Life, Volume 14, Issue 5 (May 2024) – 105 articles

Background: Implanted titanium skull plates (TSPs) in cranioplasty are used to replace or reconstruct areas of the skull that have been damaged or removed due to trauma, surgery, or other medical conditions. However, the presence of a TSP in the head may influence the distribution of the electric field induced during transcranial magnetic stimulation (TMS) procedures. The purpose of this study was to determine how the presence of TSP would interfere with TMS-induced cortical electric fields. Methods: The TMS with a figure-of-eight coil was applied to a realistic head model with TSPs. The distribution of the induced electric field in head tissues was calculated by employing the impedance method, and the results were compared with that of a normal head without TSP. Results: Simulation results show that the distribution of the induced electric field has changed greatly for the head model with TSP. The maximum value of the induced electric field in head tissues was present under one of the circular coil wings rather than in the tissues beneath the junction of the two wings of the Fo8 coil. Conclusions: The induced electric field in deep brain regions was increased for the head model with TSP, which could potentially lead to deep brain stimulation. Since the presence of metallic TSP can greatly influence the distribution of the induced electric field in TMS applications, it is important to adjust the treatment scheme when considering TMS for individuals with cranial titanium plates. Full article

Nitrogen is an essential element for maize growth, but excessive application can lead to various environmental and ecological issues, including water pollution, air pollution, greenhouse gas emissions, and biodiversity loss. Hence, developing maize hybrids resilient to low-N conditions is vital for sustainable agriculture, particularly in nitrogen-deficient soils. Combining ability and genetic relationships among parental lines is crucial for breeding superior hybrids under diverse nitrogen levels. This study aimed to assess the genetic diversity of maize inbred lines using simple sequence repeat (SSR) markers and evaluate their combining ability to identify superior hybrids under low-N and recommended conditions. Local and exotic inbred lines were genotyped using SSR markers, revealing substantial genetic variation with high gene diversity (He = 0.60), moderate polymorphism information content (PIC = 0.54), and an average of 3.64 alleles per locus. Twenty-one F1 hybrids were generated through a diallel mating design using these diverse lines. These hybrids and a high yielding commercial check (SC-131) were field-tested under low-N and recommended N conditions. Significant variations (p < 0.01) were observed among nitrogen levels, hybrids, and their interaction for all recorded traits. Additive genetic variances predominated over non-additive genetic variances for grain yield and most traits. Inbred IL3 emerged as an effective combiner for developing early maturing genotypes with lower ear placement. Additionally, inbreds IL1, IL2, and IL3 showed promise as superior combiners for enhancing grain yield and related traits under both low-N and recommended conditions. Notably, hybrids IL1×IL4, IL2×IL5, IL2×IL6, and IL5×IL7 exhibited specific combining abilities for increasing grain yield and associated traits under low-N stress conditions. Furthermore, strong positive associations were identified between grain yield and specific traits like plant height, ear length, number of rows per ear, and number of kernels per row. Due to their straightforward measurability, these relationships underscore the potential of using these traits as proxies for indirect selection in early breeding generations, particularly under low-N stress. This research contributes to breeding nitrogen-efficient maize hybrids and advances our understanding of the genetic foundations for tolerance to nitrogen limitations. Full article

The aquatic environment encompasses a wide variety of pollutants, from plastics to drug residues, pesticides, food compounds, and other food by-products, and improper disposal of waste is the main cause of the accumulation of toxic substances in water. Monitoring, assessing, and attempting to control the effects of contaminants in the aquatic environment are necessary and essential to protect the environment and thus human and animal health, and the study of aquatic ecotoxicology has become topical. In this respect, zebrafish are used as model organisms to study the bioaccumulation, toxicity, and influence of environmental pollutants due to their structural, functional, and material advantages. There are many similarities between the metabolism and physiological structures of zebrafish and humans, and the nervous system structure, blood–brain barrier function, and social behavior of zebrafish are characteristics that make them an ideal animal model for studying neurotoxicity. The aim of the study was to highlight the neurotoxicity of nanoplastics, microplastics, fipronil, deltamethrin, and rotenone and to highlight the main behavioral, histological, and oxidative status changes produced in zebrafish exposed to them. Full article

Ginkgo biloba is widely planted as a colorful foliage tree, and its leaf can be used as a biomass energy source, but it has been underutilized for a long time. The aim of this study was to investigate the potential of garden waste as a substrate component in the cultivation process of the king oyster mushroom (Pleurotus eryngii), with the goal of enhancing both the yield of P. eryngii and the efficiency of energy use. The percentages of G. biloba leaf powder in the substrate were 10.5% and 21% to replace sawdust or sugarcane bagasse in a typical substrate. A substrate formulation that could completely replace sawdust and sugarcane bagasse was selected by analyzing mycelial growth rate, days of production, fruiting body length, biological efficiency, yield, stipe thickness, pileus diameter and laccase activity. The results showed that Y1 (treatment with 21% G. biloba leaf powder and sugarcane bagasse) had the highest yield (303.1 ± 31.9 g), which was higher than that of CK (control) (259.3 ± 37.4 g). The crude fiber content of the samples grown on substrate Y1 (as 7.43%) was higher than CK (7.37%). In addition, P. eryngii grown on substrate Y1 had the highest laccase activity for the complete colonization of the mycelium. Thus, these findings suggest that G. biloba leaf powder represents a viable and economical supplement for enhancing both the yield and quality of P. eryngii. Full article

The interaction between IgM and C1q represents the first step of the classical pathway of the complement system in higher vertebrates. To identify the significance of particular IgM/C1q interactions, recombinant IgMs were used in both hexameric and pentameric configurations and with two different specificities, along with C1q derived from human serum (sC1q) and two recombinant single-chain variants of the trimeric globular region of C1q. Interaction and complement activation assays were performed using the ELISA format, and bio-layer interferometry measurements to study kinetic behavior. The differences between hexameric and pentameric IgM conformations were only slightly visible in the interaction assay, but significant in the complement activation assay. Hexameric IgM requires a lower concentration of sC1q to activate the complement compared to pentameric IgM, leading to an increased release of C4 compared to pentameric IgM. The recombinant C1q mimetics competed with sC1q in interaction assays and were able to inhibit complement activation. The bio-layer interferometry measurements revealed K_D values in the nanomolar range for the IgM/C1q interaction, while the C1q mimetics exhibited rapid on and off binding rates with the IgMs. Our results make C1q mimetics valuable tools for developing recombinant C1q, specifically its variants, for further scientific studies and clinical applications. Full article

Myelodysplastic syndrome (MDS) is a clonal disease derived from hematopoietic stem cells, characterized by ineffective hematopoiesis (resulting in peripheral blood cytopenia) and an increased risk of transformation into acute myeloid leukemia. MDS is caused by a complex combination of genetic mutations resulting in a heterogeneous genotype. Genetic studies have identified a set of aberrations that play a central role in the pathogenesis of MDS. In this article, we present a clinical case of MDS transformation into acute myeloid leukemia in the context of two cell lines exhibiting morphological, immunophenotypic, and dysmyelopoiesis markers and the presence of two heterozygous mutations in the TET2 gene. Full article

The proposed Mars missions will expose astronauts to long durations of social isolation (SI) and space radiation (SR). These stressors have been shown to alter the brain’s macrostructure and microenvironment, including the blood–brain barrier (BBB). Breakdown of the BBB is linked to impaired executive functions and physical deficits, including sensorimotor and neurocognitive impairments. However, the precise mechanisms mediating these effects remain unknown. Additionally, the synergistic effects of combined exposure to SI and SR on the structural integrity of the BBB and brain remain unknown. We assessed the BBB integrity and morphology in the brains of male rats exposed to ground-based analogs of SI and SR. The rats exposed to SR had enlarged lateral ventricles and increased BBB damage associated with a loss of astrocytes and an increased number of leaky vessels. Many deficits observed in SR-treated animals were attenuated by dual exposure to SI (DFS). SI alone did not show BBB damage but did show differences in astrocyte morphology compared to the Controls. Thus, determining how single and combined inflight stressors modulate CNS structural integrity is crucial to fully understand the multiple pathways that could impact astronaut performance and health, including the alterations to the CNS structures and cell viability observed in this study. Full article

This study was conducted to compare and analyze whether Pilates exercise and yoga exercise help improve the performance of female fencers and prevent injury, and the dynamic balance test (LQ-YBT) and functional movement screening (FMS) test score of the elite adult female fencers were compared and analyzed as evaluation indicators. Participants were randomly classified into Pilates (n = 10) and yoga groups (n = 10), members of which took part in 50 min of exercise (5 min of warm-up, 40 min of main exercise, and 5 min of cool-down) twice weekly for eight weeks. The results obtained from this study were analyzed via independent t-test and 2-way ANOVA. The results were as follows: LQ-YBT measures (reaching distance) increased significantly for both groups, as did FMS scores (deep squat, hurdle step, inline lunge, shoulder mobility, active straight-leg raise, trunk-stability push-up, and rotary stability). These results suggest that Pilates exercise and yoga exercise might be likely effective in improving the performance of adult female fencers and injury prevention by increasing their dynamic balance ability and functional movement. Full article

Objectives—Metallic elements and fibrin clot properties have been linked to stroke. We examined metallic and nonmetallic elements, fibrin clot lysis time (CLT), and maximum absorbance (Abs_max) in relation to ischemic stroke. Design—A case–control study of ischemic stroke patients vs. healthy individuals. Subjects and Methods—Plasma and serum were collected from 260 ischemic stroke patients (45.0% women; age, 68 ± 12 years) and 291 healthy controls (59.7% women; age, 50 ± 17 years). Fibrin CLT and Abs_max were measured using a validated turbidimetric assay. Serum elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). Data were analyzed by bivariate correlations and multiple or logistic regression. Results—In female stroke patients, copper, lithium, and aluminum were significantly lower compared with controls; in male stroke patients, potassium was lower, and beryllium was elevated. In female and male stroke patients, iron, zinc, nickel, calcium, magnesium, sodium, and silicon were significantly lower, while strontium was elevated. Positive correlations between fibrin clot properties and metals, observed in healthy controls, were lost in ischemic stroke patients. In multivariate regression analysis, fibrin CLT and/or Abs_max was associated with zinc, calcium, potassium, beryllium, and silicon in stroke patients and with sodium, potassium, beryllium, and aluminum in controls. In logistic regression analysis, stroke was independently associated with lithium, nickel, beryllium, strontium, boron, and silicon and with sodium, potassium, calcium, and aluminum but not with fibrin CLT/Abs_max. Conclusions—Various elements were associated with fibrin clot properties and the risk of ischemic stroke. Lithium, sodium, calcium, and aluminum abrogated the association of fibrin clot properties with ischemic stroke. Full article

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies –with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer). Full article

The rapid and accurate estimation of aboveground forest phytomass remains a challenging research task. In general, methods for estimating phytomass fall mainly into the category of field measurements performed by ground-based methods, but approaches based on remote sensing and ecological modelling have been increasingly applied. The aim is to develop the scientific and methodological framework for the remote sensing estimation of qualitative and quantitative characteristics of forest stands, using the combination of surveys and machine learning models to determine phytomass of forest stands and calculate the carbon balance. Even-aged stands of different tree species growing in the forest steppe zone of the East European Plain were chosen as test objects. We have applied the modernized methodological approaches to compare and integrate forest and tree stand characteristics obtained by ground-based and UAV-based comprehensive surveys; additionally, we developed computer vision models and methods for determining the same characteristics by remote sensing methods. The key advantage of the proposed methodology for remote monitoring and carbon balance control over existing analogues is the minimization of the amount of groundwork and, consequently, the reduction inlabor costs without loss of information quality. Reliable data on phytomass volumes will allow for operational control of the forest carbon storage, which is essential for decision-making processes. This is important for the environmental monitoring of forests and green spaces of various economic categories. The proposed methodology is necessary for the monitoring and control of ecological–climatic and anthropogenic–technogenic transformations in various landscapes. The development is useful for organizing the management of ecosystems, environmental protection, and managing the recreational and economic resources of landscapes with natural forests and forest plantations. Full article

The semimembranosus muscle inserts into several tendons that are associated with some pathologies. Although ultrasound is useful for studying, diagnosing, and managing these pathologies, the correct interpretation of any images requires a clear knowledge of the related anatomical structures and the inter-related functions. We studied 38 cryopreserved non-paired knees from adult anatomical specimens and 4 non-paired knees from 29 to 38-week-old fetuses. The semimembranosus muscle and its tendons were located, observed, and injected under ultrasound guidance. The macroscopic anatomy was studied using dissection and anatomical cuts and the tendons were analyzed histologically. Measurements of muscle were taken 10 cm from the medial epicondyle and just before the tendon divided. The ultrasound facilitated the identification of the different divisions of the tendon of semimembranosus muscle and the rotation of the muscle and tendon from medial to posterior. An anatomical study confirmed this rotation and revealed an average width, thickness, and diameter of 38.29 mm, 14.36 mm, and 112.64 mm, respectively. Important relationships were observed between the divisions of the main tendons and the medial collateral ligament, the posterior side of the knee and popliteus muscle. This information can help to explain knee pathologies and facilitate rehabilitation after surgery. Full article

This review systematically investigates the critical role of natural binding proteins (NBPs), encompassing DNA-, RNA-, carbohydrate-, fatty acid-, and chitin-binding proteins, in the realms of oncology and diagnostics. In an era where cancer continues to pose significant challenges to healthcare systems worldwide, the innovative exploration of NBPs offers a promising frontier for advancing both the diagnostic accuracy and therapeutic efficacy of cancer management strategies. This manuscript provides an in-depth examination of the unique mechanisms by which NBPs interact with specific molecular targets, highlighting their potential to revolutionize cancer diagnostics and therapy. Furthermore, it discusses the burgeoning research on aptamers, demonstrating their utility as ‘nucleic acid antibodies’ for targeted therapy and precision diagnostics. Despite the promising applications of NBPs and aptamers in enhancing early cancer detection and developing personalized treatment protocols, this review identifies a critical knowledge gap: the need for comprehensive studies to understand the diverse functionalities and therapeutic potentials of NBPs across different cancer types and diagnostic scenarios. By bridging this gap, this manuscript underscores the importance of NBPs and aptamers in paving the way for next-generation diagnostics and targeted cancer treatments. Full article

Amino acids are organic compounds that enter the protein structure, being involved in the proper functioning of the body. The role of amino acids in the onset of autism spectrum disorder (ASD) is yet to be established. Our aim was to identify correlations between urine amino acids and their derivatives and ASD. Methods: We designed a case–control study that consisted of 75 boys and girls, aged between 2 and 12 years. For amino acid profile, we used urine samples that were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results: Descriptive analysis showed higher values for glutamine, hydroxyproline, tyrosine, aspartic acid, and tryptophan and lower values for serine in the autism group than in the control group. Also, we found that boys with autism had higher values than the boys in the control group for serine, threonine, and aspartic acid. For girls from both groups, we did not find statistically significant values. In terms of age groups, we found significantly higher values for histidine, threonine, valine, methionine, aspartic acid, glutamic acid, alpha amino-adipic acid, sarcosine, alanine, and beta-alanine and significantly lower values for proline for both the autism and control groups under 5 years. Conclusions: The findings of this study support the assumption that amino acids may have a role in the expression of ASD. Full article

Fryns syndrome (FS) is a multiple congenital anomaly syndrome with different multisystemic malformations. These include congenital diaphragmatic hernia, pulmonary hypoplasia, and craniofacial dysmorphic features in combination with malformations of the central nervous system such as agenesis of the corpus callosum, cerebellar hypoplasia, and enlarged ventricles. We present a non-consanguineous northern European family with two recurrent cases of FS: a boy with multiple congenital malformations who died at the age of 2.5 months and a female fetus with a complex developmental disorder with similar features in a following pregnancy. Quad whole exome analysis revealed two likely splicing-affecting disease-causing mutations in the PIGN gene: a synonymous mutation c.2619G>A, p.(Leu873=) in the last nucleotide of exon 29 and a 30 bp-deletion c.996_1023+2del (NM_176787.5) protruding into intron 12, with both mutations in trans configuration in the affected patients. Exon skipping resulting from these two variants was confirmed via RNA sequencing. Our molecular and clinical findings identified compound heterozygosity for two novel splice-affecting variants as the underlying pathomechanism for the development of FS in two patients. Full article

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an abnormal immunological response, and fibrosis leading to dysfunction of the multiple organs. The disease is categorized into two subtypes: limited cutaneous SSc and diffuse cutaneous SSc. Scleroderma can affect vital organs with respiratory, cardiac, renal, ocular, and dermatological complications. The ocular manifestations of the disease can occur in the anterior and posterior segments of the eye. Changes in the anterior segment related to the disease include eyelid skin remodeling, dry eye syndrome, and conjunctival abnormalities. The disease’s impact on the posterior segment of the eye mostly causes pathologies in the retinal microcirculatory system and abnormalities in the optic nerve. This review provides detailed insights into ocular complications associated with scleroderma. Full article

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encode presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca²⁺) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD; however, it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess the early calcium and glutamate phenotypes of FAD by measuring the Ca²⁺ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA, and kainate compared to isogenic control and healthy lines. The data show that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca²⁺ responses to glutamate and AMPA, but not NMDA or kainate. Together, this suggests that PSEN1 mutations alter Ca²⁺ and glutamate signaling as an early phenotype of FAD. Full article

Neovascular age-related macular degeneration (AMD) is a major cause of irreversible blindness in elderly populations in developed countries. AMD’s etiopathology is multifactorial, with strong environmental and genetic components, but the exact molecular pathomechanisms underlying the disease are still unknown. In this study, we analyzed blood serum collected from 74 neovascular AMD patients and 58 healthy controls to identify proteins that may serve as potential biomarkers and expand our knowledge about the etiopathogenesis of the disease. The study revealed 17 differentially expressed proteins—11 up-regulated and 6 down-regulated—in neovascular AMD, which are involved in the biological processes previously linked with the disease—oxidative stress and persistent inflammation, impaired cellular transport, lipid metabolism and blood coagulation. In conclusion, the differences in the expressions of the proteins identified in this study may contribute to our understanding of the mechanisms underlying AMD and possibly serve in future as promising biomarkers. Full article

This retrospective cohort study evaluates the safety and efficacy of replacement therapy with regard to pregnancy outcomes in hemophilia carriers. Hemophilia carriers face elevated bleeding risks during pregnancy, necessitating meticulous management, including replacement therapy with clotting factors. This research examines the records of 64 pregnant hemophilia carriers at King Fahad Medical City, Riyadh, from January 2010 to December 2023, analyzing their demographic details, hemophilia type and severity, replacement therapy specifics, and pregnancy outcomes. The study found that 62.5% of the participants had hemophilia A, with 43.8% categorized as severe. Most subjects (87.5%) received recombinant factor VIII at a median dosage of 30 IU/kg weekly. Adverse pregnancy outcomes included gestational hypertension (15.6%), preterm labor (18.8%), and postpartum hemorrhage (12.5%). The cesarean section rate was 28.1%. Neonatal outcomes were generally favorable, with median birth weights at 3100 g and mean Apgar scores of 8.2 and 9.1 at 1 and 5 min, respectively. Logistic regression analysis revealed no significant association between adverse events and therapy type or dosage, though a trend towards significance was noted with once-weekly administration (p = 0.082). The study concludes that replacement therapy is a viable method for managing hemophilia in pregnant carriers, leading to generally favorable maternal and neonatal outcomes. However, it underscores the importance of individualized treatment plans and close monitoring to effectively manage the risks associated with hemophilia during pregnancy. Full article

Aim. To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to conventional therapies. Methods. We performed further statistical analyses on patient data from two published, double-blind, randomized, and placebo-controlled studies (DB-RCTs), which examined the effects of intra-articular corticosteroids (ia-CSs), hyaluronic acid (ia-HA)—KИ-109-3-0008/14.01.2014, and intravenous bisphosphonates (iv-BPs) -KИ- 109-3-0009/14.01.2014 compared to the country’s standard pHOA therapy. The data span an 8-year follow-up of 700 patients with pHOA, including: 1. Clinical parameters (WOMAC-A, B, C, and T; PtGA). 2. Laboratory markers (serum calcium and phosphate levels; 25-OH-D and PTH, markers for bone sCTX-I and cartilage uCTX-II turnover). 3. Radiological indicators: X-ray stage (Kellgren-Lawrence (K/L) and model (Bombelli/OOARSI), width (mJSW), speed (JSN mm/year), and zone of maximum narrowing of the joint space (max-JSN)—determining the type of femoral head migration (FHM). 4. DXA indicators: bone geometry (HAL; NSA; and MNW); changes in regional and total bone mineral density (TH-BMD, LS-BMD, and TB-BMD). 5. Therapeutic responses (OARSI/MCII; mJSW; JSNmm/yearly) to different drug regimens (iv-BP -zoledronic acid (ZA/-5 mg/yearly for 3 years)); ia-CS 40 mg methylprednisolone acetate, twice every 6 months; and ia-HA with intermediate molecular weight (20 mg/2 mL × 3 weekly applications, two courses every 6 months) were compared to standard of care therapy (Standard of Care/SC/), namely D3-supplementation according to serum levels (20–120 ng/mL; target level of 60 ng/mL), simple analgesics (paracetamol, up to 2.0 g/24 h), and physical exercises. The abovementioned data were integrated into a non-supervised hierarchical agglomerative clustering analysis (NHACA) using Ward’s linkage method and the squared Euclidean distance to identify different endophenotypes (EFs). Univariate and multivariate multinomial logistic regression analyses were performed to determine the impact of sex and FHM on clinical and radiographic regression of pHOA. Results. A baseline cluster analysis using incoming (M0) patient data identified three EFs: hypertrophic H-HOA, atrophic A-HOA, and intermediate I-HOA. These EFs had characteristics that were similar to those of patients grouped by radiographic stage and pattern (‘H’-RPs, ‘I’-RPs, and ‘A’-RPs), p < 0.05). The repeated cluster analysis of M36 data identified four EF pHOAs: 1. Hypertrophic (slow progressors, the influence of the type of femoral head migration (FHM) outweighing the influence of sex on progression), progressing to planned total hip replacement (THR) within 5 (K/LIII) to 10 (K/LII) years. 2. Intermediate (sex is more important than the FHM type for progression) with two subgroups: 2#: male-associated (slow progressors), THR within 4 (K/LIII) to 8 years. (K/LII). 2* Female-associated (rapid progressors), THR within 3 (K/LIII) to 5 (K/LII) years. 3. Atrophic (rapid progressors; the influence of FHM type outweighs that of sex), THR within 2 (K/LIII) to 4 (K/LII) years. Each EF, in addition to the patient’s individual progression rate, was also associated with a different response to the aforementioned therapies. Conclusions. Clinical endophenotyping provides guidance for a personalized approach in patients with pHOA, simultaneously assisting the creation of homogeneous patient groups necessary for conducting modern genetic and therapeutic scientific studies. Full article

Atrial fibrillation (AF) commonly occurs in approximately 2% of cancer patients, and the incidence of AF among cancer patients is greater than in the general population. This observational study presented the incidence risk of AF among cancer patients, including specific cancer types, using a population database. The Taiwan Cancer Registry was used to identify cancer patients between 2008 and 2017. The diagnosis of AF was based on the International Classification of Diseases codes (ICD-9-CM: 427.31 or ICD-10-CM: I48.0, I48.1, I48.2, and I48.91) in Taiwan national health insurance research datasets. The incidence of developing AF in the cancer population was calculated as the number of new-onset AF cases per person-year of follow-up during the study period. The overall incidence of AF among cancer patients was 50.99 per 100,000 person-years. Patients aged older than 65 years and males had higher AF incidence rates. Lung cancer males and esophageal cancer females showed the highest AF incidence risk (185.02 and 150.30 per 100,000 person-years, respectively). Our findings identified esophageal, lung, and gallbladder cancers as the top three cancers associated with a higher incidence of AF. Careful monitoring and management of patients with these cancers are crucial for early detection and intervention of AF. Full article

Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well. Full article

Scopolamine and atropine are two medicinal alkaloids derived from Datura stramonium L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth regulator, affects the biosynthesis and accumulation of these alkaloids in different plant tissues. The expression levels of putrescine N-methyltransferase (PMT), tropinone reductase I (TR1), and hyoscyamine 6β-hydroxylase (h6h), three critical enzymes in the biosynthetic pathway, were also analyzed. The results indicated that MJ at 150 µM increased the production of scopolamine and atropine in both leaves and roots, while MJ at 300 µM had an adverse effect. Furthermore, MJ enhanced the expression of PMT, TR1, and h6h genes in the roots, the primary site of alkaloid synthesis, but not in the leaves, the primary site of alkaloid storage. These results imply that MJ can be applied to regulate the biosynthesis and accumulation of scopolamine and atropine in D. stramonium, thereby improving their production efficiency. Full article

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factors, such as hypertension, diabetes, obesity, and smoking, among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D’s multifaceted and expanding actions concerning its involvement in CKD and CVD. Full article

This review provides an overview of current knowledge regarding the adaptive effects of physical training on the endothelium. The endothelium plays a crucial role in maintaining the health of vessel walls and regulating vascular tone, structure, and homeostasis. Regular exercise, known for its promotion of cardiovascular health, can enhance endothelial function through various mechanisms. The specific health benefits derived from exercise are contingent upon the type and intensity of physical training. The review examines current clinical evidence supporting exercise’s protective effects on the vascular endothelium and identifies potential therapeutic targets for endothelial dysfunction. There is an urgent need to develop preventive strategies and gain a deeper understanding of the distinct impacts of exercise on the endothelium. Full article

BRCA1 and BRCA2 mutations are responsible for a higher incidence of breast and ovarian cancer (from 55% up to 70% vs. 12% in the general population). If their functions have been widely investigated in the onset of these malignancies, still little is known about their role in fertility impairment. Cancer patients treated with antineoplastic drugs can be susceptible to their gonadotoxicity and, in women, some of them can induce apoptotic program in premature ovarian follicles, progressive depletion of ovarian reserve and, consequently, cancer treatment-related infertility (CTRI). BRCA variants seem to be associated with early infertility, thus accelerating treatment impairment of ovaries and making women face the concrete possibility of an early pregnancy. In this regard, fertility preservation (FP) procedures should be discussed in oncofertility counseling—from the first line of prevention with risk-reducing salpingo-oophorectomy (RRSO) to the new experimental ovarian stem cells (OSCs) model as a new way to obtain in vitro-differentiated oocytes, several techniques may represent a valid option to BRCA-mutated patients. In this review, we revisit knowledge about BRCA involvement in lower fertility, pregnancy feasibility, and the fertility preservation (FP) options available. Full article

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms. Full article

Tumoral calcinosis is an extremely rare genetic disease caused by mutations in three genes, GALNT3, FGF23, and KL, which disrupt phosphorus metabolism. The hallmark of this condition is the formation of tumors in the soft tissues around the joints. Other phenotypic features of tumoral calcinosis are dental involvement and brain and vascular calcifications. The clinical case reported herein presents for the first time to the scientific community the c.202A>G (p.Thr68Ala) mutation of the FGF23 gene, associated with a hyperphosphatemic variant of tumoral calcinosis and multiple severe vascular aneurysms. A female patient underwent multiple surgeries for tumor formations in her soft tissues that first appeared at the age of 12 months. On this occurrence, the patient was found to have hyperphosphatemia, low phosphate clearance, increased tubular reabsorption with normal levels of total and ionized calcium, vitamin D3, and parathyroid hormone, and no effect of treatment with sevelamer hydrochloride and a low-phosphate diet. At the age of 39, the patient underwent imaging studies due to edema and a pulsating formation in the neck area, which revealed multiple vascular aneurysms with thrombosis, for which she received operative and interventional treatment. In this connection, and because of the established phosphorus metabolism disturbance, a genetic disease was suspected. The sequence analysis and deletion/duplication testing of the 358 genes performed on this occasion revealed that the woman was homozygous for a variant of the c.202A>G (p.Thr68Ala) mutation of the FGF23 gene. The established mutation is not present in population databases. The presented clinical case is the first and only one in the world to demonstrate the role of this type of FGF23 gene mutation in the development of a hyperphosphatemic variant of tumoral calcinosis characterized by aggressive formation of multiple vascular aneurysms. Full article