Neutrophil N1 and N2 Subsets and Their Possible Association with Periodontitis: A Scoping Review.

Periodontitis is a chronic non-communicable disease caused by dysbiotic changes that affect the subgingival microbiota. During periodontitis, neutrophils play a central role in the initial recognition of bacteria, and their number increases with the appearance of the first signs of periodontal inflammation. Recent evidence has led to the proposition that neutrophils can also functionally polarize, determining selective activity patterns related to different diseases. Two well-defined neutrophil phenotypes have been described, the pro-inflammatory N1 subset and the suppressor N2 subset. To date, it has not been established whether these different neutrophil subtypes play a role in the pathogenesis of periodontitis. Thus, this scoping review aimed to determine whether there was evidence to suggest that the neutrophils present in periodontal tissues can be associated with certain phenotypes. The research question, population, concept, and context sought to identify original articles, in humans, that detected the presence of neutrophils in the periodontal tissues of people affected by periodontitis. Based on the search strategy, we found 3658 studies. After removing the papers with abstracts not related to the outcome measures and eligibility criteria, 16 articles were included for qualitative analysis. Several studies identified the presence of different neutrophil subsets, specifically, the naive, pro- and para-inflammatory, hyper-reactive and hyper-active, and high- and low-responder phenotypes. The existing evidence demonstrates the presence of pro-inflammatory, hyper-reactive and high-responder neutrophils in periodontal tissues affected with periodontitis. There is no evidence demonstrating the presence of the N1 or N2 phenotypes in periodontal tissues during periodontitis. However, the existence of pro-inflammatory phenotypes, which increase NETosis and degranulation, and increase the production of pro-inflammatory cytokines, could be suggestive of the N1 phenotypes.

LDL induces cholesterol loading and inhibits endothelial proliferation and angiogenesis in Matrigels: correlation with impaired angiogenesis during wound healing.

Hypercholesterolemia is a major risk factor for adverse cardiovascular outcomes, but its effect on angiogenesis and wound healing is not well understood. In this study, using a combination of mass spectrometry and laurdan two-photon imaging, we show that elevated levels of low-density lipoprotein (LDL), like those seen in hypercholesterolemic patients, lead to an increase in both free cholesterol and cholesterol esters, as well as increase in lipid order of endothelial cell membranes. Notably, these effects are distinct and opposite to the lack of cholesterol loading and the disruption of lipid order observed in our earlier studies in response to oxidized LDL (oxLDL). The same pathological level of LDL leads to a significant inhibition of endothelial proliferation and cell cycle arrest in G2/M phase, whereas oxLDL enhances endothelial proliferation in S phase of the cycle. LDL but not oxLDL suppresses the expression of vascular endothelial growth factor receptor-2 while enhancing the expression of vascular endothelial growth factor (VEGF). Furthermore, we show that aged (8-10 mo) hypercholesterolemic apolipoprotein E-deficient (ApoE-/-) mice display delayed wound closure compared with age-matched C57/BL6 wild-type controls following a skin punch biopsy. The delay in wound healing is associated with a decreased expression of cluster of differentiation 31 platelet endothelial cell adhesion molecule endothelial marker and decreased angiogenesis within the wound bed. Furthermore, decreased endothelial responsiveness to the growth factors VEGF and basic fibroblast growth factor is observed in ApoE-/- mice in Matrigel plugs and in Matrigels with high levels of LDL in wild-type mice. We propose that plasma hypercholesterolemia is antiangiogenic due to elevated levels of LDL.

Reduction of the Measurement Time by the Prediction of the Steady-State Response for Quartz Crystal Microbalance Gas Sensors.

This paper presents a new approach to reduce the measurement time by the prediction of the steady-state using the transient response to ethanol for quartz crystal microbalance gas sensors coated with ethyl cellulose. The experimentally measured response curves were successively fitted using a mathematical model based on the sum of two exponentials with different time constants. The parameters of the model were determined, and the time constants and the magnitude of the steady-state response were analyzed. Even though the time constants did not stabilize well, the parameter corresponding to the magnitude of the steady-state response quickly converged and stabilized after 37 s. Moreover, this calculated parameter was highly correlated with the measured values of the steady-state response, which was measured at five times the longest time constant (83 s) of the model. Therefore, the steady-state response could be predicted with a 55% reduction in the measurement (detection) time.

[Non-cirrhotic portal hypertension due to didanosina. A rare case]. / Hipertensión portal no cirrótica por didanosina. Un caso infrecuente.

Liver involvement is usually seen in patients infected with the human immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B or C, in alcohol abuse, etc. However, there is a group of patients who develop liver involvement and portal hypertension of unspecified cause. Non-cirrhotic portal hypertension (NCPH) is a liver disorder recently described, but potentially serious. It has been reported in HIV-infected patients with highly active antiretroviral therapy (HAART), specifically didanosine (DDI). The pathophysiology involves the infectious agent (HIV) and its treatment (HAART), since both generate a pre-hepatic portal venulopathy. Similarly, HIV infection produces a prothrombotic state by protein S deficiency leading to the obliteration of small hepatic venules. It has been postulated that DDI as a cofactor in the pathogenesis of NCPH. All this leads that many of the liver biopsies show nodular regenerative hyperplasia. We present the case of a HIV-infected patient who was treated with a longstanding DDI. She developed upper gastrointestinal bleeding (UGB) and ascites due to NCPH, whose diagnosis was confirmed by biopsy. However, there is no similar study in our country.

[Autoimmune pancreatitis type 1: a case report]. / Pancreatitis autoinmune tipo 1: reporte de caso.

Autoimmune pancreatitis type 1 (AIP) is the pancreatic manifestation of IgG4-related disease. The most frequent presentation of AIP is with obstructive jaundice. For definite diagnosis of type 1 Autoimmune pancreatitis international consensus diagnosis criteria (ICDC) for AIP are used. ICDC criteria include pancreatic parenchymal imaging, ductal imaging, serology, other organ involvement, histology, and response to steroid. We report a 52-years-old woman with rheumatoid arthritis without treatment presented with two months of abdominal pain in up-right quadrant with moderate intensity. She also presented jaundice, acholia, xerophtalmia, xerostomia, and a weight loss of 5 pounds. On examination jaundice, symmetrically enlarged submandibular glands, and epigastric pain was observed. On laboratory, a cholestasis pattern and conjugated bilirubin predominance was found. CT Abdominal, CMR revealed a dilated common bile duct with a diffuse pancreatic enlargement with delayed enhancement. Immunological studies show a IgG4 610 u/l and ANA 1/640. The patient responds to steroid clinically and in the laboratorial values. In conclusion, autoimmune pancreatitis type 1 should be suspected in case of an obstructive jaundice with a pancreatic inflammatory image, and complete ICDC criteria for a definite diagnosis.

[Actinic enteritis as a cause of digestive bleeding of obscure origin]. / Enteritis actínica como causa de hemorragia digestiva de origen oscuro.

Chronic actinic enteritis is a malfunction of the small bowel, occurring in the 6 months post-radiotherapy, and it can be manifestated as malabsortion, stenosis, fistula formation, local abscesses, perforation and bleeding, We report a case of an elderly patient who presents an episode of obscure gastrointestinal bleeding (OGIB) secondary to actinic enteritis. She is a 64-year- old female patient with the past medical history of cervical cancer who received radiotherapy and brachytherapy. One year after the treatment, the patient presents a chronic episode of melena and symptomatic anemia and 1 week before the admission she had hematochezia. At admission she has hemodynamic instability with a hemoglobin value of 2.7 gr/dl. We did an upper endoscopy, a colonoscopy and abdomino-pelvic tomography without any findings of the bleeding’s source. Reason why an endoscopic capsule was done, showing bleeding areas in the medial and distal small bowel. The patient had another gastrointestinal bleeding requiring a surgery where they decide to do a resection of the small bowel and a right hemicholectomy. The pathology was compatible with actinic enteritis. The patient after the surgery had a torpid evolution, and finally dies. We describe this case and do a review of all the existent data around the world, because is the first case reported in Peru of an actinic enteritis as a cause of OGIB.

Morphotype-based characterization of arbuscular mycorrhizal fungal communities in a restored tropical dry forest, Margarita island-Venezuela.

The mycorrhizal component of revegetated areas after ecological restoration or rehabilitation in arid and semiarid tropical areas has been scarcely assessed, particularly those made after mining disturbance. We evaluated and compared the presence of arbuscular mycorrhizal fungi of a small area of restored tropical dry forest destroyed by sand extraction, with a non-restored area of similar age, at the peninsula of Macanao, Margarita Island (Venezuela). Our study was undertaken in 2009, four years after planting, and the mycorrhizal status was evaluated in four restored plots (8 x 12.5 m) (two were previously treated with hydrogel (R2 and R2'), and two were left untreated (R1 and R1'), and four non-restored plots of similar size (NR1 and NR1' with graminoid physiognomy with some scattered shrubs; and NR2 and NR2', with a more species rich plant community). Apparently the restoration management promoted higher arbuscular mycorrhizal fungi (AMF) species richness and diversity, particularly in restored soils where the hydrogel was added (R2 treatment). Soil of the NRI treatment (with a higher herbaceous component) showed the highest spore density, compared to samples of soils under the other treatments. Considering species composition, Claroideoglomus etunicatum and Rhizophagus intraradices were found in all treatments; besides, Diversispora spurca and Funnefformis geosporum were only found in non-restored plots, while members of the Gigasporaceae (a family associated with little disturbed sites) were commonly observed in the plots with restored soils. Mycorrhizal colonization was similar in the restored and non-restored areas, being a less sensitive indicator of the ecosystem recovery. The trend of higher richness and diversity of AMF in the restored plot with hydrogel suggests that this management strategy contributes to accelerate the natural regeneration in those ecosystems where water plays an essential role.

The weekly P25 of the age of the influenza-like illness shows a higher correlation with COVID-19 mortality than rapid tests and could predict the evolution of COVID-19 pandemics in sentinel surveillance, Piura, Perú, 2021.

GOAL: To describe the dynamics of syndromic surveillance of ILI cases in seasonal and COVID-19 pandemic scenarios. METHODOLOGY: A descriptive study of the epidemiological behavior of ILI in the seasonal and COVID-19 pandemic scenarios. Of a sample of 16,231 cases of ILI from 2013 to 2021, the features of cases from 68 weeks before and during the pandemic were selected and compared; weekly endemic channels were built; data fluctuations on the trend of ILI cases were analyzed; and estimated weekly correlations between weekly P25 age, cases confirmed by rapid tests, and mortality from COVID-19. To analyze clinical-epidemiological and mortality data, Student's t test, Mann-Whitney U, Chi2, Spearman's Ro, polynomial, and multinomial regression with a 95% confidence interval were used. RESULTS: During the COVID-19 pandemic, those most affected with ILI were: adults and the elderly; higher median age; autochthonous cases predominated; a lower proportion of other syndromes; delays in seeking care; and a higher rate of pneumonia attack than in the seasonal period (p< 0.01). Rapid tests (serological and antigenic) confirmed 52.7% as COVID-19. Two ILI pandemic waves were seasonally consistent with confirmed COVID-19 cases and district mortality with robust correlation (p<0.01) before and during the pandemic, especially the ILI weekly P25 age, which has a more robust correlation with mortality than ILI and rapid tests (p<0.01) whose endemic channels describe and could predict the evolution of the pandemic (p<0.01). CONCLUSIONS: The pandemic changed the clinical and epidemiological behavior of ILI, and the weekly P25 of age is a more robust indicator to monitor the COVID-19 pandemic than a rapid test and could predict its evolution.

Prevalence and Progression of Gingivitis in Domestic Cats in Subtropical Mexico.

With the objective to characterize the gingival index (GI) and its progression, 218 domestic cats in a subtropical region of Mexico were studied. All teeth of each cat were examined with a periodontal probe to determine the GI; in addition, the absence of teeth was recorded. Six months later, the teeth of the 38 cats were again examined to assess any progression of the GI and loss of teeth. From the 218 cats, 33.0% of them develop some degree of gingival inflammation; from those, 61.5% were classified as GI 1. Age, sex, and neutered status were associated with tooth affections. Missed teeth were observed in 35% of the cats, particularly for molars 109 and 209 in both sexes. After six months, the number of teeth with GI 1 decreased to 20%. The gingival problems in cats have not been well studied, particularly at the speed they progress and how this can affect the loss of teeth; under the conditions of this study, a high frequency of gingival inflammation even at early age was demonstrated, with a rapid tooth loss. Although young males were more prone to develop gingivitis, females tend to loss more teeth. Non-neutered cats tended to develop more dental affections.

[Applicability of multivariate statistics for nutritional studies: bioassay rice weevil (Sitophilus oryzae L)]. / Aplicabilidad de estadística multivariada para estudios nutricionales: bioensayo con el gorgojo de arroz (Sitophilus oryzae L).

The principal component analysis (PCA), non-metric multidimensional scaling (MDS) and analysis of similarity (ANOSIM) are multivariate statistical techniques that graphically represent numerical measures of several factors and display multiple relationships that may exist between them. In this study, we evaluated the applicability of these techniques to analyze the nutritional quality of diet, using as model, the bioassay rice weevil. The diets tested were: corn starch, potato starch, 5% glucose, peas, starved and starved with water supply. The variables studied were: survival, weight change and body composition. The PCA and MDS showed positive relationships of survival and weight change with body fat and carbohydrate parameters. Fat and carbohydrates were greater in starches diets, similar to the positive control. The PCA showed differences between populations fed with different diets, whereas the MDS showed similarity between diets. Both studies defined a gradient of the nutritive value of diets in the x-axis. The ANOSIM indicate significant (p < 0.05) differences between groups. This test is necessary to support the results obtained in the PCA and MDS. The application of these statistical tools is promising to analyze complex processes such as interaction of differents variables to measure the nutritional quality of diets.

Gastroduodenal and Colorectal Tuberculosis: Report of 2 Cases.

Introduction: Tuberculosis remains a public health concern in developing countries, as well as in developed countries as a result of immigration from endemic areas. Gastroduodenal and colorectal tuberculosis are rare manifestations of gastrointestinal infection. Case Presentation: We present 2 cases of gastric, duodenal, and colorectal tuberculosis. The first case, a 17-year-old male with no medical record, presented with chronic diarrhea and abdominal pain. At endoscopy, he had multiple ulcers in the stomach, colon, and rectum, which were positive to Mycobacterium tuberculosis. The second case was a 43-year-old HIV-positive male, with a history of intermittent fever, nausea, and vomiting. Upper gastrointestinal endoscopy revealed a deep ulcer on gastric fundus that tested positive to M. tuberculosis in the acid-fast bacilli staining. Discussion/Conclusion: Gastroduodenal and colorectal tuberculosis, although rare, should be considered in the differential diagnosis in both immunosuppressed and immunocompetent patients. An adequate tissue sample and appropriate diagnostic tests are essential for the diagnosis and prompt start of first-line antituberculosis agents.

Introdução: A tuberculose continua sendo um problema de saúde pública nos países em desenvolvimento, bem como nos países desenvolvidos, em decorrência da imigração. A tuberculose gastroduodenal e colorretalsão manifestações raras de infecção gastrointestinal. Apresentação do Caso: Apresentamos dois casos de tuberculose gástrica, duodenal ecolorretal. O primeiro caso, um jovem de 17 anos, apresentou diarreia crônica e dor abdominal. Na endoscopia, tinha múltiplas úlceras no estômago, cólon e reto que foram positivas para Mycobacterium Tuberculosis. O segundo caso foi um homem de 43 anos, HIV positivo, com relato de febre intermitente, náuseas e vômitos. A endoscopia digestiva alta revelou úlcera profunda do fundo gástrico positivo para Mycobacterium tuberculosis na coloração de bacilos álcool-ácido resistentes. Discussão/Conclusão: Tuberculosegastroduodenal e colorretal, embora raras, deve ser considerada como diagnóstico em pacientes imunossuprimidos e imunocompetentes. Uma amostra de tecido adequada e testes diagnósticos apropriados são essenciais para o diagnósticoe início imediato dos tuberculostáticos de primeira linha.

Evaluation of the Local Synergistic Effect of a Dexketoprofen and Chlorhexidine Combination in the Formalin Test.

OBJECTIVE: Evidence supports the local application of non-steroidal antiinflammatory drugs such as dexketoprofen trometamol (DXT) for pain management, but little is known about the potential antinociceptive effect of chlorhexidine gluconate (CHX) and its possible synergistic effect when combined with DXT. The aim of this study was to evaluate the local effect of a DXT-CHX combination using isobolographic analysis in a formalin pain model in rats. MATERIALS AND METHODS: Briefly, 60 female Wistar rats were used for the formalin test. Individual dose effect curves were obtained using linear regression. For each drug, the percentage of antinociception and median effective dose (ED50; 50% of antinociception) were calculated, and drug combinations were prepared using the ED50s for DXT (phase 2) and CHX (phase 1). The ED50 of the DXT-CHX combination was determined, and an isobolographic analysis was performed for both phases. RESULTS: The ED50 of local DXT was 5.3867 mg/mL in phase 2 and for CHX was 3.9233 mg/mL in phase 1. When the combination was evaluated, phase 1 showed an interaction index (II) of less than 1, indicating synergism but without statistical significance. For phase 2, the II was 0.3112, with a reduction of 68.88% in the amounts of both drugs to obtain the ED50; this interaction was statistically significant (P < .05). CONCLUSION: DXT and CHX had a local antinociceptive effect and exhibited synergistic behavior when combined in phase 2 of the formalin model.

Cardiovascular health worsening in patients with autoimmune rheumatological diseases during the COVID-19 pandemic.

Rheumatic autoimmune diseases are associated with a myriad of comorbidities. Of particular importance due to their morbimortality are cardiovascular diseases. COVID-19 greatly impacted the world population in many different areas. Patients with rheumatic diseases had to face changes in their healthcare, in addition to unemployment, a decrease in physical activity, social isolation, and lack of access to certain medications. This review summarizes the impact of COVID-19 pandemic on cardiovascular risk factors, comorbidities, and unhealthy behaviors in patients with rheumatic inflammatory autoimmune diseases, particularly focused on rheumatoid arthritis and systemic lupus erythematosus. Searches were carried out in MEDLINE/PubMed and Scopus from August to December 2022. Four reviewers screened the title and abstract of retrieved records. Potentially eligible reports were then reviewed in full text. Differences were reconciled by either consensus or discussion with an external reviewer. During the COVID-19 pandemic, patients with rheumatic diseases showed an increase in the prevalence of mental health disorders (43.2-57.7%), reduced physical activity (56.8%), and a worsening in eating behaviors. Alcohol intake increased (18.2%), especially in early phases of the pandemic. Smoking prevalence decreased (28.2%). Dyslipidemia and hypertension showed no changes. The pandemic and lockdown affected rheumatic patients not only in disease-related characteristics but in the prevalence of their cardiovascular comorbidities and risk factors. Lifestyle changes, such as healthy eating, physical activity, and optimal management of their rheumatic diseases and comorbidities, are essential to manage the long-lasting consequences of the COVID-19 outbreak. Key Points • During the COVID-19 pandemic, anxiety, depression, sedentarism, obesity, and a worsening in eating behaviors increased. •Patients with rheumatic diseases and comorbidities have worse clinical outcomes and a higher cardiovascular disease burden than those without them. •Comparative studies are necessary to precisely elucidate the pandemic's impact on the prevalence of cardiovascular disease, risk factors, and comorbidities in patients with rheumatoid arthritis and systemic lupus erythematosus.

Subgingival Microbiota and Periodontal Clinical Status in Patients with Plaque Psoriasis: A Cross-Sectional Study.

Plaque Psoriasis (PP) and periodontitis are inflammatory disorders with a bidirectional association. They both have a qualitatively similar immune-modulatory cascade, cytokine profile, and a recently described dysbiosis. Different oral bacterial species compositions in the periodontal pocket might play a role in the development of PP. To describe the subgingival microbiota of the Mexican population with PP and the periodontal conditions. Subjects were divided into two groups: periodontal health (PH) (PH-non-PP, PH-PP) and periodontitis (PD) (P-non-PP, PD-PP). Following clinical examination, the patients were classified into three groups according to the degree of psoriasis as measured by the Psoriasis Area Severity Index (PASI) and the periodontal status according to the parameters of the American Academy of Periodontology (AAP). Subgingival microbiota samples of each patient were used to determine 40 species of periodontal bacteria by checkerboard DNA-DNA hybridization. IL-2 and IL-6 were measured by ELISA. Of the forty-eight patients with PP, 21 patients had PH and 27 patients had PD. PD-PP group has a significant increase in the percentage of plaque, gingival redness, pocket probing depth, and clinical attachment loss (P<0.001) compared to PH-PP group. Microbiologically PD-PP exhibited significantly higher mean counts for A. georgiae, A. israelii, A. naeslundii from blue complex (P<0.001) than PD-non-PP. Moreover, the counts of these Actinomyces in PD-PP increased according to the severity of index PASI. The concentration of IL-2 and IL-6 were increased in saliva from PH-PP and PD-PP patients compared to PH non-PP. PP individuals harbored a particular sub-gingival microbiota profile different from non-PP. The severity of psoriasis was related to dysbiosis of microbiota -PASI > 5 related to periodontitis with the predominance of Actinomyces periodontal, irrespective of their periodontal condition. Finally, the severity of psoriasis could be unbalanced in subgingival microbiota and increase the risk to develop periodontitis.

Comparative effects of levamisole, Staphylococcus, and Freund's adjuvant on rat immunization with excretory and secretory antigens of Trichinella spiralis muscle larvae.

A comparison was made of the effects of levamisole, the bacterial fractions of Staphylococcus, and Freund's adjuvant on the immunization of rats with the excretory and secretory antigens of Trichinella spiralis muscle larvae. Wistar rats were immunized with the antigen and a saline solution, levamisole (LV), Staphylococcus (ST), or Freund's adjuvant (FA). After immunization, rats were infected, and the parasite burden at muscular phase was calculated for each group. Levels of IgG1 and IgG2 antibodies, as well as levels of two cytokines, IL-4 and IFN-γ, were evaluated during the immunization and postinfection periods. Differences were found in the kinetics of antibody production between groups (p < 0.01). In all cases, there was reactivity with the main 45-, 50-, and 55-kDa antigens of Trichinella muscle larvae. Immunization with FA and ST enhanced the production of IgG1, but only FA showed a significant increase in the production of IFN-γ (p < 0.01), resulting in 86% protection against the infection. In contrast, only 60-70% protection was attained in the ST and LV groups (p < 0.01). These data support the idea that levamisole and Staphylococcus can be used as adjuvant to enhance the humoral response and, at the same time, demonstrate that IFN-γ could be involved in protection against Trichinella.

Macroscopic Stress-Strain Response and Strain-Localization Behavior of Biopolymer-Treated Soil.

The enhancement of soil engineering properties with biopolymers has been shown recently as a viable and environmentally benign alternative to cement and chemical stabilization. Interest in biopolymer-treated soil is evident from the upsurge of related research activities in the last five years, most of which have been experimental in nature. However, biopolymers have not yet found their way into engineering practice. One of the reasons for this may be the absence of computational models that would allow engineers to incorporate biopolymer-treated soil into their designs. Therefore, the main goal of this study is to numerically capture a macroscopic stress-strain response and investigate the effect of biopolymers on the onset of strain localization. Several diagnostic strain-localization analyses were conducted, thus providing strain and stress levels at the onset of strain localization, along with the orientations of the deformation band. Several unconfined compression and triaxial tests on the plain and biopolymer-treated soils were modeled. Results showed that biopolymers significantly improved the mechanical behavior of the soil and affected the onset of strain localization. The numerical results were confirmed by the digital image analysis of the unconfined compression tests. Digital image processing successfully captured high strain concentrations, which tended to occur close to the peak stress.

Paradigms of endothelial stiffening in cardiovascular disease and vascular aging.

Endothelial cells, the inner lining of the blood vessels, are well-known to play a critical role in vascular function, while endothelial dysfunction due to different cardiovascular risk factors or accumulation of disruptive mechanisms that arise with aging lead to cardiovascular disease. In this review, we focus on endothelial stiffness, a fundamental biomechanical property that reflects cell resistance to deformation. In the first part of the review, we describe the mechanisms that determine endothelial stiffness, including RhoA-dependent contractile response, actin architecture and crosslinking, as well as the contributions of the intermediate filaments, vimentin and lamin. Then, we review the factors that induce endothelial stiffening, with the emphasis on mechanical signals, such as fluid shear stress, stretch and stiffness of the extracellular matrix, which are well-known to control endothelial biomechanics. We also describe in detail the contribution of lipid factors, particularly oxidized lipids, that were also shown to be crucial in regulation of endothelial stiffness. Furthermore, we discuss the relative contributions of these two mechanisms of endothelial stiffening in vasculature in cardiovascular disease and aging. Finally, we present the current state of knowledge about the role of endothelial stiffening in the disruption of endothelial cell-cell junctions that are responsible for the maintenance of the endothelial barrier.

Caveolin-1 is a primary determinant of endothelial stiffening associated with dyslipidemia, disturbed flow, and ageing.

Endothelial stiffness is emerging as a major determinant in endothelial function. Here, we analyzed the role of caveolin-1 (Cav-1) in determining the stiffness of endothelial cells (EC) exposed to oxidized low density lipoprotein (oxLDL) under static and hemodynamic conditions in vitro and of aortic endothelium in vivo in mouse models of dyslipidemia and ageing. Elastic moduli of cultured ECs and of the endothelial monolayer of freshly isolated mouse aortas were measured using atomic force microscopy (AFM). We found that a loss of Cav-1 abrogates the uptake of oxLDL and oxLDL-induced endothelial stiffening, as well as endothelial stiffening induced by disturbed flow (DF), which was also oxLDL dependent. Mechanistically, Cav-1 is required for the expression of CD36 (cluster of differentiation 36) scavenger receptor. Genetic deletion of Cav-1 abrogated endothelial stiffening observed in the DF region of the aortic arch, and induced by a high fat diet (4-6 weeks) and significantly blunted endothelial stiffening that develops with advanced age. This effect was independent of stiffening of the sub-endothelium layer. Additionally, Cav-1 expression significantly increased with age. No differences in elastic modulus were observed between the sexes in advanced aged wild type and Cav-1 knockout mice. Taken together, this study demonstrates that Cav-1 plays a critical role in endothelial stiffening induced by oxLDL in vitro and by dyslipidemia, disturbed flow and ageing in vivo.

The challenge of detecting adverse events in adults with autism spectrum disorder who have intellectual disability.

Adults with autism spectrum disorder (ASD) and associated intellectual disability (ID) take a high number of different psychotropic drugs simultaneously. Nowadays, little is known about this multidrug pattern efficacy and safety. The present study has endeavored to fill this gap creating a local pharmacovigilance system. A 36-month, retrospective and prospective, observational, and multicenter pharmacovigilance study was carried out in adults with ASD and ID (n = 83). Information regarding ongoing medications (polypharmacy: taking simultaneously >4 drugs; safety profile: adverse events' number, adverse drug reactions' number, and affected system; and observed-to-expected [O/E] ratio using the summary of product characteristics), and current diagnoses were recorded. A median of four ongoing medications per participant was registered, half of the sample was under polypharmacy regimen. Regarding all ongoing medications, 50% were antipsychotic drugs, and 47% of participants had >1 antipsychotic prescribed. In contrast, only 64 adverse events were identified from electronic health records, mostly due to risperidone. Half of them were related either to nervous or metabolic systems, and almost a third were not previously described in the corresponding drug summary of products characteristics. Extrapyramidalism, gynecomastia, hypercholesterolemia, and urinary retention were some AEs that occurred more frequently than expected (O/E ratio > 6 times) according to our data. The highest O/E ratio scores (>120 times) were for hypercholesterolemia and rhabdomyolysis caused by valproic acid. According to the number of adverse events and adverse drug reactions reported in electronic health records locally and nationally by clinicians, we need to increase awareness about medications safety. LAY SUMMARY: A 36-month study in adults with autism, ID, and polypharmacy (>4 drugs) was done to investigate drug safety on everyone. A median of four medications per person was registered, half were antipsychotic drugs, and 47% of participants had >1 antipsychotic medication simultaneously. Only 64 adverse events were identified from electronic health records, mostly due to risperidone. Half of them were related to nervous or metabolic systems and a third were not previously described in the drug information sheet.

Quantification of Osteoprotegerin Plasma Levels in Patients with Periodontitis.

OBJECTIVE: Periodontitis (POD) is an infectious process directed at the structures supporting the teeth. Destruction of alveolar bone is considered one of the main causes of tooth loss in humans and is mediated by the host immune response. Osteoprotegerin (OPG), a protein that inhibits bone resorption by binding to the RANK ligand (RANKL), prevents osteoclastic differentiation. The aim of the study was to determine the plasma levels of OPG in patients with POD. METHODS: a case-control study with forty-nine patients with POD and 49 healthy controls were included in the study. OPG levels were determined by an ELISA test in plasma samples. RESULTS: OPG values (1.6203 ng/mL) were higher in the POD group compared with control group (1.2824 ng/mL). Among the studied groups, we detected significant differences in age, glycosylated haemoglobin (HbA1C), and plasma concentration of OPG (p < 0.05). CONCLUSION: plasma OPG levels are associated with bone formation and destruction processes, suggesting that OPG acts in a protective manner.