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15 pages, 2604 KB

Open AccessArticle

“Protective” Imazalil vs Its Negative Effects on Immune System Cells—Neutrophils

by Wioletta Ratajczak-Wrona, Aleksandra Aniszewska, Agnieszka Iwaniuk, Marzena Garley, Sławomir Wołczyński, Dariusz Jan Skarżynski, Jolanta Wrobel, Agnieszka Zebrowska, Piotr Radziwon, Barbara Pucelik and Ewa Jabłońska

Life 2026, 16(2), 365; https://doi.org/10.3390/life16020365 - 23 Feb 2026

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Abstract

Neutrophils are the most numerous population of peripheral blood leukocytes and play a key role in innate immunity, participating in antibacterial, antifungal, antiviral, and antitumor responses. Their activity can be modulated by endogenous and exogenous factors, including pesticides, among which fungicides such as [...] Read more.

Neutrophils are the most numerous population of peripheral blood leukocytes and play a key role in innate immunity, participating in antibacterial, antifungal, antiviral, and antitumor responses. Their activity can be modulated by endogenous and exogenous factors, including pesticides, among which fungicides such as the commonly used imazalil (IMZ) constitute a significant group. The objective of this study was to assess the effect of IMZ (at an environmental dose of 0.07 ng/mL, as well as 10- and 100-fold higher doses) on selected functions of neutrophils. This study demonstrated that neutrophils incubated with IMZ at a dose detectable in the serum, exhibited lower phagocytotic capacity. In addition, at a 10-fold higher dose, this compound reduced the chemotactic capacity of neutrophils and led to increased activity of NADPH oxidase in these cells. Furthermore, it was observed that at the highest concentration used in this study IMZ intensified the production of nitric oxide. The exposure of neutrophils—the first line of defense—to IMZ affected their locomotion and pathogen-eliminating function. Moreover, the response of neutrophils was not proportionate to the concentration of IMZ used in the study. Full article

(This article belongs to the Special Issue Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions—2nd Edition)

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17 pages, 1270 KB

Open AccessArticle

Fitzpatrick Skin Phototype Is Independently Associated with Differential Short-Term Cutaneous Reactivity Following Standardized Topical Provocation in Humans

by Laura Maghiar, Corina Beiușanu, Corina Moisa, Timea Claudia Ghitea, Octavia Gligor, Antonia Maria Lestyan, Marieta Lestyan, Ilarie Brihan, Teodor-Andrei Maghiar, Csaba Nagy, Mădălin Florin Ganea, Laura Grațiela Vicaș and Mariana Ganea

Life 2026, 16(2), 364; https://doi.org/10.3390/life16020364 - 22 Feb 2026

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Abstract

Background: Human cutaneous reactivity exhibits marked inter-individual variability, yet the contribution of constitutional pigmentation traits to short-term skin responses remains incompletely characterized. Fitzpatrick skin phototype reflects stable differences in pigmentation-related traits and may therefore act as a phenotypic modifier of early cutaneous reactivity [...] Read more.

Background: Human cutaneous reactivity exhibits marked inter-individual variability, yet the contribution of constitutional pigmentation traits to short-term skin responses remains incompletely characterized. Fitzpatrick skin phototype reflects stable differences in pigmentation-related traits and may therefore act as a phenotypic modifier of early cutaneous reactivity following topical exposure. Methods: In this controlled human study, 239 healthy volunteers were stratified by Fitzpatrick skin phototype into three groups: I–II (n = 138), III (n = 72), and IV–V (n = 29). A standardized emulgel-based topical provocation model was applied under occlusion to the volar forearm, and cutaneous responses were assessed at 20 min (Test A), 24 h (Test B), and 96 h (Test C) using standardized visual scoring. Group comparisons, multivariable linear regression models adjusted for age, sex, country of origin, and experimental lot, and stratified analyses by country of origin, were performed. Results: Early and short-term cutaneous responses differed significantly across phototype groups. Participants with phototypes I–II exhibited higher response scores at both 20 min and 24 h compared with phototype III (p < 0.001). In adjusted models, phototype III remained independently associated with significantly lower reactivity relative to phototypes I–II at 20 min (β = −1.61, p < 0.001) and 24 h (β = −0.98, p < 0.001). Responses among phototypes IV–V were minimal to absent; however, this subgroup was underrepresented, and findings for IV–V are descriptive. Age was a significant positive predictor of response intensity, whereas sex showed no independent association. No persistent reactions were observed at 96 h in any phototype group. Stratified analyses confirmed that the reduced reactivity associated with phototype III was independent of country of origin. Conclusions: Fitzpatrick skin phototype is independently associated with early and short-term cutaneous reactivity following standardized topical provocation in humans. Lighter phototypes (I–II) demonstrate increased susceptibility to transient inflammatory responses, whereas phototype III shows markedly reduced reactivity. These findings support the role of skin phototype as a constitutional modifier of short-term cutaneous responses and highlight the importance of considering pigmentation-related phenotypes in the design and interpretation of dermatological testing, cosmetic tolerability studies, and safety assessments of topical formulations. Full article

(This article belongs to the Section Physiology and Pathology)

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18 pages, 475 KB

Open AccessReview

The Evolving Landscape of Anti-Clonal Therapy in Newly Diagnosed Systemic Light-Chain (AL) Amyloidosis: Evidence- and Time-Based Comparison with Multiple Myeloma

by Rafael Ríos-Tamayo

Life 2026, 16(2), 363; https://doi.org/10.3390/life16020363 - 22 Feb 2026

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Abstract

Light-chain (AL) amyloidosis is a rare and incurable disease, classified under the category of plasma cell neoplasms and other diseases with paraproteins in the 5th Edition of the World Health Organization classification of lymphoid tumors. This entity shares some similarities with multiple myeloma [...] Read more.

Light-chain (AL) amyloidosis is a rare and incurable disease, classified under the category of plasma cell neoplasms and other diseases with paraproteins in the 5th Edition of the World Health Organization classification of lymphoid tumors. This entity shares some similarities with multiple myeloma (MM), remarkably a bone marrow infiltration of clonal plasma cells. Moreover, one out of five newly diagnosed cases of AL amyloidosis (NDAL) also fulfills the current diagnostic criteria for MM. A multidisciplinary therapy approach should be established, in which hematological therapy plays a crucial role. Anti-clonal therapy is the basis of hematological therapy, in addition to supportive therapy and emerging anti-fibrils therapy. In recent years, advances in the anti-clonal therapy for MM have progressively transferred to carefully selected patients with systemic AL amyloidosis, significantly improving outcomes in this rapidly changing field. This review aims to critically analyze the comparative evolution and evidence-based approach of anti-clonal therapy in NDAL vs. MM since the introduction of bortezomib. Participation in clinical trials remains the first option to consider in daily clinical practice. Full article

(This article belongs to the Section Medical Research)

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7 pages, 666 KB

Open AccessCase Report

Robot-Assisted Radical Prostatectomy After Rezūm: A Case Report and Literature Review

by Kosta Cerović and Simon Hawlina

Life 2026, 16(2), 362; https://doi.org/10.3390/life16020362 - 21 Feb 2026

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Abstract

Minimally invasive surgical therapies (MISTs), such as Rezūm™ Water Vapor Therapy, are emerging treatment options for benign prostatic obstruction (BPO). When prostate cancer is subsequently diagnosed, radical prostatectomy may still be indicated. However, evidence regarding intraoperative challenges and the surgical and functional outcomes [...] Read more.

Minimally invasive surgical therapies (MISTs), such as Rezūm™ Water Vapor Therapy, are emerging treatment options for benign prostatic obstruction (BPO). When prostate cancer is subsequently diagnosed, radical prostatectomy may still be indicated. However, evidence regarding intraoperative challenges and the surgical and functional outcomes of robot-assisted radical prostatectomy (RARP) following Rezūm remains limited. We report the first documented case of RARP following Rezūm in a 68-year-old man. He initially underwent Rezūm for symptomatic BPO. Due to rising PSA, a suspicious lesion on MRI, and a biopsy-confirmed high-risk prostate carcinoma, radical surgery was performed. Intraoperatively, dense fibrosis and altered tissue planes required precise dissection and a level 2 bilateral nerve-sparing approach. A systematic review revealed no previously published cases of RARP after Rezūm. On the other hand, RARP after transurethral resection of the prostate (TURP) is associated with increased operative time, blood loss, and bladder neck reconstruction, though late continence and biochemical recurrence rates are similar to those in treatment-naïve patients. In conclusion, RARP after ablative BPO therapies is feasible but may present unique technical challenges. Larger prospective studies are needed to develop standardized management strategies. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prognosis of Prostate Cancer)

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14 pages, 3110 KB

Open AccessSystematic Review

Diabetes Mellitus as a Risk Factor for Severe Disease and Mortality Among Patients with Melioidosis: A Systematic Review and Meta-Analysis

by Jongkonnee Thanasai, Anchalee Chittamma, Supphachoke Khemla, Atthaphong Phongphithakchai, Moragot Chatatikun, Jitbanjong Tangpong, Sa-ngob Laklaeng and Wiyada Kwanhian Klangbud

Life 2026, 16(2), 361; https://doi.org/10.3390/life16020361 - 21 Feb 2026

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Abstract

Background: Melioidosis is a potentially fatal infectious disease caused by Burkholderia pseudomallei and is highly prevalent in tropical regions. Diabetes mellitus (DM) is the most common comorbidity among patients with melioidosis and is a well-established risk factor for acquiring the infection. However, [...] Read more.

Background: Melioidosis is a potentially fatal infectious disease caused by Burkholderia pseudomallei and is highly prevalent in tropical regions. Diabetes mellitus (DM) is the most common comorbidity among patients with melioidosis and is a well-established risk factor for acquiring the infection. However, the impact of diabetes on disease severity and mortality remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies to evaluate the association between diabetes mellitus and severe clinical outcomes in patients with melioidosis. PubMed, Embase, and Scopus were searched from database inception to 6 January 2026. Outcomes of interest included bacteremia, septic shock, intensive care unit (ICU) admission, and mortality. Pooled odds ratios with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed using the I² statistic. The review was registered in PROSPERO (CRD420251237028). Results: Twelve studies comprising patients from Southeast Asia, Australia, and South Asia were included. Diabetes prevalence among patients with melioidosis ranged from 31% to 76%. Meta-analysis showed no significant association between diabetes mellitus and bacteremia (OR 1.48, 95% CI 0.97–2.27), ICU admission (OR 1.31, 95% CI 0.43–3.99), septic shock (OR 0.67, 95% CI 0.39–1.16), or mortality (OR 0.82, 95% CI 0.66–1.03). Subgroup analysis revealed lower mortality among patients with diabetes in Southeast Asia (OR 0.74, 95% CI 0.61–0.91), while no significant association was observed in Australia. Heterogeneity varied across outcomes and regions. Conclusions: Although diabetes mellitus is a major risk factor for acquiring melioidosis, our findings suggest that it is not consistently associated with increased disease severity or mortality once infection occurs. These results should be interpreted cautiously given the limited number of included studies, heterogeneity across outcomes, and potential residual confounding. Further prospective studies are required to better define the underlying biological and healthcare-related mechanisms. Full article

(This article belongs to the Section Microbiology)

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12 pages, 407 KB

Open AccessArticle

Comparison of Scrotal Orchiopexy Versus Traditional Inguinal Orchiopexy for Palpable Undescended and Retractile Testis in Children: Insights from a Greek Surgical Center

by Maria Florou, Triantafyllia Koletsa, Sophia Tsokkou, Georgia Raptou, Antonia Syrnioti, Ioannis Spyridakis and Christos Kaselas

Life 2026, 16(2), 360; https://doi.org/10.3390/life16020360 - 21 Feb 2026

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Abstract

Introduction/Purpose: Congenital cryptorchidism and retractile testis represent the most commonly presented abnormalities of the male genitourinary system. Orchiopexy is the surgical treatment for both conditions and can be performed either via the conventional two-incision surgical approach or via a singular scrotal incision. [...] Read more.

Introduction/Purpose: Congenital cryptorchidism and retractile testis represent the most commonly presented abnormalities of the male genitourinary system. Orchiopexy is the surgical treatment for both conditions and can be performed either via the conventional two-incision surgical approach or via a singular scrotal incision. The present study firstly investigated the complications associated with each orchiopexy approach in a single-center pediatric surgical department and secondly compared the surgical outcomes in children with congenital cryptorchidism or retractile testes. Methodology: A retrospective analysis was conducted in pediatric patients with either congenital cryptorchidism or retractile testes who underwent orchiopexy from 2015 to 2019. Data collected during the study included diagnosis, surgical technique and both short- and long-term complications. Patient stratification was performed in accordance with the type of orchiopexy and the diagnosis UDT vs. RT and inguinal orchidopexy vs. scrotal orchidopexy. Results: A total of 362 children underwent 443 orchiopexies of which 227 were inguinal and 216 were scrotal. Complications were reported in 16 (3.6%) surgeries and from which 14 (3.16%) were presented in for postoperative complications. Short-term complications were presented in four (0.9%) cases and consisted of wound dehiscence. Long-term complications were recorded in 12 (2.7%) cases, including recurrence in six (1.3%) testes, testicular atrophy in three (0.6%) cases and presentation of hydrocele or inguinal hernia in two (0.4%) and one (0.2%) patient, respectively. Notably, 13 orchidopexies with preoperative diagnosis of congenital cryptorchidism, were linked with complications (p = 0.01), 12 of which underwent with two-incision technique (p = 0.07). Conclusions: The findings of the study suggest that a preoperative diagnosis of congenital cryptorchidism is a possible risk factor for postoperative complications. With regard to the surgical technique performed, the single-incision scrotal orchiopexy appears to be a much safer and more effective approach palpable undescended testes, compared to the two-incision approach. For the high-lying testes, although the single-scrotal technique provides good results, more prospective studies with selected impalpable undescended testes are needed to strengthen the existing literature. Full article

(This article belongs to the Section Reproductive and Developmental Biology)

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13 pages, 272 KB

Open AccessReview

Selective Androgen Receptor Modulators in Women: What Do We Know, and What Is Still Missing

by Veselin Vasilev, Katerina Georgieva, Maria Kraeva, Raina Ardasheva, Rumyana Etova and Nikolay Boyadjiev

Life 2026, 16(2), 359; https://doi.org/10.3390/life16020359 - 20 Feb 2026

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Abstract

Androgens and androgen receptor (AR) signaling influence many aspects of female physiology, including reproduction, musculoskeletal health, metabolism, and neurological regulation, yet are less studied than in males. Selective androgen receptor modulators (SARMs) were developed to provide tissue-selective anabolic effects with reduced androgenic side [...] Read more.

Androgens and androgen receptor (AR) signaling influence many aspects of female physiology, including reproduction, musculoskeletal health, metabolism, and neurological regulation, yet are less studied than in males. Selective androgen receptor modulators (SARMs) were developed to provide tissue-selective anabolic effects with reduced androgenic side effects, but their effects in women are not well defined. This narrative review summarizes preclinical and clinical evidence on SARM use in female rodents and women, focusing on AR biology, tissue selectivity, therapeutic potential, and safety. A literature search of PubMed, Scopus, and Google Scholar identified relevant experimental and clinical studies addressing sex-specific AR signaling and SARM effects in females. Preclinical data indicate that SARMs can enhance sexual motivation and improve muscle and bone outcomes in ovariectomized models, with compound-dependent effects on reproductive tissues. Clinical studies in postmenopausal women demonstrate increases in lean body mass with generally limited androgenic effects, although functional benefits are inconsistent and alterations in lipid profiles and liver enzymes have been reported. Evidence also supports antitumor activity of AR-targeted SARMs in selected breast cancer subtypes. Overall, while SARMs show therapeutic potential in women, long-term safety and efficacy remain insufficiently characterized, warranting further sex-specific clinical investigation. Full article

(This article belongs to the Section Medical Research)

26 pages, 1890 KB

Open AccessReview

Pharmacological and Medicinal Properties of the South American Medicinal Plant Bowdichia virgilioides Kunth and Its Bioactive Products

by Christian Bailly

Life 2026, 16(2), 358; https://doi.org/10.3390/life16020358 - 20 Feb 2026

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Abstract

Bowdichia virgilioides Kunth is a tree largely present in South America, notably in the Cerrado savannah. The species is known for the quality of its dense and resistant wood, used in construction and furnishing. B. virgilioides is also a medicinal plant used, from [...] Read more.

Bowdichia virgilioides Kunth is a tree largely present in South America, notably in the Cerrado savannah. The species is known for the quality of its dense and resistant wood, used in construction and furnishing. B. virgilioides is also a medicinal plant used, from leaves to roots, for the treatment of various human pathologies (pharyngitis, bronchitis, healing wounds, diabetes, and arthritis). The present review provides an analysis of the scientific literature pertaining to B. virgilioides, with a focus on pharmacological activities. Aqueous and organic extracts have been used to treat inflammatory pathologies and to combat infectious diseases caused by microorganisms and parasites. All phytochemicals at the origin of the bioactivities of extracts have been identified, including 37 terpenoids, 8 alkaloids, 21 flavonoids and 13 other products. All natural products are discussed, with a focus on a dozen compounds with well-documented pharmacological properties and/or a known mechanism of action. Key products include ormosanine (alkaloid), vouacapane (diterpenoid), lupeol (terpenoid), isoquercetin (flavonoid), isocordoin (chalcone), and little-known specific products (bowdichine and bowdenol). The botanical and phytochemical analysis shed light on this valuable Fabaceae species with the objective to promote its preservation and cultivation, as well as further pharmacological investigations aimed at rationalizing its long-established ethnobotanical use. Full article

(This article belongs to the Special Issue Therapeutic Innovations from Plants and Their Bioactive Extracts)

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13 pages, 1494 KB

Open AccessArticle

Development and Clinical Validation of an Artificial Intelligence-Based Automated Visual Acuity Testing System

by Kelvin Zhenghao Li, Hnin Hnin Oo, Kenneth Chee Wei Liang, Najah Ismail, Jasmine Ling Ling Chua, Jackson Jie Sheng Chng, Yang Wu, Daryl Wei Ren Wong, Sumaya Rani Khan, Boon Peng Yap, Rong Tong, Choon Meng Kiew, Yufei Huang, Chun Hau Chua, Alva Khai Shin Lim and Xiuyi Fan

Life 2026, 16(2), 357; https://doi.org/10.3390/life16020357 - 20 Feb 2026

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Abstract

Background: To develop and validate an automated visual acuity (VA) testing system integrating artificial intelligence (AI)–driven speech and image recognition technologies, enabling self-administered, clinic-based VA assessment; Methods: The system incorporated a fine-tuned Whisper speech-recognition model with Silero voice activity detection and pose estimation [...] Read more.

Background: To develop and validate an automated visual acuity (VA) testing system integrating artificial intelligence (AI)–driven speech and image recognition technologies, enabling self-administered, clinic-based VA assessment; Methods: The system incorporated a fine-tuned Whisper speech-recognition model with Silero voice activity detection and pose estimation through facial landmark and ArUco marker detection. A state-driven interface guided users through sequential testing with and without a pinhole. Speech recognition was enhanced using a local Singaporean English dataset. Laboratory validation assessed speech and pose recognition performance, while clinical validation compared automated and manual VA testing at a tertiary eye clinic; Results: The fine-tuned model reduced word error rates from 17.83% to 9.81% for letters and 2.76% to 1.97% for numbers. Pose detection accurately identified valid occluder states. Among 72 participants (144 eyes), automated unaided VA showed good agreement with manual VA (ICC = 0.77, 95% CI 0.62–0.85), while pinhole VA demonstrated moderate agreement (ICC = 0.63, 95% CI 0.25–0.83). Automated testing took longer (132.1 ± 47.5 s vs. 97.1 ± 47.8 s; p < 0.001), but user experience remained positive (mean Likert scale score 4.3 ± 0.8); Conclusions: The AI-based automated VA system delivered accurate, reliable, and user-friendly performance, supporting its feasibility for clinical implementation. Full article

(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)

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18 pages, 2294 KB

Open AccessArticle

Preoperative Parameters Associated with Vitrectomy Outcomes in Myopic Traction Maculopathy Without a Full-Thickness Macular Hole

by Su Kyung Lee, Suji Yeo, Yoo-Ri Chung, Hae Rang Kim and Ji Hun Song

Life 2026, 16(2), 356; https://doi.org/10.3390/life16020356 - 19 Feb 2026

Viewed by 619

Abstract

Pathologic myopia has become a major global cause of blindness, making timely surgical management for myopic traction maculopathy (MTM) increasingly important. This study aimed to identify prognostic factors associated with functional and anatomical outcomes following surgery for MTM and to determine the optimal [...] Read more.

Pathologic myopia has become a major global cause of blindness, making timely surgical management for myopic traction maculopathy (MTM) increasingly important. This study aimed to identify prognostic factors associated with functional and anatomical outcomes following surgery for MTM and to determine the optimal timing for intervention. This retrospective study included 33 eyes from 28 patients with MTM without full-thickness macular hole who underwent pars plana vitrectomy with internal limiting membrane peeling and gas tamponade. Better preoperative best-corrected visual acuity (BCVA) and lower foveal height were associated with better postoperative BCVA, whereas longer axial length, higher MTM, and higher Atrophy–Traction–Neovascularization (ATN) classification grade were correlated with thinner postoperative central foveal thickness. Foveal detachment (FD), ellipsoid zone (EZ) disruption, and advanced MTM grade were associated with poorer functional and anatomical outcomes. Postoperative visual outcomes should be interpreted with caution, as they may have been influenced by lens-related factors, including combined cataract surgery, post-vitrectomy cataract progression, and posterior capsule opacity. Nonetheless, consistent anatomical improvement was observed, supporting early surgical consideration in eyes with MTM showing progressive macular traction or EZ disruption, even in the absence of FD. These findings highlight the importance of serial OCT monitoring and individualized surgical timing based on preoperative assessments. Full article

(This article belongs to the Special Issue Dive into Myopia)

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24 pages, 2576 KB

Open AccessArticle

Optimization of Cultivation Substrate Formula and Key Physical Parameters for Domestication of Floccularia luteovirens by Response Surface Methodology

by Xu Zhao, Siyuan Gou, Lihua Tang, Tongjia Shi, Zhiqiang Zhao, Wensheng Li and Yan Wan

Life 2026, 16(2), 355; https://doi.org/10.3390/life16020355 - 19 Feb 2026

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Abstract

Floccularia luteovirens is an edible and medicinal fungus with great development value on the Qinghai–Tibet Plateau, but its artificial domestication and cultivation are limited by the lack of systematic research on cultivation substrate formulas and key parameters. This study adopted the technical route [...] Read more.

Floccularia luteovirens is an edible and medicinal fungus with great development value on the Qinghai–Tibet Plateau, but its artificial domestication and cultivation are limited by the lack of systematic research on cultivation substrate formulas and key parameters. This study adopted the technical route of “preliminary screening—single-factor optimization—response surface collaborative optimization” to conduct research on the screening and optimization of its domestication cultivation substrate. Firstly, through the preliminary screening of 26 groups of formulas, a basic cultivation substrate formula with compatible complex nutrition and physical structure was determined. Secondly, single-factor experiments clarified that mixed sawdust was the optimal main substrate, corn flour was the optimal auxiliary substrate, the suitable substrate-to-water ratio was 1:1.6, and the suitable compactness was a substrate surface height of 12–12.5 cm (corresponding to a bulk density of 1.10–1.15 g/cm³ and a porosity of 60.6–63.3%). Finally, based on the response surface Box–Behnken model, with the main substrate, substrate-to-water ratio, and compactness as independent variables, and the total mycelial growth in 30 days as the response value, response surface optimization was performed to obtain the optimal formula: main substrate 76.002%, substrate-to-water ratio 1:1.721, and compactness 12.845 cm. Under these conditions, the mycelial growth reached 28.75 mm, which was highly consistent with the model’s predicted value (28.012 mm), and the constructed quadratic regression model showed excellent fitness (R² = 0.9920, p = 0.0008). This study clarified the core influencing factors and adaptation mechanism of the cultivation substrate for Floccularia luteovirens, filled the research gap in the domestication cultivation substrate of this fungus, and provided basic technical parameters for its large-scale artificial cultivation. Full article

(This article belongs to the Section Microbiology)

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26 pages, 593 KB

Open AccessReview

Coronary Artery Spasm in Patients with Type 2 Diabetes Mellitus

by Theodor Iulian Matei, Minerva Codruta Badescu, Alexandru Dan Costache, Ionuț Tudorancea, Ionela Lăcrămioara Șerban, Sandu Cucută, Bianca-Ana Dmour, Raluca Daria Mitea, Radu-George Ciorap, Ciprian Rezus and Irina Iuliana Costache-Enache

Life 2026, 16(2), 354; https://doi.org/10.3390/life16020354 - 19 Feb 2026

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Abstract

Cardiovascular disease and diabetes mellitus have now reached pandemic proportions, and their association has become very common. Some patients with coronary artery disease and diabetes remain symptomatic, with chest pain present despite the implementation of evidence-based medical treatment and maximal therapy. A hypothesis [...] Read more.

Cardiovascular disease and diabetes mellitus have now reached pandemic proportions, and their association has become very common. Some patients with coronary artery disease and diabetes remain symptomatic, with chest pain present despite the implementation of evidence-based medical treatment and maximal therapy. A hypothesis increasingly confirmed in clinical practice is that epicardial or microvascular spasm, or both, are frequently responsible for the lack of symptom control or for the occurrence of major adverse cardiovascular events. Our review provides the most up-to-date and in-depth analysis of the available literature to provide solid knowledge about coronary spasm in diabetes patients. We have deepened the substrate of coronary spasm in relation to the multiple and complex structural and functional abnormalities produced by chronic hyperglycemia, with the ultimate goal of allowing optimization of treatment and improving patient outcomes. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: From Basic Research to Clinical Application—3rd Edition)

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20 pages, 7835 KB

Open AccessArticle

Deciphering the Boron Toxicity Tolerance Mechanisms of Triticum dicoccoides via RNA-Sequencing

by Berna Sen, Mohd. Kamran Khan, Tomas Vyhnanek, Mehmet Hamurcu, Mustafa Harmankaya, Md. Arifuzzaman, Ali Topal, Sait Gezgin and Anamika Pandey

Life 2026, 16(2), 353; https://doi.org/10.3390/life16020353 - 19 Feb 2026

Viewed by 733

Abstract

Boron (B) toxicity is one of the major abiotic stresses limiting wheat productivity in arid and semi-arid regions of the world. Thus, it is important to understand the molecular basis of tolerance in boron-tolerant wheat genetic resources for effective breeding. Wild emmer wheat [...] Read more.

Boron (B) toxicity is one of the major abiotic stresses limiting wheat productivity in arid and semi-arid regions of the world. Thus, it is important to understand the molecular basis of tolerance in boron-tolerant wheat genetic resources for effective breeding. Wild emmer wheat is a valuable genetic resource for tolerance to multiple abiotic stresses; however, the molecular mechanisms behind boron toxicity tolerance in this species has not been sufficiently characterized. Here, we present the first RNA sequencing-based transcriptomic analysis of B toxicity response in a boron-tolerant Triticum dicoccoides genotype, PI362036. Shoot tissues exposed to high boron (10 mM B) for 7 days showed extensive transcriptional reprogramming with 2783 differentially expressed genes. Functional enrichment analyses showed that B toxicity significantly altered the genes associated with biosynthesis of secondary metabolites, metabolic pathways, ribosomal activity, carbon metabolism, RNA transport, photosynthesis–antenna proteins, and citrate cycle pathway. Several transcription factor families, including TIG, MYB, MYB-related families, NAC, C2H2-GATA, ARF, and AP2-EREBP families, showed significant differential regulation, emphasizing their regulatory roles in B stress adaptation. Collectively, this study provides the first comprehensive transcriptomic framework of boron toxicity tolerance in T. dicoccoides under short-term high boron exposure, identifying candidate genes and pathways that may be exploited for improving boron tolerance in cultivated wheat through targeted breeding strategies. Given that boron toxicity in agricultural systems primarily arises from excessive boron accumulation in soils and irrigation water, the identified pathways offer insight into early adaptive responses of shoot tissues to elevated boron availability. Full article

(This article belongs to the Section Plant Science)

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16 pages, 653 KB

Open AccessArticle

Diagnostic Value of Mean Platelet Volume and Hematological Inflammatory Ratios in Brucellosis: A Case–Control Study

by Enes Dalmanoğlu, Yeşim Çağlar and Gülce Eylül Aldemir

Life 2026, 16(2), 352; https://doi.org/10.3390/life16020352 - 18 Feb 2026

Viewed by 720

Abstract

Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital [...] Read more.

Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital in Turkey (2015–2018). Complete blood count parameters, hematological ratios (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured at diagnosis. Receiver operating characteristic (ROC) curve analysis evaluated diagnostic performance; multivariate logistic regression developed a combined model. Brucellosis patients showed significantly lower MPV (8.04 ± 0.95 vs. 8.56 ± 0.69 fL, p = 0.002), higher platelet counts (305.0 ± 116.0 vs. 246.0 ± 55.2 × 10³/μL, p = 0.002), lower NLR (median: 1.69 vs. 2.07, p = 0.013), and higher LMR (median: 5.28 vs. 4.12, p = 0.008). ESR demonstrated the best individual diagnostic performance (area under the curve [AUC] = 0.842). The combined model (MPV + ESR + CRP) achieved superior performance (AUC = 0.891, sensitivity 84%, specificity 86%). Limitations include the single-center retrospective design, lack of internal validation, and comparison with healthy controls only. Notably, healthy controls were deliberately selected to establish baseline hematological profiles associated with brucellosis rather than to differentiate it from other infections. Brucellosis presents a unique hematological profile with decreased MPV and altered inflammatory ratios. The combined model offers a potentially cost-effective screening approach for endemic settings, pending external validation. Full article

(This article belongs to the Special Issue Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions—2nd Edition)

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24 pages, 341 KB

Open AccessReview

The Role of Granulocyte Colony-Stimulating Factor in Endometrial Preparation for Embryo Implantation in In Vitro Fertilization

by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Iwakeim Sapantzoglou, Aristotelis-Marios Koulakmanidis, Vaitsis Dimitrios, Diamantis Athanasiou, Vasiliki Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Charalampos Tsimpoukelis, Athanasios Karpouzos, Maria Anastasia Daskalaki, Nikolaos Kanakas, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis Show full author list Hide full author list

Life 2026, 16(2), 351; https://doi.org/10.3390/life16020351 - 18 Feb 2026

Cited by 1 | Viewed by 739

Abstract

Granulocyte colony-stimulating factor (G-CSF) has been suggested as a supplementary approach for endometrial preparation in IVF. Clinical results continue to be inconsistent. This narrative review synthesises molecular and clinical information to elucidate the function of G-CSF in modifying endometrial receptivity and to identify [...] Read more.

Granulocyte colony-stimulating factor (G-CSF) has been suggested as a supplementary approach for endometrial preparation in IVF. Clinical results continue to be inconsistent. This narrative review synthesises molecular and clinical information to elucidate the function of G-CSF in modifying endometrial receptivity and to identify patient categories most likely to benefit. A thorough assessment was conducted on published research on G-CSF administration in women with treatment-resistant thin endometrium, recurrent implantation failure, and unselected IVF populations. The research demonstrates that G-CSF has phenotype-dependent effects. Improvements in pregnancy and live birth rates are inconsistent and seem dependent on the reversibility of underlying tissue disease; nevertheless, G-CSF reliably increases endometrial thickness in instances of thin endometrium and may restore eligibility for transfer. G-CSF improves implantation and early pregnancy outcomes in repeated implantation failure patients without modifying endometrial morphology, indicating a functional mechanism linked to immune-stromal synchronisation rather than structural expansion. In contrast, randomised controlled studies show no therapeutic benefit in unselected IVF groups. Discrepancies in research outcomes may mostly be attributed to variations in patient phenotype, initial endometrial function, and the therapy setting. Thus, G-CSF should be considered a specific approach for endometrial conditioning rather than just a supplementary component of IVF. Full article

(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)

9 pages, 707 KB

Open AccessArticle

Medial Pterygoid Muscles Penetration by Tubero-Pterygoid Implants: Clinical, Anatomical and Statistical Insights Regarding Temporo-Mandibular Disorders (TMDs)

by Łukasz Pałka, Vivek Gaur, Calin Fodor, Magdalena Gębska, Mehul Jani, Marta Bieńkowska and Bartosz Dalewski

Life 2026, 16(2), 350; https://doi.org/10.3390/life16020350 - 18 Feb 2026

Viewed by 692

Abstract

Background: The medial pterygoid muscle (MPM) is frequently implicated in pain and dysfunction in patients with temporomandibular disorders (TMDs), owing to its functional complexity, susceptibility to overload, and rich neuromuscular control. Paradoxically, in patients rehabilitated with tubero-pterygoid implants, whose apices often penetrate or [...] Read more.

Background: The medial pterygoid muscle (MPM) is frequently implicated in pain and dysfunction in patients with temporomandibular disorders (TMDs), owing to its functional complexity, susceptibility to overload, and rich neuromuscular control. Paradoxically, in patients rehabilitated with tubero-pterygoid implants, whose apices often penetrate or traverse the MPM attachment, no pain, trismus, or TMD-related symptoms are typically observed. Objective: The aim of this study was to evaluate the impact of implant penetration into the medial pterygoid muscle using CBCT and clinical examination after surgery and during follow-up visits. Methods: A retrospective observational study was conducted on 56 patients receiving a total of 116 tubero-pterygoid implants protruding beyond the pterygoid process of the sphenoid bone. Patients were divided into two groups according to implant penetration depth (<2 mm and >2 mm), with a minimum follow-up period of 12 months. Clinical outcomes related to pain, muscle disorders, and TMD symptoms were assessed. Results: Throughout the observation period, all patients remained free of pain, muscular disorders, and signs or symptoms of TMD, regardless of the degree of muscular penetration. Statistical analysis revealed no association between penetration depth and adverse clinical outcomes. Conclusions: The combined clinical and statistical evidence indicates that transmuscular penetration of the MPM by tubero-pterygoid implants is safe and well tolerated. These findings challenge traditional assumptions regarding MPM sensitivity and provide important guidance for surgical planning and maxillary rehabilitation strategies. Full article

(This article belongs to the Special Issue New Advances in the Treatment and Assessment of Temporomandibular Joint Disorders)

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13 pages, 3421 KB

Open AccessArticle

Effect of Dystocia Duration on the Placental Health in Canines

by Romina Gisele Praderio, Mauricio Javier Giuliodori, Rodolfo Luzbel de la Sota and María Alejandra Stornelli

Life 2026, 16(2), 349; https://doi.org/10.3390/life16020349 - 18 Feb 2026

Viewed by 1105

Abstract

The study aimed to determine whether placental lesions differ according to the duration of dystocia. Forty-seven placentas were obtained from 18 bitches that underwent emergency cesarean sections. For descriptive purposes, the cases were classified into four groups based on the duration of dystocia: [...] Read more.

The study aimed to determine whether placental lesions differ according to the duration of dystocia. Forty-seven placentas were obtained from 18 bitches that underwent emergency cesarean sections. For descriptive purposes, the cases were classified into four groups based on the duration of dystocia: Group A, up to 6 h; Group B, 6–11.9 h; Group C, 12–24 h; and Group D, more than 24 h. Forty-seven placentas were studied. Both macroscopic and microscopic characteristics were evaluated in each placenta. Descriptive data were presented, and logistic and multinomial regression models were used to assess whether dystocia duration (in hours) is associated with the presence and severity of placental macro- and microscopic lesions. An hour increment over the mean in the duration of dystocia showed a non-significant trend to increasing the presence of macroscopic necrosis (OR: 1.11, p = 0.09) and mineralization (OR: 1.10, p = 0.06), and it also increased the severity of macroscopic congestion (OR: 1.44; p = 0.01) and showed a non-significant trend to increasing the severity of polymorphonuclear neutrophil infiltrate (OR: 1.18; p = 0.06). These findings highlight the importance of early obstetric intervention in all cases of dystocia to minimize fetal hypoxia and improve neonatal outcomes. Moreover, the placenta could serve as a biomarker for fetal distress, as the presence of severe lesions indicates an increased risk for reduced neonatal survival. Full article

(This article belongs to the Special Issue Developmental Programming in Cats and Dogs)

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6 pages, 577 KB

Open AccessBrief Report

IL-33 Modulates Cytotoxic NK Cell Subsets in Severe Eosinophilic Asthma

by Laura Bergantini, Irene Paggi, Tommaso Pianigiani, Elena Bargagli and Paolo Cameli

Life 2026, 16(2), 348; https://doi.org/10.3390/life16020348 - 18 Feb 2026

Viewed by 592

Abstract

Natural Killer (NK) cells contribute to airway inflammation in severe eosinophilic asthma (SEA). IL-33, elevated in SEA, may modulate NK cell function, but its effects are unclear. We analyzed peripheral blood NK cell subsets from five SEA patients and five healthy controls using [...] Read more.

Natural Killer (NK) cells contribute to airway inflammation in severe eosinophilic asthma (SEA). IL-33, elevated in SEA, may modulate NK cell function, but its effects are unclear. We analyzed peripheral blood NK cell subsets from five SEA patients and five healthy controls using flow cytometry, assessing CD56/CD16-defined subsets and markers, CD57, NKG2A, CD62L, and ICAM-1, at baseline and after 72 h IL-33 stimulation. SEA patients showed reduced mature cytotoxic NK cells and altered expression of adhesion and regulatory molecules. IL-33 selectively increased ICAM-1 and NKG2A in mature NK cells, while decreasing these markers in immature subsets. These findings indicate that IL-33 differentially regulates NK-cell phenotype and function, highlighting NK cells as dynamic mediators of inflammation in SEA. Full article

(This article belongs to the Section Medical Research)

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15 pages, 870 KB

Open AccessReview

Revisiting Rosacea Through the Skin–Gut–Brain Axis: A Neuroimmune Perspective

by Elvira Lazić Mosler, Marina Vekić Mužević, Dalibor Karlović, Marko Tarle and Marina Raguž

Life 2026, 16(2), 347; https://doi.org/10.3390/life16020347 - 18 Feb 2026

Viewed by 1304

Abstract

Rosacea is increasingly recognized as a complex inflammatory disorder extending beyond isolated cutaneous pathology, involving dysregulated interactions between the skin, gastrointestinal system, and central nervous system. The skin–gut–brain axis has emerged as a relevant conceptual framework for understanding this multifactorial disease, integrating gut [...] Read more.

Rosacea is increasingly recognized as a complex inflammatory disorder extending beyond isolated cutaneous pathology, involving dysregulated interactions between the skin, gastrointestinal system, and central nervous system. The skin–gut–brain axis has emerged as a relevant conceptual framework for understanding this multifactorial disease, integrating gut microbiota dysbiosis, neuroimmune signaling, autonomic nervous system dysfunction, and stress-related mechanisms. The aim of this narrative hypothesis-driven overview is to reframe rosacea as a neuroimmune disorder in which central nervous system involvement plays an active regulatory role, rather than as a purely peripheral or dermatological condition. We synthesize the mechanistically relevant evidence linking gastrointestinal inflammation and microbial imbalance with neurogenic inflammation, mast cell activation, sebaceous gland dysfunction, and aberrant innate immune responses in the skin, with particular emphasis on neurovascular and trigeminal pathways. A key novelty of this perspective lies in highlighting brain-centered mechanisms, including central sensitization, autonomic dysregulation, and stress-related neural modulation, as integral components of the skin–gut–brain axis in rosacea. By integrating peripheral and central processes, we propose rosacea as a model condition for studying neuroimmune dysregulation across interconnected regulatory systems. Finally, we discuss the clinical and translational implications of this framework and outline future research directions, focusing on autonomic regulation, patient stratification, and personalized, multidisciplinary therapeutic approaches. Full article

(This article belongs to the Special Issue The Microbiome and Dysbiosis in Various Pathologies)

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12 pages, 873 KB

Open AccessArticle

Comparative Effectiveness and Safety of Denosumab Versus Bisphosphonates in Elderly Patients with Cancer Bone Metastases: A Target Trial Emulation Study

by Che-Wei Liu, Shun-Neng Hsu, Shao-Hsuan Chang, Wei-Cheng Chang, Chun-Liang Hsu, Hsin-Yu Chen, Po-Huang Chen and Cho-Hao Lee

Life 2026, 16(2), 346; https://doi.org/10.3390/life16020346 - 17 Feb 2026

Viewed by 1094

Abstract

Objective: Bone-modifying agents (BMA) are central to the prevention of skeletal-related events (SREs) in patients with cancer bone metastases, yet evidence guiding agent selection in very old patients remains limited. This study aimed to compare the effectiveness and safety of Denosumab versus bisphosphonates [...] Read more.

Objective: Bone-modifying agents (BMA) are central to the prevention of skeletal-related events (SREs) in patients with cancer bone metastases, yet evidence guiding agent selection in very old patients remains limited. This study aimed to compare the effectiveness and safety of Denosumab versus bisphosphonates in patients aged ≥75 years with solid tumour-related bone metastases using a target trial emulation framework. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network to emulate a hypothetical randomised trial. Patients aged ≥75 years with solid tumour-related bone metastases initiating Denosumab or bisphosphonates were included. After 1:1 propensity score matching (PSM), 10,662 patients were analysed in each treatment group. The primary outcome was time to first SRE. Secondary outcomes included individual SRE components, all-cause mortality, and safety events. Results: Among 21,324 matched patients (mean age, 75.6 years), bisphosphonate use was associated with a higher risk of SREs compared with Denosumab (hazard ratio [HR], 1.15; 95% CI, 1.06–1.25). The excess risk was driven by pathological fractures (HR, 1.28; 95% CI, 1.10–1.49), whereas other SRE components did not differ significantly. All-cause mortality was higher among bisphosphonate users (HR, 1.41; 95% CI, 1.33–1.49, p < 0.001). Hypocalcaemia occurred more frequently with Denosumab (5.7% vs. 2.4%), while risks of acute kidney injury and end-stage renal disease (ESRD) were similar. Findings were consistent across sensitivity and subgroup analyses. Conclusions: In patients aged ≥75 years with solid tumour-related bone metastases, Denosumab was associated with lower risks of skeletal-related events—particularly pathological fractures—and reduced all-cause mortality compared with bisphosphonates. These results extend randomised trial evidence to a clinically vulnerable population and support Denosumab as a preferred BMA in older adults. Full article

(This article belongs to the Special Issue Contemporary Therapeutic Strategies for Solid Tumors)

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15 pages, 552 KB

Open AccessArticle

The Association Between the Triglyceride–Glucose Index and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

by Munther S. Momani, Raneem Dalaeen, Dia Sarhan, Zaid Sarhan, Suhib Awamleh, Yazan M. Momani and Omar Abu Farsakh

Life 2026, 16(2), 345; https://doi.org/10.3390/life16020345 - 17 Feb 2026

Viewed by 912

Abstract

This study aimed to evaluate the association between the triglyceride–glucose index (TyG) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus. Methods: This study included 1347 patients with type 2 diabetes who attended the endocrinology clinic at [...] Read more.

This study aimed to evaluate the association between the triglyceride–glucose index (TyG) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus. Methods: This study included 1347 patients with type 2 diabetes who attended the endocrinology clinic at Jordan University Hospital between May 2025 and October 2025. Medical records were reviewed to identify patients with documented DKD, and the TyG index was calculated for each patient. Results: Our results showed that patients with both late-stage kidney disease (mean 9.47 ± 0.74) and early-stage kidney disease (mean 9.42 ± 0.67) demonstrated elevated TyG index values compared to those without kidney disease (mean 9.27 ± 0.70). In the fully adjusted model, the association remained robust with an OR of 1.611 (95% CI: 1.330–1.951, p < 0.001), indicating that higher TyG index values are independently associated with increased kidney risk even after controlling for major confounding variables. When comparing TyG index quartiles, the second quartile showed no significant difference from the reference group, while the third quartile showed 66% increased odds (OR = 1.66, 95% CI: 1.176–2.345, p = 0.004) and the fourth quartile demonstrated 117% increased odds (OR = 2.174, 95% CI: 1.512–3.125, p < 0.001). The association between the TyG index and DKD was more significant in patients younger than 60 years, and in women. In conclusion, the TGI was associated with increased risk of DKD; however, its discriminative ability was modest (AUC 0.57). This indicates that the TGI alone is insufficient as a predictive tool and should be interpreted alongside established screening tools. Prospective studies are needed to clarify its causal role in DKD development. Full article

(This article belongs to the Special Issue Interdisciplinary Approach to Diabetes Mellitus: From Pathophysiology to Diagnosis and Therapeutic Challenges: 2nd Edition)

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19 pages, 318 KB

Open AccessReview

A Dive into the Invisible: The Vaginal and Endometrial Microbiota in Gynecologic and Obstetric Disorders: A Narrative Review

by Giorgia Schettini, Emilio Pieri, Cristina Rizzo, Matteo Giorgi, Virginia Mancini, Nassir Habib, Ramon Rovira and Gabriele Centini

Life 2026, 16(2), 344; https://doi.org/10.3390/life16020344 - 17 Feb 2026

Viewed by 1425

Abstract

The human microbiota is increasingly recognized as a key component of women’s reproductive health. This narrative review examines the vaginal, endometrial, and gut microbiota and their roles in the pathogenesis of gynecologic and obstetric disorders, aiming to integrate current evidence into a clinically [...] Read more.

The human microbiota is increasingly recognized as a key component of women’s reproductive health. This narrative review examines the vaginal, endometrial, and gut microbiota and their roles in the pathogenesis of gynecologic and obstetric disorders, aiming to integrate current evidence into a clinically relevant framework. We review intrinsic (genetic, hormonal, and immunological) and extrinsic (environmental, lifestyle, and pharmacological) factors shaping microbial composition, with particular focus on dysbiosis and the role of the gut estrobolome within the microbiome in estrogen metabolism. The review synthesizes data on microbiota alterations associated with endometriosis, adenomyosis, uterine fibroids, endometrial polyps and hyperplasia, gynecologic malignancies, pelvic inflammatory disease, bacterial vaginosis, infertility, and adverse obstetric outcomes, including preterm birth and fetal growth restriction. Methodological approaches used to characterize the reproductive tract microbiota, such as vaginal swabs, endometrial sampling, and fecal analysis, are critically discussed, together with limitations related to low-biomass environments and contamination risk. Evidence regarding therapeutic modulation of the microbiota, including antibiotics, probiotics, hormonal therapies, and emerging microbiota-based interventions, is summarized, alongside the impact of gynecologic surgery on microbial translocation and long-term microbial balance. Overall, the available literature supports an association between microbiota alterations and multiple reproductive conditions, although causality remains incompletely established. Further standardized and longitudinal studies are needed to clarify mechanisms and guide microbiota-informed diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: From Bench to Bedside—2nd Edition)

14 pages, 810 KB

Open AccessArticle

A Three-Decade Overview of Cadmium and Lead in Placentas of Postpartum Women: A Review of Evidence from Croatia (1990s–2019)

by Tatjana Orct, Ankica Sekovanić and Zorana Kljaković-Gašpić

Life 2026, 16(2), 343; https://doi.org/10.3390/life16020343 - 16 Feb 2026

Viewed by 513

Abstract

Toxic heavy metals, including cadmium (Cd) and lead (Pb), can build up in placental tissue or pass through the placental barrier, potentially harming fetal development. Therefore, the placenta can serve as a useful tool for assessing prenatal exposure to these harmful substances. Over [...] Read more.

Toxic heavy metals, including cadmium (Cd) and lead (Pb), can build up in placental tissue or pass through the placental barrier, potentially harming fetal development. Therefore, the placenta can serve as a useful tool for assessing prenatal exposure to these harmful substances. Over the past several decades, Croatia has implemented a range of environmental and public health measures aimed at reducing exposure to Cd and Pb, including ratification of the World Health Organization Framework Convention on Tobacco Control (FCTC), ban on smoking in public places, intensified health education campaigns, and the complete phase-out of leaded gasoline in 2006. As a result, smoking prevalence among women and Pb levels in ambient air have declined substantially. This study reviews and analyzes existing literature on Cd and Pb levels in placental tissue of women in Zagreb, Croatia, in order to evaluate the effectiveness of these health and environmental policies and to identify persistent or emerging risks associated with toxic metal exposure during pregnancy by comparing placental Cd and Pb levels between smokers and nonsmokers across several time periods. Full article

(This article belongs to the Section Reproductive and Developmental Biology)

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9 pages, 2106 KB

Open AccessCase Report

Late Diagnosis of Unroofed Coronary Sinus Associated with Persistent Left Superior Vena Cava in Patient with Repaired Tetralogy of Fallot: Case Report

by Oana Gheorghe-Fronea, Mircea Robu, Sebastian Onciul, Claudia Nica, Cristian Voica, Robert Țigănașu, Gabriel-Petre Gorecki and Horațiu Moldovan

Life 2026, 16(2), 342; https://doi.org/10.3390/life16020342 - 16 Feb 2026

Viewed by 636

Abstract

Background: An unroofed coronary sinus (UCS) is a rare congenital cardiac anomaly, accounting for less than 1% of atrial septal defects and frequently associated with a persistent left superior vena cava (PLSVC). Its coexistence with Tetralogy of Fallot (TOF) is exceptionally uncommon and [...] Read more.

Background: An unroofed coronary sinus (UCS) is a rare congenital cardiac anomaly, accounting for less than 1% of atrial septal defects and frequently associated with a persistent left superior vena cava (PLSVC). Its coexistence with Tetralogy of Fallot (TOF) is exceptionally uncommon and has been reported almost exclusively in isolated case reports. Case Presentation: We report the case of a 20-year-old woman with a history of surgically corrected TOF in infancy, who presented with progressive exertional dyspnea. Multimodality imaging, including transthoracic echocardiography and cardiac magnetic resonance imaging, revealed a large atrial-level shunt caused by a type I unroofed coronary sinus associated with a persistent left superior vena cava, leading to significant right-sided chamber dilation and pulmonary hypertension. Notably, this anomaly had not been identified at the time of the initial TOF repair. The patient underwent a successful surgical correction with interatrial compartmentation and tricuspid annuloplasty, with an uneventful postoperative course. Conclusions: This case underscores the extreme rarity of the UCS–TOF association and highlights the potential for UCSs with PLSVC to remain clinically silent for years after complex congenital heart surgery. A comprehensive reassessment of the systemic venous and atrial anatomy using advanced multimodality imaging is essential in symptomatic adults with repaired TOF, as late-presenting venous anomalies may have significant hemodynamic and clinical implications. Full article

(This article belongs to the Section Medical Research)

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18 pages, 851 KB

Open AccessArticle

Effect of Physical Therapy with Combined Resistance Exercises and Vigorous Walking in Older Adult Women with Chronic Non-Specific Pain: A Randomized Controlled Trial

by Rocío Cogollos-de-la-Peña, Gemma Victoria Espí-López, Anna Arnal-Gómez, Lucas Monzani, Juan J. Carrasco and Laura Fuentes-Aparicio

Life 2026, 16(2), 341; https://doi.org/10.3390/life16020341 - 16 Feb 2026

Viewed by 902

Abstract

Background: Age-related hormonal changes in older women accelerate bone and muscle loss, leading to postural dysfunction and chronic musculoskeletal pain. This study aimed to evaluate the short-term effects of a physical therapy program combining elastic band exercises and vigorous walking on pain, thoracic [...] Read more.

Background: Age-related hormonal changes in older women accelerate bone and muscle loss, leading to postural dysfunction and chronic musculoskeletal pain. This study aimed to evaluate the short-term effects of a physical therapy program combining elastic band exercises and vigorous walking on pain, thoracic mobility, and functional capacity in older adult women. Methods: A multicenter randomized controlled trial was conducted older adult women (60–80 years) with chronic non-specific musculoskeletal pain, allocated to an elastic band plus vigorous walking group (EBWG), a vigorous walking group (VWG), or a control group (CG). A total of 91 participants completed all of the assessments. Outcomes included pressure pain threshold (PPT), self-reported pain (VAS), thoracic mobility (UPC, LWC), functional capacity (5XSTS), and perceived improvement (PGIC), evaluated at baseline, after a 4-week intervention, and at 4-week follow-up. Results: The EBWG demonstrated greater improvements in PPT (+0.66 kg/cm² at T2), upper chest expansion (+1.00 cm), and 5XSTS performance (−1.7 s) compared to the control group. The VWG showed significant reductions in overall pain (−0.9 points) and lumbar pain (−1.7 points). Improvements in PPT and thoracic mobility in the EBWG exceeded MDC/MCID thresholds, indicating clinically meaningful changes. Vigorous walking alone improved self-reported pain but was less effective than the multicomponent program. Conclusions: A 4-week combined program of elastic band exercises and vigorous walking produced clinically relevant improvements in pain threshold, thoracic mobility, functional capacity, and perceived change compared to walking alone or usual activity. These findings support the clinical utility of short, feasible, multicomponent interventions for managing chronic musculoskeletal pain in older women. Full article

(This article belongs to the Special Issue Advances on Physiotherapy and Functional Rehabilitation in Chronic Conditions)

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20 pages, 713 KB

Open AccessSystematic Review

Effectiveness of Physiotherapy in Haemodialysis: Systematic Review

by Juan Rodríguez-Mansilla, Carmen Murillo-González, María Jiménez-Palomares, Elisa María Garrido-Ardila and Blanca González-Sánchez

Life 2026, 16(2), 340; https://doi.org/10.3390/life16020340 - 15 Feb 2026

Viewed by 1037

Abstract

Background: Chronic kidney disease (CKD) is a progressive pathology that affects millions of people worldwide, becoming a public health challenge due to its high prevalence and mortality. In its advanced stages, patients require therapies such as haemodialysis (HD), which often entails physical complications, [...] Read more.

Background: Chronic kidney disease (CKD) is a progressive pathology that affects millions of people worldwide, becoming a public health challenge due to its high prevalence and mortality. In its advanced stages, patients require therapies such as haemodialysis (HD), which often entails physical complications, so incorporating physiotherapy as an essential part of the treatment of these patients becomes evident. Objective: To analyse the effectiveness of physiotherapy in patients undergoing haemodialysis before, during and after the treatment. Methodology: This study is a systematic review conducted following the PRISMA statements. An electronic literature search was performed in the following databases: PubMed, PEDro, Chorane Library, ScienceDirect and Dialnet. The inclusion criteria were: controlled and uncontrolled clinical trials published in the last 10 years in English or Spanish, in patients with chronic kidney disease on haemodialysis treatment, aged 18 years or older. Results: 22 studies were included in this review. A total of 1786 patients participated in the included studies. Most of the investigations used cycloergometers, treadmills and bicycles. The programmes varied in types of exercise, with combinations of aerobic, endurance and inspiratory muscle training, with assessments at baseline and at the end of the intervention, some with additional measurements at 8, 12 or 16 weeks, and others with no specified follow-up time. Conclusions: The analysed literature showed that therapeutic exercise can be beneficial for haemodialysis patients, improving muscle strength, aerobic capacity and quality of life. Its implementation, both before, during and after haemodialysis sessions, also helped to reduce fatigue and depression. These results support the importance of exercise in the comprehensive treatment of patients with chronic kidney disease in haemodialysis. Full article

(This article belongs to the Section Medical Research)

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13 pages, 2132 KB

Open AccessArticle

Novel Stochastic Sensors Based on Phthalocyanine Complexes for the Detection of C-NP, IL-6, and CRP in Cardiovascular Diseases

by Ruxandra-Maria Ilie-Mihai and Raluca-Ioana Stefan-van Staden

Life 2026, 16(2), 339; https://doi.org/10.3390/life16020339 - 15 Feb 2026

Viewed by 474

Abstract

The severity of cardiovascular disease is linked to C-reactive protein, interleukin 6, and C-type natriuretic peptide levels, stressing the need for a sensitive sensor that can detect these biomarkers at ultralow levels in real time. Whole blood samples from confirmed cardiovascular patients were [...] Read more.

The severity of cardiovascular disease is linked to C-reactive protein, interleukin 6, and C-type natriuretic peptide levels, stressing the need for a sensitive sensor that can detect these biomarkers at ultralow levels in real time. Whole blood samples from confirmed cardiovascular patients were analyzed for C-type natriuretic peptide, C-reactive protein, and interleukin 6 using three stochastic sensors. These sensors were designed using carbon paste matrices decorated with Ag nanoparticles (AgNPs), on which different phthalocyanines were physically immobilized. The sensors exhibited exceptionally low detection limits (1 × 10⁻²¹ g mL⁻¹) and broad linear concentration ranges (1 × 10⁻²¹ to 1 × 10⁻⁶ g mL⁻¹). The analysis conducted using the Student t-test indicated that there is no statistically significant difference between the results obtained from the three stochastic sensors used in the screening tests of whole blood, with ELISA at a confidence level of 99%. Full article

(This article belongs to the Special Issue New Screening Methods for Diagnosis of Cardiovascular Diseases)

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13 pages, 853 KB

Open AccessArticle

The Critical Role of Nutritional and Procedural Factors in CTO-PCI Patient Prognosis

by Gürkan Karaca, Ahmet Ekmekci, Ali Kimiaei, Seyedehtina Safaei, Aziz İnan Çelik and Metin Çağdaş

Life 2026, 16(2), 338; https://doi.org/10.3390/life16020338 - 15 Feb 2026

Viewed by 453

Abstract

(1) Background: Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is a complex, high-risk procedure compared to standard percutaneous coronary intervention (PCI). Scoring systems such as the Japanese Chronic Total Occlusion (J-CTO), European Chronic Total Occlusion (EuroCTO), and Prospective Global Registry for the Study [...] Read more.

(1) Background: Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is a complex, high-risk procedure compared to standard percutaneous coronary intervention (PCI). Scoring systems such as the Japanese Chronic Total Occlusion (J-CTO), European Chronic Total Occlusion (EuroCTO), and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) evaluate lesion difficulty and predict outcomes. Nutritional status, measured by the Prognostic Nutritional Index (PNI), may also affect procedural success and long-term survival. The objective of this study was to evaluate the combined impact of procedural complexity and nutritional status on the clinical outcomes of patients undergoing CTO-PCI. (2) Methods: We analyzed 118 patients undergoing CTO-PCI between May 2021 and March 2022. Procedural complexity was assessed using the J-CTO, EuroCTO, and PROGRESS-CTO scores, while nutritional status was evaluated using the PNI. Primary outcomes included all-cause mortality and repeat revascularization, which were analyzed using Cox proportional hazards regression and Kaplan–Meier survival analyses. (3) Results: Adverse outcomes occurred in 25 patients (mortality: 17; revascularization: 8). Patients with adverse outcomes had significantly lower left ventricular ejection fraction (LVEF) (46 ± 13.7% vs. 52.1 ± 10.5%, p < 0.001), lower PNI (p < 0.001), and higher J-CTO, EuroCTO, and PROGRESS-CTO scores (all p < 0.05). A PNI cut-off value of 46 predicted mortality with a sensitivity of 70.6% and specificity of 75.2% (area under the curve [AUC] = 0.739, p = 0.001). Multivariable analysis identified LVEF (hazard ratio [HR] 0.966, p = 0.036), J-CTO score (HR 1.598, p = 0.027), and PNI (HR 0.925, p = 0.022) as independent predictors of mortality. (4) Conclusion: Both procedural complexity and nutritional status significantly influence outcomes following CTO-PCI. Incorporating PNI together with procedural complexity scores into pre-procedural assessments may enhance risk stratification and optimize patient management. Full article

(This article belongs to the Special Issue Innovation and Translation in Cardiovascular Interventions)

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16 pages, 734 KB

Open AccessArticle

Associations of Neutrophil-to-Lymphocyte Ratio with Cerebral Small Vessel Disease and Functional Outcome in Acute Ischaemic Stroke Patients

by Nipit Tieachanpan, Surat Tanprawate, Atiwat Soontornpun, Chayasak Wantaneeyawong, Chutithep Teekaput, Nopdanai Sirimaharaj, Angkana Nudsasarn, Withawat Vuthiwong and Kitti Thiankhaw

Life 2026, 16(2), 337; https://doi.org/10.3390/life16020337 - 15 Feb 2026

Viewed by 593

Abstract

Background: The relationship between inflammatory markers and cerebral small vessel disease (CSVD) in patients with acute ischaemic stroke (AIS) remains unclear. This study aimed to investigate the association between simplified inflammatory biomarkers and neuroimaging markers of CSVD. Methods: This retrospective cohort study included [...] Read more.

Background: The relationship between inflammatory markers and cerebral small vessel disease (CSVD) in patients with acute ischaemic stroke (AIS) remains unclear. This study aimed to investigate the association between simplified inflammatory biomarkers and neuroimaging markers of CSVD. Methods: This retrospective cohort study included patients with AIS who had symptom onset within 72 h and underwent MRI brain between January 2019 and December 2023. The associations between tertiles (T) of the neutrophil-to-lymphocyte ratio (NLR) and CSVD markers were studied using multinomial logistic regression. Functional outcomes at discharge and 90 days, as measured by the modified Rankin Scale (mRS), were also evaluated. Results: A total of 299 eligible patients were included, with a mean age of 65.7 ± 13.8 years and 55.5% (166/299) were male, and categorised into three tertiles of NLR (T1: 101, T2: 101, T3: 97). Patients with a higher NLR tertile had more admission NIHSS (T3 vs. T1: 3 (2, 5) vs. 2 (1, 3), p = 0.005). NLR was associated with an increased risk of ≥5 lobar cerebral microbleeds (CMBs) in an unadjusted model (T3 vs. T1: relative risk ratio (RRR), 5.69 (95% confidence interval (CI) 1.21–26.68); p = 0.03); however, this was not significant when adjusted for potential confounders (RRR 3.86; 95% CI 0.79–18.89; p = 0.10). No significant associations were observed in the remaining neuroimaging markers of CSVD. Patients in the T2 of NLR had a higher likelihood of achieving an mRS of 0–1 at 90 days (RRR 2.16; 95% CI 1.05–4.44; p = 0.04) compared to those in T1. Conclusions: In AIS, admission NLR showed a possible association with higher lobar CMB burden in unadjusted analyses, but this was not robust after adjustment, and no consistent relationships were observed with other CSVD markers. Associations with functional outcomes were not uniform across tertiles, and the apparent benefit in the middle NLR tertile should be interpreted cautiously as a potentially non-linear or chance finding, indicating that NLR is not a reliable independent imaging or prognostic marker in this cohort. Full article

(This article belongs to the Section Physiology and Pathology)

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Open AccessArticle

Biomechanical Comparison of Three Fixation Constructs for Tile Type C1.2 Pelvic Ring Fractures: A Finite Element Analysis

by Adrian Claudiu Carp, Bogdan Veliceasa, Dmour Awad, Alexandru Filip, Mihaela Perțea, Norin Forna, Bogdan Puha, Ștefan Dragoș Tîrnovanu, Mihnea Theodor Sîrbu, Silviu Dumitru Pavăl and Paul Dan Sîrbu

Life 2026, 16(2), 336; https://doi.org/10.3390/life16020336 - 15 Feb 2026

Cited by 1 | Viewed by 616

Abstract

Fractures of the pelvic ring are among the most severe injuries in orthopaedic practice and Tile type C lesions are characterized by complete disruption of the posterior arch with both vertical and rotational instability. The optimal construct for posterior ring fixation remains a [...] Read more.

Fractures of the pelvic ring are among the most severe injuries in orthopaedic practice and Tile type C lesions are characterized by complete disruption of the posterior arch with both vertical and rotational instability. The optimal construct for posterior ring fixation remains a matter of debate. The aim of this study was to compare, by means of finite element analysis, the biomechanical performance of three different methods of osteosynthesis for Tile type C1.2 pelvic ring fractures: a transiliac plate, one iliosacral screw and two anterior reconstruction plates on the sacroiliac joint. A three-dimensional model of an intact pelvis was reconstructed from computed tomography images of a healthy adult male. A Tile type C1.2 injury pattern was created virtually, and three fixation constructs were designed in Ansys SpaceClaim according to manufacturer specifications. All materials were assumed to be homogeneous, isotropic and linearly elastic. Vertical loads of 400 N and 800 N were applied to the sacral endplate to simulate partial and full weight bearing, while the acetabular regions were constrained to represent standing stance. In this study, mechanical stability was operationally defined as resistance to global displacement under applied vertical load, with lower displacement indicating higher construct stiffness. Construct stiffness, total deformation and von Mises stress were assessed for bone and implants. For both loading conditions, the iliosacral screw construct showed the lowest overall displacement and provided the greatest stiffness. The transiliac plate construct presented larger displacements, whereas the anterior reconstruction plate construct provided intermediate stability with higher stresses at the sacroiliac joint. Among the analyzed constructs, the iliosacral screw provided the greatest stiffness and lowest overall displacement, suggesting superior mechanical performance under vertical loading conditions. Full article

(This article belongs to the Section Physiology and Pathology)

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Life, Volume 16, Issue 2 (February 2026) – 181 articles

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