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Nevin Manimala Statistics

Analysis of systemic cytokine levels in silicosis complicated with pulmonary infection

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2021 Feb 20;39(2):133-136. doi: 10.3760/cma.j.cn121094-20191101-00512.

ABSTRACT

Objective: To investigate the changes of cytokine profile in elderly patients with silicosis and lower respiratory tract infection and its clinical significance. Methods: In Oclober 2019, a retrospective study was conducted to select 167 elderly patients with silicosis from Xuzhou Mining Group General Hospital as subjects, including 115 patients with silicosis and lower respiratory tract infection as infected group, including 41 patients with stage I silicosis, 38 patients with stage II silicosis and 36 patients with stage III silicosis. There were 52 cases of silicosis without lower respiratory tract infection as non-infected group, and 48 cases of healthy examination in our hospital were selected as control group. All the participants were tested for cytokines (IL-6, IL-10, IL-17A, TNF-α, IFN-γ) and statistically analyzed the relevant experimental data. Results: The levels of IL-6, IL-10, IL-17A, TNF-α and IFN-γ in the infected group after treatment were significantly lower than those before treatment (P<0.05) . The levels of IL-6, IL-10, IL-17A, TNF-α and IFN-γ before and after treatment in the infected group were higher than those in the non-infected group and the control group (P<0.05) . The levels of IL-10, IL-17A, TNF-α and IFN-γ in the infected group were higher than those in the control group, and the difference were statistically significant (P<0.05) . The levels of IL-6, IL-10, IL-17A and IFN-γ in patients with stage III silicosis were higher than those in stage I silicosis in infected group (P<0.05) . The levels of IL-6 and IL-17A in the patients with stage Ⅲ silicosis were higher than those in the patients with stage II silicosis in infected group (P<0.05) . The level of IL-10 in patients with stage II silicosis was higher than that in stage I in infected group (P<0.05) . ROC curve analysis of the indicators for diagnosis of senile silicosis with lower respiratory tract infection and silicosis without lower respiratory tract infection found that IL-6 had the largest AUC (0.910) . And its specifuity and sensithcity were 85.2% and 98.1% respectivehy. Conclusion: The detection of cytokines such as IL-6 and IL-10 has better specificity and higher diagnostic efficiency in the early diagnosis and treatment of elderly patients with silicosis complicated with lower respiratory tract infection. It has good clinical application value and can provide important laboratory evidence for early treatment for clinicians.

PMID:33691369 | DOI:10.3760/cma.j.cn121094-20191101-00512

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Abnormal vascular physiology in the lower extremities as a risk factor for ischemic stroke and mortality

J Osteopath Med. 2021 Mar 10. doi: 10.1515/jom-2020-0290. Online ahead of print.

ABSTRACT

OBJECTIVES: Peripheral artery disease (PAD) is highly prevalent in the general population, affecting up to 25% of patients 55 years or older. There is a known association with acute ischemic stroke, but limited large-cohort studies exist pertaining to the relationship between PAD severity and incident ischemic stroke. The objective of this study is to evaluate the risk of incident ischemic stroke and mortality along the spectrum of low and elevated ankle brachial index (ABI) measurement.

METHODS: We performed a retrospective extraction of ABI data of all adult patients who underwent lower extremity physiology study for any indication from January 1, 1996 to June 30, 2018 in the Mayo Clinic health system. PAD was categorized into severe, moderate, mild, and borderline based on ABI measurements and poorly compressible arteries (PCA). These were compared with normal ABI measurements. Associations of PAD/PCA with new ischemic stroke events and all-cause mortality were analyzed. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals.

RESULTS: A total of 39,834 unique patients were included with a median follow up duration of 4.59 years. All abnormal ABI groups, except borderline PAD, were associated with increased risk of incident ischemic stroke after multivariate regression compared to normal ABI. A severity-dependent association was observed between PAD and ischemic stroke with moderate (HR, 1.22 [95% CI, 1.10-1.35]) and severe (HR, 1.19 [95% CI, 1.02-1.40]) categories conferring similar risk in comparison to normal ABI. Patients with PCA carried the greatest ischemic stroke risk (HR, 1.30 [95% CI, 1.15-1.46]). Similarly, abnormal ABI groups were associated with a significant risk for all-cause mortality in a severity-dependent manner, with severe PAD conferring the greatest risk (HR, 3.07 [95% CI, 2.88-3.27]).

CONCLUSIONS: This study adds to the growing body of evidence that both PAD and PCA are independent risk factors for incident ischemic stroke and all-cause mortality. The association of PAD severity and PCA with risk of ischemic stroke may help clinicians with risk stratification and determining treatment intensity.

PMID:33691353 | DOI:10.1515/jom-2020-0290

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Expression and clinical significance of SETD2 in maligant pleural mesothelioma

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2021 Feb 20;39(2):91-98. doi: 10.3760/cma.j.cn121094-20200831-00505.

ABSTRACT

Objective: To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients. Methods: The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Summarize the gene mutation profile of tissue samples in the TCGA database and analyze the relationship between the expression level of high-frequency mutation genes and the clinicopathological characteristics, asbestos exposure history and prognosis of MPM patients. The genes significantly related to MPM prognosis were screened out for gene set enrichment analysis (GSEA) . Survival analysis and GSEA were performed for the selected key genes and clinicopathological features verification using the microarray expression data from the GEO database. Results: The top 10 genes with highest single nucleotide variations frequencies were BAP1, NF2, TP53, TTN, SETD2, LATS2, CCDC168, FAT4, PTCH1 and ZNF469. The high expression rates of NF2, TP53, SETD2 and CCDC168 genes in wild type were higher than those of mutated type, and the differences were statistically significant (P<0.05) . Cox multivariate analysis of TCGA data showed that MPM patients with epithelial type (HR=0.425, 95%CI: 0.235-0.767, P<0.01) and SETD2 low expression (HR=0.516, 95%CI: 0.307-0.868, P=0.011) had lower risk of death. The survival analysis of GEO data verified that patients with epithelial type MPM had longer survival time, while patients with sarcoma type MPM had shortest survival time (P<0.01) . GSEA showed that SETD2 was involved in G2M checkpoint, E2F targets, MYC signaling pathways, protein secretion, mitotic spindle, MTORC1 pathway, TGF-β pathway, androgen response and uv response. Conclusion: MPM is accompanied with higher frequency of gene mutations represented by BAP1, NF2, TP53, TTN, SETD2, LATS2 and so on. SETD2 expression level and epithelia type of MPM may be influential factors for MPM prognosis.

PMID:33691361 | DOI:10.3760/cma.j.cn121094-20200831-00505

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Quantifying a frequency modulation response biomarker in responsive neurostimulation

J Neural Eng. 2021 Mar 10. doi: 10.1088/1741-2552/abed82. Online ahead of print.

ABSTRACT

OBJECTIVE: Responsive Neurostimulation (RNS) is an effective treatment for controlling seizures in patients with drug-resistant focal epilepsy who are not suitable candidates for resection surgery. A lack of tools for detecting and characterizing potential response biomarkers, however, contributes to a limited understanding of mechanisms by which RNS improves seizure control. We developed a method to quantify ictal frequency modulation, previously identified as a biomarker of clinical responsiveness to RNS.

APPROACH: Frequency modulation is characterized by shifts in power across spectral bands during ictal events, over several months of neurostimulation. This effect was quantified by partitioning each seizure pattern into segments with distinct spectral content and measuring the extent of change from the baseline distribution of spectral content using the squared Earthmover’s distance.

MAIN RESULTS: We analyzed intracranial electroencephalography data from 13 patients who received RNS therapy, six of whom exhibited frequency modulation on expert evaluation. Patients in the frequency modulation group had, on average, significantly larger and more sustained changes in their squared Earthmover’s distances (mean = 13.97×10-3 ± 1.197×10-3). In contrast, those patients without expert-identified frequency modulation exhibited statistically insignificant or negligible distances (mean = 4.994×10-3 ± 0.732×10-3).

SIGNIFICANCE: This method is the first step towards a quantitative, feedback-driven system for systematically optimizing RNS stimulation parameters, with an ultimate goal of truly personalized closed-loop therapy for epilepsy.

PMID:33691289 | DOI:10.1088/1741-2552/abed82

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Physical Exercise as a Resilience Factor to Mitigate COVID-Related Allostatic Overload

Psychother Psychosom. 2021 Mar 10:1-7. doi: 10.1159/000514331. Online ahead of print.

ABSTRACT

INTRODUCTION: The long-lasting threat of COVID-19 makes it necessary to explore strategies to improve coping skills which enable us to master a balanced life in the face of adversity.

OBJECTIVE: To unravel the most challenging aspects of COVID-19 in a nonclinical adult population and identify predictors of lost balance and consequent allostatic overload (AO). We examined the role of regular, moderate-intensity formula aerobic exercise (312 meridian exercise) in preventing allostatic overload through increasing well-being.

METHODS: An online survey was conducted to measure CO-VID-related allostatic overload according to clinimetric criteria. The Psychosocial Index (PSI), Kellner’s Symptom Questionnaire (KSQ), short Depression Anxiety Stress Scales (DASS-21), Public Health Surveillance Well-Being Scale -(PHS-WB), and Whiteley-7 were used to explore mental health characteristics. Univariate statistics logistic regression analysis and a general linear model were used.

RESULTS: According to 442 valid answers, 217 adults practiced physical exercise (PE) frequently (fPE, 3-5 times/every day) while 120 did it less regularly (1-2 times/week), and 105 did not exercise/practiced irregularly (controls). Restriction-related stressors were most challenging, resulting in AO in 29% (n = 128) of the sample. The main predictors were additional stressors (p = 0.005) and anxiety symptoms (p < 0.001). The prevalence of AO was lower (p = 0.018) in the fPE group when compared to controls. KSQ distress symptoms were also lower in fPE (p < 0.0001), while total well-being was increased (p < 0.001) after adjusting for sex, age, and number of chronic diseases. According to the PHS-WB, both physical and mental well-being were higher (p = 0.003 and p = 0.004, respectively) in fPE.

CONCLUSIONS: Frequent moderate exercise is associated with better mental and physical well-being and a lower prevalence of AO.

PMID:33691321 | DOI:10.1159/000514331

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Treatment of Essential Thrombocythemia with Anagrelide Is Associated with an Increased Risk of Worsened Kidney Function

Pharmacology. 2021 Mar 10:1-7. doi: 10.1159/000513377. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: When choosing a cytoreduction method for patients suffering from essential thrombocythemia (ET), it is important to know the safety profile of the medicine used. Few articles have been published about the effects of hydroxycarbamide (hydroxyurea, HU) and anagrelide (ANA) on renal function in ET patients. This study is the largest analysis of nephrotoxicity of cytoreductive drugs used in ET therapy so far, which additionally includes risk factors for the progression of kidney disease and coexisting genetic mutation.

EXPERIMENTAL APPROACH: The retrospective study included 310 patients diagnosed with ET. Demographic data, comorbidities, Cr, and estimated glomerular filtration rate (eGFR) were all taken into account prior to diagnosis and after 6 months of HU and ANA treatment.

KEY RESULTS: A statistically significant difference was found between Cr and eGFR levels at baseline and after 6 months of treatment (p < 0.001). The applied treatment (HU and ANA) had the greatest impact on kidney function. ANA significantly increased the risk of worsening renal function in contrary to hydroxycarbamide after 6 months of treatment (eGFR change: median +1 mL/min/1.73 m2 [interquartile range (IQR) (-4)-(+7)] in the HU group vss. median -13 mL/min/1.73 m2 [IQR (-18)-(-6)] in the ANA group, odds ratio [OR] 7.92 95% confidence interval [95% CI] [4.17-15.08], p < 0.001). Lowering of eGFR <60 mL/min/1.73 m2 occurred in 31 patients (31.0%) from the ANA group and 10 people (4.8%) treated with HU (p = 0.000). In 1 patient from the ANA group, >50% decrease in eGFR was observed. The chance for an increase in Cr levels was higher in people with pre-existing arterial hypertension (OR 1.92 CI = 95% [1.21-3.05], p = 0.006). Sex, type of mutation found (JAK2 V617F or CALR), and previous renal impairment did not affect renal function after 6 months of treatment. In addition, there was no difference in the efficacy of ET treatment between HU and ANA (p = 0.998).

CONCLUSIONS AND IMPLICATIONS: The observations indicate that ANA should be used in patients with ET with great caution and taking into account the risk of worsened kidney function.

PMID:33691325 | DOI:10.1159/000513377

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Exploring patient satisfaction with hospital foodservice: A Swedish study using the Acute Care Hospital Foodservice Patient Satisfaction Questionnaire

Nutr Diet. 2021 Mar 10. doi: 10.1111/1747-0080.12665. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to explore patient satisfaction with hospital foodservice in the Swedish setting, using a validated instrument, adding this context to the existing body of research.

METHODS: The study was carried out at three hospitals employing cyclic menus and conventional cook-serve foodservice systems with centralised tray assemblies and hot-trolley distributions to the wards for service. Patient satisfaction was explored using a translated version of the validated Acute Care Hospital Foodservice Patient Satisfaction Questionnaire. Groups were compared with Mann-Whitney U-test and Kruskal Wallis test with a set significance level of P < .05.

RESULTS: Questionnaires from 439 patients were included in the analysis. The majority (80%) reported an overall satisfaction of “good” or “very good.” Questions related to Staff and Service received mostly the highest possible ratings, while questions related to Food Quality and Meal Size had slightly lower ratings and higher variation. Comparisons between groups showed that differences were small even when statistically significant. Low appetite and a long hospital stay had an adverse effect on overall satisfaction and food quality-related questions. Men and younger patients reported more often being hungry after and between meals.

CONCLUSIONS: Hospital foodservice faces the challenge of catering to multiple patient needs. Monitoring patient satisfaction is crucial to ensure that foodservice operations remain evidence based. The Acute Care Hospital Foodservice Patient Satisfaction Questionnaire provided a general overview that indicated foodservice areas with potential for improvement, although patient satisfaction overall was high. However, patient satisfaction is a complex measure and reflexivity is required when interpreting empirical results.

PMID:33691342 | DOI:10.1111/1747-0080.12665

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Optimization of Microbial Rennet Encapsulation in Alginate – Chitosan Nanoparticles

Food Chem. 2021 Feb 19;352:129325. doi: 10.1016/j.foodchem.2021.129325. Online ahead of print.

ABSTRACT

The milk-coagulating enzyme, rennet, is widely used in cheese making. Recently stabilization of rennet, especially in accelerated cheese ripening, has received considerable interest. As we know encapsulation is one of the enzyme immobilization methods, which could increase enzyme stability. In this study, the effects of alginate, chitosan and, CaCl2 on rennet encapsulation were evaluated and optimized using RSM. Under the optimal conditions alginate, chitosan, and CaCl2 were 0.04%, 0.1%, and 0.1% respectively. At the optimum point, encapsulation efficiency, particle size, and zeta potential were evaluated to be 61.8%, 323 nm, and 25 mV, respectively. The effect of temperature and pH on the enzyme activity was evaluated, and the results showed that encapsulated enzyme had higher activity at various pH and temperature in comparison with the free enzyme. Also, the enzyme release data in all pH values were fitted to Korsmeyer-Peppas model and the n exponent indicated that the release mechanism was Fickian. The electrostatic interactions between enzyme, alginate, and chitosan were confirmed by infrared spectroscopy. No statistical difference was found between the Km and Vmax of encapsulated and free enzymes.

PMID:33691212 | DOI:10.1016/j.foodchem.2021.129325

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Democracy, governance, and road safety

Accid Anal Prev. 2021 Mar 7;154:106067. doi: 10.1016/j.aap.2021.106067. Online ahead of print.

ABSTRACT

Countries scoring high on the Democracy Index developed by The Economist Intelligence Unit have fewer traffic fatalities per 100,000 inhabitants than countries scoring low on this index. The statistical relationship between democracy score and fatalities per 100,000 inhabitants is statistically highly significant and robust with respect to control for potentially confounding factors. A similar relationship exists between democracy score and the number of traffic fatalities per 100,000 motor vehicles. The statistical relationship between level of democracy and level of road safety is strong, although the analyses reported in this paper do not justify a causal interpretation of the relationship. Changes over time in government effectiveness (one of the indicators of the World Governance Index developed by the World Bank) are weakly associated with changes in road safety performance.

PMID:33691228 | DOI:10.1016/j.aap.2021.106067

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Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution

EBioMedicine. 2021 Mar 7;65:103262. doi: 10.1016/j.ebiom.2021.103262. Online ahead of print.

ABSTRACT

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has cost lives and economic hardships globally. Various studies have found a number of different factors, such as hyperinflammation and exhausted/suppressed T cell responses to the etiological SARS coronavirus-2 (SARS-CoV-2), being associated with severe COVID-19. However, sieving the causative from associative factors of respiratory dysfunction has remained rudimentary.

METHODS: We postulated that the host responses causative of respiratory dysfunction would track most closely with disease progression and resolution and thus be differentiated from other factors that are statistically associated with but not causative of severe COVID-19. To track the temporal dynamics of the host responses involved, we examined the changes in gene expression in whole blood of 6 severe and 4 non-severe COVID-19 patients across 15 different timepoints spanning the nadir of respiratory function.

FINDINGS: We found that neutrophil activation but not type I interferon signaling transcripts tracked most closely with disease progression and resolution. Moreover, transcripts encoding for protein phosphorylation, particularly the serine-threonine kinases, many of which have known T cell proliferation and activation functions, were increased after and may thus contribute to the upswing of respiratory function. Notably, these associative genes were targeted by dexamethasone, but not methylprednisolone, which is consistent with efficacy outcomes in clinical trials.

INTERPRETATION: Our findings suggest neutrophil activation as a critical factor of respiratory dysfunction in COVID-19. Drugs that target this pathway could be potentially repurposed for the treatment of severe COVID-19.

FUNDING: This study was sponsored in part by a generous gift from The Hour Glass. EEO and JGL are funded by the National Medical Research Council of Singapore, through the Clinician Scientist Awards awarded by the National Research Foundation of Singapore.

PMID:33691247 | DOI:10.1016/j.ebiom.2021.103262