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1.
PLoS Biol ; 20(6): e3001678, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35687590

RESUMEN

Cells must adjust the expression levels of metabolic enzymes in response to fluctuating nutrient supply. For glucose, such metabolic remodeling is highly dependent on a master transcription factor ChREBP/MondoA. However, it remains elusive how glucose fluctuations are sensed by ChREBP/MondoA despite the stability of major glycolytic pathways. Here, we show that in both flies and mice, ChREBP/MondoA activation in response to glucose ingestion involves an evolutionarily conserved glucose-metabolizing pathway: the polyol pathway. The polyol pathway converts glucose to fructose via sorbitol. It has been believed that this pathway is almost silent, and its activation in hyperglycemic conditions has deleterious effects on human health. We show that the polyol pathway regulates the glucose-responsive nuclear translocation of Mondo, a Drosophila homologue of ChREBP/MondoA, which directs gene expression for organismal growth and metabolism. Likewise, inhibition of the polyol pathway in mice impairs ChREBP's nuclear localization and reduces glucose tolerance. We propose that the polyol pathway is an evolutionarily conserved sensing system for glucose uptake that allows metabolic remodeling.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Glucosa , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Metabolismo de los Hidratos de Carbono , Drosophila/metabolismo , Glucosa/metabolismo , Ratones , Polímeros , Factores de Transcripción/metabolismo
2.
Eur J Immunol ; 53(10): e2350452, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37565654

RESUMEN

Theiler's murine encephalomyelitis virus (TMEV) causes a chronic demyelinating disease similar to multiple sclerosis in mice. Although sialic acids have been shown to be essential for TMEV attachment to the host, the surface receptor has not been identified. While type I interferons play a pivotal role in the elimination of the chronic infectious Daniel (DA) strain, the role of plasmacytoid dendritic cells (pDCs) is controversial. We herein found that TMEV binds to conventional DCs but not to pDCs. A glycomics analysis showed that the sialylated N-glycan fractions were lower in pDCs than in conventional DCs, indicating that pDCs are not susceptible to TMEV infection due to the low levels of sialic acid. TMEV capsid proteins contain an integrin recognition motif, and dot blot assays showed that the integrin proteins bind to TMEV and that the viral binding was reduced in the desialylated αX ß2 . αX ß2 protein suppressed TMEV replication in vivo, and TMEV co-localized with integrin αM at the cell membrane and TLR 3 in the cytoplasm, suggesting that αM serves as the viral attachment and entry. These results show that the chronic encephalomyelitis virus utilizes sialylated integrins as cell surface receptors, leading to cellular tropism to evade pDC activation.


Asunto(s)
Encefalomielitis , Integrinas , Ratones , Animales , Receptores de Superficie Celular , Células Dendríticas , Tropismo
3.
PLoS Biol ; 19(4): e3001183, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33891588

RESUMEN

The Drosophila germ plasm is responsible for germ cell formation. Its assembly begins with localization of oskar mRNA to the posterior pole of the oocyte. The oskar translation produces 2 isoforms with distinct functions: short Oskar recruits germ plasm components, whereas long Oskar remodels actin to anchor the components to the cortex. The mechanism by which long Oskar anchors them remains elusive. Here, we report that Yolkless, which facilitates uptake of nutrient yolk proteins into the oocyte, is a key cofactor for long Oskar. Loss of Yolkless or depletion of yolk proteins disrupts the microtubule alignment and oskar mRNA localization at the posterior pole of the oocyte, whereas microtubule-dependent localization of bicoid mRNA to the anterior and gurken mRNA to the anterior-dorsal corner remains intact. Furthermore, these mutant oocytes do not properly respond to long Oskar, causing defects in the actin remodeling and germ plasm anchoring. Thus, the yolk uptake is not merely the process for nutrient incorporation, but also crucial for oskar mRNA localization and cortical anchorage of germ plasm components in the oocyte.


Asunto(s)
Proteínas de Drosophila , Proteínas del Huevo/metabolismo , Oocitos/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Animales Modificados Genéticamente , Transporte Biológico , Polaridad Celular/fisiología , Citoplasma/metabolismo , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiología , Proteínas del Huevo/fisiología , Endocitosis/fisiología , Femenino , Oogénesis/fisiología , ARN Mensajero/metabolismo , Receptores de Superficie Celular/fisiología , Vitelogénesis/fisiología , Vitelogeninas/fisiología
4.
J Org Chem ; 89(1): 770-777, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38113515

RESUMEN

A method for aromatic halogenation using a combination of elemental sulfur (S8) and N-halosuccinimide has been developed. A catalytic quantity of elemental sulfur (S8) with N-bromosuccinimide (NBS) and N-chlorosuccinimide (NCS) effectively halogenated less-reactive aromatic compounds, such as ester-, cyano-, and nitro-substituted anisole derivatives. No reaction occurred in the absence of S8, underscoring its crucial role in the catalytic activity. This catalytic system was also applicable to aromatic iodination with 1,3-diiodo-5,5-dimethylhydantoin.

5.
Endoscopy ; 55(3): 261-266, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35970190

RESUMEN

BACKGROUND: Although gel immersion endoscopic resection (GIER) is a potential alternative to underwater endoscopic mucosal resection (UEMR) for superficial nonampullary duodenal epithelial tumors (SNADETs), comparisons between the two are currently insufficient. METHODS: 40 consecutive procedures performed in 35 patients were retrospectively reviewed; the primary outcome was procedure time, and the secondary outcomes were en bloc and R0 resection rates, tumor and specimen size, and adverse events. RESULTS: Lesions were divided into GIER (n = 22) and UEMR groups (n = 18). The median (range) procedure time was significantly shorter in the GIER group than in the UEMR group (2.75 [1-3.5] minutes vs. 3 2 3 4 5 6 7 8 9 10 minutes; P = 0.01). The en bloc resection rate was 100 % in the GIER group, but only 83.3 % in the UEMR group. The R0 resection rate was significantly higher in the GIER group than in the UEMR group (95.5 % vs. 66.7 %; P = 0.03). The median specimen size was larger in the GIER group than in the UEMR group (14 mm vs. 7.5 mm; P < 0.001). The tumor size was not significantly different between the groups and no adverse events were observed. CONCLUSIONS: GIER is efficacious and safe to treat SNADETs, although additional studies are needed.


Asunto(s)
Carcinoma , Neoplasias Duodenales , Resección Endoscópica de la Mucosa , Humanos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Estudios de Factibilidad , Estudios Retrospectivos , Inmersión , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/patología , Resultado del Tratamiento
6.
Org Biomol Chem ; 21(6): 1134-1137, 2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36484376

RESUMEN

A mild and efficient approach for the synthesis of thioaurones via NBS-induced cyclization of methoxymethyl-protected mercapto-chalcones has been developed. This simple method is highly functional group tolerant and provides straightforward access to thioaurones in good to high yields.

7.
J Appl Microbiol ; 134(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040658

RESUMEN

AIM: Aeribacillus pallidus PI8 is a Gram-positive thermophilic bacterium that produces thermostable antimicrobial substances against several bacterial species, including Geobacillus kaustophilus HTA426. In the present study, we sought to identify genes of PI8 with antibacterial activity. METHODS AND RESULTS: We isolated, cloned, and characterized a thermostable bacteriocin from A. pallidus PI8 and named it pallidocyclin. Mass spectrometric analyses of pallidocyclin revealed that it had a circular peptide structure, and its precursor was encoded by pcynA in the PI8 genome. pcynA is the second gene within the pcynBACDEF operon. Expression of the full-length pcynBACDEF operon in Bacillus subtilis produced intact pallidocyclin, whereas expression of pcynF in G. kaustophilus HTA426 conferred resistance to pallidocyclin. CONCLUSION: Aeribacillus pallidus PI8 possesses the pcynBACDEF operon to produce pallidocyclin. pcynA encodes the pallidocyclin precursor, and pcynF acts as an antagonist of pallidocyclin.


Asunto(s)
Bacillaceae , Bacteriocinas , Bacteriocinas/genética , Bacteriocinas/farmacología , Bacillaceae/genética , Antibacterianos/farmacología
8.
J Cell Sci ; 133(15)2020 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-32661086

RESUMEN

The pluripotency-associated transcriptional network is regulated by a core circuitry of transcription factors. The PR domain-containing protein PRDM14 maintains pluripotency by activating and repressing transcription in a target gene-dependent manner. However, the mechanisms underlying dichotomic switching of PRDM14-mediated transcriptional control remain elusive. Here, we identified C-terminal binding protein 1 and 2 (CtBP1 and CtBP2; generically referred to as CtBP1/2) as components of the PRDM14-mediated repressive complex. CtBP1/2 binding to PRDM14 depends on CBFA2T2, a core component of the PRDM14 complex. The loss of Ctbp1/2 impaired the PRDM14-mediated transcriptional repression required for pluripotency maintenance and transition from primed to naïve pluripotency. Furthermore, CtBP1/2 interacted with the PRC2 complexes, and the loss of Ctbp1/2 impaired Polycomb repressive complex 2 (PRC2) and H3K27me3 enrichment at target genes after Prdm14 induction. These results provide evidence that the target gene-dependent transcriptional activity of PRDM14 is regulated by partner switching to ensure the transition from primed to naïve pluripotency.This article has an associated First Person interview with the first author of the paper.


Asunto(s)
Proteínas de Unión al ADN , Complejo Represivo Polycomb 2 , Oxidorreductasas de Alcohol/genética , Proteínas Co-Represoras , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Humanos , Complejo Represivo Polycomb 2/metabolismo , Proteínas de Unión al ARN , Factores de Transcripción
9.
Development ; 146(7)2019 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-30890569

RESUMEN

Specification of germ cells is pivotal to ensure continuation of animal species. In many animal embryos, germ cell specification depends on maternally supplied determinants in the germ plasm. Drosophila polar granule component (pgc) mRNA is a component of the germ plasm. pgc encodes a small protein that is transiently expressed in newly formed pole cells, the germline progenitors, where it globally represses mRNA transcription. pgc is also required for pole cell survival, but the mechanism linking transcriptional repression to pole cell survival remains elusive. We report that pole cells lacking pgc show premature loss of germ plasm mRNAs, including the germ cell survival factor nanos, and undergo apoptosis. We found that pgc- pole cells misexpress multiple miRNA genes. Reduction of miRNA pathway activity in pgc- embryos partially suppressed germ plasm mRNA degradation and pole cell death, suggesting that Pgc represses zygotic miRNA transcription in pole cells to protect germ plasm mRNAs. Interestingly, germ plasm mRNAs are protected from miRNA-mediated degradation in vertebrates, albeit by a different mechanism. Thus, independently evolved mechanisms are used to silence miRNAs during germ cell specification.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Embrión no Mamífero/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Antígenos de Neoplasias/metabolismo , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Drosophila/genética , Proteínas de Drosophila/genética , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Hemocitos/citología , Hemocitos/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Serina-Treonina Quinasas/genética , Estabilidad del ARN/genética , Estabilidad del ARN/fisiología , Transducción de Señal/genética , Transducción de Señal/fisiología , Cigoto/metabolismo
10.
Extremophiles ; 26(3): 37, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36416985

RESUMEN

2-Keto-3-deoxy- D-gluconate (KDG) is an important intermediate found in various sugars, sugar acids and polysaccharide catabolic pathways. Here, we report that a functionally uncharacterized type-2 malate/L-lactate dehydrogenase family protein (TTHB078) from Thermus thermophilus HB8 catalyzes a novel reaction, NAD(P)H-dependent reductase activity on KDG. This enzyme, designated KdgG, utilizes both NADH and NADPH as electron donors, but higher activity was observed with NADH. Analysis of the reaction product revealed that KdgG catalyzes reversible reduction of KDG to form 3-deoxy-D-mannonate. Molecular phylogenetic analysis indicated that KdgG and its homologs distributed in the genus Thermus form a novel clade among type-2 malate/L-lactate dehydrogenase family proteins.


Asunto(s)
L-Lactato Deshidrogenasa , Thermus thermophilus , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Malatos , Ácido Láctico , NAD/metabolismo , Filogenia
11.
PLoS Genet ; 15(5): e1008090, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31091233

RESUMEN

Repression of somatic gene expression in germline progenitors is one of the critical mechanisms involved in establishing the germ/soma dichotomy. In Drosophila, the maternal Nanos (Nos) and Polar granule component (Pgc) proteins are required for repression of somatic gene expression in the primordial germ cells, or pole cells. Pgc suppresses RNA polymerase II-dependent global transcription in pole cells, but it remains unclear how Nos represses somatic gene expression. Here, we show that Nos represses somatic gene expression by inhibiting translation of maternal importin-α2 (impα2) mRNA. Mis-expression of Impα2 caused aberrant nuclear import of a transcriptional activator, Ftz-F1, which in turn activated a somatic gene, fushi tarazu (ftz), in pole cells when Pgc-dependent transcriptional repression was impaired. Because ftz expression was not fully activated in pole cells in the absence of either Nos or Pgc, we propose that Nos-dependent repression of nuclear import of transcriptional activator(s) and Pgc-dependent suppression of global transcription act as a 'double-lock' mechanism to inhibit somatic gene expression in germline progenitors.


Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas Nucleares/genética , Óvulo/metabolismo , Proteínas de Unión al ARN/genética , Espermatozoides/metabolismo , alfa Carioferinas/genética , Transporte Activo de Núcleo Celular , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Femenino , Factores de Transcripción Fushi Tarazu/genética , Factores de Transcripción Fushi Tarazu/metabolismo , Regulación del Desarrollo de la Expresión Génica , Masculino , Proteínas Nucleares/metabolismo , Ovario/citología , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Óvulo/citología , Factor B de Elongación Transcripcional Positiva/genética , Factor B de Elongación Transcripcional Positiva/metabolismo , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Proteínas de Unión al ARN/metabolismo , Espermatozoides/citología , Testículo/citología , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética , alfa Carioferinas/metabolismo
12.
Nihon Shokakibyo Gakkai Zasshi ; 119(6): 558-565, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-35691926

RESUMEN

A 71-year-old man developed ulcerative colitis (UC) at 48 years of age. As a steroid-dependent case with poor UC control, the patient was treated with azathioprine, which resulted in clinical remission. However, a blood test revealed pancytopenia. Bone marrow examination confirmed the diagnosis of myelodysplastic syndrome (MDS). During the patient's clinical course, multiple round ulcers appeared in the terminal ileum. We suspected concomitant "colitis-like intestinal Behçet's disease" (BD). Treatment with adalimumab resolved the ulcers. To the best of our knowledge, this is a rare case of intestinal BD accompanying UC after MDS.


Asunto(s)
Síndrome de Behçet , Colitis Ulcerosa , Síndromes Mielodisplásicos , Anciano , Azatioprina/uso terapéutico , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Humanos , Masculino , Síndromes Mielodisplásicos/complicaciones , Úlcera
13.
J Biol Chem ; 295(20): 7154-7167, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32241910

RESUMEN

Ecdysteroids are the principal steroid hormones essential for insect development and physiology. In the last 18 years, several enzymes responsible for ecdysteroid biosynthesis encoded by Halloween genes were identified and genetically and biochemically characterized. However, the tertiary structures of these proteins have not yet been characterized. Here, we report the results of an integrated series of in silico, in vitro, and in vivo analyses of the Halloween GST protein Noppera-bo (Nobo). We determined crystal structures of Drosophila melanogaster Nobo (DmNobo) complexed with GSH and 17ß-estradiol, a DmNobo inhibitor. 17ß-Estradiol almost fully occupied the putative ligand-binding pocket and a prominent hydrogen bond formed between 17ß-estradiol and Asp-113 of DmNobo. We found that Asp-113 is essential for 17ß-estradiol-mediated inhibition of DmNobo enzymatic activity, as 17ß-estradiol did not inhibit and physically interacted less with the D113A DmNobo variant. Asp-113 is highly conserved among Nobo proteins, but not among other GSTs, implying that this residue is important for endogenous Nobo function. Indeed, a homozygous nobo allele with the D113A substitution exhibited embryonic lethality and an undifferentiated cuticle structure, a phenocopy of complete loss-of-function nobo homozygotes. These results suggest that the nobo family of GST proteins has acquired a unique amino acid residue that appears to be essential for binding an endogenous sterol substrate to regulate ecdysteroid biosynthesis. To the best of our knowledge, ours is the first study describing the structural characteristics of insect steroidogenic Halloween proteins. Our findings provide insights relevant for applied entomology to develop insecticides that specifically inhibit ecdysteroid biosynthesis.


Asunto(s)
Proteínas de Drosophila/química , Estradiol/química , Glutatión Transferasa/química , Aedes , Sustitución de Aminoácidos , Animales , Cristalografía por Rayos X , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Ecdisteroides/biosíntesis , Ecdisteroides/química , Ecdisteroides/genética , Estradiol/genética , Estradiol/metabolismo , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Mutación con Pérdida de Función , Mutación Missense , Relación Estructura-Actividad
14.
Development ; 145(10)2018 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-29739838

RESUMEN

Krüppel-like factors (Klfs) have a pivotal role in maintaining self-renewal of mouse embryonic stem cells (mESCs). The functions of three Klf family members (Klf2, Klf4 and Klf5) have been identified, and are suggested to largely overlap. For further dissection of their functions, we applied an inducible knockout system for these Klf family members and assessed the effects of combinatorial loss of function. As a result, we confirmed that any one of Klf2, Klf4 and Klf5 was sufficient to support self-renewal, whereas the removal of all three compromised it. The activity of any single transcription factor, except for a Klf family member, was not sufficient to restore self-renewal of triple-knockout mESCs. However, some particular combinations of transcription factors were capable of the restoration. The triple-knockout mESCs were successfully captured at primed state. These data indicate that the pivotal function of a Klf family member is transduced into the activation of multiple transcription factors in a naïve-state-specific manner.


Asunto(s)
Autorrenovación de las Células/genética , Factores de Transcripción de Tipo Kruppel/genética , Células Madre Embrionarias de Ratones/citología , Células Madre Pluripotentes/citología , Animales , Diferenciación Celular/genética , Células Cultivadas , Regulación del Desarrollo de la Expresión Génica , Técnicas de Inactivación de Genes , Factor 4 Similar a Kruppel , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
15.
FASEB J ; 34(2): 3197-3208, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31909857

RESUMEN

Nuclear factor of activated T cells (NFAT) leads to the transcription of diverse inducible genes involved in many biological processes; therefore, aberrant NFAT expression is responsible for the development and exacerbation of various disorders. Since five isoforms of NFAT (NFATc1-c4, NFAT5) exhibit distinct and overlapping functions, selective control of a part, but not all, of NFAT family members is desirable. By comparing the binding activity of each NFATc1-c4 with its regulatory enzyme, calcineurin (CN), using a quantitative immunoprecipitation assay, we found a new CN-binding region (CNBR) selectively functioning in NFATc1 and NFATc4. This region, termed CNBR3, is located between two preexisting CNBR1 and CNBR2, within the Ca2+ regulatory domain. The nuclear translocation of NFATc1 but not NFATc2 in T cells was suppressed by ectopic expression of CNBR3 and, accordingly, NFATc1-dependent cytokine expression was downregulated. Through competition assays using NFATc1-derived partial peptides and mass spectrometry with photoaffinity technology, we identified 18 amino acids in NFATc1 (Arg258 to Pro275 ) and 13 amino acids in CN catalytic subunit (CNA) (Asn77 to Gly89 ) responsible for CNA/CNBR3 binding in which Cys263 and Asp82 , respectively, played crucial roles. The possible selective regulation of NFAT-mediated biological processes by targeting this new CN/NFAT-binding region is suggested.


Asunto(s)
Calcineurina/química , Simulación del Acoplamiento Molecular , Factores de Transcripción NFATC/química , Animales , Sitios de Unión , Calcineurina/genética , Calcineurina/metabolismo , Línea Celular , Cricetinae , Cricetulus , Humanos , Células Jurkat , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Unión Proteica
16.
Scand J Gastroenterol ; 56(10): 1236-1242, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34362282

RESUMEN

OBJECTIVE: Although prophylactic clip closure after endoscopic mucosal resection may prevent delayed bleeding, information regarding colorectal endoscopic submucosal dissection (CR-ESD) is lacking. Therefore, this study evaluated the effect of prophylactic clip closure on delayed bleeding rate after CR-ESD. MATERIALS AND METHODS: A total of 614 CR-ESD procedures performed in 561 patients were retrospectively reviewed. The primary outcome, which was delayed bleeding rate, was analyzed between the prophylactic clip closure and non-closure groups. Furthermore, the predictors of delayed bleeding were also evaluated. RESULTS: The patients were divided into the clip closure group (n = 275) and non-closure group (n = 339). Delayed bleeding rate was significantly lower in the closure group than in non-closure group (6 cases [2.2%] vs. 20 cases [5.9%], p = .026). The univariate logistic regression analyses revealed that delayed bleeding was significantly associated with laterally spreading tumor-granular-nodular mixed type (LST-G-Mix; odds ratio [OR], 3.77; 95% confidence interval [CI], 1.70-8.34; p = .001). By contrast, prophylactic clip closure was significantly associated with low delayed bleeding rate (OR, 0.36; 95%CI, 0.14-0.90; p = .029). The multivariate logistic regression analyses revealed LST-G-Mix as a significant independent delayed bleeding predictor (OR, 3.25; 95%CI, 1.45-7.32; p = .004), whereas, prophylactic clip closure was identified as a significant independent preventive factor of delayed bleeding (OR, 0.39; 95%CI, 0.15-1.00; p = .049). CONCLUSIONS: Prophylactic clip closure after CR-ESD is associated with low delayed bleeding rate. LST-G-Mix promotes delayed bleeding, and performing prophylactic clip closure may be advisable.


Asunto(s)
Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/efectos adversos , Humanos , Mucosa Intestinal/cirugía , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Estudios Retrospectivos , Instrumentos Quirúrgicos , Resultado del Tratamiento
17.
BMC Gastroenterol ; 21(1): 199, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33933007

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. The number of elderly patients with CRC increases due to aging of the population. There are few studies that examined chemotherapy and prognostic factors in metastatic colorectal cancer (mCRC) patients aged ≥ 80 years. We assessed the efficacy of chemotherapy and prognostic factors among patients with mCRC aged ≥ 80 years. METHODS: We retrospectively analyzed clinical and laboratory findings of 987 patients newly diagnosed with CRC at Asahi General Hospital (Chiba, Japan) between January 2012 and December 2016. The Kaplan-Meier method was used for the overall survival (OS) and the log-rank test was used to identify difference between patients. A multivariate Cox proportional hazard regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs) of prognostic factors among super-elderly patients. RESULTS: In total, 260 patients were diagnosed with mCRC (super-elderly group: n = 43, aged ≥ 80 years and younger group, n = 217, aged < 80 years). The performance status and nutritional status were worse in the super-elderly group than in the younger group. The OS of super-elderly patients who received chemotherapy was worse than that of younger patients (18.5 vs. 28.8 months; P = 0.052), although the difference was not significant. The OS of patients who received chemotherapy tended to be longer than that of those who did not; however, there were no significant differences in OS in the super-elderly group (18.5 vs. 8.4 months P = 0.33). Multivariate analysis revealed that carcinoembryonic antigen levels ≥ 5 ng/mL (hazard ratio: 2.27; 95% CI 1.09-4.74; P = 0.03) and prognostic nutritional index ≤ 35 (hazard ratio: 8.57; 95% CI 2.63-27.9; P = 0.0003) were independently associated with poor OS in the super-elderly group. CONCLUSIONS: Patients with mCRC aged ≥ 80 years had lower OS than younger patients even though they received chemotherapy. Carcinoembryonic antigen and prognostic nutritional index were independent prognostic factors in super-elderly patients with mCRC, but chemotherapy was not. TRIAL REGISTRATION: retrospectively registered.


Asunto(s)
Neoplasias Colorrectales , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Japón , Estimación de Kaplan-Meier , Pronóstico , Estudios Retrospectivos
18.
Health Qual Life Outcomes ; 19(1): 150, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-34011361

RESUMEN

BACKGROUND: Degenerative cervical myelopathy (DCM) can significantly impair a patient's quality of life (QOL). In this study, we aimed to identify predictors associated with QOL improvement after surgery for DCM. METHODS: This study included 148 patients who underwent surgery for DCM. The European QOL-5 Dimension (EQ-5D) score, the Japanese Orthopedic Association for the assessment of cervical myelopathy (C-JOA) score, and the Nurick grade were used as outcome measures. Radiographic examinations were performed at enrollment. The associations of baseline variables with changes in EQ-5D scores from preoperative to 1-year postoperative assessment were investigated using a multivariable linear regression model. RESULTS: The EQ-5D and C-JOA scores and the Nurick grade improved after surgery (P < 0.001, P < 0.001, and P < 0.001, respectively). Univariable analysis revealed that preoperative EQ-5D and C-JOA scores were significantly associated with increased EQ-5D scores from preoperative assessment to 1 year after surgery (P < 0.0001 and P = 0.045). Multivariable regression analysis showed that the independent preoperative predictors of change in QOL were lumbar lordosis (LL), sacral slope (SS), and T1 pelvic angle (TPA). According to the prediction model, the increased EQ-5D score from preoperatively to 1 year after surgery = 0.308 - 0.493 × EQ-5D + 0.006 × LL - 0.008 × SS + 0.004 × TPA. CONCLUSIONS: Preoperative LL, SS, and TPA significantly impacted the QOL of patients who underwent surgery for DCM. Less improvement in QOL after surgery was achieved in patients with smaller LL and TPA and larger SS values. Patients with these risk factors may therefore require additional support to experience adequate improvement in QOL.


Asunto(s)
Vértebras Cervicales/cirugía , Calidad de Vida/psicología , Enfermedades de la Médula Espinal/psicología , Enfermedades de la Médula Espinal/cirugía , Procedimientos Quirúrgicos Operativos/psicología , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Anciano , Femenino , Predicción , Humanos , Japón , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Periodo Posoperatorio , Estudios Prospectivos , Resultado del Tratamiento
19.
Appl Opt ; 60(13): 3689-3698, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33983301

RESUMEN

In recent years, with the development of precise lathe-cutting equipment, special shaped contact lenses (CL) have been crafted. However, while it is possible to manufacture such a lens, its shape evaluation has not been well-established. We conducted a basic optical experiment using special lenses to measure a spherical lens and nonspherical mold. As the measurement sample, a metal ball, special CL, and a toric-shaped mold were adopted. In order to accurately measure those real shapes, we proposed an algorithm in which the probe light is vertically incident to the sample surface within a numerical aperture of the optical probe. For this algorithm, we developed the specialized time-domain optical coherence tomography (TD-OCT), which was designed to conduct circular scanning while maintaining vertical incidence by driving a two-axis (vertical and horizontal) micro-electromechanical system mirror with a phase difference of 90°. The shape, thickness distribution, and curvature radii of both front and back surfaces of a CL were estimated with this OCT signal analysis and sphere fitting. The shape and curvature radius were evaluated by using the simulated data under the same experimental conditions. They were sufficiently accurate based on the resolution of this OCT. Also, a toric-shaped mold was evaluated by comparing the relationship between each coordinate and intensity of the interference signal. As a result, it is confirmed that the experimental result and the simulated matched well.

20.
BMC Surg ; 21(1): 144, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33740929

RESUMEN

BACKGROUND: Anterior decompression with fusion (ADF) has often been performed for degenerative cervical myelopathy (DCM) in patients with poor cervical spine alignment and/or anterior cord compression. We aimed to identify clinical and radiological predictors associated with neurological recovery after ADF. METHODS: This post-hoc analysis from a prospective multicenter study included patients who were scheduled for ADF for DCM. The patients who received other surgeries (laminoplasty, posterior decompression and fusion) were excluded. The associations between baseline clinical and radiographic variables (age, sex, body mass index, etiology, cervical lordosis, range of motion, C7 slope, C2-7 sagittal vertical axis [SVA], thoracic kyphosis [TK], lumbar lordosis, sacral slope, SVA, pelvic tilt, T1 pelvic angle [TPA], the Japanese Orthopedic Association score for the assessment of cervical myelopathy [C-JOA], European Quality of Life Five Dimensions Scale [EQ-5D], Neck Disability Index [NDI], Physical Component Summary of the SF-36 [PCS], and Mental Component Summary of the SF-36) and the recovery rates as the outcome variables were investigated in the univariate regression analysis. Then, the independent predictors for increased recovery rates were evaluated using a stepwise multiple regression analysis. RESULTS: In total, 37 patients completed the 1 year follow-up. The recovery rate was significantly correlated with SVA (p = 0.001) and TPA (p = 0.03). Univariate regression analyses showed that age (Regression coefficient = - 0.92, p = 0.049), SVA (Regression coefficient  = - 0.57, p = 0.004) and PCS (Regression coefficient = 0.80, p = 0.03) score were significantly associated with recovery rate. Then, a stepwise multiple regression analysis identified the independent predictors of recovery rate after ADF as TK (p = 0.01), PCS (p = 0.03), and SVA (p = 0.03). According to this prediction model, the following equation was obtained: recovery rate = - 8.26 + 1.17 × (TK) - 0.45 × (SVA) + 0.85 × (PCS) (p = 0.002, R2 = 0.44). CONCLUSION: Patients with lower TK, lower PCS score, and higher SVA were more likely to have poor neurological recovery after ADF. Therefore, patients with DCM and these predictors who undergo ADF should be warned about poor recovery and be required to provide adequate informed consent.


Asunto(s)
Descompresión , Enfermedades de la Médula Espinal , Anciano , Vértebras Cervicales/cirugía , Descompresión/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades de la Médula Espinal/cirugía , Resultado del Tratamiento
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