Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

Performance and applications of lightweight geopolymer and alkali activated composites with incorporation of ceramic, polymeric and lignocellulosic wastes as aggregates: A review.

As the construction industry moves towards greater sustainability, the application of more durable and environmentally friendly materials, capable of providing comfort in buildings and infrastructure, is a key element to consider. In this context, the use of alkali-activated binders (AAB) and geopolymers (GP), which have a lower carbon footprint than ordinary Portland cement (OPC), has emerged as an important alternative. Moreover, the addition of waste-based lightweight aggregates (LWA) to AAB and GP matrices produces lightweight composites that offer enhanced mechanical performance and improved comfort as building materials, while offering an alternative use to the increasing number of waste materials from diverse sources. This paper presents a comprehensive review of the literature on the above-mentioned topics (waste LWA in an AAB/GP matrix) published between 2012 and 2023, mainly indexed in the Scopus database. The waste-based LWA reported in the literature were categorized, and their properties and morphology presented. Then, the influence of the size, quantity, and nature of the LWA on the composite's properties and performance was analyzed. Fresh state performance, mechanical performance, density, and thermal and acoustic insulation were considered. This review is complemented by a bibliometric analysis, where keyword correlation and co-authorship networks on this field are established. The review highlights the potential of cementitious composites including waste-based LWA as a sustainable building material for structural and non-structural applications. However, more studies are required to further understand the behaviour of these composites under innovative manufacturing processes, such as extrusion and 3D printing.

Stochastic and deterministic dynamics in networks with excitable nodes.

Networks of excitable systems provide a flexible and tractable model for various phenomena in biology, social sciences, and physics. A large class of such models undergo a continuous phase transition as the excitability of the nodes is increased. However, models of excitability that result in this continuous phase transition are based implicitly on the assumption that the probability that a node gets excited, its transfer function, is linear for small inputs. In this paper, we consider the effect of cooperative excitations, and more generally the case of a nonlinear transfer function, on the collective dynamics of networks of excitable systems. We find that the introduction of any amount of nonlinearity changes qualitatively the dynamical properties of the system, inducing a discontinuous phase transition and hysteresis. We develop a mean-field theory that allows us to understand the features of the dynamics with a one-dimensional map. We also study theoretically and numerically finite-size effects by examining the fate of initial conditions where only one node is excited in large but finite networks. Our results show that nonlinear transfer functions result in a rich effective phase diagram for finite networks, and that one should be careful when interpreting predictions of models that assume noncooperative excitations.

Efectividad del bloqueo de nervios cluneales para tratamiento de dolor lumbar crónico / Effectiveness of cluneal nerve block for the treatment of chronic low back pain

Introducción: El dolor lumbar representa una problemática de salud pública ante la discapacidad que genera, sea motora o sensitiva de etiología multifactorial, en la cual el atrapamiento de los nervios cluneales cumple un papel importante, encontrando como una alternativa al dolor por esta patología el manejo intervencionista. El objetivo principal del estudio fue establecer la efectividad del bloqueo de nervios cluneales en dolor lumbar crónico en pacientes mayores de 18 años de dos hospitales de Bogotá.Métodos: Estudio de tipo observacional, retrospectivo, realizado en pacientes diagnosticados con dolor lumbar crónico y signos y síntomas de atrapamiento de nervios cluneales o clunealgía llevados a bloqueo de nervios cluneales en quienes que se evaluó la intensidad del dolor y duración del efecto analgésico en cuatro momentos.Resultados: Se identificaron 45 pacientes; de estos, 11 no presentaban datos de seguimiento. El 93 % (n = 35) de los pacientes presentaron una EVA (escala visual análoga del dolor) mayor a 7 previo al procedimiento, el 28 % (n = 11) presentaron postbloqueo inmediato mejoría del dolor con una EVA menor a 6, en el primer control el 57 % (n = 22) conservaron la mejoría alcanzada, y el 10 % (n = 4) retornó a su estado basal de dolor. En el segundo, el 10 % (n = 4) de los pacientes no presentaron cambios en la intensidad, y el 78,9 % (n = 30) conservaba mejoría en la intensidad del dolor.Conclusiones: El bloqueo de los nervios cluneales es una alternativa vanguardista de manejo transitorio del dolor lumbar crónico que permitirá seleccionar con mayor objetividad los pacientes candidatos a intervencionismo guiado por fluoroscopia. Se propone la realización de estudios mediante estudios tipo III como los ensayos aleatorizados con grupos donde se administre placebo versus mezclas analgésicas en pacientes con clunealgia.(AU)

Introduction: Low back pain represents a public health problem due to the disability it generates, whether motor or sensory, of multifactorial etiology, in which cluneal nerve entrapment plays an important role, finding an alternative to pain from this pathology. interventional management. The main objective of the study was to establish the efficacy of cluneal nerve block in chronic low back pain in patients older than 18 years from two hospitals in Bogotá.Methods: Observational, retrospective study, carried out in patients diagnosed with chronic low back pain and signs and symptoms of cluneal nerve entrapment or clunealgia leading to cluneal nerve block in whom pain intensity and duration of the analgesic effect were evaluated in four moments.Results: 45 patients were identified; of these, 11 did not present follow-up data. 93 % (n = 35) of the patients presented a VAS (visual analogue pain scale) greater than 7 prior to the procedure, 28 % (n = 11) presented immediate post-block pain improvement with a VAS less than 6, 57 % at the first control (n = 22) maintained the improvement achieved, and 10 % (n = 4) returned to their baseline state of pain. In the second, 10 % (n = 4) of the patients did not show changes in intensity, and 78.9 % (n = 30) maintained improvement in pain intensity.Conclusions: Cluneal nerve blocks are an avant-garde alternative for the temporary management of chronic low back pain that will make it possible to more objectively select patients who are candidates for fluoroscopy-guided intervention. Studies are proposed using type III studies such as randomized trials with groups where placebo is administered versus analgesic mixtures in patients with clunealgia.(AU)

[Guillain-Barre syndrome and thrombocytopenia after SARS-CoV-2 vaccination with Moderna. A case report]. / Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso.

INTRODUCTION: The massive vaccination against the SARS-CoV-2 virus has demonstrated to be one of the major measures for the reduction of the morbidity and mortality that this virus causes. However, during the last months the administration of the vaccine has been also associated with some rare, but life-threatening, adverse effects. CASE REPORT: In this article we describe the case of a patient that developed a Guillain-Barre syndrome and an Idiopathic thrombocytopenic purpura nine days after the vaccination with the third dose for the SARS-CoV-2 virus (Moderna). He had received previously two doses of the AstraZeneca vaccine. Moreover, the patient was positive for auto-antibodies anti-SSA/Ro60 and auto-antibodies IgG anti-GM1 and IgG anti-GM3. DISCUSSION: Even though it is not possible to stablish a clear relation of causality between the administration of the vaccine booster for SARS-CoV-2 and the diseases developed by the patient, the association of two concomitant autoimmune processes is remarkable. As well as the positivity for the auto-antibodies anti-SSA/Ro60, which have been described in the bibliography in cases of SARS-CoV-2 infection.

TITLE: Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso.Introducción. La vacunación masiva contra el virus SARS-CoV-2 constituye una de las principales estrategias en la reducción de la morbimortalidad que presenta dicho virus. No obstante, a lo largo de los últimos meses, su administración también se ha relacionado con diversos efectos adversos raros, pero potencialmente graves. Caso clínico. En el presente artículo describimos el caso de un paciente que desarrolló un síndrome de Guillain-Barré y una púrpura trombocitopénica idiopática nueve días después de la vacunación con la tercera dosis contra el virus SARS-CoV-2 (Moderna), con dos dosis previas de AstraZeneca. Adicionalmente, destaca la presencia de positividad para autoanticuerpos anti-SSA/Ro60 y para anticuerpos inmunoglobulina G anti-GM1 e inmunoglobulina G anti-GM3. Conclusión. Aunque no es posible establecer una relación de causalidad entre la administración del booster de la vacuna y el desarrollo de la enfermedad, es destacable la asociación de dos procesos autoinmunes concomitantes, junto con la positividad en los autoanticuerpos anti-SSA/Ro60, lo cual se ha descrito en la bibliografía en casos de infección del virus SARS-CoV-2.

Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso / Guillain-Barré syndrome and thrombocytopenia after SARS-CoV-2 vaccination with Moderna. A case report

Introducción: La vacunación masiva contra el virus SARS-CoV-2 constituye una de las principales estrategias en la reducción de la morbimortalidad que presenta dicho virus. No obstante, a lo largo de los últimos meses, su administración también se ha relacionado con diversos efectos adversos raros, pero potencialmente graves. Caso clínico: En el presente artículo describimos el caso de un paciente que desarrolló un síndrome de Guillain-Barré y una púrpura trombocitopénica idiopática nueve días después de la vacunación con la tercera dosis contra el virus SARS-CoV-2 (Moderna), con dos dosis previas de AstraZeneca. Adicionalmente, destaca la presencia de positividad para autoanticuerpos anti-SSA/Ro60 y para anticuerpos inmunoglobulina G anti-GM1 e inmunoglobulina G anti-GM3. Conclusión: Aunque no es posible establecer una relación de causalidad entre la administración del booster de la vacuna y el desarrollo de la enfermedad, es destacable la asociación de dos procesos autoinmunes concomitantes, junto con la positividad en los autoanticuerpos anti-SSA/Ro60, lo cual se ha descrito en la bibliografía en casos de infección del virus SARS-CoV-2.(AU)

Introduction: The massive vaccination against the SARS-CoV-2 virus has demonstrated to be one of the major measures for the reduction of the morbidity and mortality that this virus causes. However, during the last months the administration of the vaccine has been also associated with some rare, but life-threatening, adverse effects. Case report: In this article we describe the case of a patient that developed a Guillain-Barré syndrome and an Idiopathic thrombocytopenic purpura nine days after the vaccination with the third dose for the SARS-CoV-2 virus (Moderna). He had received previously two doses of the AstraZeneca vaccine. Moreover, the patient was positive for auto-antibodies anti-SSA/Ro60 and auto-antibodies IgG anti-GM1 and IgG anti-GM3. Discussion: Even though it is not possible to stablish a clear relation of causality between the administration of the vaccine booster for SARS-CoV-2 and the diseases developed by the patient, the association of two concomitant autoimmune processes is remarkable. As well as the positivity for the auto-antibodies anti-SSA/Ro60, which have been described in the bibliography in cases of SARS-CoV-2 infection.(AU)

Viability and characterization trial of a novel method as an alternative to formaldehyde and Walter-Thiel cadaveric preservation for medical education and surgical simulation / Viabilidad y prueba de caracterización de un nuevo método como alternativa al formaldehído y la solución de Walther-Thiel para la preservación de cadáveres para educación médica y simulación quirúrgica

Introduction Despite its toxic and carcinogenic nature, formaldehyde is a widely used reactant for specimen preservation. With the need of specimens for both anatomical and surgical training, alternative preservation solutions (PS) have been proposed, however, their use is limited due to high costs and complexity. Hence, a new formaldehyde-free solution (FFS) is evaluated as a potential alternative for anatomical and surgical training. Methods Qualitative and Quantitative data were acquired. Specimens preserved using three different methods were selected. Flexibility was measured by joints goniometry and pneumoperitoneum pressures were evaluated followed by an exploratory laparoscopy. Undergraduate student's perceptions on cadavers preserved with different PS were obtained using surveys and focus groups. Results The main reason why cadaveric specimens were considered as useful tools was the perceived interaction with real tissues and the ‘practical’ concept of getting in touch with what students would be facing in the future as physicians, what we call “hands on” activities. FFS treated specimens showed better joint-movement ranges in comparison to other methods and pneumoperitoneum was acquired after 5mmHg CO2 pressure. Students appreciated working with corpses regardless the technique used, however FFS specimens were defined as less uncomfortable, while presenting no sensory discomfort. Conclusions Even though alternative PS are effective, high costs and complexity restrict their usage. Cadavers preserved with FFS had similar range of movements compared with Thiel. Students preferred to work with FFS rather than FF due to flexibility, color, and no sensorial hassles. Thus, we propose FFS as viable alternative to traditional PS (AU)

Introducción A pesar de su naturaleza carcinogénica y tóxica, el formaldehido continúa siendo utilizado para preservar especímenes. Debido a la necesidad de especímenes para entrenamiento anatómico y quirúrgico, se han propuesto soluciones preservadoras (SP) alternativas; sin embargo, su uso es limitado debido a los altos costos y a su complejidad. En consecuencia, se evalúa una nueva solución libre de formol (FFS) como una alternativa para el uso en entrenamiento anatómico y quirúrgico. Métodos Se obtuvieron datos cualitativos y cuantitativos. Se seleccionaron especímenes preservados utilizando diferentes métodos y se analizaron biopsias de cada uno. Se midió la flexibilidad mediante goniometría, y se evaluó la presión del neumoperitoneo. Utilizando encuestas y grupos focales se obtuvo la percepción de estudiantes de pregrado respecto a cadáveres preservados con diferentes soluciones. Resultados Los principales motivos por los que los estudiantes refirieron percibir los cadáveres como herramientas útiles fueron poder interactuar con tejidos reales y el concepto de «practicidad» generado por actividades percibidas como similares a la práctica como médicos profesionales. Los especímenes tratados con FFS demostraron mejor movimiento articular en comparación con otras soluciones, además de lograr neumoperitoneo con 5mmHg de CO2. Los estudiantes refirieron sentir menos molestias sensoriales al utilizar cadáveres preservados con FFS. Conclusiones Aunque otras SP son efectivas, los altos costos y la complejidad restringen su uso. Cadáveres preservados con FFS presentan arcos de movimiento similares a Thiel. Los estudiantes prefirieron trabajar con FFS en vez de FF, debido a la flexibilidad, el color y la ausencia de molestias sensoriales. Proponemos FFS como una alternativa viable a las SP tradicionales (AU)

Clinical course of neonatal acute kidney injury: multi-center prospective cohort study.

BACKGROUND: Neonatal acute kidney injury (AKI) has been associated with unfavorable outcomes, including increased mortality. We aimed to describe the clinical course and outcomes during the first 7 days after diagnosis in newborns with AKI in three neonatal intensive care units in Popayán-Colombia. METHODS: Multi-center prospective cohort study conducted between June 2019 and December 2020 in three NICUs after ethical approval. We included newborns between 2 and 28 days of life, first diagnosed with AKI using the KDIGO classification modified for newborns which consider increased serum creatinine values over baseline values as well as urine output over time in hours or both. Patients with chromosomal abnormalities, major kidney malformations, and complex congenital heart disease were excluded. Patients were followed for up to 7 days after diagnosis and the maximum KDIGO stage, recovery of kidney function, need for renal replacement therapy and cumulative incidence of death were evaluated. RESULTS: Over the 18 months of the study, 4132 newborns were admitted to the NICUs, and 93 patients (2.25, 95% CI 1.82-2.75%) developed neonatal AKI. 59.1% of the newborns were premature and there were no differences in severity according to gestational age. During follow-up, the maximum KDIGO was 64.5% for AKI-stage 1, 11.8% for AKI-stage 2, and 23.7% for AKI-stage 3. Kidney function recovery was higher in AKI-stage 1 patients vs. AKI-severe (AKI-stage 2 and 3) (95% vs. 48.5%). Five patients (5.4%) received renal replacement therapy and 15 died (16.1%), four in AKI-stage 1 vs. 11 in AKI-severe (6.7% vs 33.3%). CONCLUSIONS: Newborns admitted to the NICUs can develop AKI regardless of gestational age, and it is more frequent between the second and ninth days of life. More patients whit AKI-stage 1 recover and die less than those in a severe stage.

Querión de Celso, aspectos diagnósticos y terapéuticos: Presentación de un caso / Kerion Celsi, diagnostic and therapeutic aspects: a case report

RESUMEN La tiña capitis es una enfermedad que afecta con mayor frecuencia a la población pediátrica; es ocasionada por hongos dermatofitos y es el querión su forma inflamatoria severa. Su diagnóstico e intervención temprana evita posibles secuelas estéticas y psicológicas en quienes lo padecen. Se presenta caso de paciente masculino de 4 años quien consultó al servicio de dermatología por cuadro de 4 meses de placa eritemato-descamativa con pústulas que progresó a única placa de predominio alopécica y adenopatías cervicales. El reporte microbiológico confirmó su diagnóstico, y el ultrasonido contribuyó al pronóstico y conducta terapéutica.

ABSTRACT Tinea capitis is a disease that most frequently affects the pediatric population caused by dermatophyte fungi, of which kerion is the severe inflammatory form of it. Its early diagnosis and intervention avoids possible aesthetic and psychological consequences in those who suffer from it. The case of a 4-year-old male patient is presented, who attend the dermatology service for 4 months of erythematous-desquamative plaque with pustules that evolved to a single plaque of predominantly alopecia and cervical lymphadenopathy. Microbiological report confirmed its diagnosis, and ultrasound contributed to the prognosis and therapeutic behavior.

Relevant aspects in adult patient with thyroglossal duct cyst: a narrative review

OBJECTIVE: Establish the most relevant aspects in the diagnosis and treatment in adult patients with thyroglossal duct cysts. METHODS: A narrative review was performed, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science and Google Scholar, we have examined emerging evidence on diagnosis and treatment in adult patients with thyroglossal duct cysts. CONCLUSION: Thyroglossal duct cysts are the most frequent neck anomaly, however, a low percentage occurs in young adults, clinical correlation and imaging studies are important to confirm its diagnosis. In addition, surgical resec-tion has a high cure rate, however it is known that there are non-surgical alternatives that can help treat these patients

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Change in the magnetic configurations of tubular nanostructures by tuning dipolar interactions.

We have investigated the equilibrium states of ferromagnetic single wall nanotubes by means of atomistic Monte Carlo simulations of a zig-zag lattice of Heisenberg spins on the surface of a cylinder. The main focus of our study is to determine how the competition between short-range exchange (J) and long-range dipolar (D) interactions influences the low temperature magnetic order of the nanotubes as well as the thermal-driven transitions involved. Apart from the uniform and vortex states occurring for dominant J or D, we find that helical states become stable for a range of intermediate values of γ = D/J that depends on the radius and length of the nanotube. Introducing a vorticity order parameter to better characterize helical and vortex states, we find the pseudo-critical temperatures for the transitions between these states and we establish the magnetic phase diagrams of their stability regions as a function of the nanotube aspect ratio. Comparison of the energy of the states obtained by simulation with those of simpler theoretical structures that interpolate continuously between them, reveals a high degree of metastability of the helical structures that might be relevant for their reversal modes.

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age.

A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type 6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age, including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and women 16-26 years of age, showed that the 9vHPV vaccine was generally well tolerated. Additional safety analyses were conducted to include the results of new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine recipients from 1 randomized controlled trial) was evaluated. Vaccine was administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse events (AEs) were monitored. The most common AEs were injection-site events (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively), the majority of which were mild. Discontinuations due to an AE were rare (0.2% and 0.0% among prior qHPV vaccine recipients and young men, respectively). In young men, the AE profile of the 9vHPV vaccine was generally similar to that of the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients and in young men, with an AE profile generally consistent with that previously reported with the broader clinical program.

PARKIN overexpression in human mesenchymal stromal cells from Wharton's jelly suppresses 6-hydroxydopamine-induced apoptosis: Potential therapeutic strategy in Parkinson's disease.

BACKGROUND AIMS: Stem cell transplantation is an excellent option for regenerative or replacement therapy. However, deleterious microenvironmental and endogenous factors (e.g., oxidative stress) compromise ongoing graft survival and longevity. Therefore, (transient or stable) genetically modified cells may be reasonably thought to resist oxidative stress-induced damage. Genetic engineering of mesenchymal stromal cells (MSCs) obtained from Wharton's jelly tissue may offer some therapeutic potential. PARKIN is a multifunctional ubiquitin ligase able to protect dopaminergic cells against stress-related signaling. We, therefore, evaluated the effect of the neurotoxicant 6-hydroxydopamine (6-OHDA) on regulated cell death signaling in MSCs and investigated whether overexpression of PARKIN in MSCs was capable of modulating the effect of 6-OHDA. METHODS: We transiently transfected Wharton's jelly-derived MSCs with an mCherry-PARKIN vector using the Lipofectamine LTX method. Naïve MSCs and MSCs overexpressing PARKIN were exposed to increasing concentrations of 6-OHDA. We used light and fluorescence microscopy, flow cytometry, immunocytochemistry staining, in-cell Western and Western blot analysis. RESULTS: After 12-24 h of 6-OHDA exposure, we detected dichlorofluorescein (DCF)-positive cells (80%) indicative of reactive oxygen species (H2O2) production, reduced cell viability (40-50%), decreased mitochondrial membrane potential (ΔΨm, ~35-45%), DNA fragmentation (18-30%), and G1-arrested cell cycle in the MSCs. 6-OHDA exposure increased the expression of the transcription factor c-JUN, increased the expression of the mitochondria maintenance Phosphatase and tensin homologue-induced putative kinase 1 (PINK1) protein and increased the expression of pro-apoptotic PUMA, caspase-3 and apoptosis-inducing factor (AIF). 6-OHDA exposure also significantly augmented the oxidation of the oxidative stress sensor, DJ-1. Overexpression of PARKIN in MSCs not only significantly reduced the expression of cell death and oxidative stress markers but also significantly reduced DCF-positive cells (~50% reduction). DISCUSSION: 6-OHDA induced apoptosis in MSCs via generation of H2O2, activation of c-JUN and PUMA, mitochondrial depolarization and nuclei fragmentation. Our findings suggest that PARKIN protects MSCs against 6-OHDA toxicity by partly interacting with H2O2, reducing the expression of c-JUN, PUMA, AIF and caspase-3, and maintaining the mitochondrial ΔΨm.

Skewed Invariant Natural Killer T (iNKT) Cells, Impaired iNKT:B Cell Help and Decreased SAP Expression in Blood Lymphocytes from Patients with Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+. These findings were associated with an enrichment of memory-like and a tendency towards a reduction in TNF-α-expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer-pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co-cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.

Ex vivo trypanocidal activity of 1-(2-hydroxybenzylidene)thiosemicarbazide against Trypanosoma equiperdum.

Trypanosoma equiperdum is the causative agent of dourine, a venereal disease in horses and donkeys. This parasite has a widely distribution, is found in Africa, Asia, Southern and Eastern Europe, Russia, Mexico and Venezuela. The T. equiperdum is morphologically indistinguishable to other Trypanozoon species, however differs from other mammalian trypanosomes due to the fact that it is primarily a tissue parasite, generating cutaneous plaques, swelling of genitalia and neurological signs. The aim of this study was to evaluate the trypanocidal effectiveness of a set of derivatives of thiosemicarbazones on a T. equiperdum ex vivo culture. All compounds appeared to have trypanocidal activity, however one of them shown better solubility and a dose-dependent effect. The median inhibitory concentration (IC50) was 1.2µM. The selected compound exhibits a greater inhibitory activity than diminazene aceturate, a common drug for animal trypanosomosis treatment.