presents important and clear serial computed tomographic images of catheter placement in the thoracic-lumbar subdural spaces and the extent of volume spread in the subdural space following administration of contrast medium.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Dor do Parto , Trabalho de Parto , Gravidez , Feminino , Humanos , Lactente , Adulto , Espaço Subdural/diagnóstico por imagem , Dor do Parto/diagnóstico , Anestésicos Locais , Analgesia Epidural/efeitos adversos , Analgesia Epidural/métodos , Analgésicos/uso terapêutico , Catéteres/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Analgesia Obstétrica/métodos
12.
ACS Nano ; 17(6): 5757-5772, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36926834

RESUMO

Nanomedicines and macromolecular drugs can induce hypersensitivity reactions (HSRs) with symptoms ranging from flushing and breathing difficulties to hypothermia, hypotension, and death in the most severe cases. Because many normal individuals have pre-existing antibodies that bind to poly(ethylene glycol) (PEG), which is often present on the surface of nanomedicines and macromolecular drugs, we examined if and how anti-PEG antibodies induce HSRs to PEGylated liposomal doxorubicin (PLD). Anti-PEG IgG but not anti-PEG IgM induced symptoms of HSRs including hypothermia, altered lung function, and hypotension after PLD administration in C57BL/6 and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Hypothermia was significantly reduced by blocking FcγRII/III, by depleting basophils, monocytes, neutrophils, or mast cells, and by inhibiting secretion of histamine and platelet-activating factor. Anti-PEG IgG also induced hypothermia in mice after administration of other PEGylated liposomes, nanoparticles, or proteins. Humanized anti-PEG IgG promoted binding of PEGylated nanoparticles to human immune cells and induced secretion of histamine from human basophils in the presence of PLD. Anti-PEG IgE could also induce hypersensitivity reactions in mice after administration of PLD. Our results demonstrate an important role for IgG antibodies in induction of HSRs to PEGylated nanomedicines through interaction with Fcγ receptors on innate immune cells and provide a deeper understanding of HSRs to PEGylated nanoparticles and macromolecular drugs that may facilitate development of safer nanomedicines.


Assuntos
Hipotermia , Polietilenoglicóis , Camundongos , Humanos , Animais , Polietilenoglicóis/química , Nanomedicina , Histamina , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Imunoglobulina G , Imunidade Inata , Lipossomos/farmacologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-36674370

RESUMO

Lung cancer is the leading cause of cancer deaths worldwide, and squamous cell carcinoma (SQC) is Taiwan's second most common lung carcinoma histotype. This study aimed to investigate changes in the long-term trend of the SQC incidence rate in Taiwan. SQC cases between 1985 and 2019 were adopted from Taiwan's Cancer Registry System; the age-adjusted incidence rate was calculated using the World Standard Population in 2000. The long-term trends of the age, period, and birth cohort effect of SQC incidence rates were estimated using the SEER Age-Period-Cohort Web Tool. The results revealed that the incidence of lung carcinoma in Taiwan increased, while the incidence of SQC exhibited a slight decrease during this study period. The age rate ratio (ARR) of the incidence rate in men declined gradually, and the period effect changed more slowly for women than men. The cohort effect formed a bimodal curve. The annual percentage change results for women indicated that the ARR decreased from 1.652 (95% confidence interval (CI): 1.422, 1.9192) at 30 to 34 years to 0.559 (95% CI: 0.4988, 0.6265) at 75 to 79 years; the period effect decreased from 1.2204 (95% CI: 1.1148, 1.336) in 1995 to 1999 to 0.608 (95% CI: 0.5515, 0.6704) in 2015 to 2019, with a greater decline in the later period. The cohort effect was unimodal, with the SQC risk value peaking in the 1915 birth cohort and exhibiting a steady decline thereafter. The results of this study suggest that a decrease in the smoking rate may be the reason for the decline in the incidence of SQC, and we observed a similar trend between SQC and the smoking rate in men.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Incidência , Taiwan/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Pulmão/patologia
14.
Neurol Genet ; 9(2): e200057, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37090934

RESUMO

Background and Objectives: Neuronal intranuclear inclusion body disease (NIID) is a neurodegenerative disease with highly heterogeneous clinical manifestations. The present study aimed to characterize clinical features and propose a classification system based on a large cohort of NIID in China. Methods: The Chinese NIID registry was launched from 2017, and participants' demographics and clinical features were recorded. Brain MRI, skin pathologies, and the number of GGC repeat expansions in the 5' untranslated region of the NOTCH2NLC gene were evaluated in all patients. Results: In total, 223 patients (64.6% female) were recruited; the mean (SD) onset age was 56.7 (10.3) years. The most common manifestations were cognitive impairment (78.5%) and autonomic dysfunction (70.9%), followed by episodic symptoms (51.1%), movement disorders (50.7%), and muscle weakness (25.6%). Imaging markers included hyperintensity signals along the corticomedullary junction on diffusion-weighted imaging (96.6%), white matter lesions (98.1%), paravermis (55.0%), and focal cortical lesions (10.1%). The median size of the expanded GGC repeats in these patients was 115 (range, 70-525), with 2 patients carrying >300 GGC repeats. A larger number of GGC repeats was associated with younger age at onset (r = -0.329, p < 0.0001). According to the proposed clinical classification based on the most prominent manifestations, the patients were designated into 5 distinct types: cognitive impairment-dominant type (34.1%, n = 76), episodic neurogenic event-dominant type (32.3%, n = 72), movement disorder-dominant type (17.5%, n = 39), autonomic dysfunction-dominant type (8.5%, n = 19), and neuromuscular disease-dominant type (7.6%, n = 17). Notably, 32.3% of the episodic neurogenic event-dominant type of NIID has characteristic focal cortical lesions on brain MRI presenting localized cortical edema or atrophy. The mean onset age of the neuromuscular disease-dominant type was 47.2 (17.6) years, younger than the other types (p < 0.001). There was no significant difference in the sizes of GGC repeats among the patients in the 5 types (p = 0.547, Kruskal-Wallis test). Discussion: This observational study of NIID establishes an overall picture of the disease regarding clinical, imaging, and genetic characteristics. The proposed clinical classification of NIID based on the most prominent manifestation divides patients into 5 types.

15.
J Adv Res ; 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38159844

RESUMO

INTRODUCTION: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population. OBJECTIVES: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population. METHODS: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw). RESULTS: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively. CONCLUSION: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.

16.
Chem Asian J ; 17(14): e202200172, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35535638

RESUMO

A general and flexible approach toward the development of α-l-rhamnosidase (α-l-Rha-ase) inhibitors is described. Five enantiopure poly-substituted pyrrolidine-based scaffolds bearing the C1-aminomethyl moiety were designed and synthesized from five-membered cyclic nitrones. Each structurally diversified amide library of these scaffolds was rapidly generated via combinatorial parallel synthesis and applied for in-situ inhibition study against α-l-Rha-ase, allowing us to efficiently identify new inhibition hits. Surprisingly, all promising inhibitors are derived from the same scaffold 3. Among them, the most potent and selective inhibitor is pyrrolidine 19 with Ki =0.24 µM, approximately 24-fold more potent than the reference compound DAA (Ki =5.7 µM). It is the first study to comprehensively prepare pyrrolidine-based scaffolds and libraries for inhibition study against α-l-Rha-ase.


Assuntos
Glicosídeo Hidrolases , Inibidores Enzimáticos/farmacologia , Óxidos de Nitrogênio , Pirrolidinas/farmacologia
17.
Chem Sci ; 13(21): 6233-6243, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35733906

RESUMO

Modulation of N-glycosylation using human Golgi α-mannosidase II (α-hGMII) inhibitors is a potential anticancer approach, but the clinical utility of current α-hGMII inhibitors is limited by their co-inhibition of human lysosomal α-mannosidase (α-hLM), resulting in abnormal storage of oligomannoses. We describe the synthesis and screening of a small library of novel bicyclic iminosugar-based scaffolds, prepared via natural product-inspired combinatorial chemistry (NPICC), which resulted in the identification of a primary α-hGMII inhibitor with 13.5-fold selectivity over α-hLM. Derivatization of this primary inhibitor using computation-guided synthesis (CGS) yielded an advanced α-hGMII inhibitor with nanomolar potency and 106-fold selectivity over α-hLM. In vitro studies demonstrated its N-glycan modulation and inhibitory effect on hepatocellular carcinoma (HCC) cells. In vivo studies confirmed its encouraging anti-HCC activity, without evidence of oligomannose accumulation.

18.
Asian J Anesthesiol ; 58(1): 24-34, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33081431

RESUMO

OBJECTIVE: Several studies have demonstrated increased postoperative mortality rates in patients on chronic hemodialysis compared with non-dialyzed patients. However, limited studies have examined factors that may contribute to postoperative mortality. METHODS: In this retrospective cohort study, data were collected from 9,140 dialysis and 45,725 non-dialysis patients undergoing surgery between 2007 to 2009 from Taiwan's National Health Insurance Registry Database. Patient demographics, comorbidities, and anesthesia duration were used to compare 30-day postoperative mortality differences in dialysis patients. RESULTS: Dialysis patients undergoing first-time surgery were significantly older, more likely male, and possessed more comorbidities. Overall, dialysis patients had significantly higher all-cause postoperative mortality (odds ratio, 15.005; 95% confidence interval, 11.917-18.893). Gender (hazard ratio [HR], 0.762), age (HR, 1.012), longer duration of inhalation general anesthesia (HR, 1.113), and comorbidities of hypertension (HR, 0.759), diabetes (HR, 1.339), congestive heart failure (HR, 1.232), coronary artery disease (HR, 1.326), cerebral vascular accident (HR, 1.312), intracranial hemorrhage (HR, 6.765), gastrointestinal bleeding (HR, 1.396), and liver cirrhosis (HR, 2.027), independently increased postoperative mortality risk in dialysis patients. Of the comorbidities, intracranial hemorrhage posed the greatest risk. CONCLUSION: Patient demographics, anesthesia factors, and comorbidities help dialysis patients understand their postoperative mortality. These potential risk factors also inform anesthesiologists and surgeons weight perioperative conditions in dialysis patients before surgery.


Assuntos
Diálise Renal , Comorbidade , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
19.
ACS Comb Sci ; 22(11): 600-607, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-32833425

RESUMO

The preparation of natural product-inspired nucleoside analogs using solution-phase parallel synthesis is described. The key intermediates containing alkyne and N-protected amino moieties were developed to allow for further skeleton and substituent diversity using click chemistry and urea or amide bond formation. Rapid purification was accomplished using solid-phase extraction. The obtained library comprised 80 molecules incorporating two diversity positions and one chiral center, each of which was efficiently prepared in good purity and acceptable overall yield. A bacterial morphology study was also performed.


Assuntos
Produtos Biológicos/síntese química , Nucleosídeos/química , Bibliotecas de Moléculas Pequenas/síntese química , Uridina/química , Alcinos/química , Amidas/química , Bacillus subtilis , Química Click , Técnicas de Química Combinatória , Estrutura Molecular , Pró-Fármacos/química , Estereoisomerismo , Ureia/química
20.
Int J Surg ; 71: 21-28, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31525503

RESUMO

BACKGROUND: Hypothermia and shivering are undesirable morbidities that occur commonly during cesarean section. Although some active warming strategies, such as the use of forced-air, mattresses, and fluid warming, can attenuate such adverse events, no studies have yet performed multiple contrast assessments of these strategies. We, therefore, conducted a network meta-analysis to simultaneously assess the effects of various warming strategies for cesarean section and assist clinicians in making informed decisions. METHODS: We searched databases for randomized clinical trials that investigated the effects of warming strategies during cesarean section, with primary outcomes targeted on shivering and hypothermia. Trial quality was assessed using the Cochrane Risk of Bias Tool. Quantitative synthesis was performed using consistency model and surface under the cumulative ranking curve (SUCRA). Results were presented as risk ratio (RR) with 95% confidence interval (CI). RESULTS: We identified 18 trials wherein 1953 women underwent a cesarean section. These trials performed 11 active warming strategies for 1620 women, and the other 333 women were in the non-active warming group. According to SUCRA, the combination of forced-air, fluids, and warmed gown warming could be a better strategy for reducing shivering rates compared with the other strategies (SUCRA = 88.5), albeit with an insignificant result. Conduction mattress warming (SUCRA = 89.4) and combination of conduction mattress and fluids warming (SUCRA = 80.2) were better strategies than others in reducing hypothermia. No evidence showed inconsistency or small study effects in our results. CONCLUSIONS: In clinical practice, forced-air-based warming strategies can be considered to prevent shivering, and conduction mattress-based warming strategies can be used to reduce hypothermia in women undergoing cesarean section.


Assuntos
Cesárea/efeitos adversos , Hipotermia/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Reaquecimento/métodos , Adulto , Feminino , Humanos , Hipotermia/etiologia , Complicações Intraoperatórias/etiologia , Metanálise em Rede , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Estremecimento
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