Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube.

Secreted signals, known as morphogens, provide the positional information that organizes gene expression and cellular differentiation in many developing tissues. In the vertebrate neural tube, Sonic Hedgehog (Shh) acts as a morphogen to control the pattern of neuronal subtype specification. Using an in vivo reporter of Shh signaling, mouse genetics, and systems modeling, we show that a spatially and temporally changing gradient of Shh signaling is interpreted by the regulatory logic of a downstream transcriptional network. The design of the network, which links three transcription factors to Shh signaling, is responsible for differential spatial and temporal gene expression. In addition, the network renders cells insensitive to fluctuations in signaling and confers hysteresis--memory of the signal. Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning.

An eosimiid primate of South Asian affinities in the Paleogene of Western Amazonia and the origin of New World monkeys.

Recent fossil discoveries in Western Amazonia revealed that two distinct anthropoid primate clades of African origin colonized South America near the Eocene/Oligocene transition (ca. 34 Ma). Here, we describe a diminutive fossil primate from Brazilian Amazonia and suggest that, surprisingly, a third clade of anthropoids was involved in the Paleogene colonization of South America by primates. This new taxon, Ashaninkacebus simpsoni gen. et sp. nov., has strong dental affinities with Asian African stem anthropoids: the Eosimiiformes. Morphology-based phylogenetic analyses of early Old World anthropoids and extinct and extant New World monkeys (platyrrhines) support relationships of both Ashaninkacebus and Amamria (late middle Eocene, North Africa) to the South Asian Eosimiidae. Afro-Arabia, then a mega island, played the role of a biogeographic stopover between South Asia and South America for anthropoid primates and hystricognathous rodents. The earliest primates from South America bear little adaptive resemblance to later Oligocene-early Miocene platyrrhine monkeys, and the scarcity of available paleontological data precludes elucidating firmly their affinities with or within Platyrrhini. Nonetheless, these data shed light on some of their life history traits, revealing a particularly small body size and a diet consisting primarily of insects and possibly fruit, which would have increased their chances of survival on a natural floating island during this extraordinary over-water trip to South America from Africa. Divergence-time estimates between Old and New World taxa indicate that the transatlantic dispersal(s) could source in the intense flooding events associated with the late middle Eocene climatic optimum (ca. 40.5 Ma) in Western Africa.

Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival.

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.

Nerve growth factor inducible (VGF) is a secreted mediator for metastatic breast cancer tropism to the brain.

Brain metastases are one of the most serious clinical problems in breast cancer (BC) progression, associated with lower survival rates and a lack of effective therapies. Thus, to dissect the early stages of the brain metastatic process, we studied the impact of brain organotropic BC cells' secretomes on the establishment of the brain pre-metastatic niche (PMN). We found that BC cells with specific tropism to the brain caused significant blood-brain barrier (BBB) disruption, as well as microglial activation, in both in vitro and in vivo models. Further, we searched for a brain-organotropic metastatic signature, as a promising source for the discovery of new biomarkers involved in brain metastatic progression. Of relevance, we identified VGF (nerve growth factor inducible) as a key mediator in this process, also impacting the BBB and microglial functions both in vitro and in vivo. In a series of human breast tumors, VGF was found to be expressed in both cancer cells and the adjacent stroma. Importantly, VGF-positive tumors showed a significantly worse prognosis and were associated with HER2 (human epidermal growth factor receptor 2) overexpression and triple-negative molecular signatures. Further clinical validation in primary tumors from metastatic BC cases showed a significant association between VGF and the brain metastatic location, clearly and significantly impacting on the prognosis of BC patients with brain metastasis. In conclusion, our study reveals a unique secretome signature for BC with a tropism for the brain, highlighting VGF as a crucial mediator in this process. Furthermore, its specific impact as a poor prognostic predictor for BC patients with brain metastasis opens new avenues to target VGF to control the progression of brain metastatic disease. © 2024 The Pathological Society of Great Britain and Ireland.

Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival.

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site-specific N-glycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue N-glycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.

Temporal relations between peripheral and central arousals in good and poor sleepers.

Good sleepers and patients with insomnia symptoms (poor sleepers) were tracked with two measures of arousal; conventional polysomnography (PSG) for electroencephalogram (EEG) assessed cortical arousals, and a peripheral arterial tonometry device was used for the detection of peripheral nervous system (PNS) arousals associated with vasoconstrictions. The relationship between central (cortical) and peripheral (autonomic) arousals was examined by evaluating their close temporal dynamics. Cortical arousals almost invariably were preceded and followed by peripheral activations, while large peripheral autonomic arousals were followed by cortical arousals only half of the time. The temporal contiguity of these two types of arousals was altered in poor sleepers, and poor sleepers displayed a higher number of cortical and peripheral arousals compared with good sleepers. Given the difference in the number of peripheral autonomic arousals between good and poor sleepers, an evaluation of such arousals could become a means of physiologically distinguishing poor sleepers.

Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Damaged bone microarchitecture by Trabecular Bone Score (TBS) and low appendicular muscle mass: main risk factors for vertebral and non-vertebral fractures in women with long-standing rheumatoid arthritis.

We ascertained the fracture risk factors stratified by vertebral and non-vertebral sites in rheumatoid arthritis (RA) females. Bone/muscle features, but not disease activity, were the main markers for fractures in this long-standing RA population: low trabecular bone score (TBS) for vertebral fracture and decreased appendicular muscle mass for non-vertebral fracture. PURPOSE: To assess risk factors for fractures, including clinical, laboratory and dual energy X-ray absorptiometry (DXA) parameters (bone mass, trabecular bone score-TBS, muscle mass) in women with established rheumatoid arthritis (RA). METHODS: Three hundred females with RA (ACR, 2010) were studied. Clinical data were obtained by questionnaire and disease activity by composite indices (DAS28, CDAI, SDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Bone mineral density (BMD), TBS, body composition and Vertebral Fracture Assessment (VFA) were performed by DXA. Logistic regression models were constructed to identify factors independently associated with vertebral (VF) and non-vertebral fractures (NVF), separately. RESULTS: Through rigorous eligibility criteria, a total of 265 women were yielded for final data analysis (median age, 55 [22-86] years; mean disease duration, 16.2 years). Prevalence of VF and NVF were 30.6% and 17.4%, respectively. In multivariate analyzes, TBS (OR = 1.6, 95%CI = 1.09-2.36, p = 0.017), CRP (OR = 1.54, 95%CI = 1.15-2.08, p = 0.004), and parathormone (OR = 1.24, 95%CI = 1.05-1.45, p = 0.009) were risk factors for VF, whereas low appendicular muscle mass (OR = 2.71; 95%CI = 1.01-7,28; p = 0.048), body mass index (BMI) (OR = 0.90, 95%CI = 0.82-0.99; p = 0.025), ESR (OR = 1.18, 95%CI = 1.01-1,38, p = 0,038) and hip BMD (OR = 1.82, 95%CI = 1.10-3.03, p = 0.02) were associated with NVF. CONCLUSION: In women with long-term RA, markers of fractures differed between distinct skeletal sites (vertebral and non-vertebral). The magnitude of association of bone/muscle parameters with fracture (TBS for VF and appendicular muscle mass for NVF) was greater than that of the association between RA activity and fracture. TBS seems to have greater discriminative power than BMD to identify subjects with VF in long-standing RA.

Differential Effects of Cerebellar Transcranial Direct Current Stimulation with Gait Training on Functional Mobility, Balance, and Ataxia Symptoms.

Cerebellar transcranial direct current stimulation (ctDCS) has emerged as a promising, non-invasive, and safe neuromodulatory intervention capable of reducing ataxia symptoms and restoring cerebellum-motor connectivity. However, previous studies have only applied ctDCS in isolation, without association with specific training. This study aimed to assess the effect of ctDCS combined with gait training on functional mobility, balance, and symptoms and severity of ataxia. A randomized, triple-blind, sham-controlled, bi-center clinical trial was conducted with forty-four adults with cerebellar ataxia. Volunteers were randomized to receive five daily sessions of either real ctDCS (n = 11; 2 mA for 25 min) or sham ctDCS (n = 11) during gait training. Functional mobility, balance, and symptoms and severity of ataxia were assessed using the Time Up and Go test, the MiniBESTest, and the Scale for the Assessment and Rating of Ataxia (SARA), respectively, before and after the interventions. Both groups showed improvement in functional mobility, but there was no significant difference between the ctDCS and sham groups. However, the ctDCS group demonstrated significant improvements in cerebellar ataxia severity as reflected by SARA scores, particularly in tests of stance, sitting, speech disturbance, nose-finger test, and heel-shin slide test. Notably, no improvements were observed in balance. This study indicates that while ctDCS combined with gait training may improve specific symptoms of cerebellar ataxia, it does not significantly enhance overall functional mobility compared to sham treatment.

Magnesium-Induced Rapid Nucleation of Tetrahydrofuran Hydrates.

Hydrates are ice-like crystalline structures of hydrogen-bonded water molecules that trap a guest molecule. Hydrates have several applications, including carbon sequestration, gas separation, desalination, etc. A classical major challenge associated with artificial hydrate formation is the very long induction time to nucleate hydrates. This has spurred the development of multiple chemical, mechanical, and electrical strategies to promote nucleation. Presently, we discover that magnesium can significantly promote the nucleation of tetrahydrofuran (THF) hydrates. While magnesium has been recently shown (by our group) to promote the formation of carbon dioxide hydrates (gas-liquid system), this study discovers that the benefits of magnesium extend to liquid-liquid hydrate systems as well. Experiments show that magnesium reduces the induction time for THF hydrate nucleation with deionized (DI) water and saltwater by six and eight times, respectively. Magnesium-induced nucleation rate enhancements for hydrate formation with DI water and saltwater were 12 and 99 times, respectively. Importantly, we demonstrate near-instantaneous nucleation when magnesium is introduced after the hydrate-forming system reaches suitable thermodynamic conditions. We conduct statistically significant measurements of nucleation and XPS analysis to identify the underlying mechanisms responsible for nucleation. We discuss multiple phenomena at play, including chemical and mechanistic promotion pathways. The formation of hydrogen bubbles and the presence of magnesium ions in solution are seen as important to magnesium-based nucleation promotion. Importantly, very low amounts of Mg are consumed in this process unlike in traditional chemical promotion techniques. Overall, our discovery can enable on-demand nucleation of liquid-liquid hydrate systems, which is critical to the development of several applications.

Thermostable in vitro transcription-translation compatible with microfluidic droplets.

BACKGROUND: In vitro expression involves the utilization of the cellular transcription and translation machinery in an acellular context to produce one or more proteins of interest and has found widespread application in synthetic biology and in pharmaceutical biomanufacturing. Most in vitro expression systems available are active at moderate temperatures, but to screen large libraries of natural or artificial genetic diversity for highly thermostable enzymes or enzyme variants, it is instrumental to enable protein synthesis at high temperatures. OBJECTIVES: Develop an in vitro expression system operating at high temperatures compatible with enzymatic assays and with technologies that enable ultrahigh-throughput protein expression in reduced volumes, such as microfluidic water-in-oil (w/o) droplets. RESULTS: We produced cell-free extracts from Thermus thermophilus for in vitro translation including thermostable enzymatic cascades for energy regeneration and a moderately thermostable RNA polymerase for transcription, which ultimately limited the temperature of protein synthesis. The yield was comparable or superior to other thermostable in vitro expression systems, while the preparation procedure is much simpler and can be suited to different Thermus thermophilus strains. Furthermore, these extracts have enabled in vitro expression in microfluidic droplets at high temperatures for the first time. CONCLUSIONS: Cell-free extracts from Thermus thermophilus represent a simpler alternative to heavily optimized or pure component thermostable in vitro expression systems. Moreover, due to their compatibility with droplet microfluidics and enzyme assays at high temperatures, the reported system represents a convenient gateway for enzyme screening at higher temperatures with ultrahigh-throughput.

Housing Insecurity and Older Adults' Health and Well-Being in a Gentrifying City: Results from the EPIPorto Cohort Study.

Using 2022 data from 600 adults (≥ 60 years) in Porto, Portugal, we explored the association between housing insecurity and various health outcomes. We examined housing conditions, affordability, and stability in relation to loneliness, quality of life, cognitive function, perception of healthy ageing, and sleep using regression models. Older adults without house heating (ß = 2.293; 95%CI = 0.753, 3.833), with leaks/dampness/rot (ß = 3.741; 1.818, 5.664), insufficient daylight (ß = 2.787; 0.095, 5.479), living in neighborhoods with noise (ß = 1.793, 0.280 to 3.305), pollution/grime (ß = 2.580; 0.746, 4.414), and violence/crime/vandalism (ß = 3.940; 1.723, 6.157), who faced housing cost overburden (ß = 2.001; 0.426, 3.577), eviction (ß = 12.651; 0.852, 24.450), and moved frequently (ß = 4.129; 1.542, 6.716) exhibited higher levels of loneliness. Similarly, lack of house heating (ß = - 1.942; - 3.438, - 0.445), leaks/dampness/rot (ß = - 4.157; - 5.999, - 2.316), insufficient daylight (ß = - 3.124; - 5.714, - 0.534), noise (ß = - 2.143; - 3.600, - 0.686), pollution/grime (ß = - 2.093; - 3.860, - 0.325), violence/crime/vandalism (ß = - 2.819; - 4.948, - 0.691), and those with housing cost overburden (ß = - 2.435; - 3.930, - 0.940) reported lower quality of life. Those with no toilet (ß = - 1.891; - 3.760, - 0.021) or shower (ß = - 1.891; - 3.760, - 0.021) and who faced forced displacement (ß = - 2.179; - 3.516, - 0.842) presented lower cognitive function. Furthermore, those living in neighborhoods with pollution/grime (OR = 0.494; 0.322, 0.756) and violence/crime/vandalism (OR = 0.477; 0.284, 0.801), those in social housing (OR = 0.728; 0.575, 0.922), and those who moved frequently (OR = 0.475; 0.257, 0.879) reported lower levels of perceived healthy ageing. Insufficient sleep was more common among residents in social housing (OR = 2.155; 1.102, 4.213), while poor sleep quality was least likely both among those living in social housing (OR = 0.445; 0.220, 0.900) and affordable housing (OR = 0.381; 0.162, 0.896). Good quality, stable, and affordable housing seems crucial for healthy ageing.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

Association between area-level walkability and glycated haemoglobin: a Portuguese population-based study.

Diabetes poses a substantial disease burden, prompting preventive interventions. Physical inactivity, a major risk factor for type 2 diabetes, can potentially be mitigated by enhancing area-level walkability. Despite this, limited population-based studies have investigated the link between walkability and objective diabetes measures. Our study aims to estimate the association between area-level walkability and individual glycated haemoglobin levels in the Portuguese adult population without the diagnosis of diabetes. Data from the 2011 census and an updated street map were obtained to construct a walkability index based on residential density, land-use mix, and street connectivity. Individual health data were sourced from The National Health Examination Survey (INSEF) 2015, a representative survey of the Portuguese adult population. Gamma regression was employed for estimation of the main associations, revealing that residing in moderately walkable areas significantly reduced average glycated haemoglobin levels (Exp(ß) = 0.906; 95% CI: 0.821, 0.999) compared to the least walkable areas. The association was less pronounced and not statistically significant for the third tertile of walkability (Exp(ß) = 0.919; 95% CI: 0.822, 1.028). Our findings highlight a nonlinear protective association between walkability and glycated haemoglobin, emphasizing the potential policy implications for urban planning, diabetes prevention, and health promotion.

Cardioproteomics: Insights on Cardiovascular Diseases.

Cardiovascular diseases (CVDs) remain a global health challenge and are the leading cause of deaths worldwide. Proteomics has emerged as a valuable tool for unraveling the complex molecular mechanisms underlying CVDs, offering insights into biomarker discovery, drug targets, and personalized medicine. This review explores key breakthroughs in proteomic applications related to CVDs, mainly coronary artery disease (CAD), ischemic heart diseases such as myocardial infarction (MI), and cardiomyopathies. Notable findings include potential biomarkers, therapeutic targets, and insights into disease pathogenesis. The review highlights the importance of proteomics in advancing our understanding of CVDs and shaping future therapeutic approaches.

Continuous monitoring after laparoscopic Roux-En-Y gastric bypass: a pathway to ambulatory care surgery - a pilot study.

Same-day discharge (SDD) after Laparoscopic Roux-En-Y Gastric Bypass (LRYGB) faces resistance due to possible undetected postoperative complications. These present with changes in vital signs, which continuous remote monitoring devices can detect. This study compared continuous vital signs monitoring using the Isansys Patient Status Engine™ with standard nursing vital signs measurements to assess the device's reliability in postoperative surveillance of patients undergoing LRYGB. We conducted a pilot study including patients who underwent LRYGB. During their hospital stay, patients were continuously monitored using the Isansys Patient Status Engine™ with Lifetouch™, Lifetemp™, and Nonin Pulse Oximeter™ sensors. The heart rate (HR), body temperature, and oxygen saturation (SpO2) collected by the device were compared with standard nursing assessments. Thirteen patients with a mean body mass index of 41.5 ± 4.4 kg/m2 were included. No major complications occurred. The median HR assessed by standard and continuous monitoring did not significantly differ (75.5 [69-88] vs. 77 [66-91] bpm, p = 0.995), nor did the mean values of SpO2 (94.7 ± 2.0 vs. 93.7 ± 1.8%, p = 0,057). A significant difference was observed in median body temperature between the nursing staff and the monitoring device (36.3 [36.1-36.7] vs. 36.1 [34.5-36.6] degrees Celsius, p = 0.012), with a tendency for lower temperature measurements by the device. In conclusion, this is the first study on continuous postoperative surveillance using the Isansys Patient Status Engine™ monitoring device for LRYGB patients. Our results introduce a novel tool for more efficient surgery. Prospective randomized experimental studies are warranted to evaluate this method's efficacy and safety.

Advancements in Biomarkers and Molecular Targets in Hematological Neoplasias.

Hematological neoplasias are among the most common cancers worldwide, and the number of new cases has been on the rise since 1990, reaching 1 [...].

The Influence of Genetic Polymorphisms on the Expression of Interleukin-1beta, Prostaglandin E2 and Tumor Necrosis Factor Alpha in Peri-Implant Crevicular Fluid: A Cross-Sectional Study.

The aim of this study was to evaluate the possible relationships between polymorphisms in the interleukin-1 (IL-1) A, IL-1B, and IL-1RN genes and concentrations of the inflammatory mediators IL-1ß, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) in peri-implant crevicular fluid (PICF). A cross-sectional analytical study was conducted on 51 patients with dental implants. Samples from the buccal mucosa were obtained, and genetic analysis was performed using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and PCR and restriction fragment length polymorphism analysis for IL-1RN. For the biochemical analysis, the concentrations of IL-1ß and TNF-α were analyzed using multiplexed fluorescent sphere immunoassays, and PGE2 by enzyme-linked immunosorbent assay. In patients with detected IL-1RN polymorphism, there was an increase in the concentration of the three mediators with statistically significant differences in the mean values of TNF-α and PGE2, regardless of peri-implant health status (p = 0.002 and p = 0.049, respectively). The concentrations of all three mediators were positively and significantly correlated (IL-1ß vs. TNF-α Rho = 0.480, p < 0.001; IL-1ß vs. PGE2 Rho = 0.382, p = 0.006; and TNF-α vs. PGE2 Rho = 0.528, p < 0.001). We can conclude that the IL-1RN polymorphism exerts an influence on the PICF immune response, which may explain the influence of this genetic polymorphism on the occurrence of peri-implantitis.

Transport Properties in Multicomponent Systems Containing Cyclodextrins and Nickel Ions.

In this work, we propose a comprehensive experimental study of the diffusion of nickel ions in combination with different cyclodextrins as carrier molecules for enhanced solubility and facilitated transport. For this, ternary mutual diffusion coefficients measured by Taylor dispersion method are reported for aqueous solutions containing nickel salts and different cyclodextrins (that is, α-CD, ß-CD, and γ-CD) at 298.15 K. A combination of Taylor dispersion and other methods, such as UV-vis spectroscopy, will be used to obtain complementary information on these systems. The determination of the physicochemical properties of these salts with CDs in aqueous solution provides information that allows us to understand solute-solvent interactions, and gives a significant contribution to understanding the mechanisms underlying diffusional transport in aqueous solutions, and, consequently, to mitigating the potential toxicity associated with these metal ions. For example, using mutual diffusion data, it is possible to estimate the number of moles of each ion transported per mole of the cyclodextrin driven by its own concentration gradient.