Interaction of Temperature and Light in the Development of Freezing Tolerance in Plants

Abstract Freezing tolerance is the result of a wide range of physical and biochemical processes, such as the induction of antifreeze proteins, changes in membrane composition, the accumulation of osmoprotectants, and changes in the redox status, which allow plants to function at low temperatures. Even in frost-tolerant species, a certain period of growth at low but nonfreezing temperatures, known as frost or cold hardening, is required for the development of a high level of frost hardiness. It has long been known that frost hardening at low temperature under low light intensity is much less effective than under normal light conditions; it has also been shown that elevated light intensity at normal temperatures may partly replace the cold-hardening period. Earlier results indicated that cold acclimation reflects a response to a chloroplastic redox signal while the effects of excitation pressure extend beyond photosynthetic acclimation, influencing plant morphology and the expression of certain nuclear genes involved in cold acclimation. Recent results have shown that not only are parameters closely linked to the photosynthetic electron transport processes affected by light during hardening at low temperature, but light may also have an influence on the expression level of several other cold-related genes; several cold-acclimation processes can function efficiently only in the presence of light. The present review provides an overview of mechanisms that may explain how light improves the freezing tolerance of plants during the cold-hardening period

A comprehensive study of deaths due to exposure to humidifier disinfectant in Korea: Focusing on medical records, assessment of exposure to humidifier disinfectants, and causes of death

OBJECTIVES: We aimed to determine the characteristics of the deceased victims of deaths caused by exposure to humidifier disinfectants, and present the distribution of the victims data submitted for damage application, demographic characteristics, imaging findings, characteristics of humidifier disinfectant exposure, and distribution of the causes of death. METHODS: An integrated database of victims was established using the medical records data of 1,413 victims submitted during the application for death damage caused by exposure to humidifier disinfectants, and the demographic characteristics, medical records, imaging findings, exposure characteristics, and cause of death were examined. RESULTS: The average numbers of data submissions of each applicant for death damage were 3.0 medical use records. A total of 608 (43.0%) victims had more than one finding of acute, subacute, or chronic interstitial lung diseases. The average daily and cumulative use times of the victims were 14.40 and 24,645.81 hours, respectively, indicating greater exposure in this group than in the survivors. The humidifier disinfectants components comprised polyhexamethylene guanidine (72.8%), chloromethylisothiazolinone/methylisothiazolinone (10.5%), other components (15.0%), and oligo-[2-(2-ethoxy)-ethoxyethyl] guanidine chloride (1.5%). The components distribution was 67.8% for single-component use, which was higher than that in the survivors (59.8%). The distribution of the causes of death were: respiratory diseases (54.4%), neoplasms (16.8%), and circulatory diseases (6.3%). Other interstitial lung diseases (65.5%) were the most common cause of death among those who died due to respiratory diseases. CONCLUSIONS: Careful discussions of appropriate remedies should be conducted based on a comprehensive understanding of the characteristics of the deceased victims, considering their specificities and limitations

Cancer development in patients with COPD: a retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea

BACKGROUND: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. METHODS: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7789), former smokers with COPD (N = 1085), and smokers with COPD (N = 2677). RESULTS: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among smokers, p < 0.01). Old age, male sex, lower BMI, low exercise level, history of diabetes mellitus, smoking, and COPD were independent factors associated with the development of lung cancer (p < 0.01). Multi-variable analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer, and colorectal cancer and liver cancer among other major cancers (p < 0.01). CONCLUSION: Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status

The Significance of Caspase-Cleaved Cytokeratin 18 in Pleural Effusion

Background: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. Materials and Methods: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. Results: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1±1,467.3 U/mL) than in patients with lung cancer (956.5±618.5 U/mL), parapneumonic effusion (689.9±413.6 U/mL), and transudates (273.6±144.5 U/mL; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues. Conclusion: Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues

The Significance of Sedation Control in Patients Receiving Mechanical Ventilation

Background: Adequate assessment and control of sedation play crucial roles in the proper performance of mechanical ventilation. Methods: A total of 30 patients with various pulmonary diseases were prospectively enrolled. The study population was randomized into two groups. The sedation assessment group (SAG) received active protocol-based control of sedation, and in the empiric control group (ECG), the sedation levels were empirically adjusted. Subsequently, daily interruption of sedation (DIS) was conducted in the SAG. Results: In the SAG, the dose of midazolam was significantly reduced by control of sedation (day 1, 1.3±0.5 µg/kg/min; day 2, 0.9±0.4 µg/kg/min; p<0.01), and was significantly lower than the ECG on day 2 (p<0.01). Likewise, on day 2, sedation levels were significantly lower in the SAG than in the ECG. Significant relationship was found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS; rs=-0.57), Ramsay Sedation Scale and Bispectral Index (BIS; rs=0.77), and RASS and BIS (rs=-0.79). In 10 patients, who didn't require re-sedation after DIS, BIS showed the earliest and most significant changes among the sedation scales. Ventilatory parameters showed significant but less prominent changes, and hemodynamic parameters didn't show significant changes. No seriously adverse events ensued after the implementation of DIS. Conclusion: Active assessment and control of sedation significantly reduced the dosage of sedatives in patients receiving mechanical ventilation. DIS, conducted in limited cases, suggested its potential efficacy and tolerability

Analysis of thromboembolic events in patients with non-small cell lung cancer who received adjuvant chemotherapy: single-center real-world data

Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs

Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study

Background: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. Methods: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. Results: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age &gt;70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. Conclusions: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable

Combination versus single-agent as palliative chemotherapy for gastric cancer

BACKGROUND: Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting. METHODS: A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). RESULTS: Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p &lt; 0.0001, in each case). The median OS of patients who received CC was significantly longer than that of patients who received SC (11 vs. 8 months, p &lt; 0.0001). No difference in OS between CC and SC was observed in elderly patients (p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and &gt;/= second-line chemotherapy were independently associated with favorable OS (p &lt; 0.0001, in each case), whereas poor PS (p = 0.004), signet ring cell (p &lt; 0.0001), peritoneal metastasis (p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS. CONCLUSIONS: Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients

Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data

Background: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. Methods: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. Results: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. Conclusions: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy

Pharmacological treatment response according to the severity of symptoms in patients with chronic obstructive pulmonary disease.

BACKGROUND: Pharmacological management of chronic obstructive pulmonary disease (COPD) is recommended according to the individualized assessment of symptoms and exacerbation risks. The aim of this study was to determine the relationship between the baseline Modified British Medical Research Council (mMRC) dyspnea scale and the COPD Assessment Test (CAT) score and pharmacological treatment response in patients with COPD. METHODS: A total of 102 stable COPD patients who were enrolled in prospective cohort studies were analyzed. Pharmacological treatment responses after a 3-month treatment were assessed by changes on the mMRC dyspnea scale, CAT scores, and spirometric pulmonary functions. RESULTS: Sixty-two patients with a mMRC dyspnea scale ≤1 were classified as having "less dyspnea" and 40 patients with a mMRC dyspnea scale ≥2 as having "more dyspnea". After a 3-month treatment, the mean mMRC dyspnea scale in the "more dyspnea" group was significantly decreased versus the "less dyspnea" group; however, there were no significant differences in CAT score changes or spirometric pulmonary function changes between the two groups. Baseline mMRC scales (Spearman's rho =-0.591, P<0.001) and baseline CAT scores (Pearson's r =-0.337, P=0.001) were significantly correlated with their changes after a 3-month treatment. Multiple logistic regression analysis demonstrated that baseline mMRC scale and CAT score were the only independent predictors of improvement greater than a minimal clinically significant difference after treatment. CONCLUSIONS: The severity of COPD symptoms is associated with their response to pharmacotherapy. COPD patients with a higher baseline mMRC dyspnea scale and CAT score experience greater symptom reduction by pharmacotherapy