Nevin Manimala

Eur J Pharm Biopharm. 2021 Oct 15:S0939-6411(21)00260-5. doi: 10.1016/j.ejpb.2021.10.005. Online ahead of print.

ABSTRACT

Pharmaceutical nanotechnology research is focused on smart nano-vehicles, which can deliver active pharmaceutical ingredients to enhance their efficacy through any route of administration and in the most varied therapeutical application. The design and development of new nanopharmaceuticals can be very laborious. In recent years, the application of mathematics, statistics and computational tools is emerging as a convenient strategy for this purpose. The application of Quality by Design (QbD) tools has been introduced to guarantee quality for pharmaceutical products and improve translational research from the laboratory bench into applicable therapeutics. In this review, a collection of basic-concept, historical overview and application of QbD in nanomedicine are discussed. A specific focus has been put on Response Surface Methodology and Artificial Neural Network approaches in general terms and their application in the development of nanomedicine to monitor the process parameters obtaining optimized system ensuring its quality profile.

PMID:34662719 | DOI:10.1016/j.ejpb.2021.10.005

Heart Rhythm. 2021 Oct 15:S1547-5271(21)02235-9. doi: 10.1016/j.hrthm.2021.10.008. Online ahead of print.

ABSTRACT

BACKGROUND: Ventricular fibrillation (VF) is characterised by multiple wavelets and rotors. No equation to predict the number of rotors and wavelets observed during fibrillation has been validated in human VF.

OBJECTIVE: We hypothesized a single equation derived from a Markov M/M/∞ birth-death process, could predict the number of rotors and wavelets occurring in human clinical VF.

METHODS: Epicardial induced VF (256-electrodes) recordings obtained from patients undergoing cardiac surgery were studied (n=12 patients, n=62 epochs). Rate constants for phase singularity (PS, which occur at the pivot points of rotors) and wavefront (WF) formation and destruction were derived by fitting distributions to PS and WF inter-formation and lifetimes. These rate-constants were combined in an M/M/∞ governing equation to predict the number of PS and WF in VF episodes. Observed distributions were compared to those predicted by the M/M/∞ equation.

RESULTS: The M/M/∞ equation accurately predicted average PS and WF number and population distribution, demonstrated in all epochs. Self-terminating episodes of VF were distinguished from VF episodes requiring termination by a trend towards slower PS destruction, and slower rates of PS formation, and a slower mixing rate of the VF process, indicated by larger values of the second-largest eigenvalue modulus (SLEM) of the M/M/∞ birth-death matrix. The longest-lasting PS (associated with rotors) had shorter inter-activation time intervals compared to shorter lasting PS lasting <150 ms (∼1 PS rotation in human VF).

CONCLUSIONS: The M/M/∞ equation explains the number of wavelets and rotors observed, supporting a paradigm of VF based on statistical fibrillatory dynamics.

PMID:34662707 | DOI:10.1016/j.hrthm.2021.10.008

Magn Reson Imaging. 2021 Oct 15:S0730-725X(21)00185-5. doi: 10.1016/j.mri.2021.10.018. Online ahead of print.

ABSTRACT

OBJECTIVES: In this study; we aimed to evaluate the efficacy of the 3D-Dixon-Caipirinha-Vibe fat images in detecting intramural fat accumulation (IFA) and contributions of 3D-Dixon-Caipirinha-Vibe in the management of patients with Chron’s disease.

METHODS: Eighty-five patients who had a 3-tesla MR enterography (MRE) with the 3D-Dixon-Caipirinha-Vibe technique were included. Wall thickness, ADC-value, intramural edema, presence/extension of IFA, and contrast-material enhancement of the affected segments were examined. Findings of MRE were compared statistically with clinical, laboratory, endoscopy, and pathological exams.

RESULTS: The presence of IFA was more common in patients with chronic active and chronic inflammation than only active inflammation and normal cases. Patients with IFA had a longer disease duration than patients without IFA. IFA-containing segment lengths of patients with chronic active inflammation and chronic inflammation were found to be longer than those with active inflammation. It was found that patients whose pathology results were reported as active inflammation contained less IFA than patients with chronic inflammation.

CONCLUSIONS: The presence of IFA is strongly related to chronicity. 3D-Dixon-Caipirinha-Vibe is a fast, easy, and useful method for detecting IFA and evaluating Chron’s disease.

PMID:34662701 | DOI:10.1016/j.mri.2021.10.018

Biosystems. 2021 Oct 15:104562. doi: 10.1016/j.biosystems.2021.104562. Online ahead of print.

ABSTRACT

Quantitative modelling of biological systems using Petri net technologies has experienced renaissance in the past couple of decades. The overwhelming majority of these models is deterministic though underlying biological systems are usually at the mesoscopic level and small, rather than large, and employ sparse molecular structure. Sparse biological systems are accompanied by randomness due to low molecular density, intrinsic random nature of phenomena and noise in an experiment. On the other hand, biochemical reactions are inherently uncertain due to imprecision and vagueness of kinetic parameters. Stochastic methods are used to cope with randomness while fuzzy methods are developed to deal with uncertainty of biological systems, but there is lack of common voice among researchers regarding the best choice of modelling approach for a particular biological system. The main issues addressed in this paper are the choice between deterministic, stochastic and fuzzy parameters and aspects; that is, which modelling approach to follow to reach the realistic approximation of an underlying biological system, and how to measure parallels and discrepancies between different quantitative paradigms. To this end, we use Petri nets with hybrid, stochastic and fuzzy parameters to create quantitative model of p16-mediated signalling pathway in higher eukaryotes, perform deterministic, pure stochastic and fuzzy stochastic simulations to predict the behaviour of major molecular regulators of p16-mediated pathway. In the meanwhile, we show how uncertain kinetic parameters can be precisely approximated in terms of α cuts. Then we perform statistical analysis of simulation results to measure similarity between the three modelling approaches. The statistical analysis reveals significant deviations between deterministic, pure stochastic and fuzzy stochastic approaches for most of the biological components. Due to rather small size of underlying biological system, it turns out that fuzzy stochastic approach is the most appropriate for modelling of p16-mediated signalling pathway because it successfully deals with both randomness and uncertainty and produces quantitative results with biological relevance.

PMID:34662677 | DOI:10.1016/j.biosystems.2021.104562

J Ethnopharmacol. 2021 Oct 15:114754. doi: 10.1016/j.jep.2021.114754. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Erigeron canadensis has been used in traditional medicine to treat a variety of respiratory diseases, including acute upper and lower respiratory tract infections and cough-related asthma. There is as yet no relevant experimental or clinical study in the scientific literature evaluating the efficacy of plants in these disorders.

AIM OF THE STUDY: To investigate the active ingredients in Erigeron canadensis, a complex isolated from flowering parts of a plant was tested for airway defense reflexes, in particular for cough reflexes and airway reactivity. Both were experimentally induced by a chemical irritant that simulated the inflammatory conditions of their formation.

MATERIAL AND METHODS: The polyphenolic polysaccharide-protein (PPP) complex was isolated from the flowering parts of Erigeron canadensis by hot alkaline extraction and a multi-stage purification process. The antitussive activity was confirmed as a decrease in the number of citric acid-induced coughs and the bronchodilator effect was verified as a decrease in specific airway resistance (sRaw) in conscious guinea pigs.

RESULTS: The dark brown Erigeron complex with a molecular weight of 38,000 g/mol contained phenolics (13.2% wt%), proteins (16.3% wt%), and uronic acids (6.3% wt%). The neutral carbohydrate part of Erigeron consisted mainly of xylose (12.1 wt%), glucose (13.3 wt%), arabinose (24.1 wt%), and galactose (41.0 wt%) residues. Arabinogalactan and 4-OMe-glucuronoxylan have been found to be the major polysaccharides in the Erigeron complex. Using a method of chemically-induced cough reflex and guinea pigs test system the Erigeron complex exhibited statistically significant, the dose-dependent antitussive activity, which was similar to that of the centrally-acting opioid agonist codeine.

CONCLUSION: Pharmacological tests have revealed a new pharmacodynamic effect of the Erigeron complex, namely an antitussive effect. Its activity was most pronounced in comparison with all previously tested compounds from other medicinal plants and approached the effect of codeine, the most potent antitussive used in clinical practice. The results provide the scientific basis for the application of this herb in traditional medicine.

PMID:34662663 | DOI:10.1016/j.jep.2021.114754

World Neurosurg. 2021 Oct 15:S1878-8750(21)01599-0. doi: 10.1016/j.wneu.2021.10.102. Online ahead of print.

ABSTRACT

BACKGROUND: There were few literature reports on the use of perioperative parameters to predict the risk of albumin transfusion after spinal tuberculosis surgery based on the application of nomogram and propensity score matching (PSM) analysis.

PURPOSE: The purpose was to predict the risk of albumin transfusion after spinal tuberculosis surgery based on a combination of PSM and nomogram.

METHODS: The clinical data of the patients were collected in our hospital, including preoperative clinical data, preoperative laboratory tests, and postoperative clinical data. All data were divided into two groups, including the albumin transfusion group and the non-albumin transfusion group. The PSM analysis was used to adjust the baseline data of the two groups. The nomogram was further constructed. The practicability and predictive ability of the model were evaluated.

RESULTS: A total of 494 cases were collected in this article. 102 pairs by PSM analysis were used to construct the nomogram. There were statistical differences in surgical approach, aspartate aminotransferase (AST)/ alanine aminotransferase (ALT), drainage, and kyphosis by logistic analysis, and these parameters were included in the construction of the nomogram. the C-index of the prediction model was 0.734. The area under the curve (AUC) was 0.73 and the net benefit was between 0.13 and 0.99. The calculated C-index was 0.71 by the internal verification method.

CONCLUSION: The PSM analysis had a good matching effect and the nomogram had a good predictive ability. Surgical approach, AST/ ALT, drainage, and kyphosis might be predictors of albumin transfusion after spinal tuberculosis surgery.

PMID:34662656 | DOI:10.1016/j.wneu.2021.10.102

J Oral Maxillofac Surg. 2021 Sep 21:S0278-2391(21)01125-3. doi: 10.1016/j.joms.2021.09.015. Online ahead of print.

ABSTRACT

PURPOSE: Since its implementation, TMJ arthrocentesis can be performed with cannulas of different diameters. The aim of this study was to determine the differences in cannula diameter for temporomandibular joint (TMJ) arthrocentesis on intraoperative and postoperative parameters.

METHODS: A prospective randomized clinical study was conducted using the documentation of Wilkes stage 3 patients with TMJ disorders. Patients were assigned to 2 groups using a system of computer-assisted randomization. Double puncure arthrocentesis (DPA) was performed with 21-gauge cannulas (group 1) and 18-gauge cannulas (group 2). The primary predictor variable was cannula diameter. Pain values assessed using a Likert-type (0 to10) visual analog scale (VAS) were selected as primary outcome variable. Mandibular movements including maximum mouth opening (MMO), lateral excursions (LE) and protrusion (P), were selected as secondary outcomes. Mandibular movements and pain values were recorded before treatment and at 1st day and 3rd months intervals. Descriptive, comparative, and bivariate analyses were conducted. Intraoperative complications were also recorded.

RESULTS: DPA was applied to 33 patients (29 females, 4 males). Although group 1 was found to be significantly more advantageous than group 2 in terms of pain levels (P < .05), no statistically significant difference was discovered in terms of total complication numbers and mandibular movements at the follow-up periods (P >.05).

CONCLUSIONS: Despite the limited sample size cannula thickness affects postoperative pain level significantly in conventional TMJ arthrocentesis.

PMID:34662553 | DOI:10.1016/j.joms.2021.09.015

J Pediatr (Rio J). 2021 Oct 15:S0021-7557(21)00135-2. doi: 10.1016/j.jped.2021.08.005. Online ahead of print.

ABSTRACT

OBJECTIVES: The objective of this meta-analysis is to evaluate the diagnostic value of serum Cystatin C in acute kidney injury (AKI) in neonates.

SOURCES: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang Database were searched to retrieve the literature related to the diagnostic value of Cystatin C for neonatal AKI from inception to May 10, 2021. Subsequently, the quality of included studies was determined using the QUADAS-2 tool. Stata 15.0 statistical software was used to calculate the combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Additionally, meta-regression analysis and subgroup analysis contributed to explore the sources of heterogeneity.

SUMMARY OF THE FINDINGS: Twelve articles were included. The pooled sensitivity was 0.84 (95%CI: 0.74-0.91), the pooled specificity was 0.81 (95%CI: 0.75-0.86), the pooled PLR was 4.39 (95%CI: 3.23-5.97), the pooled NLR was 0.19 (95%CI: 0.11-0.34), and the DOR was 22.58 (95%CI: 10.44-48.83). The area under the receiver operating characteristic curve (AUC) was 0.88 (95%CI: 0.85-0.90). And no significant publication bias was identified (p > 0.05).

CONCLUSIONS: Serum Cystatin C has a good performance in predicting neonatal AKI; therefore, it can be used as a candidate biomarker after the optimal level is determined by large prospective studies.

PMID:34662539 | DOI:10.1016/j.jped.2021.08.005

J Matern Fetal Neonatal Med. 2021 Oct 18:1-6. doi: 10.1080/14767058.2021.1988071. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperlipidemia is a precursor of inflammation and oxidative stress and suggested to be associated with adverse pregnancy outcomes such as preterm delivery. This study evaluated the association between maternal hyperlipidemia and spontaneous preterm delivery.

METHODS: This was a prospective, multicentre cohort study in which 239 pregnant women aged 20-35 years with singleton pregnancy, were consecutively recruited at estimated gestational ages of 14-18weeks. Maternal serum lipids were determined at recruitment over a 2-month period and they were followed up until 37 weeks for the subsequent 6 months. Pregnant women with medical conditions and medications that could alter serum lipid levels were excluded from the study. Demographic and baseline variables were summarized using descriptive statistics. Comparison of continuous variables was done using the student’s t-test and categorical variables were compared using the Chi square or Fisher’s exact test as appropriate. Correlation was determined using Pearson’s correlation. Odd ratios were calculated at 95% confidence interval, width of CI as 10% (0.1) and all significances are reported at p < .05.

FINDINGS: The prevalence of spontaneous preterm delivery and maternal hypercholesterolemia was 10.2% and 33.1% respectively. There was no significant association between spontaneous preterm delivery and hyperlipidemia in pregnancy (p = .102). Mean serum total cholesterol (mmol/L), LDL cholesterol (mmol/L), HDL cholesterol (mmol/L) and triglyceride (mmol/L) was 5.31 ± 0.84, 2.60 ± 0.72, 1.64 ± 0.36 and 1.23 ± 0.40 respectively in women with spontaneous preterm delivery was similar to mean values of 5.23 ± 0.98, 2.54 ± 0.82, 1.64 ± 0.49 and 1.30 ± 0.59 respectively in women with term delivery. There was no significant correlation between mean individual serum lipids, determined at 14-18weeks gestational age, and gestational age at delivery.

CONCLUSION: Serum lipid values determined early in pregnancy were observed to be similar in women with preterm and term delivery. There was no association between hyperlipidemia and spontaneous preterm delivery. There was no correlation of individual mean lipid values, determined early in pregnancy, and gestational age at delivery.

PMID:34662530 | DOI:10.1080/14767058.2021.1988071

Clin Otolaryngol. 2021 Oct 18. doi: 10.1111/coa.13878. Online ahead of print.

ABSTRACT

OBJECTIVE: Assess long-term outcomes of ALA-PDT in treating recalcitrant laryngeal leukoplakia.

STUDY DESIGN: Retrospective Case-Control.

METHODS: We reviewed all laryngeal leukoplakia patients treated with ALA-PDT compared with angiolytic laser treatment alone (585nm PDL or 532nm KTP laser) from 2000 to 2019. Patients with laryngeal cancer (or a history of laryngeal cancer), leukoplakia previously treated with radiation and no pathologic report were excluded. Patient demographics, procedure details, and outcomes were examined including histopathologic diagnosis, procedures performed, ALA usage, recurrence of leukoplakia, and the development of cancer.

RESULTS: We identified 132 patients with laryngeal leukoplakia: 42 were treated with ALA-PDT and 90 were treated with an angiolytic laser alone (Laser group). The proportion of cases of high-grade dysplasia was 57.1% in the ALA-PDT group compared to 32.2% in the Laser group. In high-grade dysplasia cases, there was a statistically significant better recurrence-free survival (RFS) at 12 months and 60 months in those who underwent ALA-PDT 71.4% and 7.1% vs Laser 25% and 0% (P=0.01). However, for overall group there was no difference in RFS (P=0.25). Voice outcomes (Patient subjective report) improved or were stable in 75% of subjects with no serious side effects reported.

CONCLUSION: ALA-PDT for recalcitrant and high-grade dysplasia is highly effective with improved recurrence-free survival compared to laser alone. ALA-PDT may be an appropriate therapy in patients who have failed prior angiolytic laser alone.

PMID:34662496 | DOI:10.1111/coa.13878