Category: Nevin Manimala

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):633-642. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.003.

ABSTRACT

OBJECTIVE: To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).

METHODS: The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.

RESULTS: Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).

CONCLUSION: D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

PMID:37356919 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.003

J Mol Biol. 2023 Jul 15;435(14):167944. doi: 10.1016/j.jmb.2022.167944. Epub 2023 Jan 10.

ABSTRACT

Spatial proteomics aims for a global description of organelle-specific protein distribution and dynamics, which is essential for understanding the molecular functions and cellular processes in health and disease. However, the application of this technique is seriously restricted by the neglect of robustness among proteomic signatures identified using standard statistical frameworks. Moreover, it is still a major bottleneck to automatically interpretate the identified proteomic signatures due to lack of integration of subcellular information. Herein, an online-tool SISPRO was constructed to (a) identify proteomic signatures with good robustness and accuracy via collectively evaluating relative weighted consistency (CWrel) & area under the curve (AUC) and (b) interpretate the identified signature based on comprehensive subcellular information from 9 organelles and 22 subcellular structures. All in all, SISPRO provides the endeavor to realize the simultaneous improvement of robustness and accuracy in signature identification and the unique capacity in biological annotation lies in its wide coverage of proteins and comprehensive spatial information. SISPRO is expected to be critical in spatial proteomic studies, which can be freely accessed without any login requirement at https://idrblab.org/sispro/.

PMID:37356911 | DOI:10.1016/j.jmb.2022.167944

J Mol Biol. 2023 Jul 15;435(14):167978. doi: 10.1016/j.jmb.2023.167978. Epub 2023 Jan 25.

ABSTRACT

The sequence-dependent statistical mechanics of double-stranded nucleic acid, or dsNA, is believed to be essential in its biological functions. In turn, the equilibrium statistical mechanics behaviour of dsNA depends strongly both on sequence-dependent perturbations in its ground state shape away from an idealised, uniform, double-helical configuration, and on its fluctuations as governed by its sequence-dependent stiffness. We here describe the cgNA+web browser-based interactive tool for visualising the sequence-dependent ground states of dsNA fragments of arbitrary sequences, as predicted by the underlying cgNA+ coarse-grain model. Parameter sets are provided to model dsDNA, including the possibility of epigenetically modified CpG dinucleotide steps, dsRNA, and DNA:RNA Hybrid double helical fragments. The cgNA+web interface is specifically designed to compare ground state shapes of different sequences of the same dsNA, or analogous sequences of different dsNAs. The cgNA+web server is freely available at cgDNAweb.epfl.ch without any login requirement.

PMID:37356908 | DOI:10.1016/j.jmb.2023.167978

J Mol Biol. 2023 Jul 15;435(14):168142. doi: 10.1016/j.jmb.2023.168142. Epub 2023 May 5.

ABSTRACT

Although nascent RNA profiling data are widely used in transcriptional regulation studies, the development and standardization of data processing pipeline lags far behind RNA-seq. We are filling this gap by establishing the nASAP web server (https://grobase.top/nasap/) to provide practical quality evaluation and comprehensive analysis of nascent RNA datasets. In nASAP, four customized analysis modules are provided, including i) quality assessment, which summarizes the sequencing statistics, mapping ratio, and evaluates RNA integrity and mRNA contamination; ii) quantification analysis for mRNAs, lncRNAs and eRNAs; iii) pausing analysis across the whole genome based on sequencing reads distribution; and iv) network analysis to better understand the gene regulatory mechanism by obtaining annotated enhancer-promoter interactomes. The nASAP is user-friendly and outperforms the existing pipeline for quality control of nascent RNA profiling data. We anticipate that nASAP, which eases both basic and advanced analysis of nascent RNA data, will be extremely useful in various fields.

PMID:37356907 | DOI:10.1016/j.jmb.2023.168142

Air Med J. 2023 Jul-Aug;42(4):263-267. doi: 10.1016/j.amj.2023.04.004. Epub 2023 Apr 28.

ABSTRACT

OBJECTIVE: The Certified Flight Registered Nurse (CFRN) credential independently validates a registered nurse’s advanced knowledge, skills, and abilities in the unique specialty of flight nursing. Introduced in 1993 and celebrating its 30th anniversary in July 2023, the CFRN is held by over 5,500 registered nurses. The purpose of the 2022 CFRN pulse survey was to better understand the ways CFRN-certified registered nurses value this national flight nursing specialty credential. The CFRN survey is a companion to the 2022 Certified Transport Registered Nurse pulse survey, which focused on the Certified Transport Registered Nurse critical care ground transport nursing credential.

METHODS: The Board of Certification for Emergency Nursing e-mailed individuals in its database of CFRN credential holders and asked them to respond to a 14-question online survey between October 17, 2022, and November 8, 2022. Participation in the survey was voluntary. Of the 5,275 verified CFRN holders who received the survey, 992 responded, for a response rate of 18.8%. The survey instrument included discrete field and open-ended questions. Data were deidentified for analysis, and institutional review board exemption was received. Counts and percentages were reported, and descriptive statistics were used.

RESULTS: The highest percentage of flight nurses who responded have more than 10 years of experience in flight nursing (35.3%) and are employed by a stand-alone transport program (42.7%). Flight nurses reported they spent a mean of 70% of their work hours transporting via rotor wing aircraft, with a predominantly adult patient population. The top perceived benefits of being a CFRN-certified nurse were a sense of accomplishment and pride (90.7%) followed by flight physiology knowledge (85.4%), flight nursing clinical knowledge (83.4%), and confidence as a flight nurse (80.6%).

CONCLUSION: The 2022 CFRN pulse survey identified current CFRN demographics, practice environments including transport percentage by mode and patient population types, and perceived benefits of the CFRN credential. The findings suggest CFRNs are very experienced, provide care for patients across the age continuum, and perceive multiple intrinsic and extrinsic benefits of CFRN certification, all of which are essential to safe, evidence-based advanced nursing practice in the unique, complex, autonomous, and dynamic flight environment.

PMID:37356887 | DOI:10.1016/j.amj.2023.04.004

Air Med J. 2023 Jul-Aug;42(4):246-251. doi: 10.1016/j.amj.2023.03.003. Epub 2023 Mar 28.

ABSTRACT

OBJECTIVE: Twin pregnancy rates have increased in the past 30 years. We describe the experience of the Neonatal Emergency Transport Service of the Gaslini Hospital, Genoa, Italy, in the transport of twin newborns.

METHODS: This was a retrospective study (1996-2021); 7,852 medical charts from the Neonatal Emergency Transport Service were reviewed. We included all twin newborns who were transported with respiratory distress syndrome in the study. We split the included patients into 2 groups (group A and group B) based on if they were simultaneously ventilated by a single ventilator or by 2 different ventilators, and then each group was split by the different types of ventilation (nasal continuous positive airway pressure or intermittent positive pressure ventilation). The pH level, base excess, O₂ saturation, Pco₂, body temperature, plasma glucose, and Transport Risk Index of Physiologic Stability score were recorded at departure and arrival.

RESULTS: One hundred thirty-six patients were included (68 pairs of twins); group A consisted of 92 newborns and group B 44 newborns. Although some significant differences were observed (statistic), none of these had real clinical significance.

CONCLUSION: Transporting respiratory distress syndrome twin newborns is challenging. Our study provided a 27-year experience in the field. Transporting twins by a single ventilator is possible, but, in our opinion, using 2 ventilators mounted on the same transport module is the best possible choice in terms of clinical performance, logistics, and cost.

PMID:37356884 | DOI:10.1016/j.amj.2023.03.003

Mar Pollut Bull. 2023 Jun 23;193:115191. doi: 10.1016/j.marpolbul.2023.115191. Online ahead of print.

ABSTRACT

This study investigated the concentration of PAHs in 19 water samples, 34 sediment samples and 22 fish samples of Anzali Wetland, located in north of Iran. The average concentration of ∑PAHs in the wetland sediment was 89.19 μg/kg (8.28-806.64) and 78.31 ng/L (5.14-253.37) in the wetland water. Also, the average concentration of ∑PAHS in the muscle of the investigated fish in the wetland was 23 μg/kg (56.1 to 7.6). The source apportionment of PAHs in water and sediment considering isomeric ratios and statistical methods reveals the predominance of petrogenic origin of the compounds in water and pyrogenic origin in sediment. Overall, the level of contamination in fish is relatively low to moderate, considering ∑PAHs. The findings present clear evidence of low to moderate level of contamination in the wetland, the PAHs contamination however could cross their ecological thresholds in future unless control measures are taken to protect the wetland.

PMID:37356126 | DOI:10.1016/j.marpolbul.2023.115191

Adv Gerontol. 2023;36(2):247-250.

ABSTRACT

The review is devoted to the influence of the microbiota on the development of such an age-dependent disease as coronary heart disease, the formation of which depends on atherogenesis in particular. According to the World Health Organization, cardiovascular disease is the leading cause of death worldwide. Statistical data from the Federal State Statistics Service also confirm that coronary heart disease is the leading cause of death in the Russian Federation today. It is known that the vast majority of cardiovascular diseases are atherosclerosis-associated pathologies. Atherogenesis and the state of the human gut microbiome are dynamically interrelated. The gut microbiota, which consists predominantly of bacteria, plays an important role in maintaining homeostasis. The pathogenesis of atherosclerosis is based on systemic inflammation. Aging is accompanied by a wide variety of clinical manifestations, including a basic pro-inflammatory state (i.e., «inflammation-aging»), the activity of which is maintained by the microbiota in older individuals and increases their susceptibility to diseases. Intestinal microbiocenosis in elderly and senile people differs from those of young people. In persons of older age groups, there is an increase in microorganisms secreting endotoxins lipopolysaccharide and trimethylamine-n-oxide, initiating and maintaining chronic inflammation. More research is needed to study the mechanisms of action of microbial metabolites and their clinical application in various therapeutic interventions.

PMID:37356102

Adv Gerontol. 2023;36(2):206-213.

ABSTRACT

The article deals with the problem of myocardial damage of various genesis in patients of the intensive care unit and intensive care unit of various age groups. The study included patients with various pathologies with significant manifestations of multiple organ failure and high risks of adverse outcomes. Parametric (Student’s t-test) and nonparametric (Mann-Whitney U-test, Pearson’s χ2 criterion) statistical methods were used to analyze the severity of the inflammatory response, organ dysfunction, and the need for replacement therapy, in particular ventilator and vasopressor support in patients of different age groups. The frequency of myocardial damage was studied on the basis of an increase in cardiac troponin in patients of the intensive care unit. A comparison of the increase in troponin with morphological changes of the heart was carried out based on the analysis of ECHO, coronary angiography and sectional material. The role of cardiac troponin in the prognosis of adverse events in patients of different ages was analyzed. As a result of the study, it was found that the degree of severity of organ dysfunction, inflammatory response and the need for replacement therapy significantly prevail in elderly patients, as well as the phenomenon of myocardial damage. The main proportion of myocardial lesions was nonspecific. At the same time, the very fact of an increase in cardiac troponin in patients of the intensive care unit is an independent risk factor for adverse outcomes, regardless of the age of the patients.

PMID:37356096

Adv Gerontol. 2023;36(2):198-205.

ABSTRACT

An important area of medical and social research is prospective studies of a cohort of older patients with chronic non-communicable diseases aimed at studying the level of mortality, taking into account the presence/absence of senile asthenia syndrome. A prospective clinical and epidemiological study was conducted on 1 261 people aged 80 years and older receiving medical care on an outpatient basis. Three groups of patients were formed: without senile asthenia syndrome (7,6%), in a state of pre-asthenia (23,5%), with senile asthenia (68,9%). After a calendar year, an analysis was made of the causes of death of respondents in all three groups. A high statistically significant incidence of chronic diseases in patients with senile asthenia syndrome compared with those without signs of this syndrome was noted in arterial hypertension, chronic heart failure, osteoarthritis, age-related macular degeneration, chronic kidney disease, dementia, cancer, anemia, uncomplicated diabetes mellitus. In the structure of causes of death in patients aged 80 years and older, diseases of the circulatory system, nervous system, neoplasms, liver diseases, and diabetes mellitus predominated. The odds ratio of the risk of dying within a year in patients without frailty syndrome is 0,32 (compared to patients with frailty, in which the risk is taken as 1).

PMID:37356095