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Volume 15
Issue 4
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Life, Volume 15, Issue 4 (April 2025) – 172 articles

Cover Story (view full-size image): New roles for immune cells, overcoming the classical cytotoxic response, have been highlighted by growing evidence. The immune cells, such as neutrophils, monocytes/macrophages, and eosinophils, are versatile cells involved in the release of web-like DNA structures called extracellular traps (ETs) which represent a relevant mechanism by which these cells prevent microbes’ dissemination. In this review, we discuss the release mechanisms and the double-edged sword role of ETs both in physiological and in pathological contexts. In addition, we evaluated some possible strategies to target ETs aimed at either preventing their formation or degrading existing ones. View this paper
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9 pages, 211 KiB  
Article
The Role of Polysomnography for Children with Attention-Deficit/Hyperactivity Disorder
by Chien-Heng Lin, Po-Yen Wu, Syuan-Yu Hong, Yu-Tzu Chang, Sheng-Shing Lin and I-Ching Chou
Life 2025, 15(4), 678; https://doi.org/10.3390/life15040678 - 21 Apr 2025
Abstract
Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsive behavior. In recent years, studies have shown that patients with ADHD often experience sleep problems, raising clinical interest in the potential role of polysomnography (PSG) in [...] Read more.
Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsive behavior. In recent years, studies have shown that patients with ADHD often experience sleep problems, raising clinical interest in the potential role of polysomnography (PSG) in the diagnosis and management of ADHD. This study examines polysomnographic findings in children with ADHD who present with diverse sleep complaints. Methods: A cohort of children aged younger than 18 years, diagnosed with ADHD based on DSM-5 criteria, underwent overnight polysomnography. The study assessed various sleep parameters, including sleep latency, sleep efficiency, total sleep time, and the presence of sleep-disordered breathing. Results: A retrospective analysis was conducted on 36 children (29 boys and 7 girls) aged 6 to 14 years, diagnosed with ADHD, who underwent polysomnography between 2021 and 2024. Polysomnographic findings revealed that 77.78% of the children demonstrated significant snoring. Furthermore, 50.0% were diagnosed with obstructive sleep apnea syndrome (OSAS). In addition, eight children exhibited parasomnias. Among them, six had bruxism, three were diagnosed with periodic limb movement disorder (PLMD), and two experienced sleep talking. Other notable sleep-related conditions included two cases of narcolepsy, one case of prolonged sleep onset latency, and one case of central apnea syndrome. Total sleep time (TST) was significantly longer in females compared to males (400.71 ± 32.68 min vs. 361.24 ± 41.20 min, p = 0.0215), whereas rapid eye movement (REM) latency was longer in males compared to females (118.62 ± 55.60 min vs. 78.57 ± 27.82 min, p = 0.0194). These findings highlight the high prevalence of sleep-disordered breathing (SDB) in children with ADHD who present with sleep disturbances. Furthermore, sleep quality, as indicated by longer TST and shorter REM latency, appears to be better in females with ADHD. Conclusions: The findings of this study underscore the critical role of polysomnography (PSG) in the assessment of children with ADHD. PSG provides an objective evaluation of sleep abnormalities commonly associated with ADHD, which may influence symptom manifestation and treatment outcomes. Notably, the results suggest that females with ADHD exhibit better sleep quality, as indicated by longer total sleep time (TST) and shorter rapid eye movement (REM) latency compared to males. We recommend incorporating polysomnography (PSG) into the comprehensive assessment of children with ADHD who present with significant sleep disturbances. Further research is warranted to investigate the impact of targeted interventions for sleep abnormalities on ADHD symptoms, prognosis, and potential sex-specific differences. Full article
(This article belongs to the Special Issue Obstructive Sleep Apnea and Related Disorders: Pathophysiological Traits and Strategies for Treatment)
36 pages, 739 KiB  
Review
Primary Hyperparathyroidism: An Analysis Amid the Co-Occurrence of Type 2 Diabetes Mellitus
by Ana-Maria Gheorghe, Mihaela Stanciu, Claudiu Nistor, Ioana Codruta Lebada and Mara Carsote
Life 2025, 15(4), 677; https://doi.org/10.3390/life15040677 - 21 Apr 2025
Abstract
Background: Apart from classical elements in primary hyperparathyroidism (PHPT), non-classical complications, including type 2 diabetes mellitus (T2DM), are reported in some patients, but currently, they do not represent a parathyroidectomy (PTx) indication. Objective: to explore the latest data regarding glucose profile, particularly, T2DM [...] Read more.
Background: Apart from classical elements in primary hyperparathyroidism (PHPT), non-classical complications, including type 2 diabetes mellitus (T2DM), are reported in some patients, but currently, they do not represent a parathyroidectomy (PTx) indication. Objective: to explore the latest data regarding glucose profile, particularly, T2DM and metabolic syndrome (MetS) in PHPT, including post-PTx. Methods: PubMed-based review included English-published original studies between January 2020 and December 2024 (n = 20). Results: Studied population: 764,485 subjects (female-to-male ratio of 1.26:1; 23,931 were PHPT patients vs. 740,502 controls). T2DM prevalence (n = 13; N = 763,645 patients; 55.92% females): 4–60% (higher vs. controls); for the largest study (N = 699,157) of 31.3%. Age-based analysis: higher T2DM prevalence at >50 vs. <50 years (14.4% vs. 2.6%, p < 0.001), but not all studies agreed. Concurrent vitamin D deficiency as a contributor to a higher risk had limited evidence. The association MetS-PHPT (n = 2) had no clear conclusion. Post-PTx showed the following: lower glycaemia, fasting insulin, insulin resistance (HOMA-IR) improvement, and reduced rate (but not all studies agreed). PHPT patients with prediabetes might represent the population sub-group with the highest post-PTx benefit. Conclusions: The panel of PHPT-T2DM interplay remains heterogeneous. Data regarding post-PTx improvement of glucose disorders are still conflicting, recent findings suggested that surgery has beneficial effects, especially in patients with confirmed pre-existing prediabetes. Patients with the normocalcemic variant seemed to be less affected by the glucose-related disturbances, but further studies are needed. A better understanding of the intricate relationship between PHPT and glucose metabolism anomalies will help in providing optimal management to reduce the overall disease burden. Full article
(This article belongs to the Special Issue Management of Patients with Diabetes)
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13 pages, 1249 KiB  
Article
Prevalence and Prognostic Significance of Chloride Levels in Patients with Acute Medical Conditions: A Prospective Observational Study
by Rhita Bennis Nechba, Jihane Belayachi, Mina Agrou, Elmostapha El Fahime, Nawal Meknassi, Maha Louriz, Naoufel Madani and Redouane Abouqal
Life 2025, 15(4), 676; https://doi.org/10.3390/life15040676 - 21 Apr 2025
Abstract
Chloride plays a considerable role in physiology. This study aimed to assess the association between serum chloride and prognosis in the population of adults with acute medical conditions. A prospective cohort study was conducted in an acute medical unit. Chloride levels at admission [...] Read more.
Chloride plays a considerable role in physiology. This study aimed to assess the association between serum chloride and prognosis in the population of adults with acute medical conditions. A prospective cohort study was conducted in an acute medical unit. Chloride levels at admission were the main exposure factor, categorized into hypochloremia, normochloremia, and hyperchloremia. The outcomes were in-hospital mortality and length of hospital stay (LOHS). A total of 798 patients were included. The mean age was 57.3 ± 18.3 years. The prevalence of dyschloremia was 40.9%. Restricted cubic splines revealed a linear association between hypochloremia and in-hospital mortality, as well as between hypochloremia and LOHS. After adjusting for age, sex, heart failure, diabetes, sodium, bicarbonates, creatinine, and diuretic use, hypochloremia was significantly associated with in-hospital mortality (OR = 2.23; 95% CI: 1.29, 3.86, p = 0.006), but not hyperchloremia (p = 0.57). Similarly, it was associated with a longer LOHS (β = 2.19; 95% CI: 0.01, 4.39, p = 0.05), but not hyperchloremia (p = 0.8). The interaction between chloride and sodium levels was not significant (p = 0.61). Subgroup analysis showed that the effect of hypochloremia on in-hospital mortality was consistent across subgroups. The prevalence of dyschloremia in this study was high at 40.9%. Hypochloremia increased the risk of in-hospital mortality and extended the LOHS. Differentiating the effects of chloride levels from those of sodium can enhance clinical risk stratification and enable a more targeted management approach for acutely ill patients. Recognizing this distinction is essential for optimizing prognostic assessment and tailoring treatment strategies accordingly. Full article
(This article belongs to the Special Issue Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions)
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18 pages, 1312 KiB  
Review
Exploring the Relationship Between Obstructive Sleep Apnea and Olfactory Function
by Antonino Maniaci, Mario Lentini, Maria Rita Bianco, Daniele Salvatore Paternò, Salvatore Lavalle, Annalisa Pace, Giannicola Iannella, Paolo Boscolo-Rizzo, Miguel Mayo-Yanez, Christian Calvo-Henriquez, Jerome R. Lechien and Luigi La Via
Life 2025, 15(4), 675; https://doi.org/10.3390/life15040675 - 21 Apr 2025
Abstract
Obstructive sleep apnea (OSA) is increasingly recognized as a chronic condition that is closely interrelated to olfactory disorders, with a significant contribution to quality of health and overall quality of life. This narrative review aims to provide a thorough overview of the emerging [...] Read more.
Obstructive sleep apnea (OSA) is increasingly recognized as a chronic condition that is closely interrelated to olfactory disorders, with a significant contribution to quality of health and overall quality of life. This narrative review aims to provide a thorough overview of the emerging evidence that now integrates these two previously considered distinct physiologic systems. Studies published recently have reported a significantly higher frequency of olfactory dysfunction among OSA patients compared to the general population, which raises the possibility of a causal relationship. We explore the postulated mechanisms behind this association, namely, the chronic intermittent hypoxia, local inflammatory effect, and neuroanatomical changes attributed to OSA. The review further explores the clinical impacts of this relationship through proposing the potential for an olfactory assessment to be used as a diagnostic modality for OSA and the effects of OSA treatment on olfactory function. Thus, we explore the difficulties in treating patients who experience both and suggest future areas for research. This review attempts to bridge the gap between the existing literature and impending investigation necessary for a better management of the interaction of sleep apnea and the human sense of smell. Full article
(This article belongs to the Special Issue Obstructive Sleep Apnea and Related Disorders: Pathophysiological Traits and Strategies for Treatment)
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23 pages, 2966 KiB  
Article
Critical Management of Septic Orthopedic Patients: The Impact of Intensive Care on Survival and Recovery
by Angelica Bratu, Catalin Cirstoiu, Mihnea Ioan Gabriel Popa, Mihai Popescu, Oana Clementina Dumitrascu, Mihaela Agapie and Carmen Orban
Life 2025, 15(4), 674; https://doi.org/10.3390/life15040674 - 21 Apr 2025
Abstract
The management of septic orthopedic patients, particularly those with periprosthetic joint infections (PJIs) and trauma-related sepsis, remains a significant clinical challenge. This retrospective cohort study evaluated 27 patients admitted to the Intensive Care Unit (ICU) at the Emergency University Hospital in Bucharest between [...] Read more.
The management of septic orthopedic patients, particularly those with periprosthetic joint infections (PJIs) and trauma-related sepsis, remains a significant clinical challenge. This retrospective cohort study evaluated 27 patients admitted to the Intensive Care Unit (ICU) at the Emergency University Hospital in Bucharest between 2021 and 2024. Patients presented with either PJIs or polytrauma-related infections requiring critical care interventions. The PJI-TNM classification system was employed to assess infection complexity, comorbidities, and implant stability. Therapeutic strategies included one- or two-stage revision surgeries and targeted antimicrobial therapy, including the use of antibiotic-impregnated calcium sulfate beads. Infection resolution was achieved in 85.2% of patients, with a mean ICU stay of 13 days. The overall ICU mortality rate was 11%, with two deaths occurring within the first 30 days of admission. Elevated SOFA scores (≥10) and poor glycemic control (HbA1c > 8.5%) were significantly associated with prolonged ICU stays and higher complication rates. Statistical analysis revealed significant differences in CRP normalization and bone healing times across glycemic control groups (p < 0.001). Patients requiring mechanical ventilation exhibited longer ICU stays and increased mortality (25%). The PJI-TNM classification showed potential utility for risk stratification and guiding personalized treatment strategies. These findings underscore the importance of multidisciplinary ICU-level care and metabolic control in improving outcomes for septic orthopedic patients. Future multicenter studies are needed to validate these preliminary observations and refine prognostic models for this high-risk population. Full article
(This article belongs to the Section Medical Research)
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18 pages, 337 KiB  
Review
Malignant Mesenchymal Tumors of the Breast: Current Challenges and New Perspectives on Primary Sarcomas and Malignant Phyllodes Tumors
by Flavia De Lauretis, Alejandro Martin Sanchez, Cristina Accetta, Beatrice Carnassale, Sabatino D’Archi, Alba Di Leone, Antonio Franco, Federica Gagliardi, Stefano Magno, Elena Jane Mason, Francesca Moschella, Lorenzo Scardina, Marta Silenzi, Angela Bucaro, Chiara V. Pirrottina, Nicoletta D’Alessandris, Antonino Mulè, Angela Santoro, Fabio Marazzi, Valeria Masiello, Alessandra Fabi, Armando Orlandi, Antonella Palazzo, Ida Paris, Maria Pia Foschini, Riccardo Masetti and Gianluca Franceschiniadd Show full author list remove Hide full author list
Life 2025, 15(4), 673; https://doi.org/10.3390/life15040673 - 20 Apr 2025
Viewed by 113
Abstract
Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes. They are particularly aggressive, characterized by a high propensity for local [...] Read more.
Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes. They are particularly aggressive, characterized by a high propensity for local recurrence and an overall poor prognosis. The rarity of these cases has impeded the development of comprehensive clinical studies, leading to a lack of standardized diagnostic protocols and treatment guidelines. This review provides a thorough synthesis of current knowledge on breast mesenchymal tumors with a specific focus on malignant variants such as phyllodes tumors and breast sarcomas. It also addresses the diagnostic challenges faced by clinicians, evaluates current therapeutic strategies, and emphasizes the crucial role of surgical treatment. Additionally, it examines the evolving roles of chemotherapy and radiotherapy in enhancing patient outcomes. Full article
(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)
14 pages, 2599 KiB  
Article
Immune Escape and Drug Resistance Mutations in Patients with Hepatitis B Virus Infection: Clinical and Epidemiological Implications
by Maria Antonia De Francesco, Franco Gargiulo, Francesca Dello Iaco, Laert Zeneli, Serena Zaltron, Giorgio Tiecco, Simone Pellizzeri, Emanuele Focà, Arnaldo Caruso and Eugenia Quiros-Roldan
Life 2025, 15(4), 672; https://doi.org/10.3390/life15040672 - 20 Apr 2025
Viewed by 31
Abstract
Hepatitis B virus (HBV) genetic variability, shaped by high mutation rates and selective pressures, complicates its management and increases the emergence of drug-resistant and immune-escape variants. This study aims to analyze immune escape mutations (IEMs) and drug resistance mutations (DRMs) in patients with [...] Read more.
Hepatitis B virus (HBV) genetic variability, shaped by high mutation rates and selective pressures, complicates its management and increases the emergence of drug-resistant and immune-escape variants. This study aims to analyze immune escape mutations (IEMs) and drug resistance mutations (DRMs) in patients with HBV infection exposed to antiviral therapies and exhibiting detectable plasma HBV viremia. This monocentric retrospective real-life study was carried out at the ASST Spedali Civili di Brescia, Italy, from 2015 to 2023. A total of 102 consecutive patients with detectable serum HBV-DNA exposed to at least one NA and for whom a drug resistance assay was available were included in our study. HBV sequences were amplified, sequenced, and analyzed for mutations using Geno2pheno and Stanford University tools. Phylogenetic analysis and statistical regression were performed to confirm genotypes and identify mutation patterns and associated risk factors. Our study shows a 38.2% prevalence of DRMs, with M204I/V (95%) and L180M (64%) being the most common, and a 43% prevalence of IEMs, primarily in the major hydrophilic region. Genotype D3 exhibited a higher mutation burden than other genotypes. Significant associations were found between HBsAb presence and increased IEM burden, while HBeAg was protective against DRMs. Atypical serological profiles were observed in 18.6% of patients, including cases of HBV reactivation under immunosuppressive therapy. This study highlights the high prevalence of IEMs and DRMs in a real-world setting, particularly among HBV genotype D3 carriers. These findings underscore the importance of mutation surveillance to guide therapeutic strategies, vaccine design, and public health policies to address the challenges posed by HBV genetic variability. Full article
(This article belongs to the Section Epidemiology)
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32 pages, 15555 KiB  
Article
Nanometric and Hydrophobic Green Rust Minerals upon Exposure to Amino Acids and Nickel as Prerequisites for a Primitive Chemiosmosis
by Nil Gaudu, Chloé Truong, Orion Farr, Adriana Clouet, Olivier Grauby, Daniel Ferry, Philippe Parent, Carine Laffon, Georges Ona-Nguema, François Guyot, Wolfgang Nitschke and Simon Duval
Life 2025, 15(4), 671; https://doi.org/10.3390/life15040671 - 19 Apr 2025
Viewed by 72
Abstract
Geological structures known as alkaline hydrothermal vents (AHVs) likely displayed dynamic energy characteristics analogous to cellular chemiosmosis and contained iron-oxyhydroxide green rusts in the early Earth. Under specific conditions, those minerals could have acted as non-enzymatic catalysts in the development of early bioenergetic [...] Read more.
Geological structures known as alkaline hydrothermal vents (AHVs) likely displayed dynamic energy characteristics analogous to cellular chemiosmosis and contained iron-oxyhydroxide green rusts in the early Earth. Under specific conditions, those minerals could have acted as non-enzymatic catalysts in the development of early bioenergetic chemiosmotic energy systems while being integrated into the membrane of AHV-produced organic vesicles. Here, we show that the simultaneous addition of two probable AHV components, namely nickel and amino acids, impacts green rust’s physico-chemical properties, especially those required for its incorporation in lipid vesicle’s membranes, such as decreasing the mineral size to the nanometer scale and increasing its hydrophobicity. These results suggest that such hydrophobic nano green rusts could fit into lipid vesicle membranes and could have functioned as a primitive, inorganic precursor to modern chemiosmotic metalloenzymes, facilitating both electron and proton transport in early life-like systems. Full article
(This article belongs to the Special Issue 2nd Edition—Featured Papers on the Origins of Life)
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24 pages, 578 KiB  
Article
Investigating the Effect of Algal Inclusions in Broiler Chickens
by Hanan Al-Khalaifah, Afaf Al-Nasser and Tahani Al-Surrayai
Life 2025, 15(4), 670; https://doi.org/10.3390/life15040670 - 17 Apr 2025
Viewed by 106
Abstract
There is growing interest in adding marine algae to poultry feed rations. The aim of the present study is to examine the effect of various inclusions of Sargassum sp., Gracilaria sp., and Spirulina sp. on productive performance, serum proteins, liver proteins, meat quality, [...] Read more.
There is growing interest in adding marine algae to poultry feed rations. The aim of the present study is to examine the effect of various inclusions of Sargassum sp., Gracilaria sp., and Spirulina sp. on productive performance, serum proteins, liver proteins, meat quality, and antioxidant activity in broiler chickens. There were seven dietary treatments (TRTs) as follows: TRT 1 was the control group without algae; TRT 2 was enriched with Sargassum sp. at 1% of the diet; TRT 3 with Sargassum sp. at 2% of the diet; TRT 4 with Gracilaria sp. at 0.5% of the diet; TRT 5 with Gracilaria sp. at 1% of the diet; TRT 6 with Spirulina sp. at 5% of the diet; TRT 7 with Spirulina sp. at 7.5% of the diet. Each treatment was replicated ten times, with 17 birds per replicate, and the analyses were performed in triplicates. Results of the feed rations proximate analyses revealed that the formulated diets contained the required amounts of protein, fat, fiber, ash, and moisture, to be fed to the broiler chickens. There was no effect of marine algae on the production performance parameters of the birds. All the enriched birds performed normally as the control group. It was shown that enriching the broiler diet with 1% Sargassum sp. Induced an increase in the total serum proteins, while Gracilaria sp. algal inclusion reduced the total serum proteins, compared to the control group. At five weeks of age, enriching broiler diets with 5% Spirulina sp. resulted in a higher concentration of total serum protein-C than the control group and the group enriched with 7.5% inclusion. Enriching the diet of 3- wks old broilers with Sargassum sp. at 2% elevated the proportions of serum LFABP. The maximum proportion of omega 6 fatty acid (∑n-6) was observed in the group of birds that received the control diet, while the proportion of omega 3 fatty acid (∑n-3) was highest in the algae-enriched groups. The results showed that all algal inclusions lowered the ratio of omega-6 to omega-3 fatty acids (∑n-6:∑n-3). Enriching broiler chickens with Spirulina at 5% and 7.5% increased the HDL concentration, compared to the control group. The palatability of meat for color, texture, flavor, appearance, smell, and overall acceptability was not negatively affected by algal inclusions. All algal inclusions enhanced the anti-oxidative status of broilers and lipid oxidative stability of the stored feed rations. In general, it can be concluded that marine algal inclusions showed no effect on the productive performance of the broiler chickens and can be used without any detrimental effects in poultry feed rations. Full article
(This article belongs to the Section Animal Science)
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14 pages, 1411 KiB  
Article
Transient Overexpression of the Pepper WRKY2 Gene in Nicotiana benthamiana Markedly Delays the Systemic Necrosis Caused by Tobacco Mosaic Virus
by Csilla Juhász, Ágnes Szatmári, Zoltán Bozsó, Balazs Barna and Gábor Gullner
Life 2025, 15(4), 669; https://doi.org/10.3390/life15040669 - 17 Apr 2025
Viewed by 81
Abstract
The role of WRKY transcription factor proteins in plant defense reactions against fungal and bacterial pathogens is well studied, but less information is available about plant–virus interactions. We observed the rapid and strong activation of the transcription factor gene, CaWRKY2, in pepper [...] Read more.
The role of WRKY transcription factor proteins in plant defense reactions against fungal and bacterial pathogens is well studied, but less information is available about plant–virus interactions. We observed the rapid and strong activation of the transcription factor gene, CaWRKY2, in pepper leaves following inoculation with Obuda pepper virus (ObPV). In contrast, CaWRKY2 was only weakly induced by pepper mild mottle virus (PMMoV) inoculation. To carry out a functional analysis of CaWRKY2, the gene was transiently overexpressed in Nicotiana benthamiana leaves by agroinfiltration. Four days later, CaWRKY2-overexpressing and empty vector control leaves were inoculated with tobacco mosaic virus (TMV). Transiently overexpressing CaWRKY2 did not affect the replication rate of TMV in the inoculated leaves. However, TMV inoculation up-regulated the expression of a pathogenesis-related gene (NbPR-1b) and a lipoxygenase (NbLOX1) gene significantly more strongly in N. benthamiana leaves overexpressing CaWRKY2 than in empty vector control leaves. Intriguingly, CaWRKY2 overexpression delayed (by 3 days) the development of systemic necrosis and plant death caused by TMV in N. benthamiana. These results suggest that CaWRKY2 is able to hinder the spread of TMV from inoculated leaves towards vascular tissues and systemic leaves in N. benthamiana. Full article
(This article belongs to the Section Plant Science)
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17 pages, 487 KiB  
Article
Comparative Effects of Tadalafil Cream Versus Oral Tadalafil on Males with Erectile Disfunction Regarding Relationship Dynamics: A Secondary Analysis of Dyadic Adjustment Outcomes in a Randomized Crossover Trial
by Dragoș-Mihail Trifu, Daniel-Corneliu Leucuța, Martina-Luciana Pintea-Trifu, Florin Elec, Nicolae Crișan, Dan Eniu and Ioan Coman
Life 2025, 15(4), 668; https://doi.org/10.3390/life15040668 - 17 Apr 2025
Viewed by 165
Abstract
Background/Objectives: Relationship quality is closely tied to sexual health. This study compared the effects of tadalafil cream and oral tadalafil on Dyadic Adjustment Scale (DAS) subscales and assessed the influence of age on treatment outcomes. Methods: This study includes a secondary analysis of [...] Read more.
Background/Objectives: Relationship quality is closely tied to sexual health. This study compared the effects of tadalafil cream and oral tadalafil on Dyadic Adjustment Scale (DAS) subscales and assessed the influence of age on treatment outcomes. Methods: This study includes a secondary analysis of data collected during a previously published randomized controlled crossover trial, but they were not published at that time. The participants (n = 35) completed both tadalafil cream and oral tadalafil interventions in a crossover design. Dyadic Adjustment, including DAS subscales, was assessed at baseline and after each intervention. Improvements across all DAS subscales were greater in the tadalafil cream group compared to the oral tadalafil group. Statistically significant differences were observed for Affective Expression (5.45, 95% CI: 0.22–10.67, p = 0.041) in the multivariate model. Notable gains were observed in Affective Expression and Dyadic Cohesion for the cream route. Within-group analysis showed statistically significant improvements in Affective Expression for both treatments and in Dyadic Cohesion for the cream route. The results show that younger participants benefited more from treatment, particularly in Affective Expression, Consensus subscales, and overall for Dyadic Adjustment. Conclusion: This study provides evidence that tadalafil intervention had a favorable impact on relationship dynamics, particularly in Affective Expression and Dyadic Cohesion. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Erectile Dysfunction)
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10 pages, 6155 KiB  
Article
Enhancing Volume Precision in Breast Reconstruction: A BMI-Based Model for Predicting Flap Weight in Profunda Artery Perforator Flaps
by Charalampos Varnava, Shaghayegh Gorji, Sascha Wellenbrock, Tobias Hirsch, Maximilian Kückelhaus and Philipp Wiebringhaus
Life 2025, 15(4), 667; https://doi.org/10.3390/life15040667 - 17 Apr 2025
Viewed by 100
Abstract
Background: In recent years, the profunda artery perforator (PAP) flap has gained recognition as a viable technique in autologous breast reconstruction, demonstrating low donor site morbidity and favorable reconstructive outcomes. This study aims to highlight the recent refinements using the PAP flap for [...] Read more.
Background: In recent years, the profunda artery perforator (PAP) flap has gained recognition as a viable technique in autologous breast reconstruction, demonstrating low donor site morbidity and favorable reconstructive outcomes. This study aims to highlight the recent refinements using the PAP flap for breast reconstruction focusing on preoperative volume prediction. Methods: A retrospective study was conducted to evaluate the outcomes of breast reconstruction surgeries using the PAP flap at our institution between May 2018 and December 2022. A total of 114 PAP flaps performed in 96 patients were included. Statistical analysis was performed to analyze flap volume in relation to body mass index (BMI). Surgical details, such as donor site-related complications and patient characteristics, were also collected. Results: BMI was identified as a statistically significant predictor (p < 0.001) for flap weight in the resulting model. The average BMI observed was 23.0, while the mean flap weight was 304.2 g. The predictive model for flap weight was determined as follows: flap weight (g) = (19.252 × BMI) − 143.572. This model underscores the relationship between BMI and flap weight, quantifying the influence of BMI on flap weight prediction. Conclusions: Our study indicates that it is feasible to harvest an adequate volume for breast reconstruction even in patients with a low BMI. To facilitate preoperative prediction of PAP flap volume, we developed an algorithm designed to enhance preoperative planning and estimate the need for supplementary procedures to achieve the desired volume. Full article
(This article belongs to the Special Issue Novel Approaches in Plastic and Reconstructive Surgery to Improve Quality of Life)
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17 pages, 1114 KiB  
Review
T-Follicular Helper Cells and Their Role in Autoimmune Diseases
by Michalis Christodoulou, Eleni Moysidou, Georgios Lioulios, Stamatia Stai, Christina Lazarou, Aliki Xochelli, Asimina Fylaktou and Maria Stangou
Life 2025, 15(4), 666; https://doi.org/10.3390/life15040666 - 17 Apr 2025
Viewed by 119
Abstract
T-follicular helper (Tfh) cells, a specialized subset of CD4+ cells, are the immune mediators connecting cellular and humoral immunity, as they lead B-cell proliferation within germinal centers, and orchestrate their response, including activation, class switching, and production of a diverse array of [...] Read more.
T-follicular helper (Tfh) cells, a specialized subset of CD4+ cells, are the immune mediators connecting cellular and humoral immunity, as they lead B-cell proliferation within germinal centers, and orchestrate their response, including activation, class switching, and production of a diverse array of high-affinity antibodies. Their interactions with B cells is regulated by a wide complex of transcriptional and cytokine-driven pathways. A major contribution of Tfh cells to autoimmune diseases is through their production of cytokines, particularly IL-21, which supports the proliferation and differentiation of autoreactive B cells. Elevated levels of circulating Tfh-like cells and IL-21 have been observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) correlating strongly with disease severity and autoantibody levels. The feedback loop between Tfh cells and IL-21 or other signal pathways, such as Bcl-6, ICOS, and PD-1, not only sustains Tfh cell function but also drives the continuous expansion of autoreactive B cells, leading to chronic inflammation through the production of high-affinity pathogenic autoantibodies. By understanding these interactions, Tfh pathways may serve as potential therapeutic targets, with IL-21, ICOS, and PD1 blockades emerging as promising innovative therapeutic strategies to manage autoimmune diseases. Although a variety of studies have been conducted investigating the role of Tfh cells in SLE and RA, this review aims to reveal the gap in the literature regarding the role of such subpopulations in the pathogenesis of other autoimmune diseases, such as Anca-associated vasculitis (AAV), and express the need to conduct similar studies. Tfh cell-related biomarkers can be used to assess disease activity and transform autoimmune disease treatment, leading to more personalized and effective care for patients with chronic autoimmune conditions. Full article
(This article belongs to the Special Issue The Interplay between Immune System and the Kidneys: Games without Frontiers?)
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21 pages, 1487 KiB  
Review
Beyond a Single Marker: An Update on the Comprehensive Evaluation of Right Ventricular Dysfunction in Pulmonary Thromboembolism
by Sandu Cucută, Minerva Codruta Badescu, Ștefania-Teodora Duca, Adriana Chetran, Maria-Ruxandra Cepoi, Cosmina-Georgiana Ponor, Amelian Madalin Bobu, Ionela-Lacramioara Serban and Irina-Iuliana Costache-Enache
Life 2025, 15(4), 665; https://doi.org/10.3390/life15040665 - 17 Apr 2025
Viewed by 208
Abstract
Pulmonary thromboembolism (PE) is a life-threatening condition that often leads to right ventricular (RV) dysfunction, a key determinant of prognosis and clinical management. Biomarkers play a crucial role in the early detection and risk stratification of RV dysfunction in PE, complementing imaging and [...] Read more.
Pulmonary thromboembolism (PE) is a life-threatening condition that often leads to right ventricular (RV) dysfunction, a key determinant of prognosis and clinical management. Biomarkers play a crucial role in the early detection and risk stratification of RV dysfunction in PE, complementing imaging and hemodynamic assessments. Cardiac troponins, B-type natriuretic peptides, and novel biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and growth differentiation factor-15 (GDF-15), provide valuable insights into myocardial injury, overload, and stress. This article explores the clinical possible significance of these biomarkers, their predictive value, and their potential to guide therapeutic strategies in patients with PE. Understanding the role of biomarkers in RV dysfunction assessment may improve patient outcomes focusing on early intervention and personalized treatment approaches. Full article
(This article belongs to the Section Physiology and Pathology)
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14 pages, 3655 KiB  
Article
Developmental Validation of DNA Quantitation System, Extended STR Typing Multiplex, and Database Solutions for Panthera leo Genotyping
by Lenka Vankova, Johana Alaverdyan and Daniel Vanek
Life 2025, 15(4), 664; https://doi.org/10.3390/life15040664 - 17 Apr 2025
Viewed by 188
Abstract
This study describes the development of a species determination/DNA quantification system called Pleo Qplex and an individual identification STR multiplex called Pleo STRplex using Panthera leo samples. Pleo Qplex enables us to measure the quantity of extracted nuclear and mitochondrial DNA and detect [...] Read more.
This study describes the development of a species determination/DNA quantification system called Pleo Qplex and an individual identification STR multiplex called Pleo STRplex using Panthera leo samples. Pleo Qplex enables us to measure the quantity of extracted nuclear and mitochondrial DNA and detect the presence of co-purified inhibitors. Pleo STRplex, consisting of seven loci, enables the determination of the DNA profile from a sample of Panthera leo based on the analysis of short tandem repeats (STRs). The Pleo STRplex provides additional loci on top of previously published STR loci in Ptig STRplex and contains a specific STR marker that confirms Panthera leo. An allelic ladder of all STR markers was prepared to enable reliable allele calling. The STR loci can also be used to type the DNA of other members of the genus Panthera. The work on the resulting STR profiles is performed using GenoProof Suite, which offers databasing, matching, and relationship analysis. Full article
(This article belongs to the Section Animal Science)
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19 pages, 3174 KiB  
Article
Expression of 9-O-Acetylated Sialic Acid in HPV+ Oral Squamous Cell Carcinoma Cells
by Hugo Sánchez-Martínez, Victoria Jiménez-Castillo, Daniela Illescas-Barbosa, Beatriz Xochitl Ávila-Curiel, María Teresa Hernández-Huerta, Risk Díaz-Castillejos, Rafael Torres-Rosas, Edgar Zenteno, Mohamed Alí Pereyra-Morales and Carlos Josué Solórzano-Mata
Life 2025, 15(4), 663; https://doi.org/10.3390/life15040663 - 17 Apr 2025
Viewed by 296
Abstract
Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents a significant global health issue. Sialylations are common events in tumor transformation, proliferation, metastasis, and immune evasion. Modifications in sialylation can be detected by lectins, whose changes [...] Read more.
Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents a significant global health issue. Sialylations are common events in tumor transformation, proliferation, metastasis, and immune evasion. Modifications in sialylation can be detected by lectins, whose changes in OSCC have been related to grade, invasion, and metastasis. The presence of 9-O-acetylated sialic acid (Neu5,9Ac2) in OSCC cells and its potential expression, modification, and role are unknown. This study aimed to analyze the expression of Neu5,9Ac2 using the Macrobrachium rosenbergii lectin (MrL) that recognizes this sialic acid (Neu5Ac) residue and also compare its effect on the SCC-152 cell line (CRL-3240, ATCC) and immortalized keratinocytes (HaCaT) as a control. We observed by immunocytochemistry that SCC-152 cells expressed more Neu5,9Ac2 compared to HaCaT cells; the specificity of MrL was confirmed after the sialidase treatment of cells in which the loss of lectin’s recognition of Neu5,9Ac2 was observed. The electrophoretic profile was similar between both cell line types; however, the Western blot showed differences in the glycoprotein patterns recognized by lectin for each cell type. MrL increased the proliferation of SCC-152 cells, as well as the integrity and morphology of the colonies. Therefore, our results suggest that Neu5,9Ac2 glycosylated receptors could be involved in the survival and proliferation of OSCC cells, which offers a promising avenue for developing diagnostic and prognostic tools (tumor markers) against oral squamous cell carcinoma in the future. Full article
(This article belongs to the Special Issue Sialic Acid and Sialic Acid Derivatives in Biomedicine)
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13 pages, 916 KiB  
Article
Effects of Nefopam on Postoperative Analgesia in Operating Room-Extubated Patients Undergoing Living Donor Liver Transplantation: A Propensity Score-Matched Analysis
by Min Suk Chae, Jin-Oh Jeong, Kyung Kwan Lee, Wonwoo Jeong, Young Wook Moon and Ji Young Min
Life 2025, 15(4), 662; https://doi.org/10.3390/life15040662 - 17 Apr 2025
Viewed by 166
Abstract
In patients undergoing living donor liver transplantation (LDLT) with immediate postoperative extubation in the operating room (OR), rapid recovery of consciousness and spontaneous ventilation are essential, requiring effective analgesia without compromising respiratory function. This study evaluated whether intraoperative nefopam administration improves early postoperative [...] Read more.
In patients undergoing living donor liver transplantation (LDLT) with immediate postoperative extubation in the operating room (OR), rapid recovery of consciousness and spontaneous ventilation are essential, requiring effective analgesia without compromising respiratory function. This study evaluated whether intraoperative nefopam administration improves early postoperative pain control and reduces opioid consumption in this physiologically distinct population. A retrospective cohort of 376 adult LDLT recipients who met the criteria for OR extubation was analyzed. After propensity score matching, 182 patients who received intraoperative nefopam were compared with 182 matched controls. Pain intensity was measured using the visual analog scale (VAS), and total fentanyl consumption and opioid-related complications were recorded over the first 24 h postoperatively. Nefopam administration was associated with significantly lower VAS scores during the first 12 h after surgery (p < 0.001) and reduced 24 h fentanyl consumption (53.2 ± 20.8 mL vs. 58.6 ± 27.5 mL, p = 0.035). No serious adverse effects related to nefopam were observed. The incidence of postoperative nausea and vomiting did not differ significantly between the groups. These findings indicate that nefopam offers effective early analgesia and an opioid-sparing effect in LDLT recipients undergoing OR extubation, suggesting its clinical utility as a component of multimodal analgesia in this high-risk group. Although the reduction in opioid use did not translate into a decreased incidence of opioid-related complications, the favorable safety profile and analgesic efficacy of nefopam support further investigation through prospective trials to define its role in enhanced recovery protocols for OR-extubated LDLT recipients. Full article
(This article belongs to the Special Issue Trends in Clinical Research 2025)
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14 pages, 1738 KiB  
Article
An Examination of the Ethnobotanical, Phytochemical, Antimicrobial, and Biological Properties of Zygophyllum coccineum, Emphasizing Its Potential as a Valuable Forage Shrub
by Fawziah M. Albarakaty, Mashail N. AlZain and Rehab M. A. El-Desoukey
Life 2025, 15(4), 661; https://doi.org/10.3390/life15040661 - 17 Apr 2025
Viewed by 104
Abstract
The growing issue of antimicrobial resistance poses a significant challenge for microbiological research, driving the need for alternative antibiotics with minimal side effects. Zygophyllum coccineum, commonly referred to as “Tebtab” in Arabic and “Red Spinepod” in English, has traditionally been utilized as [...] Read more.
The growing issue of antimicrobial resistance poses a significant challenge for microbiological research, driving the need for alternative antibiotics with minimal side effects. Zygophyllum coccineum, commonly referred to as “Tebtab” in Arabic and “Red Spinepod” in English, has traditionally been utilized as forage for camels and ruminants. While its antimicrobial activity against human pathogens has been documented, its efficacy against animal pathogens remains underexplored. This study aims to evaluate the phytochemical composition, biological activities, and antimicrobial potential of water and organic-solvent extracts of Zygophyllum coccineum against a range of reference microbial strains and animal pathogens. The findings revealed that all extracts exhibited notable antimicrobial, antioxidant, and cytotoxic activities attributed to their bioactive constituents. Among them, the ethyl acetate extract displayed the strongest antimicrobial effects against bacterial and fungal strains. Additionally, this extract demonstrated the highest antioxidant capacity and showed promising cytotoxic activity against lung (A549) and breast (MCF-7) cancer cell lines. These results underscore the potential of Zygophyllum coccineum as a valuable natural resource for developing antimicrobial, antioxidant, and cytotoxic therapies for applications in both human and veterinary medicine. Full article
(This article belongs to the Special Issue Development and Application of Antimicrobials)
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28 pages, 3433 KiB  
Article
Assessment of Intraspecific Variability in the Forest Dormouse (Dryomys nitedula) and Woolly Dormouse (Dryomys laniger) from Türkiye and Adjacent Regions Based on Mitochondrial DNA
by Ercüment Çolak, Georgi Markov, Engin Selvi, Teoman Kankılıç, Perinçek Seçkinozan Şeker, Maria A. Kocheva, Milena K. Gospodinova, Reyhan Çolak, Hristo Dimitrov and Nuri Yiğit
Life 2025, 15(4), 660; https://doi.org/10.3390/life15040660 - 17 Apr 2025
Viewed by 196
Abstract
This study aimed to reveal intraspecific variations in two Dryomys species distributed in Türkiye, based on mitochondrial DNA cytochrome b gene sequences, and to discuss the factors driving these variations in the context of phylogeography and genetic species concepts. As a result of [...] Read more.
This study aimed to reveal intraspecific variations in two Dryomys species distributed in Türkiye, based on mitochondrial DNA cytochrome b gene sequences, and to discuss the factors driving these variations in the context of phylogeography and genetic species concepts. As a result of Maximum Likelihood, Bayesian Inference, and Network analyses, which included haplogroups or lineages from Italy, Russia, the Caucasus, and Iran identified in previous studies, along with Turkish haplotypes, three major clades (MC1, MC2, and MC3) were identified within Dryomys nitedula. These clades began to diverge evolutionarily in the middle of the Late Miocene (8.82 million years ago) and exhibit significant genetic differences from one another. The Turkish haplotypes were divided into five distinct lineages (N1–N5), each within five subclades (SC1–SC5), which were nested within these MCs. These lineages, their geographical distributions, and the subspecies defined in previous studies that correspond to these lineages are as follows: N1 from the Thrace region (Dryomys nitedula wingei), N2 from the Black Sea region (potentially a new subspecies), N3 from western and central Anatolia (Dryomys nitedula phrygius), N4 from northeastern Anatolia (Dryomys nitedula tichomirowi), and N5 from eastern Anatolia (Dryomys nitedula pictus). The N2 lineage, distributed in areas close to the coastal side of the Eastern Black Sea region and with a range close to both N3 (D. n. phrygius) and N4 (D. n. tichomirowi), exhibited high genetic differentiation from these two lineages and was a candidate to be treated as a new subspecies of Dryomys nitedula in Türkiye. The N5 lineage, which includes haplotypes from the distribution areas of the populations initially classified as Dryomys pictus and later as Dryomys nitedula pictus in previous studies, was found to be more closely related to Dryomys nitedula kurdistanicus from the Zagros Mountains than to D. n. pictus from the central regions of Iran. Combining the results of this study with previous research, it is clear that the D. nitedula lineages in Türkiye, along with haplogroups or subspecies in neighboring regions diverged between the middle Late Miocene and Middle Pleistocene. This divergence is believed to have been driven by climatic cycles and geomorphological processes that shaped the topography of their distribution range. The high genetic diversity observed in the lineages of Anatolia suggests that the region may have served as a glacial refuge for D. nitedula. Similarly to the processes and factors shaping the evolution of D. nitedula, Dryomys laniger was found to have diverged into two lineages, western (L1) and eastern (L2 or Dryomys anatolicus), within its distribution range during the Late Pliocene (2.94 Mya). To make a more accurate taxonomic assessment of D. laniger, a larger number of samples is needed, and the distribution limits should be more clearly defined. Full article
(This article belongs to the Special Issue Ecology and Conservation of Small Mammals: Exploring Biodiversity, Climate Resilience, and Ecosystem Dynamics Through Small Mammal Monitoring and Research: 2nd Edition)
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12 pages, 1045 KiB  
Review
Ketoprofen Lysine Salt vs. Ketoprofen Acid: Assessing the Evidence for Enhanced Safety and Efficacy
by Agnese Graziosi, Michele Senatore, Gianluca Gazzaniga, Stefano Agliardi, Arianna Pani and Francesco Scaglione
Life 2025, 15(4), 659; https://doi.org/10.3390/life15040659 - 16 Apr 2025
Viewed by 177
Abstract
Endoscopic investigations reveal that a significant majority of individuals taking NSAIDs exhibit acute hemorrhages and mucosal erosions within the gastroduodenal lining. Ketoprofen acid (KA) is a potent NSAID with established efficacy and cardiovascular tolerability, but its gastric tolerability is a recognized limitation. To [...] Read more.
Endoscopic investigations reveal that a significant majority of individuals taking NSAIDs exhibit acute hemorrhages and mucosal erosions within the gastroduodenal lining. Ketoprofen acid (KA) is a potent NSAID with established efficacy and cardiovascular tolerability, but its gastric tolerability is a recognized limitation. To mitigate this, ketoprofen lysine salt (KLS) was developed. This review evaluates the pharmacological advantages of KLS over KA. While both KA and KLS maintain similar potency, KLS offers distinct advantages. Firstly, KLS demonstrates superior gastrointestinal protection through enhanced antioxidant properties and upregulation of mucosal defenses, as evidenced by both in vitro and in vivo studies. Secondly, KLS exhibits significantly faster absorption, leading to a more rapid onset of analgesic effects; this is attributed to its increased solubility and faster achievement of therapeutic concentrations. In essence, KLS addresses the gastric tolerability issues of KA while providing a quicker onset of action, making it a valuable alternative for patients requiring NSAID therapy, particularly those with gastric sensitivities or in need of rapid pain relief. Full article
(This article belongs to the Special Issue Pain and Therapy: Historical Perspectives and Future Directions)
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15 pages, 3064 KiB  
Article
Assessment of Primary Stability and Micromotion of Different Fixation Techniques for Scapular Spine Bone Blocks for the Reconstruction of Critical Bone Loss of the Anterior Glenoid—A Biomechanical Study
by Anton Brehmer, Yasmin Youssef, Martin Heilemann, Toni Wendler, Jean-Pierre Fischer, Stefan Schleifenbaum, Pierre Hepp and Jan Theopold
Life 2025, 15(4), 658; https://doi.org/10.3390/life15040658 - 16 Apr 2025
Viewed by 257
Abstract
Anteroinferior shoulder dislocations require surgical intervention when related to critical glenoid bone loss. Scapular spine bone blocks have emerged as a promising alternative to traditional bone augmentation techniques. However, limited data exist on their biomechanical stability when using different suture-based fixation techniques. This [...] Read more.
Anteroinferior shoulder dislocations require surgical intervention when related to critical glenoid bone loss. Scapular spine bone blocks have emerged as a promising alternative to traditional bone augmentation techniques. However, limited data exist on their biomechanical stability when using different suture-based fixation techniques. This study aimed to evaluate primary stability and micromotion after glenoid augmentation using a scapular spine bone block. A total of 31 fresh-frozen human shoulder specimens underwent bone block augmentation. The specimens were randomized into three groups: double-screw fixation (DSF), single-suture bone block cerclage (SSBBC), and double-suture bone block cerclage (DSBBC). Biomechanical testing was conducted using cyclic loading (5000 cycles at 1 Hz) and micromotion was analyzed using an optical 3D measurement system. Statistical analysis showed that medial irreversible displacement was significantly greater in the SSBBC group compared to DSF (p = 0.0386), and no significant differences were found in anterior or inferior irreversible displacements. A significant difference was noted in posterior reversible displacement (p = 0.0035), while no differences were found in inferior or medial reversible displacements. Between DSF and DSBBC, no significant differences were found in irreversible or reversible displacements in any direction. DSBBC provided stability comparable to DSF while offering a viable metal-free alternative. In contrast, SSBBC displayed inferior biomechanical properties, raising concerns about its clinical reliability. Full article
(This article belongs to the Special Issue Reconstruction of Bone Defects)
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19 pages, 306 KiB  
Review
The Role of High-Intensity Interval Training (HIIT) in Neuromuscular Adaptations: Implications for Strength and Power Development—A Review
by Chi-Hsiang Hung, Chun-Hsien Su and Dong Wang
Life 2025, 15(4), 657; https://doi.org/10.3390/life15040657 - 16 Apr 2025
Viewed by 323
Abstract
High-intensity Interval Training (HIIT) is increasingly recognized for enhancing neuromuscular function, strength, power, and overall athletic performance. This review systematically examined peer-reviewed studies published between 2000 and 2025, focusing on HIIT’s impact on motor unit recruitment, muscle fiber composition, neuromuscular efficiency, maximal strength, [...] Read more.
High-intensity Interval Training (HIIT) is increasingly recognized for enhancing neuromuscular function, strength, power, and overall athletic performance. This review systematically examined peer-reviewed studies published between 2000 and 2025, focusing on HIIT’s impact on motor unit recruitment, muscle fiber composition, neuromuscular efficiency, maximal strength, rate of force development (RFD), muscle hypertrophy, and power output. Findings indicate that HIIT significantly improves neuromuscular activation by increasing motor unit recruitment and synchronization, particularly in fast-twitch fibers essential for explosive movements. HIIT also promotes shifts toward Type II and hybrid Type IIa fibers, enhancing strength and endurance. However, despite its effectiveness in boosting RFD and explosive power, HIIT is less efficient than traditional resistance training for maximizing absolute strength and hypertrophy due to insufficient progressive overload. Integrating resistance-based and plyometric-based HIIT protocols emerged as an effective strategy to enhance strength and power concurrently. Effective periodization and recovery strategies, including active recovery and targeted nutrition, help mitigate fatigue and optimize adaptations. Notable research gaps include the long-term impacts of HIIT on neuromuscular function and the efficacy of individualized HIIT protocols based on specific athlete characteristics. Future research should focus on refining HIIT protocols for different sports, exploring its synergy with traditional resistance training, and assessing long-term adaptations to sustain strength and power gains. HIIT presents a valuable, time-efficient complement to conventional training methods for improving strength, power, and neuromuscular efficiency. Full article
(This article belongs to the Special Issue Effects of Exercise Training on Muscle Function)
13 pages, 532 KiB  
Article
Association of Plasma Renin Activity with Risk of Late Hypertension in Pediatric Patients with Early Aortic Coarctation Repair: A Retrospective Study
by Irina-Maria Margarint, Tammam Youssef, Iulian Rotaru, Alexandru Popescu, Olguta Untaru, Cristina Filip, Ovidiu Stiru, Ancuta-Alina Constantin, Vlad Anton Iliescu and Radu Vladareanu
Life 2025, 15(4), 656; https://doi.org/10.3390/life15040656 - 16 Apr 2025
Viewed by 175
Abstract
Background: Coarctation of the aorta (CoA) represents 5% to 7% of all congenital heart diseases. Surgery and interventional methods offer great short-term results, but the occurrence of postoperative hypertension associated with cardiovascular and cerebral vascular disease increases mortality and morbidity in the long [...] Read more.
Background: Coarctation of the aorta (CoA) represents 5% to 7% of all congenital heart diseases. Surgery and interventional methods offer great short-term results, but the occurrence of postoperative hypertension associated with cardiovascular and cerebral vascular disease increases mortality and morbidity in the long term. This study aims to investigate risk factors associated with postoperative hypertension in pediatric patients with early repair of isolated aortic coarctation. Subjects and Methods: A total of 41 patients with isolated aortic coarctation were included. The mean age was 35.3 ± 46.34 days. Early repair under one month was performed in 65.9% of patients. In all except two patients, end-to-end anastomosis was used. A follow-up at two years revealed an incidence of 58.5% of hypertension. Using logistic regression, preoperative renin plasma concentration above the upper normal level (46.1 μUI/mL) was independently associated with the occurrence of hypertension (OR = 2.49, 95% CI = 2.001–5.03, p = 0.001). Conclusion: Coarctation of the aorta is not just a simple mechanical obstruction of the aorta and should be seen and managed as a systemic disease. Abnormal preoperative renin concentrations were independently associated with the occurrence of HT at follow-up, suggesting that vascular dysfunction could play a role in hypertension development after successful CoA repair, negatively influencing the long-term prognostic of these patients. Full article
(This article belongs to the Special Issue Pediatric Cardiology Frontiers: Innovations in Diagnosis and Treatment)
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28 pages, 4779 KiB  
Review
Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
by Ese S. Ekhator, Marco Fazzari and Robert H. Newman
Life 2025, 15(4), 655; https://doi.org/10.3390/life15040655 - 16 Apr 2025
Viewed by 290
Abstract
Protein kinase A (PKA) is a key regulator of cellular signaling that regulates key physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3′,5′-cyclic adenosine triphosphate (cAMP) is well characterized, recent research highlights additional regulatory [...] Read more.
Protein kinase A (PKA) is a key regulator of cellular signaling that regulates key physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3′,5′-cyclic adenosine triphosphate (cAMP) is well characterized, recent research highlights additional regulatory mechanisms, particularly oxidative post-translational modifications, that influence PKA’s structure, activity, and substrate specificity. Both the regulatory and catalytic subunits of PKA are susceptible to redox modifications, which have been shown to play important roles in the regulation of key cellular functions, including cardiac contractility, lipid metabolism, and the immune response. Likewise, redox-dependent modulation of PKA signaling has been implicated in numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions, making it a potential therapeutic target. However, the mechanisms of crosstalk between redox- and PKA-dependent signaling remain poorly understood. This review examines the structural and functional regulation of PKA, with a focus on redox-dependent modifications and their impact on PKA-dependent signaling. A deeper understanding of these mechanisms may provide new strategies for targeting oxidative stress in disease and restoring balanced PKA signaling in cells. Full article
(This article belongs to the Section Physiology and Pathology)
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26 pages, 1131 KiB  
Review
Artificial Intelligence-Powered Quality Assurance: Transforming Diagnostics, Surgery, and Patient Care—Innovations, Limitations, and Future Directions
by Yoojin Shin, Mingyu Lee, Yoonji Lee, Kyuri Kim and Taejung Kim
Life 2025, 15(4), 654; https://doi.org/10.3390/life15040654 - 16 Apr 2025
Viewed by 314
Abstract
Artificial intelligence is rapidly transforming quality assurance in healthcare, driving advancements in diagnostics, surgery, and patient care. This review presents a comprehensive analysis of artificial intelligence integration—particularly convolutional and recurrent neural networks—across key clinical domains, significantly enhancing diagnostic accuracy, surgical performance, and pathology [...] Read more.
Artificial intelligence is rapidly transforming quality assurance in healthcare, driving advancements in diagnostics, surgery, and patient care. This review presents a comprehensive analysis of artificial intelligence integration—particularly convolutional and recurrent neural networks—across key clinical domains, significantly enhancing diagnostic accuracy, surgical performance, and pathology evaluation. Artificial intelligence-based approaches have demonstrated clear superiority over conventional methods: convolutional neural networks achieved 91.56% accuracy in scanner fault detection, surpassing manual inspections; endoscopic lesion detection sensitivity rose from 2.3% to 6.1% with artificial intelligence assistance; and gastric cancer invasion depth classification reached 89.16% accuracy, outperforming human endoscopists by 17.25%. In pathology, artificial intelligence achieved 93.2% accuracy in identifying out-of-focus regions and an F1 score of 0.94 in lymphocyte quantification, promoting faster and more reliable diagnostics. Similarly, artificial intelligence improved surgical workflow recognition with over 81% accuracy and exceeded 95% accuracy in skill assessment classification. Beyond traditional diagnostics and surgical support, AI-powered wearable sensors, drug delivery systems, and biointegrated devices are advancing personalized treatment by optimizing physiological monitoring, automating care protocols, and enhancing therapeutic precision. Despite these achievements, challenges remain in areas such as data standardization, ethical governance, and model generalizability. Overall, the findings underscore artificial intelligence’s potential to outperform traditional techniques across multiple parameters, emphasizing the need for continued development, rigorous clinical validation, and interdisciplinary collaboration to fully realize its role in precision medicine and patient safety. Full article
(This article belongs to the Special Issue Current and Future Perspectives of Artificial Intelligence in Medicine)
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22 pages, 3001 KiB  
Review
Epigenetic Mechanisms of Obesity: Insights from Transgenic Animal Models
by Elisa S. Na
Life 2025, 15(4), 653; https://doi.org/10.3390/life15040653 - 16 Apr 2025
Viewed by 273
Abstract
Obesity is a chronic disease with prevalence rates that have risen dramatically over the past four decades. This increase is not due to changes in the human genome but rather to environmental factors that promote maladaptive physiological responses. Emerging evidence suggests that external [...] Read more.
Obesity is a chronic disease with prevalence rates that have risen dramatically over the past four decades. This increase is not due to changes in the human genome but rather to environmental factors that promote maladaptive physiological responses. Emerging evidence suggests that external influences, such as high-fat diets, modify the epigenome—the interface between genes and the environment—leading to persistent alterations in energy homeostasis. This review explores the role of epigenetic mechanisms in obesity, emphasizing insights from transgenic animal models and clinical studies. Additionally, we discuss the evolution of obesity research from homeostatic to allostatic frameworks, highlighting key neuroendocrine regulators of energy balance. Full article
(This article belongs to the Special Issue Neurobiological and Neuroepigenetic Factors in Childhood Disorders: Autism Spectrum Disorder and Obesity)
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16 pages, 538 KiB  
Article
Impact of COVID-19 Pandemic on Consumption of Anxiolytics, Antipsychotics, and Antidepressants in South Italian Region
by Vittoria Satriani, Emanuela Santoro, Mario Capunzo, Rosaria Flora Ferrara, Roberta Manente, Biagio Santella, Gianluigi Franci, Francesco De Caro and Giovanni Boccia
Life 2025, 15(4), 652; https://doi.org/10.3390/life15040652 - 16 Apr 2025
Viewed by 159
Abstract
The COVID-19 lockdown had significant consequences on the mental health of millions of people, leading to the increasing prescription and use of psychotropic drugs. Due to the lack of data in the current literature, this study aims to estimate the trends in the [...] Read more.
The COVID-19 lockdown had significant consequences on the mental health of millions of people, leading to the increasing prescription and use of psychotropic drugs. Due to the lack of data in the current literature, this study aims to estimate the trends in the consumption of anxiolytics, antipsychotics, and antidepressants before and during the pandemic on people in the South Italian region. We conducted a retrospective observational study, retrieving prescriptions of anxiolytics, antipsychotics, and antidepressants dispensed in pharmacies of the Basilicata region (South Italy) for the period 2019–2021. We presented the data, expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD), on a total resident population of 95,021, dividing the age groups into categories <30, 30–50, 50–70, and >70 years. We conducted a linear regression model to examinate consumption trends across years. Software XLSTAT was used for statistical analysis. During the study period, more than 85,000 boxes of psychotropic medications were dispensed. The research showed an increase in the sales of all three categories of drugs examined, with a greater rise in benzodiazepines (88.5%) and selective serotonin reuptake inhibitors (81.9%) in 2021 compared to 2019, especially among women under 30 years. The COVID-19 pandemic had led to an increase in the consumption of psychotropic drugs, confirming the significant impact on the population’s mental health. Full article
(This article belongs to the Collection COVID-19 and Life)
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18 pages, 4375 KiB  
Article
Investigation of Cytotoxic, Antioxidant, Apoptotic/Necrotic Activity of Aquilaria agallocha Root Extract and Determination of Gene Expression Levels in HepG2, MCF-7 Cancer Cell Lines
by Semih Dalkılıç, Lütfiye Kadıoğlu Dalkılıç, Elgun İsbenov, Lütfü Uygur and Ceydanur Taşdemir
Life 2025, 15(4), 651; https://doi.org/10.3390/life15040651 - 16 Apr 2025
Viewed by 234
Abstract
Cancer is a common disease worldwide, and medicinal plants are widely used for its treatment. A. agallocha is a plant from the Thymelaeaceae family that is endemic to East Asia. Popularly known as the agar tree, this plant is used in the treatment [...] Read more.
Cancer is a common disease worldwide, and medicinal plants are widely used for its treatment. A. agallocha is a plant from the Thymelaeaceae family that is endemic to East Asia. Popularly known as the agar tree, this plant is used in the treatment of heart diseases, asthma, cough, ulcers, gout, inflammation, and pain. In this study, the cytotoxic, apoptotic/necrotic, and antioxidant activities of root extracts of A. agallocha and their effects on gene expression were investigated. Cytotoxic effects were analyzed by the MTT assay method, apoptotic/necrotic effects by the double staining method, and antioxidant effects by the DPPH radical scavenging assay. According to the results, the best cytotoxic effect in HepG2 cells was observed at 1000 µg/mL hexane extract. In MCF-7 cells, 250 µg/mL hexane extract showed the best activity. Antioxidant activity was highest in dH2O and lowest in the methanol extract. In gene expression analysis, hexane and methanol extracts decreased p53 expression in HepG2 cells, while acetone extract increased it. In addition, the expression of Bax and Bcl-2 genes generally increased. This study revealed the potent cytotoxic, antioxidant, and apoptotic effects of the A. agallocha extract. Full article
(This article belongs to the Special Issue Assessments of Bioactive and Toxic Substances in Cellular and Animal Models)
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12 pages, 773 KiB  
Article
Prevalence of Congenital Anomalies and Predictive Factors in Pregnant Women in Bahrain: A Retrospective Analysis
by Asal Buhasan, Leen Al Zayer, Lana Al-Jabery, Asmahan Mohamed, Abdulraoof Almadhoob, Entesar Zaman and Rafiea Jeddy
Life 2025, 15(4), 650; https://doi.org/10.3390/life15040650 - 15 Apr 2025
Viewed by 227
Abstract
Background and Objectives: In Bahrain, congenital anomalies (CAs) account for 8.1% of the total deaths in children under 5, indicating a need to understand the patterns, predictors, and prevalence to improve antenatal standards of care and reduce the burden of disease. This [...] Read more.
Background and Objectives: In Bahrain, congenital anomalies (CAs) account for 8.1% of the total deaths in children under 5, indicating a need to understand the patterns, predictors, and prevalence to improve antenatal standards of care and reduce the burden of disease. This study aimed to determine the prevalence and characteristics of CAs in Bahrain and investigate their association with measured neonatal and maternal risk factors. Method: In this five-year retrospective study, data from 31,615 neonates were analyzed, of which 354 had confirmed CAs. Stillbirths, abortions, and CAs discovered later in life were excluded from the study. Results: The prevalence of CAs was determined to be 1.1% (incidence of 11.2 per 1000 births), with 40.1% of the CAs affecting multiple systems. A statistically significant association was found between CAs and nationality, method of conception, gender, method of delivery, diabetes mellitus status, hypertension, and gestational age at birth. However, the association between CAs and multiple gestations was deemed statistically insignificant. Conclusions: As the first study exploring the associations between CAs and potential risk factors and outcomes in Bahrain, it provided a foundation for further exploration of the topic and insight into factors healthcare providers would target during preconception and antenatal care. Full article
(This article belongs to the Special Issue From Stem Cells to Embryos, Congenital Anomalies and Epidemiology)
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Article
Establishing the Diagnostic Reference Levels for Common Dubai Health Adult Nuclear Medicine Examinations
by Entesar Z. Dalah, Najlaa K. Al Mazrouei and Zahra A. Al Ali
Life 2025, 15(4), 649; https://doi.org/10.3390/life15040649 - 15 Apr 2025
Viewed by 120
Abstract
Nuclear medicine (NM) procedures are performed using unsealed radioactive sources that are administered to patients, resulting in both internal and external exposure for patients and staff alike. Optimization is mainly concerned with ensuring the use of the lowest sufficient level of radiation to [...] Read more.
Nuclear medicine (NM) procedures are performed using unsealed radioactive sources that are administered to patients, resulting in both internal and external exposure for patients and staff alike. Optimization is mainly concerned with ensuring the use of the lowest sufficient level of radiation to perform a procedure while maintaining adequate image quality. Diagnostic reference levels (DRLs) have been proven effective in aiding optimization in clinical practice. This dose review aims to establish an inclusive DRL system for the common adult NM procedures performed at Dubai Health. Our defined DRLs will focus on both the administered radiopharmaceuticals and the radiation dose metrics derived from hybrid computed tomography (CT). Dose surveys for 1439 adult nuclear medicine procedures performed over twelve months were collected and retrospectively analyzed. DRLs were obtained for a total of eight scintigraphy procedures, four hybrid positron emission tomography procedures with CT (denoted PET/CT), and five target sites for CT hybrid single-photon emission tomography with CT (denoted as SPECT/CT). Our derived DRLs for the scintigraphy, hybrid SPECT/CT and PET/CT procedures are within the reported national DRLs, except for the CT dose of the hybrid SPECT/CT for the neck, abdomen and chest/abdomen sites and the 18F PSMA administered activity. A fixed activity dose was administered for a scintigraphy procedure that is weight dependent. This patient dose review serves as a foundational effort aiming to optimize radiation safety and standardize diagnostic practices in NM. Further research is needed to enhance adherence to safety benchmarks. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
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