Cultural adaptation and psychometric properties of the Substance Abuse Self-Stigma Scale among Latinos with Substance Use Disorders: An effective screening tool for correctional and community settings.

The present study involves a psychometric evaluation of the Substance Abuse Self-Stigma Scale (SASSS), a 40-item dimensional measure of internalized or self-stigma developed by Jason Luoma and collaborators, among Latinos with Substance Use Disorders (SUDs). The current study's specific aim is to assess the psychometric properties (factor structure and reliability) of the translated and culturally adapted SASSS instrument in a cross-sectional study of individuals (n = 412) with SUDs with or without HIV from correctional facilities and community treatment programs. A confirmatory factor analysis evidenced the four-factor structure of SASSS. Results showed significant correlations with HIV felt stigma among those participants with co-occurring SUD and HIV (n=119), internalized shame, stigma-related interpersonal rejection due to substance abuse, symptoms of depression, substance use within the last 30 days, psychological flexibility, self-esteem, and self-efficacy, supporting good convergent validity. The measure showed a strong factor structure and adequate reliability estimates supporting its applicability to Latinos with SUDs from community and criminal justice settings. Findings are discussed in terms of their implications for studies of stigma impact and intervention.

Caracterización sociodemográfica y clínica de pacientes diagnosticados con dengue y chikungunya en Nariño, Colombia / Clinical and socio-demographic characterization of patients diagnosed with dengue and chikungunya in Nariño, Colombia

RESUMEN Introducción: Existen más de 390 millones de personas infectadas y 20 000 muertes anualmente a causa del dengue en el mundo. El chikungunya ocasionó una larga epidemia en las Américas con más de 2 millones y medio de casos hasta el 2017. Objetivo: Identificar las características sociodemográficas y clínicas de los casos de dengue y chikungunya informados para el periodo 2014-2017 en Nariño, Colombia. Métodos: Se realizó un estudio observacional, descriptivo, de corte transversal. Se revisaron retrospectivamente las bases de datos del Instituto Departamental de Salud de Nariño y del Hospital Universitario Departamental de Nariño. Resultados: Para el periodo de estudio hubo 2 514 hospitalizaciones por dengue y 460 por chikungunya. Se identificaron 22 casos de dengue grave, con una muerte para el año 2017. La revisión de expedientes de 1 735 pacientes con información completa reveló que las manifestaciones clínicas más frecuentes para dengue fueron: fiebre (100 por ciento), cefalea (84,6 por ciento) y mialgias (83,7 por ciento), seguidos de artralgias, rash y dolor abdominal. El sexo masculino predominó en los casos de diagnóstico de dengue (56,8 por ciento) y el femenino en el diagnóstico de chikungunya (52,0 por ciento. Tanto dengue como chikungunya fueron más frecuentes en la población mayor de 40 años con el 24,5 por ciento y 27,2 por ciento, respectivamente. Conclusiones: La sintomatología similar y los casos complicados resaltan la necesidad de contar con diagnósticos oportunos y diferenciales y capacitación al personal de salud, apoyados por entidades gubernamentales. Se requiere generar programas de intervención enfocados a edades productivas y en regiones con condiciones medioambientales propicias para el desarrollo de vectores transmisores de enfermedades(AU)

Introduction: More than 390 million dengue cases and 20 000 deaths due to this condition are reported worldwide every year. Chikungunya caused a large epidemic in the Americas with more than two and a half million cases until the year 2017. Objective: Identify the clinical and socio-demographic characteristics of the dengue and chikungunya cases reported for the period 2014-2017 in Nariño, Colombia. Methods: A cross-sectional observational descriptive study was conducted. A retrospective review was carried out of the databases at Nariño Departmental Health Institute and Nariño Departmental University Hospital. Results: During the study period there were 2 514 hospital admissions with dengue and 460 with chikungunya. A total 22 severe dengue cases and one death were identified for the year 2017. Review of the medical records of 1 735 patients with complete information revealed that the most common clinical manifestations of dengue were fever (100 percent), headache (84.6 percent) and myalgia (83.7 percent), followed by arthralgia, rash and abdominal pain. A predominance was found of the male sex in dengue cases (56.8 percent) and of the female sex in chikungunya cases (52.0 percent). Both conditions were more frequent in the population aged over 40 years, with 24.5 percent and 27.2 percent, respectively. Conclusions: The similar symptoms and the presence of complicated cases highlight the need for timely differential diagnosis and the training of the health personnel, with the support of government agencies. It is required to develop intervention programs aimed at working ages and regions with environmental conditions favorable for the spread of disease(AU)

Comparative Study of Traveling and Standing Wave-Based Locomotion of Legged Bidirectional Miniature Piezoelectric Robots.

The use of wave-based locomotion mechanisms is already well established in the field of robotics, using either standing waves (SW) or traveling waves (TW). The motivation of this work was to compare both the SW- and the TW-based motion of a 20-mm long sub-gram glass plate, with attached 3D printed legs, and piezoelectric patches for the actuation. The fabrication of the robot did not require sophisticated techniques and the speed of motion was measured under different loading conditions. In the case of the TW mechanism, the influence of using different pairs of modes to generate the TW on the locomotion speed has been studied, as well as the effect of the coupling of the TW motion and the first flexural vibration mode of the legs. This analysis resulted in a maximum unloaded speed of 6 bodylengths/s (BL/s) at 65 V peak-to-peak (Vpp). The SW approach also examined different modes of vibration and a speed of locomotion as high as 14 BL/s was achieved, requiring, unlike the TW case, a highly precise location of the legs on the glass supporting platform and a precise tuning of the excitation frequency.

Caracterización de pacientes con otosclerosis con estapedotomia a través de abordaje trascanal y retroauricular en un hospital universitario / Characterization of patients with otosclerosis with transcanal and retroauricular stapedotomy in a university hospital

Introducción: la otosclerosis manejada quirúrgicamente con estapedotomía ha mostrado mejora del umbral auditivo mediante un abordaje transcanal o retroauricular. Objetivo: caracterizar la respuesta al tratamiento quirúrgico con estapedotomía transcanal y retroauricular en pacientes con diagnóstico de otosclerosis en un centro universitario. Diseño: estudio observacional descriptivo retrospectivo tipo serie de casos. Metodología: se incluyeron pacientes con diagnósticos de otosclerosis atendidos en el Hospital Universitario Clínica San Rafael quienes cumplieron criterios de elegibilidad entre 2014 y 2020. Resultados: Se incluyeron 33 pacientes intervenidos con abordaje transcanal y 8 con abordaje retroauricular, la edad promedio fue de 46,6 años. La mayoría de pacientes fue de sexo femenino (56,1 %). Se evidenció una mejora del umbral auditivo en el 89,9 % del total de la muestra. La presencia de variantes anatómicas se describió en un 26,8 %, la variante más común fue el prolapso del nervio cuerda del tímpano (14,5 %). La complicación intraoperatoria más común fue la sección del nervio cuerda del tímpano (9,8 %). La presencia de complicaciones y variantes anatómicas fue más prevalente con abordaje retroauricular. Conclusiones: la estapedotomía con abordaje retroauricular y transcanal mostró mejoría del umbral auditivo equiparable a la literatura mundial, la presencia de variantes anatómicas se correlacionó con complicaciones posoperatorias.

Introduction: Otosclerosis managed surgically with stapedotomy has shown improvement in hearing threshold using a transcanal or retroauricular approach. Objective: To characterize the response to surgical treatment with transcanal and retroauricular stapedotomy in patients diagnosed with otosclerosis in a university center. Design: Retrospective descriptive observational study, case series type. Methodology: Patients with a diagnosis of otosclerosis treated at the Hospital Universitario Clínica San Rafael who met the eligibility criteria between 2014 and 2020 were included. Results: 33 patients operated with transcanal approach and 8 with retroauricular approach were included, the average age was 46.6 years. Most patients were female (56.1%). Hearing threshold improvement was evidenced in 89.9% of the total sample. The presence of anatomical variants was described in 26.8%, the most common variant was the prolapse of the chorda tympani nerve (14.5%). The most common intraoperative complication was eardrum cord nerve section (9.8%). The presence of complications and anatomic variants was more prevalent with retroauricular approach. Conclusion: Stapedotomy with retroauricular and transcanal approach showed improvement of hearing threshold comparable to the world literature, the presence of anatomical variants was correlated with postoperative complications.

Modelling of surface river plume using set-up and input data files of Delft-3D model.

This data article presents set-up and input data files to model a surface river plume through curvilinear nested grid in double-way mode. The hydrodynamic modelling in river deltas with intense transport processes and complex bathymetry such as the Magdalena River delta, requires a mesh grid that ease the natural river discharge into the ocean. The aforementioned may be challenging due to the numerical scheme and stability restrictions of the numerical models that difficult having efficient and effective validated simulations. This dataset files are a reference to perform analysis of the hydrodynamic river deltas, meaningful for optimizing time and resources, easing the planning of measurement campaigns what reduce risks of the personnel and instrumentation during equipment deployment and field work .The application of the set-up and input data files of this data article is shown in Rueda-Bayona et al. [1].

Motion of a Legged Bidirectional Miniature Piezoelectric Robot Based on Traveling Wave Generation.

This article reports on the locomotion performance of a miniature robot that features 3D-printed rigid legs driven by linear traveling waves (TWs). The robot structure was a millimeter-sized rectangular glass plate with two piezoelectric patches attached, which allowed for traveling wave generation at a frequency between the resonant frequencies of two contiguous flexural modes. As a first goal, the location and size of the piezoelectric patches were calculated to maximize the structural displacement while preserving a standing wave ratio close to 1 (cancellation of wave reflections from the boundaries). The design guidelines were supported by an analytical 1D model of the structure and could be related to the second derivative of the modal shapes without the need to rely on more complex numerical simulations. Additionally, legs were bonded to the glass plate to facilitate the locomotion of the structure; these were fabricated using 3D stereolithography printing, with a range of lengths from 0.5 mm to 1.5 mm. The optimal location of the legs was deduced from the profile of the traveling wave envelope. As a result of integrating both the optimal patch length and the legs, the speed of the robot reached as high as 100 mm/s, equivalent to 5 body lengths per second (BL/s), at a voltage of 65 Vpp and a frequency of 168 kHz. The blocking force was also measured and results showed the expected increase with the mass loading. Furthermore, the robot could carry a load that was 40 times its weight, opening the potential for an autonomous version with power and circuits on board for communication, control, sensing, or other applications.

Natural dynamics overshadow anthropogenic impact on marine fauna at an urbanised coastal embayment.

Understanding vulnerabilities of coastal ecosystems facing anthropogenic use is a precondition for management decisions and development planning. This can be challenging in urbanised areas with multiple activities affecting different faunal communities. The aim of this study was to provide a holistic understanding of the relative importance of anthropogenic and natural variables for macroinfauna, epifauna and fish in a heavily modified waterbody (HMWB) designated under the EU Water Framework Directive (WFD). The study area, Swansea Bay (Wales, UK), had two regularly dredged industrial ports, three estuaries, a wastewater discharge point and a dredge-spoil disposal site. Wave and tidal current models were constructed, and environmental data were gathered by field studies. Biota were assessed by grab sampling and dredging. Modelled and empirical data were combined in a Distance-based Linear Model (DistLM) that quantified how much of the faunal variation was explained by wave exposure and tidal currents, sediment characteristics and other environmental factors, and by anthropogenic usage. Wave and tidal current parameters explained over 50% of the variation in all biota. Infauna communities were further linked with sediment properties and epibenthos with distance to estuaries. Fish and epibenthos were affected by a dredge-spoil disposal site, but none of the faunal communities was affected by the wastewater outfall. Biota were predominantly driven by the natural hydrodynamic regime while anthropogenic factors had secondary influence. The study highlighted that ecosystems driven by a strong hydrodynamic regime can be relatively resistant to human activities.

Sex differences in traumatic events and psychiatric morbidity associated to probable posttraumatic stress disorder among Latino prisoners.

Latinos comprised 17.1% of the U.S. population and 33.1% of US prisoners, yet they are underrepresented in the psychopathology literature. Despite higher rates of trauma among incarcerated individuals than in the general population, most of the previous research in this area focused primarily on women samples, and very few studies examined sex differences in PTSD and traumatic experiences. In addition, there is a need for research assessing traumatic experiences and probable PTSD in men and women Latino inmates to inform culturally competent care and sex sensitive care for this vulnerable and underserved population. Our study examined whether men and women Latino inmates with probable Posttraumatic Stress Disorder (PTSD), based on the cut off 40 or more symptoms on the Davidson Trauma Scale (DTS), differed significantly by the number of event types experienced, the type of potentially traumatizing event, and in co-occurring psychiatric conditions. A multi-stage sample design was used to select a probabilistic sample of 1,331 inmates from 26 penal institutions in PR of which 1179 participated in the study. Bivariate associations were calculated for each type of traumatic event and probable PTSD. Mean number of types of potentially traumatizing event experienced was comparable for both sexes (F = 3.83, M = 3.74) yet sex differences were found in the nature of the event. Women with probable PTSD had higher rates of experiencing rape and sexual abuse. Men had higher rates of experiencing combat in war, a life-threatening accident, of witnessing violence, and being threatened with a weapon. Men with significant ADHD symptoms in childhood and with Generalized Anxiety Disorder (GAD) during adulthood were almost 5 and 7 times as likely to score above threshold on the DTS whereas women were >3 times as likely in the presence of ADHD symptoms in childhood or depression during adulthood. This study underscores the need to improve understanding of the clinical manifestations of trauma and co-occurring psychiatric conditions for appropriate sex sensitive interventions targeting Latinos living in prisons.

Vascular labeling of the head and neck vessels: Technique, advantages and limitations.

BACKGROUND: Vascular staining techniques have been used to describe the vascular structures of several anatomic areas. However, few reports have described this procedure in the head and neck region. This paper describes a head and neck vascular labeling procedure, and describes some of the technical complications that may occur. MATERIAL AND METHODS: Fifteen specimen cadaver heads were prepared. After drying the vascular system, the internal carotid arteries were ligated and a solution with latex and a gelling agent was injected into the internal carotid arteries and external jugular veins. Two different colors were employed to differentiate arteries from veins. A total of 60ml latex was injected into each blood vessel. Subsequently, the specimens were refrigerated at 5°C for a minimum of 24 hours. Finally, a dissection was performed to identify the venous and arterial systems of the maxillofacial region. RESULTS: In most specimens, correct identification of the vascular structures (lingual artery, pterigoyd plexus, and the major palatal arteries, among others) was possible. However, in three heads a major technical problem occurred (the latex remained liquid), making the dissection unfeasible. Other minor complications such as latex obstruction due to the presence of atheromas were found in two further specimens. CONCLUSIONS: The vascular labeling technique is a predictable, effective and simple method for analyzing the vascular system of the maxillofacial area in cadaveric studies, including vessels of reduced diameter or with an intraosseous course. This procedure can be especially useful to teach vascular anatomy to dental students and postgraduate residents. Key words:Blood vessels, vascular casting, vascular labeling, head and neck arteries, carotid arteries, jugular veins.

Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model.

BACKGROUND: Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica. METHODS: The mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks. RESULTS: Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value <0.05, fold change ranging from -2.944 to 7.632. A functional study of these genes revealed changes in the pathways related to nitric oxide and reactive oxygen species production, Interleukin-12 signalling and production in macrophages and Interleukin-8 signalling with up-regulation of S100 calcium-binding protein A8, Matrix metallopeptidase 9 and CXC chemokine receptor 2 genes. CONCLUSION: The data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against F. hepatica in a murine model, which could be useful for evaluating future vaccine candidates.

Vascular Structures of the Lateral Wall of the Maxillary Sinus: A Vascular Labeling Technique.

PURPOSE: Sinus floor augmentation is a common procedure in implant dentistry. However, several intraoperative complications can occur during this procedure, such as bleeding from the lateral wall of the maxillary sinus. The aim of this study was to describe the vascular structures of the lateral wall of the maxillary sinus using a vascular labeling technique. MATERIALS AND METHODS: Ten cadaveric specimens were prepared by the vascular labeling technique. Liquid latex was injected into the large vessels of the head, and the lateral wall of the maxillary sinus was exposed by dissection. The diameter of the vessels and their distance from the alveolar ridge (AR) were recorded. RESULTS: Blood vessels could be observed in all the dissected specimens (100%). The mean distance from the lower edge of the blood vessels to the AR was 18.5 mm (SD 3.31 mm). CONCLUSIONS: The vascular labeling technique detects maxillary sinus vessels in a predictable and effective way. These structures are clinically relevant because they are located in the area where the lateral window is usually created in sinus augmentation procedures and can cause profuse bleeding.

The alkylphospholipid edelfosine shows activity against Strongyloides venezuelensis and induces apoptosis-like cell death.

Strongyloidiasis is widely distributed in the tropical and subtropical areas. Ivermectin is the drug of choice for the treatment. However, the concerns about relying treatment on a single drug make identification of new molecules a priority. Alkylphospholipid analogues, including edelfosine, are a group of synthetic compounds that have shown activity against some parasites. The objective was to assess the in vitro and in vivo activity of edelfosine, miltefosine, perifosine against Strongyloides venezuelensis. Moreover, apoptosis-like mechanism in larvae after treatment was studied. Edelfosine displayed the highest activity and the best selectivity index (LD50=49.6 ± 5.4µM, SI=1.1) compared to miltefosine or perifosine. Third stage larvae after culture with edelfosine were not able to develop an infection in mice. Treatment of mice with edelfosine showed reduction of 47% in parasitic females allocated in the gut. Moreover, DNA fragmentation was observed by TUNEL staining in larvae treated with edelfosine. These results suggest that edelfosine could be an effective drug against strongyloidiasis, probably through induction of apoptosis-like cell death.

In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis.

BACKGROUND: Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T-lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third-stage larva (L3) cultures and experimental infections in mice. METHODS: The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 µM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1-aminododecan-2-yl) carbamate) and 18 (tert-butyl N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days. RESULTS: In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9-39.1 µM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %). CONCLUSIONS: These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis.

Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems.

BACKGROUND: Schistosomiasis is a water-borne disease afflicting over 261 million people in many areas of the developing countries with high morbidity and mortality. The control relies mainly on treatment with praziquantel. Fatty acid binding proteins (FABP) have demonstrated high levels of immune-protection against trematode infections. This study reports the immunoprotection induced by cross-reacting Fasciola hepatica FABP, native (nFh12) and recombinantly expressed using two different expression systems Escherichia coli (rFh15) and baculovirus (rFh15b) against Schistosoma mansoni infection. METHODS: BALB/c mice were vaccinated with native nFh12 or recombinant rFh15 and rFh15 FABP from F. hepatica formulated in adjuvant adaptation (ADAD) system with natural or chemical synthesised immunomodulators (PAL and AA0029) and then challenged with 150 cercariae of S. mansoni. Parasite burden, hepatic lesions and antibody response were studied in vaccination trials. Furthermore differences between rFh15 and rFh15b immunological responses (cytokine production, splenocyte population and antibody levels) were studied. RESULTS: Vaccination with nFh12 induced significant reductions in worm burden (83%), eggs in tissues (82-92%) and hepatic lesions (85%) compared to infected controls using PAL. Vaccination with rFh15 showed lower total worm burden (56-64%), eggs in the liver (21-61%), eggs in the gut (30-77%) and hepatic damage (67-69%) using PAL and AA0029 as immunomodulators. In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%). We observed a significant rise in TNFα, IL-6, IL-2, IL-4 and high antibody response (IgG, IgG1, IgG2a, IgM and IgE) in mice immunised with either rFh15 or rFh15b. Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15. CONCLUSIONS: Higher level of protection is obtained by using Fasciola hepatica-derived FABP protein against Schistosoma mansoni infection. Native FABP is more effective than both recombinant systems. It could be due to post-translational modifications or FABP isoform or changes in the recombinant proteins.

Time-course investigation of the gene expression profile during Fasciola hepatica infection: A microarray-based study.

Fasciolosis is listed as one of the most important neglected tropical diseases according with the World Health Organization and is also considered as a reemerging disease in the human beings. Despite there are several studies describing the immune response induced by Fasciola hepatica in the mammalian host, investigations aimed at identifying the expression profile of genes involved in inducing hepatic injury are currently scarce. Data presented here belong to a time-course investigation of the gene expression profile in the liver of BALB/c mice infected with F. hepatica metacercariae at 7 and 21 days after experimental infection. The data published here have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE69588, previously published by Rojas-Caraballo et al. (2015) in PLoS One [1].

Gene Expression Profile in the Liver of BALB/c Mice Infected with Fasciola hepatica.

BACKGROUND: Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with F. hepatica metacercariae using a microarray-based methodology. METHODOLOGY: A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21). RESULTS: We found that F. hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death. CONCLUSION: The present study provides us insights at the molecular level about the underlying mechanisms used by F. hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma. However, more studies should be performed to confirm this hypothesis.

Inhibition of Granulomatous Inflammation and Prophylactic Treatment of Schistosomiasis with a Combination of Edelfosine and Praziquantel.

BACKGROUND: Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. This parasitic disease is due to immunologic reactions to Schistosoma eggs trapped in tissues. Egg-released antigens stimulate tissue-destructive inflammatory and granulomatous reactions, involving different immune cell populations, including T cells and granulocytes. Granulomas lead to collagen fibers deposition and fibrosis, resulting in organ damage. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. METHODOLOGY/PRINCIPAL FINDINGS: Using in vitro and in vivo approaches, we have found that the alkylphospholipid analog edelfosine kills schistosomula, and displays anti-inflammatory activity. The combined treatment of PZQ and edelfosine during a few days before and after cercariae infection in a schistosomiasis mouse model, simulating a prophylactic treatment, led to seven major effects: a) killing of Schistosoma parasites at early and late development stages; b) reduction of hepatomegaly; c) granuloma size reduction; d) down-regulation of Th1, Th2 and Th17 responses at late post-infection times, thus inhibiting granuloma formation; e) upregulation of IL-10 at early post-infection times, thus potentiating anti-inflammatory actions; f) down-regulation of IL-10 at late post-infection times, thus favoring resistance to re-infection; g) reduction in the number of blood granulocytes in late post-infection times as compared to infected untreated animals. CONCLUSIONS/SIGNIFICANCE: Taken together, these data suggest that the combined treatment of PZQ and edelfosine promotes a high decrease in granuloma formation, as well as in the cellular immune response that underlies granuloma development, with changes in the cytokine patterns, and may provide a promising and effective strategy for a prophylactic treatment of schistosomiasis.

The combination of the aliphatic diamine AA0029 in ADAD vaccination system with a recombinant fatty acid binding protein could be a good alternative for the animal schistosomiasis control.

Fatty acid binding proteins (FABP) from Fasciola hepatica have demonstrated immune cross-protection against schistosomes. The present study was conducted to develop a new formulation of the recombinant FABP rFh15 with the synthetic immunomodulator AA0029 in the adjuvant adaptation (ADAD) vaccination system and to evaluate its ability to induce immune response and protection against the challenge with Schistosoma bovis cercariae. Immunization of BALB/c mice showed high levels of TNFα, IFNγ, interleukin (IL)-2, IL-6, and IL-4 in splenocyte supernatant culture and also high levels of serum specific anti-rFh15 IgG, IgG1, IgG2a IgE and IgM antibodies suggesting a mixed Th1/Th2 immune response. Using this approach, high levels of protection against experimental challenge with S. bovis cercariae were observed in the mouse and hamster models. A marked reduction up to 64% in worm burden, as well as in the number of eggs retained in liver (66%) and intestine (77%) and hepatic lesions (42%), was achieved in vaccinated BALB/c mice. Golden hamsters vaccinated and challenged in similar conditions had reductions in recovered worms (83%), liver eggs (90%), intestine eggs (96%), liver lesions (56%) and worm fecundity (48-80%). These data suggest that formulation of rFh15 in the ADAD vaccination system using the AA0029 immunomodulator could be a good option to drive an effective immunological response against schistosomiasis.

In vitro and in vivo studies for assessing the immune response and protection-inducing ability conferred by Fasciola hepatica-derived synthetic peptides containing B- and T-cell epitopes.

Fasciolosis is considered the most widespread trematode disease affecting grazing animals around the world; it is currently recognised by the World Health Organisation as an emergent human pathogen. Triclabendazole is still the most effective drug against this disease; however, resistant strains have appeared and developing an effective vaccine against this disease has increasingly become a priority. Several bioinformatics tools were here used for predicting B- and T-cell epitopes according to the available data for Fasciola hepatica protein amino acid sequences. BALB/c mice were immunised with the synthetic peptides by using the ADAD vaccination system and several immune response parameters were measured (antibody titres, cytokine levels, T-cell populations) to evaluate their ability to elicit an immune response. Based on the immunogenicity results so obtained, seven peptides were selected to assess their protection-inducing ability against experimental infection with F. hepatica metacercariae. Twenty-four B- or T-epitope-containing peptides were predicted and chemically synthesised. Immunisation of mice with peptides so-called B1, B2, B5, B6, T14, T15 and T16 induced high levels of total IgG, IgG1 and IgG2a (p<0.05) and a mixed Th1/Th2/Th17/Treg immune response, according to IFN-γ, IL-4, IL-17 and IL-10 levels, accompanied by increased CD62L+ T-cell populations. A high level of protection was obtained in mice vaccinated with peptides B2, B5, B6 and T15 formulated in the ADAD vaccination system with the AA0029 immunomodulator. The bioinformatics approach used in the present study led to the identification of seven peptides as vaccine candidates against the infection caused by Fasciola hepatica (a liver-fluke trematode). However, vaccine efficacy must be evaluated in other host species, including those having veterinary importance.