Oral Contraception and Cognition

Oral contraception is currently used by over 100 million women worldwide. Women utilize contraception not only to prevent pregnancy but also to manage a wide range of health concerns, such as acne and polycystic ovarian syndrome. Although this medication has granted women bodily autonomy, helped them attain higher levels of education, and helped them enter the workforce in greater numbers, little is known about the consequences outside of the intended contraceptive effects, specifically the cognitive and behavioral consequences. Moreover, because doctors can prescribe contraception after the first menstrual cycle and during puberty, it’s possible that this critical window of development could be altered longitudinally as a synthetic form could change the naturally occurring hormonal levels that are in flux during this time. The present research sought to determine the effects of synthetic and naturally occurring estrogen and progesterone on behavior and cognition at a critical developmental period. To determine these effects, we used a mouse model of oral contraception and based the concentration on a commonly used contraceptive. After 31 days of administration with a combination levonorgestrel and ethinyl estradiol solution, we conducted two behavioral tests. First, we used the elevated plus maze to determine anxiety-like behaviors. We then explored fear conditioning and extinction by utilizing a three-day contextual fear extinction protocol with an additional cued fear recall day. Based on the existing literature, we hypothesized (1) animals treated with a combination OC would demonstrate decreased anxiety and fear conditioning and extinction compared to control animals. (2) Naturally cycling mice in diestrus would experience increased anxiety and fear conditioning and extinction compared to mice in estrus. (3) Animals treated in the potentially critical window during puberty would demonstrate significantly different anxiety and fear conditioning and extinction behaviors

Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach

Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections

The Role of Humoral Innate Immunity in Hepatitis C Virus Infection

Infection with Hepatitis C Virus (HCV) causes chronic disease in approximately 80% of cases, resulting in chronic inflammation and cirrhosis. Current treatments are not completely effective, and a vaccine has yet to be developed. Spontaneous resolution of infection is associated with effective host adaptive immunity to HCV, including production of both HCV-specific T cells and neutralizing antibodies. However, the supporting role of soluble innate factors in protection against HCV is less well understood. The innate immune system provides an immediate line of defense against infections, triggering inflammation and playing a critical role in activating adaptive immunity. Innate immunity comprises both cellular and humoral components, the humoral arm consisting of pattern recognition molecules such as complement C1q, collectins and ficolins. These molecules activate the complement cascade, neutralize pathogens, and recruit antigen presenting cells. Here we review the current understanding of anti-viral components of the humoral innate immune system that play a similar role to antibodies, describing their role in immunity to HCV and their potential contribution to HCV pathogenesis

Expression of psychotic symptoms by the Rorschach test

Os transtornos psicoticos, de um modo geral, e em especial a esquizofrenia, exercem um impacto patente na qualidade de vida do individuo com estes sintomas, afetando seu bemestar, sua ocupacao profissional e sua relacao com a comunidade. Quanto mais cedo se inicia o tratamento, mais breve pode ocorrer a reintegracao dessa pessoa na sociedade, porem sua eficacia depende do diagnostico precoce para que seja possivel a intervencao caso a caso. O estudo do Rorschach, como instrumento de investigacao da personalidade, pode auxiliar neste processo devido ao seu amplo escopo de aplicacoes. A maior parte dos estudos sobre as pessoas com sintomas psicoticos trata da esquizofrenia, porem poucas publicacoes pesquisaram os pacientes ainda proximos ao surto e com efeito minimo da medicacao, alem de poucos estudos estabelecerem a comparacao com um grupo de individuos normais. A presente pesquisa propos-se a enfocar estes dois aspectos: o estudo de individuos proximos ao surto psicotico que os levou a procurar pela primeira vez uma instituicao de saude e sua comparacao com um grupo controle. Assim, o grupo experimental foi composto de vinte pessoas que procuraram uma instituicao de saude entre maio de 2004 e marco de 2005 e que moravam ha pelo menos 6 meses na area delimitada pelo projeto. Os participantes do grupo controle foram pareados individualmente por vizinhanca, faixa etaria e sexo; desta forma concentrando-os em regioes geograficas relevantes e demograficamente representativas para a comparacao. A coleta de dados foi realizada em duas entrevistas, a primeira para familiarizacao do participante com a pesquisadora e a segunda para a aplicacao do Rorschach. A analise dos dados se deu quantitativamente, segundo o Sistema Frances. O Metodo de Rorschach mostrou-se sensivel a diferencas entre os dois grupos estudados. Os resultados obtidos com os sujeitos do grupo experimental, em relacao ao grupo controle, foram significativos quanto ao menor percentual de respostas de forma bem vista, menor quantidade de respostas de tonalidade e menor percentual de respostas de conteudo animal. A analise destes indices em conjunto com outros fatores do Rorschach sugeriu uma dificuldade maior das pessoas com sintomas psicoticos no contato com os outros decorrente da introjecao inadequada de estereotipos sociais, da nao diferenciacao entre realidade interna e externa e de um processo de identificacao fragilizado permeado pela angustia de desintegracao. Este projeto esta associado a um projeto maior intitulado Estudos de Casos Incidentes (Primeiro Contato com Servicos de Saude) de Psicoses Funcionais no Brasil, que esta sendo realizado por equipe do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC FMUSP), na tentativa de caracterizar, acompanhar e comparar os casos de transtornos psicoticos na cidade de Sao Paulo com um estudo semelhante feito em Londres, Reino UnidoThe psychotic disorders, as a whole, and specially schizophrenia, inflict an evident impact upon one\'s life quality with such symptoms, affecting his well-being, professional affairs and relationship with the community. The earlier treatment starts, the sooner this person can be reintegrated into society, albeit it\'s effectiveness depends upon early diagnosis for intervention to be possible on a case by case basis. The study of Rorschach as an instrument for personality assessment can help on this process due to its wide scope of applications. Most researches about individuals with psychotic symptoms are about schizophrenia, however only few publishings have studied patients still near the psychotic episode and under minimal medication, and few researches established a comparative study between afflicted population and healthy one. The current research aim was twofold in the study of individuals near the psychotic episode which resulted in his first-admission in a mental health care facility and comparison with control group. Thus, experimental group consisted of twenty individuals that were first admitted to a mental health care service between may (2004) and march (2005), that have lived in the research delimited area for at least 6 months. Control group participants were likened by neighborhood, age range and gender; this way concentrating them on both demographically representative and relevant geographic regions for comparison. Data was obtained by means of two interviews, being the first one in order to familiarize participant and researcher, and the second one to administer Rorschach test. Only quantitative analysis was performed, scored according to the French System. Rorschach Method presented sensibility to discrepancies among both researched groups. There was statistically significant differences between experimental group and comparison group with regard to lower percentage of good quality form responses, lower scores of shading responses, lower percentage of animal responses. The analisys of those three items along with other Rorschach scores suggests that people with psychotic symptoms present greater difficulties to relate with others due to introjection of inadequate social stereotypes, no differentiation from internal and external reality, and weakened identification process permeated by desintegration anguish. This project is associated to a larger project entitled Estudos de Casos Incidentes (Primeiro Contato com Servicos de Saude) de Psicoses Funcionais no Brasil, which is being conducted by the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC FMUSP) research team, in an attempt to profile, study and compare psychosis affliction cases in Sao Paulo city with similar studies being carried in London, United Kingdo

Expression of psychotic symptoms by the Rorschach test

Os transtornos psicoticos, de um modo geral, e em especial a esquizofrenia, exercem um impacto patente na qualidade de vida do individuo com estes sintomas, afetando seu bemestar, sua ocupacao profissional e sua relacao com a comunidade. Quanto mais cedo se inicia o tratamento, mais breve pode ocorrer a reintegracao dessa pessoa na sociedade, porem sua eficacia depende do diagnostico precoce para que seja possivel a intervencao caso a caso. O estudo do Rorschach, como instrumento de investigacao da personalidade, pode auxiliar neste processo devido ao seu amplo escopo de aplicacoes. A maior parte dos estudos sobre as pessoas com sintomas psicoticos trata da esquizofrenia, porem poucas publicacoes pesquisaram os pacientes ainda proximos ao surto e com efeito minimo da medicacao, alem de poucos estudos estabelecerem a comparacao com um grupo de individuos normais. A presente pesquisa propos-se a enfocar estes dois aspectos: o estudo de individuos proximos ao surto psicotico que os levou a procurar pela primeira vez uma instituicao de saude e sua comparacao com um grupo controle. Assim, o grupo experimental foi composto de vinte pessoas que procuraram uma instituicao de saude entre maio de 2004 e marco de 2005 e que moravam ha pelo menos 6 meses na area delimitada pelo projeto. Os participantes do grupo controle foram pareados individualmente por vizinhanca, faixa etaria e sexo; desta forma concentrando-os em regioes geograficas relevantes e demograficamente representativas para a comparacao. A coleta de dados foi realizada em duas entrevistas, a primeira para familiarizacao do participante com a pesquisadora e a segunda para a aplicacao do Rorschach. A analise dos dados se deu quantitativamente, segundo o Sistema Frances. O Metodo de Rorschach mostrou-se sensivel a diferencas entre os dois grupos estudados. Os resultados obtidos com os sujeitos do grupo experimental, em relacao ao grupo controle, foram significativos quanto ao menor percentual de respostas de forma bem vista, menor quantidade de respostas de tonalidade e menor percentual de respostas de conteudo animal. A analise destes indices em conjunto com outros fatores do Rorschach sugeriu uma dificuldade maior das pessoas com sintomas psicoticos no contato com os outros decorrente da introjecao inadequada de estereotipos sociais, da nao diferenciacao entre realidade interna e externa e de um processo de identificacao fragilizado permeado pela angustia de desintegracao. Este projeto esta associado a um projeto maior intitulado Estudos de Casos Incidentes (Primeiro Contato com Servicos de Saude) de Psicoses Funcionais no Brasil, que esta sendo realizado por equipe do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC FMUSP), na tentativa de caracterizar, acompanhar e comparar os casos de transtornos psicoticos na cidade de Sao Paulo com um estudo semelhante feito em Londres, Reino UnidoThe psychotic disorders, as a whole, and specially schizophrenia, inflict an evident impact upon one\'s life quality with such symptoms, affecting his well-being, professional affairs and relationship with the community. The earlier treatment starts, the sooner this person can be reintegrated into society, albeit it\'s effectiveness depends upon early diagnosis for intervention to be possible on a case by case basis. The study of Rorschach as an instrument for personality assessment can help on this process due to its wide scope of applications. Most researches about individuals with psychotic symptoms are about schizophrenia, however only few publishings have studied patients still near the psychotic episode and under minimal medication, and few researches established a comparative study between afflicted population and healthy one. The current research aim was twofold in the study of individuals near the psychotic episode which resulted in his first-admission in a mental health care facility and comparison with control group. Thus, experimental group consisted of twenty individuals that were first admitted to a mental health care service between may (2004) and march (2005), that have lived in the research delimited area for at least 6 months. Control group participants were likened by neighborhood, age range and gender; this way concentrating them on both demographically representative and relevant geographic regions for comparison. Data was obtained by means of two interviews, being the first one in order to familiarize participant and researcher, and the second one to administer Rorschach test. Only quantitative analysis was performed, scored according to the French System. Rorschach Method presented sensibility to discrepancies among both researched groups. There was statistically significant differences between experimental group and comparison group with regard to lower percentage of good quality form responses, lower scores of shading responses, lower percentage of animal responses. The analisys of those three items along with other Rorschach scores suggests that people with psychotic symptoms present greater difficulties to relate with others due to introjection of inadequate social stereotypes, no differentiation from internal and external reality, and weakened identification process permeated by desintegration anguish. This project is associated to a larger project entitled Estudos de Casos Incidentes (Primeiro Contato com Servicos de Saude) de Psicoses Funcionais no Brasil, which is being conducted by the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC FMUSP) research team, in an attempt to profile, study and compare psychosis affliction cases in Sao Paulo city with similar studies being carried in London, United Kingdo

Are the integrin binding motifs within SARS CoV-2 spike protein and MHC class II alleles playing the key role in COVID-19?

The previous studies on the RGD motif (aa403-405) within the SARS CoV-2 spike (S) protein receptor binding domain (RBD) suggest that the RGD motif binding integrin(s) may play an important role in infection of the host cells. We also discussed the possible role of two other integrin binding motifs that are present in S protein: LDI (aa585-587) and ECD (661-663), the motifs used by some other viruses in the course of infection. The MultiFOLD models for protein structure analysis have shown that the ECD motif is clearly accessible in the S protein, whereas the RGD and LDI motifs are partially accessible in S protein. Furthermore, the amino acids that are present in Epstein-Barr virus protein (EBV) gp42 playing very important role in binding to the HLA-DRB1 molecule and in the subsequent immune response evasion, are also present in the S protein heptad repeat-2. Our MultiFOLD model analyses have shown that these amino acids are clearly accessible on the surface in each S protein chain as monomers and in the homotrimer complex and bind to HLA-DRB1 β chain. Accordingly, they may have the identical role in SARS CoV-2 immune evasion as in EBV infection. The prediction analyses of the MHC class II binding peptides within the S protein have shown that the RGD motif is present in the core 9-mer peptide IRGDEVRQI within the two HLA-DRB1*03:01 and HLA-DRB3*01.01 strong binding 15-mer peptides suggesting that RGD motif may be the potential immune epitope. Accordingly, infected HLA-DRB1*03:01 or HLA-DRB3*01.01 positive individuals may develop high affinity anti-RGD motif antibodies that react with the RGD motif in the host proteins, like fibrinogen, thrombin or von Willebrand factor, affecting haemostasis or participating in autoimmune disorders