Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia.

BACKGROUND: Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death. METHODS: We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm(-/-)). RESULTS: ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm(-/-) mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed. CONCLUSIONS: Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.

Development and Validation of Deep Learning-Based Automated Detection of Cervical Lymphadenopathy in Patients with Lymphoma for Treatment Response Assessment: A Bi-institutional Feasibility Study.

The purpose is to train and evaluate a deep learning (DL) model for the accurate detection and segmentation of abnormal cervical lymph nodes (LN) on head and neck contrast-enhanced CT scans in patients diagnosed with lymphoma and evaluate the clinical utility of the DL model in response assessment. This retrospective study included patients who underwent CT for abnormal cervical LN and lymphoma assessment between January 2021 and July 2022. Patients were grouped into the development (n = 76), internal test 1 (n = 27), internal test 2 (n = 87), and external test (n = 26) cohorts. A 3D SegResNet model was used to train the CT images. The volume change rates of cervical LN across longitudinal CT scans were compared among patients with different treatment outcomes (stable, response, and progression). Dice similarity coefficient (DSC) and the Bland-Altman plot were used to assess the model's segmentation performance and reliability, respectively. No significant differences in baseline clinical characteristics were found across cohorts (age, P = 0.55; sex, P = 0.13; diagnoses, P = 0.06). The mean DSC was 0.39 ± 0.2 with a precision and recall of 60.9% and 57.0%, respectively. Most LN volumes were within the limits of agreement on the Bland-Altman plot. The volume change rates among the three groups differed significantly (progression (n = 74), 342.2%; response (n = 8), - 79.2%; stable (n = 5), - 8.1%; all P < 0.01). Our proposed DL segmentation model showed modest performance in quantifying the cervical LN burden on CT in patients with lymphoma. Longitudinal changes in cervical LN volume, as predicted by the DL model, were useful for treatment response assessment.

Constraints on carbon monoxide emissions based on tall tower measurements in the US Upper Midwest.

We interpret a full year of high-frequency CO measurements from a tall tower in the U.S. Upper Midwest with a time-reversed Lagrangian Particle Dispersion Model (STILT LPDM) and an Eulerian chemical transport model (GEOS-Chem CTM) to develop top-down constraints on U.S. CO sources in 2009. Our best estimate is that anthropogenic CO emissions in the U.S. Upper Midwest in 2009 were 2.9 Tg, 61% lower (a posteriori scale factor of 0.39) than our a priori prediction based on the U.S. EPA's National Emission Inventory for 2005 (NEI 2005). If the same bias applies across the contiguous U.S., the inferred CO emissions are 26 Tg/y, compared to the a priori estimate of 66 Tg/y. This discrepancy is significantly greater than would be expected based solely on emission decreases between 2005 and 2009 (EPA estimate: 23% decrease). Model transport error is an important source of uncertainty in the analysis, and we employ an ensemble of sensitivity runs using multiple meteorological data sets and model configurations to assess its impact on our results. A posteriori scale factors for the U.S. anthropogenic CO source from these sensitivity runs range from 0.22 to 0.64, corresponding to emissions of 1.6-4.8 Tg/y for the U.S. Upper Midwest and 15-42 Tg/y for the contiguous U.S. The data have limited sensitivity for constraining biomass + biofuel burning emissions and photochemical CO production from precursor organic compounds. Our finding of a NEI 2005 overestimate of CO emissions is consistent with recent assessments for individual cities and with earlier analyses based on the NEI 1999, implying the need for a better mechanism for refining such bottom-up emission estimates in response to top-down constraints.

Coordination-driven robust antibacterial coatings using catechol-conjugated carboxymethyl chitosan.

To prevent bacterial contamination on solid surfaces, a simple yet efficient antibacterial coating was developed in a substrate-independent manner by using the catechol-conjugated carboxymethyl chitosan (CMC-DOPA). The CMC-DOPA was firstly synthesized via an aza-Michael reaction with methyl acrylate and the subsequent acyl substitution with dopamine. The coating strategy consists of spin-coating-assisted deposition of CMC-DOPA on polydopamine-coated substrates and coordination-driven crosslinks between catechol groups and Fe3+ ions in sequence, producing the multilayered CMC-DOPA films. The film thickness was controllable depending on the concentration of CMC-DOPA. Compared to bare controls, the CMC-DOPA-coated substrates reduced the bacterial adhesion by up to 99.8 % and 96.2 % for E. coli and S. aureus, respectively. It is demonstrated that the CMC-DOPA coating can be a robust antibacterial coating across various pH environments, inhibiting bacterial adhesion by 78.7 %, 95.1 %, and 93.2 %, respectively, compared to the control, even after 7 days of acidic, physiological, and alkaline pH treatment. The current coating approach could be applied to various substrates including silicon dioxide, titanium dioxide, and polyurethane. Given its simple and versatile coating capability, we think that the coordination-driven CMC-DOPA coating could be useful for various medical devices and implants.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

Safety/Efficacy of Prucalopride in Korean Patients with Chronic Constipation: Post-marketing Surveillance.

Background/Aims: Constipation is a common gastrointestinal disorder. Prucalopride is a dihydrobenzofurancarboxamide derivative with gastrointestinal prokinetic activities and is recommended as an appropriate choice in patients unresponsive to laxatives. This study assessed the safety and efficacy of prucalopride in Korean patients with chronic constipation, in whom laxatives were ineffective. Methods: This prospective, non-interventional post-marketing surveillance of prucalopride was conducted from 2012 to 2018 at 28 hospitals in Korea. Adults who received prucalopride for the symptomatic treatment of chronic constipation were included. The patients received 2 mg of prucalopride once daily or 1 mg once daily in patients older than 65 years. The baseline characteristics, adverse events (AEs), and seven-point scale of Clinical Global Impression-Improvement were collected. Results: Of 601 patients, 67.7% were female, and the mean age was 62.3 years. Three hundred patients (49.9%) were older than 65 years. At the baseline, 70.0% of patients reported less than two instances of spontaneous complete bowel movements per week. AEs were reported in 107 patients (17.7%), including headache (3.2%) and diarrhea (2.8%). Seven serious AEs (SAEs) were reported in five patients (0.8%). The SAEs were resolved without complications; there were no cases of death. All SAEs were assessed as 'unlikely' causality with prucalopride. In 72.7% of patients, chronic constipation was improved by the prucalopride treatment during the study period. Conclusions: This study demonstrated the promising safety and efficacy profile of prucalopride in clinical practice. Thus, prucalopride should be considered in patients with chronic constipation when bowel symptoms are refractory to simple laxatives.

Genome wide expression analysis of the effect of Pinelliae Rhizoma extract on psychological stress.

Pinelliae Rhizoma has been used traditionally as an antidepressant in Oriental medicine. In this study, the effect of Pinelliae Rhizoma extract (PRe) on psychological stress was investigated in mice. The results of an elevated plus-maze experiment revealed that application of psychological stress to mice led to the development of an abnormal behavioral pattern. However, oral administration of PRe significantly reduced the abnormal behavior of mice with a recovery rate of 75.5%. To elucidate the molecular mechanism by PRe, a microarray analysis of the brains of mice was conducted. The results of this analysis revealed that 456 genes were up-regulated and 392 genes were down-regulated in response to psychological stress. The expression of most of the genes that were altered in response to psychological stress was restored to normal levels in PRe treated mice, with a recovery rate of 81.5% and 85.2% being observed for up- and down-regulated genes, respectively. Finally, when the interaction network information was analysed, the recovery rate of the core node genes (46 up- and 29 down-regulated genes) in PRe treated mice was found to be over 95%, which indicates that this final set of genes may be the effective target of PRe.

Clinical Outcomes of Decitabine Treatment for Patients With Lower-Risk Myelodysplastic Syndrome on the Basis of the International Prognostic Scoring System.

INTRODUCTION: Decitabine has shown clinical benefits in patients with intermediate (INT)-2 or high-risk myelodysplastic syndrome (MDS), determined according to the International Prognostic Scoring System (IPSS), but the benefits have not been well demonstrated in patients with lower-risk (IPSS low or INT-1) disease. Recently, it was proposed that the prognosis for patients with IPSS lower-risk disease is heterogeneous, with a substantial proportion of these patients having poor survival. PATIENTS AND METHODS: This study included patients with IPSS lower-risk MDS from the DRAMA (An Observational Study for Dacogen Long-Term Treatment in Patients With Myelodysplastic Syndrome; NCT01400633) and DIVA (A Study for Dacogen Treatment in Patients With Myelodysplastic Syndrome; NCT01041846) studies, which were prospective observational studies on the efficacy and safety of decitabine treatment in patients with MDS. Using the Lower-Risk Prognostic Scoring System [LR-PSS], we classified IPSS lower-risk MDS. Patients in each LR-PSS category were divided according to overall response (OR) to decitabine treatment, and survival outcomes were compared. RESULTS: One hundred sixteen patients were enrolled: LR-PSS category 1 (n = 12; 10.3%), category 2 (n = 56; 48.3%), and category 3 (n = 48; 41.4%). Survival outcomes differed among the 3 categories (P = .046). The overall survival according to OR showed a significant difference in total patients (P = .008) and category 3 patients (P = .003). We analyzed predictive factors for OR, but no variable was found to significantly affect OR. CONCLUSION: Decitabine treatment showed a survival benefit in the higher-risk group of IPSS lower-risk MDS patients who responded to treatment, and classification using the LR-PSS category was helpful for this subgroup, indicating that decitabine treatment might alter the natural course of disease in these patients.

Occult hepatitis B virus infection in pregnant woman and its clinical implication.

BACKGROUND/AIMS: The objective of this study was to document the prevalence rate of occult hepatitis B virus (HBV) in healthy pregnant woman and the possibility of transmission to the foetus. METHODS: This study was performed prospectively with 202 healthy pregnant women. HBV-DNA testing was performed using two specific quantitative tests with two independent sets of sera and cord blood. DNA sequencing analysis was carried out to confirm the specificity of polymerase chain reaction (PCR) product of HBV-DNA testing. RESULTS: Eight of 202 (4%) individuals with the TaqMan PCR assay and 23 of 202 (11.4%) with the COBAS Amplicor HBV Monitor test were HBV-DNA positive. Six (3%) individuals were positive with both methods. Sequencing and genotyping analysis of HBV polymerase gene with sera of the 75th subject resulted in genotype C. HBV-DNA testing with four cord blood samples showed that all were HBV-DNA negative. CONCLUSION: Occult HBV infection shows a difference in prevalence rate depending on the test method but the existence has been confirmed by sequencing analysis. Our results also suggest that vertical transmission through the cord blood is not so high as to be clinical problems and warrants further investigation.

Structural and electronic properties of ZnO nanoparticles grown on p-Si and Al2O3 substrates by using spin coating and thermal treatment.

ZnO nanoparticles were formed on p-Si and Al2O3 substrates by using spin coating and thermal treatment method. Scanning electron microscopy images and X-ray energy dispersive spectrometry profiles showed that ZnO nanoparticles were formed on p-Si and Al2O3 substrates. X-ray diffraction patterns showed that ZnO nanoparticles formed on the p-Si substrates had polycrystalline hexagonal wurtzite structures and that those formed on the Al2O3 substrates had a c-axis preferential orientation. X-ray photoelectron spectroscopy profiles showed that the O 1s and the Zn 2p peaks corresponding to the ZnO nanoparticles were observed.

A prospective, open-label, multicenter, observational study to evaluate the efficacy and safety of bortezomib-melphalan-prednisone as initial treatment for autologous stem cell transplantation-ineligible patients with multiple myeloma.

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), ß2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP.In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

New developments in acne treatment: role of combination adapalene-benzoylperoxide.

The fixed-dose combination adapalene 0.1%/benzoylperoxide 2.5% (A/BPO) was introduced as an acne vulgaris therapeutic in 2007. It combines anti-inflammatory, keratolytic, comedolytic, and antibacterial properties. Thus, it addresses several pathophysiological factors involved in the pathophysiology of acne. This review highlights the rationale for the use of this fixed-dose combination product, its therapeutic efficacy including effects on adherence and quality of life, its use for different forms of acne, and the side-effect profile. In summary, the fixed-dose combination of A/BPO gel can be regarded as a highly effective and safe formulation. It is not associated with antibiotic resistance. It reduces factors that cause nonadherence and has positive effects on the quality of life of affected patients. The tolerance is good. The initial mild irritation potential can be addressed by adequate counseling. A/BPO can be used for all forms of inflammatory acne, including severe forms, as part of a combination with systemic antibiotics. Finally, it can also be used for the long-term treatment of chronic acne. Thus, it is a very valuable therapeutic option in daily practice, which is reflected by its strong recommendation in the "European S3-guidelines".

Hair mercury level in smokers and its influence on blood pressure and lipid metabolism.

OBJECT: Smoking is a major risk factor for the development and progression of cardiovascular disease and cigarettes contain a slight amount of mercury. Mercury has been causally linked to cardiovascular diseases. This study evaluated the mercury content in hair according to smoking exposure status and the influence of the mercury level on blood pressure and lipid metabolism. METHODS: We examined mercury concentration in the hair samples from 236 healthy people 16-75-years-of-age who had visited the health promotion center of a university hospital from January 2004 to January 2007. Self-reported cigarette smoking status and baseline health information were obtained using a questionnaire. Blood pressure and serum lipid level according to the mercury concentration were assessed. RESULTS: The mean systolic blood pressure in the smoking exposure group and non-exposure group were 123.2±15.4mmHg and 117.2±15.9mmHg, respectively (p=0.005). The mean diastolic pressure in the smoking exposure group and non-exposed group were 80.2±10.9mmHg and 75.1±11.3mmHg, respectively (p<0.001). Mercury concentration had a positive relationship with systolic and diastolic blood pressure. Compared with the normal and high mercury groups, the normal mercury group demonstrated lower blood pressure, lower triglyceride, and lower smoking amount, but higher high density lipoprotein cholesterol than the high mercury group. There was an increase of mercury concentration in the smoking exposure group. The 20-29 packyear group showed significantly increased odds ratio of mercury content, compared with the non-exposure group (14.00, 95% confidence interval, 5.03-38.96). CONCLUSIONS: Smoking is positively associated with mercury accumulation, and high mercury concentration is associated with increased blood pressure and abnormal lipid metabolism.

An event-specific DNA microarray to identify genetically modified organisms in processed foods.

We developed an event-specific DNA microarray system to identify 19 genetically modified organisms (GMOs), including two GM soybeans (GTS-40-3-2 and A2704-12), thirteen GM maizes (Bt176, Bt11, MON810, MON863, NK603, GA21, T25, TC1507, Bt10, DAS59122-7, TC6275, MIR604, and LY038), three GM canolas (GT73, MS8xRF3, and T45), and one GM cotton (LLcotton25). The microarray included 27 oligonucleotide probes optimized to identify endogenous reference targets, event-specific targets, screening targets (35S promoter and nos terminator), and an internal target (18S rRNA gene). Thirty-seven maize-containing food products purchased from South Korean and US markets were tested for the presence of GM maize using this microarray system. Thirteen GM maize events were simultaneously detected using multiplex PCR coupled with microarray on a single chip, at a limit of detection of approximately 0.5%. Using the system described here, we detected GM maize in 11 of the 37 food samples tested. These results suggest that an event-specific DNA microarray system can reliably detect GMOs in processed foods.