Transient dynamics and rhythm coordination of inferior olive spatio-temporal patterns

This Document is protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.The inferior olive (IO) is a neural network belonging to the olivo-cerebellar system whose neurons are coupled with electrical synapses and display subthreshold oscillations and spiking activity. The IO is frequently proposed as the generator of timing signals to the cerebellum. Electrophysiological and imaging recordings show that the IO network generates complex spatio-temporal patterns. The generation and modulation of coherent spiking activity in the IO is one key issue in cerebellar research. In this work, we build a large scale IO network model of electrically coupled conductance-based neurons to study the emerging spatio-temporal patterns of its transient neuronal activity. Our modeling reproduces and helps to understand important phenomena observed in IO in vitro and in vivo experiments, and draws new predictions regarding the computational properties of this network and the associated cerebellar circuits. The main factors studied governing the collective dynamics of the IO network were: the degree of electrical coupling, the extent of the electrotonic connections, the presence of stimuli or regions with different excitability levels and the modulatory effect of an inhibitory loop (IL). The spatio-temporal patterns were analyzed using a discrete wavelet transform to provide a quantitative characterization. Our results show that the electrotonic coupling produces quasi-synchronized subthreshold oscillations over a wide dynamical range. The synchronized oscillatory activity plays the role of a timer for a coordinated representation of spiking rhythms with different frequencies. The encoding and coexistence of several coordinated rhythms is related to the different clusterization and coherence of transient spatio-temporal patterns in the network, where the spiking activity is commensurate with the quasi-synchronized subthreshold oscillations. In the presence of stimuli, different rhythms are encoded in the spiking activity of the IO neurons that nevertheless remains constrained to a commensurate value of the subthreshold frequency. The stimuli induced spatio-temporal patterns can reverberate for long periods, which contributes to the computational properties of the IO. We also show that the presence of regions with different excitability levels creates sinks and sources of coordinated activity which shape the propagation of spike wave fronts. These results can be generalized beyond IO studies, as the control of wave pattern propagation is a highly relevant problem in the context of normal and pathological states in neural systems (e.g., related to tremor, migraine, epilepsy) where the study of the modulation of activity sinks and sources can have a potential large impact.Roberto Latorre, Carlos Aguirre, and Pablo Varona were supported by MINECOTIN 2012-30883 and MikhailI. Rabinovich by ONRGrantN00014310205

Effectiveness of Smartphone Devices in Promoting Physical Activity and Exercise in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review.

No procedeThe objectives of this systematic review were to analyse existing evidence on the efficacy of smartphone devices in promoting physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) and to identify the validity and precision of their measurements. A systematic review was undertaken across nine electronic databases: WOS Core Collection, PubMed, CINAHL, AMED, Academic Search Complete, Cochrane Central Register of Controlled Trials, SciELO, LILACS and ScienceDirect. Randomized and non-randomized controlled clinical trials were identified. To obtain additional eligible articles, the reference lists of the selected studies were also checked. Eligibility criteria and risk of bias were assessed by two independent authors. A total of eight articles met eligibility criteria. The studies were focused on promoting PA (n = 5) and the precision of device measurements (n = 3). The effectiveness of smartphones in increasing PA level (steps/day) at short and long term is very limited. Mobile-based exercise programs reported improvements in exercise capacity (i.e. incremental Shuttle-Walk-Test) at short and long term (18.3% and 21%, respectively). The precision of device measurements was good-to-excellent (r = 0.69-0.99); however, these data should be interpreted with caution due to methodological limitations of studies. The effectiveness of smartphone devices in promoting PA levels in patients with COPD is scarce. Further high-quality studies are needed to evaluate the effectiveness of smartphone devices in promoting PA levels. Registration number: CRD42016050048.NoActividad Física y DeporteTerapia y Rehabilitació

Biological Control of the Chagas Disease Vector Triatoma infestans with the Entomopathogenic Fungus Beauveria bassiana Combined with an Aggregation Cue: Field, Laboratory and Mathematical Modeling Assessment

Background: Current Chagas disease vector control strategies, based on chemical insecticide spraying, are growingly threatened by the emergence of pyrethroid-resistant Triatoma infestans populations in the Gran Chaco region of South America. Methodology and findings: We have already shown that the entomopathogenic fungus Beauveria bassiana has the ability to breach the insect cuticle and is effective both against pyrethroid-susceptible and pyrethroid-resistant T. infestans, in laboratory as well as field assays. It is also known that T. infestans cuticle lipids play a major role as contact aggregation pheromones. We estimated the effectiveness of pheromonebased infection boxes containing B. bassiana spores to kill indoor bugs, and its effect on the vector population dynamics. Laboratory assays were performed to estimate the effect of fungal infection on female reproductive parameters. The effect of insect exuviae as an aggregation signal in the performance of the infection boxes was estimated both in the laboratory and in the field. We developed a stage-specific matrix model of T. infestans to describe the fungal infection effects on insect population dynamics, and to analyze the performance of the biopesticide device in vector biological control. Conclusions: The pheromone-containing infective box is a promising new tool against indoor populations of this Chagas disease vector, with the number of boxes per house being the main driver of the reduction of the total domestic bug population. This ecologically safe approach is the first proven alternative to chemical insecticides in the control of T. infestans. The advantageous reduction in vector population by delayedaction fungal biopesticides in a contained environment is here shown supported by mathematical modeling.Fil: Forlani, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Pedrini, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Girotti, Juan Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Mijailovsky, Sergio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Cardozo, Rubén Marino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Provincia de Salta. Ministerio de Salud Pública. Coordinación de Gestión Epidemiológica; ArgentinaFil: Gentile, Alberto G.. Provincia de Salta. Ministerio de Salud Pública. Coordinación de Gestión Epidemiológica; ArgentinaFil: Hernández Suárez, Carlos. Universidad de Colima. Facultad de Ciencias; MéxicoFil: Rabinovich, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Juarez, Marta Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; Argentin

Role of accelerated aging in limb muscle wasting of patients with COPD

Purpose: Skeletal muscle wasting is an independent predictor of health-related quality of life and survival in patients with COPD, but the complexity of molecular mechanisms associated with this process has not been fully elucidated. We aimed to determine whether an impaired ability to repair DNA damage contributes to muscle wasting and the accelerated aging phenotype in patients with COPD. Patients and methods: The levels of phosphorylated H2AX (γH2AX), a molecule that promotes DNA repair, were assessed in vastus lateralis biopsies from 10 COPD patients with low fat-free mass index (FFMI; COPDL), 10 with preserved FFMI and 10 age- and gender-matched healthy controls. A panel of selected markers for cellular aging processes (CDKN2A/p16ink4a, SIRT1, SIRT6, and telomere length) were also assessed. Markers of oxidative stress and cell damage and a panel of pro-inflammatory and anti-inflammatory cytokines were evaluated. Markers of muscle regeneration and apoptosis were also measured. Results: We observed a decrease in γH2AX expression in COPDL, which occurred in association with a tendency to increase in CDKN2A/p16ink4a, and a significant decrease in SIRT1 and SIRT6 protein levels. Cellular damage and muscle inflammatory markers were also increased in COPDL. Conclusion: These data are in keeping with an accelerated aging phenotype as a result of impaired DNA repair and dysregulation of cellular homeostasis in the muscle of COPDL. These data indicate cellular degeneration via stress-induced premature senescence and associated inflammatory responses abetted by the senescence-associated secretory phenotype and reflect an increased expression of markers of oxidative stress and inflammation

High frequency of Nichols-like strains and increased levels of macrolide resistance in Treponema pallidum in clinical samples from Buenos Aires, Argentina

Globally, 94% of Treponema pallidum subsp. pallidum (TPA) clinical strains belong to the SS14-like group and 6% to the Nichols-like group, with a prevalence of macrolide resistance of 90%. Our goal was to determine whether local TPA strain distribution and macrolide resistance frequency have changed significantly since our last report, which revealed that Buenos Aires had a high frequency of Nichols-like strains (27%) and low levels of macrolide resistance (14%). Swab samples from patients with suspected syphilis were collected during 2015–2019 and loci TP0136, TP0548, TP0705 were sequenced in order to perform multilocus sequence typing. Strains were classified as Nichols-like or SS14-like. The presence of macrolide resistance-associated mutations was determined by examination of the 23S rDNA gene sequence. Of 46 typeable samples, 37% were classified as Nichols-like and 63% as SS14-like. Macrolide resistance prevalence was 45.7%. Seven allelic profiles were found, five were SS14-like and two were Nichols-like. The frequency of Nichols-like strains increased between studies (26.8% vs. 37%, p = 0.36). A dramatic increase was found in the frequency of macrolide resistant strains between studies (14.3% vs. 45.7%, p = 0.005). Our results are in agreement with international trends and underscore the need to pursue further TPA molecular typing studies in South America.Fil: Morando, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Vrbová, Elika. Masaryk University; República ChecaFil: Melgar, Asunta. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rabinovich, Roberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Smajs, David. Masaryk University; República ChecaFil: Pando, María de los Ángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Exploring the perceptions of Patients with Chronic Respiratory Diseases and their insights into Pulmonary Rehabilitation in Bangladesh

Background: Chronic respiratory diseases (CRDs) require holistic management reflecting patient preferences, appropriate pharmacotherapy, pulmonary rehabilitation, and integrated care. We aimed to understand the perceptions of people with CRDs about their condition and pulmonary rehabilitation in Bangladesh.Methods: We conducted semi-structured interviews with a maximum variation sample of people with CRD who had participated in a feasibility study of pulmonary rehabilitation in 2021/ 2022. Interviews were transcribed verbatim, analysed in Bengali using a grounded theory approach and interpreted by a multidisciplinary team.Results: We interviewed 15 participants with COPD, asthma, or post-tuberculosis. Analysis revealed three themes. 1) Understanding CRD: patients characterised their condition by the symptoms (e.g., ‘Hapani’ meaning ‘breathlessness’) rather than describing a disease entity. Some identified occupation, previous infection or family history that they believed was the cause. 2) Perceptions of pulmonary rehabilitation: Exercise was counterintuitive as it exacerbated the breathlessness symptom that defined their disease. Views varied, though many acknowledged the benefits after a few sessions. Even with home-based programmes, participants described practical barriers to finding time for the sessions and adopted strategies to overcome the challenges. 3) Implementation: Participants highlighted the need for raising awareness of CRD and the potential of pulmonary rehabilitation in the community, adapting to the local context, and establishing an accessible resourced service. Conclusion: Understanding how patients and their communities perceive their condition and the barriers (both conceptual and logistical) to acceptance is the first step to embedding this highly effective intervention into routine healthcare services in Bangladesh with potential benefits for the increasing number of people living with CRDs in LMICs.<br/

Presence of IgG anti-gp160/120 antibodies confers higher HIV capture capacity to erythrocytes from HIV-positive individuals

Background: HIV binding has been demonstrated in erythrocytes from HIV-positive and HIV-negative individuals. However, the presence of immunoglobulins G anti-HIV (IgG anti-HIV) in erythrocytes from HIV-positive individuals is still to be elucidated. Moreover, the capacity of erythrocytes from HIV-positive individuals to capture an additional amount of HIV has not been studied. Indeed, it is unknown if HIV binding to erythrocytes in HIV-positive persons could have consequences on the cell-free infectious virus available. Methodology/Principal Findings: IgGs anti-HIV associated to erythrocytes were found in 77.3% (58/75) of the HIV-positive individuals studied and the IgGs anti-gp160 and anti-p24 were the most frequently found. We found a positive association between detectable plasma viral load (pVL) and presence of IgGs anti-HIV associated to erythrocyte (p<0.005), though the anti-p24/160 were present with or without detectable pVL. The HIV capture capacity was higher in erythrocytes from HIV-positive than HIV-negative individuals (p<0.0001). Furthermore, among the HIV-positive individuals the higher viral capture capacity was associated with the presence of anti-gp160/gp120 on erythrocytes. Moreover, the viral capture by erythrocytes was independent of pVL (rho = 0.022, p = 0.8817). Additionally, reduction of cell-free infectious virus and available viral load was observed in the presence of erythrocytes from HIV-positive individuals. Conclusions/Significance: Results suggest that in HIV-positive individuals, erythrocytes are capable of capturing high amounts of HIV by the presence of IgGs anti-gp160/120 on their membranes and this may produce a reduction in the available free virus. Finally, the current measurement of pVL would underestimate the real viral quantity due to the HIV binding through specific antibodies to erythrocytes.Fil: Garcia, Maria Noe. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dos Ramos Farías, María Sol. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fazzi, Lucia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grasso, Daniel Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rabinovich, Roberto Daniel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Avila, Maria Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin