Aims Patient education is a very important part of diabetes care. However, until now, little data has been presented about the long‐term effectiveness of structured intensive diabetes education ...programmes (SIDEP) for people with Type 2 diabetes mellitus.
Methods People with Type 2 diabetes (n = 547) hospitalized from December 1999 to December 2000 were randomly assigned to two groups. Two hundred and nineteen patients undertook an inpatient SIDEP and the remaining patients received conventional glycaemic control without intensive education. After discharge, all patients were monitored regularly. Laboratory data were obtained, and adherence to self‐care behaviour was determined on a five‐point scale by questionnaires completed annually.
Results Of the patients who completed the SIDEP, 160 (73.1%) were followed up for more than 4 years. The mean HbA1c (7.9 ± 1.2 vs. 8.7 ± 1.6%; P < 0.05) and the frequency of hospitalization related to diabetes per patient per year (0.3 ± 0.6 vs. 0.8 ± 0.9; P < 0.05) was significantly lower in the SIDEP group than in the control group. The SIDEP group adhered more closely to self‐care behaviour than the control group over 4 years (P < 0.05). People with Type 2 diabetes mellitus of longer duration and those treated with insulin had poorer HbA1c at follow‐up.
Conclusions A well‐designed, intensive patient education programme is necessary for people with diabetes. However, regular and sustained reinforcement with encouragement is also required to maintain optimal glycaemic control, especially in insulin‐treated patients.
Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding ...brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers.
Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, ...and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009–2013). One hundred and twenty‐six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA/l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.
Recent advances in atopic dermatitis Ahn, Kangmo; Kim, Byung Eui; Kim, Jihyun ...
Current opinion in immunology,
10/2020, Letnik:
66
Journal Article
Recenzirano
Odprti dostop
The prevalence and disease burden of atopic dermatitis (AD) is substantial. AD causes significant impairment in quality of life. It is also associated with mental disorders as well as cardiovascular ...diseases. Many factors including race, environment, skin barrier dysfunction, immune regulatory abnormalities, and microbiome have been reported to affect the pathophysiology of AD. A variety of cell types including Th2, Th17, Th22, and type 2 innate lymphoid cells contribute to AD. Cytokines from these immune cells cause abnormal epidermal differentiation and skin barrier dysfunction. Moreover, microbial dysbiosis and deficiency of antimicrobial peptides result in Staphylococcus aureus infection. Recently, new drugs have been successfully launched to target polarized immune pathways that lead to moderate-to-severe AD.
Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor ...inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin β3 is another potential target for combination treatment with SAIT301. Suppression of integrin β3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin β3 are resistant to crizotinib treatment, suggesting that FGFR and integrin β3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.
Mass spectrometry was carried out as previously described.E1 Samples were run in triplicate on an Agilent 1200 series HPLC (Agilent Technologies, Santa Clara, Calif) and Agilent ETD ion trap (model ...6340) mass spectrometer with an HPLC chip to evaluate the expression of filaggrin, alpha enolase, corneodesmosin, fatty acid-binding protein, serpin B3, transglutaminase 3, and TSLP. In a univariable analysis, candidate variables for adjustment included epidermal protein levels, sex, parental history of allergic diseases, delivery mode, maternal education levels, move to a new house during pregnancy, mold exposure during pregnancy, exclusive breast-feeding during the first 4 months of life, and TEWL at age 2 months.
Reactor experiment for neutrino oscillation (RENO) began data-taking from August 2011. It successfully observed reactor antineutrino disappearance in April 2012 to measure the smallest mixing angle ...of θ13. Two identical detectors, one at near location and the other at far location, are constructed at the Yonggwang nuclear power plant in South Korea, to compare the observed reactor neutrino fluxes. Each RENO detector is filled with 16 mass tons of Gadolinium loaded liquid scintillator (GdLS) in the neutrino target region, and with 28 mass tons of unloaded liquid scintillator (LS) in the γ-catcher region surrounding the target. LS was developed to satisfy chemical, physical, optical properties, and safety requirements. Linear alkyl benzene (LAB) was chosen as a solvent because of its high flash-point, sufficient light yield, and being environmentally friendly. GdLS is carefully developed to keep a long attenuation length and high light yield for a long time period. In this paper, we report the characteristics and mass production of the RENO LS and GdLS.
To determine the prognostic significance of CT‐determined cachexia scores (CSs) in 127 consecutive male small cell lung cancer (SCLC) patients, cross‐sectional areas of muscle and fat tissues at the ...third lumbar vertebra (L3) were retrospectively measured on baseline CT images. CSs were determined based on the presence of sarcopenia and/or adipopenia. According to the presence of sarcopenia (L3 muscle index <55 cm2/m2, 86.8%) and adipopenia (L3 fat index <22 cm2/m2, 11.8%), CSs were defined as follows: CS2 (sarcopenia and adipopenia, 11.8%), CS1 (sarcopenia only, 74.8%) and CS0 (13.4%). CS2 was significantly related to lower body mass index (p < .001) and poor performance status (p = .002), and patients with CS2 had shorter OS than patients with CS1 or CS0 (median OS, 5.0 months vs. 8.9 months vs. 18.3 months; p = .007). Multivariable analysis revealed that CS was an independent prognostic factor of poor survival (HR, 1.99 for CS1 and 2.59 for CS2, p = .036 and .023, CS0 as a reference), along with extensive stage (p < .001), supportive care only (p < .001) and an elevated lactate dehydrogenase (p = .005). CT‐determined CSs, based on the presence of sarcopenia and/or adipopenia, could be used to predict prognosis in male SCLC.
Aims
We investigated the association between lipoprotein(a) Lp(a) level and new‐onset chronic kidney disease (CKD) in patients with Type 2 diabetes.
Methods
We conducted a prospective cohort study ...from March 2003 to December 2004 with a median follow‐up time of 10.1 years. Patients aged 25–75 years with Type 2 diabetes and without CKD estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2) were consecutively enrolled. The eGFR was measured at least twice every year , and new‐onset CKD was defined as a decreased eGFR status of < 60 ml/min/1.73 m2 using a Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation.
Results
Of the 862 patients who were enrolled, 560 (65.0%) completed the follow‐up and 125 (22.3%) progressed to CKD. The mean age and duration of diabetes were 53.3 ± 9.6 and 7.5 ± 6.0 years, respectively. The baseline eGFR was 101.8 ± 11.3 ml/min/1.73 m2. After adjusting for multiple confounding factors, a Cox hazard regression analysis revealed that the third tertile of Lp(a) was significantly associated with the development of CKD during the observation period when compared with the first tertile hazard ratio 2.12 (95% confidence interval 1.33–3.36); P = 0.001).
Conclusions
In this prospective, longitudinal, observational cohort study, we demonstrated that the Lp(a) level was an independent prognostic factor for the future development of CKD in patients with Type 2 diabetes.
What's new?
Our study confirms that an elevated lipoprotein(a) level is an independent predictable risk factor for the future development of new‐onset chronic kidney disease in Type 2 diabetes.
The median calculated estimated glomerular filtration rate reduction showed an increasing trend as the lipoprotein(a) level increased.
We suggest that cardiovascular risk factors in patients with diabetes who have high lipoprotein(a) should be treated more aggressively to prevent the future development of chronic kidney disease.
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