Corrigendum to "Trypanosoma spp. Neobats: Insights about those poorly known trypanosomatids" [Int. J. Parasitol. Parasites Wildl. 16 (2021) 145-152].

[This corrects the article DOI: 10.1016/j.ijppaw.2021.09.003.].

Maternal and long-term offspring outcomes of obesity during pregnancy.

PURPOSE: Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also rising during pregnancy. This condition not only increases the risk of noncommunicable diseases on the mother, such as cardiovascular disease and diabetes, but also transfers this risk to the offspring. METHODS: This is a narrative review based on scientific and review articles on the matter. RESULTS: Obesity is associated with an increased risk of gestational diabetes mellitus, gestational hypertension and preeclampsia, venous thromboembolism, infection, and mental health problems. Furthermore, it has an impact on the progress of labor and induction matters. Regarding offspring outcomes, it is related to higher incidence of congenital anomalies, perinatal mortality, and the occurrence of large for gestational age newborns. Still, it has implications on cardiometabolic risk and neurodevelopment in offspring. CONCLUSION: It is, therefore, imperative to encourage the adoption of healthy lifestyles, especially in the peri-conception and interpregnancy periods. Likewise, there must be support in the multidisciplinary monitoring of these pregnant women to minimize associated complication rates.

Trypanosomatid diversity in a bat community of an urban area in Campo Grande, Mato Grosso do Sul, Brazil.

Bats have a long evolutionary history with trypanosomatids, but the role of these flying mammals on parasite transmission cycles in urban areas, especially for Trypanosoma and Leishmania species, remains poorly known. The objective of this study was to evaluate the species richness of trypanosomatids parasitizing a bat community in Campo Grande (CG), a state capital within the Cerrado of the Brazilian Midwest. We evaluated 237 bats of 13 species by means of hemoculture and molecular detection in spleen samples. The bat community of CG appears to participate in the transmission cycles of various species of trypanosomatids. We report an overall trypanosomatid detection rate of 34.2% (n = 81), involving 11 out of 13 sampled bat species. We identified six species of trypanosomatids from 61 bats by analyzing SSU rRNA and/or kDNA: Trypanosoma cruzi DTU TcI, T. c. marinkellei, T. dionisii, Leishmania infantum, L. amazonensis, and T. janseni, with this latter being detected by hemoculture for the first time in a bat species. We also detected a Molecular Operational Taxonomic Unit, Trypanosoma sp. DID, in the phyllostomids Glossophaga soricina and Platyrrhinus lineatus. The highest trypanosomatid richness was observed for Sturnira lilium, which hosted three species: L. infantum, T. dionisii and T. janseni. Given that visceral leishmaniasis is endemic in CG, special focus should be placed on L. infantum. Moreover, L. amazonensis and T. cruzi warrant attention, since these are zoonotic parasites responsible for human cases of tegumentary leishmaniasis and Chagas disease, respectively. In this respect, we discuss how bat communities may influence the Leishmania spp. transmission in endemic areas.

Breastfeeding and autism spectrum disorder: case-control study / Transtorno do espectro do autismo e aleitamento materno: estudo de caso controle

Abstract Objectives: to evaluate the association between breastfeeding and Autism Spectrum Disorder (ASD) in children and adolescents. Methods: this is a case-control study carried out in the north of the state of Minas Gerais, Brazil, which included 248 children and adolescents diagnosed with ASD (case group) and 886 children and adolescents without a diagnosis of ASD (control group).Interviews were conducted with the mothers of children and adolescents and a semi-structured questionnaire was used to collect data. For data analysis, a multiple logistic regression model was adopted. The magnitude of associations was estimated by the odds ratio (OR). Three multiple models were fitted: Model 1: presence or absence of breastfeeding; Model 2: duration of breastfeeding; Model 3: duration of exclusive breastfeeding. Results: ASD was associated with the absence of breastfeeding in the three adjusted models: Model 1: OR=2.1, CI95%=1.1-4.1; Model 2: OR=2.3, CI95%=1.2-4.5; Model 3: OR=2.3, CI95%=1.2-4.5. Conclusions: individuals with ASD were more likely to have not received breastfeeding, however, due to the nature of case control studies, it cannot be stated that breastfeeding prevents ASD. Conducting a cohort study may clarify this relationship.

Resumo Objetivos: avaliar a associação entre aleitamento materno e Transtorno do Espectro do Autismo (TEA) em crianças e adolescentes. Métodos: trata-se de um estudo caso-controle realizado no norte de Minas Gerais, Brasil, que incluiu 248 crianças e adolescentes com diagnóstico de TEA (grupo caso) e 886 crianças e adolescentes sem diagnóstico de TEA (grupo controle). Foram realizadas entrevistas com as mães das crianças e adolescentes e utilizado um questionário semiestruturado para coleta dos dados. Para análise dos dados foi adotado modelo de regressão logística múltipla. A magnitude das associações foi estimada pela Odds Ratio (OR). Três modelos múltiplos foram ajustados: Modelo 1: presença ou ausência de aleitamento materno; Modelo 2: duração do aleitamento materno; Modelo 3: duração do aleitamento materno exclusivo. Resultados: o TEA foi associado à ausência de aleitamento materno nos três modelos ajustados: Modelo 1: OR=2,1, IC95%=1,1-4,1; Modelo 2: OR=2,3, IC95%=1,2-4,5; Modelo 3: OR=2,3, IC95%=1,2-4,5. Conclusões: os indivíduos com TEA tiveram maiores chances de não terem recebido aleitamento materno, no entanto, devido à natureza dos estudos de caso-controle, não se pode afirmar que o aleitamento materno previna o TEA. A realização de um estudo de coorte poderá esclarecer essa relação.

Unraveling the diversity of Trypanosoma species from Central Mexico: Molecular confirmation on the presence of Trypanosoma dionisii and novel Neobat linages.

Bats are one of the groups of mammals with the highest number of associated Trypanosoma taxa. There are 50 Trypanosoma species and genotypes infecting more than 75 species of bats across five continents. However, in Mexico, the inventory of species of the genus Trypanosoma associated with bats is limited to only two species (Trypanosoma vespertilionis and Trypanosoma cruzi) even though 140 species of bats inhabit this country. Specifically, 91 bat species have been recorded in the state of Veracruz, but records of trypanosomatids associated with this mammalian group are absent. Due to the complex Trypanosoma-bat relationship, the high diversity of bat species in Veracruz, as well as the lack of records of trypanosomatids associated with bats for this state, the aim of this work was to analyze the diversity of species of the genus Trypanosoma and their presence from a bat community in the central area of the state of Veracruz, Mexico. During the period of January to August 2022 in the Tequecholapa Environmental Management Unit where bats were collected using mist nets and blood samples were obtained from their thumbs. We extracted genetic material and amplified a fragment of 800 bp of the 18S ribosomal gene of the genus Trypanosoma by conventional PCR. The positive amplicons were sequenced, and phylogenetic reconstruction was performed to identify the parasite species. A total of 285 bats (149♀, 136♂) belonging to 13 species from 10 genera and a single family (Phyllostomidae) were collected. Twenty-three specimens from six species tested positive for the presence of Trypanosoma dionisii, Trypanosoma sp. Neobat 4, and a potential novelty species provisionally named as Trypanosoma sp. Neobat 6. The results of the present work increase the number of species of the genus Trypanosoma infecting bats in Mexico and in the Neotropical region.

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence.

Serotonin and interleukin 10 (IL-10) may play a role in gestational diabetes mellitus. Hyperglycemic environment, the detrusor musculature of the bladder and pelvic floor muscles may become damaged, leading to urination problems and urine viscosity in pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. Urine and blood samples were collected from pregnant women between 24 and 28 weeks of gestation. The serotonin concentration and cytokine IL-10 levels were evaluated in plasma and urine. In the total blood and urine, the viscosity was evaluated in the presence and absence of exogenous serotonin and IL-10. The plasma serotonin levels decreased, while the urine serotonin levels increased in the normoglycemic incontinent (NG-I), hyperglycemic continent (GDM-C), and hyperglycemic incontinent (GDM-I) groups. The IL-10 in the plasma decreased in the GDM-I group and was higher in the urine in the NG-I and GDM-I groups. The blood viscosity was higher, independently of urinary incontinence, in the GDM groups. The serotonin increased the blood viscosity from women with GDM-C and urine in the NG-I, GDM-C, and GDM-I groups. Blood and urine in the presence of IL-10 showed a similar viscosity in all groups studied. Also, no difference was observed in the viscosity in either the blood or urine when in the presence of serotonin and IL-10. These findings suggest that serotonin and IL-10 have the potential to reduce blood viscosity in pregnant women with gestational diabetes and specific urinary incontinence, maintaining values similar to those in normoglycemic women's blood.

Supraphysiological doses of nandrolone decanoate disrupts spermatogenesis but did not interfere on embryo rate.

The aim of this study was to investigate the effects of 10 mg/kg/week of nandrolone decanoate (DECA - Deca Durabolin®) on body composition, hormonal levels, spermatic parameters, redox status, and morphometric parameters of testicle and epididymis; furthermore, the fertility capacity of Wistar rats was measured thought in vitro fertilization (IVF). The animals (n = 16) were divided into two groups: control group (CTRL, n = 8), which received only vehicle composed by peanut oil and 10% of the benzoic alcohol and nandrolone decanoate group (DECA, n = 8), which received intramuscular injections of DECA for 8 weeks, both groups were treated for 8 weeks. The results demonstrate significative decrease in visceral fat, testosterone levels, and thiol content on epididymis, reduction on normal sperm parameters, and deleterious effect on testicles and epididymis tissue morphology showing reduction of germ height and luminal diameter on the DECA group. Thus, it can be concluded that high doses of nandrolone decanoate impairs male reproductive parameters.

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue.

Studies have documented the high occurrence of several tumors, including female breast cancer, in populations occupationally exposed to pesticides worldwide. It is believed that in addition to direct DNA damage, other molecular alterations that indicate genomic instability are associated, such as epigenetic modifications and the production of inflammation mediators. The present study characterized the profile of inflammatory changes in the breast tissue of women without cancer occupationally exposed to pesticides. In samples of normal breast tissue collected during biopsy and evaluated as negative for cancer by a pathologist, oxidative stress levels were assessed as inflammatory markers through measurements of lipoperoxides and total antioxidant capacity of the sample (TRAP) by high-sensitivity chemiluminescence, as well as levels of nitric oxide (NOx) metabolites. The levels of inflammation-modulating transcription factors PPAR-γ (peroxisome proliferator-activated receptor gamma) and NF-κB (nuclear factor kappa B) were also quantified, in addition to the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12). The levels of lipoperoxides, TRAP, and NOx were significantly lower in the exposed group. On the other hand, PPAR-γ levels were increased in the breast tissue of exposed women, with no variation in NF-κB. There was also a rise of TNF-α in exposed women samples without significant variations in IL-12 levels. These findings suggest an inflammatory signature of the breast tissue associated with pesticide exposure, which may trigger mechanisms related to mutations and breast carcinogenesis.

Effects on Colonization Factors and Mechanisms Involved in Antimicrobial Sonophotodynamic Inactivation Mediated by Curcumin.

Photodynamic (PDI) and sonodynamic (SDI) inactivation have been successfully employed as antimicrobial treatments. Moreover, sonophotodynamic inactivation (SPDI), which is the simultaneous application of PDI and SDI, has demonstrated greater effects. This study assessed the effects of PDI (PDI group), SDI (SDI group) and SPDI (SPDI group) using curcumin as a sensitizer on the metabolism, adhesion capability, biofilm formation ability and structural effects in a Staphylococcus aureus biofilm. Moreover, the production of reactive oxygen species (ROS) and the degradation spectrum of curcumin under the irradiation sources were measured. SPDI was more effective in inactivating the biofilm than PDI and SDI. All treatments reduced the adhesion ability of the bacteria: 58 ± 2%, 58 ± 1% and 71 ± 1% of the bacterial cells adhered to the polystyrene plate after the SPDI, SDI and PDI, respectively, when compared to 79 ± 1% of the untreated cells (control group). This result is probably related to the metabolism cell reduction after treatments. The metabolism of cells from the PDI group was 89 ± 1% lower than the untreated cells, while the metabolic activity of SDI and SPDI groups were 82 ± 2% and 90 ± 1% lower, respectively. Regarding the biofilm formation ability, all treatments (SPDI, SDI and PDI) reduced the total biomass. The total biomass of the PDI, SDI and SPDI groups were 26 ± 2%, 31 ± 5% and 35 ± 6% lower than the untreated biofilm (control group), respectively. Additionally, all treatments produced ROS and caused significant structural changes, reducing cells and the extracellular matrix. The light caused a greater absorbance decay of the curcumin; however, the US did not expressively alter its spectrum. Finally, SPDI had improved antimicrobial effects, and all treatments exhibited similar effects in the colonization factors evaluated.

Photoantimicrobial chitosan-gelatin-pomegranate peel extract films for strawberries preservation: From microbiological analysis to in vivo safety assessment.

This study aimed to investigate the application of biopolymeric materials (chitosan, gelatin, and pomegranate peel extract as photosensitizer) and antimicrobial photodynamic therapy (aPDT) on the physicochemical and microbial safety of strawberries. The photosensitizer potential of the materials was confirmed by a light-dose-dependent photobleaching profile. The application of light (525 nm; 50 J cm-2) decreased by >2 log CFU mL-1 the survival of Staphylococcus aureus on the surface of the photoactive-biopolymeric films. Moreover, the materials did not present in vivo cytotoxicity using Danio rerio (Zebrafish) as well as cytophytotoxic, genotoxic, or mutagenic potentials against Allium cepa plant model, which points out their safety to be used as films without posing a risk to the humans and the environment. The photoactive-polymeric coatings were able to maintain the strawberries weight, and the association with green light was 100 % effective in delaying fungal contamination. These coated-strawberries presented a significant reduction in S. aureus survival after light application (5.47-4.34 log CFU mL-1). The molecular level analysis of the photoactive compound cyanidin-3-glucoside indicates absorption on UV-Vis consistent with aPDT action. Therefore, this study showed that the antimicrobial effects of aPDT combined with photoactive-biopolymeric coatings were enhanced, while the quality of the strawberries was maintained.

Sonophotodynamic inactivation of Pseudomonas aeruginosa biofilm mediated by curcumin.

The inactivation of Pseudomonas aeruginosa biofilm is a major challenge, as biofilms are less responsive to conventional treatments and responsible for persistent infections. This has led to the investigation of alternative approaches for biofilm control such as photodynamic (PDI) and sonodynamic (SDI) inactivation. The combination of them, known as Sonophotodynamic Inactivation (SPDI), has improved the effectiveness of the process. Curcumin, a well-established photosensitizer, has been identified as a potential sonosensitizer. This study evaluated the most effective combination for SPDI against P. aeruginosa biofilms in vitro, varying curcumin concentrations and ultrasound intensities. The results indicated that the inactivation was directly proportional to the curcumin concentration. Using curcumin 120 µM and 3.0 W.cm-2 of ultrasound intensity, SPDI demonstrated the highest and the best synergistic results, equivalent to 6.9 ± 2.1 logs of reduction. PDI reduced 0.7 ± 0.9 log and SDI had no effect. In conclusion, SPDI with curcumin is a promising approach for biofilm inactivation.

Fast Fabrication of Multifunctional PCL/Curcumin Nanofibrous Membranes for Wound Dressings.

Therapeutic intervention to skin wounds requires covering the affected area with wound dressings. Interdisciplinary efforts have focused on the development of smart bandages that can perform multiple functions. In this direction, here, we designed a low cost (U$0.012 per cm2) multifunctional therapeutic wound dressing fabricated by loading curcumin (CC) into poly(ϵ-caprolactone) (PCL) nanofibers using solution blow spinning (SBS). The freestanding PCL/CC bandages were characterized by distinct physicochemical approaches and were successful in performing varied functions, including controlled release of CC, colorimetric indication of the wound conditions, barrier against microorganisms, being biocompatible, and providing a photosensitive platform for antimicrobial photodynamic therapy (aPDT). The chemical nature of PCL and CC and the interactions between these components allowed CC to be released for 192 h (ca. 8 days), which could be correlated with the Korsmeyer-Peppas model, with a burst release suitable to treat the inflammatory phase. Due to the CC keto-enol tautomerism, an optical indication of the healing status could be obtained using PCL/CC, which occurred immediately, ranging between red/orange and yellow shades. The effect against pathogenic microorganisms evaluated by agar disc-diffusion, affected skin wound simulation (ex vivo), and microbial penetration tests demonstrated the ability to block and inhibit microbial permeation in different environments. The biocompatibilities of PCL and PCL/CC were verified by in vitro cytotoxicity study, which demonstrated that cell viabilities average above 94 and 96% for human dermal fibroblasts. In addition, the proposed bandage responded to aPDT applied to an in vivo assay, showing that, when irritated, PCL/CC was able to reduce the bacteria present on the real wound of mice. In summary, our findings demonstrate that using PCL and CC to produce nonwovens by the SBS technique offers potential for the rapid fabrication of biocompatible and multifunctional wound dressings, paving the way for large-scale production and utilization of such dressings in the treatment of skin wounds.

Excess body weight significantly affects systemic and tumor inflammatory status and correlates to poor prognosis parameters in patients with breast cancer.

Introduction: Obesity is a pro-inflammatory disease critical for developing breast cancer (BC), which impacts the profiles of systemic inflammatory mediators and determinants of different disease clinical outcomes remains little explored. Methods: A total of 195 patients diagnosed with breast cancer were included. Aiming to exclude chemotherapy interference on circulating mediators, samples were collected at diagnosis, out of the treatment period. Patients were classified as normal weight (BMI up to 24.9 kg/m2) or overweight (BMI ≥25.0 kg/m2). Serum levels of IL-4, IL-12, hydroperoxides, and nitric oxide metabolites (NOx) were measured. Also, tumor expression of inducible nitric oxide synthase (iNOS), TGF-ß1, CD4+, and CD8+ lymphocytes were evaluated. Results: IL-4 levels were significantly increased in the overweight BC group (p = 0.0329), including patients with luminal B subtype (p = 0.0443), presence of lymph node metastases (p = 0.0115) and age of diagnosis below 50 years, (p = 0.0488). IL-12 levels were significantly increased in overweight BC patients with lymph node metastases (p = 0.0115). Hydroperoxides were increased in overweight BC patients (p = 0.0437), including those with tumors smaller than 2 cm (p = 0.05). NOx levels were also increased in overweight BC patients, including those with luminal B disorders (p = 0.0443), high-grade tumors (p = 0.0351) and lymph node metastases (p = 0.0155). The expression of iNOS (p < 0.001) and TCD4+ lymphocytes (p = 0.0378) was significantly investigated in tumor biopsies from overweight BC women. Conclusions: These data provide a picture of the influence of excess body weight on inflammatory mediators' systemic and tumoral profiles, especially in patients displaying poor outcome BC.

The Expression of CTLA-4 in Breast Tumors and Tumor-Infiltrating Leukocytes Affects Patients' Systemic Inflammatory Status and Varies According to Their Molecular Subtypes.

Recent evidence has pointed out that the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression is a poor prognosis factor. However, the implications of CTLA-4 expression on circulating inflammatory mediators are unclear for breast cancer. Tumor biopsies and blood samples were collected from 117 breast cancer patients. Oxidative stress parameters were evaluated in plasma samples by measuring the lipoperoxidation profile and nitric oxide metabolites (NOx). Interleukins 12 (IL-12) and 4 (IL-4) were assessed by ELISA. CTLA-4 expression was determined by immunofluorescence assessed by its labeling in tumor-infiltrating leukocytes (TILs) or breast tumors. Correlations between CTLA-4 expression in breast tumors with TCD4/TCD8 infiltrating lymphocyte and inflammation-related genes were performed using data from TIMER 2.0/TCGA databases (n = 2160). CTLA-4 expression in TILs significantly correlated to triple-negative breast tumors. Patients carrying CTLA-4-positive tumors exhibited lower plasmatic NOx levels, and those expressing CTLA-4 in TILs had reduced levels of IL-12 in plasma. No changes in either IL-4 or lipid peroxidation profiles were detected concerning any CTLA4 status. Compared to the Luminal A ones, oxidative stress parameters and cytokines were observed in patients bearing triple-negative tumors. CTLA-4 expression in all breast cancer subtypes positively correlated to TCD4/TCD8 lymphocyte infiltrates, as well as to the pro-inflammatory genes IL12A, IL4, NFKB1, NFKB2, NOS1, NOS2, and NOS3. CTLA-4 expression in both tumor and TILs can affect the systemic inflammatory status of breast cancer patients, especially antitumor molecules such as IL-12 and NOx that correlate to more aggressive disease.

Using conservation genetics to prioritise management options for an endangered songbird.

Genetic data can be highly informative for answering questions relevant to practical conservation efforts, but remain one of the most neglected aspects of species recovery plans. Framing genetic questions with reference to practical and tractable conservation objectives can help bypass this limitation of the application of genetics in conservation. Using a single-nucleotide polymorphism dataset from reduced-representation sequencing (DArTSeq), we conducted a genetic assessment of remnant populations of the endangered forty-spotted pardalote (Pardalotus quadragintus), a songbird endemic to Tasmania, Australia. Our objectives were to inform strategies for the conservation of genetic diversity in the species and estimate effective population sizes and patterns of inter-population movement to identify management units relevant to population conservation and habitat restoration. We show population genetic structure and identify two small populations on mainland Tasmania as 'satellites' of larger Bruny Island populations connected by migration. Our data identify management units for conservation objectives relating to genetic diversity and habitat restoration. Although our results do not indicate the immediate need to genetically manage populations, the small effective population sizes we estimated for some populations indicate that they are vulnerable to genetic drift, highlighting the urgent need to implement habitat restoration to increase population size and to conduct genetic monitoring. We discuss how our genetic assessment can be used to inform management interventions for the forty-spotted pardalote and show that by assessing contemporary genetic aspects, valuable information for conservation planning and decision-making can be produced to guide actions that account for genetic diversity and increase chances of recovery in species of conservation concern.

Corrigendum: Leishmania infantum infecting the carnivore Nasua nasua from urban forest fragments in an endemic area of visceral leishmaniasis in Brazilian Midwest.

[This corrects the article DOI: 10.3389/fcimb.2022.1050339.].

Old Methods, New Insights: Reviewing Concepts on the Ecology of Trypanosomatids and Bodo sp. by Improving Conventional Diagnostic Tools.

Mixed infections by different Trypanosoma species or genotypes are a common and puzzling phenomenon. Therefore, it is critical to refine the diagnostic techniques and to understand to what extent these methods detect trypanosomes. We aimed to develop an accessible strategy to enhance the sensitivity of the hemoculture, as well as to understand the limitations of the hemoculture and the blood clot as a source of parasitic DNA. We investigated trypanosomatid infections in 472 bats by molecular characterization (18S rDNA gene) of the DNA obtained from the blood clot and, innovatively, from three hemoculture sample types: the amplified flagellates ("isolate"), the pellet of the culture harvested in its very initial growth stage ("first aliquot"), and the pellet of non-grown cultures with failure of amplification ("sediment"). We compared (a) the characterization of the flagellates obtained by first aliquots and isolates; and (b) the performance of the hemoculture and blood clot for trypanosomatid detection. We observed: (i) a putative new species of Bodo in Artibeus lituratus; (ii) the potential of Trypanosoma cruzi selection in the hemoculture; (iii) that the first aliquots and sediments overcome the selective pressure of the hemoculture; and (iv) that the blood clot technique performs better than the hemoculture. However, combining these methods enhances the detection of single and mixed infections.

Consequences of the exposome to gestational diabetes mellitus.

The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including those from the environment, diet, behaviour, and endogenous processes. The exposome concept and the 2030 Agenda for the Sustainable Development Goals (SDGs) from the United Nations are the basis for understanding the aetiology and consequences of non-communicable diseases, including gestational diabetes mellitus (GDM). Pregnancy may be developed in an environment with adverse factors part of the immediate internal medium for fetus development and the external medium to which the pregnant woman is exposed. The placenta is the interface between maternal and fetal compartments and acts as a protective barrier or easing agent to transfer exposome from mother to fetus. Under and over-nutrition in utero, exposure to adverse environmental pollutants such as heavy metals, endocrine-disrupting chemicals, pesticides, drugs, pharmaceuticals, lifestyle, air pollutants, and tobacco smoke plays a determinant role in the development of GDM. This phenomenon is worsened by metabolic stress postnatally, such as obesity which increases the risk of GDM and other diseases. Clinical risk factors for GDM development include its aetiology. It is proposed that knowledge-based interventions to change the potential interdependent ecto-exposome and endo-exposome could avoid the occurrence and consequences of GDM.

Larval morphology of the avian parasitic genus Passeromyia: playing hide and seek with a parastomal bar.

The enigmatic larvae of the Old World genus Passeromyia Rodhain & Villeneuve, 1915 (Diptera: Muscidae) inhabit the nests of birds as saprophages or as haematophagous agents of myiasis among nestlings. Using light microscopy, confocal laser scanning microscopy and scanning electron microscopy, we provide the first morphological descriptions of the first, second and third instar of P. longicornis (Macquart, 1851) (Diptera: Muscidae), the first and third instar of P. indecora (Walker, 1858) (Diptera: Muscidae), and we revise the larval morphology of P. heterochaeta (Villenueve, 1915) (Diptera: Muscidae) and P. steini Pont, 1970 (Diptera: Muscidae). We provide a key to the third instar of examined species (excluding P. steini and P. veitchi Bezzi, 1928 (Diptera: Muscidae)). Examination of the cephaloskeleton revealed paired rod-like sclerites, named 'rami', between the lateral arms of the intermediate sclerite in the second and third instar larva. We reveal parastomal bars fused apically with the intermediate sclerite, the absence of which has so far been considered as apomorphic for second and third instar muscid larvae. Examination of additional material suggests that modified parastomal bars are not exclusive features of Passeromyia but occur widespread in the Muscidae, and rami may occur widespread in the Cyclorrhapha.

Rational-Based Discovery of Novel ß-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria.

Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In this context and considering the emergence and spread of drug-resistant P. falciparum isolates, the search for new antimalarial candidates becomes urgent. ß-carbolines alkaloids are good candidates since a wide range of biological activity for these compounds has been reported. Herein, we designed 20 chemical entities and performed an in silico virtual screening against a pool of P. falciparum molecular targets, the Brazilian Malaria Molecular Targets (BRAMMT). Seven structures showed potential to interact with PfFNR, PfPK7, PfGrx1, and PfATP6, being synthesized and evaluated for in vitro antiplasmodial activity. Among them, compounds 3−6 and 10 inhibited the growth of the W2 strain at µM concentrations, with low cytotoxicity against the human cell line. In silico physicochemical and pharmacokinetic properties were found to be favorable for oral administration. The compound 10 provided the best results against CM, with important values of parasite growth inhibition on the 5th day post-infection for both curative (67.9%) and suppressive (82%) assays. Furthermore, this compound was able to elongate mice survival and protect them against the development of the experimental model of CM (>65%). Compound 10 also induced reduction of the NO level, possibly by interaction with iNOS. Therefore, this alkaloid showed promising activity for the treatment of malaria and was able to prevent the development of experimental cerebral malaria (ECM), probably by reducing NO synthesis.