Maternal chronic caffeine intake impairs fertility, placental vascularization and fetal development in mice.

Caffeine is commonly consumed by pregnant women to avoid fatigue or as a habit. However, it is not clearly determined its side effects to the conceptuses. This study evaluated placental morphofunctional alterations after maternal chronic caffeine intake and the effects on fetal growth. Female Swiss mice received, via gavage, caffeine doses (either 60, 120 or 240 mg/kg/day) seven days before mating until gestational days-(GD) 11.5 or 17.5. Fetal biometrical parameters were assessed, and placentae were either submitted to histomorphometrical or molecular evaluation of angiogenesis (placental growth factor-1[PlGF-1]), apoptosis (Caspase-3) and proliferation (Ki-67) markers (evaluated in Swiss dams) and to intravital microscopy (evaluated in C57BL/6 dams). Caffeine exposed fetuses exhibited intrauterine growth restriction in a sex-dependent manner, with greater commitment of female fetuses (P < 0.05). In addition, placentae from dams that received 120 mg/kg/day showed less irrigation by maternal blood and greater development of fetal vasculature, characterized by higher number of larger vessels (P < 0.05). Although no effects on apoptosis (Caspase-3) and angiogenesis (PlGF-1) were observed, dams treated with 60 mg/kg/day showed greater placental cell proliferation (Ki-67 staining) at GD 11.5 (P < 0.05). The group treated with 240 mg/kg/day exhibited only one pregnant dam for each gestational age, suggesting that this high caffeine consumption may compromise fertility. Taken together, even in the doses currently ingested by many pregnant women, caffeine has detrimental effects on placental vasculature and fetal development in mice. Therefore, our results strongly suggest that caffeine consumption in human pregnancies greater than the recommended doses should be avoided.

Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics.

Introduction: The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Methods: Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Results: Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5 ± 72.3, p<0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 arbitrary units. Conclusions: Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.

Comparison of diagnostic performance of RT-qPCR, RT-LAMP and IgM/IgG rapid tests for detection of SARS-CoV-2 among healthcare workers in Brazil.

BACKGROUND: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. METHODS: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests - RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP - and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. RESULTS: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. CONCLUSION: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19.

Intrauterine growth restriction and its impact on intestinal morphophysiology throughout postnatal development in pigs.

Intrauterine growth restriction (IUGR) compromises fetal development, leading to low birth weight, and predisposes to gastrointestinal disorders. Pigs that suffered IUGR present poor postnatal development, resulting in great economic losses to the industry. The small intestine may be involved with impaired development, but studies investigating this issue are still limited. Thus, the present study aimed to investigate small intestine morphofunctional alterations in IUGR pigs throughout the production phases (birth to 150 days). IUGR pigs presented lower body weight from birth to the finishing phase (P < 0.05). Although histomorphometrical parameters were not affected during the pre-weaning period, their commitment was observed specifically in the duodenum of the IUGR group at older ages (P < 0.05). The most detrimental effects on the small intestine, such as deeper duodenum crypts' depth, lower villus height:crypt depth ratio and absorptive area, increased apoptosis and lower proliferation of the duodenum epithelium were noticed at 70 days of age (P < 0.05). Additionally, IUGR pigs presented the lowest chymotrypsin and amylase activities at 70 and 150 days of age, respectively (P < 0.05). These findings may contribute to the elucidation of morphofunctional disorders of the small intestine in IUGR pigs throughout the different production phases, suggesting that poor postnatal development may be due to intestinal damage.

Intrauterine growth restriction: screening and diagnosis using animal models.

Intrauterine growth restriction (IUGR) is a serious condition of multifactorial origin, mainly caused by maternal malnutrition, multiple gestation associated with nutrient competition, abuse of nocive substances and infections. The diagnosis of such syndrome is complex, as its own manifestations can mask its occurrence, requiring a thorough assessment of body weight and size. Moreover, it is not responsive to any kind of treatment. There is evidence that IUGR may predispose the individual to several pathologies, such as diabetes, hypertension and metabolic syndrome in adulthood, and it has also been linked to thrifty phenotype hypothesis. Thus, a healthy lifestyle is needed to better prevent those pathologies. Given the world high prevalence and importance of IUGR, mainly in developing countries, this review is focused on discussing how different animal models contribute to the biological screening and diagnosis of this condition.