Brazilian Green Propolis: Effects In Vitro and In Vivo on Trypanosoma cruzi

The composition of a Brazilian green propolis ethanolic extract (Et-Bra) and its effect on Trypanosoma cruzi trypomastigotes and other pathogenic microorganisms have already been reported. Here, we further investigated Et-Bra targets in T. cruzi and its effect on experimental infection of mice. The IC50/4 days for inhibition of amastigote proliferation was 8.5 ± 1.8 μg mL−1, with no damage to the host cells. In epimastigotes Et-Bra induced alterations in reservosomes, Golgi complex and mitochondrion. These effects were confirmed by flow cytometry analysis. In trypomastigotes, Et-Bra led to the loss of plasma membrane integrity. The in vitro studies indicate that Et-Bra interferes in the functionality of the plasma membrane in trypomastigotes and of reservosomes and mitochondrion in epimastigotes. Acutely infected mice were treated orally with Et-Bra and the parasitemia, mortality and GPT, GOT, CK and urea levels were monitored. The extract (25–300 mg kg−1 body weight/day for 10 days) reduced the parasitemia, although not at significant levels; increased the survival of the animals and did not induce any hepatic, muscular lesion or renal toxicity. Since Et-Bra was not toxic to the animals, it could be assayed in combination with other drugs. Et-Bra could be a potential metacyclogenesis blocker, considering its effect on reservosomes, which are an important energy source during parasite differentiation

Impact of Covid-19 on Mental Health among Healthcare Workers in India: A Mixed-Methods Systematic Review

Healthcare workers (HCWs) experienced significant mental health challenges during the COVID-19 pandemic. This review aimed comprehensively assess the impact of the COVID-19 pandemic on the mental health of HCWs in India. A mixed-methods review adopted a results-based convergent approach incorporating quantitative and qualitative data. A comprehensive literature search was conducted in relevant databases: PubMed-MEDLINE, CINAHL, Web of Science, and ProQuest. All available full-text studies in the English language that assessed the mental health outcomes (anxiety, stress, depression) of HCWs during the pandemic and published till February 28, 2022, were included. A total of 31 studies were included in this review (27 quantitative studies, three qualitative studies, and one mixed-method study). The pooled prevalence of depression, anxiety, and stress was 32.96%, 29.49%, and 33.47 %, respectively among the HCWs in India. The qualitative analysis resulted in the themes: challenges faced, and coping strategies used during the COVID-19 pandemic. Integration of quantitative and qualitative findings using social determinants of health framework resulted in various contributing factors and coping strategies. There is a need for a supportive work environment, mental health support, and mental health policies for HCWs in India

Silent circulation of Chikungunya virus among pregnant women and newborns in the Western Brazilian Amazon before the first outbreak of chikungunya fever

The prevalence of immunity to Chikungunya virus (CHIKV) in pregnant women and newborns in the Western Brazilian Amazon was assessed at a time when previous studies did not report chikungunya fever in the area. In 435 asymptomatic pregnant women and 642 healthy unrelated newborns, the presence of IgM and IgG antibodies to CHIKV were determined by a commercial ELISA. All participants were negative to IgM anti-CHIKV. Anti-CHIKV IgG was identified in 41 (9.4%) pregnant women and 66 (10.3%) newborns. The presence of anti-CHIKV IgG was positively associated with the lowest socioeconomic status in pregnant women (OR 2.54, 95% CI 1.15-5.62, p=0.021) and in the newborns’ mothers (OR 5.10, 95% CI 2.15-12.09, p< 0.001). Anti-CHIKV IgG was also associated with maternal age in both, the pregnant women (OR 1.06, 95% CI 1.00-1.11, p=0.037) and the newborns’mothers (OR 1.08, 95% CI 1.03-1.12, p=0.001). Pregnancy outcomes in which the mother or the newborn was anti-CHIKV IgG positive proceeded normally. Negative CHIKV serology was associated with being positive for DENV antibodies and having had malaria during pregnancy. These findings showed that there was already a silent circulation of CHIKV in this Amazon region before the first outbreak of chikungunya fever. Furthermore, seropositivity for CHIKV was surprisingly frequent (10%) in both, pregnant women and newborns, affecting mainly low-income women

How likely are adaptive responses to mitigate the threats of climate change for amphibians globally?

Whether species are capable of adapting to rapid shifts in climate raises considerable interest. Analyses based on niche models often assume niche conservatism and equilibrium with climate, implying that species will persist only in regions where future climatic conditions match their current conditions and that they will colonize these regions promptly. However, species may adapt to changing climate and persist where future climates differ from their current optimum. Here, we provide a first macroecological generalization to the approach of evolutionary rescue, by comparing the expected shift in mean temperature within the geographic range of 7193 species of amphibians worldwide, under alternative warming scenarios. Expected evolutionary change is expressed in units of standard deviations of mean temperature, per generation (Haldanes) and compared with theoretical models defining the maximum sustainable evolutionary rates (MSER) for each species. For the pessimistic emission scenario RCP8.5, shifts in mean temperature vary between near-zero and 6°C within the geographic ranges for most species, with a median equal to 3.75°C. The probability of evolutionary rescue in temperature peaks is higher than 0.05 for about 55% of the species and higher than 0.95 for only 12% of the species. Therefore, the predicted shift in mean temperature would be too extreme to deal with for almost half of the species. When evolutionary plasticity is incorporated, this scenario becomes more optimistic, with about 44% of the species being likely to shift their thermal peaks tracking future warming. These figures are not random in geographical space: evolutionary rescue would be unlikely in the tropics, especially in South America (Amazonia), parts of Africa, Indonesia, and in the Mediterranean region. Given the uncertainty in demographic and genetic parameters for species’ responses to climate change, we caution that it remains difficult to assess the realism of the macroecological generalization. In any case, it may be precautionary to assume that our results are not liberal, showing low probability of adaptation for most of the species and thus that the persistence of populations by evolutionary rescue may, in general, be unlikely in the long term

Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

Acupuncture at “Zusanli” (St.36) and “Sanyinjiao” (SP.6) Points on the Gastrointestinal Tract: A Study of the Bioavailability of 99mTc-Sodium Pertechnetate in Rats

The objective of this study is to investigate the differences of acupuncture effect between the Zusanli (St.36) and Sanyinjiao (SP.6) points on the gastrointestinal-tract (GIT) segment performed by the bioavailability of 99mTc-sodium-pertechnetate (Na99mTcO4) in rats. Male Wistar rats (n = 21) were allocated into three groups of seven each. Group 1 was treated by acupuncture bilaterally at St.36; Group 2 at SP.6; and Group 3 was untreated (control). After 10 min of needle insertion in anesthetized rats, 0.3 mL of Na99mTcO4 (7.4 MBq) was injected via ocular-plexus. After 20 min, the exitus of animals was induced by cervical-dislocation and GIT organs isolated. However, immediately before the exitus procedure, blood was collected by cardiac-puncture for blood radio-labeling (BRL). The radioactivity uptake of the blood constituents was calculated together with the GIT organs by a well gamma counter. The percentage of injected dose per gram of tissue (%ID/g) of Na99mTcO4 was calculated for each GIT organs, while BRL was calculated in %ID. According to the one-way ANOVA, the stomach, jejunum, ileum from the treated groups (Group 1 and Group 2) had significant differences compared to the controls (Group 3). However, between the treated groups (Group 1 and Group 2), there were significant differences (P < .05) in the stomach, jejunum, ileum, cecum, transverse and rectum. In BRL analysis, Group 2 showed significant increase and decrease of the insoluble and soluble fractions of the blood cells, respectively (P < .0001). The authors suggest that St.36 may have a tendency of up-regulation effect on GIT, whereas SP.6, down-regulation effect. However, further rigorous experimental studies to examine the effectiveness of acupuncture in either acupuncture points need to be carried out

Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi