The 2023 MDPI Annual Report has
been released!
 
16 pages, 1347 KiB  
Article
RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial
by Olga Holubovska, Pavlo Babich, Alla Mironenko, Jens Milde, Yuriy Lebed, Holger Stammer, Lutz Mueller, Aartjan J. W. te Velthuis, Victor Margitich and Andrew Goy
Adv. Respir. Med. 2024, 92(3), 202-217; https://doi.org/10.3390/arm92030021 (registering DOI) - 06 May 2024
Abstract
Enisamium is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication. We evaluated the clinical efficacy of enisamium treatment combined with standard care in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were [...] Read more.
Enisamium is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication. We evaluated the clinical efficacy of enisamium treatment combined with standard care in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were randomly assigned to receive either enisamium (500 mg per dose, four times a day) or a placebo. The primary outcome was an improvement of at least two points on an eight-point severity rating (SR) scale within 29 days of randomization. We initially set out to study the effect of enisamium on patients with a baseline SR of 4 or 5. However, because the study was started early in the COVID-19 pandemic, and COVID-19 had been insufficiently studied at the start of our study, an interim analysis was performed alongside a conditional power analysis in order to ensure patient safety and assess whether the treatment was likely to be beneficial for one or both groups. Following this analysis, a beneficial effect was observed for patients with an SR of 4 only, i.e., patients with moderate COVID-19 requiring supplementary oxygen. The study was continued for these COVID-19 patients. Overall, a total of 592 patients were enrolled and randomized between May 2020 and March 2021. Patients with a baseline SR of 4 were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 (50.2%) to the placebo group. An analysis of the population showed that if patients were treated within 4 days of the onset of COVID-19 symptoms (n = 33), the median time to improvement was 8 days for the enisamium group and 13 days for the placebo group (p = 0.005). For patients treated within 10 days of the onset of COVID-19 symptoms (n = 154), the median time to improvement was 10 days for the enisamium group and 12 days for the placebo group (p = 0.002). Our findings suggest that enisamium is safe to use with COVID-19 patients, and that the observed clinical benefit of enisamium is worth reporting and studying in detail. Full article
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27 pages, 2011 KiB  
Review
The Intersection of HIV and Pulmonary Vascular Health: From HIV Evolution to Vascular Cell Types to Disease Mechanisms
by Amanda K. Garcia and Sharilyn Almodovar
J. Vasc. Dis. 2024, 3(2), 174-200; https://doi.org/10.3390/jvd3020015 (registering DOI) - 06 May 2024
Abstract
People living with HIV (PLWH) face a growing burden of chronic diseases, owing to the combinations of aging, environmental triggers, lifestyle choices, and virus-induced chronic inflammation. The rising incidence of pulmonary vascular diseases represents a major concern for PLWH. The study of HIV-associated [...] Read more.
People living with HIV (PLWH) face a growing burden of chronic diseases, owing to the combinations of aging, environmental triggers, lifestyle choices, and virus-induced chronic inflammation. The rising incidence of pulmonary vascular diseases represents a major concern for PLWH. The study of HIV-associated pulmonary vascular complications ideally requires a strong understanding of pulmonary vascular cell biology and HIV pathogenesis at the molecular level for effective applications in infectious diseases and vascular medicine. Active HIV infection and/or HIV proteins disturb the delicate balance between vascular tone and constriction, which is pivotal for maintaining pulmonary vascular health. One of the defining features of HIV is its high genetic diversity owing to several factors including its high mutation rate, recombination between viral strains, immune selective pressures, or even geographical factors. The intrinsic HIV genetic diversity has several important implications for pathogenic outcomes of infection and the overall battle to combat HIV. Challenges in the field present themselves from two sides of the same coin: those imposed by the virus itself and those stemming from the host. The field may be advanced by further developing in vivo and in vitro models that are well described for both pulmonary vascular diseases and HIV for mechanistic studies. In essence, the study of HIV-associated pulmonary vascular complications requires a multidisciplinary approach, drawing upon insights from both infectious diseases and vascular medicine. In this review article, we discuss the fundamentals of HIV virology and their impact on pulmonary disease, aiming to enhance the understanding of either area or both simultaneously. Bridging the gap between preclinical research findings and clinical practice is essential for improving patient care. Addressing these knowledge gaps requires interdisciplinary collaborations, innovative research approaches, and dedicated efforts to prioritize HIV-related pulmonary complications on the global research agenda. Full article
(This article belongs to the Section Cardiovascular Diseases)
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11 pages, 258 KiB  
Review
Outcome Measures of Clinical Trials in Pediatric Chronic Kidney Disease
by Ziyun Liang, Guohua He, Liyuan Tao, Xuhui Zhong, Tianxin Lin, Xiaoyun Jiang and Jie Ding
Future 2024, 2(2), 56-66; https://doi.org/10.3390/future2020005 (registering DOI) - 06 May 2024
Abstract
Clinical trials of chronic kidney disease (CKD) in children have important implications for the early identification and management of CKD. The selection of clinical trial outcomes is critical for assessing the effectiveness of interventions in pediatric CKD clinical trials. This review systematically examines [...] Read more.
Clinical trials of chronic kidney disease (CKD) in children have important implications for the early identification and management of CKD. The selection of clinical trial outcomes is critical for assessing the effectiveness of interventions in pediatric CKD clinical trials. This review systematically examines the spectrum of outcome measures deployed in pediatric CKD clinical trials, which includes clinical and alternative outcomes, patient-reported outcome measures (PROMs), and safety indicators. Alternative outcome measures were stratified into four levels of evidence strength: convincing, probable, suggestive, and inconclusive. Consequently, the selection of outcome measures for pediatric CKD clinical trials mandates careful consideration of both their methodological feasibility and the robustness of their evidence base. Moreover, the burgeoning field of PROMs warrants integration into the design of future pediatric clinical trials to enrich the relevance and impact of research findings. Full article
10 pages, 655 KiB  
Review
Transformative Landscape of Anesthesia Education: Simulation, AI Integration, and Learner-Centric Reforms: A Narrative Review
by Nobuyasu Komasawa
Anesth. Res. 2024, 1(1), 34-43; https://doi.org/10.3390/anesthres1010005 (registering DOI) - 06 May 2024
Abstract
This article examines the intersection of simulation-based education and the AI revolution in anesthesia medicine. With AI technologies reshaping perioperative management, simulation education faces both challenges and opportunities. The integration of AI into anesthesia practice offers personalized management possibilities, particularly in preoperative assessment [...] Read more.
This article examines the intersection of simulation-based education and the AI revolution in anesthesia medicine. With AI technologies reshaping perioperative management, simulation education faces both challenges and opportunities. The integration of AI into anesthesia practice offers personalized management possibilities, particularly in preoperative assessment and monitoring. However, the ethical, legal, and social implications necessitate careful navigation, emphasizing patient data privacy and accountability. Anesthesiologists must develop non-technical skills, including ethical decision-making and effective AI management, to adapt to the AI era. The experience-based medical education (EXPBME) framework underscores reflective learning and AI literacy acquisition, fostering lifelong learning and adaptation. Learner-centered approaches are pivotal in anesthesia education, promoting active engagement and self-regulated learning. Simulation-based learning, augmented by AI technologies, provides a dynamic platform for technical and non-technical skills development. Ultimately, by prioritizing non-technical skills, embracing learner-centered education, and responsibly leveraging AI technologies, anesthesiologists can contribute to enhanced patient care and safety in the evolving perioperative landscape. Full article
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24 pages, 1103 KiB  
Review
Modulation of Oxidative Stress and Neuroinflammation by Cannabidiol (CBD): Promising Targets for the Treatment of Alzheimer’s Disease
by Jordan P. Hickey, Andrila E. Collins, Mackayla L. Nelson, Helen Chen and Bettina E. Kalisch
Curr. Issues Mol. Biol. 2024, 46(5), 4379-4402; https://doi.org/10.3390/cimb46050266 (registering DOI) - 06 May 2024
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common form of dementia globally. Although the direct cause of AD remains under debate, neuroinflammation and oxidative stress are critical components in its pathogenesis and progression. As a result, compounds like cannabidiol [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common form of dementia globally. Although the direct cause of AD remains under debate, neuroinflammation and oxidative stress are critical components in its pathogenesis and progression. As a result, compounds like cannabidiol (CBD) are being increasingly investigated for their ability to provide antioxidant and anti-inflammatory neuroprotection. CBD is the primary non-psychotropic phytocannabinoid derived from Cannabis sativa. It has been found to provide beneficial outcomes in a variety of medical conditions and is gaining increasing attention for its potential therapeutic application in AD. CBD is not psychoactive and its lipophilic nature allows its rapid distribution throughout the body, including across the blood–brain barrier (BBB). CBD also possesses anti-inflammatory, antioxidant, and neuroprotective properties, making it a viable candidate for AD treatment. This review outlines CBD’s mechanism of action, the role of oxidative stress and neuroinflammation in AD, and the effectiveness and limitations of CBD in preclinical models of AD. Full article
(This article belongs to the Special Issue Advanced Research in Neuroinflammation)
21 pages, 1384 KiB  
Review
Exploring Maternal Diet-Epigenetic-Gut Microbiome Crosstalk as an Intervention Strategy to Counter Early Obesity Programming
by Maria Felicia Faienza, Flavia Urbano, Federico Anaclerio, Luigi Antonio Moscogiuri, Fani Konstantinidou, Liborio Stuppia and Valentina Gatta
Curr. Issues Mol. Biol. 2024, 46(5), 4358-4378; https://doi.org/10.3390/cimb46050265 (registering DOI) - 06 May 2024
Abstract
Alterations in a mother’s metabolism and endocrine system, due to unbalanced nutrition, may increase the risk of both metabolic and non-metabolic disorders in the offspring’s childhood and adulthood. The risk of obesity in the offspring can be determined by the interplay between maternal [...] Read more.
Alterations in a mother’s metabolism and endocrine system, due to unbalanced nutrition, may increase the risk of both metabolic and non-metabolic disorders in the offspring’s childhood and adulthood. The risk of obesity in the offspring can be determined by the interplay between maternal nutrition and lifestyle, intrauterine environment, epigenetic modifications, and early postnatal factors. Several studies have indicated that the fetal bowel begins to colonize before birth and that, during birth and nursing, the gut microbiota continues to change. The mother’s gut microbiota is primarily transferred to the fetus through maternal nutrition and the environment. In this way, it is able to impact the establishment of the early fetal and neonatal microbiome, resulting in epigenetic signatures that can possibly predispose the offspring to the development of obesity in later life. However, antioxidants and exercise in the mother have been shown to improve the offspring’s metabolism, with improvements in leptin, triglycerides, adiponectin, and insulin resistance, as well as in the fetal birth weight through epigenetic mechanisms. Therefore, in this extensive literature review, we aimed to investigate the relationship between maternal diet, epigenetics, and gut microbiota in order to expand on current knowledge and identify novel potential preventative strategies for lowering the risk of obesity in children and adults. Full article
(This article belongs to the Section Molecular Medicine)
21 pages, 26614 KiB  
Article
Effect of the 35 nm and 70 nm Size Exclusion Chromatography (SEC) Column and Plasma Storage Time on Separated Extracellular Vesicles
by Bernadett György, Krisztina Pálóczi, Mirjam Balbisi, Lilla Turiák, László Drahos, Tamás Visnovitz, Erika Koltai and Zsolt Radák
Curr. Issues Mol. Biol. 2024, 46(5), 4337-4357; https://doi.org/10.3390/cimb46050264 (registering DOI) - 06 May 2024
Abstract
The technical difficulty of separating extracellular vesicles (EVs) from plasma proteins in human blood presents a significant hurdle in EV research, particularly during nano ultra-high-performance liquid chromatography–tandem mass spectrometric (UHPLC-MS/MS) analysis, where detecting “vesicular” proteins among abundant plasma proteins is challenging. Standardisation is [...] Read more.
The technical difficulty of separating extracellular vesicles (EVs) from plasma proteins in human blood presents a significant hurdle in EV research, particularly during nano ultra-high-performance liquid chromatography–tandem mass spectrometric (UHPLC-MS/MS) analysis, where detecting “vesicular” proteins among abundant plasma proteins is challenging. Standardisation is a pressing issue in EV research, prompting collaborative global efforts to address it. While the MISEV guidelines offer valuable recommendations, unanswered questions remain, particularly regarding sample storage. We compared size exclusion chromatography (SEC) columns with pore sizes of 35 nm and 70 nm to identify fractions with minimal contaminating proteins and the highest concentration of small EVs (sEVs). Following column selection, we explored potential differences in the quality and quantity of sEVs isolated from platelet-free plasma (PFP) after long-term storage at −80 °C (>2.5 years) compared to freshly drawn blood. Our methodologically rigorous study indicates that prolonged storage, under correct storage and processing conditions, does not compromise sEV quality. Both columns effectively isolated vesicles, with the 70 nm column exhibiting a higher abundance of “vesicular” proteins. We propose a relatively rapid and moderately efficient protocol for obtaining a comparatively pure sEV fraction from plasma, facilitating sEV processing in clinical trials. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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13 pages, 2355 KiB  
Article
Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors
by Dong Hwan Ho, Hyejung Kim, Daleum Nam, Mi Kyoung Seo, Sung Woo Park and Ilhong Son
Curr. Issues Mol. Biol. 2024, 46(5), 4324-4336; https://doi.org/10.3390/cimb46050263 (registering DOI) - 06 May 2024
Abstract
Astrocytes in the brain contribute to various essential functions, including maintenance of the neuronal framework, survival, communication, metabolic processes, and neurotransmitter levels. Leucine-rich repeat kinase 2 (LRRK2) is associated with the pathogenesis of Parkinson’s disease (PD). LRRK2 is expressed in neurons, microglia, and [...] Read more.
Astrocytes in the brain contribute to various essential functions, including maintenance of the neuronal framework, survival, communication, metabolic processes, and neurotransmitter levels. Leucine-rich repeat kinase 2 (LRRK2) is associated with the pathogenesis of Parkinson’s disease (PD). LRRK2 is expressed in neurons, microglia, and astrocytes and plays diverse roles in these cell types. We aimed to determine the effects of mutant human G2019S-LRRK2 (GS-hLRRK2) in rat primary astrocytes (rASTROs). Transfection with GS-hLRRK2 significantly decreased cell viability compared to transfection with the vector and wild-type human LRRK2 (WT-hLRRK2). GS-hLRRK2 expression significantly reduced the levels of nerve growth factor and increased the levels of proinflammatory cytokines (interleukin-1β and tumor necrosis factor α) compared to the vector and WT-hLRRK2 expression. Furthermore, GS-hLRRK2 expression in rASTROs promoted astrogliosis, which was characterized by increased expression of glial fibrillary acidic protein and vimentin. Treatment with the conditioned medium of G2019S LRRK2-expressing rASTROs decreased N27 cell viability compared to treatment with that of WT-hLRRK2-expressing rASTROs. Consequently, the regulation of the dopamine synthesis pathway was affected in N27 cells, thereby leading to altered levels of tyrosine hydroxylase, dopamine transporter, Nurr1, and dopamine release. Overall, the G2019S LRRK2 mutation disrupted astrocyte function, thereby aggravating PD progression. Full article
(This article belongs to the Special Issue Advanced Research in Neuroinflammation)
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16 pages, 7184 KiB  
Article
A Study of Singular Similarity Solutions to Laplace’s Equation with Dirichlet Boundary Conditions
by Chao-Kang Feng and Jyh-Haw Tang
AppliedMath 2024, 4(2), 596-611; https://doi.org/10.3390/appliedmath4020033 (registering DOI) - 06 May 2024
Abstract
The infinite series solution to the boundary-value problems of Laplace’s equation with discontinuous Dirichlet boundary conditions was found by using the basic method of separation of variables. The merit of this paper is that the closed-form solution, or the singular similarity solution in [...] Read more.
The infinite series solution to the boundary-value problems of Laplace’s equation with discontinuous Dirichlet boundary conditions was found by using the basic method of separation of variables. The merit of this paper is that the closed-form solution, or the singular similarity solution in the semi-infinite strip domain and the first-quadrant domain, can be generated from the basic infinite series solution in the rectangular domain. Moreover, based on the superposition principle, the infinite series solution in the rectangular domain can be related to the singular similarity solution in the semi-infinite strip domain. It is proven that the analytical source-type singular behavior in the infinite series solution near certain singular points in the rectangular domain can be revealed from the singular similarity solution in the semi-infinite strip domain. By extending the boundary of the rectangular domain, the infinite series solution to Laplace’s equation in the first-quadrant domain can be derived to obtain the analytical singular similarity solution in a direct and much easier way than by using the methods of Fourier transform, images, and conformal mapping. Full article
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12 pages, 1071 KiB  
Article
Treatment Patterns and Clinical Outcomes of Patients with Moderate to Severe Acute Graft-Versus-Host Disease: A Multicenter Chart Review Study
by David Michonneau, Raynier Devillier, Mikko Keränen, Marie Thérèse Rubio, Malin Nicklasson, Hélène Labussière-Wallet, Martin Carre, Anne Huynh, Elisabet Viayna, Montserrat Roset, Jonathan Finzi, Minja Pfeiffer, Daniel Thunström, Núria Lara, Lorenzo Sabatelli, Patrice Chevallier and Maija Itälä-Remes
Hematol. Rep. 2024, 16(2), 283-294; https://doi.org/10.3390/hematolrep16020028 (registering DOI) - 06 May 2024
Abstract
Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, [...] Read more.
Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, retrospective chart review describes treatment patterns and clinical outcomes among patients (≥18 years old) from Finland, Sweden, and France who developed grades II–IV aGVHD after their first HSCT (January 2016–June 2017). From 13 participating centers, 151 patients were included. The median (Q1, Q3) age at HSCT was 56 (45, 62) years old. One line of aGVHD treatment was received by 47.7%, and the most common first-line treatment was methylprednisolone (alone or in a combination regimen, 74.2%; monotherapy, 25.8%). Among patients treated with methylprednisolone, 79.5% achieved a complete or partial response. The median (Q1, Q3) number of treatment lines was 2.0 (1.0, 3.0). The median (Q1, Q3) time to obtain an aGVHD diagnosis from transplant was 29.5 (21.0, 44.0) days, and 14.5 (7.0, 34.0) days to achieve the best response for 110 evaluable patients. At 6 and 12 months, 53.6% and 49.0%, respectively, achieved a complete response. Chronic GVHD occurred in 37.7% of patients, and aGVHD reoccurred in 26.5%. Following aGVHD diagnosis, mortality rates were 30.0% at 6 months and 37.3% at 12 months. Findings from this study demonstrate a continuing unmet need for new therapies that control aGVHD and improve mortality. Full article
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13 pages, 278 KiB  
Review
Unlocking the Potential of Meldonium: From Performance Enhancement to Therapeutic Insights
by Val Bellman
Psychoactives 2024, 3(2), 235-247; https://doi.org/10.3390/psychoactives3020015 (registering DOI) - 06 May 2024
Abstract
Meldonium, a promising pharmacological agent initially developed for cardiovascular indications, has sparked considerable interest in recent years due to its potential performance-enhancing effects. This review manuscript delves into the multifaceted roles of meldonium, examining its pharmacological mechanisms, therapeutic applications, and controversial implications in [...] Read more.
Meldonium, a promising pharmacological agent initially developed for cardiovascular indications, has sparked considerable interest in recent years due to its potential performance-enhancing effects. This review manuscript delves into the multifaceted roles of meldonium, examining its pharmacological mechanisms, therapeutic applications, and controversial implications in medicine. Beyond its cardiovascular applications, emerging research has shed light on meldonium’s neuroprotective properties and its potential for mitigating various psychiatric conditions. Moreover, recent investigations have explored meldonium’s potential in treating neurodegenerative disorders, alcohol use disorder, and even enhancing cognitive function. However, meldonium’s journey extends beyond the realm of medicine, as its use among athletes has stirred debates surrounding performance enhancement and fair competition. The substance’s inclusion in the World Anti-Doping Agency’s (WADA) prohibited list has intensified scrutiny and raised ethical considerations regarding its use in sports. This manuscript aims to provide a comprehensive resource for researchers, clinicians, and enthusiasts alike, fostering a deeper understanding of meldonium’s complex biological interactions and its potential contributions to psychiatry. Full article
14 pages, 1299 KiB  
Article
Analysing Pre-Operative Gait Patterns Using Inertial Wearable Sensors: An Observational Study of Participants Undergoing Total Hip and Knee Replacement
by Pragadesh Natarajan, Ashley Lim Cha Yin, R. Dineth Fonseka, David Abi-Hanna, Kaitlin Rooke, Luke Sy, Monish Maharaj, David Broe, Lianne Koinis and Ralph Jasper Mobbs
Surg. Tech. Dev. 2024, 13(2), 178-191; https://doi.org/10.3390/std13020011 (registering DOI) - 06 May 2024
Abstract
Background. Knee and hip arthroplasty are two of the most frequently performed procedures in orthopaedic surgery. They are associated with positive patient-reported outcomes and significant improvements in quality of life for patients. Despite this, there may be room for further progress by quantifying [...] Read more.
Background. Knee and hip arthroplasty are two of the most frequently performed procedures in orthopaedic surgery. They are associated with positive patient-reported outcomes and significant improvements in quality of life for patients. Despite this, there may be room for further progress by quantifying functional improvements with gait analysis. Our study therefore aims to characterise the disease-specific gait pattern of participants with knee and hip osteoarthritis undergoing total joint replacement using a single chest-based wearable sensor. Methods. Twenty-nine participants awaiting total hip replacement and 28 participants awaiting total knee replacement underwent three-dimensional motion analysis with inertial wearable sensors. These gait metrics were then compared with 28 healthy controls of similar ages. Differences in gait metrics were evaluated using a T-test. The participants were recruited through a single centre to participate in this cross-sectional observational study. Participants with osteoarthritis severity sufficient to warrant surgical intervention were considered for inclusion in our study. The participants were instructed to walk 15–120 m in a hospital environment while fitted with a chest-based wearable sensor. Results. In total, three domains were evaluated, including spatiotemporal, variability and asymmetry parameters. There were marked variations in the gait asymmetry parameters and step length variation in both the hip and knee osteoarthritis patients compared with the healthy controls. The magnitude of gait deterioration in terms of step length asymmetry was greater on average in the hip osteoarthritis group than the knee group. The hip osteoarthritis (+180%, p < 0.001) and knee osteoarthritis (+129%, p = 0.001) groups demonstrated marked differences in step length asymmetry. Discussion. A single chest-based sensor was found to be capable of detecting pathological gait signatures in osteoarthritis patients when compared with age-matched controls. Future studies should compare pre- and postoperative changes to disease-specific gait impairments to validate the use of wearable sensors as a clinical adjunct. Full article
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43 pages, 8516 KiB  
Article
Multi-Scale Analysis of Lyme Disease Ecology
by Rebecca Michelle Bingham-Byrne and Esra Ozdenerol
Rheumato 2024, 4(2), 88-130; https://doi.org/10.3390/rheumato4020008 (registering DOI) - 06 May 2024
Abstract
Lyme disease is a zoonotic infectious disease. Increased public interest in Lyme disease has caused increased efforts by researchers for its surveillance and control. The main concept for this paper is to determine the mammalian species composition of areas at high risk for [...] Read more.
Lyme disease is a zoonotic infectious disease. Increased public interest in Lyme disease has caused increased efforts by researchers for its surveillance and control. The main concept for this paper is to determine the mammalian species composition of areas at high risk for Lyme disease utilizing GIS-based (Geographic Information Systems) techniques coupled with k-means clustering, random forest, and multinomial logistic regression. Cluster analysis results were similar to previous work involving maps that display areas where people are at high risk for developing Lyme disease. There were differences in which mammal species presence had associations with Lyme disease risk observed at the two different scales within this analysis, with some overlap observed between the national scale and the smaller regions, as well as some overlap between the Rocky Mountain and Southeast regions that was not found at the national scale. This is an investigative analysis to determine which species are needed for habitat suitability analyses in efforts to prioritize vaccine deployment locations. There has been limited research on vaccine deployment for Lyme disease. Increasing our understanding of not only the vaccine but also the interactions between the components of disease transmission is necessary to control this infectious disease successfully. Full article
8 pages, 412 KiB  
Article
Accelerated Fractionated Radiation Therapy for Localized Glottic Carcinoma
by Tatsuji Mizukami, Kentaro Yamagishi, Masaki Tobikawa, Akira Nakazato, Hideharu Abe, Yuka Morita and Jun-ichi Saitoh
Curr. Oncol. 2024, 31(5), 2636-2643; https://doi.org/10.3390/curroncol31050198 (registering DOI) - 06 May 2024
Abstract
Background: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma. Methods: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six [...] Read more.
Background: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma. Methods: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six had T1b disease, and ten had T2 disease. A fractional dose of 2.1 Gy was administered to seven patients. The total doses were 65.1 and 67.2 Gy in four and three patients, respectively. A fractional dose of 2.25 Gy was administered to 22 patients. The total doses were 63 and 67.5 Gy in 21 patients and 1 patient with T2 disease, respectively. Additionally, 13 patients underwent the use of TS-1 (80–100 mg per day). Results: The median follow-up period was 33 months, and the 3-year local control rate was 95.6%. No patient had a lymph node or distant recurrence. As acute adverse events, grades 2 and 3 dermatitis were observed in 18 patients and 1 patient, and grades 2 and 3 mucositis were observed in 15 patients and 1 patient. As a late adverse event, one patient required tracheotomy because of laryngeal edema occurring. Conclusions: Accelerated fractionated irradiation may be an option in the radiation therapy of N0 glottic carcinoma because of its ability to shorten the treatment time. Full article
(This article belongs to the Section Head and Neck Oncology)
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14 pages, 1051 KiB  
Article
Evaluating Weight Loss Efficacy in Obesity Treatment with Allurion’s Ingestible Gastric Balloon: A Retrospective Study Utilizing the Scale App Health Tracker
by Danut Dejeu, Paula Dejeu, Paula Bradea, Anita Muresan and Viorel Dejeu
Clin. Pract. 2024, 14(3), 765-778; https://doi.org/10.3390/clinpract14030061 (registering DOI) - 06 May 2024
Abstract
Obesity represents a growing public health concern, affecting more than 15% of the global adult population and involving a multi-billion market that comprises nutritional, surgical, psychological, and multidisciplinary interventions. The objective of this retrospective study was to evaluate the short-term efficacy and body [...] Read more.
Obesity represents a growing public health concern, affecting more than 15% of the global adult population and involving a multi-billion market that comprises nutritional, surgical, psychological, and multidisciplinary interventions. The objective of this retrospective study was to evaluate the short-term efficacy and body weight measurements associated with differing levels of physical activity following the use of Allurion’s ingestible gastric balloon that was designed to increase feelings of fullness and decrease food consumption, being naturally eliminated after approximately 16 weeks. This study involved 571 individuals who qualified for the intervention for being older than 20 years with a body mass index (BMI) of 27 kg/m2 or more. Utilizing the Scale App Health Tracker and Allurion’s smartwatch, this study was able to track vital signs and physical activity in real time. The participants had an average initial BMI of 34.1 kg/m2 and a median age of 41 years. Notable outcomes were observed in both study groups, “Less Active” and “More Active”, which were classified by achieving less or more than a median number of 8000 daily steps. Specifically, body fat percentage saw a reduction from 33.1 ± 9.4 to 28.3 ± 10.2 in the less active group and from 32.2 to 27.5 in the more active group, with both groups achieving statistical significance (p < 0.001). Additionally, there was a significant reduction in average weight, dropping from 98.2 ± 22.8 kg to 84.6 ± 19.3 kg in the less active group and from 97.7 ± 21.0 kg to 82.1 ± 22.9 kg in the more active group (both p < 0.001). Interestingly, those in the more active group also experienced a significant increase in lean mass compared to their less active counterparts (p = 0.045), although no substantial differences in weight loss, BMI reduction, and total body fat decrease were observed between the two groups. This investigation confirms the hypothesis that Allurion’s ingestible gastric balloon significantly reduces weight in the short term and enhances several physical health metrics, demonstrating effectiveness as an autonomous method for challenging weight management, regardless of the level of daily physical activity. Full article
(This article belongs to the Special Issue Clinical Nutrition in Metabolic Disorders)
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13 pages, 824 KiB  
Article
Estimating Partnership Duration among MSM in Belgium—A Modeling Study
by Achilleas Tsoumanis, Wim Vanden Berghe, Niel Hens and Christophe Van Dijck
Infect. Dis. Rep. 2024, 16(3), 435-447; https://doi.org/10.3390/idr16030032 (registering DOI) - 06 May 2024
Abstract
Mathematical modeling is widely used for describing infection transmission and evaluating interventions. The lack of reliable social parameters in the literature has been mentioned by many modeling studies, leading to limitations in the validity and interpretation of the results. Using data from the [...] Read more.
Mathematical modeling is widely used for describing infection transmission and evaluating interventions. The lack of reliable social parameters in the literature has been mentioned by many modeling studies, leading to limitations in the validity and interpretation of the results. Using data from the European MSM Internet survey 2017, we developed a network model to describe sex acts among MSM in Belgium. The model simulates daily sex acts among steady, persistent casual and one-off partners in a population of 10,000 MSM, grouped as low- or high-activity by using three different definitions. Model calibration was used to estimate partnership duration and homophily rates to match the distribution of cumulative sex partners over 12 months. We estimated an average duration between 1065 and 1409 days for steady partnerships, 4–6 and 251–299 days for assortative high- and low-activity individuals and 8–13 days for disassortative persistent casual partnerships, respectively, varying across the three definitions. High-quality data on social network and behavioral parameters are scarce in the literature. Our study addresses this lack of information by providing a method to estimate crucial parameters for network specification. Full article
39 pages, 4818 KiB  
Review
Revolutionizing Sustainable Nonwoven Fabrics: The Potential Use of Agricultural Waste and Natural Fibres for Nonwoven Fabric
by Hamdam Gaminian, Behzad Ahvazi, J. John Vidmar, Usukuma Ekuere and Sharon Regan
Biomass 2024, 4(2), 363-401; https://doi.org/10.3390/biomass4020018 (registering DOI) - 06 May 2024
Abstract
There has been a growing interest in recycling and upcycling different waste streams due to concerns for environmental protection. This has prompted the desire to develop circular economies and optimize the utilization of bioresources for different industrial sectors. Turning agricultural and forestry waste [...] Read more.
There has been a growing interest in recycling and upcycling different waste streams due to concerns for environmental protection. This has prompted the desire to develop circular economies and optimize the utilization of bioresources for different industrial sectors. Turning agricultural and forestry waste streams into high-performance materials is a promising and meaningful strategy for creating value-added materials. Lignocellulose fibres from plants are emerging as a potential candidate for eco-friendly feedstock in the textile industry. Nonwoven fabric is one of the most innovative and promising categories for the textile industry since it currently utilizes about 66% synthetic materials. In the upcoming wave of nonwoven products, we can expect an increased utilization of natural and renewable materials, particularly with a focus on incorporating lignocellulosic materials as both binders and fibre components. The introduction of low-cost fibres from waste residue materials to produce high-performance nonwoven fabrics represents a shift towards more environmentally sustainable paradigms in various applications and they represent ecological and inexpensive alternatives to conventional petroleum-derived materials. Here, we review potential technologies for using agricultural waste fibres in nonwoven products. Full article
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15 pages, 587 KiB  
Brief Report
Adolescents Identify Modifiable Community-Level Barriers to Accessing Mental Health and Addiction Services in a Rural Canadian Town: A Survey Study
by Hana Marmura, Regina R. F. Cozzi, Heather Blackburn and Oliva Ortiz-Alvarez
Pediatr. Rep. 2024, 16(2), 353-367; https://doi.org/10.3390/pediatric16020031 (registering DOI) - 06 May 2024
Abstract
Adolescents are particularly vulnerable to inadequate provision of mental health and addictions care, as services have been traditionally conceptualized to serve the needs of children or adults. Additionally, rural communities have been largely excluded from research investigating mental healthcare access and exhibit unique [...] Read more.
Adolescents are particularly vulnerable to inadequate provision of mental health and addictions care, as services have been traditionally conceptualized to serve the needs of children or adults. Additionally, rural communities have been largely excluded from research investigating mental healthcare access and exhibit unique barriers that warrant targeted interventions. Finally, perspectives from the target population will be most important when understanding how to optimize adolescent mental health and addictions care. Therefore, the purpose of this study was to identify what adolescents in a rural town perceive as barriers to accessing mental health services. We conducted a cross-sectional survey study with high school students to generate ranked lists of the top perceived individual-level, community-level, and overall barriers. A total of 243 high school students responded to the survey. Perceived barriers were predominantly at the community level. Overall, the top barriers reported were a lack of awareness and education regarding mental health, resources, and the nature of treatment. Students who had previously accessed mental health services identified primary barriers related to mental health professionals, whereas students who had not accessed care reported fear and uncertainty as primary barriers. Modifiable community-level factors related to (1) mental health literacy and (2) mental healthcare professionals were identified by adolescents as the main perceived barriers to accessing mental health and addiction services in a rural town. The findings of this preliminary study should inform intervention strategies and further rigorous research for this traditionally underserved target population. Full article
14 pages, 1459 KiB  
Article
Utilization of Blackmouth Catshark (Galeus melastomus) Skins as an Alternative Source of Gelatin: Extraction and Physicochemical Characterization in Comparison to Porcine Skin Gelatin
by Panayotis D. Karayannakidis, Soumela E. Chatziantoniou and Chong M. Lee
Biomass 2024, 4(2), 349-362; https://doi.org/10.3390/biomass4020017 (registering DOI) - 06 May 2024
Abstract
The present study investigated the potential use of blackmouth catshark (Galeus melastomus) skins for gelatin production by employing a combined alkaline and acidic process. The yield of dry gelatin was relatively high (13.95%), showing a high protein content (87.80%), but low [...] Read more.
The present study investigated the potential use of blackmouth catshark (Galeus melastomus) skins for gelatin production by employing a combined alkaline and acidic process. The yield of dry gelatin was relatively high (13.95%), showing a high protein content (87.80%), but low moisture (10.64%), ash (1.34%) and lipid (0.03%) contents, on a wet weight basis. Fish skin gelatin showed better color properties (>L*, <+b* values) than porcine skin gelatin and exhibited similar gel strength (315.4 g) and higher viscosity (5.90 cP) than the latter (p < 0.05). Although the electrophoretic study revealed that fish skin gelatin was degraded to a lesser extent than its mammalian counterpart, the resulting fish skin gelatin gels melted at a significantly lower temperature (Tm = 21.5 °C), whereas the reverse process (i.e., gelling) also occurred at a lower temperature (Ts = 10.6 °C) and required more time (ts = 29.5 min) compared to porcine skin gelatin gels (Tm = 30.4 °C, Ts = 19.4 °C and ts = 20.7 min). These differences were attributed to the different imino acid content, which was greater in mammalian gelatin (p < 0.05). The results suggested that the skins from blackmouth catshark can be potentially used as an alternative raw material for gelatin production, which will fill the needs of more diverse cultures that do not consume pork- or cow-related products. Full article
19 pages, 949 KiB  
Review
The Effect of Oral GABA on the Nervous System: Potential for Therapeutic Intervention
by Shahad Almutairi, Amaya Sivadas and Andrea Kwakowsky
Nutraceuticals 2024, 4(2), 241-259; https://doi.org/10.3390/nutraceuticals4020015 (registering DOI) - 06 May 2024
Abstract
Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical [...] Read more.
Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical role of GABA in disease-free brain function. The review examines the intricate interplay between the gut–brain axis and CNS function. The potential impact of dietary GABA on the brain, either by traversing the blood–brain barrier (BBB) or indirectly through the gut–brain axis, is explored. While traditional beliefs questioned GABA’s ability to cross the BBB, recent research challenges this notion, proposing specific transporter systems facilitating GABA passage. Animal studies provide some evidence that small amounts of GABA can cross the BBB but there is a lack of human data to support the role of transporter-mediated GABA entry into the brain. This review also explores GABA-containing food supplements, investigating their impact on brain activity and functions. The potential benefits of GABA supplementation on pain management and sleep quality are highlighted, supported by alterations in electroencephalography (EEG) brain responses following oral GABA intake. The comprehensive overview encompasses GABA’s sources in the diet, including brown rice, soy, adzuki beans, and fermented foods. GABA’s presence in various foods and supplements, its association with gut microbiota, and its potential as a therapeutic strategy for neurological disorders are thoroughly examined. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords “GABA”, “oral GABA“, “sleep”, “cognition”, “neurodegenerative”, “blood-brain barrier”, “gut microbiota”, “supplements” and “therapeutic”, and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that suggest oral GABA benefits range from neuroprotection to blood pressure control. The literature suggests that oral intake of GABA affects the brain illustrated by changes in EEG scans and cognitive performance, with evidence showing that GABA can have beneficial effects for multiple age groups and conditions. The potential clinical and research implications of utilizing GABA supplementation are vast, spanning a spectrum of diseases ranging from neurodegeneration to blood pressure regulation. Importantly, recommendations for the use of oral GABA should consider the dosage, formulation, and duration of treatment as well as potential side effects. Effects of GABA need to be more thoroughly investigated in robust clinical trials to validate efficacy to progress the development of alternative treatments for a variety of disorders. Full article
(This article belongs to the Special Issue The Role of Nutraceuticals in Central Nervous System Disorders)
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11 pages, 1035 KiB  
Article
The Incidence of Type 2 Diabetes Mellitus and Weight Gain in People Living with HIV Receiving a Dolutegravir-Based Antiretroviral Therapy in Addis Ababa, Ethiopia: A Pilot Single-Arm Historical Cohort Study
by Tariku Shimels, Arebu Issa Bilal, Desta Samuel, Desalew Gedamu, Eden Solomon and Zewdneh Shewamene
Venereology 2024, 3(2), 96-106; https://doi.org/10.3390/venereology3020008 (registering DOI) - 06 May 2024
Abstract
Introduction: The development of antiretroviral therapy (ART) has immensely improved the quality of life of people living with HIV/AIDS. Despite such a change, concerns continue to persist regarding the safety of the latest drugs added to the regimens. This study aims to evaluate [...] Read more.
Introduction: The development of antiretroviral therapy (ART) has immensely improved the quality of life of people living with HIV/AIDS. Despite such a change, concerns continue to persist regarding the safety of the latest drugs added to the regimens. This study aims to evaluate the incidence of type 2 diabetes mellitus (T2DM) and weight gain in individuals receiving antiretroviral therapy containing dolutegravir at a general hospital in Addis Ababa, Ethiopia. Methods: A retrospective cohort study was conducted at RDDMH from 1 February to 30 March 2022. The study included PLHIV who had dolutegravir substituted into their combined regimen in November 2019. Collected data underwent cleaning, entry, and analysis using Statistical Package for Social Sciences (SPSS) v. 26.0 and R programing. Descriptive statistics were employed for univariate and bivariate analysis. The Kaplan–Meier model in R was used to illustrate the hazard function. A significance level of p < 0.05 and a 95% confidence interval were employed for statistical reporting. Results: The study followed 185 PLHIV who were on ART who either substituted their previous regimens or initiated a new dolutegravir-based regimen for 12 months. Most were females (59.5%), aged over 38 years (57.5%), married (50.8%), and had lived with HIV for 7 or more years (51.9%). The incidence proportion of T2DM in this sample was 7.0% (95% CI: 3.8–10.3). The age category (X2(1, N = 185) = 12.29, p < 0.001) exhibited a statistically significant relationship with the incidence of T2DM. The cumulative rate of T2DM in the age group over 38 years was approximately 15.4%. The pairwise Wilcoxon signed rank test revealed statistically significant differences in BMI scores between time points. Conclusion: This study observed a noteworthy incidence of T2DM among PLHIV receiving a dolutegravir-based first-line ART. Healthcare providers should prioritize early follow-up and management options for PLHIV who are on dolutegravir-based ART regimens. Full article
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9 pages, 6488 KiB  
Case Report
A Single Nucleotide Variant in Ankyrin-2 Influencing Ventricular Tachycardia in COVID-19 Associated Myocarditis
by Erin Haase, Chandana Kulkarni, Peyton Moore, Akash Ramanathan and Mohanakrishnan Sathyamoorthy
Cardiogenetics 2024, 14(2), 84-92; https://doi.org/10.3390/cardiogenetics14020007 (registering DOI) - 06 May 2024
Abstract
Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn’s disease and asthma developed COVID-19. Shortly after infection, she experienced [...] Read more.
Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn’s disease and asthma developed COVID-19. Shortly after infection, she experienced symptoms of chest pressure, palpitations, and shortness of breath, leading to the eventual diagnosis of myocarditis complicated by recurrent ventricular tachycardia. Treatment with mechanistically driven anti-arrhythmic therapy and beta-blockers suppressed this highly symptomatic ventricular tachycardia. Genetic testing to further risk stratify and influence long term care identified a single nucleotide variant in the ANK-2 gene, which is known to be associated with arrhythmic risk. Discussion: This case study highlights the use of rationally selected anti-arrhythmic therapy, mexiletine, in the management of ventricular tachycardia associated with COVID-19 myocarditis and the presence of a single nucleotide variant in ANK-2, raising the possibility of its contribution to VT susceptibility and severity. Our patient demonstrated significant improvement with administered therapeutics, including the resolution of myocarditis and ventricular tachycardia. The normalization of the QT interval during the resolution phase further supports the potential influence of the genetic variant in ANK-2 on potassium channel activity. Full article
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16 pages, 311 KiB  
Article
Evaluating Attitudes and Preferences towards Walking in Two European Cities
by Fernando Fonseca, George Papageorgiou, Elisa Conticelli, Mona Jabbari, Paulo J. G. Ribeiro, Simona Tondelli and Rui Ramos
Future Transp. 2024, 4(2), 475-490; https://doi.org/10.3390/futuretransp4020023 (registering DOI) - 06 May 2024
Abstract
Understanding pedestrian perceptions and attitudes is crucial for promoting walking as a daily transportation mode for sustainable mobility and the effective development of smart cities. Pedestrian preferences, shaped by factors such as age, gender, and urban infrastructure, play a pivotal role in travel [...] Read more.
Understanding pedestrian perceptions and attitudes is crucial for promoting walking as a daily transportation mode for sustainable mobility and the effective development of smart cities. Pedestrian preferences, shaped by factors such as age, gender, and urban infrastructure, play a pivotal role in travel behaviors. Based on a survey study, this paper examines the impact of individual and urban factors on pedestrian perceptions and attitudes towards walking in the cities of Bologna and Porto. Results reveal that individuals generally value short, safe, and green walking routes, appreciating walking for physical activity, cost savings, and time efficiency. Disliked aspects include adverse weather conditions and walking on inadequate sidewalks. Through carrying out Chi-square statistical analysis tests, a variety of significant correlations between individual and urban variables have been revealed on what people like or dislike about walking. For instance, males, young individuals, and students were more likely to prefer short pedestrian routes, while adults and seniors favored safe and green routes. These findings can assist urban planners in identifying factors that make walking both convenient and enjoyable and in supporting sustainable urban mobility policies. Full article

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