Estudio de la citoqueratina- 18 como marcador no invasivo en pacientes con enfermedad de hígado graso no alcohólico

Introducción: La enfermedad por hígado graso no alcohólico es una de las principales causas de afección hepática. La citoqueratina 18 surge como marcador no invasivo para la valoración de fibrosis hepática. El objetivo del trabajo fue validar el uso de la citoqueratina 18 en sangre periférica en el diagnóstico y evolución de los pacientes con enfermedad por hígado graso no alcohólico. Metodología: Para validar la citoqueratina 18 en el diagnóstico se realizó un estudio de tipo caso-control. El grupo caso fueron los pacientes mayores de 18 años, de ambos sexos, con diagnóstico de enfermedad por hígado graso no alcohólico vinculado al síndrome metabólico, captados entre 2/2/2019 al 2/2/2020. El grupo control fueron personas donantes de sangre. Se parearon 1-1 por edad y sexo. Se cuantificó la citoqueratina 18 en sangre periférica de ambos grupos. Para validar la citoqueratina 18 en la evolución de los pacientes con enfermedad de hígado graso no alcohólico se realizó un trabajo prospectivo, longitudinal. El grupo de pacientes captados fueron seguidos durante un año bajo tratamiento estándar, finalizando el mismo se realizó la cuantificación de citoqueratina 18 en sangre periférica. Las variables continuas se expresan con la media y desvío estándar. Se analizó con test de t Student, error α < 5% Resultados: 13 pacientes integran el grupo caso (12 mujeres), de 53 ± 11 años, con IMC 35.01 ± 8.9 kg/m2. El valor de citoqueratina 18 pre-tratamiento fue de 1410 ± 120 UI, y el valor post-tratamiento fue de 117 ± 56, p < 0,005.El grupo control fueron 13 personas (12 mujeres), de 43,4 ± 8,1 años e IMC 28,10 ± 5,4 kg/m2 El valor de citoqueratina 18 fue de 193 ± 7.2 UI, p < 0.005 vs grupo caso pretratamiento. Conclusiones: La citoqueratina 18 es más elevada en los pacientes con enfermedad hígado graso no alcohólico, siendo estadísticamente significativa y disminuye con el tratamiento con significación estadística, pudiendo constituirse en un marcador útil en este grupo de pacientes.

Introduction: Nonalcoholic fatty liver disease is one of the main causes of liver disease. Cytokeratin 18 emerges as a non-invasive marker for the assessment of liver fibrosis. The objective of the work was to validate the use of cytokeratin 18 in peripheral blood in the diagnosis and evolution of patients with non-alcoholic fatty liver disease. Methodology: To validate cytokeratin 18 in the diagnosis, a case-control study was carried out. The case group was patients over 18 years of age, of both sexes, with a diagnosis of non-alcoholic fatty liver disease linked to metabolic syndrome, recruited between 2/2/2019 to 2/2/2020. The control group were blood donors. They were matched 1-1 for age and sex. Cytokeratin 18 was quantified in peripheral blood of both groups. To validate cytokeratin 18 in the evolution of patients with non-alcoholic fatty liver disease, a prospective, longitudinal study was carried out. The group of patients recruited were followed for one year under standard treatment, at the end of which cytokeratin 18 was quantified in peripheral blood. Continuous variables are expressed with the mean and standard deviation. It was analyzed with Student's t test, α error < 5%. Results: 13 patients make up the case group (12 women), 53 ± 11 years old, with BMI 35.01 ± 8.9 kg/m2. The pre-treatment cytokeratin 18 value was 1410 ± 120 IU, and the post-treatment value was 117 ± 56, p < 0.005. The control group was 13 people (12 women), 43.4 ± 8.1 years and BMI 28.10 ± 5.4 kg/m2 The cytokeratin 18 value was 193 ± 7.2 IU, p < 0.005 vs. pretreatment case group. Conclusions: Cytokeratin 18 is higher in patients with non-alcoholic fatty liver disease, being statistically significant, and decreases with treatment with statistical significance, and may become a useful marker in this group of patients.

Introdução: A doença hepática gordurosa não alcoólica é uma das principais causas de doença hepática. A citoqueratina 18 surge como um marcador não invasivo para avaliação de fibrose hepática. O objetivo do trabalho foi validar o uso da citoqueratina 18 no sangue periférico no diagnóstico e evolução de pacientes com doença hepática gordurosa não alcoólica. Metodologia: Para validar a citoqueratina 18 no diagnóstico, foi realizado um estudo caso-controle. O grupo caso foi composto por pacientes maiores de 18 anos, de ambos os sexos, com diagnóstico de doença hepática gordurosa não alcoólica ligada à síndrome metabólica, recrutados entre 02/02/2019 a 02/02/2020. O grupo controle eram doadores de sangue. Eles foram comparados em 1 a 1 por idade e sexo. A citoqueratina 18 foi quantificada no sangue periférico de ambos os grupos. Para validar a citoqueratina 18 na evolução de pacientes com doença hepática gordurosa não alcoólica, foi realizado um estudo prospectivo e longitudinal. O grupo de pacientes recrutados foi acompanhado durante um ano sob tratamento padrão, ao final do qual a citoqueratina 18 foi quantificada no sangue periférico. As variáveis ​​contínuas são expressas com média e desvio padrão. Foi analisado com teste t de Student, erro α < 5%. Resultados: Compõem o grupo caso 13 pacientes (12 mulheres), 53 ± 11 anos, com IMC 35,01 ± 8,9 kg/m2. O valor de citoqueratina 18 pré-tratamento foi de 1410 ± 120 UI e o valor pós-tratamento foi de 117 ± 56, p < 0,005. O grupo controle foi de 13 pessoas (12 mulheres), 43,4 ± 8,1 anos e IMC 28,10 ± 5,4 kg/m2 O valor da citoqueratina 18 foi de 193 ± 7,2 UI, p < 0,005 vs. grupo de casos pré-tratamento. Conclusões: A citoqueratina 18 é maior em pacientes com doença hepática gordurosa não alcoólica, sendo estatisticamente significativa, e diminui com o tratamento com significância estatística, podendo se tornar um marcador útil neste grupo de pacientes.

Biodegradable nanoplatforms for antigen delivery: part II - nanoparticles, hydrogels, and microneedles for cancer immunotherapy.

INTRODUCTION: In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved. AREASCOVERED: CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial. EXPERT OPINION: We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells further.

Interrogation of a fluoropolymer dispersion manufactured with a non-fluorinated polymerization aid for targeted and non-targeted fluorinated residuals by liquid chromatography high resolution mass spectrometry.

Recent advances in fluoropolymer polymerization have focused on replacing perfluorinated polymerization aids (PAs) with hydrocarbon-based alternatives. Hydrocarbon PAs are vulnerable to fluorinated radicals during polymerization, leading to the creation of hundreds of process-specific polyfluorinated residuals. These residuals, which include low molecular weight extractable or leachable impurities, are challenging to detect at trace levels. This study investigates a polytetrafluoroethylene (PTFE) dispersion prepared with a hydrocarbon-based surfactant (DOSS) to measure these process-specific fluorinated residues. Liquid chromatography high resolution mass spectrometry is one of the few analytical methods that offers the sensitivity and selectivity required to detect these residuals in complex matrices at concentrations as low as parts per billion. The results indicate that using a hydrocarbon PA during emulsion polymerization produces numerous polyfluorinated residuals. These must be identified and monitored to develop effective abatement strategies, ensuring responsible fluoropolymer manufacturing.

The Bony Nasal Cavity and Paranasal Sinuses of Big Felids and Domestic Cat: A Study Using Anatomical Techniques, Computed Tomographic Images Reconstructed in Maximum-Intensity Projection, Volume Rendering and 3D Printing Models.

This study aims to develop three-dimensional printing models of the bony nasal cavity and paranasal sinuses of big and domestic cats using reconstructed computed tomographic images. This work included an exhaustive study of the osseous nasal anatomy of the domestic cat carried out through dissections, bone trepanations and sectional anatomy. With the use of OsiriX viewer, the DICOM images were postprocessed to obtaining maximum-intensity projection and volume-rendering reconstructions, which allowed for the visualization of the nasal cavity structures and the paranasal sinuses, providing an improvement in the future anatomical studies and diagnosis of pathologies. DICOM images were also processed with AMIRA software to obtain three-dimensional images using semiautomatic segmentation application. These images were then exported using 3D Slicer software for three-dimensional printing. Molds were printed with the Stratasys 3D printer. In human medicine, three-dimensional printing is already of great importance in the clinical field; however, it has not yet been implemented in veterinary medicine and is a technique that will, in the future, in addition to facilitating the anatomical study and diagnosis of diseases, allow for the development of implants that will improve the treatment of pathologies and the survival of big felids.

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues Mediate the Immunoregulation of T Cells through the Purinergic Pathway.

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3+ T cells and promoted the generation of CD4+CD25+FoxP3+CD39+CD73+ Tregs and Th17+CD39+ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs.

Comparing Sarcopenia Definitions and Muscle Power Reduction: Associations with Health Outcomes in Spanish Community-Dwelling Older Adults.

Objectives: To analyze the associations between the different operational definitions of sarcopenia published in the last decade and reduced muscle power with a set of adverse health-related outcomes, such as comorbidities, depression, polypharmacy, self-perceived health, educational attainment, socioeconomic status, falls, and hospitalizations in Spanish community-dwelling older adults. Methods: A total of 686 community-dwelling older adults (median age: 72; women: 59.2%; physically active: 84%) were included in this cross-sectional analysis (ClinicalTrials.gov: NCT05148351). Sarcopenia was assessed using the FNIH, EWGSOP2, AWGS, and SDOC algorithms. Reduced muscle power was defined as the lowest sex-specific tertile and measured during the rising phase of the sit-to-stand test using a validated mobile application. Unadjusted and adjusted logistic regressions by potential confounders were performed to identify the association between sarcopenia and reduced muscle power with health-related outcomes. Results: Sarcopenia prevalence was 3.4%, 3.8%, 12.4%, and 21.3% according to the SDOC, FNIH, EWGSOP2, and AWGS, respectively. Among these definitions, moderate and large associations with health-related outcomes were observed for EWGSOP2 and SDOC, respectively, but few associations were found for FNIH and AWGS criteria. Reduced muscle power was associated more frequently and moderately with health-related outcomes compared to sarcopenia definitions. These associations remained constant after adjusting for confounders. Conclusions: The prevalence and impact of sarcopenia varied depending on the definitions used. Among the sarcopenia definitions, the SDOC exhibited the strongest associations, while reduced muscle power was the variable most frequently associated with health-related outcomes compared to any of the four sarcopenia definitions in well-functioning and physically active community-dwelling older adults.

Prevalence of Thrombocytopenia in Pregnant Women with COVID-19: A Systematic Review and Meta-Analysis.

Background/Objectives: Although articles and reviews have been published on the effect of SARS-CoV-2 infection on pregnancy outcomes, they show mixed results with different hypotheses, and no work has focused specifically on the prevalence of thrombocytopenia. The objective of this systematic review and meta-analysis was to synthesize previous evidence and estimate the prevalence of thrombocytopenia in pregnant women with COVID-19. Methods: This systematic review was conducted according to the PRISMA-2020 and MOOSE guidelines. The Medline and Web of Science databases were searched in February 2024, and a meta-analysis of the overall prevalence of thrombocytopenia in pregnant women with COVID-19 was performed. The risk of bias was assessed using the Joanna Briggs Institute checklists. A leave-1-out sensitivity analysis was performed to test for disproportionate effect. Publication bias was assessed by visual inspection of funnel plots and Egger's test. Results: A total of 23 studies met the inclusion criteria, of which 8 were included in the meta-analysis. There was significant (Q = 101.04) and substantial heterogeneity among the studies (I2 = 93.07%). There were no quality-based exclusions from the review of eligible studies. The combined effect of the studies showed a prevalence of thrombocytopenia of 22.9% (95%CI 4.8-41.0%). Subgroup analysis revealed no statistically significant difference in the pooled prevalence of thrombocytopenia ([16.5%; 30.3%]; p = 0.375. Egger's test for bias was not significant, indicating that smaller studies did not report larger estimates of prevalence (t = 1.01, p = 0.353). Moreover, no potential publication bias was found. Our results are consistent with those obtained in pregnant women without COVID-19 infection and extend those of previous reviews of the effect of COVID-19 infection on pregnancy outcomes. Conclusions: Infection during pregnancy does not seem to be an additional risk factor for platelet count, although monitoring platelet count in pregnant women with COVID-19 may be of great importance to determine possible therapeutic strategies, especially in emergency cases.

Efficient Hydroxyapatite Extraction from Salmon Bone Waste: An Improved Lab-Scaled Physico-Chemico-Biological Process.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods-alkaline hydrolysis, calcination, and NaOH hydrolysis-to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis-calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications.

Spatial distribution of PAHs, nickel, and vanadium in sediments from a large coastal lagoon near a petroleum extraction area in the southern Gulf of Mexico.

One of the world's crucial areas for crude oil exploration and extraction is the southern Gulf of Mexico, where Terminos Lagoon (TL) is located. Sediments from the TL region were used to assess the spatial patterns, origins, and ecotoxicological risks associated with 16 priority polycyclic aromatic hydrocarbons (PAHs; 3.1-248.9 ng⸳g-1 dry weight basis, dw) and trace metals (Ni = 11.0-104.0 mg⸳kg-1; V = 2.0-35.0 mg⸳kg-1 dw) linked to anthropogenic activities. Although origin indices based on PAHs and metals concentrations indicate no crude oil pollution in the region, sources of pyrogenic PAHs were identified. A chemometric approach demonstrated associations between organic matter and PAHs, and that metal accumulation depends mostly by the input of lithogenic materials. Ecotoxicological risk estimations showed a higher risk of possible adverse effects in sites near swamps and mangrove zones, highlighting the need of future monitoring. This study provides a reference for policymakers to conserve Mexico's largest coastal lagoon and other oil-impacted coastal areas worldwide.

Respiratory, cardio-metabolic and neurodevelopmental long-term outcomes of moderate to late preterm birth: not just a near term-population. A follow-up study.

Introduction: Moderate-to-late preterm infants constitute the majority within the preterm infant population. Most research on preterm infants has focused on very preterm children, often treating moderate-to-late preterm infants as similar to full-term infants. Our objective was to compare clinical, respiratory, cardio-metabolic and neurodevelopmental outcomes in adolescents aged 12-15 years born moderate and late preterm with a control group of the same age born full-term. Methods: Observational cross-sectional study, comparing moderate-to-late preterm (32-36+6 weeks' gestational age) with full-term adolescents (37-41+6 weeks' gestational age; 75 each group). Perinatal and neonatal history were collected as well as data on respiratory evolution (ISAAC questionnaire for asthma symptoms for adolescents 13-14 years), anthropometric values, learning difficulties, behavioral test (screening questionnaire for high-performance autism spectrum disorder and evaluation test for attention deficit hyperactivity disorder), skin prick test, pulmonary function test, echocardiogram and blood pressure. A blood test with metabolic profile was conducted. Results: Moderate-to-late preterm adolescents had more current asthma [p = 0.008, OR3 (95% CI 1.26-7.14)] and longer duration of combined treatments to control asthma (inhaled corticosteroids and anti-leukotrienes; p = 0.048). Forced vital capacity <80% was detected more often in moderate-to-late preterm patients (p = 0.013). When assessing right ventricle, moderate-to-late preterm adolescents showed better tricuspid annular plane systolic excursion z-score (p = 0.003), shortening fraction (p < 0.001) and E/A ratio z-score (p = 0.002). Regarding left ventricular assessment, moderate-to-late preterm group had smaller ventricle diastolic diameter (p = 0.04) and lower posterior wall z-score values (p = 0.037). They also showed a better S'wave z-score (p = 0.027), E wave (p = 0.005), E/A ratio (p = 0.003) and a higher septal myocardial performance index z-score (p = 0.025). Moderate-to-late preterm adolescents presented lower weight z-score (p = 0.039), body mass index z-score (p = 0.013), Waterlow weight index (p = 0.006) and higher undernutrition index [p = 0.04; OR 1.4 (95% CI 1-1.9)]. Although there were no differences in neurodevelopmental survey or behavioral tests. Conclusion: Our findings underscore the importance of extended follow-up for this predominant group of premature infants to identify potential respiratory, cardiac and anthropometric issues that may emerge in the future.

Identification of predictive models including polymorphisms in cytokines genes and clinical variables associated with post-transplant complications after identical HLA-allogeneic stem cell transplantation.

Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001. Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.

Molecular Modeling Insights on the Pharmaceuticals and Hypotheses of Alzheimer's Disease.

Alzheimer's disease (AD) stands as the predominant contributor to dementia cases. The ongoing developments in our understanding of its pathogenesis have sparked the interest of researchers, driving them to explore innovative treatment approaches. Existing therapies incorporating cholinesterase inhibitors and/or NMDA antagonists have shown limited improvement in alleviating symptoms. This, in turn, highlights the urgency for the pursuit of more effective therapeutic options. Given the annual rise in the number of individuals affected by dementia, it is imperative to allocate resources and efforts towards the exploration of novel therapeutic options. This review aims to provide a comprehensive overview of the AD-related hypotheses, along with the computational approaches employed in research within each hypothesis. In this comprehensive review, the authors shed light on using various computational tools, including diverse case studies, in the pursuit of finding efficacious treatments for AD. The development of more sophisticated diagnostic techniques is crucial, enabling early detection and intervention in the battle against this challenging condition. The potential treatments investigated in this analysis are poised to assume ever more significant functions in both preventing and treating AD, ultimately enhancing the management of the condition and the overall well-being of individuals affected by AD.

Effects of Arborvitae (Thuja plicata) Essential Oil on Cervical Cancer Cells: Insights into Molecular Mechanisms.

AIMS: This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression. BACKGROUND: Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted. OBJECTIVE: The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines. METHODS: The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis. RESULTS: The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells. CONCLUSION: Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.

Chronic disease incidence explained by stepwise models and co-occurrence among them.

Multimorbidity (MM) is the co-occurrence of two or more chronic diseases. We provided a dynamic approach revealing the MM complexity constructing a multistep incidence-age model for all patients with MM between 2014 and 2021 in the Basque Health System, Spain. The multistep model, with eight steps for males and nine for females, is a very well-fitting representation of MM. To gain insight into the MM components, we modeled the 19 diseases used to calculate the Charlson Comorbidity Index (CCI). We observed that the CCI diseases formed a complex interaction network. Hierarchical clustering of the incidence-age profiles clustered the CCI diseases into low- and high-risk of dying pathologies. Diseases with a higher number of steps are better represented by a multistep model. Anatomically, diseases associated with the central nervous system have the highest number of steps, followed by those associated with the kidney, heart, peripheral vasulature, pancreas, joints, cerebral vasculature, lung, stomach, and liver.

Latent infection of an active giant endogenous virus in a unicellular green alga.

Latency is a common strategy in a wide range of viral lineages, but its prevalence in giant viruses remains unknown. Here we describe the activity and viral production from a 617 kbp integrated giant viral element in the model green alga Chlamydomonas reinhardtii. We resolve the integrated viral region using long-read sequencing and show that viral particles are produced and released in otherwise healthy cultures. A diverse array of viral-encoded selfish genetic elements are expressed during GEVE reactivation and produce proteins that are packaged in virions. In addition, we show that field isolates of Chlamydomonas sp. harbor latent giant viruses related to the C. reinhardtii GEVE that exhibit similar infection dynamics, demonstrating that giant virus latency is prevalent in natural host communities. Our work reports the largest temperate virus documented to date and the first active GEVE identified in a unicellular eukaryote, substantially expanding the known limits of viral latency.

Biodegradable nanoplatforms for antigen delivery: part I - state of the art review of polymeric nanoparticles for cancer immunotherapy.

INTRODUCTION: Polymeric nanoparticles used for antigen delivery against infections and for cancer immunotherapy are an emerging therapeutic strategy in promoting the development of innovative vaccines. Beyond their capability to create targeted delivery systems with controlled release of payloads, biodegradable polymers are utilized for their ability to enhance the immunogenicity and stability of antigens. AREAS COVERED: This review extensively discusses the physicochemical parameters that affect the behavior of nanoparticles as antigen-delivery systems. Additionally, various types of natural and synthetic polymers and recent advancements in nanoparticle-based targeted vaccine production are reviewed. EXPERT OPINION: Biodegradable polymeric nanoparticles have gained major interest in the vaccination filed and have been extensively used to encapsulate antigens against a wide variety of tumors. Moreover, their versatility in terms of tunning their physicochemical characteristics, and their surface, facilitates the targeting to antigen presenting cells and enhances immune response.

The relationship between Parkinson's disease and sexual hyperactivity secondary to drug treatment: A systematic review.

INTRODUCTION: This review addresses the prevalence of hypersexual behavior in Parkinson's patients and the underlying neurobiological mechanisms, identifying risk and protective factors, comparing incidence among different treatments, and proposing recommendations for management and prevention. OBJECTIVE: To conduct a review on the relationship between Parkinson's disease and hypersexual behavior as a result of pharmacological treatment. METHODOLOGY: The search strategy, guided by PRISMA and PICOS criteria, focuses on the correlation between Parkinson's disease and hypersexual behavior due to pharmacological treatment. Utilizing databases like PubMed and Proquest, studies from the last 10 years in English or Spanish were selected, emphasizing clinical trials with Parkinson's patients under treatment. Inaccessible, irrelevant, or mixed-sample studies were excluded. The Cochrane Scale assessed the risk of bias. RESULTS: Out of 122 records, 103 remained after eliminating duplicates; 48 were reviewed, and ultimately, 6 studies met the inclusion criteria for analysis. CONCLUSIONS: Synthesizing the risk and protective factors linked to hypersexual behavior in Parkinson's patients receiving pharmacological treatment underscores the critical need for early detection and incorporation of these factors into clinical care. The suggested guidelines for managing and preventing hypersexual behavior in these patients carry substantial practical implications.

Effect of seminal plasma cholesterol and triacylglycerides concentrations and sperm morphology on semen freezability in domestic cats (Felis silvestris catus).

There is scarce information about the effect of sperm morphology and seminal plasma composition on cat semen freezability. Thus, this study aims to assess the effect of cat sperm morphology and seminal plasma cholesterol (CHOL) and triacylglyceride (TAG) concentrations on sperm post-thaw survival. Ejaculates (n = 49) were evaluated, and seminal plasma was separated and frozen until CHOL and TAG concentrations were measured. The sperm pellet was diluted in a tris-based egg yolk extender, frozen (n = 38), or processed for sperm ultrastructure study (n = 11). Abnormalities recorded were abnormal head shape and size, detached heads, knobbed or ruffled acrosomes, eccentric mid-piece insertion, proximal and distal cytoplasmic droplets, folded and coiled tails, and Dag defect. Ultramicroscopic evaluation detected several sperm abnormalities in fresh semen and some sperm damage in frozen semen. Seminal plasma lipids components were positively correlated with post-thaw motility and acrosome integrity. Higher freezability indices for motility and acrosome integrity were observed in frozen-thawed semen with high seminal plasma CHOL and TAG concentrations. No freezability differences were observed between teratozoospermic and normozoospermic ejaculates. Our results showed that even when seminal plasma was removed before cryopreservation, sperm survival after thawing was significantly higher in samples with high seminal plasma CHOL and TAG concentrations, indicating a rapid adherence to these compounds to the sperm plasma membrane, protecting sperm cells from temperature changes. Nevertheless, there were no differences in sperm freezability by sperm morphology.