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1.
Proc Natl Acad Sci U S A ; 119(38): e2205682119, 2022 09 20.
Article in English | MEDLINE | ID: mdl-36095211

ABSTRACT

Understanding and predicting the relationship between leaf temperature (Tleaf) and air temperature (Tair) is essential for projecting responses to a warming climate, as studies suggest that many forests are near thermal thresholds for carbon uptake. Based on leaf measurements, the limited leaf homeothermy hypothesis argues that daytime Tleaf is maintained near photosynthetic temperature optima and below damaging temperature thresholds. Specifically, leaves should cool below Tair at higher temperatures (i.e., > ∼25-30°C) leading to slopes <1 in Tleaf/Tair relationships and substantial carbon uptake when leaves are cooler than air. This hypothesis implies that climate warming will be mitigated by a compensatory leaf cooling response. A key uncertainty is understanding whether such thermoregulatory behavior occurs in natural forest canopies. We present an unprecedented set of growing season canopy-level leaf temperature (Tcan) data measured with thermal imaging at multiple well-instrumented forest sites in North and Central America. Our data do not support the limited homeothermy hypothesis: canopy leaves are warmer than air during most of the day and only cool below air in mid to late afternoon, leading to Tcan/Tair slopes >1 and hysteretic behavior. We find that the majority of ecosystem photosynthesis occurs when canopy leaves are warmer than air. Using energy balance and physiological modeling, we show that key leaf traits influence leaf-air coupling and ultimately the Tcan/Tair relationship. Canopy structure also plays an important role in Tcan dynamics. Future climate warming is likely to lead to even greater Tcan, with attendant impacts on forest carbon cycling and mortality risk.


Subject(s)
Carbon Cycle , Carbon , Forests , Plant Leaves , Carbon/metabolism , Plant Leaves/anatomy & histology , Plant Leaves/metabolism , Temperature
2.
Article in English | MEDLINE | ID: mdl-38184097

ABSTRACT

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for superficial gastrointestinal (GI) cancers.1,2 ESD practice is expanding significantly in the United States and Western countries. This is attributed to a shorter hospital stay, better quality of life, and fewer adverse events compared with surgery. In the United States, ESD usually is performed and managed in an outpatient setting (ambulatory ESD) or with an overnight hospital stay. This practice is in contrast to Eastern Asian countries, where 3 to 5 days of hospital stay is a routine process for observation after ESD. A Swedish study showed that patients with well-selected colorectal neoplasms (median tumor size, 37 mm) could be managed safely in an outpatient setting after ESD.3 A North American multicenter ESD study also reported that ambulatory ESD was safe and feasible in selected cases (noninvasive cancers, no adverse events, high-volume endoscopists with short procedure time).4 However, procedural and technical aspects that enable safe outpatient management of patients after ESD need to be investigated.

3.
Strahlenther Onkol ; 200(5): 418-424, 2024 May.
Article in English | MEDLINE | ID: mdl-38488899

ABSTRACT

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.


Subject(s)
Cone-Beam Computed Tomography , Glottis , Laryngeal Neoplasms , Magnetic Resonance Imaging, Cine , Humans , Cone-Beam Computed Tomography/methods , Magnetic Resonance Imaging, Cine/methods , Glottis/diagnostic imaging , Male , Laryngeal Neoplasms/diagnostic imaging , Laryngeal Neoplasms/radiotherapy , Middle Aged , Female , Adult , Aged , Organ Motion , Computer Systems , Radiotherapy Planning, Computer-Assisted/methods , Reproducibility of Results , Sensitivity and Specificity
4.
Respir Res ; 25(1): 81, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38326848

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF. In this study, 70 patients with IPF underwent assessment of body composition, lung function, 6-min walk distance (6MWD) testing, hand grip strength, quality of life (QoL) assessment by St. George's Respiratory questionnaire (SGRQ) and frailty assessment using the SHARE-FI tool. FFMI was calculated using pectoralis muscle cross-sectional area (PM-CSA) on CT chest images and the lowest quartile defined reduced muscle mass. Sarcopenia was defined as low FFMI and handgrip strength. Regression analyses were conducted to determine predictive value of frailty, low FFMI and sarcopenia on clinical outcomes. The Cox proportional hazards model was used to analyze the impact of FFMI and frailty score on survival. The mean age was 70 years with moderate impairment in lung function (mean ppFVC 68.5%, ppDLCO 45.6%). Baseline forced vital capacity (p < 0.001), diffusion capacity of lung for carbon monoxide (p = < 0.01), 6WMD (p < 0.05) were significantly lower in frail patients compared to non-frail patients. BMI was found to closely correlate with FFMI (r = 0.79, p < 0.001), but not with frailty score (r = - 0.2, p = 0.07). Frailty was a significant predictor of FVC, DLCO, 6MWD, SGRQ scores when adjusted for age and gender. Muscle mass and sarcopenia were significant predictors of FVC, DLCO, but not 6MWD or QoL scores. Multivariate cox-proportional hazards ratio model adjusting for age and gender showed that frailty was significantly associated with increased mortality (HR = 2.6, 95% CI 1.1-6.1). Low FFMI (HR = 1.3, 95% CI 0.6-2.8), and sarcopenia (HR = 2.1, 95% CI 0.8-5.3), though associated with a trend to increased mortality, were not statistically significant. Frailty is associated with lower lung function and higher mortality in patients with IPF. Longitudinal evaluations are necessary to further determine the associations between low FFMI, sarcopenia and frailty with outcomes in IPF.


Subject(s)
Frailty , Idiopathic Pulmonary Fibrosis , Sarcopenia , Humans , Aged , Quality of Life , Hand Strength , Sarcopenia/diagnosis , Lung
5.
Genes Dev ; 30(9): 1047-57, 2016 05 01.
Article in English | MEDLINE | ID: mdl-27125673

ABSTRACT

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Food , Forkhead Transcription Factors/genetics , Gene Expression Regulation , Insulin/genetics , Longevity/genetics , Peptide Hormones/genetics , Caenorhabditis elegans Proteins/metabolism , Cues , Environment , Forkhead Transcription Factors/metabolism , Insulin/metabolism , Optogenetics , Peptide Hormones/metabolism , Sensory Receptor Cells/physiology , Signal Transduction
6.
Am J Respir Cell Mol Biol ; 68(5): 485-497, 2023 05.
Article in English | MEDLINE | ID: mdl-36780670

ABSTRACT

Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as acute respiratory distress syndrome. In survivors, long-term effects such as the development of respiratory ailments are reported for the organoarsenical sulfur mustard; however, no long-term pulmonary effects are documented for lewisite and DPCA. No animal models exist to explore the relationship between skin exposure to vesicants and constrictive bronchiolitis. We developed and characterized a mouse model to study the long-term effects of cutaneous exposure on the lungs after exposure to a sublethal dose of organoarsenicals. We exposed mice to lewisite, DPCA, or a less toxic surrogate organoarsenic chemical, phenyl arsine oxide, on the skin. The surviving mice were followed for 20 weeks after skin exposure to arsenicals. Lung microcomputed tomography, lung function, and histology demonstrated increased airway resistance, increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and peribronchial lymphocyte infiltration in mice exposed to arsenical on skin.


Subject(s)
Arsenicals , Bronchiolitis Obliterans , Chemical Warfare Agents , Mustard Gas , Humans , Animals , Mice , X-Ray Microtomography , Skin , Chemical Warfare Agents/toxicity , Mustard Gas/toxicity
7.
N Engl J Med ; 382(5): 427-436, 2020 01 30.
Article in English | MEDLINE | ID: mdl-31995688

ABSTRACT

BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).


Subject(s)
Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori , Proton Pump Inhibitors/therapeutic use , Stomach Neoplasms/prevention & control , Adenoma/epidemiology , Adenoma/etiology , Adenoma/prevention & control , Adult , Aged , Amoxicillin/therapeutic use , Clarithromycin/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Helicobacter Infections/complications , Humans , Incidence , Kaplan-Meier Estimate , Lansoprazole/therapeutic use , Male , Middle Aged , Republic of Korea , Stomach Neoplasms/epidemiology , Stomach Neoplasms/etiology , Stomach Neoplasms/genetics
8.
J Virol ; 96(6): e0187321, 2022 03 23.
Article in English | MEDLINE | ID: mdl-35107382

ABSTRACT

Given the current coronavirus disease 2019 (COVID-19) pandemic, coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) is a major concern for public health. However, the immunopathogenic events occurring with coinfections of SARS-CoV-2 and IAV remain unclear. Here, we report the pathogenic and immunological consequences of SARS-CoV-2 and IAV H1N1 coinfection in the K18-hACE2 transgenic mouse model. Compared with a single infection with SARS-CoV-2 or IAV, coinfections not only prolonged the primary virus infection period but also increased immune cell infiltration and inflammatory cytokine levels in bronchoalveolar lavage fluid leading to severe pneumonia and lung damage. Moreover, coinfections caused severe lymphopenia in peripheral blood, resulting in reduced total IgG, neutralizing antibody titers, and CD4+ T cell responses against each virus. This study sheds light on the immunopathogenesis of SARS-CoV-2 and IAV coinfection, which may guide the development of effective therapeutic strategies for the treatment of patients coinfected with these viruses. IMPORTANCE The cocirculation of influenza virus merging with the COVID-19 pandemic raises a potentially severe threat to public health. Recently, increasing numbers of SARS-CoV-2 and influenza virus coinfection have been reported from many countries. It is a worrisome issue that SARS-CoV-2 coinfection with other pathogens may worsen the clinical outcome and severity of COVID-19 and increase fatality. Here, we evaluated SARS-CoV-2 and IAV coinfection using the K18-hACE2 mouse model. Coinfected mice exhibited increased mortality with prolonged IAV shedding. Furthermore, coinfected mice showed a higher level of cytokines and chemokines than a single infection condition. Interestingly, our data show that coinfected mice showed significantly fewer virus-specific and neutralizing antibodies than the mice with a single infection. Overall, this study suggests that coinfection aggravates viral pathology by impaired neutralizing antibody response.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype , Orthomyxoviridae Infections , SARS-CoV-2 , Animals , Antibodies, Neutralizing , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Coinfection/immunology , Disease Models, Animal , Humans , Influenza A Virus, H1N1 Subtype/immunology , Mice , Orthomyxoviridae Infections/immunology , SARS-CoV-2/immunology , Severity of Illness Index
9.
Gastrointest Endosc ; 98(3): 381-391, 2023 09.
Article in English | MEDLINE | ID: mdl-37061137

ABSTRACT

BACKGROUND AND AIMS: Endoscopic suturing enables full closure of large defects after endoscopic submucosal dissection (ESD). However, its use is limited by the need for a double-channel endoscope. A novel closure system, the OverStitch Sx (Apollo Endosurgery, Austin, Tex, USA), compatible with any single-channel endoscope, was introduced to address these shortcomings. The aim of this study was to assess the safety and feasibility of OverStitch Sx for the closure of large defects after ESD. METHODS: This is a prospective single-center feasibility study of patients who underwent closure of large defects after ESD using the OverStitch Sx system. Main outcomes of the study are technical and clinical success, same-day discharge rate, and adverse event rate. RESULTS: Thirty-three patients were enrolled. The mean diameter of included lesions was 5.38 ± 2.52 cm. The defect occupied ≥50% of the lumen circumference in 70% of the cases. En-bloc resection, R0 resection, and curative resection were achieved in 97%, 87.5%, and 78.8% of patients, respectively. Technical success and clinical success were seen in 93.9% and 90.9% of the cases, respectively. Same-day hospital discharge was achieved in 77.4% of patients. Total adverse event rate was 35.7%, including delayed bleeding in 1 patient after rectal ESD that was managed conservatively, self-resolving rectal pain in 7 patients, rectal stricture requiring dilation in 1 patient, and temporary dysphagia in 1 patient. No immediate or delayed perforation was reported. CONCLUSIONS: OverStitch Sx enabled safe and effective closure of large defects after ESD. Future trials are needed to determine its superiority over OverStitch for the closure of defects in challenging locations. (Clinical trial registration number: NCT04361227.).


Subject(s)
Endoscopic Mucosal Resection , Humans , Endoscopic Mucosal Resection/adverse effects , Prospective Studies , Rectum , Treatment Outcome , Retrospective Studies
10.
Cancer Control ; 30: 10732748231211764, 2023.
Article in English | MEDLINE | ID: mdl-37926828

ABSTRACT

INTRODUCTION: Information about survival outcomes in metastatic biliary tract cancer (BTC) is sparse, and the numbers often quoted are based on reports of clinical trials data that may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of a standardized combination chemotherapy regimen since 2010 on survival is unclear. METHODS: We performed an analysis of the Surveillance, Epidemiology, and End Results database to determine the real-world overall survival trends in a cohort of patients with metastatic BTC diagnosed between the years 2000 and 2017 with follow-up until 2018. We analyzed data for the entire cohort, evaluated short-term and long-term survival rates, and compared survival outcomes in the pre-2010 and post-2010 periods. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to evaluate factors associated with survival. RESULTS: Among 13, 287 patients, the median age was 68 years. There was a preponderance of female (57%) and white (77%) patients. Forty-one percent died within 3 months of diagnosis (short-term survivors) and 20% were long-term survivors (12 months or longer). The median overall survival (OS) for the entire cohort was 4.5 months. Median OS improved post-2010 (4.5 months) compared to pre-2010 (3.5 months) (P < .0001). On multivariate analysis, age <55 years, intrahepatic cholangiocarcinoma, surgical resection, and diagnosis post-2010 were associated with lower hazard of death. CONCLUSION: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials because a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , United States/epidemiology , Humans , Female , Aged , Middle Aged , Bile Duct Neoplasms/therapy , Databases, Factual , Multivariate Analysis , Bile Ducts, Intrahepatic
11.
J Org Chem ; 88(1): 172-188, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36516444

ABSTRACT

Photooxygenation reactions of electron-deficient enaminoesters bearing an oxophilic silyl tether at the α-position of the nitrogen atom using methylene blue (MB) were explored to develop a mild and efficient photochemical strategy for oxidative C-C double bond cleavage reactions via singlet oxygen (1O2). Photochemically generated 1O2, through energy transfer from the triplet excited state of MB (3MB*) to molecular oxygen (3O2), was added across a C-C double bond moiety of enaminoesters to form perepoxides, which rearranged to form dioxetane intermediates. The cycloreversion of the formed dioxetane via both C-C and O-O bond cleavage processes led to the formation of oxamates. Importantly, contrary to alkyl group tether-substituted electron-deficient enaminoesters that typically disfavor photooxygenation, the silyl tether-substituted analogues undergo this photochemical transformation efficiently with the assistance of a silyl tether, which facilitates formation of the perepoxide. The observations in this study provide useful information about photosensitized oxygenation reactions of unsaturated C-C bonds, and, moreover, this photochemical strategy can be utilized as a mild and feasible method for the preparation of diversely functionalized carbonyl compounds including oxamates.


Subject(s)
Electrons , Oxygen , Oxygen/chemistry , Singlet Oxygen/chemistry
12.
Br J Nutr ; 130(5): 887-894, 2023 09 14.
Article in English | MEDLINE | ID: mdl-36484091

ABSTRACT

Mineral consumption has been suggested to have an impact on gastric cancer (GC) prevention. However, the protective effect of potassium against gastric carcinogenesis remains inconclusive. The causal link between inflammation and cancer is well established. Notably, potassium intake and potassium channels may play certain roles in regulating the production of TNF-α (TNF-α). We aimed to determine whether dietary potassium intake is related to the risk of GC. We further observed whether this association was modified by TNF-α rs1800629. We designed a case-control study comprising 377 GC cases and 756 controls. Information on dietary potassium intake was collected using a semiquantitative food frequency questionnaire. Genotyping was performed by the Affymetrix Axiom Exom 319 Array platform. Unconditional logistic regression models were used to assess associations. A significantly reduced GC risk was found for those who consumed higher dietary potassium levels (OR = 0·63, 95 % CI = 0·45, 0·89, P for trend = 0·009). In the dominant model, we observed a non-significant association between TNF-α rs1800629 and GC risk (OR = 1·01, 95 % CI = 0·68, 1·49). In females, those who were homozygous for the major allele (G) of rs1800629 with a higher intake of dietary potassium exhibited a decreased risk of GC (OR = 0·40, 95 % CI = 0·20, 0·78, P interaction = 0·041). This finding emphasises the beneficial effect of potassium intake on GC prevention. However, this association could be modified by TNF-α rs1800629 genotypes. A greater protective effect was exhibited for females with GG homozygotes and high potassium intake.


Subject(s)
Stomach Neoplasms , Tumor Necrosis Factor-alpha , Female , Humans , Case-Control Studies , Tumor Necrosis Factor-alpha/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/prevention & control , Potassium, Dietary , Genetic Predisposition to Disease , Polymorphism, Genetic , Genotype , Republic of Korea , Polymorphism, Single Nucleotide
13.
Am J Physiol Lung Cell Mol Physiol ; 322(4): L593-L606, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35200041

ABSTRACT

The etiologies of chronic obstructive pulmonary disease (COPD) remain unclear. Cadmium (Cd) causes both pulmonary fibrosis and emphysema; however, the predictors for Cd exposure and the mechanisms by which Cd causes COPD remain unknown. We demonstrated that Cd burden was increased in lung tissue from subjects with COPD and this was associated with cigarette smoking. Fibrinogen levels increased markedly in lung tissue of patients with smoked COPD compared with never-smokers and control subjects. Fibrinogen concentration also correlated positively with lung Cd load, but inversely with the predicted % of FEV1 and FEV1/FVC. Cd enhanced the secretion of fibrinogen in a cdc2-dependent manner, whereas fibrinogen further mediated Cd-induced peptidylarginine deiminase 2 (PAD2)-dependent macrophage activation. Using lung fibroblasts from CdCl2-treated Toll-like receptor 4 (TLR4) wild-type and mutant mice, we demonstrated that fibrinogen enhanced Cd-induced TLR4-dependent collagen synthesis and cytokine/chemokine production. We further showed that fibrinogen complexed with connective tissue growth factor (CTGF), which in turn promoted the synthesis of plasminogen activator inhibitor-2 (PAI-2) and fibrinogen and inhibited fibrinolysis in Cd-treated mice. The amounts of fibrinogen were increased in the bronchoalveolar lavage fluid (BALF) of Cd-exposed mice. Positive correlations were observed between fibrinogen with hydroxyproline. Our data suggest that fibrinogen is involved in Cd-induced macrophage activation and increases in fibrinogen in patients with COPD may be used as a marker of Cd exposure and predict disease progression.


Subject(s)
Cadmium , Pulmonary Disease, Chronic Obstructive , Animals , Cadmium/toxicity , Fibrinogen/adverse effects , Humans , Lung/metabolism , Macrophage Activation , Mice , Pulmonary Disease, Chronic Obstructive/metabolism , Toll-Like Receptor 4
14.
Radiology ; 305(3): 699-708, 2022 12.
Article in English | MEDLINE | ID: mdl-35916677

ABSTRACT

Background The prevalence of chronic obstructive pulmonary disease (COPD) in women is fast approaching that in men, and women experience greater symptom burden. Although sex differences in emphysema have been reported, differences in airways have not been systematically characterized. Purpose To evaluate whether structural differences in airways may underlie some of the sex differences in COPD prevalence and clinical outcomes. Materials and Methods In a secondary analyses of a multicenter study of never-, current-, and former-smokers enrolled from January 2008 to June 2011 and followed up longitudinally until November 2020, airway disease on CT images was quantified using seven metrics: airway wall thickness, wall area percent, and square root of the wall thickness of a hypothetical airway with internal perimeter of 10 mm (referred to as Pi10) for airway wall; and lumen diameter, airway volume, total airway count, and airway fractal dimension for airway lumen. Least-squares mean values for each airway metric were calculated and adjusted for age, height, ethnicity, body mass index, pack-years of smoking, current smoking status, total lung capacity, display field of view, and scanner type. In ever-smokers, associations were tested between each airway metric and postbronchodilator forced expiratory volume in 1 second (FEV1)-to-forced vital capacity (FVC) ratio, modified Medical Research Council dyspnea scale, St George's Respiratory Questionnaire score, and 6-minute walk distance. Multivariable Cox proportional hazards models were created to evaluate the sex-specific association between each airway metric and mortality. Results In never-smokers (n = 420), men had thicker airway walls than women as quantified on CT images for segmental airway wall area percentage (least-squares mean, 47.68 ± 0.61 [standard error] vs 45.78 ± 0.55; difference, -1.90; P = .02), whereas airway lumen dimensions were lower in women than men after accounting for height and total lung capacity (segmental lumen diameter, 8.05 mm ± 0.14 vs 9.05 mm ± 0.16; difference, -1.00 mm; P < .001). In ever-smokers (n = 9363), men had greater segmental airway wall area percentage (least-squares mean, 52.19 ± 0.16 vs 48.89 ± 0.18; difference, -3.30; P < .001), whereas women had narrower segmental lumen diameter (7.80 mm ± 0.05 vs 8.69 mm ± 0.04; difference, -0.89; P < .001). A unit change in each of the airway metrics (higher wall or lower lumen measure) resulted in lower FEV1-to-FVC ratio, more dyspnea, poorer respiratory quality of life, lower 6-minute walk distance, and worse survival in women compared with men (all P < .01). Conclusion Airway lumen sizes quantified at chest CT were smaller in women than in men after accounting for height and lung size, and these lower baseline values in women conferred lower reserves against respiratory morbidity and mortality for equivalent changes compared with men. © RSNA, 2022 Online supplemental material is available for this article.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Quality of Life , Female , Humans , Male , Sex Characteristics , Forced Expiratory Volume , Tomography, X-Ray Computed/methods , Lung/diagnostic imaging , Dyspnea
15.
Cancer Causes Control ; 33(8): 1059-1069, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35404020

ABSTRACT

PURPOSE: Inclusion of racial/ethnic minorities in cancer research can reduce disparities in health outcomes; however, data regarding barriers and motivators to participation are sparse. This study assessed African American (AA) and Latinx healthy volunteers' perspectives regarding willingness to participate in noninvasive and invasive research activities. METHODS: Using a 38-item questionnaire adapted from the Tuskegee Legacy Project Questionnaire, we assessed willingness to participate in 12 research activities, offering 27 possible barriers and 14 motivators. The sample was segmented into four subgroups by AA/Latinx and rural/urban. RESULTS: Across five states and Puerto Rico, 533 participants completed questionnaires. Overall, participants were more willing to participate in noninvasive versus invasive procedures, although, all subgroups were willing to participate in research if asked. Rural AA were most willing to complete a survey or saliva sample, while rural Latinx were least willing. Urban AA were least willing to provide cheek swab, while rural counterparts were most willing. Self-benefit and benefit to others were among the top three motivators for all subgroups. Curiosity was a primary motivator for urban AA while obtaining health information motivated rural Latinx. Primary barriers included fears of side effects and being experimented on, lack of information, and lack of confidentiality. CONCLUSIONS: Latinx and AAs are willing to participate in the continuum of nontherapeutic research activities suggesting their lack of participation may be related to not being asked. Inclusive enrollment may be achieved by assessing needs of participants during the design phase of a study in order to reduce barriers to participation.


Subject(s)
Black or African American , Neoplasms , Healthy Volunteers , Humans , Neoplasms/therapy , Research , Rural Population
16.
J Org Chem ; 87(5): 2289-2300, 2022 03 04.
Article in English | MEDLINE | ID: mdl-35045708

ABSTRACT

Finding a selective and efficient fragmentation process under ambient conditions is pivotal for the generation of fuels and chemical feedstocks from lignoceullosic biomass. In the present study, visible-light and amine-functionalized fullerene-based photocatalyst-promoted photodegradation reactions of dimeric ß-O-4 and ß-1 lignin model compounds, containing varying numbers of methoxy substituents on the arene ring, were explored to find and develop mild, eco-friendly photochemical techniques for efficient delignification. The results showed that, in contrast to well-known organic photoredox catalysts, amine-functionalized fullerene photocatalyst promoted photochemical reactions of lignin model compounds could lead to more efficient lignin fragmentation reactions through a pathway involving a selective Cα-Cß bond cleavage process, and in addition, Cα-hydroxyl moiety in lignin model compounds played a significant role in the success of the Cα-Cß bond cleavage reaction of lignin model substrates.


Subject(s)
Fullerenes , Lignin , Amines , Catalysis , Lignin/chemistry , Lignin/metabolism
17.
Br J Nutr ; 127(7): 1026-1033, 2022 04 14.
Article in English | MEDLINE | ID: mdl-34078503

ABSTRACT

The vitamin B group, including riboflavin, plays paramount roles in one-carbon metabolism (OCM), and disorders related to this pathway have been linked to cancer development. The variants of genes encoding OCM enzymes and the insufficiency of B vitamins could contribute to carcinogenesis. Very few observational studies have revealed a relationship between riboflavin and gastric cancer (GC), especially under conditions of modified genetic factors. We carried out a study examining the association of riboflavin intake and its interaction with MTRR (rs1532268) genetic variants with GC risk among 756 controls and 377 cases. The OR and 95 % CI were evaluated using unconditional logistic regression models. We observed protective effects of riboflavin intake against GC, particularly in the female subgroup (OR = 0·52, 95 % CI 0·28, 0·97, Ptrend = 0·031). In the MTRR (rs1532268) genotypes analysis, the dominant model showed that the effects of riboflavin differed between the CC and CT + TT genotypes. Compared with CC carriers, low riboflavin intake in T+ carriers was significantly associated with a 93 % higher GC risk (OR = 1·93, 95 % CI 1·09, 3·42, Pinteraction = 0·037). In general, higher riboflavin intake might help reduce the risk of GC in both CC and TC + TT carriers, particularly the T+ carriers, with marginal significance (OR = 0·54, 95 % CI 0·28, 1·02, Pinteraction = 0·037). Our study indicates a protective effect of riboflavin intake against GC. Those who carry at least one minor allele and have low riboflavin intake could modify this association to increase GC risk in the Korean population.


Subject(s)
Stomach Neoplasms , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Polymorphism, Single Nucleotide , Republic of Korea/epidemiology , Riboflavin , Risk Factors , Stomach Neoplasms/epidemiology , Stomach Neoplasms/genetics , Stomach Neoplasms/prevention & control
18.
Surg Endosc ; 36(5): 2896-2905, 2022 05.
Article in English | MEDLINE | ID: mdl-34254185

ABSTRACT

BACKGROUND: Anastomotic leakage (AL) after gastrectomy in gastric cancer patients is associated with high mortality rates. Various endoscopic procedures are available to manage this postoperative complication. The aim of study was to evaluate the outcome of two endoscopic modalities, clippings and stents, for the treatment of AL. PATIENTS AND METHODS: There were 4916 gastric cancer patients who underwent gastrectomy between December 2007 and January 2016 at the National Cancer Center, Korea. A total of 115 patients (2.3%) developed AL. Of these, 85 patients (1.7%) received endoscopic therapy for AL and were included in this retrospective study. The endpoints were the complete leakage closure rates and risk factors associated with failure of endoscopic therapy. RESULTS: Of the 85 patients, 62 received endoscopic clippings (with or without detachable snares), and 23 received a stent insertion. Overall, the complete leakage closure rate was 80%, and no significant difference was found between the clipping and stent groups (79.0% vs. 82.6%, respectively; P = 0.89). The complete leakage closure rate was significantly lower in the duodenal and jejunal stump sites (60%) than esophageal sites (86.1%) and gastric sites (94.1%; P = 0.026). The multivariate analysis showed that stump leakage sites (adjusted odds ratio [aOR], 4.51; P = 0.031) and the presence of intra-abdominal abscess (aOR, 4.92; P = -0.025) were associated with unsuccessful leakage closures. CONCLUSIONS: Endoscopic therapy using clippings or stents is an effective method for the postoperative management of AL in gastric cancer patients. This therapy can be considered a primary treatment option due to its demonstrated efficacy, safety, and minimally invasive nature.


Subject(s)
Anastomotic Leak , Stomach Neoplasms , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Endoscopy/adverse effects , Gastrectomy/adverse effects , Gastrectomy/methods , Humans , Retrospective Studies , Stents/adverse effects , Stomach Neoplasms/complications , Stomach Neoplasms/surgery , Treatment Outcome
19.
Surg Endosc ; 36(2): 1414-1423, 2022 02.
Article in English | MEDLINE | ID: mdl-33725190

ABSTRACT

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.


Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Cross-Sectional Studies , Gastric Mucosa/pathology , Gastric Mucosa/surgery , Humans , Republic of Korea , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Treatment Outcome
20.
Surg Endosc ; 36(3): 1847-1856, 2022 03.
Article in English | MEDLINE | ID: mdl-33825017

ABSTRACT

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.


Subject(s)
Carcinoma, Signet Ring Cell , Endoscopic Mucosal Resection , Stomach Neoplasms , Carcinoma, Signet Ring Cell/pathology , Gastric Mucosa/pathology , Humans , Retrospective Studies , Stomach Neoplasms/pathology , Treatment Outcome
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