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20 pages, 496 KiB  
Article
“I Don’t Know Whether It’s Priority, or Capacity, or Both”: Implementation Gaps in Employment Policies Targeting People with Disabilities in Kenya and Bangladesh
by Shaffa Hameed, Lopita Huq, David J. N. Musendo, Lena Morgon Banks, Joyce Olenja and Tom Shakespeare
Disabilities 2024, 4(4), 781-800; https://doi.org/10.3390/disabilities4040048 (registering DOI) - 7 Oct 2024
Abstract
Disabled people are often excluded from employment, particularly in accessing waged employment. This exclusion persists despite enabling policies and legislature, indicating a need to address gaps in implementation. To improve policy implementation, it is crucial to better understand the gap between policy intention [...] Read more.
Disabled people are often excluded from employment, particularly in accessing waged employment. This exclusion persists despite enabling policies and legislature, indicating a need to address gaps in implementation. To improve policy implementation, it is crucial to better understand the gap between policy intention (what was planned) and effect (what happens), including reasons that widen this gap (what explains what happened). This study explores this in the context of Kenya and Bangladesh, drawing on key informant interviews and analysis of policies and programmes related to employment, social protection, and disability. Using the policy triangle framework, we analysed the policy context, process, actors, and content of relevant policies and programmes. The study identified key policy provisions on employment quota, social assistance, job placement services, tax incentives, and training opportunities, all of which were designed to promote employment for disabled people. However, implementation is limited in both countries, for reasons including ambiguity in policies, unavailability of data for monitoring, and lack of transparency among implementers. The data suggest that addressing these aspects would promote accountability among duty-bearers, advocacy power among rights-holders, and ultimately improve implementation and inclusion of disabled people in employment. Full article
14 pages, 3213 KiB  
Article
Isolation of Clonostachys rosea and Characterizing Its Entomopathogenic Activity against Dubas Bug (Ommatissus lybicus) Nymphs and Adults
by Salem S. Al-Nabhani, Elham Ahmed Kazerooni, Suad Al-Raqmi, Maryam Al-Hashmi, Shah Hussain, Rethinasamy Velazhahan and Abdullah M. Al-Sadi
Agriculture 2024, 14(10), 1770; https://doi.org/10.3390/agriculture14101770 - 7 Oct 2024
Abstract
The Dubas bug is a serious and widespread pest of date palms in several countries in the Middle East. Chemical pesticides are widely used for managing this pest; however, most pesticides fail due to the continuous development of pesticide resistance. The primary goal [...] Read more.
The Dubas bug is a serious and widespread pest of date palms in several countries in the Middle East. Chemical pesticides are widely used for managing this pest; however, most pesticides fail due to the continuous development of pesticide resistance. The primary goal of this research was to isolate endophytic fungi and test their entomopathogenic activity against Dubas bug nymphs and adults. A total of 27 fungal isolates were obtained and identified using the nuc rDNA internal transcribed spacer (ITS1-5.8S-ITS2 = ITS) region. These strains represent 16 species, belonging to 10 genera of seven different families, Ascomycota with six families and Basidiomycota with a single family, Quambalariaceae. Due to its remarkable biological control ability against insect pests, Clonostachys rosea was further studied for its entomopathogenic activity against Ommatissus lybicus nymphs and adults in comparison to a commercial strain of Beauveria bassiana. The concentration of 1 × 108 conidia/mL of the selected endophytic isolate was used in lab experiments targeting Dubas bug healthy nymphs and adults. After 7 days of C. rosea treatment, the isolate caused significant mortality rates of 85% in the adult insects, while the mortality rates were moderate in the nymphs (33%). The commercial strain of B. bassiana resulted in 100% mortality levels in nymphs and adults of the Dubas bug. Scanning electron microscopy (SEM) of O. lybicus adults treated with C. rosea and B. bassiana showed mycelium growing on the eye, antenna, cuticle, and egg oviposition parts of O. lybicus. Mycelium growth of both fungi was also evident on the nymphs. This study reports for the first time the isolation of C. rosea from the Dubas bug, and its high entomopathogenic activity against an adult population of O. lybicus. Full article
(This article belongs to the Section Crop Protection, Diseases, Pests and Weeds)
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12 pages, 1019 KiB  
Article
Modelling a Western Lifestyle in Mice: A Novel Approach to Eradicating Aerobic Spore-Forming Bacteria from the Colonic Microbiome and Assessing Long-Term Clinical Outcomes
by Edward Horwell, William Ferreira, Huynh Hong, Philip Bearn and Simon Cutting
Biomedicines 2024, 12(10), 2274; https://doi.org/10.3390/biomedicines12102274 - 7 Oct 2024
Abstract
Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal [...] Read more.
Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. Methodology: A new protocol, termed Super Clean, which involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food/water and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony-forming units (CFUs). This was then compared to mice in standard conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the “diseases of the West”). Results: Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. Conclusions: This new murine model successfully isolates EAS-Fs and has potential utility for future research, allowing for an investigation into the clinical impact of living in relative hygienic conditions. Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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14 pages, 1402 KiB  
Article
Age Is a New Indicator of Long-Ball Kicking Performance in Young Soccer Players: Analysing Kinanthropometry, Flexibility and Strength
by Antonio Cejudo, José Manuel Armada-Zarco and Riccardo Izzo
Appl. Sci. 2024, 14(19), 9052; https://doi.org/10.3390/app14199052 - 7 Oct 2024
Abstract
(1) Background: The kick of the ball in soccer is considered one of the most important technical gestures in soccer. Despite this, there is little evidence on ball-striking performance factors in base soccer. The main objectives of the present study were to identify [...] Read more.
(1) Background: The kick of the ball in soccer is considered one of the most important technical gestures in soccer. Despite this, there is little evidence on ball-striking performance factors in base soccer. The main objectives of the present study were to identify the potential factors of long-ball kicking (LBK) performance and to determine the target training cut-off for LBK performance in young soccer players. (2) Methods: A cross-sectional observational study was conducted with 31 soccer players, with ages ranging from 12 to 18 years. Age, anthropometric data, sport experience, range of motion (ROM) and maximal isometric strength (MIS) of the lower limb were noted. Kick-of-the-ball performance was assessed by maximum ball displacement per kick. A k-mean cluster analysis determined two groups according to ball-kicking performance: low group (LPG-LBK) and high group (HPG-LBK). (3) Results: Differences were found between both groups in age, body mass, body mass index, leg length and knee flexion ROM (BF10 ≤ 6.33; δ ≥ 0.86 (moderate or higher)). Among the factors discussed above, age was the strongest predictor of ball-striking performance (odds ratio = 2.867; p = 0.003). The optimal cut-off for age predicting those players most likely to have a higher ball-striking performance was determined to be 13.5 years (p = 0.001; area under the curve = 85.3%). (4) Conclusions: Age over 13.5 increases the chances of a higher optimal ball-striking performance. The flexibility (knee flexion ROM) and strength (knee flexors) must be specifically trained in soccer players beginning at an early age. Full article
(This article belongs to the Special Issue Advances in Assessment of Physical Performance)
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18 pages, 2669 KiB  
Article
Templating Iron(III) Oxides on DNA Molecules
by Siyaka Mj Zubairu, Sulaiman O. Idris, Casmir E. Gimba, Adamu Uzairu, Andrew Houlton and Benjamin R. Horrocks
Nanomaterials 2024, 14(19), 1609; https://doi.org/10.3390/nano14191609 - 7 Oct 2024
Abstract
Fe(III) oxides were prepared as free nanoparticles and on DNA templates via the precipitation of Fe(III) salts with NaOH in the presence/absence of DNA. Through control of the pH and temperature, FeOOH and Fe2O3 were synthesised. The formation of templated materials FeOOH /DNA [...] Read more.
Fe(III) oxides were prepared as free nanoparticles and on DNA templates via the precipitation of Fe(III) salts with NaOH in the presence/absence of DNA. Through control of the pH and temperature, FeOOH and Fe2O3 were synthesised. The formation of templated materials FeOOH /DNA and Fe2O3 /DNA was confirmed using UV-Vis absorption and FTIR spectra. The direct optical gap of Fe2O3 /DNA was estimated as 3.2 eV; the absorption by FeOOH /DNA and Fe2O3 /DNA at longer wavelengths is weaker, but consistent with indirect gaps near 2 eV. X-ray photoelectron spectra confirmed the presence of Fe(III) and DNA in the templated samples. Analysis of the X-ray diffraction patterns of both templated and non-templated FeOOH and Fe2O3 demonstrated that the materials were the α-FeOOH and α-Fe2O3 polymorphs with crystallite diameters of the DNA-templated materials estimated as 7.6 nm and 6.8 nm. Transmission electron microscopy showed needle-like crystals of both FeOOH and Fe2O3, but the Fe2O3 contains some globular structures. In contrast, the morphology of FeOOH /DNA and Fe2O3 /DNA consists of needle-like crystallites of the respective oxides organised into complex dendritic structures with a length on the 10 μm scale formed by the DNA molecules. Finally, scanned conductance microscopy provided evidence for the conductivity of the FeOOH /DNA after alignment via molecular combing on an Si/SiO2 substrate. Fe2O3 /DNA did not exhibit any detectable conductivity. Full article
(This article belongs to the Section Inorganic Materials and Metal-Organic Frameworks)
20 pages, 3973 KiB  
Article
Safety Profiles Related to Dosing Errors of Rapid-Acting Insulin Analogs: A Comparative Analysis Using the EudraVigilance Database
by Ioana Rada Popa Ilie, Andreea Loredana Vonica-Tincu, Carmen Maximiliana Dobrea, Anca Butuca, Adina Frum, Claudiu Morgovan, Felicia Gabriela Gligor and Steliana Ghibu
Biomedicines 2024, 12(10), 2273; https://doi.org/10.3390/biomedicines12102273 - 7 Oct 2024
Abstract
Insulin is essential for treating type 1 diabetes and insulin-requiring type 2 diabetes. Background/Objectives: Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. [...] Read more.
Insulin is essential for treating type 1 diabetes and insulin-requiring type 2 diabetes. Background/Objectives: Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. RAIAs are expected to be associated with a higher number of dosing errors because of their rapid onset, short duration of action, and the need for frequent dosing, compared to other insulin analogs. There are three approved RAIAs on the market: insulin lispro (LIS), insulin aspart (ASP), and insulin glulisine (GLU). The aim of this study is to evaluate the real-world evidence on dosing errors reported for RAIAs in EudraVigilance (EV), an established pharmacovigilance database, in comparison to other insulin analogs and human insulins. Methods: A descriptive analysis and a disproportionality analysis were conducted. Results: ASP and LIS were associated with high percentages of adverse drug reactions (ADRs) (22% and 17%, respectively), with over 70% of the reports involving serious ADRs. A higher frequency of cardiac and eye disorder ADRs was observed for LIS compared with ASP and GLU. GLU showed a higher frequency of ADRs in the skin and subcutaneous tissue disorders category. LIS dosing errors accounted for 5% of the total number of cases, while dosing errors for ASP and GLU were less than 3%. The most frequently reported dosing errors involved improper dosing (49%). Conclusions: Although there were fewer dosing errors of RAIAs in comparison to other insulins, the severity of the potential outcome highlights the importance of precise dosing and timing. Improved the monitoring and reporting of these dosing errors could enhance diabetes patient care. Additionally, smart medical devices could improve therapeutic outcomes. Full article
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18 pages, 2896 KiB  
Article
Dynamics of CD4+ and CD8+ Lymphocytic Inflammatory Infiltrates in Lupus Nephritis
by Tudor Azoicăi, Elena-Roxana Avădănei, Simona-Eliza Giusca, Mihai Onofriescu, Adrian C. Covic, Cristina Gena Dascalu and Irina-Draga Căruntu
Int. J. Mol. Sci. 2024, 25(19), 10775; https://doi.org/10.3390/ijms251910775 - 7 Oct 2024
Abstract
Lupus nephritis (LN) is a common clinical manifestation of systemic lupus erythematosus (SLE). Our study aims to quantitatively analyze CD4+ and CD8+ lymphocytes in different areas and LN classes and describe a specific distribution pattern that is correlated with the severity of LN-specific [...] Read more.
Lupus nephritis (LN) is a common clinical manifestation of systemic lupus erythematosus (SLE). Our study aims to quantitatively analyze CD4+ and CD8+ lymphocytes in different areas and LN classes and describe a specific distribution pattern that is correlated with the severity of LN-specific lesions. In total, 53 LN renal biopsies were immunohistochemically investigated using anti-CD4 and anti-CD8 antibodies. T lymphocytes were counted in 3 areas, including intraglomerular, periglomerular, and interstitial regions. The severity of glomerular and tubulo-interstitial lesions was assessed using an original semi-quantitative algorithm based on the renal corpuscle score (RC_S) and the tubulo-interstitial score (TI_S). The number of CD8+ T lymphocytes was higher than that of CD4+ T lymphocytes in each of the three areas and in each LN class, showing statistically significant differences. ANOVA analysis of all LN classes showed significant differences between periglomerular and interstitial CD4+ and CD8+ T lymphocytes, respectively. Irrespective of location, the number of CD8+ T lymphocytes statistically correlates with the RC_S and the TI_S; no significant correlations were found between the number of CD4+ T lymphocytes and the RC_S and the TI_S for all three considered areas. Our data provide strong evidence supporting the major role of CD8+ lymphocytes in LN lesion progression, with CD4+ lymphocytes playing a limited role. Full article
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11 pages, 221 KiB  
Article
Pregnancy and Neonatal Outcomes in Women Treated for Bowel Endometriosis: A Seven-Year Single-Centre Retrospective Matched Cohort Study
by Vesna Šalamun, Gaetano Riemma, Tina Sirc, Eda Vrtacnik Bokal and Helena Ban Frangež
J. Clin. Med. 2024, 13(19), 5956; https://doi.org/10.3390/jcm13195956 - 7 Oct 2024
Abstract
Background/Objectives: Deep infiltrating endometriosis has been linked to worsened maternal and neonatal outcomes. However, reports regarding bowel endometriosis are still scanty. We aimed to evaluate pregnancy, delivery, and newborn adverse outcomes in women after laparoscopic-assisted surgery for bowel endometriosis. Methods: A single-center [...] Read more.
Background/Objectives: Deep infiltrating endometriosis has been linked to worsened maternal and neonatal outcomes. However, reports regarding bowel endometriosis are still scanty. We aimed to evaluate pregnancy, delivery, and newborn adverse outcomes in women after laparoscopic-assisted surgery for bowel endometriosis. Methods: A single-center retrospective cohort study was conducted at a tertiary-care university hospital. From January 2015 to December 2021, pregnant women who were diagnosed and treated for bowel endometriosis were matched using a 1:3 ratio with pregnant women with no history of endometriosis. Patients were matched using the Cox proportional hazards model to determine parity, age, BMI and gestational age-adjusted relative risk (aRR) with a 95% confidence interval (CI). Co-primary outcomes were the incidence of labor abnormalities and cesarean section (CS) rate. Co-secondary outcomes were incidence of complications related to pregnancy, delivery, and newborn. Results: A total of 71 pregnancies among women treated for bowel endometriosis and 213 from healthy controls were included. Patients requiring IVF/ET for getting pregnant were in the bowel endometriosis group relative to controls (43.7% vs. 11.7%; p < 0.001). Increased risk of labor abnormalities was present for bowel endometriosis relative to controls (21.1% vs. 17.4%; p = 0.040; aRR 1.39 [95% CI 1.06–2.05]). Risk of non-cephalic fetal presentation (14.1% vs. 6.1%; p = 0.016; aRR 3.08 [95% CI 2.03–4.68]), CS rate (43.7% vs. 24.9%; p = 0.003; aRR 1.75 [95% CI 1.23–2.49]), and emergent CS rate (19.7% vs. 8.5%; p = 0.009; aRR 2.21 [95% CI 1.55–3.16]) were significantly higher in women treated for colorectal endometriosis compared with controls. Moreover, placenta previa (9.9% vs. 0.0%; p < 0.001; aRR 21.82 [95% CI 2.19–116.40]), second-trimester hemorrhage (5.6% vs. 0.9%; p = 0.017; aRR 6.00 [95% CI 1.12–32.06]), postpartum hemorrhage (15.5% vs. 3.3%; p < 0.001; aRR 4.71 [95% CI 1.90–11.70]), and the need for transfusion during labor (5.6% vs. 0.5%; p = 0.004; aRR 12.00 [95% CI 1.36–105.60]) were increased in treatments vs. controls. Concerning neonatal outcomes, an increased risk for neonatal intensive care unit admission was seen in postsurgical endometriotic women relative to healthy controls (26.0% vs. 6.9%; p < 0.001; aRR 3.75 [2.04–3.86]). Conclusions: Women treated for bowel endometriosis seem more exposed to adverse pregnancy and neonatal outcomes relative to healthy controls. However, additional prospective and comparative studies are needed to validate the available evidence. Full article
(This article belongs to the Special Issue Clinical Aspects of Diagnosis and Treatment of Endometriosis)
15 pages, 920 KiB  
Article
Capillary Blood Docosahexaenoic Acid Levels Predict Electrocardiographic Markers in a Sample Population of Premenopausal Women
by Breno P. Casagrande, George Sherrard, Mike S. Fowler, Débora Estadella and Allain A. Bueno
J. Clin. Med. 2024, 13(19), 5957; https://doi.org/10.3390/jcm13195957 - 7 Oct 2024
Abstract
Introduction: The relationship between blood N-3 polyunsaturated fatty acid (PUFA) levels and cardiovascular health is known, but direct evidence that N-3 PUFA levels influence electrocardiographic (ECG) parameters is non-existent. In the study described herein, we investigated the relationship between anthropometric biomarkers and [...] Read more.
Introduction: The relationship between blood N-3 polyunsaturated fatty acid (PUFA) levels and cardiovascular health is known, but direct evidence that N-3 PUFA levels influence electrocardiographic (ECG) parameters is non-existent. In the study described herein, we investigated the relationship between anthropometric biomarkers and capillary blood PUFAs with ECG outputs in a sample population of healthy pre-menopausal women. Method: Twenty-three consenting females were recruited, with the study power analysis sufficiently demonstrated. Food intake, anthropometric and cardiovascular parameters were obtained. Capillary blood was collected for fatty acid chromatographic analysis. Results: Body mass index, haematocrit, heart rate (HR), mean arterial pressure (MAP) and ECG readings all fell within healthy ranges. Principal component analysis-mediated correlations were carried out controlling for combined Components 1 (age, body fat % and waist-to-hip ratio) and 2 (height, HR and MAP) as control variables. Docosahexaenoic acid (DHA) unequivocally decreased the QRS area under the curve (AUC-QRS) regardless of the impact of control variables, with each unit increase in DHA corresponding to a 2.3-unit decrease in AUC-QRS. Mediation analysis revealed a significant overall effect of DHA on AUC-QRS, with the impact of DHA on R wave amplitude accounting for 77% of the total observed effect. Discussion: Our new findings revealed an inverse relationship between AUC-QRS with capillary blood DHA, suggesting that the association between ventricular mass and its QRS depolarising voltage is mediated by DHA. Our findings bridge a knowledge gap on the relationship between ventricular mass and ventricular efficiency. Further research will confirm whether the relationship identified in our study also exists in diseased patients. Full article
(This article belongs to the Section Cardiovascular Medicine)
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20 pages, 724 KiB  
Review
Proton Pump Inhibitors and Oral–Gut Microbiota: From Mechanism to Clinical Significance
by Xian Zhang, Qing Li, Siyuan Xia, Yan He, Yuqiang Liu, Jinlin Yang and Xue Xiao
Biomedicines 2024, 12(10), 2271; https://doi.org/10.3390/biomedicines12102271 - 7 Oct 2024
Abstract
Proton pump inhibitors (PPIs) are some of the most commonly prescribed drugs worldwide, but there are increasing concerns about digestive complications linked to PPIs. Next-generation sequencing studies have suggested that PPIs can significantly affect the composition of the gut microbiota, which in turn [...] Read more.
Proton pump inhibitors (PPIs) are some of the most commonly prescribed drugs worldwide, but there are increasing concerns about digestive complications linked to PPIs. Next-generation sequencing studies have suggested that PPIs can significantly affect the composition of the gut microbiota, which in turn may substantially contribute to the development of these complications. Recently, emerging evidence has suggested that the translocation of oral microbes into the gut may be the primary mechanism underlying the alterations in the gut microbiota induced by PPIs in the presence of gastric acid suppression and impaired oral–gut barrier function. Moreover, the significance of oral–gut microbial translocation in health and disease conditions has gained increasing recognition. Consequently, it is imperative to enhance our understanding of the functions of the oral–gut microbiota axis in digestive disorders associated with PPI therapies. This review aims to summarize current research findings and further elucidate the contribution of the oral–gut microbiota to the pathogenesis of PPI-related digestive diseases. We aim to provide a theoretical foundation for future therapeutic and preventive strategies targeting PPI-related digestive complications through modulation of the oral–gut microbiota. Full article
(This article belongs to the Special Issue Impact of Microbiota in Response to Therapy)
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19 pages, 517 KiB  
Article
The Mediating Role of Posttraumatic Stress Symptoms in the Relationship between Adult Attachment and Quality of Life
by Gianluca Santoro, Vittorio Lenzo, Alessandro Musetti, Cristiana Caneglias, Lina Rita Crimi, Lucia Sideli and Adriano Schimmenti
Eur. J. Investig. Health Psychol. Educ. 2024, 14(10), 2735-2753; https://doi.org/10.3390/ejihpe14100180 - 7 Oct 2024
Abstract
There is evidence that anxiety and avoidance toward close relationships (i.e., insecure attachment orientations), as well as posttraumatic stress symptoms (PTSSs), are linked to a poor quality of life. The current study aimed to investigate the potential mediating effects of PTSSs on the [...] Read more.
There is evidence that anxiety and avoidance toward close relationships (i.e., insecure attachment orientations), as well as posttraumatic stress symptoms (PTSSs), are linked to a poor quality of life. The current study aimed to investigate the potential mediating effects of PTSSs on the associations between insecure attachment orientations and domains of quality of life. A convenience sample of 497 adults (375 females, 75.5%), ranging in age between 18 and 65 years old (M = 32.48, SD = 13.26), was recruited. Participants were administered self-report instruments assessing attachment anxiety and avoidance, PTSSs, and domains of quality of life, including physical health, psychological status, social relationships, and environment. A series of mediation analyses were performed to test the mediating role of PTSSs in the relationships between attachment orientations and domains of quality of life. Results showed that attachment anxiety was related to decreased levels of quality of life in all domains, and that their associations were mediated by PTSSs. Also, attachment avoidance was related to a worse quality of psychological status and social relationships, and PTSSs were a significant mediating variable in these associations. Prevention programs and clinical interventions focused on promoting effective strategies for managing distress might be critical in reducing the impact of distressing events on the quality of life of individuals with insecure attachment. Full article
23 pages, 1427 KiB  
Review
Azole Combinations and Multi-Targeting Drugs That Synergistically Inhibit Candidozyma auris
by Stephanie Toepfer, Mikhail V. Keniya, Michaela Lackner and Brian C. Monk
J. Fungi 2024, 10(10), 698; https://doi.org/10.3390/jof10100698 - 7 Oct 2024
Abstract
Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different [...] Read more.
Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different cellular pathways with the goals of increasing treatment options and reducing development of resistance. However, some circumstances can prevent the implementation of combination therapy in clinical practice. These could include the increased risk of adverse effects, drug interactions, and even the promotion of drug resistance. Furthermore, robust clinical evidence supporting the superiority of combination therapy over monotherapy is limited and underscores the need for further research. Despite these challenges, synergies detected with different antifungal classes, such as the azoles and echinocandins, suggest that treatment strategies can be optimized by better understanding the underlying mechanisms. This review provides an overview of multi-targeting combination strategies with a primary focus on Candidozyma auris infections. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 3rd Edition)
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24 pages, 2371 KiB  
Review
Microalgal Phenolics: Systematic Review with a Focus on Methodological Assessment and Meta-Analysis
by Vasilis Andriopoulos and Michael Kornaros
Mar. Drugs 2024, 22(10), 460; https://doi.org/10.3390/md22100460 - 7 Oct 2024
Abstract
A critical review and analysis of the literature relevant to the phenolic content of eucaryotic microalgae was performed. Several issues were identified and discussed. In summary, the main problems with the reporting on the phenolic content of microalgae are the following: (1) despite [...] Read more.
A critical review and analysis of the literature relevant to the phenolic content of eucaryotic microalgae was performed. Several issues were identified and discussed. In summary, the main problems with the reporting on the phenolic content of microalgae are the following: (1) despite its usefulness in the determination of phenolic content in plant samples, the Folin–Ciocalteu assay is non-suitable for microalgal research due to the high presence of interfering compounds in microalgal extracts such as chlorophyll and its derivatives in organic extracts and free aromatic amino acids or nucleotides in aqueous extracts; (2) while there is chromatographic evidence for the presence of simple phenolic acids in most microalgal clades, the lack of critical enzymes of phenolic biosynthesis in most microalgae, as well as the high variability of phenolic profiles even in the same genus, require more extensive research before conclusions are drawn; (3) the accumulation and metabolism of external phenolics by microalgae has been almost universally neglected in studies focusing on the phenolic content of microalgae, even when natural seawater or complex organic media are used in the cultivation process. Despite these issues, the literature focusing on the bioremediation of waste streams rich in phenolics through microalgae demonstrates the ability of those organisms to adsorb, internalize, and in many cases oxidize or transform a wide range of phenolic compounds, even at very high concentrations. Simple phenolics found in waste streams, such as olive mill waste, have been shown to enhance the antioxidant activity and various bioactivities of microalgal extracts, while complex biotransformation products of phenolics have also been characterized. In conclusion, the de novo biosynthesis of phenolic compounds via eucaryotic microalgae requires further investigation with better designed experiments and suitable analytical methods, while the response of microalgae to phenolic compounds in their growth medium is of great practical interest, both in terms of waste treatment and for the production of functional foods, cosmetics, and pharmaceuticals. Full article
(This article belongs to the Special Issue High-Value Algae Products)
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21 pages, 1405 KiB  
Review
Cannabinoids and Genetic Epilepsy Models: A Review with Focus on CDKL5 Deficiency Disorder
by Sean Massey, Anita Quigley, Simone Rochfort, John Christodoulou and Nicole J. Van Bergen
Int. J. Mol. Sci. 2024, 25(19), 10768; https://doi.org/10.3390/ijms251910768 - 7 Oct 2024
Abstract
Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients [...] Read more.
Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD. Full article
(This article belongs to the Special Issue CDKL5 Deficiency Disorders: From Molecular Mechanisms to Therapeutics)
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18 pages, 5215 KiB  
Article
Cascaded Vehicle State Estimation Method of 4WIDEVs Considering System Delay and Noise
by Zibin Yang, Xiang Liu and Qiu Xia
World Electr. Veh. J. 2024, 15(10), 454; https://doi.org/10.3390/wevj15100454 - 7 Oct 2024
Abstract
Considering the negative effects of time delay and noise on vehicle state estimation, a cascaded estimation means for the vehicle sideslip angle is proposed utilizing the ODUKF algorithm. To achieve strong-correlation decoupling between state variables and model interference of the EDWM, an augmented [...] Read more.
Considering the negative effects of time delay and noise on vehicle state estimation, a cascaded estimation means for the vehicle sideslip angle is proposed utilizing the ODUKF algorithm. To achieve strong-correlation decoupling between state variables and model interference of the EDWM, an augmented EDWM was constructed by introducing the tire relaxation length dynamic equation, which enables the precise model relationship between the longitudinal and transverse tire force relaxation length to be constructed while also achieving the decoupling of the system state from the unknown input. To achieve a vehicle driving state estimation, a hierarchical estimation architecture was adopted to design a cascading estimation method for the vehicle driving state. By using tire force estimation values as input for the vehicle driving state estimation, the required vehicle body postures can be estimated. At the same time, facing the problems of system delay and noise, an estimator derived from the ODUKF is designed by combining the model and cascade estimation strategy. The simulation comparative analysis and quantitative statistical results under multiple operating conditions provide evidence that the developed means effectively heighten the estimation accurateness and real-time performance while considering system time delay and noise. Full article
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