Tag: pubmed

Acc Chem Res. 2021 Nov 11. doi: 10.1021/acs.accounts.1c00575. Online ahead of print.

ABSTRACT

ConspectusHomogeneous metal-mediated organometallic reactions represent a very large and diverse reaction class. Density functional theory calculations are now routinely carried out and reported for analyzing organometallic mechanisms and reaction pathways. While density functional theory calculations are extremely powerful to understand the energy and structure of organometallic reactions, there are several assumptions in their use and interpretation to define reaction mechanisms and to analyze reaction selectivity. Almost always it is assumed that potential energy structures calculated with density functional theory adequately describe mechanisms and selectivity within the framework of statistical theories, for example, transition state theory and RRKM theory. However, these static structures and corresponding energy landscapes do not provide atomic motion information during reactions that could reveal nonstatistical intermediates without complete intramolecular vibrational redistribution and nonintrinsic reaction coordinate (non-IRC) pathways. While nonstatistical intermediates and non-IRC reaction pathways are now relatively well established for organic reactions, these dynamic effects have heretofore been highly underexplored in organometallic reactions. Through a series of quasiclassical density functional theory direct dynamics trajectory studies, my group has recently demonstrated that dynamic effects occur in a variety of fundamental organometallic reactions, especially bond activation reactions. For example, in the C-H activation reaction between methane and [Cp*(PMe₃)Ir^III(CH₃)]⁺, while the density functional theory energy landscape showed a two-step oxidative cleavage and reductive coupling mechanism, trajectories revealed a mixture of this two-step mechanism and a dynamic one-step mechanism that skipped the [Cp*(PMe₃)Ir^V(H)(CH₃)₂]⁺ intermediate. This study also showed that despite a methane σ-complex being located on the density functional theory surface before oxidative cleavage and after reductive coupling, this intermediate is always skipped and should not be considered an intermediate during reactive trajectories. For non-IRC reaction pathways, quasiclassical direct dynamics trajectories showed that for the isomerization of [Tp(NO)(PMe₃)W(η²-benzene)] to [Tp(NO)(PMe₃)W(H)(Ph)], there are many dynamic reaction pathway connections due to a relatively flat energy landscape and π coordination is not necessary for C-H bond activation through oxidative cleavage. Trajectories also showed that dynamic effects are important in selectivity for ethylene C-H activation versus π coordination in reaction with Cp(PMe₃)₂Re, and trajectories provide a more quantitative model of selectivity than transition state theory. Quasiclassical trajectories examining Au-catalyzed monoallylic diol cyclizations showed dynamic coupling of several reaction steps that include alkoxylation π bond addition, proton shuttling, and water elimination reaction steps. Overall, these studies highlight the need to use direct dynamics trajectory simulations to consider atomic motion during reactions to understand organometallic reaction mechanisms and selectivity.

PMID:34761673 | DOI:10.1021/acs.accounts.1c00575

Ann Med. 2021 Dec;53(1):2034-2040. doi: 10.1080/07853890.2021.1999490.

ABSTRACT

BACKGROUND: The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality.

METHODS AND PATIENTS: Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality.

RESULTS: A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p<.0001; p<.0001; p=.0007, respectively). The AUC for overall mortality was similar for BSI, FACED score, and DSP (0.80 versus 0.85, p=.491; 0.85 versus 0.83, p=.831).

CONCLUSION: DSP had comparable predictive power for mortality as the well-validated BSI and FACED scores and is relatively easy to use in clinical practice.KEY MESSAGEDistance-saturation product (DSP) comprised with the product of distance walked, and lowest oxygen saturation during the 6-min walk test, which is common used in clinical practice.DSP demonstrated strong and comparable predictive power of mortality as the well-validated BSI and FACED scores in non-CF bronchiectasis patients.

PMID:34761709 | DOI:10.1080/07853890.2021.1999490

Allergol Immunopathol (Madr). 2021 Nov 1;49(6):48-55. doi: 10.15586/aei.v49i6.338. eCollection 2021.

ABSTRACT

INTRODUCTION: There is an increasing amount of data relating the dietetic pattern to health variables, although data concerning the child population are scarce. The aim of the study was to assess the effects of affinity to the Traditional Mediterranean Diet (TMD) pattern, together with breastfeeding, on the incidence of childhood asthma and other inflammatory and recurrent diseases (IRD) in children under 2 years of age.

METHODS: Single-group intervention study evaluating differences in results according to degree of adherence to TMD recommendations. According to their adhesion to the TMD-Breastfed Test, patients were classified into two groups: Group 1 (with greater adherence) and Group 2 (with less adherence). The incidence of childhood asthma and IRD was evaluated and compared with both groups.

RESULTS: The score of the TMD-Breastfed Test was optimal in Group 1 and good in Group 2. It shows a marked reduction in both consultation groups “on request” compared with “planned,” with low morbidity and low use of antibiotics. The incidence of infectious diseases and recurrent bacterial complications shows a clinically relevant difference between both groups. The incidence of childhood asthma was greater and statistically significant in Group 2, with less adherence to breastfeeding.

CONCLUSIONS: In these cohorts of breastfed patients with good adherence to TMD patterns, there was evidence of a low incidence of childhood asthma and the IRD, more pronounced in the highest adherence Group 1. Some non-TMD foods have been linked to the occurrence of childhood asthma and IRD, as their dietary limitations have contributed to decreasing morbidity.

PMID:34761656 | DOI:10.15586/aei.v49i6.338

J BUON. 2021 Sep-Oct;26(5):2157-2168.

ABSTRACT

PURPOSE: To determine the relationship between inflammatory cell types in the microenvironment of papillary thyroid microcarcinoma (PTMC) and prognostic factors.

METHODS: The previous diagnoses and subtypes-variants of 163 patients with papillary thyroid microcarcinoma were re-evaluated according to the 2017 WHO classification. The peritumoral lymphocyte, plasma cell, neutrophil, eosinophil, and mast cell density were classified as none (0.24 mm2), mild (0-10/0.24 mm2), moderate (10-50/0.24 mm2), and severe (˃50/0.24 mm2) under 40x magnification and the relationship with prognostic factors was investigated.

RESULTS: There was a statistically significant relationship between tumor capsule invasion (p=0.024) and surgical margin (p=0.049) with mast cell infiltration. A statistically significant relationship was observed between tumor capsule invasion (p=0.0001) and the postoperative disease-free period (p=0.0001) with neutrophil cell infiltration. The postoperative disease-free period of those with neutrophil infiltration was statistically significantly shorter than that of those with no infiltration. The tumor diameter of those with no plasma cells was statistically significantly smaller than that of patients with plasma cells (p=0.003).

CONCLUSIONS: Closer follow-up of patients with neutrophils, mast cells, and plasma cells, which have been found to be associated with poor prognostic factors in terms of recurrence, lymph node involvement, and distant metastasis, may increase survival.

PMID:34761630

J BUON. 2021 Sep-Oct;26(5):2176-2182.

ABSTRACT

PURPOSE: To assess patient satisfaction from chemotherapy and investigate the effect of demographic factors, disease symptoms and treatment on satisfaction.

METHODS: A non-randomized cross-sectional survey was conducted on a sample of 100 patients undergoing chemotherapy at “Metaxa” Cancer Hospital, Piraeus, Greece for 6 months. A demographic data questionnaire, a Cancer Treatment Satisfaction Questionnaire (CTSQ) and visual analog scales were used to evaluate pain, anxiety, fatigue, and nausea while presence or absence of vomit were also assessed.

RESULTS: The majority of the patients in the sample were men (51%), with a mean age of 58.5 ± 10.82 years. The mean value of expectations from treatment was 60.55, from treatment’s satisfaction was 75.86 and from feelings about treatment’s side effects was 44.56. The most serious symptoms were fatigue and anxiety (7.2 ± 1.95 and 6.71 ± 2.5, respectively). Statistical tests have shown that sub-dimensions of CTSQ are associated with pain, anxiety, fatigue, and nausea.

CONCLUSIONS: Generally, chemotherapy meets patients’ expectations with cancer. Symptoms such as fatigue, anxiety, pain, and nausea affect their satisfaction. Treatment’s satisfaction can be improved by evaluating symptoms, which will lead to appropriate interventions.

PMID:34761632

J BUON. 2021 Sep-Oct;26(5):2106-2110.

ABSTRACT

PURPOSE: To evaluate the sexual functions of prostate cancer patients receiving radiotherapy (RT) with curative intent.

METHODS: Fifty patients with low-risk prostate cancer who responded to the international index of erectile function (IIEF) questionnaire before and after RT were included in the study Results: Statistically significant decline was observed in sexual functions by the end of RT. While the average sexual desire scores of the patients before RT was 6.24, it decreased to 3.62 (p=0.001) after RT. The average of sexual satisfaction scores dropped from 8.94 to 4.6 (p=0.001), the average of erection function scores dropped from 20.14 to 11.76 (p=0.001), orgasmic function scores dropped from 9.6 to 3.9 (p=0.001) and the average of overall satisfaction scores dropped from 7.48 to 4.36 (p=0.001).

CONCLUSION: Sexual functions evaluated by the IIEF questionnaire decrease by the end of RT.

PMID:34761623

J BUON. 2021 Sep-Oct;26(5):2117-2125.

ABSTRACT

PURPOSE: Platin-based chemotherapies are first-line treatment methods after surgery in bladder cancer. Recently, novel immunotherapies emerged after platin-based regimens. The purpose of this study was to evaluate the prognostic significance of microsatellite instability (MSI), tumor infiltrating lymphocytes (TILs) and programmed cell death ligand-1 (PD-L1) expression which are used as predictive biomarkers in immunotherapy.

METHODS: Clinical and pathological features of bladder cancer patients who underwent radical cystectomy were retrospectively analyzed from their records in this single-center study. PD-L1, PD-L1 on TIL, PMS2, MSH2, MSH6 and MLH1 immunohistochemistry staining were carried out to archieve resected tumor specimens of the eligible patients. MSI was evaluated according to existing of PMS2, MSH2, MSH6 and MLH1.

RESULTS: MSI was high in 24.6% of 61 patients. PD-L1 expression on tumor cells and PD-L1 expression on TIL were positive in 14.8% and 16.4% of the patients, respectively. Intratumoral TIL rate was >10% in 12 patients (19.7%). There was no statistically significant relationship between PD-L1, PD-L1 on TIL, MSI and TIL rate and patients’ characteristics including sex, stage, pathologic grade and lymph node status. There was a positive trend between MSI-high patients and overall survival (OS) (p=0.089). Univariate analysis did not reveal any significant difference at 3-years OS with PD-L1 tumor expression and PD-L1 expression on TIL and TIL rate >10% (p=0.822, p=0.638, p=0.318, respectively) Conclusion: This study revealed that there is a positive trend between OS and MSI but no prognostic significance of PD-L1 and TIL which are proven predictive biomarkers of immunotherapy in patients with bladder cancer.

PMID:34761625

J BUON. 2021 Sep-Oct;26(5):1918-1924.

ABSTRACT

PURPOSE: To compare the efficacy and safety between endoscopic submucosal dissection (ESD) and conventional surgical treatment in the treatment of colorectal cancer (CRC) and the precancerous lesions.

METHODS: A retrospective analysis was performed on the clinical data of 65 patients with CRC or precancerous lesions (ESD group) and another 65 patients receiving surgical treatment at the same period (Surgery group). The surgical indicators, incidence of complications, and quality of life score were compared between the two groups, and the survival and tumor progression were followed up and recorded.

RESULTS: The rate of en bloc tumor resection was 89.2% (58/65) and 100% (65/65) and the rate of tumor curative resection was 92.3% (60/65) and 100% (65/65) in ESD group and Surgery group. Moreover, ESD group had markedly shorter operation time and mean hospital stay. After treatment, ESD group had higher scores of emotional functioning, fatigue, constipation, and diarrhea symptoms and general quality of life on the European Organization for Research and Treatment of Cancer quality of life questionnaire Core 30 (EORTC QLQ-C30) than Surgery group. The follow-up results showed no statistically significant difference in the 5-year recurrence rate between ESD group and Surgery group (7.7% vs. 0%, p=0.208).

CONCLUSION: ESD and surgery have similar long-term clinical efficacy in treating early CRC and precancerous lesions, but ESD is more minimally invasive and safer, and is superior in accelerating postoperative recovery and improving the overall survival of patients.

PMID:34761600

J BUON. 2021 Sep-Oct;26(5):1893-1897.

ABSTRACT

PURPOSE: Peroxiredoxins (Prdxs) represent a family of proteins that act as antioxidant enzymes and are involved in a variety of metabolic functions including mainly the intracellular hydrogen peroxide (H2O2) levels reduction. Especially, Prdx-6 protein encoded by the PRDX6 gene (1q25.1) regulates also phospholipid modifications and induces response to oxidative stress and injuries. Our aim was to investigate the expression of Prdx-6 in colon adenocarcinoma (CA).

METHODS: A series of 30 formalin-fixed, paraffin-embedded primary CAs tissue sections were used and analyzed. Immunohistochemistry was performed using an anti-Prdx-6 antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained cells.

RESULTS: Prdx-6 protein overexpression (increased immunostaining levels) was observed in 12/30 (40%) cases, whereas 18/30 (60%) CA tissues demonstrated low to moderate protein levels, respectively. Prdx-6 overall expression was strongly associated with the stage of the examined tumors (p=0.011), whereas other statistical significances were not assessed (inflammatory infiltration: p=0.364; carcinoma location: p=0.93; differentiation grade: p=0.517; tumor diameter: p=0.983; ulceration: p=0.622).

CONCLUSIONS: Prdx-6 overexpression is observed in a significant subset of CAs correlating with aggressive biological behavior (advanced stage). Prdx-6 is a crucial enzyme for oxidative stress/injury endogenous cell response and should be an interesting agent as a biomarker and potential therapeutic target.

PMID:34761597

J BUON. 2021 Sep-Oct;26(5):1887-1892.

ABSTRACT

PURPOSE: In this study, we aimed to determine the factors which affect post-progression survival (PPS) and overall survival (OS) in patients with metastatic colorectal cancer.

METHODS: 87 patients with metastatic colorectal cancer had been followed up with palliative care due to disease progression or ECOG performance status after receiving at least two cycles of chemotherapy. PPS was estimated as the time between the last progression date and last control or death date in patients who were followed up with palliative care.

RESULTS: 87 patients with metastatic colorectal cancer were included in the study. Evaluation with multivariate analysis of factors affecting PPS revealed a significantly longer PPS (10.8 weeks) in patients with ECOG score 0 or 1 than the PPS of patients with ECOG score 2-5 (3 weeks) (p=0.01). It was also found that PPS was 14.4 weeks in patients with CEA levels <5ng/ml,while it was 6.7 weeks in patients with CEA levels ≥5 ng/ml (p=0.001) and PPS was 13.7 weeks in patients with controlled disease after first-line chemotherapy while it was 8 weeks in patients with progression (p=0.03); both were statistically significant. No significant association was found between PPS and age, gender, tumor location, sites of metastasis, and RAS status.

CONCLUSION: ECOG performance status score of 0-1, CEA levels below 5 ng/ml, and disease control with first-line chemotherapy are related to longer PPS in patients with metastatic colorectal cancer.

PMID:34761596