Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers

Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/cmice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocularmucosa was well tolerated without signs of inflammation. N-PmpC- specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFN gamma immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage

Transforming growth factor-β induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis

CONTEXT: TGF-β is believed to play a major role in the etiology of peritoneal endometriosis. In tumors, TGF-β induces the metabolic conversion of glucose to lactate via glycolysis, a process referred to as the “Warburg effect.” Lactate increases cell invasion, angiogenesis, and immune suppression, all crucial steps in the development of endometriosis. OBJECTIVE: The aim of this study was to determine whether TGF-β induces a “Warburg-like” effect in peritoneal endometriosis. DESIGN: The study was informed by human tissue analysis and cel culture. SETTING: The study was conducted at the university research institute. PATIENTS OR OTHER PARTICIPANTS: We studied women undergoing surgical investigation for endometriosis. INTERVENTIONS: Concentrations of lactate and TGF-β1 in peritoneal fluid (n = 16) were measured by commercial assay. Expression of genes implicated in glycolysis was measured in endometrial and peritoneal biopsies (n = 31) by quantitative RT-PCR and immunohistochemistry. The effect of TGF-β1 on primary human peritoneal mesothelial cells (n = 6) and immortalized mesothelial (MeT-5A) cells (n = 3) was assessed by quantitative RT-PCR, Western blot, and commercial assays. MAIN OUTCOME MEASURES: Lactate, TGF-β1, and markers of glycolysis were measured. RESULTS: Concentrations of lactate in peritoneal fluid paralleled those of TGF-β1, being significantly higher in women with endometriosis compared to women without (P < .05). Endometriosis lesions expressed higher levels of glycolysis-associated genes HIF1A, PDK1, and LDHA than eutopic endometrium, and adjacent peritoneum had higher levels of HIF1A and SLC2A1 than peritoneum from women without disease (P < .05 to P < .001). Exposure of mesothelial cells to TGF-β1 increased production of lactate (P < .05), increased HIF1A mRNA (P < .05), and protein, and increased concentrations of mRNAs encoded by glycolysis-associated genes (LDHA, PDK1, SLC2A1; P < .05). CONCLUSIONS: A change in the metabolic phenotype of endometriosis lesions and peritoneal mesothelium in women with endometriosis may favor development of endometriosis

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Un programa de lectura y escritura universitario: Lineamientos teóricos, características y resultados de aplicación

ResumenEste artículo tiene por objetivo presentar el Programa de Lectura y Escritura Académicas (PROLEA-UFLO) que se está implementando en la Universidad de Flores (Buenos Aires, Argentina). Para ello, se presentan los lineamientos teóricos que orientan el programa, su metodología de aplicación didáctica, sus características y algunos resultados obtenidos en una instancia de aplicación. Así, se desarrollan primero las razones por las que un programa de este tipo debe ser instalado; una teoría de aprendizaje mediada por el lenguaje; una teoría de género y discurso enmarcada en la Lingüística Sistémico-Funcional que se propone como base para la enseñanza y, como metodología, un dispositivo didáctico adaptado del de la Escuela de Sydney. En segundo término, se presenta la intervención del Programa llevada a cabo en una materia ubicada en el primer cuatrimestre del primer año de la carrera de Psicología, a fin de mostrar la evolución de la escritura de los estudiantes en ese contexto.Palabras clave: Programa de lectura y escritura académicas – Lingüística Sistémico-Funcional – aprendizaje – enseñanza - géneros discursivos – evolución de habilidades de lectura y escritura – universidad.*************************************************************************A tertiary reading and writing program: theoretical guidelines, characteristics and application resultsAbstract:The goal of this article is to present the Academic Reading and Writing Program (PROLEA-UFLO) which is being implemented at Flores University (Buenos Aires, Argentina). For that purpose, the theoretical guidelines that found the program are presented, as well as its didactic application methodology, its characteristics and some of the results achieved in one instance of application. Thus, in the first place the rationale for the establishment of such type of program is developed; a theory of learning mediated by language; a theory of genre and discourse framed within Systemic-Functional Linguistics which is proposed as a basis for teaching and, a didactic device adapted from the Sydney School as the methodology. Secondly, an intervention carried out in the first term of the year in the major of Psychology is exposed in order to show the evolution of the students’ written production within that context. Key words: academic reading and writing program, Systemic-Functional linguistics, learning, teaching, discourse genres, reading and writing skills evolution.*************************************************************************Um programa de leitura e escrita universitário. Lineamentos teóricos, características e resultados de aplicaçãoResumoEste artigo tem por objetivo apresentar o Programa de Leitura e Escrita Acadêmicas (PROLEA-UFLO) que está sendo implementado na Universidade de Flores (Buenos Aires, Argentina). Para isso se apresentam os lineamentos teóricos que orientam o programa, sua metodologia de aplicação didática, suas características e alguns resultados obtidos numa instância de aplicação. Assim sendo, desenvolvem-se primeiro as razões pelas que um programa de este tipo deve ser instalado; uma teoria da aprendizagem mediada pela linguagem; uma teoria de gênero e discurso emoldurada na Linguística Sistêmico-Funcional que é proposta como base para o ensino e, como metodologia, um dispositivo didático adatado do da Escola de Sydney. Em segundo termo, se apresenta a intervenção do programa levada a cabo numa disciplina programada dentro  do primeiro quadrimestre do primeiro ano do curso de Psicologia, com a finalidade de mostrar a evolução dos estudantes neste contexto.Palavras chave: Programa de leitura e escrita acadêmicas, linguística sistêmico-funcional, aprendizagem, ensino, gêneros discursivos, evolução de habilidades de escrita e leitura, universidade

Negotiation between peers: strategic device for a reading and writing program at the university level

The following paper focuses on the description and exemplification of a device which is the core of the Academic Reading and Writing Program (PROLEA, for its acronym in Spanish) conducting at University of Flores (UFLO): the “negotiation between peers” or “negotiation between teaching partners”. The Program design is based on the Sydney School's developments in Systemic Functional Linguistics. The negotiation between peers comprises the work between a professor on academic and professional literacies, who is a member of the Program, and the professors of each of the specific subjects involved. In order to successfully implement this modality, the realization of the negotiation between peers is necessary. This device entails a series of agreements between the professors involved about the teaching of the curricula contents through reading and writing tasks. First in this paper, the negotiation between peers is characterized, and its function and value in the Program are highlighted; second, two scenarios of application are presented in order to show the device contribution as well as its difficulties and the way of resolution of the problems found

Prácticas de lectura y escritura en el marco de la enseñanza de la Psicología: avances de una investigación interdisciplinaria

This article presents the results obtained from interviews with the professors of ten courses considered fundamental in the psychology major of an Argentine university. A questionnaire open to interaction asked the professors about the reading and writing practices that they promote in their classrooms. In order to triangulate information, the professors were also requested to provide samples of bibliographical material and writing or evaluation requirements for passing their courses. The results led to an initial diagnosis of professors' difficulties in guiding their students' reading and writing practices. The interaction with the teachers promoted a process of reflection that motivated positive practices in the framework of teaching psychology, and that established the bases for implementing a program of academic reading and writing.Este trabajo presenta los resultados obtenidos a partir de la realización de entrevistas a profesores de diez materias consideradas troncales en la carrera de Psicología de una universidad argentina. Se utilizó un cuestionario-base abierto a la interacción, que los interrogó sobre las prácticas de lectura y de escritura que promueven en sus aulas. También se les solicitaron muestras del material bibliográfico y consignas de escritura o de evaluación propuestas como requisitos de aprobación a fin de triangular información. Los resultados arrojaron un primer diagnóstico sobre las dificultades que los profesores tienen para guiar las prácticas de lectura y escritura que sus alumnos deben llevar a cabo. La interacción con los docentes promovió un proceso de reflexión que pudo dar inicio a una incidencia positiva en sus prácticas en el marco de la enseñanza de la carrera y sentar las bases para poner en marcha un programa de lectura y escritura académicas