Historias misioneras. Una experiencia interdisciplinaria desde Cerro Corá (Misiones, Argentina)

This work shows the results of the outreach project called "Telling the story of a town: Cerro Corá. Contributions for the strengthening of the community’s cultural identity and territorial development II (2nd part) ". The project originated in a demand from the people in the town themselves, who wished to rescue and record the experiences and the social memory of the town’s inhabitants. There emerged a problem based on disputes over the definition and the character of the town's identity. A methodological proposal consisting of four axes was developed: work with archives, collection of oral narratives, the realization of a documentary film and community workshops in schools.Este trabajo muestra los resultados del proyecto de extensión “Contando la historia de un pueblo: Cerro Corá. Aportes para el fortalecimiento de la identidad cultural y el desarrollo territorial de la comunidad II (2da parte)”.El proyecto surge a partir de una demanda del pueblo, que deseaba rescatar y registrar las vivencias y la memoria social de sus habitantes. Se puso de manifiesto una problemática fundada en las disputas por la definición y el carácter de la identidad del pueblo.Se desarrolló una propuesta metodológica de cuatros ejes: los trabajos de archivos, el relevamiento de relatos orales, la realización de un documental y talleres comunitarios en las escuelas.

Autocrine CSF-1R activation promotes Src-dependent disruption of mammary epithelial architecture

Elevated coexpression of colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, correlates with invasiveness and poor prognosis of a variety of epithelial tumors (Kacinski, B.M. 1995. Ann. Med. 27:79–85). Apart from recruitment of macrophages to the tumor site, the mechanisms by which CSF-1 may potentiate invasion are poorly understood. We show that autocrine CSF-1R activation induces hyperproliferation and a profound, progressive disruption of junctional integrity in acinar structures formed by human mammary epithelial cells in three-dimensional culture. Acini coexpressing receptor and ligand exhibit a dramatic relocalization of E-cadherin from the plasma membrane to punctate intracellular vesicles, accompanied by its loss from the Triton-insoluble fraction. Interfering with Src kinase activity, either by pharmacological inhibition or mutation of the Y561 docking site on CSF-1R, prevents E-cadherin translocation, suggesting that CSF-1R disrupts cell adhesion by uncoupling adherens junction complexes from the cytoskeleton and promoting cadherin internalization through a Src-dependent mechanism. These findings provide a mechanistic basis whereby CSF-1R could contribute to invasive progression in epithelial cancers

Descubriendo historias misioneras: el caso de Cerro Corá

En este artículo se propone mostrar los resultados del proyecto de extensión “Contando la historia de un pueblo: Cerro Corá. Aportes para el fortalecimiento de la identidad cultural y el desarrollo territorial de la comunidad II (2da parte)” (Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales. PROFAE, 2017). El mismo surge a partir de una demanda del pueblo de Cerro Corá que -con motivos de celebrar el aniversario 120° de su fundación- tenía intenciones de rescatar y registrar las vivencias y la memoria social de los habitantes del lugar. En el transcurso de la primera etapa de trabajo se puso de manifiesto una problemática central fundada en las disputas por la definición y el carácter de la identidad del pueblo. A posteriori, se definió como estrategia a seguir, ampliar y mejorar los canales de socialización de lo ya producido en la primera parte (libro en prensa y audiovisual) favoreciendo espacios de auto reflexión de la comunidad y capitalizando esos resultados. En ese marco, se desarrollaron talleres comunitarios en el pueblo, destinado a estudiantes y docente del nivel secundario, cuyos principales temas fueron patrimonio, identidad, historia y turismo.Fil: Wrobel, Claudia Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Ocampo, Amanda Eva. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Ríos, Rosmary. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales; Argentin

Validation of the Patient Health Questionnaire‐4 for longitudinal mental health evaluation in elite Para athletes

Background Despite the increasing amount of research regarding mental health in elite athletes in recent years, athletes with impairments are hardly represented. Due to this lack of data and the significant need of athlete-specific mental health screening tools, a continuous mental health monitoring program for elite Para athletes was implemented. Objective Validation of the Patient Health Questionnaire-4 (PHQ-4) as a suitable tool for continuous mental health evaluation in elite Para athletes. Design A 43-week prospective observational cohort study. Setting Online questionnaire, provided weekly via web browser and mobile app. Participants Seventy-eight Para athletes preparing for Paralympic Summer and Winter Games. Interventions Not applicable. Main Outcome Measures Weekly PHQ-4 scores, stress level, and mood. Results With a mean weekly response rate of 82.7% (SD = 8.0), 2149 PHQ-4, 2159 stress level and 2153 mood assessments were completed. Mean PHQ-4 score among all participating athletes was 1.2 (SD = 1.8; 95% confidence interval [CI], [1.1–1.3]). Individual weekly scores ranged from 0 to 12 and showed significant floor effects, with 54% of the scores being zero. PHQ-4 scores were significantly higher among female athletes and team sport members (p < .001). Internal consistency of the PHQ-4 was satisfying, Cronbach's α being 0.839. There were significant cross-sectional as well as longitudinal correlations of PHQ-4 and stress level as well as mood values (p < .001). 39.7% of all athletes (n = 31) had at least one positive screen for mental health symptoms. Conclusions The PHQ-4 was shown to be a valid tool for mental health surveillance in elite Para athletes. Significant correlations of the PHQ-4 and stress level as well as mood were shown. High weekly response rates among participating athletes indicated good acceptance of the program. The weekly monitoring allowed for the identification of individual fluctuations and could identify potential athletes at risk for mental health problems when combined with clinical follow-up

Mental Health in German Paralympic Athletes During the 1st Year of the COVID-19 Pandemic Compared to a General Population Sample

Introduction: The COVID-19 pandemic has huge influences on daily life and is not only associated with physical but also with major psychological impacts. Mental health problems and disorders are frequently present in elite paralympic athletes. Due to the pandemic situation, new stressors (e.g., loss of routine, financial insecurity) might act upon the athletes. Therefore, the assessment of mental health in athletes during the COVID-19 pandemic is important to identify prevalence of psychological problems and propose countermeasures. Methods: The mental health of German paralympic athletes was longitudinally monitored (starting in May 2019). The athletes completed the Patient Health Questionnaire 4 (PHQ-4) on a weekly basis and reported a stress level, training hours, and training load. During the pandemic, 8 measurement time points (March 2020 to April 2021) were used to reflect the psychological health course of the athletes. In parallel, a convenience sample of the general population was questioned about their psychological distress, including the PHQ-4. To be included in the analysis, participants of both groups had to complete at least 4 measurement time points. Matching of the para-athletes and the general population sample was prioritized upon completion of the same measurement time points, gender, and age. Results: Seventy-eight paralympic athletes (40 women, 38 men, age: 29.8 ± 11.4 years) met the inclusion criteria. Seventy-eight matched pairs of the general population (40 women; 38 men; age: 30.5 ± 10.9 years) were identified. The para-athletes had a significantly (p < 0.0001; 0.39 < r < 0.48) lower PHQ-4 value at each measurement time point compared to the matched control group. No significant age or sex differences were evident regarding the symptom burden. In para-athletes, no significant and a weak positive correlation was found between decreased training load and PHQ-4 values and Mental Health in Para-Athletes During COVID-19 a stress level, respectively. Reduced physical activity was significantly (p < 0.0001) associated with higher PHQ-4 values in the general population sample. Discussion: Lower PHQ-4 values were reported by the para-athletes compared to the general population sample. However, small sample sizes must be considered while interpreting the data. Nevertheless, adequate support for individuals suffering from severe psychopathological symptoms should be provided for para-athletes as well as for the general population

In Vitro Analyses of Novel HCN4 Gene Mutations

Background/Aims: The hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 contributes significantly to the generation of basic cardiac electrical activity in the sinus node and is a mediator of modulation by β–adrenergic stimulation. Heterologous expression of sick sinus syndrome (SSS) and bradycardia associated mutations within the human HCN4 gene results in altered channel function. The main aim was to describe the functional characterization of three (two novel and one known) missense mutations of HCN4 identified in families with SSS. Methods: Here, the two-electrode voltage clamp technique on Xenopus laevis oocytes and confocal imaging on transfected COS7 cells respectively, were used to analyze the functional effects of three HCN4 mutations; R378C, R550H, and E1193Q. Membrane surface expressions of wild type and the mutant channels were assessed by confocal microscopy, chemiluminescence assay, and Western blot in COS7 and HeLa cells. Results: The homomeric mutant channels R550H and E1193Q showed loss of function through increased rates of deactivation and distinctly reduced surface expression in all three homomeric mutant channels. HCN4 channels containing R550H and E1193Q mutant subunits only showed minor effects on the voltage dependence and rates of activation/deactivation. In contrast, homomeric R378C exerted a left-shifted activation curve and slowed activation kinetics. These effects were reduced in heteromeric co-expression of R378C with wild-type (WT) channels. Conclusion: Dysfunction of homomeric/heteromeric mutant HCN4-R378C, R550H, and E1193Q channels in the present study was primarily caused by loss of function due to decreased channel surface expression

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Viral coinfections in hospitalized coronavirus disease 2019 patients recruited to the international severe acute respiratory and emerging infections consortium WHO clinical characterisation protocol UK study

Background We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed on upper respiratory tract samples from 1002 patients with COVID-19, aged <1 year to 102 years old, recruited to the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK study. Comprehensive demographic, clinical, and outcome data were collected prospectively up to 28 days post discharge. Results A coinfecting virus was detected in 20 (2.0%) participants. Multivariable analysis revealed no significant risk factors for coinfection, although this may be due to rarity of coinfection. Likewise, ordinal logistic regression analysis did not demonstrate a significant association between coinfection and increased disease severity. Conclusions Viral coinfection was rare among hospitalized COVID-19 patients in the United Kingdom during the first 18 months of the pandemic. With unbiased prospective sampling, we found no evidence of an association between viral coinfection and disease severity. Public health interventions disrupted normal seasonal transmission of respiratory viruses; relaxation of these measures mean it will be important to monitor the prevalence and impact of respiratory viral coinfections going forward