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1.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638959

RESUMO

Though Morusin isolated from the root of Morus alba was known to have antioxidant, anti-inflammatory, antiangiogenic, antimigratory, and apoptotic effects, the underlying antitumor effect of Morusin is not fully understood on the glycolysis of liver cancers. Hence, in the current study, the antitumor mechanism of Morusin was explored in Hep3B and Huh7 hepatocellular carcninomas (HCC) in association with glycolysis and G1 arrest. Herein, Morusin significantly reduced the viability and the number of colonies in Hep3B and Huh7 cells. Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. Interestingly, Morusin significantly activated phosphorylation of the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but attenuated the expression of the p-mammalian target of protein kinase B (AKT), rapamycin (mTOR), c-Myc, hexokinase 2(HK2), pyruvate kinases type M2 (PKM2), and lactate dehydrogenase (LDH) in Hep3B and Huh7 cells. Consistently, Morusin suppressed lactate, glucose, and adenosine triphosphate (ATP) in Hep3B and Huh7 cells. Conversely, the AMPK inhibitor compound C reduced the ability of Morusin to activate AMPK and attenuate the expression of p-mTOR, HK2, PKM2, and LDH-A and suppressed G1 arrest induced by Morusin in Hep3B cells. Overall, these findings suggest that Morusin exerts an antitumor effect in HCCs via AMPK mediated G1 arrest and antiglycolysis as a potent dietary anticancer candidate.

2.
Clin Exp Pediatr ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34645257

RESUMO

Background: Viral load and shedding duration are highly associated with the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, limited studies have reported on viral load or shedding in children and adolescents infected with sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose: This study aimed to investigate the natural course of viral load in asymptomatic or mild pediatric cases. Methods: Thirty-one children (<18 years) with confirmed SARS-CoV-2 infection were hospitalized and enrolled in this study. Viral loads were evaluated in nasopharyngeal swab samples using real-time reverse transcription polymerase chain reaction (E, RdRp, N genes). Ct values were measured when patients met the clinical criteria to be released from quarantine. Results: The mean age of the patients was 9.8 years, 18 (58%) had mild disease, and 13 (42%) were asymptomatic. Most children were infected by adult family members, most commonly by their mothers. The most common symptoms were fever and sputum (26%), followed by cough and runny nose. Nine patients (29%) had a high or intermediate viral load (Ct value≤30) when they had no clinical symptoms. Viral load showed no difference between symptomatic and asymptomatic patients. Viral rebounds were found in 15 cases (48%), which contributed to prolonged viral detection. The mean duration of viral detection was 25.6 days. Viral loads were significantly lower in patients with viral rebounds than in those with no rebound (E, p=0.003; RdRp, p=0.01; N, p=0.02). Conclusion: Our study showed that many pediatric patients with COVID-19 experienced viral rebound and showed viral detection for more than 3 weeks. Further studies are needed to investigate the relationship between viral rebound and infectiousness in COVID-19.

3.
Sensors (Basel) ; 21(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34577427

RESUMO

Pinching motions are important for holding and retaining objects with precision. Therefore, training exercises for the thumb and index finger are extremely important in the field of hand rehabilitation. Considering the need for training convenience, we developed a device and a driving system to assist pinching motions actively via a lightweight, simple, and wireless mechanism driven by the magnetic forces and torques generated by magnets attached to the tip of these two fingers. This device provides accurate pinching motions through the linking structures connecting the two magnets. The fabricated device has minimal mechanical elements with an ultralightweight of 57.2 g. The magnetic field, the intensity of which is based on the time variant, generates a pinching motion between the thumb and index finger, thus rendering it possible to achieve repetitive training. To verify the generation of an active pinching motion, we fabricated a finger model using a 3D printer and a rubber sheet and observed the active motions generated by the newly developed device. We also verified the performance of the proposed mechanism and driving method via various experiments and magnetic simulations. The proposed mechanism represents an important breakthrough for patients requiring hand rehabilitation and wearable assistive motion devices.


Assuntos
Dedos , Mãos , Fenômenos Biomecânicos , Humanos , Movimento , Polegar
4.
Blood Press Monit ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34569988

RESUMO

OBJECTIVE: There is an unmet need for noninvasive continuous blood pressure (BP) monitoring technologies in various clinical settings. Continuous and noninvasive central aortic BP monitoring is technically not feasible currently, but if realized, would provide more accurate and real-time global hemodynamic information than any form of peripheral arterial BP monitoring in an acute care setting. As part of our efforts to develop such, herein we examined the tracking correlation between noninvasively-derived peripheral arterial BP by Caretaker device against invasively measured central aortic BP. METHODS: Beat-to-beat BP by Caretaker was recorded simultaneously with central aortic BP measured in patients undergoing cardiac catheterization. Pearson's correlation was also derived for SBP and DBP. A trend comparison analysis of the beat-to-beat BP change was performed using a four-quadrant plot analysis with the exclusion zones of 0.5 mmHg/s to determine concordance, (i.e. the direction of beat-to-beat changes in SBP and DBP). RESULTS: A total of 47 patients were included in the study. A total of 31 369 beats representing an average of 17.3 min of recording were used for analysis. The trend analysis yielded concordances of 84.4 and 83.5% for SBP and DBP, respectively. Respective correlations (Pearson's r) for SBP and DBP trends were 0.87 and 0.86 (P < 0.01). Tracking of beat-to-beat BP by Caretaker showed excellent concordance and correlation in the direction and the degree of BP change with central aortic BP, respectively. CONCLUSION: This study supports the satisfactory performance of the Caretaker device in continuous tracking of central aortic BP beat-to-beat BP and provides a basis to develop an algorithm for absolute central aortic BP estimation in the future.

5.
Yonsei Med J ; 62(10): 928-935, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34558872

RESUMO

PURPOSE: In young patients with varicocele, preservation of the internal spermatic artery may be advantageous for catch-up growth, but it may also increase the likelihood of treatment failure. Intraoperative venography reduces the likelihood that unsealed veins will remain after varicocelectomy. We analyzed the characteristics of remnant veins visualized through intraoperative venography to investigate the cause of surgical failure in artery-sparing varicocelectomy (ASV). MATERIALS AND METHODS: We retrospectively analyzed clinical characteristics and outcomes of patients aged 18 years or younger who underwent varicocelectomy with intraoperative venography from January 2005 to December 2017. During varicocelectomy, intraoperative venography was performed to distinguish veins from other structures. Any unsealed veins that were discovered were ligated and classified using the Bahren system. RESULTS: One hundred and sixty-two patients underwent intraoperative venography: 153 cases (94.4%) were for primary varicocelectomy, and 9 cases (5.6%) were for repeat varicocelectomy. Open varicocelectomy was performed in 105 cases (64.8%), and laparoscopic varicocelectomy was performed in 57 cases (35.2%). Venography revealed remnant veins after the first ligation in 51 cases (31.2%), 46 (90.2%) and 5 (9.8%) of which were Bähren types 3 and 4, respectively. Five patients (3.1%) experienced varicocele recurrence, classified as persistence in 1 patient (0.6%) and relapse in 4 patients (2.5%). CONCLUSION: Remnant collateral veins of the internal spermatic vein (ISV) (Bahren type 3) are the most common cause of failure in ASV. In a few patients, an external spermatic vein merges with the ISV at a higher level (Bahren type 4) and is unidentifiable without venography.


Assuntos
Cordão Espermático , Varicocele , Humanos , Masculino , Flebografia , Estudos Retrospectivos , Cordão Espermático/diagnóstico por imagem , Cordão Espermático/cirurgia , Testículo , Varicocele/diagnóstico por imagem , Varicocele/cirurgia , Veias/diagnóstico por imagem , Veias/cirurgia
6.
Medicine (Baltimore) ; 100(32): e26880, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397904

RESUMO

ABSTRACT: Poor oral hygiene can be potentially life-threatening in inpatients. However, no basic protocol on oral hygiene customized for inpatients exists, and lack of oral care related knowledge, attitude, and skills among caregivers could be detrimental to the general health of patients. This study sought to identify the oral care practices and oral health status of inpatients with varying physical activity limitations in a rehabilitation ward.Sixty-one inpatients in a rehabilitation ward were evaluated for their medical and physical conditions and oral health status. These were assessed using the bedside oral exam, decayed, missing, filled teeth index, plaque index, gingival index, and caries activity test.In total, 40 men and 21 women (mean age, 56.6 years) were included in this study. Among them, 50.8% of the patients could brush their teeth unassisted, whereas 49.2% required assistance from an assistant for oral care. The proportion of patients receiving nasogastric tube feeding was higher in the group that could not provide oral self-care; 36.7% and 33.3% of these patients showed moderate and severe dysfunction, respectively, based on bedside oral exam. Scores for the swallowing, tongue, and total domains of bedside oral exam were poorer for patients who could not provide oral self-care (P < .01). The caries activity test indicated a moderate risk for both groups.Our findings suggest that an oral care protocol that considers the physical activity limitations in inpatients in rehabilitation wards is necessary to minimize negative influences on the systemic health of these patients.


Assuntos
Atividades Cotidianas , Cárie Dentária , Saúde Bucal/normas , Higiene Bucal , Autocuidado , Cuidadores/educação , Cárie Dentária/diagnóstico , Cárie Dentária/prevenção & controle , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Higiene Bucal/educação , Higiene Bucal/métodos , Índice Periodontal , Desempenho Físico Funcional , Centros de Reabilitação/estatística & dados numéricos , República da Coreia/epidemiologia , Autocuidado/métodos , Autocuidado/estatística & dados numéricos
7.
Semin Cancer Biol ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34428551

RESUMO

Since cancer immunotherapy with immune checkpoint inhibitors of PD/PDL-1 and CTLA-4 limited efficacy to the patients due to resistance during the current decade, novel target is required for customized treatment due to tumor heterogeneity. V-domain Ig-containing suppressor of T cell activation (VISTA), a programmed death protein-1(PD-1) homolog expressed on T cells and on antigen presenting cells(APC), has emerged as a new target in several cancers. Though VISTA inhibitors including CA-170 are considered attractive in cancer immunotherapy to date, the information on VISTA as a potent biomarker of cancer prognosis and its combination therapy is still lacking to date. Thus, in this review, we discussed extracellular domain, ligands, expression, immune functions and clinical implications of VISTA and finally suggested conclusion and perspectives.

8.
Cells ; 10(8)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34440834

RESUMO

Novel target therapy is on the spotlight for effective cancer therapy. Hence, in the present study, the underlying apoptotic mechanism of Morusin was explored in association with miR193a-5p mediated ZNF746/c-Myc signaling axis in colorectal cancer cells (CRCs). Herein, Morusin reduced the viability and the number of colonies in HCT116 and SW480 CRCs. Additionally, Morusin increased sub-G1 population, cleavages of poly (ADP-ribose) polymerase (PARP) and caspase-3 and inhibited the expression of zinc finger protein 746 (ZNF746) and c-Myc in HCT116 and SW480 cells. Conversely, overexpression of ZNF746 suppressed the ability of Morusin to abrogate the expression of c-Myc in HCT116 cells, as ZNF746 enhanced the stability of c-Myc via their direct binding through nuclear colocalization in HCT116 cells by immunofluorescence and immunoprecipitation. Notably, Morusin upregulated miR193a-5p as a tumor suppressor, while miR193a-5p inhibitor masked the ability of Morusin to reduce the expression of ZNF746, c-Myc, and pro-PARP in HCT116 cells. To our knowledge, these findings provide the novel insight on miR193a-5p mediated inhibition of ZNF746/c-Myc signaling in Morusin induced apoptosis in CRCs.

9.
Cells ; 10(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34440920

RESUMO

Since the signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) signaling plays an important role in tumor-immune microenvironments, in the present study, the role of STAT3/PD-L1 signaling in the apoptotic mechanism of an active ginseng saponin metabolite compound K (CK) was investigated in human prostate cancer cells. Here, CK exerted significant cytotoxicity without hurting RWPE1 normal prostate epithelial cells, increased sub-G1 and cleavage of Poly ADP-ribose polymerase (PARP) and attenuated the expression of pro-PARP and Pro-cysteine aspartyl-specific protease3 (pro-caspase-3) in LANCap, PC-3 and DU145 cells. Further, CK attenuated the expression of p-STAT3 and PD-L1 in DU145 cells along with disrupted the binding of STAT3 to PD-L1. Furthermore, CK effectively abrogated the expression of p-STAT3 and PD-L1 in interferon-gamma (INF-γ)-stimulated DU145cells. Additionally, CK suppressed the expression of vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), interleukin 6 (IL-6) and interleukin 10 (IL-10) as immune escape-related genes in DU145 cells. Likewise, as STAT3 targets genes, the expression of CyclinD1, c-Myc and B-cell lymphoma-extra-large (Bcl-xL) was attenuated in CK-treated DU145 cells. Notably, CK upregulated the expression of microRNA193a-5p (miR193a-5p) in DU145 cells. Consistently, miR193a-5p mimic suppressed p-STAT3, PD-L1 and pro-PARP, while miR193a-5p inhibitor reversed the ability of CK to attenuate the expression of p-STAT3, PD-L1 and pro-PARP in DU145 cells. Taken together, these findings support evidence that CK induces apoptosis via the activation of miR193a-5p and inhibition of PD-L1 and STAT3 signaling in prostate cancer cells.

10.
Proc Natl Acad Sci U S A ; 118(35)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34452998

RESUMO

Efforts to improve estrogen receptor-α (ER)-targeted therapies in breast cancer have relied upon a single mechanism, with ligands having a single side chain on the ligand core that extends outward to determine antagonism of breast cancer growth. Here, we describe inhibitors with two ER-targeting moieties, one of which uses an alternate structural mechanism to generate full antagonism, freeing the side chain to independently determine other critical properties of the ligands. By combining two molecular targeting approaches into a single ER ligand, we have generated antiestrogens that function through new mechanisms and structural paradigms to achieve antagonism. These dual-mechanism ER inhibitors (DMERIs) cause alternate, noncanonical structural perturbations of the receptor ligand-binding domain (LBD) to antagonize proliferation in ER-positive breast cancer cells and in allele-specific resistance models. Our structural analyses with DMERIs highlight marked differences from current standard-of-care, single-mechanism antiestrogens. These findings uncover an enhanced flexibility of the ER LBD through which it can access nonconsensus conformational modes in response to DMERI binding, broadly and effectively suppressing ER activity.

11.
Investig Clin Urol ; 62(5): 592-599, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34387035

RESUMO

PURPOSE: We compared the intraoperative and postoperative outcomes of single-port robot-assisted laparoscopic pyeloplasty (S-RALP) using the da Vinci SP® system and conventional multi-port robot-assisted laparoscopic pyeloplasty (M-RALP) in pediatric patients. MATERIALS AND METHODS: Multi-port and single-port pyeloplasty have been performed in pediatric patients in our institution since October 2015 and February 2019, respectively. We conducted an entire cohort comparison. Considering the learning curve of M-RALP, we defined the last 15 cases of M-RALP as a subgroup of M-RALP and compared this subgroup with the entire cohort of S-RALP patients. RESULTS: Thirty-one patients who underwent multi-port pyeloplasty and 15 patients who underwent single-port pyeloplasty were enrolled in this study. Age, height, body weight, laterality, surgical indication, and ipsilateral differential renal function were statistically similar in the M-RALP and S-RALP groups. The median operative time (3.0 h vs. 2.4 h; p=0.01) and the median console time (2.2 h vs. 1.5 h; p<0.001) were longer in the M-RALP group than in the S-RALP group. There was no significant difference in operative time or console time between the M-RALP subgroup and the S-RALP group. There were no significant differences in the length of hospitalization, pain score, morphine-equivalent use of analgesics, or postoperative differential renal function in all comparisons. CONCLUSIONS: This study confirmed that pyeloplasty using the da Vinci® SP system can be started by robotic surgeons who can overcome the learning curve. Robot-assisted laparoscopic single-port pyeloplasty is feasible in noninfant pediatric patients.

12.
Sensors (Basel) ; 21(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34372366

RESUMO

BACKGROUND: We aimed to create a novel model using a deep learning method to estimate stroke volume variation (SVV), a widely used predictor of fluid responsiveness, from arterial blood pressure waveform (ABPW). METHODS: In total, 557 patients and 8,512,564 SVV datasets were collected and were divided into three groups: training, validation, and test. Data was composed of 10 s of ABPW and corresponding SVV data recorded every 2 s. We built a convolutional neural network (CNN) model to estimate SVV from the ABPW with pre-existing commercialized model (EV1000) as a reference. We applied pre-processing, multichannel, and dimension reduction to improve the CNN model with diversified inputs. RESULTS: Our CNN model showed an acceptable performance with sample data (r = 0.91, MSE = 6.92). Diversification of inputs, such as normalization, frequency, and slope of ABPW significantly improved the model correlation (r = 0.95), lowered mean squared error (MSE = 2.13), and resulted in a high concordance rate (96.26%) with the SVV from the commercialized model. CONCLUSIONS: We developed a new CNN deep-learning model to estimate SVV. Our CNN model seems to be a viable alternative when the necessary medical device is not available, thereby allowing a wider range of application and resulting in optimal patient management.


Assuntos
Pressão Arterial , Redes Neurais de Computação , Pressão Sanguínea , Humanos , Volume Sistólico
13.
Nutrients ; 13(7)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199110

RESUMO

BACKGROUND: Sarcopenia contributes to increased morbidity and mortality in patients undergoing surgery for abdominal aortic aneurysms (AAA). However, few reports have demonstrated whether sarcopenia would affect the development of postoperative acute kidney injury (AKI) in these patients. This study aimed to examine whether sarcopenia is associated with AKI and morbidity and mortality after infrarenal AAA operation. METHODS: We retrospectively analysed 379 patients who underwent infrarenal AAA surgery. The diagnosis of sarcopenia was performed using the skeletal muscle index, which was calculated from axial computed tomography at the level of L3. The patients were separated into those with sarcopenia (n = 104) and those without sarcopenia (n = 275). We applied multivariable and Cox regression analyses to evaluate the risk factors for AKI and overall mortality. A propensity score matching (PSM) evaluation was done to assess the postoperative results. RESULTS: The incidence of AKI was greater in sarcopenia than non-sarcopenia group before (34.6% vs. 15.3%; p < 0.001) and after the PSM analysis (34.6% vs. 15.4%; p = 0.002). Multivariable analysis revealed sarcopenia to be associated with AKI before (p = 0.010) and after PSM (p = 0.016). Sarcopenia was also associated with overall mortality before (p = 0.048) and after PSM (p = 0.032). A Kaplan-Meier analysis revealed that overall mortality was elevated patients with sarcopenia before and after PSM than in those without (log-rank test, p < 0.001, p = 0.022). CONCLUSIONS: Sarcopenia was associated with increased postoperative AKI incidence and overall mortality among individuals who underwent infrarenal AAA operation.


Assuntos
Injúria Renal Aguda/etiologia , Aneurisma da Aorta Abdominal/complicações , Sarcopenia/etiologia , Injúria Renal Aguda/mortalidade , Idoso , Aorta Abdominal , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Músculo Esquelético , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/mortalidade
14.
J Crohns Colitis ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309652

RESUMO

BACKGROUND AND AIMS: The long-term outcomes of pediatric-onset inflammatory bowel disease (pIBD) in non-Caucasian populations are unknown. We, therefore, evaluated and compared the clinical features and long-term outcomes of pIBD with those of adult-onset IBD (aIBD) using a population-based cohort in the Songpa-Kangdong district of Seoul, Korea. METHODS: Clinical characteristics and prognoses were compared between the two groups: pIBD (defined as <18 years of age at diagnosis) and aIBD (18-59 years of age at diagnosis). RESULTS: We identified 131 patients with pIBD (48 ulcerative colitis [UC], 83 Crohn's disease [CD]) and 1192 patients with aIBD (866 UC, 326 CD) during 1986-2015. An extensive colitis at diagnosis was more prevalent in pUC than in aUC (45.8% vs. 22.3%, P<0.001), and the overall exposure to corticosteroids, thiopurines, and anti-tumor necrosis factor agents was higher in pUC than in aUC (P<0.001). The cumulative risk of colectomy was higher in pUC than in aUC during a median follow-up of 125.0 and 112.1 months, respectively (8.9% vs. 1.8% at 10 years after diagnosis, P=0.030). Ileocolonic location and inflammatory behavior at diagnosis were more common in pCD than in aCD; however, patients with pCD and aCD did not differ regarding treatment or disease course during a median follow-up of 137.2 and 120.9 months, respectively. CONCLUSION: Our study showed clear differences between pIBD and aIBD, especially in UC. pUC presents with more extensive diseases and may have a more severe disease course, as suggested by an earlier time to administering medications and performing colectomy.

15.
J Clin Sleep Med ; 17(8): 1521-1532, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34313214

RESUMO

STUDY OBJECTIVES: Sleep problems are common in allergic rhinitis (AR) and are a modifiable risk factor for suicidal ideation. However, the effect of sleep duration and weekend catch-up sleep (WCUS)-sleep time on weekends that exceeds sleep time on weekdays-on suicidal ideation for adolescents with AR is unknown. The objective of this study was to explore whether sleep duration and WCUS have an impact on suicidal ideation among adolescents with AR. METHODS: From the annual Korean Youth Risk Behavior Web-Based Surveys (completed from 2013-2017), data were obtained from a stratified, multistage, clustered sample. Using self-reported questionnaires, students provided doctor-diagnosed AR and sleep time. RESULTS: Among 134,417 and 262,653 adolescents with and without AR, respectively, those with AR compared with those without AR had more sleep dissatisfaction (46.6% vs 40.8%), slept less (sleep duration: 6.71 ± 1.37 hours vs 7.01 ± 1.48 hours), and had longer WCUS (3.46 ± 0.11 hours vs 2.11 ± 0.14 hours). After adjustment, the odds ratio of patients with sleep dissatisfaction was a 1.22 (95% confidence interval, 1.17-1.28) times higher risk of suicidal ideation than in those with sleep satisfaction. For average sleep duration (defining 7-8 hours as the reference), the odds ratio of short sleep (≤ 5 hours) was 1.45 (95% confidence interval, 1.32-1.53). Notably, long WCUS (≥ 2 hours) was significantly associated with decreased suicidal ideation (odds ratio, 0.85; 95% confidence interval, 0.81-0.92). CONCLUSIONS: Although further research is needed to clarify this association, under the condition of sleep deprivation, WCUS at a certain extent may be associated with a low risk for suicidal ideation in adolescents with AR. CITATION: Kim CW, Jeong SC, Hwang SW, Jo SH, Kim SH. Evidence of sleep duration and weekend sleep recovery impact on suicidal ideation in adolescents with allergic rhinitis. J Clin Sleep Med. 2021;17(8):1521-1532.


Assuntos
Rinite Alérgica , Ideação Suicida , Adolescente , Estudos Transversais , Humanos , Rinite Alérgica/complicações , Fatores de Risco , Assunção de Riscos , Sono
16.
J Diabetes ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34288415

RESUMO

BACKGROUND: Appendicular skeletal muscle mass (ASM) and grip strength (GS) have been suggested to be related to cardiovascular diseases (CVDs), but their association with type 2 diabetes (T2D) remains unclear. Therefore, we examined the combined association of ASM and GS with the prevalence of CVD in patients with T2D. METHODS: A total of 1230 patients with T2D were recruited and divided into four groups based on the sex-specific median values of ASM adjusted for body mass index (ASM/BMI; short: SM) and GS: high SM/high GS (HSM/HGS), high SM/low GS (HSM/LGS), low SM/high GS (LSM/HGS), and low SM/low GS (LSM/LGS). RESULTS: The LSM/LGS group was older and had higher values of systolic blood pressure, homeostasis model assessment of insulin resistance, waist circumference, and C-reactive protein but lower high-density lipoprotein cholesterol concentrations than the HSM/HGS group. After adjusting for potential confounders, the odds ratios (ORs) and 95% CIs for CVD, coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease (PAD) in the LSM/LGS group were 2.90 (1.89-4.47), 2.39 (1.46-3.92), 1.77 (0.84-3.71), and 5.83 (1.58-21.48), respectively. After adjusting for variable confounders among patients with higher glycosylated hemoglobin (HbA1c) (≥7.1%), the ORs and 95% CIs for CVD and CHD in the LSM/LGS group were 7.27 (3.37-15.67) and 6.17 (2.65-14.37), respectively. CONCLUSIONS: The combination of low SM and GS was strongly associated with CVD, CHD, and PAD in patients with T2D, especially in those with higher HbA1c levels.

17.
Gut Liver ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34148870

RESUMO

Background/Aims: The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68). Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.

18.
Phytother Res ; 35(8): 4538-4546, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34114707

RESUMO

In the current study, the underlying anti-metastatic mechanism of melatonin contained in some edible plants was explored in association with transmembrane protease serine 4 (TMPRSS4) mediated metastasis and epithelial-mesenchymal transition (EMT) signaling in human HCT15 and SW620 colorectal cancer cells. Here, TMPRSS4 was highly expressed in HCT15, but was weakly expressed in SW620 cells. Melatonin exerted weak cytotoxicity, decreased invasion, adhesion, and migration, and attenuated the expression of TMPRSS4, cyclin E, pro-urokinase-type plasminogen activator (pro-uPA), p-signal transducer and activator of transcription 3 (p-STAT3), p-focal adhesion kinase (p-FAK), Snail and increased the expression of E-cadherin, p27, pp38 and p-Jun N-terminal kinases (p-JNK) in HCT15 cells. Conversely, overexpression of TMPRSS4 reduced the ability of melatonin to activate E-cadherin and reduce Snail. Furthermore, even in SW620 cells transfected with TMPRSS4-overexpression plasmid, melatonin effectively suppressed invasion and migration along with decreased expression of Snail, cyclin A, cyclin E, pro-uPA and p-FAK and increased expression of E-cadherin and p27. Overall, these findings provide evidence that melatonin suppresses metastasis in colon cancer cells via inhibition of TMPRSS4 mediated EMT.


Assuntos
Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Melatonina , Proteínas de Membrana/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Melatonina/farmacologia , Serina , Serina Endopeptidases
19.
Phytother Res ; 35(8): 4547-4554, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34132431

RESUMO

In the current study, the pivotal roles of serum and glucocorticoid-induced protein kinase (SGK1) and NF-kB related signalings known as prognostic biomarkers in cervical cancers were explored in the antitumor effect of a ginseng saponin metabolite compound K (CK) in HeLa and SiHa cervical cancer cells. CK exerted significant cytotoxicity, induced sub-G1 accumulation, and attenuated the expression of proPoly (ADP-ribose) polymerase (pro-PARP) and Pro-cysteine aspartyl-specific protease (pro-caspase3) in HeLa cells more than in SiHa cells. CK inhibited phosphorylation of SGK1 and its upstream genes, phosphoinositide 3-kinases (PI3K), and phosphoinositide-dependent kinase-1 (PDK1) in HeLa cells. In addition, CK suppressed the phosphorylation of SGK1, NF-κB, and inhibitor of kappa B (IκB) and also NF-κB target genes such as X-linked inhibitor of apoptosis protein and B-cell lymphoma 2 (Bcl-2) in HeLa cells. Notably, Immunoprecipitation revealed that SGK1 binds to PI3K or PDK1 and also CK disturbed the binding between SGK1 and PI3K or PDK1 in HeLa cells. Furthermore, PI3K inhibitor LY294002 decreased expression of PI3K, p-PDK1, p-SGK1, and pro-caspase3 and SGK1 inhibitor GSK650394 also reduced expression of NF-κB and pro-caspase3 just like CK in HeLa cells. Overall, these findings suggest that CK induces apoptosis via suppression of PI3K/PDK1/SGK1 and NF-κB signaling axis.


Assuntos
Ginsenosídeos/farmacologia , Proteínas Imediatamente Precoces/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Serina-Treonina Quinases/metabolismo , Células HeLa , Humanos , Quinase I-kappa B/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Quinases , Transdução de Sinais
20.
Hum Reprod ; 36(9): 2452-2462, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34179971

RESUMO

STUDY QUESTION: Is ovarian stimulation with follitropin delta in its individualised fixed-dose regimen at least as efficacious as follitropin alfa in a conventional dosing regimen in Asian population? SUMMARY ANSWER: Ovarian stimulation with individualised follitropin delta dosing resulted in a non-inferior ongoing pregnancy rate, a significantly higher live birth rate and a significantly lower incidence of early ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions compared to conventional follitropin alfa dosing. WHAT IS KNOWN ALREADY: Previous randomised controlled trials conducted in Japan as well as in Europe, North- and South America have demonstrated that ovarian stimulation with the individualised follitropin delta dosing regimen based on serum anti-Müllerian hormone (AMH) level and body weight modulated the ovarian response and reduced the risk of OHSS without compromising pregnancy and live birth rates. STUDY DESIGN, SIZE, DURATION: Randomised, controlled, multi-centre, assessor-blind trial conducted in 1009 Asian patients from mainland China, South Korea, Vietnam and Taiwan, undergoing their first IVF/ICSI cycle. Randomisation was stratified by age (<35, 35-37, 38-40 years). The primary endpoint was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority limit -10.0%; analysis adjusted for age stratum). PARTICIPANTS/MATERIALS, SETTING, METHODS: The follitropin delta treatment consisted of a fixed daily dose individualised according to each patient's initial AMH level and body weight (AMH <15 pmol/l: 12 µg; AMH ≥15 pmol/l: 0.19 to 0.10 µg/kg; min-max 6-12 µg). The follitropin alfa dose was 150 IU/day for the first 5 days with subsequent potential dose adjustments according to individual response. A GnRH antagonist protocol was applied. OHSS was classified based on Golan's system. Women with an ongoing pregnancy were followed until live birth and 4 weeks after. MAIN RESULTS AND THE ROLE OF CHANCE: The number of oocytes retrieved was significantly (P < 0.001) lower with individualised follitropin delta versus conventional follitropin alfa (10.0 ± 6.1 versus 12.4 ± 7.3). Nevertheless, compared to the conventional dosing approach, the individualised follitropin delta dosing regimen resulted in on average 2 more oocytes (9.6 ± 5.3 versus 7.6 ± 3.5) in potential low responders as indicated by AMH <15 pmol/l, and on average 3 fewer oocytes (10.1 ± 6.3 versus 13.8 ± 7.5) in potential high responders as indicated by AMH ≥15 pmol/l. Among women with AMH ≥15 pmol/l, excessive response occurred less frequently with individualised follitropin delta than with follitropin alfa (≥15 oocytes: 20.2% versus 39.1%; ≥20 oocytes: 6.7% versus 18.5%; both P < 0.001). The incidence of early OHSS and/or preventive interventions for early OHSS was significantly (P = 0.004) reduced from 9.6% with follitropin alfa to 5.0% with individualised follitropin delta. The total gonadotropin use was significantly (P < 0.001) reduced from an average of 109.9 ± 32.9 µg (1498 ± 448 IU) follitropin alfa to 77.5 ± 24.4 µg follitropin delta. Non-inferiority of follitropin delta in its individualised dosing regimen to conventional follitropin alfa was established with respect to the primary endpoint of ongoing pregnancy rate which was 31.3% with follitropin delta compared to 25.7% with follitropin alfa (estimated mean difference 5.4% [95% CI: -0.2%; 11.0%]). The live birth rate was significantly higher at 31.3% with individualised follitropin delta compared to 24.7% with follitropin alfa (estimated mean difference 6.4% [95% CI: 0.9%; 11.9%]; P = 0.023). The live birth rate for each stratum were as follows for follitropin delta and follitropin alfa, respectively; <35 years: 31.0% versus 25.0%, 35-37 years: 35.3% versus 26.7%, 38-40 years: 20.0% versus 14.3%. LIMITATIONS, REASONS FOR CAUTION: The trial only covered the clinical outcome of one treatment cycle with fresh cleavage-stage embryo transfers. WIDER IMPLICATIONS OF THE FINDINGS: The present trial shows that in addition to reducing the early OHSS risk, follitropin delta in its individualised fixed-dose regimen has the potential to improve the success rate in fresh cycles across all ages and with a lower gonadotropin consumption compared to conventional follitropin alfa dosing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Ferring Pharmaceuticals. J.Q., Y.Z., X.L., T.H., H.-Y.H. and S.-H.K. have received institutional (not personal) clinical trial fees from Ferring Pharmaceuticals. M.G., B.M. and J.-C.A. are employees of Ferring Pharmaceuticals. J.-C.A. has pending and issued patent applications in the WO 2013/020996 and WO 2019/043143 patent families that comprise allowed and granted patent rights related to follitropin delta. TRIAL REGISTRATION NUMBER: NCT03296527 (clinicaltrials.gov). TRIAL REGISTRATION DATE: 28 September 2017. DATE OF FIRST PATIENT'S ENROLMENT: 1 December 2017.


Assuntos
Fertilização In Vitro , Injeções de Esperma Intracitoplásmicas , Adulto , Feminino , Hormônio Foliculoestimulante Humano , Humanos , Indução da Ovulação , Gravidez , Taxa de Gravidez , Proteínas Recombinantes
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