Significance of the Wnt signaling pathway in coronary artery atherosclerosis.

Introduction: The progression of coronary atherosclerosis is an active and regulated process. The Wnt signaling pathway is thought to play an active role in the pathogenesis of several cardiovascular diseases; however, a better understanding of this system in atherosclerosis is yet to be unraveled. Methods: In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were used to quantify the expression of Wnt3a, Wnt5a, and Wnt5b in the human coronary plaque, and immunohistochemistry was used to identify sites of local expression. To determine the pathologic significance of increased Wnt, human vascular smooth muscle cells (vSMCs) were treated with Wnt3a, Wnt5a, and Wnt5b recombinant proteins and assessed for changes in cell differentiation and function. Results: RT-PCR and Western blotting showed a significant increase in the expression of Wnt3a, Wnt5a, Wnt5b, and their receptors in diseased coronary arteries compared with that in non-diseased coronary arteries. Immunohistochemistry revealed an abundant expression of Wnt3a and Wnt5b in diseased coronary arteries, which contrasted with little or no signals in normal coronary arteries. Immunostaining of Wnt3a and Wnt5b was found largely in inflammatory cells and myointimal cells. The treatment of vSMCs with Wnt3a, Wnt5a, and Wnt5b resulted in increased vSMC differentiation, migration, calcification, oxidative stress, and impaired cholesterol handling. Conclusions: This study demonstrates the upregulation of three important members of canonical and non-canonical Wnt signaling pathways and their receptors in coronary atherosclerosis and shows an important role for these molecules in plaque development through increased cellular remodeling and impaired cholesterol handling.

The Efficiency of Serum Biomarkers in Predicting the Clinical Outcome of Patients with Mesenteric Ischemia during Follow-Up: A Systematic Review.

The initial clinical manifestation of acute mesenteric ischemia poses a diagnostic challenge, often leading to delays in identification and subsequent surgical intervention, contributing to adverse outcomes. Serum biomarkers, offering insights into the underlying pathophysiology, hold promise as prognostic indicators for acute mesenteric ischemia. This systematic review comprehensively explores the role of blood biomarkers in predicting clinical outcomes during follow-up for patients with mesenteric ischemia. A thorough literature search across the PubMed, Cochrane Library, and EMBASE databases yielded 33 relevant publications investigating the efficacy of serum biomarkers in predicting outcomes for mesenteric ischemia. Numerous studies underscore the utility of blood biomarkers in swiftly and accurately differentiating between causes of mesenteric ischemia, facilitating a prompt diagnosis. Elevated levels of specific biomarkers, particularly D-dimers, consistently correlate with heightened mortality risk and poorer clinical outcomes. While certain serum indicators exhibit substantial potential in associating with mesenteric ischemia, further research through rigorous human trials is imperative to enhance their consistent predictive ability during the follow-up period. This study underscores the diagnostic and prognostic significance of specific biomarkers for mesenteric ischemia, emphasizing the necessity for standardized procedures in future investigations.

Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives.

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between -1.25 and -0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.

Coping Strategies and Inflammatory Bowel Disease: A Narrative Review.

Background: Coping strategies play a crucial role in managing inflammatory bowel disease (IBD), influencing both health-related quality of life (HRQoL) and psychological well-being. This study systematically reviews the available literature to analyze coping mechanisms in IBD populations and their impact. Methods: Relevant English-language studies published until 2023 were identified through a comprehensive search of PubMed, EMBASE, EBSCOhost, and Cochrane Library. After applying inclusion and exclusion criteria, 57 articles underwent full analysis. Results: The findings highlight the diversity of coping strategies used by individuals with IBD and emphasize the need for a nuanced approach considering factors like disease severity, duration, and individual characteristics. This review underlines the influence of coping mechanisms on QoL and indicates their potential to aid IBD management and rehabilitation. Conclusions: This study underscores the value of investigating coping strategies to promote better outcomes for individuals with IBD. Future research should explore personalized interventions that address the heterogeneity of the IBD population.

Unlocking protein-based biomarker potential for graft-versus-host disease following allogenic hematopoietic stem cell transplants.

Despite the numerous advantages of allogeneic hematopoietic stem cell transplants (allo-HSCT), there exists a notable association with risks, particularly during the preconditioning period and predominantly post-intervention, exemplified by the occurrence of graft-versus-host disease (GVHD). Risk stratification prior to symptom manifestation, along with precise diagnosis and prognosis, relies heavily on clinical features. A critical imperative is the development of tools capable of early identification and effective management of patients undergoing allo-HSCT. A promising avenue in this pursuit is the utilization of proteomics-based biomarkers obtained from non-invasive biospecimens. This review comprehensively outlines the application of proteomics and proteomics-based biomarkers in GVHD patients. It delves into both single protein markers and protein panels, offering insights into their relevance in acute and chronic GVHD. Furthermore, the review provides a detailed examination of the site-specific involvement of GVHD. In summary, this article explores the potential of proteomics as a tool for timely and accurate intervention in the context of GVHD following allo-HSCT.

Herbal Remedies for Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Constipation-predominant irritable bowel syndrome (IBS-C) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Conventional treatments for IBS-C often provide limited efficiency, leading to an increasing interest in exploring herbal remedies. This systematic review aims to evaluate the efficacy and safety of herbal remedies in the management of IBS-C. MATERIALS AND METHODS: A comprehensive search of PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library was conducted to identify relevant studies published up to July 2023 and data extraction was performed independently by two reviewers. RESULTS: Overall, the included studies demonstrated some evidence of the beneficial effects of herbal remedies on IBS-C symptoms, including improvements in bowel frequency, stool consistency, abdominal pain, and quality of life. However, the heterogeneity of the interventions and outcome measures limited the ability to perform a meta-analysis. CONCLUSION: This systematic review suggests that herbal remedies may have potential benefits in the management of IBS-C. However, the quality of evidence is limited, and further well-designed, large-scale RCTs are needed to establish the efficacy and safety of specific herbal remedies for IBS-C. Clinicians should exercise caution when recommending herbal remedies and consider individual patient characteristics and preferences.

The Effect of Polyphenols, Minerals, Fibers, and Fruits on Irritable Bowel Syndrome: A Systematic Review.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, bloating, and changes in bowel habits. Various dietary factors have been implicated in the pathogenesis and management of IBS symptoms. This systematic review aims to evaluate the effects of polyphenols, minerals, fibers, and fruits on the symptoms and overall well-being of individuals with IBS. MATERIALS AND METHODS: A comprehensive literature search was conducted in several electronic databases, including PubMed, Scopus, and Web of Science. Studies published up until July 2023 were included. RESULTS: The selected studies varied in terms of study design, participant characteristics, intervention duration, and outcome measures. Overall, the findings suggest that dietary interventions involving polyphenols, minerals, fibers, and fruits can have a positive impact on IBS symptoms. Dietary fiber supplementation, particularly soluble fiber, has been associated with reduced bloating and enhanced stool consistency. CONCLUSIONS: This systematic review provides evidence supporting the beneficial effects of polyphenols, minerals, fibers, and fruits in IBS patients. These dietary components hold promise as complementary approaches for managing IBS symptoms. However, due to the heterogeneity of the included studies and the limited number of high-quality randomized controlled trials, further well-designed trials are warranted to establish the optimal dosages, duration, and long-term effects of these interventions. Understanding the role of specific dietary components in IBS management may pave the way for personalized dietary recommendations and improve the quality of life for individuals suffering from this complex disorder.

Intimate Compromise: Reproduction, Piety, and Medicine Among American Orthodox Christians.

Drawing on ethnographic findings from an American Orthodox Christian community, I examine how forms of intimate reproductive compromise facilitate the assertive refusal to negotiate on abortion. The American Orthodox harness the values and practices of biomedicine to validate their refusal of abortion, but their inflexible views emerge from prior compromises. By not giving up modern contraception, women self-fashion forms of piety that allow them to navigate composite identities while remaining dedicated to a pro-life stance. That steadfast refusal of abortion may be the consequence of previous concessions opens up new ways of theorizing refusal as inextricably bound to - rather than exclusive of - prior compromises.

Diagnosis of Liver Fibrosis Using Artificial Intelligence: A Systematic Review.

Background and Objectives: The development of liver fibrosis as a consequence of continuous inflammation represents a turning point in the evolution of chronic liver diseases. The recent developments of artificial intelligence (AI) applications show a high potential for improving the accuracy of diagnosis, involving large sets of clinical data. For this reason, the aim of this systematic review is to provide a comprehensive overview of current AI applications and analyze the accuracy of these systems to perform an automated diagnosis of liver fibrosis. Materials and Methods: We searched PubMed, Cochrane Library, EMBASE, and WILEY databases using predefined keywords. Articles were screened for relevant publications about AI applications capable of diagnosing liver fibrosis. Exclusion criteria were animal studies, case reports, abstracts, letters to the editor, conference presentations, pediatric studies, studies written in languages other than English, and editorials. Results: Our search identified a total of 24 articles analyzing the automated imagistic diagnosis of liver fibrosis, out of which six studies analyze liver ultrasound images, seven studies analyze computer tomography images, five studies analyze magnetic resonance images, and six studies analyze liver biopsies. The studies included in our systematic review showed that AI-assisted non-invasive techniques performed as accurately as human experts in detecting and staging liver fibrosis. Nevertheless, the findings of these studies need to be confirmed through clinical trials to be implemented into clinical practice. Conclusions: The current systematic review provides a comprehensive analysis of the performance of AI systems in diagnosing liver fibrosis. Automatic diagnosis, staging, and risk stratification for liver fibrosis is currently possible considering the accuracy of the AI systems, which can overcome the limitations of non-invasive diagnosis methods.

Stabilization of Sunflower Oil with Biologically Active Compounds from Berries.

Sunflower oil (Helianthus annuus) contains a rich concentration of polyunsaturated fatty acids, which are susceptible to rapid oxidative processes. The aim of this study was to evaluate the stabilizing effect of lipophilic extracts from two types of berries, sea buckthorn and rose hips, on sunflower oil. This research included the analysis of sunflower oil oxidation products and mechanisms, including the determination of chemical changes occurring in the lipid oxidation process via LC-MS/MS using electrospray ionization in negative and positive mode. Pentanal, hexanal, heptanal, octanal, and nonanal were identified as key compounds formed during oxidation. The individual profiles of the carotenoids from sea buckthorn berries were determined using RP-HPLC. The influence of the carotenoid extraction parameters ascertained from the berries on the oxidative stability of sunflower oil was analyzed. The dynamics of the accumulation of the primary and secondary products of lipid oxidation and the variation of the carotenoid pigment content in the lipophilic extracts of sea buckthorn and rose hips during storage demonstrated good stability at 4 °C in the absence of light for 12 months. The experimental results were applied to mathematical modeling using fuzzy sets and mutual information analysis, which allowed for the prediction of the oxidation of sunflower oil.

Utilization of psychotropic medicines in Romania during 1998-2018.

Background: Mental disorders can have a significant impact on patients' life, including economic, social and individual consequences, and psychotropic medication is essential to treat these conditions. Psychotropic drug utilization studies contribute to a clearer picture of the management of these conditions. Data published from Romania on this topic is limited. The present study aims to characterize the utilization patterns of anxiolytics, antidepressants (ADs), and antipsychotics (APs) in Romania during 1998-2018. Methods: Drug utilization data were provided by Management Center for Documentation, Information and Marketing (CEGEDIM) Romania and quantitative data for each psychotropic medicine were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The total use of medicines in DDD/TID was computed in order to obtain the drug utilization 90% (DU90%) segment. Results: An increasing trend in total utilization of psychotropic medicines in Romania started in 2004. Anxiolytics use was predominant until 2013 and the yearly anxiolytic use over the entire study period remained between 10 and 15 DDD/TID. Diazepam lost popularity over time in detriment of the utilization of other anxiolytic benzodiazepines, such as alprazolam and lorazepam. ADs utilization markedly increased during the study period (the average annual growth rate was 13.66% starting 1999). Selective serotonin reuptake inhibitors (SSRIs) became present on the 2008 DU90% and was the dominant class of ADs, with sertraline being the most prescribed, followed by escitalopram and paroxetine. APs utilization showed an increasing trend from 2003 until 2018. Atypical APs became present on the 2008 DU90%, while typical APs were no longer included in the 2018 DU90%. Among atypical APs, olanzapine was the main agent prescribed, and starting 2010 was followed by quetiapine and risperidone. The uptake of APs long-acting formulations became more evident during the last analyzed years (2015-2018). Conclusion: We observed an increasing utilization of APs and a more prominent increase in ADs utilization in Romania during 1998-2018. The anxiolytic prescribing remained nearly stable during this time. Further research can bring more information on the various factors influencing psychotropic utilization in Romania.

Exploring the Villalta scale to capture postthrombotic syndrome using alternative approaches: A subanalysis of the ATTRACT trial.

Background: Clinical trials that evaluated interventions to prevent postthrombotic syndrome (PTS) used the Villalta scale (VS) to define PTS, but there is a lack of consistency in its use. Objectives: This study aimed to improve the ability to identify patients with clinically meaningful PTS after DVT in participants of the ATTRACT trial. Methods: We conducted a post hoc exploratory analysis of 691 patients from the ATTRACT study, a randomized trial evaluating the effectiveness of pharmacomechanical thrombolysis to prevent PTS in proximal deep vein thrombosis. We compared 8 VS approaches to classify patients with or without PTS in terms of their ability to discriminate between those with poorer vs better venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL]) between 6- and 24-months follow-up. The difference in the average area under the fitted curve of VEINES-QOL scores between PTS and no PTS ( Δ A U C ¯ ) were compared among approaches. Results: For any PTS (a single VS score ≥5), approaches 1 to 3 had similar Δ A U C ¯ (-21.2, -23.7, -22.0, respectively). Adjusting the VS for contralateral chronic venous insufficiency (CVI) or restricting to patients without baseline CVI (approaches 7 and 8) did not improve Δ A U C ¯ (-13.6, -19.9, respectively; P >.01). For moderate-to-severe PTS (a single VS score ≥10), approaches 5 and 6 requiring 2 positive assessments had greater but not statistically significant Δ A U C ¯ than approach 4, using one single positive assessment (-31.7, -31.0, -25.5, respectively; P >.01). Conclusion: A single VS score of ≥ 5 reliably distinguishes patients with clinically meaningful PTS as assessed by impact on QOL and is preferred because of greater convenience (only one assessment needed). Alternative methods to define PTS (ie, adjusting for CVI) do not improve the scale's ability to identify clinically meaningful PTS.

A Clean-Label Formulation of Fortified Yogurt Based on Rhododendron Flower Powder as a Functional Ingredient.

The world-wide-dispersed Rhododendron is a tiny, evergreen plant with vivid red or pale pink blossoms that is a member of the Ericaceae family and is well-known for its stunning flowers. To improve yogurt's nutritional profile and sensory qualities, this study investigates an innovative application of Rhododendron flower powder (RFP). The potential health benefits of Rhododendron flowers, which are a rich source of bioactive compounds such as polyphenols and antioxidants, have attracted attention. Consequently, the physicochemical, phytochemical, and sensory qualities of fortifying yogurt with RFP at various concentrations were studied. The results showed that the texture and color of the yogurt were highly influenced by the addition of RFP. The addition of this functional ingredient also resulted in a significant increase in the yogurt's polyphenol content and antioxidant capacity. These findings demonstrate the suitability of RFP in yogurt formulations as a functional food ingredient, being a good source of phenolics.

Deep Learning and Antibiotic Resistance.

Antibiotic resistance (AR) is a naturally occurring phenomenon with the capacity to render useless all known antibiotics in the fight against bacterial infections. Although bacterial resistance appeared before any human life form, this process has accelerated in the past years. Important causes of AR in modern times could be the over-prescription of antibiotics, the presence of faulty infection-prevention strategies, pollution in overcrowded areas, or the use of antibiotics in agriculture and farming, together with a decreased interest from the pharmaceutical industry in researching and testing new antibiotics. The last cause is primarily due to the high costs of developing antibiotics. The aim of the present review is to highlight the techniques that are being developed for the identification of new antibiotics to assist this lengthy process, using artificial intelligence (AI). AI can shorten the preclinical phase by rapidly generating many substances based on algorithms created by machine learning (ML) through techniques such as neural networks (NN) or deep learning (DL). Recently, a text mining system that incorporates DL algorithms was used to help and speed up the data curation process. Moreover, new and old methods are being used to identify new antibiotics, such as the combination of quantitative structure-activity relationship (QSAR) methods with ML or Raman spectroscopy and MALDI-TOF MS combined with NN, offering faster and easier interpretation of results. Thus, AI techniques are important additional tools for researchers and clinicians in the race for new methods of overcoming bacterial resistance.

Duodenopancreatectomy for PDAC Associated with MALS: A Case Report.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic malignancy which occurs in over 90% of such cases. Pancreaticoduodenectomy (PD) is used with a curative purpose for localized PDAC. Case presentation: A 68-year-old woman presented to our service through a transfer from another service, to be investigated and treated for a head of the pancreas tumor in a tertiary referral hospital. After a complete clinical and paraclinical evaluation, the patient was diagnosed with a PDAC and also with a median arcuate ligament syndrome (MALS). The surgical treatment was considered adequate, therefore, the patient underwent a PD with transmesocolic hepaticojejunostomy, pancreaticogastric anastomosis, precolic end-to-side gastrojejunostomy, Witzel jejunostomy and with the help of the cardiovascular surgery team from the Heart Institute, Cluj- Napoca, an aortohepatic bypass using saphenous vein graft was performed. Conclusion: Bypass was essential because the blood flow in the proper hepatic artery was not restored after sectioning the median arcuate ligament and clamping the gastroduodenal artery. The patient had a favorable outcome. The particularity of the present case consists of the complete occlusion of the celiac trunk by MALS and the total vascularization of the supramesocolic organs due to the superior mesenteric artery through the gastroduodenal artery.

Deep Learning, Mining, and Collaborative Clustering to Identify Flexible Daily Activities Patterns.

The monitoring of the daily life activities routine is beneficial, especially in old age. It can provide relevant information on the person's health state and wellbeing and can help identify deviations that signal care deterioration or incidents that require intervention. Existing approaches consider the daily routine as a rather strict sequence of activities which is not usually the case. In this paper, we propose a solution to identify flexible daily routines of older adults considering variations related to the order of activities and activities timespan. It combines the Gap-BIDE algorithm with a collaborative clustering technique. The Gap-BIDE algorithm is used to identify the most common patterns of behavior considering the elements of variations in activities sequence and the period of the day (i.e., night, morning, afternoon, and evening) for increased pattern mining flexibility. K-means and Hierarchical Clustering Agglomerative algorithms are collaboratively used to address the time-related elements of variability in daily routine like activities timespan vectors. A prototype was developed to monitor and detect the daily living activities based on smartwatch data using a deep learning architecture and the InceptionTime model, for which the highest accuracy was obtained. The results obtained are showing that the proposed solution can successfully identify the routines considering the aspects of flexibility such as activity sequences, optional and compulsory activities, timespan, and start and end time. The best results were obtained for the collaborative clustering solution that considers flexibility aspects in routine identification, providing coverage of monitored data of 89.63%.

Nation-Wide Survey Assessing the Knowledge and Attitudes of Romanian Pharmacists Concerning Pharmacogenetics.

Background: Pharmacogenetics (PGx) is an important component of personalized medicine that has the potential to improve medicines' effectiveness and safety. However, despite progress in technology and availability, PGx testing application into patient-care in Eastern Europe countries, has been slow. Objectives: Our aim was to describe knowledge and attitudes of Romanian pharmacists concerning PGx, and identify potential factors limiting PGx implementation. Method: An anonymous, web-based questionnaire was distributed to Romanian pharmacists registered in the National Pharmacists' Association (NPA) via an official e-mail sent by NPA representatives. Results: A total of 1,058 pharmacists completed the questionnaires, resulting in a response rate of 7.6%. Pharmacists were predominantly female (90.1%), younger than 49 years (87.5%) and mostly worked in community pharmacies (80.2%). Most pharmacists (64.8%) had a knowledge score between 30 and 49 points out of 60, and (75.4%) had attitude scores between 9 and 7 out of 10. Attitude and knowledge scores positively correlated. Conclusion: Despite performing fairly well on general questions regarding PGx, Romanian pharmacists may lack in-depth knowledge, which can affect their readiness to discuss PGx information with patients or other healthcare professionals. High pricing was considered an important impediment in PGx implementation.

Exclusion Diets in Functional Dyspepsia.

Functional dyspepsia represents one of the most common and prevalent disorders of the brain-gut interaction, with a large number of widespread risk factors being identified. With an intricate pathogenesis and symptomatology, it heavily impacts the quality of life and, due to the limited efficacy of traditional pharmacological agents, patients are likely to seek other medical and non-medical solutions to their problem. Over the last few years, significant research in this domain has emphasized the importance of various psychological therapies and nutritional recommendations. Nevertheless, a correlation has been established between functional dyspepsia and food intolerances, with more and more patients adopting different kinds of exclusion diets, leading to weight loss, restrictive eating behaviour and an imbalanced nutritional state, further negatively impacting their quality of life. Thus, in this systematic review, we aimed at analysing the impact and efficiency of certain exclusion diets undertook by patients, more precisely, the gluten-free diet and the low-FODMAP diet.