Beta-Blockers Lower First Decompensation in Patients With Cirrhosis and Enduring Portal Hypertension After Etiological Treatment.

BACKGROUND AND AIMS: Non-selective beta-blockers (NSBBs) can lower the risk of first decompensation in patients with cirrhosis and clinically significant portal hypertension (CSPH) (identified by a hepatic venous pressure gradient ≥10 mm Hg) with active etiology. Our aim was to examine the effect of NSBBs on first decompensation occurrence in patients with cirrhosis and enduring CSPH after etiological treatment. METHODS: Patients with compensated cirrhosis and clinical evidence of CSPH (gastroesophageal varices [GEVs] and/or spontaneous portosystemic collaterals [SPSSs]) after 2 years from etiological treatment. The primary endpoint was first decompensation (occurrence of variceal bleeding, ascites, or hepatic encephalopathy) in patients on NSBBs vs off NSBBs. RESULTS: The final cohort included 406 patients. Baseline characteristics of patients on NSBBs (n = 187) and off NSBBs (n = 219) were comparable, except for signs of portal hypertension that were more pronounced in the on-NSBBs group. During a mean follow-up of 32 months, 127 (31%) patients decompensated, with ascites being the most common (77%) decompensating event. Decompensation rates were lower in patients on NSBBs (16% vs 44%; P < .0001). The benefit of NSBBs on decompensation was maintained in patients with small GEVs (17% vs 43%; P < .0001), in those with spontaneous portosystemic shunt only (8% vs 43%; P = .003), and in each different etiology, including hepatitis C virus-cured cirrhosis (9% vs 32%; P < .0001). At Cox regression analysis, hemoglobin, Child-Pugh, Model for End-Stage Liver Disease-Sodium, diabetes at baseline, and previous bacterial infections were independent predictors of decompensation, while NSBBs use had a protective effect (hazard ratio, 0.32; 95% confidence interval, 0.20-0.49; P < .0001). NSBBs use significantly reduced bacterial infection rates (hazard ratio, 0.36; 95% confidence interval, 0.22-0.58; P < .0001). CONCLUSION: NSBBs decrease the risk of first decompensation in patients with cirrhosis and enduring CSPH after etiological treatment.

RNA-seq analyses on gametogenic tissues of alfalfa (Medicago sativa) revealed plant reproduction- and ploidy-related genes.

BACKGROUND: In alfalfa (Medicago sativa), the coexistence of interfertile subspecies (i.e. sativa, falcata and coerulea) characterized by different ploidy levels (diploidy and tetraploidy) and the occurrence of meiotic mutants capable of producing unreduced (2n) gametes, have been efficiently combined for the establishment of new polyploids. The wealth of agronomic data concerning forage quality and yield provides a thorough insight into the practical benefits of polyploidization. However, many of the underlying molecular mechanisms regarding gene expression and regulation remained completely unexplored. In this study, we aimed to address this gap by examining the transcriptome profiles of leaves and reproductive tissues, corresponding to anthers and pistils, sampled at different time points from diploid and tetraploid Medicago sativa individuals belonging to progenies produced by bilateral sexual polyploidization (dBSP and tBSP, respectively) and tetraploid individuals stemmed from unilateral sexual polyploidization (tUSP). RESULTS: Considering the crucial role played by anthers and pistils in the reduced and unreduced gametes formation, we firstly analyzed the transcriptional profiles of the reproductive tissues at different stages, regardless of the ploidy level and the origin of the samples. By using and combining three different analytical methodologies, namely weighted-gene co-expression network analysis (WGCNA), tau (τ) analysis, and differentially expressed genes (DEGs) analysis, we identified a robust set of genes and transcription factors potentially involved in both male sporogenesis and gametogenesis processes, particularly in crossing-over, callose synthesis, and exine formation. Subsequently, we assessed at the same floral stage, the differences attributable to the ploidy level (tBSP vs. dBSP) or the origin (tBSP vs. tUSP) of the samples, leading to the identification of ploidy and parent-specific genes. In this way, we identified, for example, genes that are specifically upregulated and downregulated in flower buds in the comparison between tBSP and dBSP, which could explain the reduced fertility of the former compared to the latter materials. CONCLUSIONS: While this study primarily functions as an extensive investigation at the transcriptomic level, the data provided could represent not only a valuable original asset for the scientific community but also a fully exploitable genomic resource for functional analyses in alfalfa.

Analysis of phenotypic changes in high temperature and low pH extreme conditions of Alicyclobacillus sendaiensis PA2 related with the cell wall and sporulation genes.

The A. sendaiensis PA2 is a polyextremophile bacterium. In this study, we analyze the A. sendaiensis PA2 genome. The genome was assembled and annotated. The A. sendaiensis PA2 genome structure consists of a 2,956,928 bp long chromosome and 62.77% of G + C content. 3056 CDSs were predicted, and 2921 genes were assigned to a putative function. The ANIm and ANIb value resulted in 97.17% and 96.65%, the DDH value was 75.5%, and the value of TETRA (Z-score) was 0.98. Comparative genomic analyses indicated that three systems are enriched in A. sendaiensis PA2. This strain has phenotypic changes in cell wall during batch culture at 65 °C, pH 5.0 and without carbon and nitrogen source. The presence of unique genes of cell wall and sporulation subsystem could be related to the adaptation of A. sendaiensis PA2 to hostile conditions.

Assessing through a longitudinal study of dietary habits among Romanian school children: effects of COVID-19 pandemic as well as of a school based educational program for promotion of healthy nutrition.

PURPOSE: The outbreak of COVID-19 has forced implementation of safety measures, leading to changes in people's lives. This study investigated several dietary habits among Romanian children before and during the pandemic. Also, it assessed the effectiveness of an educational program promoting healthy diet and evaluated factors influencing certain eating habits. METHODS: A longitudinal study was conducted in schools. Students were assigned to Control and Intervention groups. Data were collected at baseline (T1) (October -November 2019, 880 children) and post-intervention (T2) (December 2020-February 2021, 484 students). 350 children participated in both assessments. RESULTS: Baseline measurements revealed inadequate consumptions of fruits, vegetables, dairy products, and increased intake of soft drinks and sweets. At follow-up, the Intervention showed significant improvements on average intake of fruits and vegetables and in children eating ≥ 5 servings/day, compared to its baseline. Regarding self-perceptions on dietary habits during confinement, children from both groups reported healthier behaviors, with a significant decrease of comfort food. Compared to the Control group, Intervention increased its average intake of fruits and vegetables, consumed more ≥ 5 portions/day, reduced the number ≥ 2 cups/day of carbonated beverages and ≥ 3 portions/day of sweets. Age, gender, weight management, body mass index were associated with dietary habits at T1. Age, gender, Intervention group, weight management influenced eating patterns at T2. Eating behaviors at T1 influenced dietary habits at T2. CONCLUSION: Our program demonstrated positive changes in students' dietary habits, despite challenges of COVID-19. Results highlight the role of health education and emphasize the importance of integrating such programs consistently in schools.

The role of genetic variability of the host on the resistance to Neospora caninum infection in cattle.

Neospora caninum is one of the most frequently diagnosed abortifacient pathogens in cattle. There is abundant genomic information about the parasite itself, but very little is known about the genetic variability of resistance in the most common intermediate host. The aim of this review was to compile all the available information about the genetic variability associated with the resistance to N. caninum both between and within cattle breeds. We systematically searched for published studies that investigated the influence of genetics of the host on the prevalence of N. caninum and risk of abortion. Beyond the potential confounding effects of feeding systems, management and animal density, some lines of evidence suggest that Holstein, the most popular breed for milk production, has a comparatively higher risk of abortion due to infections by N. caninum, whereas some beef breeds from Continental Europe seem to be more resistant. It is still not clear if different genetic mechanisms of resistance are involved in the two known routes of infection: postnatal ingestion of oocysts or transplacental transmission from the infected dam to the fetus. Genomic information associated with susceptibility to infection and risk of abortion in different cattle breeds is still scarce. The information reported here could be useful to identify new research alternatives and to define novel strategies to deal with this major problem of animal production.

Comparative analysis of factors and barriers intervening in research participation among romanian and international medical graduates from one romanian medical faculty across three generations.

OBJECTIVES: This study focuses on the factors that encouraged engagement in research activities, as well as the barriers that restricted their involvement, until the final year of study at Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Faculty of Medicine. The main objectives of this study are to investigate potential disparities in research culture and student engagement in various research opportunities between Romanian and international medical graduates, as well as to conduct an examination of the observed patterns across various graduating years (2021-2023). MATERIALS AND METHODS: A cross-sectional investigation was conducted among graduate students of the Faculty of Medicine at the Iuliu Hațieganu University of Medicine and Pharmacy in Cluj-Napoca, Romania. From 2021 to 2023, all graduate students from the Romanian and international programs of the faculty were asked to participate in the study by filling out an anonymous online questionnaire. The final sample included 572 participants, of whom 392 were students from the Romanian section and 180 were students from international programs. RESULTS: Motivation and personal interest drive research engagement, according to over half of graduates. For over one-third of graduates, institutional elements like financial support and education also play a major role, as does the desire to enhance their curriculum vitae. More than 25% of graduates value community influence, 70% of graduates attended medical congresses, 12-15% presented papers at medical conferences, 23% wrote medical articles, 10-15% published at least one scientific paper in medical journals, and 20% participated in medical school research projects. Comparative analysis showed that Romanian students start research earlier, attend more medical conferences, present posters, collect data for studies, and are more interested in publishing graduation thesis data in scientific journals. To encourage international students to participate in research, the study found that colleagues' examples were more important, and both time and funds were key barriers. The research also shows that 2022 and 2023 graduates will organize more scientific conferences. According to the study, 2022 graduates began their research earlier than others. CONCLUSIONS: To increase student engagement in research activities, medical schools should prioritize the promotion of positive factors, minimize common barriers, offer customized support and resources, encourage collaborative research activities, and facilitate cross-cultural learning.

Role of Vitamin D Receptor (BsmI-VDR) and Insulin Receptor (NsiI-A/G) Gene Polymorphisms in Colorectal Adenoma Susceptibility.

Vitamin D deficiency and type 2 diabetes mellitus are risk factors for colorectal cancer, suggesting a role for vitamin D receptor (VDR) and insulin receptor (INSR) gene polymorphisms. We investigated the prevalence of the VDR-BsmI (rs1544410) and NsiI A/G-INSR (rs2059806) polymorphisms and their associations with colorectal adenoma (CRA) in a Romanian population. A case-control study was conducted with 110 participants (67 with CRA and 43 controls) who underwent colonoscopy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genotype and allele frequencies of the two polymorphisms. Regarding rs1544410 and CRA patients, genotype distribution was 35% B/B, 47% B/b, and 19% b/b. In the controls, the distribution was 21% B/B, 45% B/b, and 34% b/b. For rs2059806, 12% of CRA patients had A/A, 30% A/G, and 58% G/G, while 8% of the controls had A/A, 40% A/G, and 52% G/G. The recessive model showed an odds ratio of 2.84 (95% CI: 1.04-7.72, p = 0.033) for the b/b genotype. CRA patients with b/b or G/G genotypes were diagnosed at a younger age. The b allele of the rs1544410 was a risk factor for CRA. Patients with the b/b and G/G genotypes were diagnosed earlier.

TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients.

The COVID-19 pandemic has raised awareness of the virus's long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C, and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T, dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID (p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (ß = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) (p = 0.028 95% CI: 0.040-7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) (p = 0.025 95% CI: 0.624-7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A, a difference in ventricular filling pressure (E/E'ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients.

Metal-Based Drug-DNA Interactions and Analytical Determination Methods.

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA-metal complex interactions (including some representative examples) and on presenting the methods currently used to study them.

The Impact of Vitamin D Receptor Gene Polymorphisms (FokI, ApaI, TaqI) in Correlation with Oxidative Stress and Hormonal and Dermatologic Manifestations in Polycystic Ovary Syndrome.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent and complex multidisciplinary disorder. Data regarding the role of genes involved in vitamin D metabolism in PCOS are as-yet elusive but suggest an association of VDR (vitamin D receptor) and vitamin D levels with metabolic, endocrine and cutaneous manifestations. The aim of this study was to evaluate the association between VDR gene polymorphisms and cutaneous manifestations, to find a correlation between hormonal parameters, oxidative stress and skin manifestations in women with PCOS, and to determine the impact of VDR gene polymorphisms on these parameters. Materials and Methods: This case-control study included 39 controls and 46 women with PCOS, matched by age and BMI distribution. Acne, hirsutism, seborrhea, androgenetic alopecia, oxidative stress and androgen hormones were recorded. VDR gene polymorphisms ApaI, FokI and TaqI were examined by polymerase chain reaction restriction fragment length polymorphism, and the androgen hormone (total testosterone, DHEAS), SHBG and malondialdehyde levels were assessed. Results: The most frequent skin manifestations in PCOS cases were acne followed by seborrhea, hirsutism and androgenic alopecia. The VDR-FokI polymorphism CC genotype had a significant protective role in the odds of acne (OR = 0.11, 95% CI: [0.02, 0.70], p = 0.015, p-corrected = 0.040) and seborrhea (OR = 0.15, 95% CI: [0.03, 0.75], p = 0.019, p-corrected = 0.039). The results demonstrated a significant protective effect of the C allele on the odds of acne and seborrhea in PCOS cases. Moreover, the dominant genotype of VDR-TaqI could have a protective role against oxidative stress (lower MDA levels) compared to patients carrying the TT genotype. Conclusions: In summary, this is the first study to demonstrate that the FokI CC genotype may have a protective role against both acne and seborrhea in women with PCOS, while the VDR-TaqI dominant genotype is associated with diminished oxidative stress in PCOS patients.

The Importance of Genetic Testing for Familial Hypercholesterolemia: A Pediatric Pilot Study.

Background and Objectives: Familial hypercholesterolemia (FH) is a genetic disease that is massively underdiagnosed worldwide. Affected patients are at high risk of cardiovascular events at young ages. Early intervention in childhood could help prevent heart attacks and cerebral strokes in these patients. Materials and Methods: We conducted an interventional study including 10 patients that previously underwent genetic testing for familial hypercholesterolemia. These patients received lifestyle and diet recommendations that they followed for a year before being reevaluated. Results: Patients with negative genetic testing were able to achieve lower levels in their lipid panel values compared to the patients with positive genetic testing, with lifestyle changes alone. LDL-cholesterol levels decreased by 18.5% in patients without FH while patients genetically confirmed with FH failed to achieve lower LDL-cholesterol levels without medication. Conclusions: Genetic testing for FH is not always part of screening algorithms for FH. Some studies even advise against it. Our study proved the importance of genetic testing for FH when suspecting this disorder and choosing the treatment course for patients.

Neuromodulation of the Left Inferior Frontal Cortex Affects Social Monitoring during Motor Interactions.

Motor interactions require observing and monitoring a partner's performance as the interaction unfolds. Studies in monkeys suggest that this form of social monitoring might be mediated by the activity of the ventral premotor cortex (vPMc), a critical brain region in action observation and motor planning. Our previous fMRI studies in humans showed that the left vPMc is indeed recruited during social monitoring, but its causal role is unexplored. In three experiments, we applied online anodal or cathodal transcranial direct current stimulation over the left lateral frontal cortex during a music-like interactive task to test the hypothesis that neuromodulation of the left vPMc affects participants' performance when a partner violates the agent's expectations. Participants played short musical sequences together with a virtual partner by playing one note each in turn-taking. In 50% of the trials, the partner violated the participant's expectations by generating the correct note through an unexpected movement. During sham stimulation, the partner's unexpected behavior led to a slowdown in the participant's performance (observation-induced posterror slowing). A significant interaction with the stimulation type showed that cathodal and anodal transcranial direct current stimulation induced modulation of the observation-induced posterror slowing in opposite directions by reducing or enhancing it, respectively. Cathodal stimulation significantly reduced the effect compared to sham stimulation. No effect of neuromodulation was found when the partner behaved as expected or when the observed violation occurred within a context that was perceptually matched but noninteractive in nature. These results provide evidence for the critical causal role that the left vPMc might play in social monitoring during motor interactions, possibly through the interplay with other brain regions in the posterior medial frontal cortex.

When action prediction grows old: An fMRI study.

Predicting the unfolding of others' actions (action prediction) is crucial for successfully navigating the social world and interacting efficiently. Age-related changes in this domain have remained largely unexplored, especially for predictions regarding simple gestures and independent of contextual information or motor expertise. Here, we evaluated whether healthy aging impacts the neurophysiological processes recruited to anticipate, from the observation of implied-motion postures, the correct conclusion of simple grasping and pointing actions. A color-discrimination task served as a control condition to assess the specificity of the age-related effects. Older adults showed reduced efficiency in performance that was yet not specific to the action prediction task. Nevertheless, fMRI results revealed task-specific age-related differences: while both groups showed stronger recruitment of the lateral occipito-temporal cortex bilaterally during the action prediction than the control task, the younger participants additionally showed a higher bilateral engagement of parietal regions. Importantly, in both groups, the recruitment of visuo-motor processes in the right posterior parietal cortex was a predictor of good performance. These results support the hypothesis of decreased involvement of sensorimotor processes in cognitive tasks when processing action- and body-related stimuli in healthy aging. These results have implications for social interaction, which requires the fast reading of others' gestures.

How shared goals shape action monitoring.

Cooperation triggers expectations on our partners' contributions to achieve a common goal. A partner, however, may sometimes violate such expectations, driving us to perform immediate adjustments. What neurophysiological mechanisms support these adaptations? We tested the hypothesis of an interaction-specific brain system that can decode a partner's error and promote adaptive responses when cooperating toward a shared goal. During functional magnetic resonance imaging, the participants played short melodies with a virtual partner by performing one note each in turn-taking. A colored cue indicated which melody they had to execute at each trial, thus generating expectations on what notes the partner would play. The participants also performed the task in a perceptually matched Non-Interactive context. The results showed that task interactivity modulates the brain responses to a partner's error in dorsal fronto-temporoparietal and medial cingulo-opercular networks. Multivariate pattern analysis revealed that these neural activations reflect deep decoding of the partner's mistake. Within these networks, the automatic tendency to correct the partner's errors, as indexed by specific reaction times adaptations, depended on the activity of a right-lateralized fronto-opercular system that may enable mutual support during real-life cooperation. Future studies may unveil the role of this putative "interaction monitoring" brain system in social dysfunctions and their motor foundations.

Encoding interactive scripts at 10 months of age.

Understanding action-reaction associations that give origin to interactive scripts (e.g., give-and-take interactions) is essential for appreciating social exchanges. However, studies on infants' action understanding have mainly investigated the case of actions performed by individual agents. Moreover, although extensive literature has explored infants' comprehension of action-effect relationships in object functioning, no study has addressed whether it also plays a role when observing social interactions, an issue we addressed here. In a first study, 10-month-old infants observed short videos of dyadic exchanges. We investigated whether they were able to link specific human gestures directed toward another person to specific vocal reactions in the receiver. We used a double-habituation paradigm in which infants were sequentially habituated to two specific action-reaction associations. In the test phase, infants watched one of the two habituated (Familiar) videos, a video with a reversed action-reaction association (Violation), and a Novel video. Results showed that the infants looked longer at both the Novel and Violation test trials than at the Familiar test trials. In a control study, we show that these results could not be accounted for by associative learning; indeed, learning of the action-reaction association did not occur when the vocalization was not produced by the receiver but only contingent on the agent's action. Thus, we show that 10-month-old infants can encode specific social action-effect relationships during the observation of dyadic interactions and that the interactivity of the social context may be critical to shaping young infants' understanding of others' behaviors.

The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.

Land-use intensity alters networks between biodiversity, ecosystem functions, and services.

Land-use intensification can increase provisioning ecosystem services, such as food and timber production, but it also drives changes in ecosystem functioning and biodiversity loss, which may ultimately compromise human wellbeing. To understand how changes in land-use intensity affect the relationships between biodiversity, ecosystem functions, and services, we built networks from correlations between the species richness of 16 trophic groups, 10 ecosystem functions, and 15 ecosystem services. We evaluated how the properties of these networks varied across land-use intensity gradients for 150 forests and 150 grasslands. Land-use intensity significantly affected network structure in both habitats. Changes in connectance were larger in forests, while changes in modularity and evenness were more evident in grasslands. Our results show that increasing land-use intensity leads to more homogeneous networks with less integration within modules in both habitats, driven by the belowground compartment in grasslands, while forest responses to land management were more complex. Land-use intensity strongly altered hub identity and module composition in both habitats, showing that the positive correlations of provisioning services with biodiversity and ecosystem functions found at low land-use intensity levels, decline at higher intensity levels. Our approach provides a comprehensive view of the relationships between multiple components of biodiversity, ecosystem functions, and ecosystem services and how they respond to land use. This can be used to identify overall changes in the ecosystem, to derive mechanistic hypotheses, and it can be readily applied to further global change drivers.

Molecular identification of Trypanosoma cruzi in domestic animals in municipalities of the State of Rio Grande do Norte, Brazil.

Trypanosoma cruzi, the etiologic agent of American trypanosomiasis, is a vector-borne zoonotic parasite which has been little studied regarding its infection in domestic animals. In this study, we evaluated the occurrence of natural infection by T. cruzi in farm animals using molecular markers and phylogenetic analysis in blood clot samples of 60 sheep (Ovis aires), 22 goats (Capra hircus), and 14 horses (Equus caballus) in eight municipalities located in an infection risk area in the state of Rio Grande do Norte (RN), Northeast Region of Brazil. Trypanosoma spp. infection was identified by amplifying the rRNA 18S SSU gene in 48.9% of the samples. The SH022 sample showed 99.8% similarity with the Y strain of T. cruzi in phylogeny, grouped in the DTU II clade. Blood clots of sheep, goats, and horses detected T. cruzi kDNA in 28.3% (17/60), 22.7% (5/22), and 15.4% (2/14) of the samples, respectively. These animals were distributed in the three studied mesoregions throughout the state of RN. The identification of natural infection in domestic animals contributes to expand the epidemiological transmission scenario in an area where T. brasiliensis is the main vector.