scholarly journals Structure–Activity Prediction of ACE Inhibitory/Bitter Dipeptides—A Chemometric Approach Based on Stepwise Regression

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 950 ◽  
Author(s):  
Monika Hrynkiewicz ◽  
Anna Iwaniak ◽  
Justyna Bucholska ◽  
Piotr Minkiewicz ◽  
Małgorzata Darewicz
Keyword(s):  
Stepwise Regression ◽  
Statistical Significance ◽  
Ace Inhibition ◽  
Dual Function ◽  
Activity Prediction ◽  
Bitter Peptides ◽  
Bioactivity Prediction ◽  
Chemometric Approach ◽  
The Impact ◽  
Ace Inhibitory

Forward and backward stepwise regression (FR and BR, respectively) was applied for the structure–bioactivity prediction of angiotensin converting enzyme (ACE)-inhibitory/bitter-tasting dipeptides. The datasets used in this study consisted of 28 sequences and numerical variables reflecting dipeptides’ physicochemical nature. The data were acquired from the BIOPEP-UWM, Biological Magnetic Resonance Databank, ProtScale, and AAindex databases. The calculations were computed using STATISTICA®13.1. FR/BR models differed in R2 (0.91/0.76, respectively). The impact of C-atC(−) and N-Molw(+) on the dual function of dipeptides was observed. Positive (+) and negative (−) correlations with log IC50 are presented in parens. Moreover, C-Bur(+), N-atH(+), and N-Pol(−) were also found to be important in the FR model. The additional statistical significance of N-bul(−), N-Bur(−), and N-Hdr(+) was reported in the BR model. These attributes reflected the composition of the dipeptides. We report that the “ideal” bitter ACE inhibitor should be composed of P, Y, F (C-end) and G, V, I, L (N-end). Functions: log Rcaf. = f (observed log IC50) and log Rcaf. = f (predicted log IC50) revealed no direct relationships between ACE inhibition and the bitterness of the dipeptides. It probably resulted from some structural discrepancies between the ACE inhibitory/bitter peptides and/or the measure of activity describing one of the two bioactivities. Our protocol can be applicable for the structure–bioactivity prediction of other bioactivities peptides.

Effect of simulated gastrointestinal digestion on the antihypertensive properties of synthetic β-lactoglobulin peptide sequences

2007 ◽  
Vol 74 (3) ◽  
pp. 336-339 ◽  
Author(s):  
Blanca Hernández-Ledesma ◽  
Marta Miguel ◽  
Lourdes Amigo ◽  
Maria Amaya Aleixandre ◽  
Isidra Recio
Keyword(s):  
Inhibitory Activity ◽  
Ace Inhibition ◽  
Antihypertensive Activity ◽  
Gastrointestinal Digestion ◽  
Ace Inhibitory Activity ◽  
Simulated Gastrointestinal Digestion ◽  
The Impact ◽  
Β Lactoglobulin ◽  
Ace Inhibitory

In this study, the antihypertensive activity in spontaneously hypertensive rats of two peptides isolated from β-lactoglobulin hydrolysates with thermolysin was evaluated. These peptides, with sequences LLF [β-lg f(103–105)] and LQKW [β-lg f(58–61)], showed potent in vitro ACE-inhibitory activity. Two hours after administration, both sequences caused a clear and significant decrease in the blood pressure of these rats. The impact of a simulated gastrointestinal digestion on ACE-inhibitory and antihypertensive activities of these peptides was also studied. The results showed that both fragments were susceptible to proteolytic degradation after incubation with pepsin and Corolase PP®. In addition, their in vitro ACE-inhibitory activity decreased after the simulated digestion. It is likely that fragment LQK was the active end product of the gastrointestinal digestion of peptide LQKW. The fragment LL, observed after digestion of peptide LLF, probably exert its antihypertensive effect through a mechanism of action different than ACE-inhibition.

Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

2012 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Donald E Cutlip ◽  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Statistical Significance ◽  
Bare Metal Stents ◽  
Coronary Intervention ◽  
Metal Stents ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Patients With Diabetes ◽  
The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

Dietary Patterns: A New Therapeutic Approach for Depression?

2019 ◽  
Vol 20 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Mariana Jesus ◽  
Tânia Silva ◽  
César Cagigal ◽  
Vera Martins ◽  
Carla Silva
Keyword(s):  
Depressive Symptoms ◽  
Dietary Patterns ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Dietary Intervention ◽  
Common Mental Disorder ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Inverse Association ◽  
The Impact

Introduction: The field of nutritional psychiatry is a fast-growing one. Although initially, it focused on the effects of vitamins and micronutrients in mental health, in the last decade, its focus also extended to the dietary patterns. The possibility of a dietary cost-effective intervention in the most common mental disorder, depression, cannot be overlooked due to its potential large-scale impact. Method: A classic review of the literature was conducted, and studies published between 2010 and 2018 focusing on the impact of dietary patterns in depression and depressive symptoms were included. Results: We found 10 studies that matched our criteria. Most studies showed an inverse association between healthy dietary patterns, rich in fruits, vegetables, lean meats, nuts and whole grains, and with low intake of processed and sugary foods, and depression and depressive symptoms throughout an array of age groups, although some authors reported statistical significance only in women. While most studies were of cross-sectional design, making it difficult to infer causality, a randomized controlled trial presented similar results. Discussion: he association between dietary patterns and depression is now well-established, although the exact etiological pathways are still unknown. Dietary intervention, with the implementation of healthier dietary patterns, closer to the traditional ones, can play an important role in the prevention and adjunctive therapy of depression and depressive symptoms. Conclusion: More large-scale randomized clinical trials need to be conducted, in order to confirm the association between high-quality dietary patterns and lower risk of depression and depressive symptoms.

Do we Need Maintenance Chemotherapy in Advanced NSCLC in the Era of Immune and Targeted Therapy?

2019 ◽  
Vol 15 (1) ◽  
pp. 50-55
Author(s):  
Ahmed Nagy ◽  
Omar Abdel Rahman ◽  
Heba Abdullah ◽  
Ahmed Negida
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Statistical Significance ◽  
Small Cell ◽  
Maintenance Chemotherapy ◽  
Small Cell Lung ◽  
The Impact

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

scholarly journals Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count

2013 ◽  
Vol 88 (4) ◽  
pp. 570-577 ◽  
Author(s):  
Flávia Machado Gonçalves Soares ◽  
Izelda Maria Carvalho Costa
Keyword(s):  
Viral Load ◽  
Disease Progression ◽  
Statistical Significance ◽  
Undetectable Viral Load ◽  
Fat Distribution ◽  
Cd4 Count ◽  
Before And After ◽  
Facial Lipoatrophy ◽  
A Prospective Study ◽  
The Impact

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome.OBJECTIVES:To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count.METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment.RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02.CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

scholarly journals Does Social Support Affect the Health of the Elderly in Rural China? A Meta-Analysis Approach

2019 ◽  
Vol 16 (18) ◽  
pp. 3471 ◽  
Author(s):  
Natuya Zhuori ◽  
Yu Cai ◽  
Yan Yan ◽  
Yu Cui ◽  
Minjuan Zhao
Keyword(s):  
Social Support ◽  
Rural Areas ◽  
Rural China ◽  
Statistical Significance ◽  
Empirical Studies ◽  
Relevant Literature ◽  
The Elderly ◽  
Significant Difference ◽  
Meta Regression ◽  
The Impact

As the trend of aging in rural China has intensified, research on the factors affecting the health of the elderly in rural areas has become a hot issue. However, the conclusions of existing studies are inconsistent and even contradictory, making it difficult to form constructive policies with practical value. To explore the reasons for the inconsistent conclusions drawn by relevant research, in this paper we constructed a meta-regression database based on 65 pieces of relevant literature published in the past 25 years. For more valid samples to reduce publication bias, we also set the statistical significance of social support to the health of the elderly in rural areas as a dependent variable. Finally, combined with multi-dimensional social support and its implications for the health of the elderly, meta-regression analysis was carried out on the results of 171 empirical studies. The results show that (1) subjective support rather than objective support can have a significant impact on the health of the elderly in rural areas, and there is no significant difference between other dimensions of social support and objective support; (2) the health status of the elderly in rural areas in samples involving western regions is more sensitive to social support than that in samples not involving the western regions; (3) among the elderly in rural areas, social support for the older male elderly is more likely to improve their health than that for the younger female elderly; and (4) besides this, both data sources and econometric models greatly affect the heterogeneity of the effect of social support on the health of the elderly in rural areas, but neither the published year nor the journal is significant. Finally, relevant policies and follow-up studies on the impact of social support on the health of the elderly in rural areas are discussed.

33 An Evidence Based Laser Therapy Algorithm for the Treatment of Burn Scars

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S26-S27
Author(s):  
Rajiv Sood
Keyword(s):  
Laser Treatment ◽  
Laser Therapy ◽  
Co2 Laser ◽  
Statistical Significance ◽  
Evidence Based ◽  
Baseline Measurement ◽  
Burn Scar ◽  
Therapy Algorithm ◽  
Laser Treatments ◽  
The Impact

Abstract Introduction Hypertrophic scarring after burn injury can be extremely painful, cause profound itching, and affect the way patients view themselves and how the outside world perceives them. We have utilized laser therapy as a modality for scar modulation for our patients since 2013. In 2014, we initiated and completed a prospective IRB approved study to evaluate the outcome of scars treated with fractional CO2 laser therapy (FLT) utilizing objective and subjective tools. Recently, we have completed a prospective study evaluating the use of pulse dye laser (PDL) therapy and the impact on post-burn pruritis. In reviewing the outcomes from these two studies, we have developed an evidence-based laser therapy algorithm for burn scar management. Methods The FLT study entailed a series of three CO2 laser treatments minimally 4–6 weeks apart with scar measurements and POSAS form completion performed prior to each laser treatment and four weeks after the last FLT. Scar measurements that included color, pliability, and scar thickness; and completion of the POSAS form were obtained prior to each laser therapy session and four weeks after the third laser treatment. The measurements of color, pliability, and scar thickness were measured with the Colorimeter, Cutometer, and ultrasound. The PDL study utilized the 5-D Itch scale to evaluate post-burn pruritis. A baseline measurement was obtained prior to any laser treatments. Each patient underwent two PDL sessions and a 5-D itch scale was completed four to six weeks after the second PDL session. The baseline measurement was then compared to the final 5-D itch scale measurement. Results Data from the FLT study is in Table 1 and shows that there were statistically significant improvements in the Patient and Observer POSAS scores, patient rated Itch score, scar thickness, and measured skin density. Changes to patient rated scar pain, scar color, and pliability were noted but were not of statistical significance. Data from the PDL study is in Table 2 and shows a statistically significant decrease in the treated patients’ post-burn pruritis. Conclusions In reviewing the outcomes of these two studies, we have developed an algorithm based on our studies. All of our patients undergoing laser therapy receive two PDL sessions that are four to six weeks apart followed by 3 FLT sessions. The use of both PDL and FLT decreases post-burn pruritis, decreases scar thickness, decreases pain, and increases patient satisfaction as shown in our research.

CD34 immunostain increases sensitivity of the diagnosis of fetal vascular malperfusion in placentas from ex-utero intrapartum treatment

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jerzy Stanek
Keyword(s):  
Statistical Significance ◽  
Treatment Procedure ◽  
Fetal Survival ◽  
Ex Utero Intrapartum Treatment ◽  
Life Threatening ◽  
Group 2 ◽  
Cd34 Immunostain ◽  
The Impact ◽  
Diaphragmatic Hernias ◽  
Group 1

AbstractShort CommunicationsEXIT (ex-utero intrapartum treatment) procedure is a fetal survival-increasing modification of cesarean section. Previously we found an increase incidence of fetal vascular malperfusion (FVM) in placentas from EXIT procedures which indicates the underlying stasis of fetal blood flow in such cases. This retrospective analysis analyzes the impact of the recently introduced CD34 immunostain for the FVM diagnosis in placentas from EXIT procedures.Objectives and MethodsA total of 105 placentas from EXIT procedures (48 to airway, 43 to ECMO and 14 to resection) were studied. In 73 older cases, the placental histological diagnosis of segmental FVM was made on H&E stained placental sections only (segmental villous avascularity) (Group 1), while in 32 most recent cases, the CD34 component of a double E-cadherin/CD34 immunostain slides was also routinely used to detect the early FVM (endothelial fragmentation, villous hypovascularity) (Group 2). 23 clinical and 47 independent placental phenotypes were compared by χ2 or ANOVA, where appropriate.ResultsThere was no statistical significance between the groups in rates of segmental villous avascularity (29 vs. 34%), but performing CD34 immunostain resulted in adding and/or upgrading 12 more cases of segmental FVM in Group 2, thus increasing the sensitivity of placental examination for FVM by 37%. There were no other statistically significantly differences in clinical (except for congenital diaphragmatic hernias statistically significantly more common in Group 2, 34 vs 56%, p=0.03) and placental phenotypes, proving the otherwise comparability of the groups.ConclusionsThe use of CD34 immunostain increases the sensitivity of placental examination for FVM by 1/3, which may improve the neonatal management by revealing the increased likelihood of the potentially life-threatening neonatal complications.

scholarly journals Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Neemat M. Kassem ◽  
Gamal Emera ◽  
Hebatallah A. Kassem ◽  
Nashwa Medhat ◽  
Basant Nagdy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Human Cancer ◽  
Statistical Significance ◽  
Public Health Problem ◽  
World Health ◽  
Cpg Island Methylator Phenotype ◽  
Number Of Patients ◽  
The Impact

Abstract Background Colorectal cancer (CRC) is the third most common cause of cancer-related deaths which contributes to a significant public health problem worldwide with 1.8 million new cases and almost 861,000 deaths in 2018 according to the World Health Organization. It exhibits 7.4% of all diagnosed cancer cases in the region of the Middle East and North Africa. Molecular changes that happen in CRCs are chromosomal instability, microsatellite instability (MSI), and CpG island methylator phenotype. The human RAS family (KRAS, NRAS, and HRAS) is the most frequently mutated oncogenes in human cancer appearing in 45% of colon cancers. Determining MSI status across CRCs offers the opportunity to identify patients who are likely to respond to targeted therapies such as anti-PD-1. Therefore, a method to efficiently determine MSI status for every cancer patient is needed. Results KRAS mutations were detected in 31.6% of CRC patients, namely in older patients (p = 0.003). Codons 12 and 13 constituted 5/6 (83.3%) and 1/6 (16.7%) of all KRAS mutations, respectively. We found three mutations G12D, G12C, and G13D which occur as a result of substitution at c.35G>A, c.34G>T, and c.38G>A and have been detected in 4/6 (66.6%), 1/6 (16.7%), and 1/6 (16.7%) patients, respectively. Eleven (57.9%) patients had microsatellite instability-high (MSI-H) CRC. A higher percentage of MSI-H CRC was detected in female patients (p = 0.048). Eight patients had both MSI-H CRC and wild KRAS mutation with no statistical significance was found between MSI status and KRAS mutation in these studied patients. Conclusion In conclusion, considering that KRAS mutations confer resistance to EGFR inhibitors, patients who have CRC with KRAS mutation could receive more tailored management by defining MSI status. MSI-high patients have enhanced responsiveness to anti-PD-1 therapies. Thus, the question arises as to whether it is worth investigating this association in the routine clinical setting or not. Further studies with a larger number of patients are needed to assess the impact of MSI status on Egyptian CRC care.

Impact of Hybrid Operating Rooms on Long-Term Clinical Outcomes Following Fenestrated and Branched Endovascular Aortic Repair

2021 ◽  
pp. 152660282199672
Author(s):  
Giovanni Tinelli ◽  
Marie Bonnet ◽  
Adrien Hertault ◽  
Simona Sica ◽  
Gian Luca Di Tanna ◽  
...  
Keyword(s):  
Operating Room ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Statistical Significance ◽  
Aortic Aneurysms ◽  
Study Patient ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
The Impact

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.

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