Genetic variability shapes the alternative pathway complement activity and predisposition to complement-related diseases.

The implementation of next-generation sequencing technologies has provided a sharp picture of the genetic variability in the components and regulators of the alternative pathway (AP) of the complement system and has revealed the association of many AP variants with different rare and common diseases. An important finding that has emerged from these analyses is that each of these complement-related diseases associate with genetic variants altering specific aspects of the activation and regulation of the AP. These genotype-phenotype correlations have provided valuable insights into their pathogenic mechanisms with important diagnostic and therapeutic implications. While genetic variants in coding regions and structural variants are reasonably well characterized and occasionally have been instrumental to uncover unknown features of the complement proteins, data about complement expressed quantitative trait loci are still very limited. A crucial task for future studies will be to identify these quantitative variations and to determine their impact in the overall activity of the AP. This is fundamental as it is now clear that the consequences of genetic variants in the AP are additive and that susceptibility or resistance to disease is the result of specific combinations of genetic variants in different complement components and regulators ("complotypes").

Vacunas de la infancia podrían estar contribuyendo a menor incidencia y severidad de COVID-19 en edades pediátricas

RESUMEN A más de un año de que la pandemia de COVID-19 emergiera en la ciudad China de Wuhan, un hecho sigue llamando la atención de la comunidad científica enfrentada a esta virosis: la menor susceptibilidad de los niños a la infección por SARS CoV-2 y al desarrollo de cuadros severos de COVID-19. Un grupo de factores, no excluyentes, ha sido aludido para explicar la mayor resistencia de los menores a la virosis y a sus consecuencias clínicas. El objetivo de este trabajo es incursionar en un factor adicional, todavía poco abordado en la literatura médica relacionada con el tema: la resistencia inespecífica a SARS-CoV-2 que podría estar siendo generada por las vacunas administradas durante la infancia. Con esta incursión se pretende, además, aportar a una mejor comprensión del carácter relativamente benévolo de la virosis en los menores. El análisis realizado permite concluir que un grupo de las vacunas administradas durante esa etapa, la mayoría de las cuales forman parte del esquema de inmunización de los niños cubanos, se asocia a una menor incidencia y severidad de la infección por SARS CoV-2 en edades pediátricas.

ABSTRACT More than one year after the emergence of COVID-19 in the Chinese city of Wuhan, a fact continues to draw the attention of the scientific community engaged in the response to the virus: the lower susceptibility of children to SARS-CoV-2 infection and to the development of severe COVID-19. A number of non-mutually exclusive factors have been mentioned to explain the higher resistance of minors to the virus and its clinical consequences. The purpose of the study was to address an additional factor, so far not much dealt with in the medical bibliography about the topic: unspecific resistance to SARS-CoV-2 could be the result of the vaccines administered during childhood. This analysis is also aimed at contributing a better understanding of the relatively benevolent nature of the virus among children. It is concluded that a number of vaccines administered in childhood, most of them included in the immunization scheme for Cuban children, are associated to a lower incidence and severity of SARS-CoV-2 infection in pediatric ages.

Low risk of invasive lobular carcinoma of the breast in carriers of BRCA1 (hereditary breast and ovarian cancer) and TP53 (Li-Fraumeni syndrome) germline mutations.

BACKGROUND: Invasive lobular carcinoma (ILC) of the breast has epidemiological, molecular and clinical specificities, and should likely be considered a unique entity. As for genetic susceptibility, CDH1 germline mutations predispose exclusively to ILC. Data are however scarce regarding ILC in women with BRCA1/2 (Hereditary Breast and Ovarian Cancer) and TP53 (Li-Fraumeni syndrome) germline mutations. METHODS: We included all breast cancers from female patients tested at our institute between 1992 and 2016 (n = 3469) for which pathology data were available. ILC proportion comparison according to mutational status was performed by a chi-squared test. The impact of susceptibility genes on ILC proportion was investigated by univariate logistic regression with wild-type patients as reference. RESULTS AND DISCUSSION: There were 265 (7.64%) ILC: 2/342 (0.58%) in BRCA1 patients, 24/238 (10%) in BRCA2 patients, 1/57 (1.75%) in TP53 patients and 238/2832 (8.4%) in non-carriers. The majority of breast cancers in all groups were invasive ductal and ductal in situ carcinomas. The difference in ILC proportion was highly significant (P < 0.001). Compared to wild-type patients, BRCA1 was associated with a lower ILC proportion (OR 0.064 [95% CI 0.016;0.259], P < 0.0001). BRCA2 OR was 1.222 [95%CI 0.785;1.902] (P = 0.374), TP53 OR was 0.195 [95%CI 0.027;1.412] (P = 0.105). ILC are therefore underrepresented in BRCA1 and TP53 mutation carriers. Formal significance (P = 0.05) was not reached for TP53, but statistical power was only 38%. Based on ILC incidence in the general population, we make the hypothesis that BRCA1 and TP53 do not predispose to ILC, as the few occurrences of ILC in mutation carriers could be attributed to chance and not to germline mutations. Our observations will be useful to clinical cancer geneticists managing patients with ILC, as a BRCA1 or TP53 mutation in these patients would be unlikely. Genetic counseling should be adapted accordingly.

Environmental contaminant mixtures modulate in vitro influenza infection.

Environmental chemicals, particularly organochlorinated contaminants (OCs), are associated with a ranged of adverse health effects, including impairment of the immune system and antiviral immunity. Influenza A virus (IAV) is an infectious disease of major global public health concern and exposure to OCs can increase the susceptibility, morbidity, and mortality to disease. It is however unclear how pollutants are interacting and affecting the outcome of viral infections at the cellular level. In this study, we investigated the effects of a mixture of environmentally relevant OCs on IAV infectivity upon in vitro exposure in Madin Darby Canine Kidney (MDCK) cells and human lung epithelial cells (A549). Exposure to OCs reduced IAV infectivity in MDCK and A549 cells during both short (18-24h) and long-term (72h) infections at 0.05 and 0.5ppm, and effects were more pronounced in cells co-treated with OCs and IAV than pre-treated with OCs prior to IAV (p<0.001). Pre-treatment of host cells with OCs did not affect IAV cell surface attachment or entry. Visualization of IAV by transmission electron microscopy revealed increased envelope deformations and fewer intact virions during OC exposure. Taken together, our results suggest that disruption of IAV infection upon in vitro exposure to OCs was not due to host-cell effects influencing viral attachment and entry, but perhaps mediated by direct effects on viral particles or cellular processes involved in host-virus interactions. In vitro infectivity studies such as ours can shed light on the complex processes underlying host-pathogen-pollutant interactions.

Impact of mycotoxin on immune response and consequences for pig health.

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities, especially cereals. Due to their high consumption of cereals, pigs are exposed to these toxins. In the European Union, regulations and/or recommendations exist in pig feed for aflatoxins, ochratoxin A, fumonisins, zearalenone, and trichothecenes, deoxynivalenol and T-2 toxin. These mycotoxins have different toxic effects, but they all target the immune system. They have immunostimulatory or immunosuppressive effects depending on the toxin, the concentration and the parameter investigated. The immune system is primarily responsible for defense against invading organisms. The consequences of the ingestion of mycotoxin-contaminated feed are an increased susceptibility to infectious diseases, a reactivation of chronic infection and a decreased vaccine efficacy. In this review we summarized the data available on the effect of mycotoxins on the immune system and the consequences for pig health.

Estresse no cotidiano acadêmico: um estudo com pós-graduandos em Odontologia / Stress in the academic routine: a study with post-graduate students in Dentistry

No universo acadêmico a condição estresse vem sendo caracterizada como fato psicossocial com repercussão biológica, que ocorre quando há a percepção de ameaça real ou imaginária, avaliada como capaz de alterar o estado de conforto subjetivo provocando sensações de mal-estar transitório ou persistente. O objetivo desta pesquisa quantiqualitativa foi investigar a presença e o perfil do estresse entre pós-graduandos, considerando-se o período do curso vivenciado, bem como apreender os valores instituídos pelos sujeitos frente a esta perspectiva. O público-alvo foi a totalidade de acadêmicos ingressantes e concluintes de pós-graduação em Odontologia (n=39), considerando-se concomitantemente mestrandos e doutorandos. A coleta de dados foi realizada através do Inventário de Sintomas de Stress para Adultos de Lipp e da técnica em entrevista Grupo Focal. Os resultados expuseram a condição estresse presente em 59,1% dos pósgraduandos ingressantes, e em 41,2% dos concluintes. Entretanto, a associação entre estresse e momento vivenciado no curso não apresentou significância estatística. Em ambos os grupos houve predomínio da fase intitulada resistência e tendência ao desenvolvimento de sintomas psicológicos. As compreensões dos acadêmicos a respeito da etiologia do estresse revelaram concepções relacionadas ao projeto pedagógico, atuação docente e à incerteza sobre a contribuição do curso; assim como expuseram alguns desdobramentos físicos e psicológicos. Conclui-se que o fenômeno estresse esteve consideravelmente presente no ambiente da pós-graduação investigado e sugere-se o uso das percepções apreendidas como subsídio para a reformulação de práticas pedagógicas e o repensar da atuação docente, de forma a implementar ações que visem a melhoria da qualidade de vida e do desenvolvimento acadêmico (AU).

In the academic world the stress condition has been characterized as a psychosocial fact with biological impact, which occurs when there is a perception of real or imagined threat, assessed as able to change the subjective state of comfort causing sensations of transient or persistent malaise. The objective of this quantitative and qualitative research was to investigate the presence and profile of stress among post-graduate students, considering the period of the course, as well as to learn the values established by individuals in this perspective. The target audience was the freshman and senior academics from postgraduation in Dentistry (n=39), considering concurrently masters and doctoral students. The data collection was performed using the Stress Symptoms Inventory for Adults Lipp and a technical interview focusing in theses Groups. The results showed that stress conditions were present in 59.1% of freshman post-graduate students, and 41.2% in seniors. However, the association between stress and the experienced moment in the major was not statistically significant (p = 0, 276). In both groups there was a predominance of a stage titled strength and tendency to develop psychological symptoms. The insights of academics regarding the etiology of stress revealed concepts related to the pedagogical project, teaching performance, and the uncertainty about the contribution of the postgraduation course; as well as they exposed some physical and psychological developments. It is concluded that the stress phenomenon was significantly present in the investigated post-graduate environment and it also recommends the use of the perceptions learned as an input for the reformulation of educational practices and also in the rethinking of teaching performance, in order to implement actions that aim improving quality of life and academic development (AU).

ER-?gene polymorphisms and the risk of non-BRCA1/2 hereditary breast cancer / 中国普通外科杂志

Objective The present study was to explore association of PvuⅡand XbaⅠpolymorphism in ER-?gene with genetic susceptibility for breast cancer without BRCAl/2 gene mutation. Methods 113 BRCA1/2 negative hereditary breast cancer patients from independent families and 113 agematched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) was calculated by unconditional logistic regression model. Results The frequency of PvuⅡpolymorphism CC(PP) ,CT(Pp) ,TT(pp) genotype in patients was found in 16 cases(14.2% ), 58 cases(51. 3% ) , and 39 cases (34. 5% ). The distribution of AA (xx) , AG (Xx) , GG (XX) genotype of XbaⅠpolymorphism were found in 76 cases ( 67. 2% ) , 34 cases ( 30. 1% ), and 3 cases ( 2. 7% ) among patients. Among premenopausal women, CT genotype of PvuⅡconfered a significantly increased risk for breast cancer compared with CC genotype ( adjusted OR = 2. 07; 95% CI, 0. 68 - 6. 30) ; Carriers of GG of XbaⅠhad a decreased risk for breast cancer (adjusted OR =0. 11; 95 % CI, 0. 01 - 1. 27) compared with AA genotype. Furthermore, combined analysis of two polymorphisms indicated individuals carrying PvuⅡCT and XbaⅠAA genotype were at increased risk for breast cancer as compared with those with PvuⅡCC and XbaⅠGG genotype (Oft = 11.43, 95% CI, 1.12-116.7) among premenopausal women. Conclusions PvuⅡand XbaⅠpolymorphisms in ER-?gene could be a candidate locus for low penetrance breast cancer susceptibility in Chinese population, especially among premenopausal women.

Effects of larval age and prolonged simulated acid rain on the susceptibility of European pine sawfly to virus infection.

We studied the effect of simulated acid rain treatment of host trees on the susceptibility of the European pine sawfly larvae to virus, and possible differences when larvae of two different ages were infected. Older larvae were less susceptible to virus. Most larvae treated with virus 2 days after they started feeding on experimental foliage (group A) died rapidly within 10 days after the virus treatment, and survival to the end of the larval period was only 8-25%. Larvae treated with virus 1 week later (group B) were less affected by the virus and 36-49% survived. In group A the larval survival in the pH 3 treatment was higher than in other treatments; at the end of the larval period the difference was twofold. In group B there were no clear effects of acid rain on the susceptibility of larvae to virus. The study yielded the following new information: (1) the effect of prolonged acid rain treatment on reducing the efficacy of virus on young larvae was more distinct than in a previous study with shorter exposure to acid rain, and the difference was maintained to the end of larval period; (2) the susceptibility of older larvae to virus was not affected by acid rain treatments; (3) pH inside the needles did not explain the larval mortality caused by virus.