How has research on the effectiveness and safety of COVID-19 vaccination been evaluated: a scope review with emphasis on CoronaVac.

Introduction: The control of the COVID-19 epidemic has been focused on the development of vaccines against SARS-CoV-2. All developed vaccines have reported safety and efficacy results in preventing infection and its consequences, although the quality of evidence varies depending on the vaccine considered. Different methodological designs have been used for their evaluation, which can influence our understanding of the effects of these interventions. CoronaVac is an inactivated vaccine, and it has been assessed in various studies, including clinical trials and observational studies. Given these differences, our objective was to explore the published information to answer the question: how has the efficacy/effectiveness and safety of CoronaVac been evaluated in different studies? This is to identify potential gaps and challenges to be addressed in understanding its effect. Methods: A scoping review was carried out following the methodology proposed by the Joanna Briggs Institute, which included studies carried out in humans as of 2020, corresponding to systematic reviews, clinical trials, analytical or descriptive observational studies, in which the effectiveness and/or safety of vaccines for COVID19 were evaluated or described. There were no age restrictions for the study participants. Results: The efficacy/effectiveness and safety of this vaccine was assessed through 113 studies. Nineteen corresponded to experimental studies, 7 of Phase II, 5 of Phase IV, and 4 were clinical trials with random assignment. Although some clinical trials with random assignment have been carried out, these have limitations in terms of feasibility, follow-up times, and with this, the possibility of evaluating safety outcomes that occur with low frequencies. Not all studies have used homogeneous methods of analysis. Both the prevention of infection, and the prevention of outcomes such as hospitalization or death, have been valued through similar outcomes, but some through multivariate analysis of dependencies, and others through analysis that try to infer causally through different control methods of confounding. Conclusion: Published information on the evaluation of the efficacy/effectiveness and safety of the CoronaVac is abundant. However, there are differences in terms of vaccine application schedules, population definition, outcomes evaluated, follow-up times, and safety assessment, as well as non-standardization in the reporting of results, which may hinder the generalizability of the findings. It is important to generate meetings and consensus strategies for the methods and reporting of this type of studies, which will allow to reduce the heterogeneity in their presentation and a better understanding of the effect of these vaccines.

RIPK3 promotes brain region-specific interferon signaling and restriction of tick-borne flavivirus infection.

Innate immune signaling in the central nervous system (CNS) exhibits many remarkable specializations that vary across cell types and CNS regions. In the setting of neuroinvasive flavivirus infection, neurons employ the immunologic kinase receptor-interacting kinase 3 (RIPK3) to promote an antiviral transcriptional program, independently of the traditional function of this enzyme in promoting necroptotic cell death. However, while recent work has established roles for neuronal RIPK3 signaling in controlling mosquito-borne flavivirus infections, including West Nile virus and Zika virus, functions for RIPK3 signaling in the CNS during tick-borne flavivirus infection have not yet been explored. Here, we use a model of Langat virus (LGTV) encephalitis to show that RIPK3 signaling is specifically required in neurons of the cerebellum to control LGTV replication and restrict disease pathogenesis. This effect did not require the necroptotic executioner molecule mixed lineage kinase domain like protein (MLKL), a finding similar to previous observations in models of mosquito-borne flavivirus infection. However, control of LGTV infection required a unique, region-specific dependence on RIPK3 to promote expression of key antiviral interferon-stimulated genes (ISG) in the cerebellum. This RIPK3-mediated potentiation of ISG expression was associated with robust cell-intrinsic restriction of LGTV replication in cerebellar granule cell neurons. These findings further illuminate the complex roles of RIPK3 signaling in the coordination of neuroimmune responses to viral infection, as well as provide new insight into the mechanisms of region-specific innate immune signaling in the CNS.

Flexoelectric Ionic Liquid-Grafted Triblock Copolymers for Energy Harvesting under Flexural Deformation.

The goal of the present article is to develop flexoelectric polyelectrolyte elastomers for energy harvesting based on a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) dimethacrylate (PEG-b-PPG-b-PEG-DMA) triblock grafted with an ionic liquid (IL) such as allylmethylimidazolium bis(trifluoromethane sulfonyl) imide (AMIMTFSI). The IL-grafted triblock copolymer network possesses a balance of reasonably good ionic conductivity and high ion polarization during cantilever bending. Of particular importance is the achievement of high flexoelectric coefficients in some flexoelectric polyelectrolyte elastomer (FPE) compositions reaching 1368 µC/m at ambient temperature during mechanical deformation under intermittent square-wave bending mode. With the addition of a 10 wt % lithium bis(trifluoromethane sulfonyl) imide (LiTFSI) salt, the flexoelectric coefficient further improved to 1737 µC/m, which is the highest among all piezoelectric and flexoelectric materials hitherto reported, and thus it opens a new opportunity for clean energy harvesting from a vibrating natural environment.

Prevalencia y caracterización de las neoplasias malignas en personas viviendo con VIH en Colombia / Prevalence and characterization of cancer in people living with HIV in Colombia

INTRODUCCIÓN: En el síndrome de inmunodeficiencia adquirida las neoplasias han jugado un papel preponderante, y con el advenimiento del tratamiento antirretroviral (TAR), la infección por VIH se ha transformado en una enfermedad crónica, siendo los tumores malignos una causa importante de morbilidad y mortalidad. OBJETIVO: Describir las características demográficas, clínicas y de laboratorio de las personas que viven con VIH (PVVIH) y han sido diagnosticadas con cáncer en Colombia y comparar los grupos de neoplasias definitorias y no definitorias de Sida. MÉTODOS: Revisión multicéntrica retrospectiva, en la que se recolectó y analizó datos relacionados con la infección por VIH y de diagnóstico de cáncer y tipo. Incluyó PVVIH diagnosticadas con neoplasias malignas atendidas en 23 centros de atención de pacientes con VIH en 11 ciudades de Colombia desde 1986 hasta 2018. RESULTADOS: En 23.189 pacientes, se identificaron 650 casos de malignidad (prevalencia de 2,8 % [IC de 95%: 2,6-2,9]). La neoplasia definitoria de Sida (NDS) sigue siendo el tipo de cáncer prevalente (71,1%), las neoplasias malignas más frecuentes fueron sarcoma de Kaposi (n: 330; 50,8%), linfoma no Hodgkin (n: 110; 16,9%), cáncer de piel (n: 48; 7,4%) y linfoma de Hodgkin (n: 25; 3,8%). Los pacientes con NDS tenían más probabilidades de ser HSH y estar en un estadio CDC 3, un recuento de linfocitos T CD4 < 200/μL y una carga viral del VIH ≥ 50 copias/mL al momento del diagnóstico de malignidad. Las personas con neoplasias no definitorias de Sida (NNDS) eran significativamente mayores y tenían más probabilidades de ser fumadores. CONCLUSIONES: Estos hallazgos son relevantes considerando la creciente carga de cáncer en las PVVIH que envejecen y las causas cambiantes de morbilidad y mortalidad. La presentación tardía a la atención del VIH y el retraso en el inicio del TAR son probablemente factores que contribuyen al cambio más lento hacia NNDS en comparación con las regiones de altos ingresos donde hay un acceso más rápido y temprano al TAR. El conocimiento de las tendencias epidemiológicas actuales y el perfil del cáncer en las PVVIH es fundamental para mejorar los esfuerzos de prevención y tratamiento del cáncer en el contexto de la atención integral del VIH.

BACKGROUND: In the acquired immunodeficiency syndrome, neoplasms have played a preponderant role, and with the advent of antiretroviral treatment (ART), HIV has become a chronic disease, with malignant tumors being an important cause of morbidity and mortality. AIM: To describe the demographic, clinical, and laboratory characteristics of people living with HIV (PLHIV) who have been diagnosed with cancer in Colombia and to compare the groups of AIDS-defining (ADC) and non-AIDS-defining neoplasms (NADC). METHODS: Retrospective, multicenter study that included people living with HIV/AIDS (PLHIV) diagnosed with malignancies treated at 23 HIV care centers located in 11 Colombian cities from 1986 to 2018. Data related to HIV infection and cancer diagnosis were collected and analyzed. RESULTS: Among 23,189 patients, 650 malignancy cases were identified (prevalence of 2.8% [95% CI 2.6-2.9]). AIDS-defining neoplasm remains the most prevalent type of cancer (71.1%), The most frequent individual malignancies were Kaposi sarcoma (n: 330; 50.8%), non-Hodgkin lymphoma (n: 110; 16.9%), skin cancer (n: 48; 7.4%), and Hodgkin lymphoma (n: 25; 3.8%). Compared people with NADC, with ADC were more likely to be MSM and have a CDC HIV stage 3, CD4 T cell count < 200/μL, and HIV viral load ≥ 50 copies/mL at the time of malignancy diagnosis. PLHIV and with NADC were significantly older and were more likely to be smokers. CONCLUSIONS: These findings are relevant considering the increasing burden of cancer in the aging PLHIV and the changing causes of morbidity and mortality. Late presentation to HIV care and delayed ART initiation are likely factors contributing to the slower shift toward NADCs compared with high-income regions where access to ART is better. Knowledge of the current epidemiological trends and profile of cancer in PLWHA is critical to improve cancer prevention and treatment efforts in the context of comprehensive HIV care.

Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology.

NURR1 (Nuclear receptor-related 1 protein or NR4A2) is a nuclear protein receptor transcription factor with an essential role in the development, regulation, and maintenance of dopaminergic neurons and mediates the response to stressful stimuli during the perinatal period in mammalian brain development. The dysregulation of NURR1 activity may play a role in various diseases, including the onset and progression of neurodegenerative diseases, and several other pathologies. NURR1 is regulated by multiple mechanisms, among which phosphorylation by kinases or SUMOylation are the best characterized. Both post-translational modifications can regulate the activity of NURR1, affecting its stability and transcriptional activity. Other non-post-translational regulatory mechanisms include changes in its subcellular distribution or interaction with other protein partners by heterodimerization, also affecting its transcription activity. Here, we summarize the currently known regulatory mechanisms of NURR1 and provide a brief overview of its participation in pathological alterations.

Reasons for antiretroviral switching in Colombia: A retrospective cohort study.

INTRODUCTION: Long-term use of antiretroviral therapy (ART) for HIV infection might lead to the necessity of switching regimens. We aimed to analyze the reasons for the ART switch, the time-to-switch of ART, and its associated factors in a Colombian cohort. METHODS: We conducted a retrospective cohort in 20 HIV clinics, including participants ≥18 years old with confirmed HIV infection who underwent an ART switch from January 2017 to December 2019 with at least 6 months of follow-up. A time-to-event analysis and an exploratory Cox model were performed. RESULTS: 796 participants switched ART during the study period. The leading cause of ART switch was drug intolerance (n = 449; 56.4%) with a median time-to-switch of 12.2 months. The longest median time-to-switch was due to regimen simplification (42.4 months). People ≥50 years old (HR = 0.6; 95% CI (0.5-0.7) and CDC stage 3 at diagnosis (HR = 0.8; 95% CI (0.6-0.9) had less hazard for switching ART over time. CONCLUSIONS: In this Colombian cohort, drug intolerance was the main cause of the ART switch, and the time-to-switch is shorter than reports from other countries. In Colombia, it is crucial to apply current recommendations for ART initiation to choose regimens with a better tolerability profile.

Clinical and epidemiological characteristics of mpox: A descriptive cases series in Colombia.

INTRODUCTION: Colombia is the fifth most affected country by the global monkeypox outbreak and the second in LAC after Brazil. We describe the clinical and epidemiological characteristics of 521 patients with mpox in the country. METHODS: We conducted an observational analysis of laboratory-confirmed Mpox cases between June 29 and November 16, 2022. RESULTS: Most cases were young men living with HIV. The clinical evolution was primarily benign, with two deaths reported. We found some differences between women and men regarding their BMI, presence of lymphadenopathies, localization of lesions, and the antecedent of HIV infection. CONCLUSION: Although it seems that the epidemic curve for this outbreak of Mpox is decreasing not only in Colombia but globally, it could remain endemic. Therefore, it is necessary to maintain very close surveillance.

Challenges for Plant Growth Promoting Microorganism Transfer from Science to Industry: A Case Study from Chile.

Research on the plant growth promoting microorganisms (PGPM) is increasing strongly due to the biotechnological potential for the agricultural, forestry, and food industry. The benefits of using PGPM in crop production are well proven; however, their incorporation in agricultural management is still limited. Therefore, we wanted to explore the gaps and challenges for the transfer of biotechnological innovations based on PGPM to the agricultural sector. Our systematic review of the state of the art of PGPM research and knowledge transfer takes Chile as an example. Several transfer limiting aspects are identified and discussed. Our two main conclusions are: neither academia nor industry can meet unfounded expectations during technology transfer, but mutually clarifying their needs, capabilities, and limitations is the starting point for successful collaborations; the generation of a collaborative innovation environment, where academia as well as public and private stakeholders (including the local community) take part, is crucial to enhance the acceptance and integration of PGPM on the way to sustainable agriculture.

Linfoma de células T/natural killer extranodal de tipo nasal enmascarado en una sinusopatia

Introducción: El linfoma de células T citotóxico/natural killer extranodal de tipo nasal es poco frecuente, pero con alta tasa de mortalidad. Las manifestaciones clínicas de la enfermedad pueden simular una infección de senos paranasales. Objetivo: Presentar las manifestaciones clínicas de un paciente de 34 años de edad con diagnóstico de linfoma de células T citotóxico/natural killer extranodal de tipo nasal. Caso clínico: Se presenta un paciente masculino de 34 años de edad con rinorrea verdosa fétida recurrente y obstrucción en fosa nasal derecha. En la evaluación inicial sugiere sinusitis crónica, sin embargo, debido al empeoramiento de las manifestaciones clínicas se realiza una tomografía computarizada que muestra lesiones sugestivas de infiltración neoplásica, una biopsia de la lesión confirma el diagnóstico de linfoma de células T/natural killer extranodal de tipo nasal. Conclusiones: Los linfomas de células T citotóxico/natural killer extranodal de tipo nasal son considerados neoplasias poco frecuentes, caracterizadas por el patrón rápidamente progresivo con afectación ósea; en su etapa inicial presenta manifestaciones clínicas similares a una sinusitis. La tomografía computarizada y la histopatología, son indispensables en el diagnóstico de la enfermedad.

Introduction: Nasal-type extranodal natural killer/cytotoxic T-cell lymphoma is rare but has a high mortality rate. The clinical manifestations of the disease can mimic a paranasal sinus infection. Objective: To present the clinical manifestations of a 34-year-old patient diagnosed with nasal-type extranodal natural killer/cytotoxic T-cell lymphoma. Clinical case: A 34-year-old male patient with recurrent greenish fetid rhinorrhea and obstruction in the right nostril is presented. In the initial evaluation, it suggests chronic sinusitis, however, due to the worsening of the clinical manifestations, a computed tomography is performed that shows lesions suggestive of neoplastic infiltration, a biopsy of the lesion confirms the diagnosis of T-cell lymphoma/extranodal natural killer. Conclusions: Nasal-type extranodal natural killer/cytotoxic T-cell lymphomas are considered rare neoplasms characterized by a rapidly progressive pattern with bone involvement; in its initial stage it presents clinical manifestations similar to sinusitis. Computed tomography and histopathology are essential in the diagnosis of the disease.

RIPK3 promotes brain region-specific interferon signaling and restriction of tick-borne flavivirus infection.

Innate immune signaling in the central nervous system (CNS) exhibits many remarkable specializations that vary across cell types and CNS regions. In the setting of neuroinvasive flavivirus infection, neurons employ the immunologic kinase receptor-interacting kinase 3 (RIPK3) to promote an antiviral transcriptional program, independently of the traditional function of this enzyme in promoting necroptotic cell death. However, while recent work has established roles for neuronal RIPK3 signaling in controlling mosquito-borne flavivirus infections, including West Nile virus and Zika virus, functions for RIPK3 signaling in the CNS during tick-borne flavivirus infection have not yet been explored. Here, we use a model of Langat virus (LGTV) encephalitis to show that RIPK3 signaling is specifically required in neurons of the cerebellum to control LGTV replication and restrict disease pathogenesis. This effect did not require the necroptotic executioner molecule mixed lineage kinase domain like protein (MLKL), a finding similar to previous observations in models of mosquito-borne flavivirus infection. However, control of LGTV infection required a unique, region-specific dependence on RIPK3 to promote expression of key antiviral interferon-stimulated genes (ISG) in the cerebellum. This RIPK3-mediated potentiation of ISG expression was associated with robust cell-intrinsic restriction of LGTV replication in cerebellar granule cell neurons. These findings further illuminate the complex roles of RIPK3 signaling in the coordination of neuroimmune responses to viral infection, as well as provide new insight into the mechanisms of region-specific innate immune signaling in the CNS.

Implementation of an integrated care strategy for child contacts of tuberculosis patients: a quasi-experimental study protocol.

BACKGROUND: Childhood tuberculosis continues to be a major public health problem. Although the visibility of the epidemic in this population group has increased, further research is needed. OBJECTIVE: To design, implement and evaluate an integrated care strategy for children under five years old who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients in Medellín and the Metropolitan Area. METHODS: A quasi-experimental study in which approximately 300 children who are household contacts of bacteriologically confirmed pulmonary tuberculosis patients from Medellín and the Metropolitan Area will be evaluated and recruited over one year. A subgroup of these children, estimated at 85, who require treatment for latent tuberculosis, will receive an integrated care strategy that includes: some modifications of the current standardized scheme in Colombia, with rifampicin treatment daily for four months, follow-up under the project scheme with nursing personnel, general practitioners, specialists, professionals from other disciplines such as social work, psychology, and nutritionist. Additionally, transportation and food assistance will be provided to encourage treatment compliance. This strategy will be compared with isoniazid treatment received by a cohort of children between 2015 and 2018 following the standardized scheme in the country. The study was approved by the CIB Research Ethics Committee and UPB. CLINICALTRIALS: gov identifier NCT04331262. DISCUSSION: This study is expected to contribute to the development of integrated care strategies for the treatment of latent tuberculosis in children. The results will have a direct impact on the management of childhood tuberculosis contributing to achieving the goals proposed by the World Health Organization's End TB Strategy. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04331262 . Implementation of an Integrated Care Strategy for Children Contacts of Patients with Tuberculosis. Registered 2 April 2020.

Paradoxical roles for programmed cell death signaling during viral infection of the central nervous system.

Programmed cell death (PCD) is an essential mechanism of antimicrobial defense. Recent work has revealed an unexpected diversity in the types of PCD elicited during infection, as well as defined unique roles for different PCD modalities in shaping the immune response. Here, we review recent work describing unique ways in which PCD signaling operates within the infected central nervous system (CNS). These studies reveal striking complexity in the regulation of PCD signaling by CNS cells, including both protective and pathological outcomes in the control of infection. Studies defining the specialized molecular mechanisms shaping PCD responses in the CNS promise to yield much needed new insights into the pathogenesis of neuroinvasive viral infection, informing future therapeutic development.

Cardiovascular risk factors and comorbidities in people living with HIV: A cross-sectional multicenter study from Colombia comorbidities in a Colombian PLWHIV population.

INTRODUCTION: HIV is an independent risk factor for cardiovascular diseases (CVD). There is insufficient information regarding comorbidities and cardiovascular risk factors in the Colombian HIV population. The aim of this study is to describe the prevalence of cardiovascular risk factors and comorbidities in patients from the HIV Colombian Group VIHCOL. METHODS: This is a multicenter, cross-sectional study conducted in the VIHCOL network in Colombia. Patients 18 years or older who had at least 6 months of follow-up were included. A stratified random sampling was performed to estimate the adjusted prevalence of cardiovascular risk factors and comorbidities. RESULTS: A total of 1616 patients were included. 83.2% were men, and the median age was 34 years. The adjusted prevalence for dyslipidemia, active tobacco use, hypothyroidism, and arterial hypertension was 51.2% (99% CI: 48.0%-54.4%), 7.6% (99% CI: 5.9%-9.3%), 7.4% (99% CI: 5.7%-9.1%), and 6.3% (99% CI: 4.8%-7.9%), respectively. CONCLUSIONS: In this Colombian HIV cohort, there is a high prevalence of modifiable CVD risk factors such as dyslipidemia and active smoking. Non-pharmacological and pharmacological measures for the prevention and management of these risk factors should be reinforced.

Functional Profile of CD8+ T-Cells in Response to HLA-A*02:01-Restricted Mutated Epitopes Derived from the Gag Protein of Circulating HIV-1 Strains from Medellín, Colombia.

CD8+ T-cells play a crucial role in the control of HIV replication. HIV-specific CD8+ T-cell responses rapidly expand since the acute phase of the infection, and it has been observed that HIV controllers harbor CD8+ T-cells with potent anti-HIV capacity. The development of CD8+ T-cell-based vaccine against HIV-1 has focused on searching for immunodominant epitopes. However, the strong immune pressure of CD8+ T-cells causes the selection of viral variants with mutations in immunodominant epitopes. Since HIV-1 mutations are selected under the context of a specific HLA-I, the circulation of viral variants with these mutations is highly predictable based on the most prevalent HLA-I within a population. We previously demonstrated the adaptation of circulating strains of HIV-1 to the HLA-A*02 molecule by identifying mutations under positive selection located in GC9 and SL9 epitopes derived from the Gag protein. Also, we used an in silico prediction approach and evaluated whether the mutations found had a higher or lower affinity to the HLA-A*02. Although this strategy allowed predicting the interaction between mutated peptides and HLA-I, the functional response of CD8+ T-cells that these peptides induce is unknown. In the present work, peripheral blood mononuclear cells from 12 HIV-1+ HLA-A*02:01+ individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. The functional profile of CD8+ T-cells was evaluated using flow cytometry, and the frequency of subpopulations was determined according to their number of functions and the polyfunctionality index. The results suggest that the quality of the response (polyfunctionality) could be associated with the binding affinity of the peptide to the HLA molecule, and the functional profile of specific CD8+ T-cells to mutated epitopes in individuals under cART is maintained.

The Usefulness of Antigen Testing in Predicting Contagiousness in COVID-19.

Increasing the diagnostic capacity for COVID-19 (SARS-CoV-2 infection) is required to improve case detection, reduce COVID-19 expansion, and boost the world economy. Rapid antigen detection tests are less expensive and easier to implement, but their diagnostic performance has been questioned compared to reverse transcription-PCR (RT-PCR). Here, we evaluate the performance of the Standard Q COVID-19 antigen test for diagnosing SARS-CoV-2 infection and predicting contagiousness compared to RT-PCR and viral culture, respectively. The antigen test was 100.0% specific but only 40.9% sensitive for diagnosing infection compared to RT-PCR. Interestingly, SARS-CoV-2 contagiousness is highly unlikely with a negative antigen test since it exhibited a negative predictive value of 99.9% compared to viral culture. Furthermore, a cycle threshold (CT) value of 18.1 in RT-PCR was shown to be the one that best predicts contagiousness (area under the curve [AUC], 97.6%). Thus, screening people with antigen testing is a good approach to prevent SARS-CoV-2 contagion and allow returning to daily activities. IMPORTANCE The importance of our results is the excellent agreement between the Standard Q COVID-19 antigen test and the viral culture, indicating that it is important as a marker of contagiousness. Due to its high positive predictive value in situations of a high prevalence of infection, positive results do not require confirmation with another test. Likewise, its high negative predictive value for contagiousness makes possible to use this test as a criterion to discharge patients in isolation and screen people moving into environments that could facilitate the transmission of the virus. Screening people with antigen testing is a good approach to prevent SARS-CoV-2 contagion and allow returning to daily activities.

α-Synuclein Induces the GSK-3-Mediated Phosphorylation and Degradation of NURR1 and Loss of Dopaminergic Hallmarks.

In Parkinson's disease, the dysfunction of the dopaminergic nigrostriatal tract involves the loss of function of dopaminergic neurons of the substantia nigra pars compacta followed by death of these neurons. The functional recovery of these neurons requires a deep knowledge of the molecules that maintain the dopaminergic phenotype during adulthood and the mechanisms that subvert their activity. Previous studies have shown that transcription factor NURR1, involved in differentiation and maintenance of the dopaminergic phenotype, is downregulated by α-synuclein (α-SYN). In this study, we provide a mechanistic explanation to this finding by connecting α-SYN-induced activation of glycogen synthase kinase-3 (GSK-3) with NURR1 phosphorylation followed by proteasomal degradation. The use of sequential deletion mutants and single point mutants of NURR1 allowed the identification of a domain comprising amino acids 123-PSSPPTPSTPS-134 that is targeted by GSK-3 and leads to subsequent ubiquitination and proteasome degradation. This study provides a detailed analysis of the regulation of NURR1 stability by phosphorylation in synucleinopathies such as Parkinson's disease.

Prevalence of intestinal parasites in a cohort of HIV- infected patients from Antioquia, Colombia / Prevalencia de parásitos intestinales en una cohorte de pacientes positivos para HIV en Antioquia, Colombia

Abstract | Introduction: HIV infection is still a public health problem worldwide and co-infections with other infectious agents including intestinal parasites are of particular concern, mainly in developing countries like Colombia. Objective: To conduct a cross-sectional study in patients attending an HIV care program in Antioquia given that there have been few intestinal parasites prevalence studies among the HIV population in the country. Material and methods: We evaluated stool samples from 192 patients by direct wet mount and concentration, modified Ziehl Neelsen staining, and agar plate culture. Univariate and correlation analyses were done to explore the association between socio-demographic and clinical characteristics and parasitological data. Results: The overall prevalence of intestinal parasites in HIV-positive subjects was 29.2% (56/192; 95% CI: 22.8% - 35.6%). Entamoeba histolytica/dispar/moshkosvkii with 13.0% (25/192; 95% CI: 8.2% - 17.8%) and Blastocystis with 12.0% (23/192; 95% CI: 7.4% -16.6%) were the most frequent. Opportunistic parasites like Cryptosporidium spp. and Cystoisospora belli were less prevalent, each one with 0.5% of positive samples (1/192; 95% CI: 0.1% - 1.5%). Commensal protozoa were also detected with a prevalence of 18.8% (36/192; 95% CI: 13.3% - 24.3%). Most of the individuals in the study had a controlled viral load and an LTCD4 count greater than 200 cel/µL. A small percentage (9.3%) had diarrhea. Bivariate analysis and multivariate logistic regression showed that only age and having pets had a significant association with intestinal parasites in this cohort. Conclusions: Our results confirmed that the evaluated population is at high risk of intestinal parasite infection, which highlights the need for routine screening of gastrointestinal parasites to provide prompt treatment and reduce possible complications.

Resumen | Introducción. La infección por HIV y las coinfecciones con otros agentes infecciosos, incluidos los parásitos intestinales, son motivo de especial preocupación en países en desarrollo como Colombia. Objetivo. Hacer un estudio transversal en pacientes que asisten a un programa de atención de HIV en el departamento de Antioquia, dado que los estudios de prevalencia de parásitos intestinales en la población con HIV son escasos en el país. Materiales y métodos. Se evaluaron 192 muestras de materia fecal mediante examen coprológico directo y por concentración, tinción de Ziehl-Neelsen modificada, y aislamiento en agar. Se hicieron análisis univariados y de correlación, para explorar la asociación entre las características sociodemográficas y clínicas, y los datos parasitológicos. Resultados. La prevalencia global de parásitos intestinales en pacientes positivos para VIH fue del 29.2 % (56/192; IC95% 22.8-35.6 %), siendo Entamoeba histolytica/dispar/moshkosvkii, con 13.0 % (25/192; IC95% 8.2-17.8 %), y Blastocystis, con 12.0 % (23/192; IC95% 7.4-16.6 %), los mas frecuentes. Los parásitos oportunistas Cryptosporidium spp. Y Cystoisospora belli fueron menos prevalentes, cada uno con 0.5 % (1/192; IC95% 0.1-1.5 %) de muestras positivas. También, se detectaron protozoos comensales, con una prevalencia del 18,8 % (36/192; IC95% 13,3-24,3 %). La mayoría de los individuos tenía una carga viral controlada y un recuento de linfocitos T CD4 superior a 200 células/μl. Un pequeño porcentaje (9,3 %) presentó diarrea. La edad y el tener mascotas mostraron una asociación significativa con la presencia de parásitos intestinales. Conclusión. Se confirmó que la población evaluada tiene un alto riesgo de infección por parásitos intestinales, lo que resalta la necesidad de un protocolo de diagnóstico para el cribado de dichos agentes, con el fin de brindar un tratamiento rápido y reducir las posibles complicaciones.

Coastal subsidence increases vulnerability to sea level rise over twenty first century in Cartagena, Caribbean Colombia.

Cartagena is subsiding at a higher rate compared to that of global climate-driven sea level rise. We investigate the relative sea level rise (RSLR) and the influence of vertical land movements in Cartagena through the integration of different datasets, including tide gauge records, GPS geodetic subsidence data, and Interferometric Synthetic Aperture Radar (InSAR) observations of vertical motions. Results reveal a long-term rate (> 60 years) of RSLR of 5.98 ± 0.01 mm/yr. The last two decades exhibited an even greater rate of RSLR of 7.02 ± 0.06 mm/yr. GPS subsidence rates range between - 5.71 ± 2.18 and - 2.85 ± 0.84 mm/yr. InSAR data for the 2014-2020 period show cumulative subsidence rates of up to 72.3 mm. We find that geologically induced vertical motions represent 41% of the observed changes in RSLR and that subsidence poses a major threat to Cartagena's preservation. The geodetic subsidence rates found would imply a further additional RSLR of 83 mm by 2050 and 225 mm by 2100. The Colombian government should plan for the future and serve as an example to similar cities across the Caribbean.

Fibrillar α-synuclein induces neurotoxic astrocyte activation via RIP kinase signaling and NF-κB.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of midbrain dopamine neurons. The pathogenesis of PD is poorly understood, though misfolded and/or aggregated forms of the protein α-synuclein have been implicated in several neurodegenerative disease processes, including neuroinflammation and astrocyte activation. Astrocytes in the midbrain play complex roles during PD, initiating both harmful and protective processes that vary over the course of the disease. However, despite their significant regulatory roles during neurodegeneration, the cellular and molecular mechanisms that promote pathogenic astrocyte activity remain mysterious. Here, we show that α-synuclein preformed fibrils (PFFs) induce pathogenic activation of human midbrain astrocytes, marked by inflammatory transcriptional responses, downregulation of phagocytic function, and conferral of neurotoxic activity. These effects required the necroptotic kinases RIPK1 and RIPK3, but were independent of MLKL and necroptosis. Instead, both transcriptional and functional markers of astrocyte activation occurred via RIPK-dependent activation of NF-κB signaling. Our study identifies a previously unknown function for α-synuclein in promoting neurotoxic astrocyte activation, as well as new cell death-independent roles for RIP kinase signaling in the regulation of glial cell biology and neuroinflammation. Together, these findings highlight previously unappreciated molecular mechanisms of pathologic astrocyte activation and neuronal cell death with implications for Parkinsonian neurodegeneration.

The environment topography alters the way to multicellularity in Myxococcus xanthus.

The social soil-dwelling bacterium Myxococcus xanthus can form multicellular structures, known as fruiting bodies. Experiments in homogeneous environments have shown that this process is affected by the physicochemical properties of the substrate, but they have largely neglected the role of complex topographies. We experimentally demonstrate that the topography alters single-cell motility and multicellular organization in M. xanthus In topographies realized by randomly placing silica particles over agar plates, we observe that the cells' interaction with particles drastically modifies the dynamics of cellular aggregation, leading to changes in the number, size, and shape of the fruiting bodies and even to arresting their formation in certain conditions. We further explore this type of cell-particle interaction in a computational model. These results provide fundamental insights into how the environment topography influences the emergence of complex multicellular structures from single cells, which is a fundamental problem of biological, ecological, and medical relevance.