The trophoblast surface becomes refractory to adhesion by congenitally transmitted Toxoplasma gondii and Listeria monocytogenes during cytotrophoblast to syncytiotrophoblast development.

The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanisms and challenges in replicating trophoblast-pathogen interactions using in vitro models, we tested an existing stem-cell-derived model of trophoblast development for its relevance to infection with Toxoplasma gondii. We grew human trophoblast stem cells (TSCT) under conditions leading to either syncytiotrophoblast (TSSYN) or cytotrophoblast (TSCYT) and infected them with T. gondii. We evaluated T. gondii proliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TSSYNs cells showed similar ultrastructure compared to primary cells and villous explants when analyzed by transmission electron microscopy and scanning electron microscopy (SEM), a resistance to T. gondii adhesion could be visualized on the SEM level. Furthermore, TSSYNs were highly refractory to parasite adhesion and replication, while TSCYTs were not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded to T. gondii infection. We also evaluated if TSSC-derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen, Listeria monocytogenes. We demonstrate that TSSYNs are highly resistant to L. monocytogenes, while TSCYTs are not. Like T. gondii, TSSYN resistance to L. monocytogenes was at the level of bacterial adhesion. Altogether, our data indicate that stem-cell-derived trophoblasts recapitulate resistance profiles of primary cells to T. gondii and highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.IMPORTANCECongenital toxoplasmosis can cause a devastating consequence to the fetus. To reach the fetus's tissues, Toxoplasma gondii must cross the placenta barrier. However, how this parasite crosses the placenta and the precise molecular mechanisms of placental resistance to this parasite are still unknown. In this study, we aimed to characterize a new cellular model of human trophoblast stem cells to determine their resistance, susceptibility, and response to T. gondii. Syncytiotrophoblast derived from trophoblast stem cells recapitulate the resistance profile similarly to placenta cells. We also showed that these cells are highly resistant to Listeria monocytogenes, at the level of bacterial adhesion. Our results suggest that resisting pathogen adhesion/attachment may be a generalized mechanism of syncytiotrophoblast resistance, and trophoblast stem cells represent a promising model to investigate cell-intrinsic mechanisms of resistance to pathogen adhesion and replication.

Treatment of peri-implantitis using nonsurgical debridement combined with bioresorbable doxycycline nanospheres: a case report with 3-year follow-up.

Treatment of peri-implant diseases focuses on reducing the bacterial load and consequent infection control. The use of local antimicrobials as an adjunct to mechanical therapy may result in a better outcome. Among antimicrobials, doxycycline stands out because of its local modulation of cytokines, microbial reduction, and clinical parameters in the treatment of periodontal diseases. The objective of this case report was to describe the combined application of mechanical debridement and bioresorbable doxycycline-loaded nanospheres for the treatment of peri-implantitis in a 71-year-old man. At the 3-year evaluation, the peri-implant tissues had improved, showing decreased probing depths, an absence of bleeding on probing, and no suppuration. This case report highlights the importance of supportive therapy, which is essential for the long-term success of peri-implantitis treatment.

A Single-Port, Multiple-Access, Custom-Made Device Used in Laparoscopically Assisted Cryptorchidectomy in Standing Horses-A Preliminary Study.

This study evaluates a new multiport device with single access to the abdominal cavity produced with routine hospital supplies that could be applied to laparoscopically assisted cryptorchidectomy in standing horses. Initially, the new device was evaluated on five cadavers of bovine fetuses (n = 5), placed assisted in a minilaparotomy performed in the flank region. Subsequently, the device was evaluated in four cryptorchid horses treated during the hospital routine. During the evaluation of the new device, the possibilities of exploring the abdominal cavity, inspection, and intra-abdominal manipulation with two Babcock forceps were verified. The possibilities were described, and surgical time data were recorded and analyzed using descriptive statistics. In the cadavers, a wide exploration of the abdominal cavity was possible, with a laparoscopic inspection through the right paralumbar fossa and manipulation of intra-abdominal structures with Babcock forceps inserted by the new device. In cryptorchid horses, laparoscopically assisted cryptorchidectomy with a new device was feasible in two patients, and in the others, it allowed the diagnosis of adhesions and ectopic locations in the inguinal region of testicles retained in the cavity. Therefore, the new device was efficient in exploring the inguinal region of cryptorchid horses in the standing position. The present study is preliminary and can support future studies that aim to improve the developed prototype.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation.

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Exploring novel pyrazole-nitroimidazole hybrids: Synthesis and antiprotozoal activity against the human pathogen trichomonas vaginalis.

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 µM and ≤ 41 µM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 µM), 1e (IC50 4.8 µM), and 1i (IC50 5.2 µM) exhibited potencies equivalent to MTZ (IC50 4.9 µM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 µM) and 48 h (IC50 2.1 µM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 µM) or low cytotoxicity (CC50 between 69 and 100 µM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.

Calorie restriction protects against acute systemic LPS-induced inflammation.

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets.Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus.Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays.Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response.Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies.

Implications of MTHFD2 expression in renal cell carcinoma aggressiveness.

Renal cell carcinoma (RCC) is the most common type of cancer in kidney and is often diagnosed in advanced stages. Until now, there is no reliable biomarker to assess tumor prognosis during histopathological diagnosis. The Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) overexpression has been suggested as prognostic indicator for RCC, however, its protein profile needs to be clarified. This study investigated the MTHFD2 expression in different RCC cohorts, associating it with tumor characteristics and prognostic factors. Gene expression comparisons between non-neoplastic (NN) and tumor samples, as well as patients' survival analysis, were assessed using KM-Plotter tool. MTHFD2 protein pattern was evaluated in 117 RCC by immunohistochemistry and associations with prognosis, clinical and pathological data were investigated. The tumors exhibited higher MTHFD2 transcript levels than NN, being even higher in the metastatic group. Opposite gene expression patterns were found among clear cell renal cell carcinoma (ccRCC) and pappilary renal cell carcinoma (pRCC) subtypes, showing higher and lower expressions compared to NN samples respectively. Overexpression was associated with shorter overall survival for ccRCC and pRCC subtypes, and shorter recurrence-free survival for pRCC. The immunolabeling profile varied according to tumor subtypes, with lower intensity and expression scores in ccRCC compared to pRCC and to chromophobe renal cell carcinoma (chRCC). MTHFD2 protein expression was associated with larger tumors and higher Fuhrman grades. Although prognostic value of protein immunostaining was not confirmed, patients with higher MTHFD2 tended to have lower survival rates in the pRCC group. The results highlight MTHFD2 different patterns according to RCC histological subtypes, revealing marked variations at both the genetic and protein levels. The mRNA indicated tumor prognosis, and greater expression in the tumor samples. Although MTHFD2 immunolabeling suggests tumor aggressiveness, it needs to be validated in other cohorts as potential prognostic factor.

Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges.

Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis. Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis. Results: Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity. Conclusion: Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges.

Intensity and lifetime ratiometric luminescent thermometer based on a Tb(III) coordination polymer.

A three-dimensional terbium(III) coordination polymer of formula [Tb(bttb)0.5(2,5-pzdc)0.5]n (1) [H4bttb = 1,2,4,5-tetrakis(4'-carboxyphenyl)benzene and H2-2,5-pzdc = 2,5-pyrazinedicarboxylic acid] was obtained under hydrothermal conditions. The bttb4- tetraanion in 1 adopts the bridging and chelating-bridging pseudo-oxo coordination modes while the 2,5-pzdc2- dianion exhibits a rather unusual bis-bidentate bridging pseudo-oxo coordination mode, both ligands being responsible for the stiffness of the resulting 3D structure. Solid-state photoluminescent measurements illustrate that 1 exhibits remarkable green luminescence emission, the most intense band occurring in the region of 550 nm (5D4 → 7F5) with lifetimes at the millisecond scale. Thermometric performances of 1 reveal a maximum relative sensitivity (Sm) of 0.76% K-1 at 295 K (δT = 0.05 K), constituting a TbIII ratiometric solid luminescent thermometer over the physiological temperature range. Variable-temperature static (dc) magnetic susceptibility measurements for 1 in the temperature range 2.0-300 K show the expected behavior for the depopulation of the splitted mJ levels of the 7F7 ground state of the magnetically anisotropic terbium(III) ion plus a weak antiferromagnetic interaction through the carboxylate bridges. No significant out-of-phase magnetic susceptibility signals were observed for 1 in the temperature range 2.0-10.0 K, either in the absence or presence of a static dc magnetic field.

Toxicity assessment of commercial herbicide formulations to Eisenia andrei (Bouché, 1972) in oxisols.

The use of long-residual herbicides can have adverse effects on terrestrial ecosystems. This study assessed the acute and chronic toxicity and avoidance behavior of Eisenia andrei earthworms exposed to nominal concentrations of clomazone, indaziflam, and sulfentrazone, using recommended commercial formulations for sugarcane cultivation. The formulations included Gamit® 360 CS (360 g L-1 of the active ingredient - a.i. - clomazone), Boral® 500 SC (500 g L-1 of a.i. sulfentrazone), and Alion® (500 g L-1 of a.i. indaziflam). Boral® 500 SC induced avoidance at concentrations as low as 1 mg kg-1, while Gamit® 360 CS and Alion® exhibited higher avoidance at 50-75 mg kg-1 and 75-100 mg a.i. kg-1, respectively. Reproduction tests showed significant impacts from Gamit® 360 CS (EC50: 0.572 mg kg-1, EC10: 0.2144 mg kg-1) and Boral® 500 SC (EC50: 0.3941 mg kg-1, EC10: 0.134 mg kg-1). Acute toxicity tests indicated moderate toxicity for Gamit® 360 CS (LC50: 184.12 mg kg-1) and Boral® 500 SC (LC50: 1000 mg kg-1). Gamit® 360 CS reduced biomass at all concentrations, while Boral® 500 SC influenced only at higher levels (500 and 1000 mg kg-1). Results suggest significant acute risks with Gamit® 360 CS, while chronic exposure raises concerns for both Gamit® 360 CS and Boral® 500 SC, indicating potential long-term risks. Alion®'s acute effects were inconclusive, but chronic exposure hints at a possible risk. These findings provide crucial insights for environmental agencies establishing protective limits against herbicide exposure to non-target soil invertebrates.

Cortical matrix remodeling as a hallmark of relapsing-remitting neuroinflammation in MR elastography and quantitative MRI.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients.

Alamandine attenuates oxidative stress in the right carotid following transverse aortic constriction in mice.

OBJECTIVE: Pressure overload can result in significant changes to the structure of blood vessels, a process known as vascular remodeling. High levels of tension can cause vascular inflammation, fibrosis, and structural alterations to the vascular wall. Prior research from our team has demonstrated that the oral administration of alamandine can promote vasculoprotective effects in mice aorta that have undergone transverse aortic constriction (TAC). Furthermore, changes in local hemodynamics can affect the right and left carotid arteries differently after TAC. Thus, in this study, we aimed to assess the effects of alamandine treatment on right carotid remodeling and the expression of oxidative stress-related substances induced by TAC. METHODS AND RESULTS: Male C57BL/6 mice were categorized into three groups: Sham, TAC, and TAC treated with alamandine (TAC+ALA). Alamandine treatment was administered orally by gavage (30 µg/kg/day), starting three days before the surgery, and continuing for a period of fourteen days. Morphometric analysis of hematoxylin and eosin-stained sections revealed that TAC induced hypertrophic and positive remodeling in the right carotid artery. Picrosirius Red staining also demonstrated an increase in total collagen deposition in the right carotid artery due to TAC-induced vascular changes. Alamandine treatment effectively prevented the increase in reactive oxygen species production and depletion of nitric oxide levels, which were induced by TAC. Finally, alamandine treatment was also shown to prevent the increased expression of nuclear factor erythroid 2-related factor 2 and 3-nitrotyrosine that were induced by TAC. CONCLUSION: Our results suggest that alamandine can effectively attenuate pathophysiological stress in the right carotid artery of animals subjected to TAC.

PARTIAL HEPATECTOMY USING LINEAR CUTTER STAPLER: ARE THERE ADVANTAGES?

BACKGROUND: Morbidity of liver resections is related to intraoperative bleeding and postoperative biliary fistulas. The Endo-GIA stapler (EG) in liver resections is well established, but its cost is high, limiting its use. The linear cutting stapler (LCS) is a lower cost device. AIMS: To report open liver resections, using LCS for transection of the liver parenchyma and en bloc stapling of vessels and bile ducts. METHODS: Ten patients were included in the study. Four patients with severe abdominal pain had benign liver tumors (three adenomas and one focal nodular hyperplasia). Among the remaining six patients, four underwent liver resection for the treatment of colorectal liver metastases, three of which had undergone preoperative chemotherapy. The other two cases were one patient with metastasis from a testicular teratoma and the other with metastasis from a gastrointestinal neuroectodermal tumor. RESULTS: The average length of stay was five days (range 4-7 days). Of the seven patients who underwent resections of segments II/III, two presented postoperative complications: one developed a seroma and the other a collection of abdominal fluid who underwent percutaneous drainage, antibiotic therapy, and blood transfusion. Furthermore, the three patients who underwent major resections had postoperative complications: two developed anemia and received blood transfusions and one had biloma and underwent percutaneous drainage and antibiotic therapy. CONCLUSIONS: The use of the linear stapler in hepatectomies was efficient and at lower costs, making it suitable for use whenever EG is not available. The size of the LCS stapler shaft is more suitable for en bloc transection of the left lateral segment of the liver, which is thinner than the right one. Further studies are needed to evaluate the safety of LCS for large liver resections and resections of tumors located in the right hepatic lobe.

Recovery of Ce and La from phosphogypsum leachate by adsorption using grape wastes.

The present research aimed to evaluate the use of grape stalk in the adsorption of lanthanum and cerium to identify the best operating conditions enabling the application of the bioadsorbent in REEs leached from phosphogypsum. The grape stalk was characterized and showed an amorphous structure with a heterogeneous and very porous surface. Also, it was possible to identify the groups corresponding to carboxylic acids, phenols, alcohols, aliphatic acids, and aromatic rings. The pH effect study showed that the adsorption process of La3+ and Ce3+ ions was favored at pH 5.0. The adsorption kinetics followed the pseudo-second-order model. In just 20 min, 80% saturation was reached, while equilibrium was reached after 120 min. The adsorption isotherms were appropriately adjusted to the Langmuir model, and the maximum adsorption capacities were obtained at 298 K, which were 35.22 mg g-1 for La3+ and 37.99 mg g-1 for Ce3+. Furthermore, the adsorption process was favorable, spontaneous, and exothermic. In the study's second phase, phosphogypsum was leached with a sulfuric acid solution. Then, the adsorption of REEs was carried out under the experimental conditions of pH after leaching and pH 5.0 (adjustment carried out with sodium hydroxide solution) at 298 K for 120 min and with adsorbent dosages of 1 and 5 g L-1. This process resulted in removal percentages above 95% for the most abundant REEs, such as neodymium, lanthanum, and cerium, at pH 5.0 and a dosage of 5 g L-1, demonstrating the effectiveness of the bioadsorbent used. These results indicate the potential of using grape residue as a promising bioadsorbent in recovering rare earth elements from phosphogypsum leachate.

Human trophoblast stem cells can be used to model placental susceptibility to Toxoplasma gondii and highlight the critical importance of the trophoblast cell surface in pathogen resistance.

The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance to understand these mechanisms and challenges in replicating trophoblast- pathogen interactions using in vitro models, we tested an existing stem-cell derived model of trophoblast development for its relevance to infection with Toxoplasma gondii . We grew human trophoblast stem cells (TS CT ) under conditions leading to either syncytiotrophoblast (TS SYN ) or cytotrophoblast (TS CYT ) and infected them with T. gondii . We evaluated T. gondii proliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TS SYNs cells showed similar ultrastructure compared to primary cells and villous explants when analyzed by TEM and SEM, a resistance to T. gondii adhesion could be visualized on the SEM level. Furthermore, TS SYNs were highly refractory to parasite adhesion and replication, while TS CYT were not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded to T. gondii infection. We also evaluated if TS SC -derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen, Listeria monocytogenes . We demonstrate that TS SYNs are highly resistant to L. monocytogenes , while TS CYTs are not. Like T. gondii , TS SYN resistance to L. monocytogenes was at the level of bacterial adhesion. Altogether, our data indicate that stem-cell derived trophoblasts recapitulate resistance profiles of primary cells to T. gondii and highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.

Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal-fetal interface.

Introduction: Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection. Methods: In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants. Results: Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production. Discussion: In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.

Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation.

Objective: This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation. Methods: The pain model was induced by intraplantar (i.pl.) injection of Freund's complete adjuvant (CFA). Sixty-four male Swiss mice (35-40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days. Results: pVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord. Conclusion: pVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.

Exploring the Immune Response against RSV and SARS-CoV-2 Infection in Children.

Viral respiratory tract infections are a significant public health concern, particularly in children. RSV is a prominent cause of lower respiratory tract infections among infants, whereas SARS-CoV-2 has caused a global pandemic with lower overall severity in children than in adults. In this review, we aimed to compare the innate and adaptive immune responses induced by RSV and SARS-CoV-2 to better understand differences in the pathogenesis of infection. Some studies have demonstrated that children present a more robust immune response against SARS-CoV-2 than adults; however, this response is dissimilar to that of RSV. Each virus has a distinctive mechanism to escape the immune response. Understanding the mechanisms underlying these differences is crucial for developing effective treatments and improving the management of pediatric respiratory infections.

Challenges in Perioperative Cerebral Oximetry Monitoring: A Case of Clofazimine-Induced Skin Pigmentation Interference.

Perioperative stroke is a potentially devastating complication in patients undergoing noncardiac surgery. The most consistent risk factor associated with the condition is a history of a prior stroke. Cerebral oximetry is a simple, non-invasive, and continuous monitoring device that uses near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation. However, like other monitoring devices, cerebral oximetry has certain limitations, and it must be interpreted cautiously and by taking into account all available clinical information related to the patient. We present a case of a 62-year-old Caucasian woman with a past medical history of a transient ischemic attack (TIA), who had been advised to undergo a right pneumectomy by video-assisted thoracoscopic surgery for treating chronic infection of bronchiectasis. Before administering any drug and while the patient was still alert, we monitored NIRS, and the values recorded were 15 on the left side and 26 on the right side. Despite being Caucasian, she had a darker brownish skin color due to chronic clofazimine use, which is known to cause skin pigmentation. Skin pigmentation is known to attenuate the transmission of near-infrared (NIR) light, potentially affecting the estimation of cerebral oxygen saturation. Thus, our patient suffered from clofazimine-induced skin pigmentation, which may have interfered with the NIR light transmission, which explains the extremely low values observed. Regional intracerebral oxygen saturation should be interpreted in the context of all available clinical information since NIRS transmission can be influenced by several factors and skin pigment has been found to independently influence regional intracerebral oxygen saturation. Apart from race or high serum bilirubin concentration, we should also consider other causes of skin pigmentation alterations, such as pharmacological therapy.