Attitudes scale toward cancer-related cognitive changes - an initial Colombian validation.

OBJECTIVE: The aim of this study was to develop an initial valid tool to measure attitudes toward cancer-related cognitive changes. SUBJECTS AND METHODS: After revising the literature, three main dimensions were hypothesized. Eight judges were contacted to obtain content validity evidence. A robust Exploratory Factor Analysis (EFA) was performed via a parallel analysis with an Unweighted Least Squares (ULS) estimator and polychoric correlations. The results were crossed with sociodemographic variables to find possible statistical differences and estimate the size effect. Analysis was performed in the software Factor and the statistical package R. RESULTS: A sample of 374 participants was obtained, involving oncology patients, their caregivers, and people from the general community. A statistical fit was found in two dimensions: Awareness and Judgments [root mean squared error of approximation (RMSEA) = 0.042, standardized root mean square residual (SRMR) = 0.02, comparative fit index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98] with a moderate correlation between them (r = 0.612). Optimal reliability indices were obtained for the total scale and its dimensions. No real statistical difference was found between sociodemographic variables; the interpretation norms were established via the quartiles. CONCLUSIONS: The first attempt to measure the construct of interest was developed with two primary validity evidence based on the content and its internal structure. This instrument could help strengthen the prevention of cancer-related cognitive changes. More research is needed to adhere more valid evidence to the scale.

Assessing risk of vector transmission of Chagas disease through blood source analysis using LC-MS/MS for hemoglobin sequence identification.

Chagas disease is mainly transmitted by triatomine insect vectors that feed on vertebrate blood. The disease has complex domiciliary infestation patterns and parasite transmission dynamics, influenced by biological, ecological, and socioeconomic factors. In this context, feeding patterns have been used to understand vector movement and transmission risk. Recently, a new technique using Liquid chromatography tandem mass spectrometry (LC-MS/MS) targeting hemoglobin peptides has showed excellent results for understanding triatomines' feeding patterns. The aim of this study was to further develop the automated computational analysis pipeline for peptide sequence taxonomic identification, enhancing the ability to analyze large datasets data. We then used the enhanced pipeline to evaluate the feeding patterns of Triatoma dimidiata, along with domiciliary infestation risk variables, such as unkempt piles of firewood or construction material, cracks in bajareque and adobe walls and intradomiciliary animals. Our new python scripts were able to detect blood meal sources in 100% of the bugs analyzed and identified nine different species of blood meal sources. Human, chicken, and dog were the main blood sources found in 78.7%, 50.4% and 44.8% of the bugs, respectively. In addition, 14% of the bugs feeding on chicken and 15% of those feeding on dogs were captured in houses with no evidence of those animals being present. This suggests a high mobility among ecotopes and houses. Two of the three main blood sources, dog and chicken, were significantly (p < 0.05) affected by domiciliary infestation risk variables, including cracks in walls, construction material and birds sleeping in the intradomicile. This suggests that these variables are important for maintaining reproducing Triatoma dimidiata populations and that it is critical to mitigate these variables in all the houses of a village for effective control of these mobile vectors.

A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia.

BackgroundAntibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia.MethodsWe performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti-SARS-CoV-2 antibodies.ResultsEighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti-SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5-30] vs. 7 [2.75-12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP.ConclusionTwo units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early.Trial RegistrationClinicalTrials.gov NCT04397757.FundingUniversity of Pennsylvania.

Colorenal fistula and urinary tract infection in a pediatric patient with acute lymphoblastic leukemia. / Fístula colorrenal e infección de vías urinarias en paciente pediátrico con leucemia linfoide aguda.

INTRODUCTION: Colorenal fistula is rare in the pediatric population. It may occur at any segment involved by ischemia, chronic inflammation, or necrosis. It is typically associated with a preliminary renal lesion that may arise as a result of interventional procedures, inflammatory conditions, colon tumor, and xanthogranulomatous pyelonephritis, among others. CASE REPORT: 15-year-old female patient diagnosed with acute lymphoblastic leukemia admitted at our institution for baseline condition management. During her stay, she experienced gastrointestinal and urinary infectious events. In the assessment and management of those, a left colorenal fistula was found. Surgical treatment was decided upon. DISCUSSION: Colorenal fistula typically occurs secondary to renal inflammation or infection. Clinical signs are highly variable, and treatment is surgical, with the fistulous tract being resected in all cases.

INTRODUCCION: Las fístulas colorrenales son infrecuentes en la población pediátrica. Pueden desarrollarse en cualquier segmento afectado por isquemia, inflamación crónica o necrosis. Suelen estar asociadas a una lesión primitiva en el riñón que puede producirse por procedimientos intervencionistas, enfermedades inflamatorias, tumorales del colon, pielonefritis xantogranulomatosa, entre otras. CASO CLINICO: Paciente femenina de 15 años, con diagnóstico de leucemia linfoide aguda, ingresa a la institución para recibir manejo de su enfermedad de base. Durante su evolución, desarrolla eventos infecciosos (gastrointestinales y urinarios), y en evaluación y manejo de estos se documenta fístula colorrenal izquierda, motivo por el cual se da un enfoque de tratamiento quirúrgico. COMENTARIOS: La fístula renocólica generalmente se presenta secundaria a procesos inflamatorios o infecciosos renales; su presentación clínica es muy variada, y el tratamiento es quirúrgico, incluyendo siempre la resección del trayecto fistuloso.

Fístula colorrenal e infección de vías urinarias en paciente pediátrico con leucemia linfoide aguda / Colorenal fistula and urinary tract infection in a pediatric patient with acute lymphoblastic leukemia

Introducción: Las fístulas colorrenales son infrecuentes en la población pediátrica. Pueden desarrollarse en cualquier segmento afectadopor isquemia, inflamación crónica o necrosis. Suelen estar asociadas auna lesión primitiva en el riñón que puede producirse por procedimientos intervencionistas, enfermedades inflamatorias, tumorales del colon,pielonefritis xantogranulomatosa, entre otras. Caso clínico: Paciente femenina de 15 años, con diagnóstico deleucemia linfoide aguda, ingresa a la institución para recibir manejode su enfermedad de base. Durante su evolución, desarrolla eventosinfecciosos (gastrointestinales y urinarios), y en evaluación y manejode estos se documenta fístula colorrenal izquierda, motivo por el cualse da un enfoque de tratamiento quirúrgico. Comentarios: La fístula renocólica generalmente se presenta secundaria a procesos inflamatorios o infecciosos renales; su presentaciónclínica es muy variada, y el tratamiento es quirúrgico, incluyendo siempre la resección del trayecto fistuloso.(AU)

Introduction: Colorenal fistula is rare in the pediatric population.It may occur at any segment involved by ischemia, chronic inflammation, or necrosis. It is typically associated with a preliminary renallesion that may arise as a result of interventional procedures, inflammatory conditions, colon tumor, and xanthogranulomatous pyelonephritis,among others. Clinical case: 15-year-old female patient diagnosed with acutelymphoblastic leukemia admitted at our institution for baseline condition management. During her stay, she experienced gastrointestinal andurinary infectious events. In the assessment and management of those,a left colorenal fistula was found. Surgical treatment was decided upon. Discussion: Colorenal fistula typically occurs secondary to renalinflammation or infection. Clinical signs are highly variable, and treatment is surgical, with the fistulous tract being resected in all cases.(AU)

Catch me if you can: Under-detection of Trypanosoma cruzi (Kinetoplastea: Trypanosomatida) infections in Triatoma dimidiata s.l. (Hemiptera: Reduviidae) from Central America.

Assays for parasite detection in insect vectors provide important information for disease control. American Trypanosomiasis (Chagas disease) is the most devastating vector-borne illness and the fourth most common in Central America behind HIV/AIDS and acute respiratory and diarrheal infections (Peterson et al., 2019). Under-detection of parasites is a general problem which may be influenced by parasite genetic variation; however, little is known about the genetic variation of the Chagas parasite, especially in this region. In this study we compared six assays for detecting the Chagas parasite, Trypanosoma cruzi: genomic reduced representation sequencing (here referred to as genotype-by-sequencing or GBS), two with conventional PCR (i.e., agarose gel detection), two with qPCR, and microscopy. Our results show that, compared to GBS genomic analysis, microscopy and PCR under-detected T. cruzi in vectors from Central America. Of 94 samples, 44% (50/94) were positive based on genomic analysis. The lowest detection, 9% (3/32) was in a subset assayed with microscopy. Four PCR assays, two with conventional PCR and two with qPCR showed intermediate levels of detection. Both qPCR tests and one conventional PCR test targeted the 195 bp repeat of satellite DNA while the fourth test targeted the 18S gene. Statistical analyses of the genomic and PCR results indicate that the PCR assays significantly under detect infections of Central American T. cruzi genotypes.

Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption.

Type 1 interferons (IFN-I) are potent innate antiviral effectors that constrain HIV-1 transmission. However, harnessing these cytokines for HIV-1 cure strategies has been hampered by an incomplete understanding of their antiviral activities at later stages of infection. Here, we characterized the IFN-I sensitivity of 500 clonally derived HIV-1 isolates from the plasma and CD4+ T cells of 26 individuals sampled longitudinally after transmission or after antiretroviral therapy (ART) and analytical treatment interruption. We determined the concentration of IFNα2 and IFNß that reduced viral replication in vitro by 50% (IC50) and found consistent changes in the sensitivity of HIV-1 to IFN-I inhibition both across individuals and over time. Resistance of HIV-1 isolates to IFN-I was uniformly high during acute infection, decreased in all individuals in the first year after infection, was reacquired concomitant with CD4+ T cell loss, and remained elevated in individuals with accelerated disease. HIV-1 isolates obtained by viral outgrowth during suppressive ART were relatively IFN-I sensitive, resembling viruses circulating just before ART initiation. However, viruses that rebounded after treatment interruption displayed the highest degree of IFNα2 and IFNß resistance observed at any time during the infection course. These findings indicate a dynamic interplay between host innate responses and the evolving HIV-1 quasispecies, with the relative contribution of IFN-I to HIV-1 control affected by both ART and analytical treatment interruption. Although elevated at transmission, host innate pressures are the highest during viral rebound, limiting the viruses that successfully become reactivated from latency to those that are IFN-I resistant.

Bone development and fracture healing is normal in mice that have a defect in the development of the lymphatic system.

Ectopic lymphatics form in bone and promote bone destruction in diseases such as Gorham-Stout disease, generalized lymphatic anomaly, and kaposiform lymphangiomatosis. However, the role lymphatics serve in normal bone development and repair is poorly understood. The objective of this study was to characterize bone development and fracture healing in mice that have a defect in the development of the lymphatic vasculature. We found that bones in wild-type adult mice and mouse embryos did not have lymphatics. We also found that bone development was normal in Vegfr3 (Chy/Chy) embryos. These mice do not have lymphatics and die shortly after birth. To determine whether lymphatics serve a role in postnatal bone development and fracture healing, we analyzed bones from Vegfr3 (wt/Chy) mice. These mice are viable and have fewer lymphatics than wild-type mice. We found that postnatal bone development and fracture healing was normal in Vegfr3 (wt/Chy) mice. Taken together, our results suggest that lymphatics do not play a major role in normal bone development or repair.

Protein mass spectrometry detects multiple bloodmeals for enhanced Chagas disease vector ecology.

Chagas disease, a neglected tropical disease endemic in Latin America, is caused by the protozoan parasite Trypanosoma cruzi and is responsible for significant health impacts, especially in rural communities. The parasite is transmitted by insect vectors in the Triatominae subfamily and due to lack of vaccines and limited treatment options, vector control is the main way of controlling the disease. Knowing what vectors are feeding on directly enhances our understanding of the ecology and biology of the different vector species and can potentially aid in engaging communities in active disease control, a concept known as Ecohealth management. We evaluated bloodmeals in rural community, house-caught insect vectors previously evaluated for bloodmeals via DNA analysis as part of a larger collaborative project from three countries in Central America, including Guatemala. In addition to identifying bloodmeals in 100% of all samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) (n = 50), strikingly for 53% of these samples there was no evidence of a recent bloodmeal by DNA-PCR. As individual vectors often feed on multiple sources, we developed an enhanced detection pipeline, and showed the ability to quantify a bloodmeal using stable-isotope-containing synthetic references peptides, a first step in further exploration of species-specific bloodmeal composition. Furthermore, we show that a lower resolution mass spectrometer is sufficient to correctly identify taxa from bloodmeals, an important and strong attribute of our LC-MS/MS-based method, opening the door to using proteomics in countries where Chagas disease is endemic.

Hypoglycaemic and Antioxidant Effects of Propolis of Chihuahua in a Model of Experimental Diabetes.

Propolis is a bee-collected natural product that has been proven to have various bioactivities. This study tested the effects of a Mexican propolis on streptozotocin-induced diabetes mellitus in a murine model. The results showed that an ethanolic extract of propolis of Chihuahua (EEPCh) significantly inhibited increases in blood glucose and the loss of body weight in diabetic mice. EEPCh increased plasma insulin levels in STZ-diabetic mice, whereas, in untreated diabetic mice, there was no detection of insulin. EEPCh had a high antioxidant capacity (SA50 = 15.75 µg/mL), which was directly related to the concentrations of total phenols (314 mg GAE/g of extract) and flavonoids (6.25 mg QE/g of extract). In addition, increased activities of the enzymes superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic mice treated with EEPCh. Compounds such as pinocembrin, quercetin, naringin, naringenin, kaempferol, acacetin, luteolin, and chrysin were identified by HPLC-MS analysis. This investigation demonstrated that propolis of Chihuahua possesses hypoglycaemic and antioxidant activities and can alleviate symptoms of diabetes mellitus in mice. These effects may be directly related to the chemical composition of propolis, as most of the compounds identified in propolis are reportedly active in terms of the different parameters evaluated in this work.

Prolonged high force high repetition pulling induces osteocyte apoptosis and trabecular bone loss in distal radius, while low force high repetition pulling induces bone anabolism.

We have an operant rat model of upper extremity reaching and grasping in which we examined the impact of performing a high force high repetition (High-ForceHR) versus a low force low repetition (Low-ForceHR) task for 18weeks on the radius and ulna, compared to age-matched controls. High-ForceHR rats performed at 4 reaches/min and 50% of their maximum voluntary pulling force for 2h/day, 3days/week. Low-ForceHR rats performed at 6% maximum voluntary pulling force. High-ForceHR rats showed decreased trabecular bone volume in the distal metaphyseal radius, decreased anabolic indices in this same bone region (e.g., decreased osteoblasts and bone formation rate), and increased catabolic indices (e.g., microcracks, increased osteocyte apoptosis, secreted sclerostin, RANKL, and osteoclast numbers), compared to controls. Distal metaphyseal trabeculae in the ulna of High-ForceHR rats showed a non-significant decrease in bone volume, some catabolic indices (e.g., decreased trabecular numbers) yet also some anabolic indices (e.g., increased osteoblasts and trabecular thickness). In contrast, the mid-diaphyseal region of High-ForceHR rats' radial and ulnar bones showed few to no microarchitecture differences and no changes in apoptosis, sclerostin or RANKL levels, compared to controls. In further contrast, Low-ForceHR rats showed increased trabecular bone volume in the radius in the distal metaphysis and increased cortical bone area its mid-diaphysis. These changes were accompanied by increased anabolic indices, no microcracks or osteocyte apoptosis, and decreased RANKL in each region, compared to controls. Ulnar bones of Low-ForceHR rats also showed increased anabolic indices, although fewer than in the adjacent radius. Thus, prolonged performance of an upper extremity reaching and grasping task is loading-, region-, and bone-dependent, with high force loads at high repetition rates inducing region-specific increases in bone degradative changes that were most prominent in distal radial trabeculae, while low force task loads at high repetition rates induced adaptive bone responses.

Chagas disease vector blood meal sources identified by protein mass spectrometry.

Chagas disease is a complex vector borne parasitic disease involving blood feeding Triatominae (Hemiptera: Reduviidae) insects, also known as kissing bugs, and the vertebrates they feed on. This disease has tremendous impacts on millions of people and is a global health problem. The etiological agent of Chagas disease, Trypanosoma cruzi (Kinetoplastea: Trypanosomatida: Trypanosomatidae), is deposited on the mammalian host in the insect's feces during a blood meal, and enters the host's blood stream through mucous membranes or a break in the skin. Identifying the blood meal sources of triatomine vectors is critical in understanding Chagas disease transmission dynamics, can lead to identification of other vertebrates important in the transmission cycle, and aids management decisions. The latter is particularly important as there is little in the way of effective therapeutics for Chagas disease. Several techniques, mostly DNA-based, are available for blood meal identification. However, further methods are needed, particularly when sample conditions lead to low-quality DNA or to assess the risk of human cross-contamination. We demonstrate a proteomics-based approach, using liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify host-specific hemoglobin peptides for blood meal identification in mouse blood control samples and apply LC-MS/MS for the first time to Triatoma dimidiata insect vectors, tracing blood sources to species. In contrast to most proteins, hemoglobin, stabilized by iron, is incredibly stable even being preserved through geologic time. We compared blood stored with and without an anticoagulant and examined field-collected insect specimens stored in suboptimal conditions such as at room temperature for long periods of time. To our knowledge, this is the first study using LC-MS/MS on field-collected arthropod disease vectors to identify blood meal composition, and where blood meal identification was confirmed with more traditional DNA-based methods. We also demonstrate the potential of synthetic peptide standards to estimate relative amounts of hemoglobin acquired when insects feed on multiple blood sources. These LC-MS/MS methods can contribute to developing Ecohealth control strategies for Chagas disease transmission and can be applied to other arthropod disease vectors.

IN VIVO AND IN VITRO ANTILEISHMANIAL EFFECTS OF METHANOLIC EXTRACT FROM BARK OF BURSERA APTERA.

BACKGROUND: Cutaneous leishmaniasis lacks effective and well-tolerated treatments. The current therapies mainly rely on antimonial drugs that are inadequate because of their poor efficacy. Traditional medicine offers a complementary alternative for the treatment of various diseases. Additionally, several plants have shown success as anti-leishmanial agents. Therefore, we sought to evaluate the in vitro and in vivo activity of MEBA against Leishmania mexicana. MATERIALS AND METHODS: Methanolic extract of B. aptera was obtained by macetration, after we determined in vitro anti-leishmanial activity of MEBA by MTT assay and the induced apoptosis in promastigotes by flow cytometry. To analyze the in vivo anti-leishmanial activity, we used infected mice that were treated and not treated with MEBA and we determined the levels of cytokines using ELISA. The phytochemical properties were determined by CG-MS and DPPH assay. RESULTS: We determined of LC50 of 0.408 mg/mL of MEBA for in vitro anti-leishmanial activity. MEBA induced apoptosis in promastigotes (15.3% ± 0.86). Treated mice exhibited smaller lesions and contained significantly fewer parasites than did untreated mice; in addition, we found that IFN-γ and TNF-α increased in the sera of MEBA-treated mice. GC-MS analysis showed that podophyllotoxin was the most abundant compound. Evaluation of the activity by DPPH assay demonstrated an SC50 of 11.72 µg/mL. CONCLUSION: Based on the above data, it was concluded that MEBA is a good candidate in the search for new anti-leishmanial agents.

Antimicrobial and anti-inflammatory activities, wound-healing effectiveness and chemical characterization of the latex of Jatropha neopauciflora Pax.

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha neopauciflora Pax is an endemic species to Mexico, and its latex is used in traditional medicine to treat mouth infections when there are loose teeth and to heal wounds. In this research, we evaluated the antimicrobial activity, wound healing efficacy and chemical characterization of J. neopauciflora latex in a murine model. MATERIALS AND METHODS: The antibacterial activity was determined using Gram positive and negative strains, the antifungal activity was determined using yeast and filamentous fungi, and the wound healing efficacy of the latex was determined using the tensiometric method. The anti-inflammatory activity was evaluated using the plantar oedema model in rats, administering the latex orally and topically. Cytotoxic activity was determined in vitro in two different cell lines. Antioxidant capacity, total phenolics, total flavonoids, reducing carbohydrates and latex proteins were quantified. The latex analysis was performed by High Performance Liquid Chromatography (HPLC). Finally, molecular exclusion chromatography was performed. RESULTS: The latex demonstrated antibacterial activity. The most sensitive strains were Gram positive bacteria, particularly S. aureus (MIC=2mg/mL), and the latex had bacteriostatic activity. The latex did not show antifungal activity. The latex demonstrated a wound-healing efficacy, even the positive control (Recoveron). The orally administered latex demonstrated the best anti-inflammatory activity and was not toxic to either of the 2 cell lines. The latex had a high antioxidant capacity (SA50=5.4µg/mL), directly related to the total phenolic (6.9mg GAE/mL) and flavonoid (12.53µg QE/mL) concentration. The carbohydrate concentration was 18.52µg/mL, and fructose was the most abundantly expressed carbohydrate in the latex (14.63µg/mL, 79.03%). Additionally, the latex contained proteins (7.62µg/mL) in its chemical constitution. As secondary metabolites, the HPLC analysis indicated the presence of phenols and flavonoids. CONCLUSIONS: The J. neopauciflora latex promotes the wound healing process by avoiding microorganism infections, inhibiting inflammation and acting as an antioxidant.

BIOLOGICAL PROPERTIES AND CHEMICAL COMPOSITION OF JATROPHA NEOPAUCIFLORA PAX.

BACKGROUND: Ethnopharmacological relevance. Jatropha neopauciflora (Pax) is an endemic species of the Tehuacan- Cuicatlan Valley, Mexico. This species has long been used as a remedy to alleviate illnesses of bacterial, fungal and viral origin. Aim of the study. Experimentally test the traditional use of Jatropha neopauciflora in Mexican traditional medicine. MATERIALS AND METHODS: The methanol extract (MeOH1), of Jatropha neopauciflora (Euphorbiaceae) was obtained by maceration. Next, the methanol (MeOH2) and hexane (H) fractions were obtained. The essential oil was obtained by hydro- distillation. The extract, fractions and essential oil were analyzed by GC-MS. The antimicrobial activity was measured by the disc diffusion agar and radial inhibition growth methods. RESULTS: The extract and fractions showed antibacterial activity against eleven strains (five Gram-positive and six Gram- negative) and a bacteriostatic effect in the survival curves for Staphylococcus aureus and Vibrio cholerae. The extract and fractions were also shown to have antifungal activity, particularly against Trichophyton mentagrophytes (CF50 = MeOH1: 1.07 mg/mL, MeOH2: 1.32 mg/mL and H: 1.08 mg/mL). The antioxidant activity of MeOH1 (68.6 µg/mL) was higher than for MeOH2 (108.1 µg/mL). The main compounds of the essential oil were ß-pinene, 1,3,8-p-menthatriene, ledene, m- menthane, linalyl acetate and 3-carene. The main compounds of MeOH1 were ß-sitosterol, lupeol and pyrogallol; the main compounds of MeOH2 were ß-sitosterol, spathulenol, coniferyl alcohol and lupeol; and the main compounds of H were ß-sitostenone, γ-sitosterol and stigmasterol. CONCLUSIONS: This study indicates that Jatropha neopauciflora is a potential antibacterial and antifungal agent.

Granulomatosis with polyangiitis confined to lacrimal gland, a case report. / Granulomatosis con poliangeítis localizado en la glándula lagrimal, a propósito de un caso.

CLINICAL CASE: A 43 year-old woman consulted due to 2 months of swelling on the superolateral side of the left orbit, with pain and erythema. An excisional biopsy was performed that revealed vasculitis with polyangiitis of the lacrimal gland. A systemic study showed that no other system was compromised. DISCUSSION: Orbital involvement occurs in up to 60% of patients with granulomatosis with polyangiitis. The involvement of the lacrimal gland is rare and often unilateral. Serological tests are generally negative, both in initial stages, as in localized forms of the disease.

Migration and Gene Flow Among Domestic Populations of the Chagas Insect Vector Triatoma dimidiata (Hemiptera: Reduviidae) Detected by Microsatellite Loci.

Triatoma dimidiata (Latreille, 1811) is the most abundant and significant insect vector of the parasite Trypanosoma cruzi in Central America, and particularly in Guatemala. Tr. cruzi is the causative agent of Chagas disease, and successful disease control requires understanding the geographic distribution and degree of migration of vectors such as T. dimidiata that frequently re-infest houses within months following insecticide application. The population genetic structure of T. dimidiata collected from six villages in southern Guatemala was studied to gain insight into the migration patterns of the insects in this region where populations are largely domestic. This study provided insight into the likelihood of eliminating T. dimidiata by pesticide application as has been observed in some areas for other domestic triatomines such as Triatoma infestans. Genotypes of microsatellite loci for 178 insects from six villages were found to represent five genetic clusters using a Bayesian Markov Chain Monte Carlo method. Individual clusters were found in multiple villages, with multiple clusters in the same house. Although migration occurred, there was statistically significant genetic differentiation among villages (FR T = 0.05) and high genetic differentiation among houses within villages (FSR = 0.11). Relatedness of insects within houses varied from 0 to 0.25, i.e., from unrelated to half-sibs. The results suggest that T. dimidiata in southern Guatemala moves between houses and villages often enough that recolonization is likely, implying the use of insecticides alone is not sufficient for effective control of Chagas disease in this region and more sustainable solutions are required.

Integrin mediated adhesion of osteoblasts to connective tissue growth factor (CTGF/CCN2) induces cytoskeleton reorganization and cell differentiation.

Pre-osteoblast adhesion and interaction with extracellular matrix (ECM) proteins through integrin receptors result in activation of signaling pathways regulating osteoblast differentiation. Connective tissue growth factor (CTGF/CCN2) is a matricellular protein secreted into the ECM. Prior studies in various cell types have shown that cell adhesion to CTGF via integrin receptors results in activation of specific signaling pathways that regulate cell functions, such as differentiation and cytoskeletal reorganization. To date, there are no studies that have examined whether CTGF can serve as an adhesive substrate for osteoblasts. In this study, we used the MC3T3-E1 cell line to demonstrate that CTGF serves as an adhesive matrix for osteoblasts. Anti-integrin blocking experiments and co-immunoprecipitation assays demonstrated that the integrin αvß1 plays a key role in osteoblast adhesion to a CTGF matrix. Immunofluorescence staining of osteoblasts cultured on a CTGF matrix confirmed actin cytoskeletal reorganization, enhanced spreading, formation of focal adhesions, and activation of Rac1. Alkaline phosphatase (ALP) staining and activity assays, as well as Alizarin red staining demonstrated that osteoblast attachment to CTGF matrix enhanced maturation, bone nodule formation and matrix mineralization. To investigate whether the effect of CTGF on osteoblast differentiation involves integrin-mediated activation of specific signaling pathways, we performed Western blot, chromatin immunoprecipitation (ChIP) and qPCR assays. Osteoblasts cultured on a CTGF matrix showed increased total and phosphorylated (activated) forms of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). Inhibition of ERK blocked osteogenic differentiation in cells cultured on a CTGF matrix. There was an increase in runt-related transcription factor 2 (Runx2) binding to the osteocalcin gene promoter, and in the expression of osteogenic markers regulated by Runx2. Collectively, the results of this study are the first to demonstrate CTGF serves as a suitable matrix protein, enhancing osteoblast adhesion (via αvß1 integrin) and promoting cell spreading via cytoskeletal reorganization and Rac1 activation. Furthermore, integrin-mediated activation of ERK signaling resulted in increased osteoblast differentiation accompanied by an increase in Runx2 binding to the osteocalcin promoter and in the expression of osteogenic markers.

Early hyperlipidemia promotes endothelial activation via a caspase-1-sirtuin 1 pathway.

OBJECTIVE: The role of receptors for endogenous metabolic danger signals-associated molecular patterns has been characterized recently as bridging innate immune sensory systems for danger signals-associated molecular patterns to initiation of inflammation in bone marrow-derived cells, such as macrophages. However, it remains unknown whether endothelial cells (ECs), the cell type with the largest numbers and the first vessel cell type exposed to circulating danger signals-associated molecular patterns in the blood, can sense hyperlipidemia. This report determined whether caspase-1 plays a role in ECs in sensing hyperlipidemia and promoting EC activation. APPROACH AND RESULTS: Using biochemical, immunologic, pathological, and bone marrow transplantation methods together with the generation of new apoplipoprotein E (ApoE)(-/-)/caspase-1(-/-) double knockout mice, we made the following observations: (1) early hyperlipidemia induced caspase-1 activation in ApoE(-/-) mouse aorta; (2) caspase-1(-/-)/ApoE(-/-) mice attenuated early atherosclerosis; (3) caspase-1(-/-)/ApoE(-/-) mice had decreased aortic expression of proinflammatory cytokines and attenuated aortic monocyte recruitment; and (4) caspase-1(-/-)/ApoE(-/-) mice had decreased EC activation, including reduced adhesion molecule expression and cytokine secretion. Mechanistically, oxidized lipids activated caspase-1 and promoted pyroptosis in ECs by a reactive oxygen species mechanism. Caspase-1 inhibition resulted in accumulation of sirtuin 1 in the ApoE(-/-) aorta, and sirtuin 1 inhibited caspase-1 upregulated genes via activator protein-1 pathway. CONCLUSIONS: Our results demonstrate for the first time that early hyperlipidemia promotes EC activation before monocyte recruitment via a caspase-1-sirtuin 1-activator protein-1 pathway, which provides an important insight into the development of novel therapeutics for blocking caspase-1 activation as early intervention of metabolic cardiovascular diseases and inflammations.