Neurodevelopment following exposure to antiseizure medications in utero: a review

: Exposure in the womb to antiseizure medications and their potential impact on the developing child's brain has long been researched. Despite this long period of interest, this review highlights above the well-known risks associated with valproate exposure; more data is required for conclusions regarding all other antiseizure medications. Limited experience with phenytoin and phenobarbital in monotherapy clearly defines the risk to later child postnatal functioning difficult. However, the evidence of an impact is stronger for phenobarbital than for phenytoin. The widely prescribed lamotrigine is limited in its investigation compared to unexposed control children. It has been demonstrated to carry a lower risk than valproate for specific outcomes; whether associated with a more moderate impact on broader aspects of neurodevelopmental functioning is still to be understood. Data for levetiracetam, topiramate, and oxcarbazepine are too limited to conclude most neurodevelopmental outcomes confidently. This slow accumulation of evidence impacts the safest use of medications in pregnancy and makes counseling women regarding the risks and benefits of specific antiseizure drugs difficult. Improved focus, funding, and research methodologies are urgently needed.

Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray

The emergence and rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of varying lengths and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multi-coronavirus arrays to identify specific antibody reactivity. High level IgG, IgM and IgA reactivity to structural proteins S, M and N, as well as accessory proteins, of SARS-CoV-2 were observed that was specific to COVID-19 patients. Overlapping 100, 50 and 30 amino acid fragments of SARS-CoV-2 proteins identified antigenic regions. Numerous proteins of SARS-CoV, MERS-CoV and the endemic human coronaviruses, HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients.

Prenatal indole-3-carbinol administration activates aryl hydrocarbon receptor-responsive genes and attenuates lung injury in a bronchopulmonary dysplasia model

Hyperoxia−hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia–hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway ( Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia–hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P < 0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia–hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup’s lungs and hence attenuates lung damage caused by hyperoxia–hypoxia exposure in newborns.

Individual and combined anti-trypanosomal effects of arteether and diminazene aceturate in the treatment of experimental Trypanosoma brucei brucei infection in rats

Aim: Trypanosomosis is a vital protozoan disease of man and animals with devastating consequences in the tropical parts of the world, necessitating the investigation of the effects of diminazene aceturate (DA) and arteether (AR) on Trypanosoma brucei brucei experimental infection in rats. Materials and Methods: We used a total of 98 rats, which were divided into 14 groups (A-N) of seven rats each over 36 days after acclimatizing them. We administered 1×106 trypanosomes to the infected groups (B-N) with Group A as the unexposed control rats. Groups C-F became the infected and treated rats with 3.5 mg/kg, 7.0 mg/kg, 10.5 mg/kg, and 14.0 mg/kg of DA while Groups G-J became the infected and treated rats with 0.01 ml/kg, 0.02 ml/kg, 0.03 ml/kg, and 0.04 ml/kg of AR. Groups K-N became infected and treated rats with DA and AR combinations at similar doses. Results: Parasitemia suppression occurred in Groups G-J only but became cleared in Groups C-F and K-N. Survival time varied significantly (p<0.05) between Group B and the other infected groups. We recorded anemia in all the infected rats while significant (p<0.05) splenomegaly and hepatomegaly occurred in Groups G-J only compared to the other groups. Conclusion: AR did not inhibit or potentiate the anti-trypanosomal efficacy of DA, and therefore, it is comparatively less effective in combating T. brucei infection at the present doses and treatment regimen.

HPV infection and endometriosis: a systematic review and meta-analysis

Introduction: Recent research has focused on the role of persistent ascending bacterial infections and sexually transmitted infections (STI) as a factor associated to endometriosis. Indeed, some studies investigated the possible role of HPV in endometriosis, but this topic remains inconclusive. Objective:The present study aims to meta-analyze research that assessed the presence of HPV infection in patients with endometriosis. Methods: MEDLINE, Embase, Scopus, LILACS, Cochrane Library, and OpenGrey were searched until February 10th, 2020. Search terms included “endometriosis” and “HPV” without language restrictions. The combined relative risks and 95% confidence interval (95%CI) were calculated, and heterogeneity was assessed with I-square (I2 ). Results: Meta-analysis with low heterogeneity found a relative risk of twice as much in women exposed to HPV in relation to the unexposed control. Conclusion: Results indicate that HPV could be a risk factor for developing endometriosis.

The “Gateway Belief” illusion: reanalyzing the results of a scientific-consensus messaging study

This paper analyzes data collected but not reported in the study featured in van der Linden, Leiserowitz, Feinberg, and Maibach [van der Linden et al., 2015]. VLFM report finding that a “scientific consensus” message “increased” experiment subjects' “key beliefs about climate change” and “in turn” their “support for public action” to mitigate it. However, VLFM fail to report that message-exposed subjects' “beliefs about climate change” and “support for public action” did not vary significantly, in statistical or practical terms, from those of a message-unexposed control group. The paper also shows how this absence of an experimental effect was obscured by a misspecified structural equation model.

Apoptotic cell death in rat lung following mustard gas inhalation

To investigate apoptosis as a mechanism of sulfur mustard (SM) inhalation injury in animals, we studied different caspases (caspase-8, -9, -3, and -6) in the lungs from a ventilated rat SM aerosol inhalation model. SM activated all four caspases in cells obtained from bronchoalveolar lavage fluid (BALF) as early as 6 h after exposure. Caspase-8, which is known to initiate the extrinsic Fas-mediated pathway of apoptosis, was increased fivefold between 6 and 24 h, decreasing to the unexposed-control level at 48 h. The initiator, caspase-9, in the intrinsic mitochondrial pathway of apoptosis as well as the executioner caspases, caspase-3 and -6, all peaked ( P < 0.01) at 24 h; caspase-3 and -6 remained elevated, but caspase-9 decreased to unexposed-control level at 48 h. To study further the Fas pathway, we examined soluble as well as membrane-bound Fas ligand (sFas-L and mFas-L, respectively) and Fas receptor (Fas-R) in both BALF cells and BALF. At 24 h after SM exposure, sFas-L increased significantly in both BALF cells ( P < 0.01) and BALF ( P < 0.05). However, mFas-L increased only in BALF cells between 24 and 48 h ( P < 0.1 and P < 0.001, respectively). Fas-R increased only in BALF cells by 6 h ( P < 0.01) after SM exposure. Apoptosis in SM-inhaled rat lung specimens was also confirmed by both immunohistochemical staining using cleaved caspase-3 and -9 antibodies and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as early as 6 h in the proximal trachea and bronchi, but not before 48 h in distal airways. These findings suggest pathogenic mechanisms at the cellular and molecular levels and logical therapeutic target(s) for SM inhalation injury in animals.

EFFECTS OF ULTRASOUND ON ARTEMIA CYST INCUBATION

The present work aims to test the bioeffects of ultrasounds on cyst formation in the crustacean Artemia salina. It is designed to identify which durations of ultrasonic exposure are capable of influencing hatching rates. The transducers used in the experiment were operated at resonant (0.23[Formula: see text]MHz and 4.7[Formula: see text]MHz) and non-resonant (0.5[Formula: see text]MHz and 1[Formula: see text]MHz) frequencies and the intensities of 3.25[Formula: see text]mW/cm2 and 13.63[Formula: see text]mW/cm2. The Rayleigh–Plesset theoretical framework was used to calculate the dynamics of shell-encapsulated cysts. The duration of ultrasound exposure was approximately 2[Formula: see text]min every 2[Formula: see text]h, repeated 6 times in the culture range of 1–15[Formula: see text]h. The results demonstrate that irradiation at an intensity of 13.63[Formula: see text]mW/cm2 and a driving frequency of 0.23[Formula: see text]MHz increased the number of hatched larvae by approximately 31.7%, compared with unexposed control samples. In conclusion, the theoretical model provided a useful means of predicting the most efficient frequency of sonication.

Frequency of sucrose exposure on the cariogenicity of a biofilm-caries model

ABSTRACT Objective: Although sucrose is considered the most cariogenic carbohydrate in the human diet, the question of how many exposures are needed to induce damage on the hard dental tissues remains unclear. To approach this question, different frequencies of daily sucrose exposure were tested on a relevant biological caries model. Materials and Methods: Biofilms of the Streptococcus mutans were formed on enamel slabs and exposed to cariogenic challenges with 10% sucrose for 5 min at 0, 1, 3, 5, 8, or 10 times per day. After 5 days, biofilms were retrieved to analyze biomass, protein content, viable bacteria, and polysaccharide formation. Enamel demineralization was evaluated by percentage of microhardness loss (percentage surface hardness loss [%SHL]). Results: Biomass, protein content, polysaccharide production, acidogenicity of the biofilm, and %SHL proportionally increased with the number of daily exposures to sucrose (P < 0.05). One daily sucrose exposure was enough to induce 20% more demineralization than the negative unexposed control. Higher frequencies induced greater demineralization and more virulent biofilms, but eight and ten exposures were not different between them in most of the analyzed variables (P > 0.05). Conclusions: Higher sucrose exposure seems to increase cariogenicity, in a frequency-dependent manner, by the modification of bacterial virulent properties.

Effect of Acetylation on Stability to Retrogradation of Starch Extracted from Wild Polynesian Arrowroot (Tacca leontopetaloides (L.) Kuntze) for Utilization as Adhesive on Paper

Starch was isolated from T. leontopetaloides tubers, chemically modified by acetylation with varying amounts of acetic anhydride. Monolayer of the ten acetylated and control starch powders was exposed on roof top for five weeks and pastes of both exposed and unexposed (control) samples were prepared with distilled water (1 : 3 w/w). The effects of acetylation, degree of substitution (DS), and exposure to sunlight were investigated to evaluate the retrogradation tendency of the adhesive pastes from changes in syneresis, tack strength, optical clarity, viscosity, gelation time, and drying time. The results obtained showed that all the adhesive properties studied were affected by both DS and exposure to sunlight. While tack strength, viscosity, and drying time were found to increase with increase in DS, syneresis, optical clarity, and gelation time were found to decrease with increase in DS. Increase in tack strength and reduction in syneresis imply that the acetylation treatment has made T. leontopetaloides starch more suitable for use in remoistenable adhesive applications. The reduction in syneresis, optical clarity, and gelation time with increase in DS was attributed to the strengthening of the bonds between the amylose and amylopectin molecules, preventing water leaching out of the starch granules.