Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology.

The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

Epidemiological profile and genetic resistance of Neisseria gonorrhoeae infection in women in a poor region of São Paulo, Brazil.

BACKGROUND AND AIM: Gonorrhea is a bacterial infection in the urogenital tract, transmitted by sexual or perinatal contact, caused by Neisseria gonorrhoeae, a gram-negative diplococcus. The present study evaluates the frequency of N. gonorrhoeae in women treated at Hospital Wladimir Arruda in poor area of São Paulo and also verifies the presence of genetic resistance against three antimicrobials of different classes: Tetracycline, Azithromycin and Ciprofloxacin. METHODS: This is an observational and descriptive study with a quantitative approach. Samples were collected at Hospital Escola Wladimir Arruda. The volunteers are women from 16 to 65 years of age. Sociodemographic, gynecological, sexual and health data are collected through a questionnaire, their symptoms/clinical manifestation were requested by the medical records, and then the participant is referred for collection of samples of cervical vaginal smear. The samples were screened for N. gonorrhoeae (dcmH gene) and tested for resistance genes to Tetracycline, Azithromycin and Ciprofloxacin through PCR. RESULTS: In the total of 127 samples analyzed by Real-Time PCR, 23 were positive and correspond to a general prevalence of a gonococcal infection in the studied population of 17% (CI:95%), and the participants were married (43.4%), had active sexual life (56.5%) and did not use any type of condom during sexual intercourse (52.1%). The resistance to the tetM ribosomal gene was found in 14 samples, prevalence of 60% (CI= 95%). CONCLUSIONS: We have described a concerning frequency of N. gonorrhoeae infection in females attended in an outcare patient. Also, most of the strains detected presented resistance to one or more antimicrobials.

Dengue and climate changes: Increase of DENV-1 in São Paulo/Brazil - 2023.

Dengue is a vector borne disease caused by virus serotypes DENV-1, DENV-2, DENV-3, and DENV-4, representing a significant public health concern in the Region of the Americas (2,997,097 cases in 2023). This study explores the relationship between dengue incidence and climate changes in the city of São Paulo-Brazil. During the first semester of 2023, Brazil reported the highest number of dengue cases in Americas' Region. Our data reveals a correlation between the high temperature and rainfall season persistence and the extension of dengue incidence into the winter season. The findings highlight the importance of understanding the relationship between climate change and disease transmission patterns to develop effective strategies for prevention and control.

Differential modulation of IL-4, IL-10, IL-17, and IFN-γ production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and γδ) and B cells.

Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-γ-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-γ-producing γδT cells without influence on IL-17- and IL4-producing γδT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-γ producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.

Assessment of the Interferon-Lambda-3 Polymorphism in the Antibody Response to COVID-19 in Older Adults Seropositive for CMV.

BACKGROUND: Here, we investigated the impact of IFN-lambda-3 polymorphism on specific IgG responses for COVID-19 in older adults seropositive for CMV. METHODS: Blood samples of 25 older adults of both sexes were obtained at three different times: during a micro-outbreak (MO) of SARS-CoV-2 in 2020; eight months after (CURE); and 30 days after the administration of the second dose of ChadOx-1 vaccine (VAC). The specific IgG for both SARS-CoV-2 and CMV antigens, neutralizing antibodies against SARS-CoV-2, and also the polymorphism profile for IFN-lambda-3 (rs12979860 C > T) were assessed. RESULTS: Higher levels of specific IgG for SARS-CoV-2 antigens were found in the MO and VAC than in the CURE time-point. Volunteers with specific neutralizing antibodies against SARS-CoV-2 showed better specific IgG responses for SARS-CoV-2 and lower specific IgG levels for CMV than volunteers without specific neutralizing antibodies. Significant negative correlations between the specific IgG levels for SARS-CoV-2 and CMV were found at the MO time-point, as well as in the group of individuals homozygous for allele 1 (C/C) in the MO time-point and heterozygotes (C/T) in the CURE time-point. CONCLUSION: Our results suggested that both CMV seropositivity and the homozygosis for allele 1 (C/C) in IFN-lambda-3 gene can negatively impact the antibody response to COVID-19 infection and vaccination in older adults.

Effect of Total Hip Arthroplasty with Ceramic Acetabular Component on Clinical, Radiographic and Functional Parameters in Older Patients with Hip Osteoarthritis: Two-Year Follow-Up.

Background: Total hip arthroplasty (THA) is a widely used surgical procedure to reduce pain and improve function and quality of life in patients with hip disorders. The most common condition that leads to THA is osteoarthritis, with most surgeries being performed to treat severe osteoarthritis with pain and functional limitations. Despite the evident success of THA, the search for its improvement and better results, especially in the long term, continues, especially in older patients, for which there is still little scientific evidence. Objective: To evaluate the clinical, radiological, and functional aspects preoperatively and two years after THA with a ceramic acetabular component device in older patients with hip osteoarthritis. Methods: A retrospective cohort study was conducted to evaluate 65 older individuals who underwent THA of the hip with an acetabular component (MD® ceramic head with a ceramic acetabular insert) associated with the MD6® Phenom® femoral rod type, in Hospital of the Luz, São Paulo/SP, between 2018 and 2019. Anthropometric and clinical information about the operative procedure and two years follow-up were collected from the patients' medical records. For the clinical-functional evaluation, the Harris Hip Score (HHS) questionnaire and hip movement goniometry were applied. For the radiographic parameters, the following were evaluated: the positioning of the acetabular component, the Zone of DeLee and the offset of the femoroacetabular component. Results: There was a higher prevalence of performing THA in males (53.8%). Preoperative and two-year postoperative radiographic parameters of surgical treatment for THA showed maintenance of the acetabular (p = 0.083) and femoral (p = 0.102) positioning angles and increased functionality (p < 0.001) and joint mobility of the hip (p = 0.001) with reduced pain after two years of THA. Complications related to dislocation, loosening, infection, and inadequate positioning of the implant were low, ranging from 1.5 to 3%. Conclusion: Older people who underwent cementless THA with an ceramic acetabular component device, in a two-year follow-up, showed effectiveness in improved clinical, radiological, and functional aspects.

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness.

Human Endogenous Retroviruses (HERVs) are derived from ancient exogenous retroviral infections that have infected our ancestors' germline cells, underwent endogenization process, and were passed throughout the generations by retrotransposition and hereditary transmission. HERVs comprise 8% of the human genome and are critical for several physiological activities. Yet, HERVs reactivation is involved in pathological process as cancer and autoimmune diseases. In this review, we summarize the multiple aspects of HERVs' role within the human genome, as well as virological and molecular aspects, and their fusogenic property. We also discuss possibilities of how the HERVs are possibly transactivated and participate in modulating the inflammatory response in health conditions. An update on their role in several autoimmune, inflammatory, and aging-related diseases is also presented.

Fake news and covid-19: a concern due to the low vaccine coverage in Brazil / Fake News e covid-19: uma preocupação devido à baixa cobertura de vacinação no Brasil

Abstract This study comprised the application of a survey in São Paulo, Brazil, in 2 different periods of 2020: the beginning of the covid-19 pandemic and the disease's first peak (from March to April, 100 interviews) to the time of stability in case fatality rates (from May to July, 100 interviews); the questionnaire included was composed of 14 multiple-choice questions to evaluate the importance of mass communication channels, including social media, and the level of importance attributed to preventive measures at the beginning of the pandemic. The changes in people's behavior, even in a group with more schooling, which initially considered preventive measures to be very important (91%) but, in the second survey, was reduced to 82%. The reinforcement of preventive measures to reduce cases and deaths by covid-19 in Brazil is urgent, allied to recommendations with clear information on the importance of vaccination to avoid low rates as the current situation of vaccine coverage for preventable diseases.

Resumo Foi conduzida uma pesquisa em São Paulo, no Brasil, em 2 períodos distintos de 2020: sendo o primeiro no início da pandemia do covid-19 com um elevado pico de incidência da doença (de março a abril, foram realizadas 100 entrevistas) até o momento de estabilidade nas taxas de letalidade (de maio a julho, foram realizadas outras 100 entrevistas), composto por 14 questões de múltipla escolha para avaliar a importância dos canais de comunicação em massa (incluindo as redes sociais) e o nível de importância atribuído às medidas preventivas no início da pandemia. As mudanças no comportamento das pessoas, mesmo dentro de um grupo de nível educacional alto, que inicialmente considerava as medidas preventivas muito importantes (91%), apresenta considerável queda na segunda pesquisa realizada (redução para 82%). Há a necessidade urgente de reforço de medidas preventivas para redução de casos e óbitos por covid-19 no Brasil, aliadas a recomendações com informações claras como a importância da vacinação para evitar baixas taxas de cobertura vacinal que se apresentam em outras doenças preveníveis por vacinas.

Characterization and evaluation of the enzymatic activity of tetanus toxin submitted to cobalt-60 gamma radiation.

BACKGROUND: Tetanus toxin blocks the release of the inhibitory neurotransmitters in the central nervous system and causes tetanus and its main form of prevention is through vaccination. The vaccine is produced by inactivation of tetanus toxin with formaldehyde, which may cause side effects. An alternative way is the use of ionizing radiation for inactivation of the toxin and also to improve the potential immunogenic response and to reduce the post-vaccination side effects. Therefore, the aim of this study was to characterize the tetanus toxin structure after different doses of ionizing radiation of 60Co. METHODS: Irradiated and native tetanus toxin was characterized by SDS PAGE in reducing and non-reducing conditions and MALD-TOF. Enzymatic activity was measured by FRET substrate. Also, antigenic properties were assessed by ELISA and Western Blot data. RESULTS: Characterization analysis revealed gradual modification on the tetanus toxin structure according to doses increase. Also, fragmentation and possible aggregations of the protein fragments were observed in higher doses. In the analysis of peptide preservation by enzymatic digestion and mass spectrometry, there was a slight modification in the identification up to the dose of 4 kGy. At subsequent doses, peptide identification was minimal. The analysis of the enzymatic activity by fluorescence showed 35 % attenuation in the activity even at higher doses. In the antigenic evaluation, anti-tetanus toxin antibodies were detected against the irradiated toxins at the different doses, with a gradual decrease as the dose increased, but remaining at satisfactory levels. CONCLUSION: Ionizing radiation promoted structural changes in the tetanus toxin such as fragmentation and/or aggregation and attenuation of enzymatic activity as the dose increased, but antigenic recognition of the toxin remained at good levels indicating its possible use as an immunogen. However, studies of enzymatic activity of tetanus toxin irradiated with doses above 8 kGy should be further analyzed.

Medical Students Show Lower Physical Activity Levels and Higher Anxiety Than Physical Education Students: A Cross-Sectional Study During the COVID-19 Pandemic.

Objective: This study aimed to compare the time in physical activity (PA) [light (LPA), moderate and vigorous (MVPA)] and sedentary behavior (SB) (weekdays, weekends, or both) between Medical (MED) and Physical Education (PE) students who underwent remote classes imposed by the COVID-19. In addition, we compared symptoms of depression and anxiety and sleep quality. Methods: A cross-sectional study (272 MED and 95 PE students). The International Physical Activity Questionnaire (IPAQ), Beck Inventory (Anxiety, Depression), and Pittsburgh Sleep Quality were used to assess PA and SB, anxiety and depression symptoms, and quality of sleep, respectively. The data are presented as median and interquartile intervals 25-75. Results: We observed statistically significant differences between MED and PE students for MVPA [MED: 165 min per week (0-360) vs. PE: 420 min per week (180-670), p < 0.001], SB Total [MED: 10 h per day (8-12) vs. PE: 7 h per day (5-10), p < 0.001)], and anxiety symptoms [MED: 13 points (5-23) vs. PE: six points (2-16), p < 0.001)]. Conclusion: Together, our findings indicate that MED students spent less time in MVPA and more time in SB than PE students. MED students also presented worse mental health in the pandemic situation imposed by the COVID-19.

Characterization and evaluation of the enzymatic activity of tetanus toxin submitted to cobalt-60 gamma radiation

Tetanus toxin blocks the release of the inhibitory neurotransmitters in the central nervous system and causes tetanus and its main form of prevention is through vaccination. The vaccine is produced by inactivation of tetanus toxin with formaldehyde, which may cause side effects. An alternative way is the use of ionizing radiation for inactivation of the toxin and also to improve the potential immunogenic response and to reduce the post-vaccination side effects. Therefore, the aim of this study was to characterize the tetanus toxin structure after different doses of ionizing radiation of 60Co. Methods Irradiated and native tetanus toxin was characterized by SDS PAGE in reducing and non-reducing conditions and MALD-TOF. Enzymatic activity was measured by FRET substrate. Also, antigenic properties were assessed by ELISA and Western Blot data. Results Characterization analysis revealed gradual modification on the tetanus toxin structure according to doses increase. Also, fragmentation and possible aggregations of the protein fragments were observed in higher doses. In the analysis of peptide preservation by enzymatic digestion and mass spectrometry, there was a slight modification in the identification up to the dose of 4 kGy. At subsequent doses, peptide identification was minimal. The analysis of the enzymatic activity by fluorescence showed 35 % attenuation in the activity even at higher doses. In the antigenic evaluation, anti-tetanus toxin antibodies were detected against the irradiated toxins at the different doses, with a gradual decrease as the dose increased, but remaining at satisfactory levels. Conclusion Ionizing radiation promoted structural changes in the tetanus toxin such as fragmentation and/or aggregation and attenuation of enzymatic activity as the dose increased, but antigenic recognition of the toxin remained at good levels indicating its possible use as an immunogen. However, studies of enzymatic activity of tetanus toxin irradiated with doses above 8 kGy should be further analyzed.(AU)

Characterization and evaluation of the enzymatic activity of tetanus toxin submitted to cobalt-60 gamma radiation

Background: Tetanus toxin blocks the release of the inhibitory neurotransmitters in the central nervous system and causes tetanus and its main form of prevention is through vaccination. The vaccine is produced by inactivation of tetanus toxin with formaldehyde, which may cause side effects. An alternative way is the use of ionizing radiation for inactivation of the toxin and also to improve the potential immunogenic response and to reduce the post-vaccination side effects. Therefore, the aim of this study was to characterize the tetanus toxin structure after different doses of ionizing radiation of 60Co. Methods: Irradiated and native tetanus toxin was characterized by SDS PAGE in reducing and non-reducing conditions and MALD-TOF. Enzymatic activity was measured by FRET substrate. Also, antigenic properties were assessed by ELISA and Western Blot data. Results: Characterization analysis revealed gradual modification on the tetanus toxin structure according to doses increase. Also, fragmentation and possible aggregations of the protein fragments were observed in higher doses. In the analysis of peptide preservation by enzymatic digestion and mass spectrometry, there was a slight modification in the identification up to the dose of 4 kGy. At subsequent doses, peptide identification was minimal. The analysis of the enzymatic activity by fluorescence showed 35 % attenuation in the activity even at higher doses. In the antigenic evaluation, anti-tetanus toxin antibodies were detected against the irradiated toxins at the different doses, with a gradual decrease as the dose increased, but remaining at satisfactory levels. Conclusion: Ionizing radiation promoted structural changes in the tetanus toxin such as fragmentation and/or aggregation and attenuation of enzymatic activity as the dose increased, but antigenic recognition of the toxin remained at good levels indicating its possible use as an immunogen. However, studies of enzymatic activity of tetanus toxin irradiated with doses above 8 kGy should be further analyzed.

Viremia and viruria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient.

Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus denominated Tricodisplasia Polyomavirus (TSPyV). We report a case of TS 6 months after kidney transplantation in a 65 years-old woman under immunosuppression therapy with prednisone, mycophenolate and tacrolimus. The patient developed follicular papules on the face with a thickening of the skin and alopecia of the eyebrows, leading to distortion of the face and a leonine appearance characteristic of the disease. The skin biopsy confirmed the clinical diagnosis and the presence of TSPyV DNA in the skin was detected. Staining for SV40 was positive. Immunosuppression was changed: mycophenolate was withdrawn, tacrolimus reduced and everolimus added. Intravenous cidofovir and later on leflunomide were added. Although the literature has reported clinical success with topical cidofovir, we were unable to use it because this drug is not available. There was an improvement of skin lesions and on cosmetic appearance. The patient had three rejections (one clinically diagnosed and two other biopsy proven), progressed with renal failure and graft loss. Retrospective analysis of stored urine and blood samples detected TSPyV DNA in some of those samples two months before the TS clinical development. This case highlights the TSPyV detection in blood and urine samples before the development of skin lesions.