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1.
Aging Cell ; : e13252, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040455

RESUMO

The risk of colitis and colorectal cancer increases markedly throughout adult life, endangering the health and lives of elderly individuals. Previous studies have proposed that bacterial translocation and infection are the main risk factors for these diseases. Therefore, in the present study, we aimed to identify the underlying mechanism by focusing on the mucus barrier function and mucin-type O-glycosylation. We evaluated alterations in the colon mucus layer in 2-, 16-, and 24-month-old mice and aged humans. Aged colons showed defective intestinal mucosal barrier and changed mucus properties. The miR-124-3p expression level was significantly increased in the aged distal colonic mucosa, which was accompanied by an increase in pathogens and bacterial translocation. Meanwhile, T-synthase, the rate-limiting enzyme in O-glycosylation, displayed an age-related decline in protein expression. Further experiments indicated that miR-124-3p modulated O-glycosylation by directly targeting T-synthase. Moreover, young mice overexpressing miR-124-3p exhibited abnormal glycosylation, early-onset, and more severe colitis. These data suggest that miR-124-3p predisposes to senile colitis by reducing T-synthase, and the miR-124-3p/T-synthase/O-glycans axis plays an essential role in maintaining the physiochemical properties of colonic mucus and intestinal homeostasis.

2.
Clin Rehabil ; : 269215520961637, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040592

RESUMO

OBJECTIVE: This study aimed to investigate the efficacy of high-intensity functional exercise among older adults with dementia. METHODS: In this systematic review and meta-analysis of randomized controlled trials, we collected articles published before August 2020 from PubMed, Embase, and the Cochrane Library to evaluate the effect of high-intensity functional exercise on older adults with dementia. Primary outcomes included improvements in balance function and gait performance (speed, cadence, and stride length). The secondary outcomes included lower limb strength, activities of daily living, psychiatric well-being, depression, and cognition. Furthermore, we performed subgroup analysis with two high-intensity functional exercise programs: the Umeå program and Hauer's program. RESULTS: We identified 15 articles describing six trials including older adults with dementia undergoing high-intensity functional exercise or control activity. The meta-analysis indicated that high-intensity functional exercise, both in Hauer's program and in the Umeå program, significantly improved balance function (pooled standardized mean difference 0.57, 95% confidence interval 0.31-0.83). Hauer's program significantly improved gait speed, cadence, stride length, and lower limb strength. Beneficial effects on speed, cadence, and lower limb strength were retained for several months. The Umeå program facilitated activities of daily living and psychiatric well-being, with effects on activities of daily living lasting several months. In the only eligible trial, no effects on cognition were observed. Adverse effects of high-intensity functional exercise were minimal to none. CONCLUSIONS: High-intensity functional exercise is generally safe and is recommended for older individuals with mild or moderate dementia to provide benefits in motor performance and daily functioning.

3.
J Vis Exp ; (163)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33044454

RESUMO

Sleep disturbance is generally common in populations as a chronic disease or a complained event. Chronic sleep disturbance is proposed to be closely linked to the pathogenesis of diseases, especially neurodegenerative diseases. We recently found that 2 months of sleep fragmentation initiated Alzheimer's disease (AD)-like behavioral and pathological changes in young wild-type mice. Herein, we present a standardized protocol to achieve chronic sleep fragmentation (CSF). Briefly, CSF was induced by an orbital rotor vibrating at 110 rpm and operating with a repetitive cycle of 10 s-on, 110 s-off, during light-ON phase (8:00 AM-8:00 PM) continuously for up to 2 months. Impairments of spatial learning and memory, anxiety-like but not depression-like behavior in mice as consequences of CSF modeling, were evaluated with Morris water maze (MWM), Novel object recognition (NOR), Open field test (OFT) and Forced swimming test (FST). In comparison with other sleep manipulations, this protocol minimizes the handling labors and maximizes the modeling efficiency. It produces stable phenotypes in young wild-type mice and can be potentially generated for a variety of research purposes.

4.
World J Clin Cases ; 8(19): 4505-4511, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083411

RESUMO

BACKGROUND: Urinary tract lymphoepithelioma-like carcinoma is rarely seen. Although it is termed after lymphoepithelioma at the nasopharynx, it behaves more like high grade urothelial carcinoma by immunohistochemical features. Most published literatures focused on its rarity but few discussed results of long-term follow-ups. As no available guidelines are applicable, we postulated that principles should be similar to that of urothelial carcinoma at urinary tract. As of now, this work features the longest follow-up of this cancer at the upper urinary tract. CASE SUMMARY: A 63-year-old female had a chief complaint of intermittent left flank pain for 2 mo, along with accompanying symptoms including vomiting and body weight loss, about 7 kg over 2 mo. Laboratory data showed normocytic anemia, mildly poor renal function, and hyperparathyroidism. Urine analysis showed mild hematuria. Computed tomography showed a 4.2-cm-width irregular mass over left renal pelvic and enlarged lymph node at the left renal hilum. Whole-body bone scan was negative of active bone lesions. Biopsy from ureteroscopy showed urothelial carcinoma. Specimen from laparoscopic nephroureterectomy with bladder cuff resection showed lymphoepithelioma-like carcinoma with muscular invasion (pT3). She took adjuvant chemotherapies of 2 cycles and full courses of radiation therapy. No recurrence was observed with designed investigative programs. CONCLUSION: Locally advanced urinary tract lymphoepithelioma-like carcinoma could benefit from nephroureterectomy and bladder cuff excision in terms of recurrence-free survival.

5.
Clin Chim Acta ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: covidwho-871805

RESUMO

To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P<0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.

6.
Reprod Biol Endocrinol ; 18(1): 102, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059712

RESUMO

BACKGROUND: Patients found to be poor ovarian responders (POR) are a challenging patient population for any assisted reproduction technology. Despite attempts at various controlled ovarian stimulation schemes, reproductive outcomes in this patient population have not improved. In recent years, the DuoStim protocol (both follicular and luteal phase stimulation during the same menstrual cycle) has shown a potential for use in patients with POR. METHODS: This retrospective study reviewed the medical records of 304 women who were diagnosed as POR and underwent the DuoStim protocol. We compared follicular phase stimulation (FPS) data and luteal phase stimulation (LPS) data of the same patients. We also compared the effects of different trigger drugs including urine human chorionic gonadotropin (uHCG; 10,000 IU), recombinant human chorionic gonadotropin (rHCG; 250 µg), and gonadotropin-releasing hormone agonist (GnRH-a; 0.2 mg) at the FPS and LPS stages. RESULTS: POR undergoing the DuoStim protocol resulted in a significantly higher number of oocytes retrieved, normal fertilised oocytes, cleaved embryos, cryopreserved embryos, and good quality embryos at the LPS stage than at the FPS stage. Trigger drugs at the FPS stage did not affect the FPS stage data. Regardless of the stage, rHCG and GnRH-a yielded significantly more cryopreserved embryos and good quality embryos than uHCG. CONCLUSION: The use of GnRH-a or rHCG as the trigger drug may be better than uHCG in both the FPS and LPS stages for POR undergoing the DuoStim protocol. This will increase the number of good quality embryos at the LPS stage. We found that the LPS stage results in more oocytes (and therefore more embryos) than the FPS stage.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33000472

RESUMO

INTRODUCTION: Combined catheter ablation (CA) and left atrial appendage closure (LAAC) have proven to be a feasible and safe strategy in treating patients with nonvalvular atrial fibrillation (AF). However, the interactions between CA and LAAC have not been systematically explored. We analyzed the impact of CA on long-term outcomes of LAAC in patients with AF treated with the hybrid procedure. METHODS: A total of 107 consecutive patients with AF who underwent LAAC were divided into two groups: group A (n = 61) included patients who underwent CA followed by LAAC during the same procedure and group B (n = 46) included patients who underwent LAAC only. All patients underwent systematic transesophageal echocardiography (TEE) follow-up. RESULTS: In group A, CA resulted in severe edema of the left atrial ridge (LAR), which manifested as an increase in LAR thickness from 4.6 ± 0.4 mm before CA to 6.8 ± 0.6 mm (P < .01) after CA. TEE at 45 days showed that the incidence of peri-device leakage was significantly higher in group A than in group B (45.9% vs 4.3%, P < .001). At the 12-month follow-up, the peri-device leakage rate remained higher in group A than in group B (14.8% vs 2.2%, P < .01). Three (4.9%) patients in group A experienced transient ischemia attacks; no events were reported in group B during the 1-year follow-up. CONCLUSION: Edema of LAR with the single-stage procedure that consists of CA followed by LAAC could result in increased peri-device leakage and decreased compression rate over time, which may be also associated with elevated risk profiles when compared with an LAAC-only procedure.

8.
Clin Chim Acta ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068630

RESUMO

To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P<0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.

9.
Transl Psychiatry ; 10(1): 353, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077728

RESUMO

Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.

10.
Urol Clin North Am ; 47(4): 487-510, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008499

RESUMO

The advent of immunotherapy has revolutionized cancer treatment. Prostate cancer has an immunosuppressive microenvironment and a low tumor mutation burden, resulting in low neoantigen expression. The consensus was that immunotherapy would be less effective in prostate cancer. However, recent studies have reported that prostate cancer does have a high number of DNA damage and repair gene defects. Immunotherapies that have been tested in prostate cancer so far have been mainly vaccines and checkpoint inhibitors. A combination of genomically targeted therapies, with approaches to alleviate immune response and thereby make the tumor microenvironment immunologically hot, is promising.


Assuntos
Produtos Biológicos/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Microambiente Tumoral/efeitos dos fármacos , Idoso , Animais , Antígenos de Neoplasias/efeitos dos fármacos , Antígenos de Neoplasias/imunologia , Previsões , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/imunologia , Estadiamento de Neoplasias , Neoplasias da Próstata/genética , Resultado do Tratamento , Microambiente Tumoral/genética
11.
J Chin Med Assoc ; 83(10): 918-922, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33017125

RESUMO

BACKGROUND: To surgically remove osteoma and to keep an optimal cosmetic profile would be very challenging. To solve the difficulty, we utilized the three-dimensional (3D) printing technologies in generating a patient-specific instrument guide (PSIG) for the safe removal of a skull bone tumor. METHODS: The preoperational brain computed tomography (CT) provided the digital imaging with thin slices, and then images were reconstructed into a 3D skull model. Based on the model, we designed a PSIG to make landmarks on the osteoma to avoid excessive removal of the skull bone. During the operation, the surgeons could remove the osteoma piece by piece by using the landmark as a reference point. RESULTS: The PSIG was successfully applied to remove an osteoma that measured 60 × 48 × 40 mm over the left frontoparietal skull of a female patient. The 3D CT reconstruction taken both before and 4 months after surgery showed a significant change in the appearance of the osteoma. CONCLUSION: The PSIG was able to guide the surgeon in the safe removal of the skull osteoma, as well as in maintaining the cosmetic skull profile.

12.
J Craniofac Surg ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038178

RESUMO

BACKGROUND: The aim of this study was to explore the characteristics and correlation of maxillofacial fractures and concurrent injuries with different injury causes. METHODS: In this retrospective study, data were collected from patients treated for maxillofacial fractures in 3 oral and maxillofacial surgery departments in Southeast China, from January 2010 to December 2019. The information was obtained from clinical notes and surgical records using a standardized data collection form, and some causes of injuries were confirmed by telephone follow-ups and police records. These patients were divided into 7 groups according to the etiology: bicycle accident, electric bicycle accident, motorcycle accident, automobile accident, fall at ground level, fall from a height, and assault-related accident. Statistical tests were performed using R software (version 3.1.1), and all P-values were computed based on Chi-square tests and set at 0.05. RESULTS: During this 10-year retrospective study, a total of 1772 patients with definite causes were analyzed. The average age was approximately 35.04 years (9 months-94 years). All patients were treated with open reduction and rigidly internal fixation, and the average duration was approximately 6.51 days (range 0 day-50 days), that from the time of the injury to the time of treatment. Traffic accidents were identified as the main cause of maxillofacial fracture (57.62%; n = 1021 of 1772 cases). In different etiology groups, there were statistically significant differences in the distribution of age, sex, maxillofacial fracture type, and concurrent injuries (all P < 0.001). However, the main cause of maxillofacial injuries was falls (fall at ground level and fall from a height) in children, and the highest incidence of the cause of maxillofacial injuries was bicycle accident in adolescents. Compared with the other groups, zygomatic complex fracture was more common in the electric bicycle accident group, panfacial fracture was more common in the automobile accident group, and mandible fracture was more common in the other groups. CONCLUSION: The results of this study suggest that patients with maxillofacial fractures caused by different injuries had their own unique characteristics. These findings may assist us in avoiding misdiagnosis and treatment delays, and may make treatment plans faster.

13.
Diabetes Obes Metab ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016522

RESUMO

AIMS: To quantitatively analyse the association between the durability of glycaemic control and body weight changes during treatment. METHODS: This study adhered to an appropriate methodology according to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Studies with follow-ups longer than 12 months and final and intermediate assessments of haemoglobin A1c (HbA1c) and body weight were included. Four outcomes assessing therapeutic durability were extracted and synthesized using Stata statistical software, including changes in HbA1c, the goal-achievement rate, the failure rate, and the coefficient of failure (CoF). RESULT: After 8.9 months of treatment, HbA1c levels declined from 8.03% (95% confidence interval (CI), 7.91 to 8.15; I2 = 99.2%) to 7.15% (95% CI, 7.02 to 7.27; I2 = 99.4%) and then gradually increased up to 7.72% (95% CI, 7.50 to 7.94; I2 = 99.0%) five years later. The goal-achievement rate decreased from 54.8% (after one year of treatment) to 19.4% five years later. The CoF was 0.123±0.022 %/year (P < 0.001). After stratification, the CoFs were 0.224 ± 0.025%/y (p < 0.001) for weight gain, 0.137 ±0.034%/y (p <0.001) for neutral weight and -0.024 ± 0.032%/y (p = 0.450) for weight loss. After stratification by treatment approaches, the CoFs were 0.45%/y for insulin, 0.43%/y for sulfonylurea, 0.34%/y for thiazolidinediones, 0.29%/y for metformin, 0.16% for glucagon-like polypeptide-1 receptor agonists, 0.12% for surgery, -0.03% for sodium-glucose cotransporter-2 inhibitors and -0.21% for dipeptidyl peptidase-IV inhibitors. CONCLUSION: Modest weight loss with a goal of 2-3% of body weight should be recommended to improve therapeutic durability and prevent beta-cell deterioration.

14.
Neoplasma ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030958

RESUMO

Highly expressed high mobility group box-1 protein (HMGB1) promotes tumor metastasis. Whether HMGB1 participates in breast cancer cell activation of fibroblasts is unknown. The culture medium of 6 breast cancer cell lines with different migration potential, and with HMGB1 overexpression or knockdown was used to induce fibroblast activation, and collagen and α-SMA expression were measured. We evaluated the migration potential of MDA-MB-231 cells with fibroblasts treated with 3-PO (3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one) inhibitor, anti-HMGB1 treatment, or RAGE (receptor for advanced glycation end products) knockdown. A lung metastasis murine model was used to evaluate whether the RAGE-knockdown fibroblasts mitigates MDA-MB-231 metastasis. Breast cancer cells that are highly migratory and have a high invasive potential, had higher HMGB1 expression and induced greater fibroblast activation strongly than cells with poorer motility. hrHMGB1 and the supernatants of HMGB1-overexpressed MCF-7 cells promoted fibroblast activation, but loss-HMGB1 of MDA-MB-231 abolished potential. Moreover, a novel mechanism was identified by which HMGB1 facilitated fibroblast activation by RAGE/aerobic glycolysis. Consistently, fibroblasts enhanced MDA-MB-231 metastasis, but the enhancement was reversed by 3-PO inhibition, anti-HMGB1 treatment, or RAGE knockdown in vitro and in vivo. We identified that HMGB1 secreted by breast cancer cells promotes fibroblast activation via RAGE/aerobic glycolysis, and activated fibroblasts enhance breast cancer cell metastasis through increased lactate.

15.
J Affect Disord ; 276: 327-334, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871663

RESUMO

BACKGROUND: Minimally adequate treatment (MAT) is intended to represent treatment minimally sufficient for common mental health problems. For children, MAT has been defined over a twelve-month period as either eight or more mental health visits, or four to seven visits plus relevant medication. MAT is used to identify those missing out on adequate care, but it is unknown whether MAT improves children's outcomes. METHODS: This paper examines whether MAT is associated with improved outcomes for children. It uses survey data from the nationally representative Longitudinal Study of Australian children on 596 children with mental health problems based on the Strengths and Difficulties Questionnaire at ages 8-15 years, linked to health service administrative data from 2012 to 2016. Statistical analysis examines the association of MAT with later quality of life (Pediatric Quality of Life Inventory), using a lagged dependent variable model to account for time-varying unobserved confounding. RESULTS: Compared to children with lower levels of treatment, those who received MAT between baseline and follow up had no statistically significant improvement in either quality of life or mental health symptoms. LIMITATIONS: The observational data provide insight into real-world practice but require statistical methods to account for selection into treatment. CONCLUSIONS: While clinical trials show mental health treatments can be efficacious, this study shows no evidence that children receiving MAT in routine practice have better outcomes. These findings demonstrate the need for better understanding of the nature and impact of children's mental health care as it is delivered and received in routine practice.

16.
Biomed Res Int ; 2020: 6472456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923483

RESUMO

Objective: Our goal was to evaluate the efficacy of muscle spasm before and after rehabilitation by comparing shear wave propagation velocity (SWV) and Young's modulus (YM) in the normal and spastic biceps brachii in stroke patients. Methods: A study of 60 stroke patients with upper limb spasm was performed; these patients were admitted from April 2018 to September 2019. The modified Ashworth scale (MAS) scores of the spastic biceps brachii before and after rehabilitation treatment were compared. SWV and YM on the spastic and normal biceps brachii before rehabilitation treatment, SWV and YM on the spastic and normal biceps brachii after rehabilitation treatment, and SWV and YM on the spastic biceps brachii before and after rehabilitation treatment were compared. Whether SWV and YM on the spastic biceps brachii are related to MAS was compared. Results: There was a statistically significant difference in SWV and YM between the normal and spastic biceps brachii before (P < 0.01) and after (P < 0.05) the rehabilitation treatment. There was no statistically significant difference in SWV and YM in the normal biceps brachii before and after the rehabilitation treatment (P > 0.05). There was a statistically significant difference in SWV and YM in the spastic biceps brachii before and after the rehabilitation treatment (P < 0.01). SWV and FM of the spastic biceps brachii are correlated with MAS before and after rehabilitation treatment, and the correlation coefficient for SWV was 0.563 and 0.605 for YM (P < 0.05). Conclusion: SWE can be used as a means of assessment before and after rehabilitation treatment.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32948902

RESUMO

KEY MESSAGE: We identified FLY as a previously uncharacterized RNA-binding-family protein that controls flowering time by positively regulating the expression of FLC clade members. The ability of flowering plants to adjust the timing of the floral transition based on endogenous and environmental signals contributes to their adaptive success. In Arabidopsis thaliana, the MADS-domain protein FLOWERING LOCUS C (FLC) and the FLC clade members FLOWERING LOCUS M/MADS AFFECTING FLOWERING1 (FLM/MAF1), MAF2, MAF3, MAF4, and MAF5 form nuclear complexes that repress flowering under noninductive conditions. However, how FLM/MAF genes are regulated requires further study. Using a genetic strategy, we showed that the previously uncharacterized K-homology (KH) domain protein FLOWERING LOCUS Y (FLY) modulates flowering time. The fly-1 knockout mutant and FLY artificial microRNA knockdown line flowered earlier than the wild type under long- and short-day conditions. The knockout fly-1 allele, a SALK T-DNA insertion mutant, contains an ~ 110-kb genomic deletion induced by T-DNA integration. FLC clade members were downregulated in the fly-1 mutants and FLY artificial microRNA knockdown line, whereas the level of the FLC antisense transcript COOLAIR was similar to that of the wild type. Our results identify FLY as a regulator that affects flowering time through upregulation of FLC clade members.

18.
Abdom Radiol (NY) ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32964274

RESUMO

PURPOSE: To determine the utility of diffusion kurtosis imaging (DKI) for assessing bowel fibrosis and to establish a new magnetic resonance imaging (MRI)-based classification based on DKI and conventional MRI parameters for characterizing intestinal strictures in Crohn's disease (CD) using the histological evaluation of resected intestine samples as the reference standard. METHODS: Thirty-one patients with CD undergoing preoperative conventional MRI and diffusion-weighted imaging (DWI) (b values = 0-2000 s/mm2) were consecutively enrolled. We classified the mural T2-weighted signal intensity and arterial-phase enhancement patterns on conventional MRI. We also measured DWI-derived apparent diffusion coefficients (ADCs) and DKI-derived apparent diffusion for non-Gaussian distribution (Dapp) and apparent diffusional kurtosis (Kapp). A new MRI-based classification was established to characterize intestinal strictures in CD. Its performance was validated in nine additional patients with CD. RESULTS: Histological inflammation grades were significantly correlated to T2-weighted signal intensity (r = 0.477; P < 0.001) and ADC (r = - 0.226; P = 0.044). Histological fibrosis grades were moderately correlated to Kapp (r = 0.604, P < 0.001); they were also correlated to Dapp (r = - 0.491; P < 0.001) and ADC (r = - 0.270; P = 0.015). T2-weighted signal intensity could differentiate between no-to-mild and moderate-to-severe bowel inflammation (sensitivity, 0.970; specificity, 0.479). Kapp could differentiate between no-to-mild and moderate-to-severe bowel fibrosis (sensitivity, 0.959; specificity, 0.781). The agreement between the new MRI-based classification and the histological classification was moderate in the test (κ = 0.507; P < 0.001) and validation (κ = 0.530; P < 0.001) sets. CONCLUSIONS: DKI can be used to assess bowel fibrosis. The new MRI-based classification can help to distinguish between fibrotic and inflammatory intestinal strictures in patients with CD.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32958710

RESUMO

Streptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which could be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such kind of lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococci-specific lysin ClyJ comprising the binding domain from the putative endolysin gp20 from the Streptococcus phage SPSL1 and the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the PlyC lysin. And a variant of ClyJ with shortened linker, i.e. ClyJ-3, shows improved activity and reduced cytotoxicity. Resembling typical CBM-containing lysins, ClyJ-3 dimerized upon binding with choline. Herein, we further report a choline-recognizing variant of ClyJ-3, i.e. ClyJ-3m, constructed by deleting its C-terminal tail. Biochemical characterization showed that ClyJ-3m remains a monomer after bound to choline, yet exhibits improved bactericidal activity against multiple pneumococcal strains with different serotypes. In a S. pneumoniae-infected bacteremia model, a single intraperitoneal administration of 2.32 µg/mouse of ClyJ-3m showed 70% protection, while only 20% of mice survived in the group receiving an equal dose of ClyJ-3 (p < 0.05). A pharmacokinetic analysis following single intravenously doses of 0.29 and 1.16 mg/kg of ClyJ-3 or ClyJ-3m in BALB/c mice revealed that ClyJ-3m shows a similar half-life, but smaller Cl (clearance) and higher AUC (area under curve) than ClyJ-3. Taken together, the choline-recognizing monomer ClyJ-3m exhibited enhanced bactericidal activity and improved pharmacokinetic proprieties than its parental ClyJ-3 lysin. Our study also provides a new way for rational design and programmed engineering of lysins targeting on S. pneumoniae.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32978076

RESUMO

PURPOSE: This study aimed to compare the safety and efficacy of clarithromycin-naproxen-oseltamivir combination therapy to that of oseltamivir therapy alone in hospitalized pediatric influenza patients. METHODS: This prospective, single-blind study included children aged 1-18 years hospitalized with influenza, in MacKay Children's Hospital, Taiwan, between December 2017 and December 2019. The primary outcomes were the time to defervescence and decrease of the Pediatric Respiratory Severity Score (PRESS) during hospitalization. The secondary outcomes were serial changes in virus titers, measured using real-time polymerase chain reaction. RESULTS: Fifty-four patients were enrolled (28 in the control group and 26 in the combination group) in total. There were no differences in the patients' baseline characteristics between the groups. The time to defervescence was significantly shorter in the combination group than the oseltamivir group (13.2 h vs. 32.1 h, p = 0.002). The decrease in the virus titer from days 1-3 (log Δ13) was more pronounced in the combination group than the oseltamivir group. (39% vs. 19%, p = 0.001). There were no differences in adverse effects such as vomiting, diarrhea, and abdominal pain during the study or within 30 days after antiviral therapy. CONCLUSION: The clarithromycin-naproxen-oseltamivir combination group experienced a more rapid defervescence and a more rapid decline of influenza virus titer than the group treated with oseltamivir alone. Further consideration should be given to whether the overall benefits of combination therapy in hospitalized pediatric influenza patients outweigh the risks.

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