Burden of Parkinsonism and Parkinson\u27s Disease on Health Service Use and Outcomes in Latin America

\ua9 2023 - The authors. Published by IOS Press.Background: Little is known about the burden of parkinsonism and Parkinson\u27s disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. Objective: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. Methods: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. Results: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. Conclusions: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services

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 antileishmanial 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 antileishmanial agents

Fanconi anemia cells with unrepaired DNA damage activate components of the checkpoint recovery process

International audienceBACKGROUND:The FA/BRCA pathway repairs DNA interstrand crosslinks. Mutations in this pathway cause Fanconi anemia (FA), a chromosome instability syndrome with bone marrow failure and cancer predisposition. Upon DNA damage, normal and FA cells inhibit the cell cycle progression, until the G2/M checkpoint is turned off by the checkpoint recovery, which becomes activated when the DNA damage has been repaired. Interestingly, highly damaged FA cells seem to override the G2/M checkpoint. In this study we explored with a Boolean network model and key experiments whether checkpoint recovery activation occurs in FA cells with extensive unrepaired DNA damage.METHODS:We performed synchronous/asynchronous simulations of the FA/BRCA pathway Boolean network model. FA-A and normal lymphoblastoid cell lines were used to study checkpoint and checkpoint recovery activation after DNA damage induction. The experimental approach included flow cytometry cell cycle analysis, cell division tracking, chromosome aberration analysis and gene expression analysis through qRT-PCR and western blot.RESULTS:Computational simulations suggested that in FA mutants checkpoint recovery activity inhibits the checkpoint components despite unrepaired DNA damage, a behavior that we did not observed in wild-type simulations. This result implies that FA cells would eventually reenter the cell cycle after a DNA damage induced G2/M checkpoint arrest, but before the damage has been fixed. We observed that FA-A cells activate the G2/M checkpoint and arrest in G2 phase, but eventually reach mitosis and divide with unrepaired DNA damage, thus resolving the initial checkpoint arrest. Based on our model result we look for ectopic activity of checkpoint recovery components. We found that checkpoint recovery components, such as PLK1, are expressed to a similar extent as normal undamaged cells do, even though FA-A cells harbor highly damaged DNA.CONCLUSIONS:Our results show that FA cells, despite extensive DNA damage, do not loss the capacity to express the transcriptional and protein components of checkpoint recovery that might eventually allow their division with unrepaired DNA damage. This might allow cell survival but increases the genomic instability inherent to FA individuals and promotes cancer

The development of a mouse model to explore resistance and susceptibility to early Ascaris suum infection

Ascaris suum and Ascaris lumbricoides exhibit an over-dispersed frequency distribution in their host populations in both the adult and larval stages. The impact of host factors on this observed distribution is still poorly understood and difficult to investigate in the natural host populations. The use of a mouse model has been supported by the observations that the larval migratory pattern, in this host, mimics the pattern observed in the pig. We explored the extrinsic factors that might affect the quantitative recovery of larvae during this migration in order to standardize a model system facilitating accurate future assessment of host genetic variation on this phase of the infection. In Exp. 1 larvae accumulated in the livers of both C57BL/6j and BALB/c mice up to and including days 4–5 p.i. and then declined in both strains until day 9. Loss of larvae from the livers corresponded to arrival in the lungs and maximum accumulation on day 7 p.i. but recovery was considerably higher in C57BL/6j mice. It was concluded that day 7 recoveries gave the best indication of relative resistance/susceptibility to this parasite. In Exp. 2 A/J, BALB/c, CBA/Ca, C57BL/6j, C3H/HeN, DBA/2, NIH, SJL, and SWR mice were compared. C57BL/6j mice were identified as the most susceptible strain and CBA/Ca mice as having the most contrasting phenotype, but with a similar kinetic pattern of migration. Finally, in Exp. 3, a strong positive correlation between the size of the inoculum and the mean worm recovery from the lungs was found in CBA/Ca and C57BL/6j mice, but the difference between these strains was highly consistent, 66.6–80%, regardless of the initial dose. These results demonstrate that, using our protocols for infection and recovery, between-experiment variation in A. suum worm burdens is minimal, and that C57BL/6j mice are highly susceptible to infection compared to other strains. The mechanistic basis of this susceptibility in relation to the resistance of other strains is unknown, but the possibilities are reviewed

Input-Admittance Passivity Compliance for Grid-Connected Converters With an LCL Filter

This work presents a design methodology and its experimental validation for the input-admittance passivity compliance of LCL grid-connected converters. The designs of the LCL filter parameters and discrete controller are addressed systematically, and suitable design guidelines are provided. The controller design is developed in the z-domain, with capacitor voltage based active damping used as degree of freedom to compensate for system delay effects. The role of resistive components in the circuit, which have inherent dissipative properties, is also discussed. As an outcome of the design, a passive input admittance shaping is obtained. The theoretical development is further verified in a low-scale prototype supplied from a controllable grid simulator. For the sake of generality, different combinations of resonant to sampling frequency are tested. Experimental results fully prove the input-admittance passivity compliance

Can domestic dogs be considered a good reservoir of Leishmania (L.) infantum chagasi in an endemic area of nonulcerated cutaneous leishmaniasis in Southern Honduras?

Dogs are considered to be the main domestic reservoir associated with the transmission of Leishmania (L.) infantum chagasi to humans in endemic areas of visceral leishmaniasis in America. However, little is known about the role of canines as a source of infection in endemic areas of nonulcerated cutaneous leishmaniasis (NUCL). Therefore, the objective of the present study was to investigate the role of dogs as a possible reservoir of the parasite in Southern Honduras. Dogs (n = 107) living with individuals affected by NUCL were clinically examined and biological material was collected for parasitological and immunological diagnosis. Most animals showed a healthy appearance and a few presented slight weight loss (64%), alopecia (7%), onychogryphosis (5%) and skin lesions (1%). The overall seroprevalence of Leishmania infection based on the DDP ® quick test and/or in-house ELISA serological test was 41%. The presence of the parasite’s DNA was confirmed in 94% of the dogs; however, the average parasite load in the buffy coat was low at 6.09 parasites/µL, ranging between 0.221 and 50.2. The skin of seropositive dogs examined by histopathology using paraffin sections stained by hematoxylin and immunohistochemistry did not show cutaneous lesions or parasite amastigotes. Based on the absence of parasites in the skin and the low parasite load detected in the buffy coat, it seems that the dog does not represent a good source of infection for the vector in the endemic area of NUCL transmission in Southern Honduras. Other domestic and/or wild animals should be investigated

Perfil de resistencia de Staphylococcus spp aislados de hemocultivos en el Hospital Central del Instituto de Previsión Social

Las infecciones nosocomiales por Staphylococcus spp constituyen uno de los problemas de mayor preocupación en salud pública en todo el mundo. Debido a que existen diferencias según centro hospitalario, paciente, área y tiempo de internación es esencial conocer el perfil de resistencia a los antibióticos más utilizados de las cepas de Staphylococcus involucradas en estas infecciones. El objetivo del presente estudio fue determinar el perfil de resistencia de los aislados de Staphylococcus aureus (Sau) y Estafilococo coagulasa negativo (ECN) de muestras de hemocultivos de pacientes adultos, pediátricos y recién nacidos internados entre el 1 de junio de 2005 al 30 de junio de2006, en varios servicios del Hospital Central del Instituto de Previsión Social (IPS.).Se realizó un análisis retrospectivo de los resultados de antibiograma realizados en el Servicio de Microbiología del IPS. Los antibióticos evaluados fueron oxacilina (OXA),penicilina (PEN), eritromicina (ERY), clindamicina (CLI), ciprofloxacina (CIP), gentamicina (GEN), trimetoprim-sulfametoxazol (TMS), tetraciclina (TET) y vancomicina (VAN). De 5698 hemocultivos realizados en este periodo, 1706 (30%) fueron positivos. De estos, en755 (44%) se aisló Staphylococcus spp; correspondiendo 327 (43,3%) a Sau y 428 (56,7%) a ECN. El perfil de resistencia para Sau y ECN fue respectivamente como sigue: OXA 64% y 87%, PEN 96% y 95%, ERY 48% y 52%, CIP 42% y 40%, GEN 48% y 48% yno presentaron R a VAN. El 58% de los Sau y el 56% de los ECN fueron resistentes a más de 4 antibióticos. La alta frecuencia de resistencia a la meticilina y la poliresistencia hallada en este trabajo deben ser tenidos en cuenta a la hora de indicar esquemas deantibióticos empíricos y para realizar ajustes oportunos de los ya iniciados. No se encontró ninguna cepa resistente a la vancomicina, que es considerada el mejor antimicrobiano disponible para el tratamiento de infecciones por estafilococos resistentesa las penicilinas que no son inhibidas por las penicilinasas

The Bariloche Neutron Physics Group Current Activities

Our group has evolved around a small accelerator-based neutron source (ABNS), the 25 million electron Volt (MeV) linear electron accelerator at the Bariloche Atomic Centre. It is dedicated to applications of neutronic methods to tackle problems of basic sciences and to technological applications. Among these, the determination of total cross section of a material as a function of neutron energy by means of transmission experiments for thermal and sub-thermal neutrons is very sensitive to the geometric arrangement and movement of the atoms, over distances ranging from the 'first-neighbour scale' up to the microstructural level or 'grain scale'. This also allowed to test theoretical models of calculated cross sections and scattering kernels. Interest has moved from pulsed neutron diffraction towards deep inelastic neutron scattering (DINS), a powerful tool for the determination of atomic momentum distribution in condensed matter and for non-destructive mass spectroscopy. In recent years non-intrusive techniques aimed at the scanning of large cargo containers have started to be developed with this ABNS, testing the capacity and limitations to detect special nuclear material and dangerous substances in thick cargo arrangements. More recently, the use of the ever-present “bremsstrahlung” radiation has been recognized as a useful complement to instrumental neutron activation, as it permits to detect other nuclear species through high-energy photon activation. The facility is also used for graduate and undergraduate students experimental work within the frame of Instituto Balseiro Physics and Nuclear Engineering courses of study, and also MSc and PhD theses work.Fil: Mayer, Roberto Edmundo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: D'Amico, N. M. B.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Granada, Jose Rolando. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dawidowski, Javier. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santisteban, Javier Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blostein, Juan Jeronimo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tartaglione, Aureliano. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez Palomino, Luis Alberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marquez Damian, Jose Ignacio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sepúlveda Sosa, C.. Comision Chilena de Energia Nuclear; Chil