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Diarrhea is a prevalent and economically impactful ailment in cattle herds, resulting in substantial losses attributed to mortality, treatment expenses, and impaired calf growth. The aim of this study was to establish data about the occurrence of the main bacterial agents involved in diarrhea in dairy calves in the state of Maranhão, as well as to determine the most effective and/or resistant antibiotics, establishing a foundation for treatment and prevention protocols. The samples were collected with rectal swabs and initially cultivated on sheep blood agar (5%) and MacConkey agar and later on Salmonella-Shigella agar and eosin-methylene blue agar. Gram staining, biochemical tests, and antibiograms were performed on the obtained colonies. Ten municipalities were studied, with 230 calves evaluated from ten dairy farms. A total of 21 animals exhibited clinical signs of diarrhea, representing a frequency of 9.13%. The frequency of positive farms was 35%, and in 50% of municipalities. Bacteria isolated belonged to the Enterobacteriaceae family, with 71.4% Escherichia coli, 14.3% Enterobacter sp., 9.5% Proteus sp. and 4.8% Klebsiella sp. On the antibiogram, the bacteria that showed the highest resistance levels were those of the Proteus genus, followed by Enterobacter sp. and E. coli. The bacteria found are relevant for both animal and human health due to their zoonotic potential and serve as a public health alert since the isolates in this study showed in vitro resistance to several antibiotics, which predisposes them to the emergence of multidrug-resistant bacteria.

Background: The feline immunodeficiency virus (FIV) is responsible for a retroviral disease that affects domestic and wild cats worldwide, causing Feline Acquired Immunodeficiency Syndrome (FAIDS). FIV is a lentivirus from the family Retroviridae and its genome has 3 main structural genes: gag, pol and env. Phylogenetic studies have classified FIV into 7 subtypes according to the diversity among strains from the World, mainly in the env gene. Epidemiological analyses have demonstrated the high predominance of FIV-A and FIV-B. This in silico study aimed to perform a phylogenetic analysis to study FIV diversity worldwide. Materials, Methods & Results: A total of 60 whole genome sequences (WGS) and 122 FIV env gene sequences were included in 2 datasets, which were aligned using MAFFT version 7. Recombination among genomes and/or env genes was analyzed with RDP5 software. Phylogenetic analyses with both datasets were performed, after removing the recombinant sequences, by the W-IQ-TREE and constructed and edited by the FigTree. A total of 12 recombination events involving 19 WGS were detected. In addition, 27 recombination events involving 49 sequences were observed in the env gene. A high rate of recombinants was observed inter-subtypes (A/B and B/D) and intra-subtypes (A/A). All recombinants were removed from the subsequent phylogenetic analyses. Phylogenies demonstrated 6 distinct main clades, 5 from domestic cats (A, B, C, E, U) and 1 from wild cat sequences (W) in the WGS, as well as in the specific env gene analyses. Most clustered with subtype B sequences. In the WGS analysis, clade B had a prevalence of 65.9% Brazilian sequences (27/41) and 2.4% Japanese sequences (1/41). In the env gene analyses, clade B showed a prevalence of 43.8% of Brazilian sequences (32/73) and 20.5% of USA sequences (15/73). The results of both analyses also confirm the FIV-wide geographical distribution around the world. In the phylogenetic analyses carried out with WGS, sequences from China (1/41; 2.4%), Colombia (1/41; 2.4%) and the USA (1/41; 2.4%) were identified in clade A; sequence from Canada in clade C (1/41; 2.4%); sequence from Botswana belonged to clade E (1/41; 2.4%); sequences from Brazil clustered into clade U (2/41; 5% - data not yet published); and sequences belonging to the clade W were from Canada (1/41; 2.4%) and the USA (5/41; 12.3%). Specific env gene phylogenetic analyses showed sequences from Colombia (1/73; 1.4%), France (2/73; 2.7%), the Netherlands (3/73; 4.1%), Switzerland (2/73; 2.7%), USA (6/73; 8.3%), belonging to clade A; sequence from Canada belonging to clade C (1/73; 1.4%); sequences from Brazil belonging to clade U (2/73; 5% - data not yet published); and sequences belonging to clade W from the USA (6/73; 8.3%). Discussion: The results presented here demonstrate that FIV has a rapid viral evolution due to recombination and mutation events, more specifically in the env gene, which is highly variable. Currently, this retrovirus is classified into 7 subtypes (A, B, C, D, E, F and U-NZenv) according to their high genomic diversity. It also highlighted the importance of in silico sequence and phylogeny studies to demonstrate evolutionary processes. This was the first study to address the WGS FIV diversity with a phylogenetic approach. [ABSTRACT FROM AUTHOR]

Simulations of explosive nucleosynthesis in novae predict the production of 22Na, a key astronomical observable to constrain nova models. Its gamma-ray line at 1.275 MeV has not yet been observed by the gamma-ray space telescopes. The 20Ne/22Ne ratio in presolar grains, a possible tool to identify nova grains, also depends on 22Na produced. Uncertainties on its yield in classical novae currently originate from the rate of the 22Na(p, γ)23Mg reaction. At peak novae temperatures, this reaction is dominated by a resonance at ER=0.204 MeV, corresponding to the Ex=7.785 MeV excited state in 23Mg. The resonance strengths measured so far disagree by one order of magnitude. An experiment has been performed at GANIL to measure the lifetime and the proton branching ratio of this key state, with a femtosecond resolution for the former. The reactions populating states in 23Mg have been studied with a high resolution detection set-up, i.e. the particle VAMOS, SPIDER and gamma tracking AGATA spectrometers, allowing the measurements of lifetimes and proton branchings. We present here a comparison between experimental results and shell-model calculations, that allowed us to assign the spin and parity of the key state. Rather small values obtained for reduced M1 matrix elements, M(M1) ≲ 0.5 µN, and proton spectroscopic factors, C2Sp

In this work we present the preliminary results of analysing the 46Mn β+ decay channel as a way to study the 45V(p, γ)46Cr reaction. 46Mn was selected among other species in the cocktail beam delivered by the LISE fragment separator at GANIL (Caen, France) in order to study its beta decay and the excited states of its daughter nucleus 46Cr. As part of the validation process we present the 46Mn half-life, the proton and gamma emission peaks related to the 46Mn decay and compare them with the results from previous works.

The proton, deuteron and alpha induced reactions are of a great interest for the assessment of induced radioactivity of accelerator components, targets and beam stoppers as well as isotope production for medicine and also to nuclear astrophysics. We present a new irradiation chamber for activation measurements, that forms a prolongation of long-term experimental activities using stacked-foil activation technique in NPI CAS, Řež. The chamber is based on an airlock system and is coupled to a pneumatic transfer system delivered by KIT Karlsruhe. This system is installed in GANIL/SPIRAL2-NFS and will be used for proton, deuteron and alpha particle activation measurements with long- and short-lived isotopes.

Lipids of human milk or infant formula convey most of the energy necessary to support the newborn growth. Until recently, infant formula chemical composition had been optimized but not their structure. And yet, more and more proofs of evidence have shown that lipids structure in human milk modulates digestion kinetics and is involved in metabolic programming. Indeed there is a striking difference of structure between human milk which is an emulsion based on dispersed milk fat globules (4 μm) secreted by the mammary gland and submicronic neoformed lipid droplets (0.5 μm) found in infant formula. These droplets result from a series of operation units. This difference of structure modifies digestion kinetics and emulsion disintegration in the intestinal tract of the newborn. This difference persists along gastric phase which is mainly dominated by acid and enzyme-induced aggregation. Lipid droplets size is thus the key parameter to control gastric lipolysis and emptying and intestinal lipolysis. This parameter also controls proteolysis since adsorbed proteins are more rapidly hydrolyzed than when in solution. In animal models, these differences of lipid structure would also impact digestive and immune systems' maturation and microbiota. Lipid structure during neonatal period would also be involved in the early programming of adipose tissues and metabolism. The supplementation of infant formulas with bovine milk fractions (milk fat globule membrane extracts, triacylglycerol) or recent development of large droplets infant formula, along with new fields of innovation in neonatal nutrition, are here reviewed.

Elastic scattering of nuclei at energies typically below 10 MeV/nucleon can be used as a powerful method for studying nuclear spectroscopy. Resonances are observed in the excitation function, corresponding to unbound states in the compound nucleus. The analysis of the shape of these resonances can provide the excitation energy, the total width, the partial width, and the spin of the excited states.

The objective of this study was to evaluate variation in the lumbar spine extension (LSE) muscular strength index and the hydroxyproline (HP) urinary concentrations as a function of flexibility training with maximum intensity (flexibilizing) statically, by proprioceptive neuromuscular facilitation (PNF) and submaximally. The sample population - with an age of 17.13 ± 1.23; body mass of 63.23 ± 6.36 kg; height of 173.62 ± 5.465 cm and body fat percentage of 10 ± 3.62% - comprised 60 male individuals divided randomly into four equal groups: CG (control), StrG (stretching), SFG (static flexibilizing) and PNFG (flexibilizing by PNF). The statistical program SPSS 14.0 for Windows was used to perform a Shapiro Wilk test to verify the normality of the data and Levene's test to analyze the homogeneity of the sample, repeated measures ANOVA for multiple comparisons among groups and the Tukey's HSD Post Hoc test to determine the statistical difference within groups of the variables. A significance level of 95% (p

The Resonant Elastic Scattering (RES) method has been used at GANIL with Radioactive Ions Beams (RIB) in order to study important unbound states. Three examples of studies are given: the first one is related to the important astrophysical reaction 18F(p,α)15O, the second one to the two-proton radioactivity of 19Mg, and the third one to the prediction of the existence of a narrow state in the unbound nucleus 15F. The three experiments have benefited from high quality radioactive beams produced by the Spiral Facility.

Abstract Background Childhood cancer differs from most common adult cancers, suggesting a distinct aetiology for some types of childhood cancer. Our objective in this study was to test the difference in incidence rates of 4 non-CNS embryonic tumours and their correlation with socioeconomic status (SES) in Brazil. Methods Data was obtained from 13 Brazilian population-based cancer registries (PBCRs) of neuroblastoma (NB), Wilms'tumour (WT), retinoblastoma (RB), and hepatoblastoma (HB). Incidence rates by tumour type, age, and gender were calculated per one million children. Correlations between social exclusion index (SEI) as an indicator of socioeconomic status (SES) and incidence rates was investigated using the Spearman's test. Results WT, RB, and HB presented with the highest age-adjusted incidence rates (AAIRs) in 1 to 4 year old of both genders, whereas NB presented the highest AAIR in ≤11 month-olds. However, differences in the incidence rates among PBCRs were observed. Higher incidence rates were found for WT and RB, whereas lower incidence rates were observed for NB. Higher SEI was correlated with higher incidences of NB (0.731; p = 0.0117), whereas no SEI correlation was observed between incidence rates for WT, RB, and HB. In two Brazilian cities, the incidence rates of NB and RB were directly correlated with SEI; NB had the highest incidence rates (14.2, 95% CI, 8.6-19.7), and RB the lowest (3.5, 95% CI, 0.7-6.3) in Curitiba (SEI, 0.730). In Natal (SEI, 0.595), we observed just the opposite; the highest incidence rate was for RB and the lowest was for NB (4.6, 95% CI, 0.1-9.1). Conclusion Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus caused the coronavirus disease 2019 pandemic, and the prevalence of deaths among men is higher than among women. The epididymis, divided into caput, corpus, and cauda, shows a region-specific immunity. The K18-hACE2 mouse expresses human angiotensin-converting enzyme 2 (hACE2), the receptor that allows SARS-CoV-2 infection. However, studies using this transgenic mouse to evaluate the impact of this viral infection in epididymis have not yet been performed., Objectives: We evaluated the expression of hACE2 in the epididymis of SARS-CoV-2-infected K18-hACE2 mice, and assessed the epididymal immune response, focusing on F4/80 + mononuclear phagocytes and tumor necrosis factor-alpha expression., Materials and Methods: The following analyses were performed in the epididymal sections of infected mice: epithelial height and duct diameter, birefringent collagen, Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labelling, immunoreactions for detection of hACE2, spike, FGF, V-ATPase, F4/80, tumor necrosis factor-alpha, and iNOS. Viral particles were identified under electron microscopy. hACE2, Rigi, Tgfb1 and Tnfa expression were also evaluated by real-time quantitative polymerase chain reaction., Results: All epididymal regions expressed hACE2, which increased in all epididymal regions in the infected mice. However, the caput appeared to be the most infected region. Despite this, the caput region showed minimal changes while the cauda showed significant epithelial changes associated with increased iNOS immunoexpression. The F4/80 + mononuclear phagocyte area increased significantly in both stroma and epithelium. In addition to the epithelial and stromal mononuclear phagocytes, tumor necrosis factor-alpha was also detected in clear cells, whose cytoplasm showed a significant increase of this cytokine in the infected animals., Discussion and Conclusion: The K18-hACE2 mouse is a useful model for evaluating the impact of SARS-CoV-2 infection in the epididymis. The infection induced hACE2 upregulation, favoring the virulence in the epididymis. The epididymal regions responded differentially to infection, and the activation of F4/80 + mononuclear phagocytes associated with the increased tumor necrosis factor-alpha immunolabeling in clear cells indicates a role of clear cells/mononuclear phagocytes immunoregulatory mechanisms in the epididymal immune response to SARS-CoV-2 infection., (© 2024 American Society of Andrology and European Academy of Andrology.)

Heat stress during lactation affects the physiological responses, hormonal release, health, and productivity of dairy cows. However, the adverse effects of heat stress on milk synthesis, immune response, and cellular apoptosis in mammary cells remains unknown in Bos indicus cows. This study aimed to understand the relationship between milk yield, milk quality, and the expression of genes related to milk synthesis, cell apoptosis, and immune response in mammary cells of Girolando cows. Twenty-four Girolando cows (3/4 Holstein and 1/4 Gir) were subjected to control (CT, with a temperature-humidity index ranging from 60 to 74, n = 12) or heat stress treatments (HS, with a temperature- humidity index ranging from 60 to 85, n = 12), from 111 to 120 d of lactation. Heat stress significantly increased the expression of heat shock proteins (HSPD1 and HSPD90AA1), insulin receptors (INSR), and prolactin receptors (PRLRsf) genes, and decreased the expression of glucocorticoid receptor (NR3C1) gene in mammary cells of the HS cows when compared with the CT cows. The HS cows exhibited significantly higher vaginal temperatures and cortisol release compared with the CT cows. Moreover, the HS cows had significantly lower dry matter intake and milk yield than CT cows. Although, HS cows showed higher percentage of lymphocytes in milk when compared with that from CT cows. There was no effect of heat stress on other leukocyte counts, somatic cell counts, bacterial counts in milk, or milk composition. Finally, this study demonstrated that Girolando cows are susceptible to heat stress, which decreases milk yield and affects the expression of genes linked to milk synthesis in the mammary cells., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objectives: To monitor by the first 24 months of life, children born to mothers with laboratory evidence of chikungunya virus (CHIKV) infection during pregnancy or up to 8 weeks before it, and to describe abnormalities in head circumference (HC), auditory and ophthalmological assessments and neuroimaging tests during the follow-up period., Method: This is a observational, descriptive, longitudinal and prospective study of children born to mothers who had a rash and a positive test for CHIKV during pregnancy or up to 8 weeks before it. They were admitted between November 2015 and May 2019 in the outpatient multidisciplinary clinic to investigate acute exanthematous disease. The exposed children were followed up by a multidisciplinary team and underwent periodic measurements of the HC. The Denver II test was applied, in addition to transfontanellar ultrasound (TU) to evaluate neurodevelopmental outcomes during the study period. Ophthalmological and auditory examinations, echocardiography and laboratory tests were also included., Results: We included in the study 27 children vertically exposed to CHIKV. All children had a negative polymerase chain reaction test for the virus collected at the first outpatient visit (mean age of 16.8 days and standard deviation of 8 days). No clinical condition compatible with congenital infection at birth was reported. A change in HC characterized by macrocephaly and mild global delay development was observed in a 1-year-old child whose mother was infected in the peripartum, but with normal TU. Changes in the TU were observed in 2 other children with nonspecific subependymal cystic malformation that was not evident by the cranial computed tomography. The other children monitored showed normal results in the Denver II test, in the HC and TU. No changes were identified on ocular ophthalmoscopy or auditory brainstem response test. Two children had an increase in serum ferritin levels during the first year of life, with the others' inflammatory disease markers normal., Conclusions: Our study added knowledge about the neurodevelopment of children exposed to CHIKV during pregnancy by a longitudinal and prospective follow-up, throughout their first 24 months of life. We did not observe a negative impact of exposure to the virus on the neurological examination, global developmental test or measurements of the HC of these children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Liver cancer has been reported to be one of the most malignant diseases in the world. It is late diagnosis consequently leads to a difficult treatment, as the cancer reached an advanced stage. Hepatocellular carcinoma (HCC) is the primary type of cancer diagnosed in the liver, with deadly characteristics and a poor prognosis. The first-in-line treatment for advanced HCC is sorafenib. Sorafenib acts by inhibiting cell proliferation and by inducing apoptosis as well as blocks receptors associated with these mechanisms. Due to its constant use, sorafenib resistance has been described, especially to proteins of the Bcl-2 family, and their overexpression of Bcl-XL and Mcl-1. This review focuses on the role of the Bcl-2 proteins in relation to sorafenib resistance as a consequence of first-in-line treatment in HCC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Alex José de Melo Silva et al.)

Although SARS-CoV-2 induces mucin hypersecretion in the respiratory tract, hyposalivation/xerostomia has been reported by COVID-19 patients. We evaluate the submandibular gland (SMGs) pathogenesis in SARS-CoV-2-infected K18-hACE2 mice, focusing on the impact of infection on the mucin production and structural integrity of acini, ductal system, myoepithelial cells (MECs) and telocytes. The spike protein, the nucleocapsid protein, hACE2, actin, EGF, TNF-α and IL-1β were detected by immunofluorescence, and the Egfr and Muc5b expression was evaluated. In the infected animals, significant acinar hypertrophy was observed in contrast to ductal atrophy. Nucleocapsid proteins and/or viral particles were detected in the SMG cells, mainly in the nuclear membrane-derived vesicles, confirming the nuclear role in the viral formation. The acinar cells showed intense TNF-α and IL-1β immunoexpression, and the EGF-EGFR signaling increased, together with Muc5b upregulation. This finding explains mucin hypersecretion and acinar hypertrophy, which compress the ducts. Dying MECs and actin reduction were also observed, indicating failure of contraction and acinar support, favoring acinar hypertrophy. Viral assembly was found in the dying telocytes, pointing to these intercommunicating cells as viral transmitters in SMGs. Therefore, EGF-EGFR-induced mucin hypersecretion was triggered by SARS-CoV-2 in acinar cells, likely mediated by cytokines. The damage to telocytes and MECs may have favored the acinar hypertrophy, leading to ductal obstruction, explaining xerostomia in COVID-19 patients. Thus, acinar cells, telocytes and MECs may be viral targets, which favor replication and cell-to-cell viral transmission in the SMG, corroborating the high viral load in saliva of infected individuals.

Background: Paroxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant, has caused male sexual dysfunction; however, the paroxetine mechanisms of action in testes are still unclear., Objectives: Paroxetine serotonergic effects in testes were evaluated, focusing on steroidogenesis and the correlation between macrophages population and possible TNF-α-derived oxidative stress. We also verified whether the changes are reversible following treatment interruption., Materials and Methods: Adult rats received paroxetine (PG35 and PG65) or tap water (CG) for 35 days. PG65 was maintained without treatment for 30 more days. Intratesticular testosterone (IT), nitrite, and malondialdehyde concentrations were measured. To confirm serotonergic and estrogenic effects, Htr1b and Esr1 expressions were analyzed. The daily sperm production (DSP), frequency of abnormal seminiferous tubules (ST), SC number, ST area, and Leydig cells nuclear area (LCnu) were evaluated. TUNEL + germ cells, M1 (CD68 + ), and M2 (Perls + ) macrophages were quantified. 17β-HSD7, CYP19A1, NDRG2, oxytocin, TNF-α, and iNOS were evaluated by immunoreactions. Oxytocin and NDRG2 protein levels as well as Tnfa mRNA expression were also analyzed., Results: The Htr1b downregulation in testes confirmed the paroxetine serotonergic effect. The testicular sections showed abnormal ST frequency, ST atrophy and reduction of DSP, LCnu, SC number and Perls + macrophages. TUNEL + germ cells and LC were associated with strong NDRG2 immunoexpression. Paroxetine reduced IT levels and 17β-HSD7 immunoexpression in parallel to increased CYP19A1, oxytocin, TNF-α and iNOS. Esr1 and Tnfa overexpression and increased number of CD68 + macrophages were also observed together with high nitrite and malondialdehyde levels. Most parameters were not recovered in PG65., Conclusions: Paroxetine serotonergic effect impairs LC steroidogenesis, via aromatization, increasing estrogen/testosterone ratio, which in turn upregulate NDRG2, promoting apoptosis, and impairing sperm production. Serotonin-estrogen pathways may be responsible for M2/M1 polarization, Tnfa upregulation, and induction of oxidative stress. The unrecovered testicular changes after treatment discontinuation are due to persistent paroxetine serotonin/estrogen effects., (© 2023 American Society of Andrology and European Academy of Andrology.)

The World Health Organization (WHO) recognizes schistosomiasis as one of the Neglected Tropical Diseases targeted for global elimination in the 2030 Agenda of the Sustainable Development Goals. In Brazil, schistosomiasis mansoni is considered a public health problem, particularly prevalent among vulnerable populations living in areas with poor environmental and sanitary conditions. In 2022, the WHO published a Guideline encompassing recommendations to assist national programs in endemic countries in achieving morbidity control, eliminating schistosomiasis as a public health problem, and advancing towards interrupting transmission. The perspectives presented here, collectively prepared by members of the Oswaldo Cruz Foundation's (Fiocruz) Schistosomiasis Translational Program (FioSchisto), along with invited experts, examine the feasibility of the WHO recommendations for the Brazilian settings, providing appropriate recommendations for public health policies applicable to the epidemiological reality of Brazil, and suggests future research to address relevant issues. In Brazil, the provision of safe water and sanitation should be the key action to achieve schistosomiasis elimination goals. The agencies involved in measures implementation should act together with the Primary Care teams for planning, executing, monitoring, and evaluating actions in priority municipalities based on their epidemiological indicators. Host snails control should prioritize judicious ecological interventions at breeding sites. The Information, Education, and Communication (IEC) strategy should be associated with water and sanitation and other control actions, actively involving school community. To identify infected carriers, FioSchisto recommends a two-stage approach of immunological and molecular tests to verify transmission interruption during the intervention and beyond. Praziquantel administration should be done under medical supervision at the Primary Care level. MDA should be considered in exceptional settings, as a measure of initial attack strategy in locations presenting high endemicity, always integrated with water and sanitation, IEC, and snail control. To assist decision-making, as well as the monitoring and evaluation of strategic actions, there is a need for an Information System. FioSchisto considers this systematization essential to make investments in strategic research to support the improvement of schistosomiasis control actions. Efforts toward schistosomiasis elimination in Brazil will succeed with a paradigm shift from the vertical prescriptive framework to a community-centered approach involving intersectoral and interdisciplinary collaboration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Menezes, Montresor, Jangola, de Mattos, Domingues, Júnior, Silva, Barbosa, de Mendonça, Massara, Fonseca, de Oliveira, Gomes, da Silva, Bezerra, Silva, de Siqueira, Silva, Heller, Farias, Beck, Santos, Lima, Mourão, Enk, Fernandez, Katz, Carvalho, Parreiras, Neves, Gava, de Oliveira, Thiengo, Favre, Graeff-Teixeira, Pieri, Caldeira, da Silva-Pereira, Rocha and Oliveira.)

Germline-encoded pattern recognition receptors, particularly C-type lectin receptors (CLRs), are essential for phagocytes to sense invading fungal cells. Among CLRs, Dectin-2 (encoded by Clec4n) plays a critical role in the antifungal immune response as it recognizes high-mannose polysaccharides on the fungal cell wall, triggering phagocyte functional activities and ultimately determining adaptive responses. Here, we assessed the role of Dectin-2 on the course of primary Paracoccidioides brasiliensis systemic infection in mice with Dectin-2-targeted deletion. Paracoccidioides brasiliensis constitutes the principal etiologic agent of paracoccidioidomycosis, the most prominent invasive mycosis in Latin American countries. The deficiency of Dectin-2 resulted in shortened survival rates, high lung fungal burden, and increased lung pathology in mice infected with P. brasiliensis. Consistently, dendritic cells (DCs) from mice lacking Dectin-2 infected ex vivo with P. brasiliensis showed impaired secretion of several proinflammatory and regulatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10. Additionally, when cocultured with splenic lymphocytes, DCs were less efficient in promoting a type 1 cytokine pattern secretion (i.e., IFN-γ). In macrophages, Dectin-2-mediated signaling was required to ensure phagocytosis and fungicidal activity associated with nitric oxide production. Overall, Dectin-2-mediated signaling is critical to promote host protection against P. brasiliensis infection, and its exploitation might lead to the development of new vaccines and immunotherapeutic approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni , S. japonicum , and S. haematobium , each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.

Introduction: Congenital Zika syndrome (CZS) is a recently described disease. Our main objective was to evaluate and monitor, over 3 years, the ophthalmoscopic findings in children exposed to zika virus (ZIKV) during gestation., Methods: This prospective observational study was conducted in Rio de Janeiro, Brazil, between April 2016 and May 2019. We evaluated two groups with exanthema serving as a proxy for viremia: (i) children whose mothers had exanthema during pregnancy and (ii) children who had microcephaly without maternal exanthema during pregnancy. We performed indirect ophthalmoscopy at recruitment and every 6 months thereafter. We also tested the association between ocular findings with maternal exanthema, microcephaly, CZS and maternal infection confirmed by reverse transcriptase quantitative polymerase chain reaction and gender., Results: Of the 72 children included, 16 (22.2%) had optic nerve and/or retinal lesions. All 16 had CZS and 15 (93.7%) had microcephaly (14 at birth and 1 postnatally). The child with postnatally acquired microcephaly was born to a mother without exanthema during pregnancy. Fifty-six (77.8%) of the 72 children were followed for a median time of 24 months and none exhibited differences between admission and follow-up examinations. After logistic regression, only microcephaly at birth was associated with eye abnormalities (odds ratio, 77.015; 95% confidence interval, 8.85-670.38; p < 0.001)., Conclusion: We observed that there was no progression of the lesions over the follow-up period. We also showed that the eye findings were associated only with microcephaly at birth. Attention should be paid to all children born during a ZIKV epidemic, regardless of maternal exanthema and/or microcephaly at birth., (© The Author(s) [2023]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess the clinical and radiographic characteristics of hip joint deformities in children with congenital Zika syndrome (CZS), and the evolution of hip joint deformities in affected infants for the first 3 years of life., Study Design: This prospective observational study evaluated orthopedic clinical examinations performed every 3 months to assess hip flexion and extension, lateral and medial rotation, and abduction and adduction, as well as lower limb muscle length and tone. The biannual radiograph comprised anteroposterior panoramic pelvic radiographs with the lower limbs in extension. Percentage of migration was used as a radiographic study tool to measure and evaluate linear hip displacement., Results: From November 2018 to March 2020, we followed 30 children with CZS, of whom 15 (50%) had normal pelvic radiographs on admission; 5 (33.3%) developed hip displacement by the second radiograph examination. During follow-up radiographic examinations, 20 of the 30 children (66.7%) were diagnosed with hip displacement and/or dislocation of at least 1 side, and 10 of the 30 (33.3%) remained normal. Among 30 affected patients, 13 (43.3%) had hip displacement on the right side and 9 (30%) on the left side. Logistic regression analysis revealed that spasticity (P = .0033; OR, 15.9) and ophthalmologic abnormalities (P = .0163; OR, 16.9) were associated with hip dislocation during follow-up., Conclusions: Pelvic radiographic follow-up for all children with CZS will complement physical examination, diagnosis, and monitoring for hip joint deformities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD)., Objective: We evaluated whether autologous bone marrow-derived cells (BMC) contribute to additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG)., Methods: In a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 ± 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC ( n = 77) or placebo ( n = 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG., Results: The reduction in global SIMI after CABG was comparable ( p = 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group ( p = 0.047). Baseline regional SIMI values were comparable [18.5 (16.2-21.0) vs. 18.5 (16.5-20.7)] and reached the lowest values at 1 month [9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85)] for BMC and placebo groups, respectively. The ischemia's improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) ( p = 0.34) and all-cause mortality ( p = 0.08) did not differ between groups 1 month post intervention., Conclusion: We provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction., Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT01727063., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gowdak, Schettert, Rochitte, de Carvalho, Vieira, Dallan, de Oliveira, César, Brito, Guarita-Souza, de Carvalho and Krieger.)

Ankylosing spondylitis (AS) is a common form of axial spondyloarthritis, characterized by inflammatory back pain, radiographic sacroiliitis, excess spinal bone formation, and a high prevalence of HLA-B27. Commonly, AS patients require spinal surgery for kyphotic deformities, spinal trauma, and spinal infections. For preoperative management, proper interruption considering each specific half-lives of disease-modifying antirheumatic drugs are necessary to avoid complications, such as infections. When feasible, bone quality assessment before surgery is mandatory. For intraoperative measurements, airway management should be carefully evaluated, especially in patients with severe cervical deformities. Cardiac, renal, and pulmonary assessment should be made considering specific pathologic characteristics involved in AS patients, such as pulmonary restrictive disease and chronic anti-inflammatory drugs use. Multimodal neurophysiological intraoperative monitoring is recommended once these patients had a high risk for neurological deterioration. At the postoperative period, early oral intake, early mobilization, and aggressive pain control may decrease complications and enhance recovery. AS presents several unique challenges that require specific attention around spine surgery. This includes handling preoperative and postoperative pharmacotherapeutics, intraoperative airway management, and the mitigation of postoperative complications. In this paper, we provide a literature review of optimal strategies for the perioperative management for patients with AS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The use of oral fluid (OF) samples for serological diagnosis of parvovirus B19 infection during outbreaks of erythema infectiosum had already been demonstrated, but the feasibility of using OF for the characterization of B19 genotypes circulating during outbreaks has not been described. The aim of this study was to assess the use of "in-house" PCR-based assays as a powerful tool for a rapid diagnosis and molecular characterization of B19 strains in OF samples during outbreaks. Paired serum and OF samples collected from anti-B19 IgM-positive patients, during two outbreaks of ertythema infectiosum (1999-2000 and 2004-2005), were tested by conventional (cPCR) and quantitative PCR (qPCR). qPCR was more sensitive than cPCR for detecting B19-DNA in both OF and serum. Overall, OF presented lower viral load (9.97 × 10 6 UI/mL) than serum (2.42 × 10 10 UI/mL) and this difference was statistically significant. All OF samples obtained from patients in the age group < 14 years presented low viral load (< 10 4  IU/mL). No correlation was found between viral load and the number of days of onset of rash. Sequence analysis from PCR positive OF samples confirmed the circulation of subgenotype 1a (G1a) during these outbreaks. Our findings indicate that PCR-based assays may fail to detect B19-DNA in approximately 50% of OF compared to serum samples. Nevertheless, our study has shown for the first time that the genome sequence of the amplicon from non-invasive clinical sample is useful for molecular genotyping and may be a tool to clarify the genetic diversity of B19 strains circulating in distinct outbreaks., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Lockdowns have been fundamental to decreasing disease transmission during the COVID-19 pandemic even after vaccines were available. We aimed to evaluate and compare changes in air quality during the first year of the pandemic in different cities around the world, investigate how these changes correlate with changes in mobility, and analyse how lockdowns affected air pollutants' annual means., Methods: We compared the concentrations of NO 2 , PM 2.5 , and PM 10 in 42 cities around the world in the first months of the pandemic in 2020 to data from 2016-2019 and correlated them with changes in mobility using Human Development Indexes (HDIs). Cities with the highest decreases in air pollutants during this period were evaluated for the whole year 2020. We calculated the annual means for these cities and compared them to the new World Health Organization (WHO) Air Quality Guidelines. A Student's t-test (95% confidence interval) was used to evaluate significant changes., Results: Highest decreases in NO 2 , PM 2.5 , and PM 10 were between -50 and -70%. Cities evaluated for the whole year 2020 generally showed a recovery in air pollution levels after the initial months of the pandemic, except for London. These changes positively correlated with year-long mobility indexes for NO 2 and PM 2.5 for some cities. The highest reductions in air pollutants' annual means were from -20 to -35%. In general, decreases were higher for NO 2 , compared to PM 2.5 and PM 10 . All analysed cities showed annual means incompliant with the new WHO Air Quality Guidelines for NO 2 of 10 μg/m 3 , with values 1.7 and 4.3 times higher. For PM 2.5 , all cities showed values 1.3 to 7.6 times higher than the WHO Guidelines of 5 μg/m 3 , except for New Delhi, with a value 18 times higher. For PM 10 , only New York complied with the new guidelines of 15 μg/m 3 and all the other cities were 1.1 to 4.2 times higher, except for New Delhi, which was 11 times higher., Conclusions: These data show that even during a pandemic that highly affected mobility and economic activities and decreased air pollution around the world, complying with the new WHO Guidelines will demand a global strategical effort in the way we generate energy, move in and around the cities, and manufacture products., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

This research paper addresses the hypothesis that stress, induced by ACTH administration and cortisol release increases somatic cell count (SCC) in mammary secretion, and improves the effectiveness of dry off in goats. We report indicators of milk synthesis and mammary gland involution during dry off. Thirty Saanen goats were subjected to abrupt dry off and treatments: (1) ACTH administration (ACTH) or (2) placebo (Control) on days 1, 3, 6, 9, 12, 15, 30, and 60 of dry off. The expression of target genes in mammary tissue that are related to milk synthesis and cell survival such as insulin-like growth factor 1 receptor (IGF1R), phosphatidylinositol-3-kinase (PIK3CA), protein kinase B (AKT1) and mechanistic target of rapamycin (MTOR), casein (CSN2), lactalbumin (LALBA) and lactoferrin (LF) were evaluated, and plasma cortisol concentration, SCC, leucocyte count, and microbiological analyses in milk and mammary secretions were assessed. ACTH significantly downregulated the expression of IGF1R and upregulated the expression of PIK3CA in mammary tissue, increased lactoferrin concentration and SCC, and changed immune cell levels in mammary secretions compared to Control. Furthermore, ACTH administration increased the percentage of dry goats compared to the Control (73 vs. 46%, respectively). We conclude that the effect of stress via ACTH administration and cortisol release accelerated mammary involution during the early dry-off period.

Schistosomiasis mansoni is considered a serious public health problem. As praziquantel is the only drug recommended by the World Health Organization for the treatment and control of schistosomiasis, the development of new drugs is of great significance. In this work, we present the antischistosomal activity of a small set of phthalimido-thiazole derivatives against Schistosoma mansoni. The effects of those derivatives on the viability of larvae juveniles and adult parasites, production and development of eggs, mortality of schistosomules in vitro by counting worms, and stages of eggs of infected animals in acute and chronic phases were evaluated, resulting in the identification of new multistage antischistosomal compounds. Additionally, a study of liver fibrogenesis was released. The phthalimido-thiazole derivatives, compounds 2b-d, 2h-j, had shown activity on schistosomules, achieving 100% mortality even at 5 mg/mL, in the first 24 h. In the chronic phase of schistosomiasis infection, compound 2i promoted a reduction in the number of immature eggs, an increase in the number of non-viable parasite eggs, a reduction in the average number of eggs in the liver and intestine, decrease in the levels of hydroxyproline in the liver, and a reduction in the areas of hepatic fibrosis. This compound also promoted an increase of IL-10 and a reduction in the level of TNF-α in the liver. Accordingly, the phthalimide-thiazole scaffold is a new starting point for the development of multistage compounds that affect S. mansoni viability, egg formation, and production., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To assess the prevalence of depression, anxiety and stress symptoms in health professionals in the COVID-19 pandemic context., Method: Cross-sectional study with non-probabilistic (snow-ball) sampling method. The assessment was performed using the Depression, Anxiety, and Stress Scale (DASS-21) and the prevalence of symptoms severity was calculated by point and 95% confidence interval. The analysis of the psychometric properties of DASS-21 was performed using confirmatory factor analysis (CFA) and the following goodness of fit indices: χ 2 /df (chi-square ratio by degrees of freedom), Tucker-Lewis index (TLI), comparative fit index (CFI) and root mean square error of approximation (RMSEA) with a 90% confidence interval., Results: The study participants were 529 health professionals (82.4% women and 66.7% nursing professionals). CFA of the DASS-21 structural model presented adequate fit for the sample (χ 2 /df = 3.530; CFI = 0.979; TLI = 0.976; RMSEA = 0.069). Regarding prevalence, moderate to extremely severe symptoms of depression, anxiety and stress were found in 48.6%, 55.0% and 47.9% of the participants, respectively., Conclusion: The use of DASS-21 confirmed the validity and reliability of the data. The prevalence of depression, anxiety and stress symptoms in the participants indicated a high risk of mental illness in health professionals in the COVID-19 pandemic.

In seasonal breeders, such as amphibians, testicular functions depend on complex processes that change according to seasonality, including Leydig cell (LC) differentiation and lipid-dependent steroidogenesis, extracellular proteins remodeling and actin-dependent cellular dynamics. Speculating that fat bodies (FB) could support some of these processes in L. catesbeianus, we evaluated bilaterally the FB weights, correlating them to testicular parameters such as weight, testosterone (T) immunoexpression, mast cells (MC) number, vascularization and structural proteins. In an attempt to better understand the testicular asymmetry in amphibians, correlations between these different testicular parameters were also established. Right testes (RT), left testes (LT) and associated FB of bullfrogs were weighed, and testes were processed for light and transmission electron microscopy. Collagen content (COL) and MC number were quantified. T and actin immunoexpressions and vascular areas were measured. Statistical analyses and Pearson's correlation were performed. The LT and its associated FB were heavier than the right ones, and showed intense T and actin immunoexpressions, numerous lipid-rich LC, and greater MC number, COL and vascularization than the RT. Positive correlations were detected between: a) FB and testis weights, b) T immunoexpression and testis and FB weights, c) T and actin immunoexpressions and COL. Otherwise, MC number was inversely correlated to T immunoexpression and COL. In right and left sides, the proportional correlation between T immunoexpression and FB weight suggests that FB-stored lipid amount depends on the steroidogenic demand of its associated testis. Thus, the asymmetry in the testes and FB may be associated, at least in part, to the LC steroidogenic activity, which tends to be more intense in LT than in RT. The results also point to a role of COL and mast cells in the LC differentiation and steroidogenesis. Actin was also greater in LT and correlated with T immunoexpression, indicating that the amount of this structural protein depends on androgenic control. Therefore, the testicular asymmetry in bullfrogs seems to be associated to different morphofunctional processes occurring, bilaterally, at different intensities. In this case, there is a tendency of LT, in association with its FB, to be more active than RT. The findings highlight the FB-testis interplay for the comprehension of reproduction in amphibians., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis is the most widespread clinical form of leishmaniasis in the Americas. Migonemyia migonei is a widely distributed phlebotomine sand fly species in Brazil and has been implicated as a vector for L. (V.) braziliensis. In the present study, we investigated the effects of salivary gland homogenates (SGH) of Mg. migonei on the course of L. (V.) braziliensis infection in BALB/c mice. Mice were separated into four groups (six mice per group): CTRL (uninfected mice); SGH (mice inoculated with Mg. migonei SGH); SGH+LEISH (mice inoculated with Mg. migonei SGH plus L. (V.) braziliensis promastigotes); LEISH (mice inoculated with L. (V.) braziliensis promastigotes). Mice were followed up for 8 weeks and the cellular immune response was evaluated by flow cytometry at the end of the experiment. Analysis of cytokine production by splenic cells stimulated with 0.5 SGH, 0.25 SGH of Mg. migonei or L. (V.) braziliensis soluble antigen stimulation (LSA) demonstrated that upon stimulation with SGH 0.25, the production of IL-17A and TNF was not sustained in the SGH group, with decreasing levels of these cytokines after 5 days compared to 3 days of incubation. Analyzing the production of cytokines after LSA stimulation, we observed lower levels of IL-17A in the SGH group after 5 days compared to 3 days. The same was observed for IFN-γ in the SGH group. Yet, the levels of TNF were significantly higher in the LEISH group after 5 days compared to 3 days. Among SGH+LEISH and LEISH mice, three animals in each group developed skin lesions on the tail, the mean lesion size was significantly higher in the LEISH group. Our study suggests that Mg. migonei SGH may modulate BALB/c immune response, as reflected by the low production or early decrease of pro-inflammatory cytokines in splenic cell cultures following stimulation with L. (V.) braziliensis antigen. Our data also suggest that Mg. migonei saliva may reduce the lesion size in BALB/c mice, but further research with a larger sample size is needed to confirm this hypothesis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of the study was to describe neurological manifestations in children with congenital Zika syndrome (CZS) in the first 2 years of age. In this prospective observational study, children with CZS treated at a university hospital received a neurological assessment and were evaluated using two neurodevelopmental scales (the Denver II test and the assessment of gross motor development of the World Health Organization) by a pediatric neurologist on admission to the study and at 4, 8, 12, 18, and 24 months of age. The data collected were stored in Microsoft Excel version 14.6.3. Thirty-eight children (27 males and 11 females; a median age of 4.3 months (interquartile range (IQR): 1.6-11.4)) with CZS were evaluated. Irritability was present in 50% and 27% of the children at 8 months and 24 months, respectively. Axial hypertonia was highly prevalent at 4 months (77%), with a decrease to 50% at 24 months. At all ages, spastic tetraparesis was the most common motor abnormality (> 80%). Twenty-seven (71%) participants were diagnosed with epilepsy, and the median age at seizure onset was 6 months (IQR: 3.5-8). The most frequent types of seizures were focal seizures and spasms, with spasms being the most frequent in the first year of life (52%) and focal crises being the most frequent in the second year of life (50%).Conclusion: This study allowed observation of neurological abnormalities over time, the evolution of epileptic manifestations, and recognition of new patterns of clinical neurological abnormalities, helping clinicians to recognize CZS earlier, minimizing the impact of new outbreaks. What is Known: • Clinical patterns of SZC patients at pre-established ages or date of data collection • More frequent studies with data collection of clinical-radiological features of patient's over his first year of life What is New: • Comprehensive clinical neurological progression data regarding CZS in the first 2 years of life, recognizing patterns • Hypothesis including a new CZS spectrum with milder clinical-radiological features., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cortisol (CORT) induces mammary development in late gestation and is fundamental to the differentiation of mammary epithelial cells and lactogenesis. The objective of this study was to investigate the relationship between CORT, insulin, prolactin, growth hormone, and insulin-like growth factor-1 in milk as well as the effect of CORT on the expression of receptors of insulin (INSR), prolactin (PRLR), growth hormone (GHR); we also studied the insulin-like growth factor-1 (IGF1R), glucocorticoid (NR3C1), mineralocorticoid (NR3C2), B-cell lymphoma 2 (BCL2), BCL-2-like protein X (BAX) genes, and the apoptosis rate of mammary epithelial cells of lactating Saanen goats in vivo and in vitro. The following experiments were conducted: (1) comparing hormone release in milk and blood after ACTH or a placebo administration; (2) evaluating the effect of acute CORT increases in mammary gland expression and milk yield in vivo; and (3) evaluating the effect of a chronic increase in CORT concentration in epithelial mammary cell apoptosis in vitro. In vivo, ACTH administration significantly increased CORT release but did not affect insulin, prolactin, growth hormone, and insulin-like growth factor-1 release in plasma and milk versus placebo. The results show also that a low CORT release after ACTH administration increased the expression of GHR and PRLR genes in the mammary tissue. Indeed, CORT release significantly increased the milk yield from goats subjected to ACTH versus goats subjected to the placebo. However, a higher amount of CORT added in vitro upregulated the NR3C1, GHR, PRLR, and BAX genes and downregulated the IGF1R and INSR genes, which could negatively modulate the apoptosis of mammary epithelial cells. Finally, the effect of CORT in vivo after ACTH administration demonstrated the increased expression of the PRLR and GHR genes, which may improve epithelial cell responsiveness and be associated with the positive effect of CORT observed on milk yield at mid-end lactation., (© 2022, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The role of cytokines in testicular function under normal conditions has not been completely understood. Here, we evaluated testicular macrophages (TM), steroidogenesis by Leydig cells (LC) and seminiferous tubules integrity in cytokines-deficient rat testes induced by diacerein, an anti-inflammatory drug that inhibits interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). Male rats received daily 100 mg/kg of diacerein (DIAG; n = 8) or saline (CG; n = 8) for 30 days. Serum testosterone (T) levels were measured and the seminiferous tubule (ST) area, epithelial area (EA), frequency of damaged ST and number of Sertoli cells (SC) were evaluated. TUNEL method and immunoreactions for detection of pro-IL-1β, TNF-α, steroidogenic acute regulatory protein (StAR), 17β-hydroxysteroid dehydrogenase (17β-HSD), androgen receptor (AR) and scavenger receptor for hemoglobin-haptoglobin complexes (CD163), a TM marker, were performed. Testicular AR, 17β-HSD and IL-1β levels were detected by Western blot. Data were submitted to Student t test (p ≤ 0.05). In DIAG, T and testicular AR, 17β-HSD and IL-1β levels decreased significantly (p < 0.05). The number of TUNEL-positive interstitial cells increased and LC showed weak StAR, 17β-HSD and AR immunoexpression in association with reduced IL-1β immunoexpression and number of CD163-positive TM in the interstitial tissue from diacerein-treated rats. Numerous damaged ST were found in DIAG, and reduction in the EA were associated with germ cells death. Moreover, the number of SC reduced and weak AR and TNF-α immunoexpression was observed in SC and germ cells, respectively. The cytokines deficiency induced by diacerein impairs TM, LC and spermatogenesis, and points to a role of IL-1β in steroidogenesis under normal conditions. In the ST, the weak AR and TNF-α immunoexpression in SC and germ cells, respectively, reinforces the idea that TNF-α plays a role in the SC androgenic control., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The long exposure to heat negatively changes performance and productivity of animals, particularly when heat stress is associated with gestation. Indeed, little is known about the negative effects of long-term heat stress on the final gestation of dairy goats. In this context, the physiological and cellular responses of Saanen goats submitted to heat stress (37°C from 10:00 to 16:00 h) were investigated from day 60th pre-partum to day 60th post-partum. At final gestation, 46 pregnant Saanen goats were randomly assigned to the treatments: control (CT; thermal neutral conditions) and heat stress (HS; climatic chamber). After partum, all experimental goats were maintained in thermal neutral conditions. The rectal, dorsal, mammary temperatures and respiratory frequency, cortisol release, milk yield, milk quality, and the genes HSP60, HSP70, HSP90, Glucocorticoid receptor and ACTHR. Goats subjected to HS showed significantly (P < 0.05) higher rectal, dorsal, and mammary temperatures and significantly mobilized the increase of respiratory frequency to lose heat as compared to CT goats. The HS challenge significantly increased cortisol release from day 15th pre-partum to day 15th post-partum. CT goats produced more milk than HS from weeks 4 to 10 of lactation (P <0.001), with no difference in milk quality. However, on day 15th post-partum, there was a significant effect of HS treatment on the expression of HSP70 and ACTHR genes as compared to CT treatment, confirming the long-term effect of HS on Saanen goats. In conclusion, the physiological parameters studied increased pre-partum in the hottest hour, and cortisol peaked on day 15 pre-partum for heat-stressed goats. Although on the 15th day post-partum, all goats were in thermal comfort, and the physiological parameters were within the normal range, the concentration of cortisol continued to be significantly higher for goats submitted to thermal stress. Indeed, milk yield was greater for goats subjected to pre-partum thermal comfort. Furthermore, the expression of HSP70 and ACTHR genes on peripheral blood mononuclear cells are interesting biomarkers for studying the long-term effect of heat stress on Saanen goats., (© 2021. ISB.)

Traditional cancer treatments, such as surgery, radiotherapy, and chemotherapy, are still the most effective clinical practice options. However, these treatments may display moderate to severe side effects caused by their low temporal or spatial resolution. In this sense, photonic nanomedicine therapies have been arising as an alternative to traditional cancer treatments since they display more control of temporal and spatial resolution, thereby yielding fewer side effects. In this work, we reviewed the challenge of current cancer treatments, using the PubMed and Web of Science database, focusing on the advances of three prominent therapies approached by photonic nanomedicine: (i) photothermal therapy; (ii) photodynamic therapy; (iii) photoresponsive drug delivery systems. These photonic nanomedicines act on the cancer cells through different mechanisms, such as hyperthermic effect and delivery of chemotherapeutics and species that cause oxidative stress. Furthermore, we covered the recent advances in materials science applied in photonic nanomedicine, highlighting the main classes of materials used in each therapy, their applications in the context of cancer treatment, as well as their advantages, limitations, and future perspectives. Finally, although some photonic nanomedicines are undergoing clinical trials, their effectiveness in cancer treatment have already been highlighted by pre-clinical studies.

Background: Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016-2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones. Results: Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP. Conclusion: Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Badolato-Corrêa, Carvalho, Paiva, Familiar-Macedo, Dias, Pauvolid-Corrêa, Fernandes-Santos, Lima, Gandini, Silva, Baeta Cavalcanti, de Oliveira, de Oliveira Vianna, de Azeredo, Cardoso, Grifoni, Sette, Weiskopf and de-Oliveira-Pinto.)