Epileptogenesis and drug-resistant in focal cortical dysplasias: Update on clinical, cellular, and molecular markers.

Focal cortical dysplasia (FCD) is a cortical malformation in brain development and is considered as one of the major causes of drug-resistant epilepsiesin children and adults. The pathogenesis of FCD is yet to be fully understood. Imaging markers such as MRI are currently the surgeons major obstacle due to the difficulty in delimiting the precise dysplasic area and a mosaic brain where there is epileptogenic tissue invisible to MRI. Also increased gene expression and activity may be responsible for the alterations in cell proliferation, migration, growth, and survival. Altered expressions were found, particularly in the PI3K/AKT/mTOR pathway. Surgery is still considered the most effective treatment option, due to drug-resistance, and up to 60 % of patients experience complete seizure control, varying according to the type and location of FCD. Both genetic and epigenetic factors may be involved in the pathogenesis of FCD, and there is no conclusive evidence whether these alterations are inherited or have an environmental origin.

Immediate effect of extracorporeal shockwave therapy in patients with chronic non-specific low back pain: A randomised placebo-controlled triple-blind trial.

OBJECTIVE: To compare the immediate effects of shockwave therapy using two different tips in patients with chronic non-specific low back pain. DESIGN: Randomised placebo-controlled study with three intervention groups. SETTING: The patients recruited for this study were sent for physiotherapy treatment at primary care between May and July 2022. PARTICIPANTS: Eighty-one patients with chronic non-specific low back pain aged 18-80 years with pain for ≥3 months and pain intensity ≥3 were randomly recruited for the study. INTERVENTION: The patients received a single intervention of radial shockwave therapy with 2000 discharges at 100 mJ energy and 5 Hz frequency using concave or convex tips or placebo treatment. MAIN MEASURES: The primary outcome was pain intensity immediately post-intervention. The secondary outcomes were pressure pain threshold, temporal summation of pain, and functional performance. Data were collected at baseline and post-intervention. RESULTS: The post-intervention pain intensity in the concave tip group is an average of two points lower (95% CI = -3.6, -0.4; p < 0.01) than that in the placebo group. The post-intervention pressure pain threshold for the concave tip group was an average of 62.8 kPa higher (95% CI = 0.4, 125.1; p < 0.05) than for the convex tip group and 76.4 kPa higher (95% CI = 14, 138.7; p < 0.01) than in the placebo group. CONCLUSION: The concave tip shockwave therapy is effective in reducing pain and local hyperalgesia in patients with chronic non-specific low back pain.

Postmenopausal women treated for breast cancer with insulin resistance: clinical, analytical, cross-sectional.

This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.

State-Dependent Blockade of Dorsal Root Ganglion Voltage-Gated Na+ Channels by Anethole.

Anethole is a phenolic compound synthesized by many aromatic plants. Anethole is a substance that humans can safely consume and has been studied for years as a biologically active molecule to treat a variety of conditions, including nerve damage, gastritis, inflammation, and nociception. Anethole is thought to carry out its biological activities through direct interaction with ion channels. Anethole is beneficial for neurodegenerative Alzheimer's and Parkinson's diseases. Nevertheless, nothing has been investigated regarding the effects of anethole on voltage-gated Na+ channels (VGSCs), which are major players in neuronal function. We used cultured dorsal root ganglion neurons from neonatal rats as a source of natively expressed VGSCs for electrophysiological studies using the whole-cell patch-clamp technique. Our data show that anethole interacts directly with VGSCs. Anethole quickly blocks and unblocks (when removed) voltage-activated Na+ currents in this preparation in a fully reversible manner. Anethole's binding affinity to these channels increases when the inactive states of these channels are populated, similar to lidocaine's effect on the same channels. Our data show that anethole inhibits neuronal activity by blocking VGSCs in a state-dependent manner. These findings relate to the putative anesthetic activity attributable to anethole, in addition to its potential benefit in neurodegenerative diseases.

Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.

Ecological risk of mercury in bottom sediments and spatial correlation with land use in Neotropical savanna floodplain lakes, Araguaia River, Central Brazil.

The Araguaia River floodplain is an important biogeographic boundary between the two largest South American biomes: the Cerrado (Brazilian Savanna) and the Amazon rainforest. The large-scale degradation due to land use conversion experienced in the Araguaia River watershed represents a potential source of mercury (Hg) transport to aquatic ecosystems. However, more information is needed about the dynamics of Hg distribution in savanna floodplains, including the Araguaia River floodplain. We analyzed total mercury (THg) concentrations in the bottom sediments of 30 lakes connected to the Araguaia River and four tributaries, aiming to evaluate the environment's integrity based on the geoaccumulation index (Igeo) and the ecological risk index (ERI). The principal component analysis was applied to examine associations between Hg concentrations, environmental conditions, and land use intensity among lakes associated with different river systems. We used indicator cokriging to identify areas with a greater probability of Hg pollution and ecological risk associated with land use intensity. The land use data showed the predominance of areas used for pasture in the Araguaia River basin. THg concentrations in the sediments varied between 22.6 and 81.9 ng g-1 (mean: 46.5 ± 17.7 ng g-1). Sediments showed no significant pollution (Igeo: 1.35 - 0.50; Classes 1 and 2) and low to considerable ecological risks (ERI: 23.5-85.1; Classes 1 to 3). THg in bottom sediments was associated with land use, water turbidity and electrical conductivity, and sediment organic matter. The indicator cokriging indicates a moderate to strong spatial dependence between land use intensity and Hg, confirming the contribution of anthropic sources to the increment of ecological risk but also the influence of extrinsic factors (such as environmental conditions, geology, and hydrology). Integrating sediment assessment and land use indices with geostatistical methods proved a valuable tool for identifying priority areas for Hg accumulation at a regional scale.

Intraoperative and early postoperative pain in cats that underwent ovariohysterectomy using a spay hook: a randomised, masked, experimental study.

BACKGROUND: This study aimed to compare the feasibility and practicality of the ovariohysterectomy (OHE) technique in cats with or without a spay hook with respect to the incision size, surgical time, surgical variables, and intra- and postoperative pain. Twenty-nine female cats underwent OHE using a spay hook (spay hook group [SHG], n = 15) or without using a spay hook (control group [CG], n = 14) to achieve the ovaries and cervix. Physiological parameters were monitored during the intraoperative period, and postoperative pain was assessed using a multidimensional composite and visual analogue pain scales. RESULTS: The SHG had a significantly shorter operative time than the CG. The variables in the intraoperative period showed no statistically significant difference between both groups, as well as the early postoperative pain. CONCLUSIONS: Less invasive OHE using a spay hook could potentially be a viable and feasible technique when performed by an inexperienced surgeon with appropriate training, especially in sterilisation campaigns, reducing the time to perform the procedure and increasing the number of animals spayed per time.

Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia.

Despite a growing number of ion channel genes implicated in hereditary ataxia, it remains unclear how ion channel mutations lead to loss-of-function or death of cerebellar neurons. Mutations in the gene KCNMA1, encoding the α-subunit of the BK channel have emerged as responsible for a variety of neurological phenotypes. We describe a mutation (BKG354S) in KCNMA1, in a child with congenital and progressive cerebellar ataxia with cognitive impairment. The mutation in the BK channel selectivity filter dramatically reduced single-channel conductance and ion selectivity. The BKG354S channel trafficked normally to plasma, nuclear, and mitochondrial membranes, but caused reduced neurite outgrowth, cell viability, and mitochondrial content. Small interfering RNA (siRNA) knockdown of endogenous BK channels had similar effects. The BK activator, NS1619, rescued BKG354S cells but not siRNA-treated cells, by selectively blocking the mutant channels. When expressed in cerebellum via adenoassociated virus (AAV) viral transfection in mice, the mutant BKG354S channel, but not the BKWT channel, caused progressive impairment of several gait parameters consistent with cerebellar dysfunction from 40- to 80-d-old mice. Finally, treatment of the patient with chlorzoxazone, a BK/SK channel activator, partially improved motor function, but ataxia continued to progress. These studies indicate that a loss-of-function BK channel mutation causes ataxia and acts by reducing mitochondrial and subsequently cellular viability.

Postoperative local interventions for the palate as a gingival graft donor area: a scoping review.

OBJECTIVE: This scoping review aimed to systematically identify evidence-based interventions to stimulate healing or protect the harvested palate of patients undergoing gingival grafting. MATERIAL AND METHODS: The study followed guidelines from the Joanna Briggs Institute and PRISMA-ScR (protocol available at osf.io/zhafn). PubMed, Embase, and seven other databases were searched on November 2022, with additional monitoring until April 2023. The inclusion criteria focused on studies evaluating outcomes related to the donor area (palate) and interventions for healing or protecting it, regardless of publication year and language. Data from the included publications was extracted and presented through narrative text, tables, and figures. RESULTS: Eighty-one studies (including 64 clinical trials, four case series, five theses, and eight systematic reviews) and 37 clinical trial records were included. The number of studies on this topic has significantly increased, reflecting a growing interest in the field. Thirty-six interventions with published results and 12 interventions with unpublished results from clinical trial registers were identified. Some promising interventions that showed potential for improving patient-reported outcomes include cyanoacrylate adhesive, platelet-rich fibrin (PRF), and the combination of palatal stents and healing agents. CONCLUSIONS: Thirty-six interventions with published results were identified for postoperative use on the harvested palate, showing varying levels of evidence and conflicting effectiveness for specific outcomes. CLINICAL RELEVANCE: Postoperative discomfort and pain in the palate are commonly experienced by patients undergoing grafting procedures using this region as the donor area. Awareness of the available options and their levels of evidence is crucial for informed decision-making.

Mechanistic Investigation of the Androgen Receptor DNA-Binding Domain and Modulation via Direct Interactions with DNA Abasic Sites: Understanding the Mechanisms Involved in Castration-Resistant Prostate Cancer.

The androgen receptor (AR) is an important drug target in prostate cancer and a driver of castration-resistant prostate cancer (CRPC). A significant challenge in designing effective drugs lies in targeting constitutively active AR variants and, most importantly, nearly all AR variants lacking the ligand-binding domain (LBD). Recent findings show that an AR's constitutive activity may occur in the presence of somatic DNA mutations within non-coding regions, but the role of these mutations remains elusive. The discovery of new drugs targeting CRPC is hampered by the limited molecular understanding of how AR binds mutated DNA sequences, frequently observed in prostate cancer, and how mutations within the protein and DNA regulate AR-DNA interactions. Using atomistic molecular dynamics (MD) simulations and quantum mechanical calculations, we focused our efforts on (i) rationalising the role of several activating DBD mutations linked to prostate cancer, and (ii) DBD interactions in the presence of abasic DNA lesions, which frequently occur in CRPC. Our results elucidate the role of mutations within DBD through their modulation of the intrinsic dynamics of the DBD-DNA ternary complex. Furthermore, our results indicate that the DNA apurinic lesions occurring in the androgen-responsive element (ARE) enhance direct AR-DNA interactions and stabilise the DBD homodimerisation interface. Moreover, our results strongly suggest that those abasic lesions may form reversible covalent crosslinks between DNA and lysine residues of an AR via a Schiff base. In addition to providing an atomistic model explaining how protein mutations within the AR DNA-binding domain affect AR dimerisation and AR-DNA interactions, our findings provide insight into how somatic mutations occurring in DNA non-coding regions may activate ARs. These mutations are frequently observed in prostate cancer and may contribute to disease progression by enhancing direct AR-DNA interactions.

Organic-Inorganic Hybrid Pigments Based on Bentonite: Strategies to Stabilize the Quinoidal Base Form of Anthocyanin.

Anthocyanins are one of the natural pigments that humanity has employed the most and can substitute synthetic food dyes, which are considered toxic. They are responsible for most purple, blue, and red pigment nuances in tubers, fruits, and flowers. However, they have some limitations in light, pH, oxygen, and temperature conditions. Combining biomolecules and inorganic materials such as clay minerals can help to reverse these limitations. The present work aims to produce materials obtained using cetyltrimethylammonium bromide in bentonite clay for incorporation and photostabilization of anthocyanin dye. Characterizations showed that the organic molecules were intercalated between the clay mineral layers, and the dye was successfully incorporated at a different pH. Visible light-driven photostability tests were performed with 200 h of irradiation, confirming that the organic-inorganic matrices were efficient enough to stabilize the quinoidal base form of anthocyanin. The pigment prepared at pH 10 was three-fold more stable than pH 4, showing that the increase in the synthesis pH promotes more stable colors, probably due to the stronger intermolecular interaction obtained under these conditions. Therefore, organobentonite hybrids allow to stabilize the fragile color coming from the quinoidal base form of anthocyanin dyes.

Histological investigation in aging male and female gerbil prostates after prenatal exposure to pequi (Caryocar brasiliense Cambess) oil and 17α-ethinylestradiol.

The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.

Spatio-temporal study of water quality variables in the Rio de Ondas Hydrographic Basin, west of Bahia, Brazil using multivariate analysis.

Water bodies are containers that receive a large load of water quality variables through the release of domestic, industrial, and agricultural effluents. With this focus, this work aimed to conduct a temporal-spatial variability study in the Rio de Ondas Hydrographic Basin through multivariate statistical analysis. For this, seventeen collection sites were established in four stations along the Rio de Ondas and its tributaries between 2017 and 2018. Ionic chromatography with suppressed conductivity was used for ions determination, while ICP-OES determined metals' total concentrations. The land use and occupation assessment between 1985 and 2021 was using data from MapBiomas were used and the descriptive and multivariate analysis of the data using version free of the Statistica software. The results showed that, in 30 years, there was a growth of 569% of agricultural activities in the watershed area, with significant suppression of native vegetation, favoring the transport of contaminants to rivers. Ca2+, PO42-, Al, Cu, and Zn concentrations showed a statistically significant difference between the seasons, with higher medians in the rainy season. Rainy season influenced the formation of three groups in the PCA, consisting of electrical conductivity, salinity, TDS, and PO42- (group 1); temperature, Fe, SO42-, and Cl- (group 2); and Ca2+, Mg2+, Na+, and HCO3- (group 3). The strong correlation between parameters of each group indicates anthropic influence on the watershed's water quality. However, levels are within the potability standard.

Cryptococcosis in HIV/AIDS patients in northern Brazil: Clinical aspects, molecular types and isolation of agents from environmental samples associated with patients.

OBJECTIVES: In the state of Amazonas, northern Brazil, cryptococcosis is endemic, with a predominance of Cryptococcus neoformans in individuals with HIV/AIDS, and Cryptococcus gattii VGII in non-HIV individuals. This study analysed the clinical isolates and clinical-epidemiological characteristics of HIV/AIDS patients diagnosed with cryptococcosis in a tertiary healthcare facility in Manaus, Amazonas and investigated the presence of agents of cryptococcosis in environmental samples. METHODS: A survey was made of data from HIV/AIDS patients diagnosed with cryptococcosis between January 2017 and December 2019, and environmental samples were collected at the patients' and their neighbours' homes. The isolates were submitted to morphophysiological analysis and PCR-RFLP typing to determine the molecular types. RESULTS: Clinical-epidemiological characteristics of 55 patients and 75 clinical isolates were analysed. Neurocriptococcosis was the clinical form observed in 98.2% (n = 54/55) of patients. A total of 38.1% (n = 21/55) of patients died within 100 weeks, of which 21.8% (n = 12/55) died less than a month after the diagnosis of cryptococcosis. C. neoformans VNI (n = 68/75), C. neoformans VNII (n = 1/75), C. gattii VGI (n = 3/75) and C. gattii VGII (n = 3/75) were identified. Mixed infection was observed in two patients, one by C. neoformans VNI and VNII and the other by C. neoformans VNI and C. gattii VGI. Cryptococcus VNI was detected in three (n = 3/51) households, one of a patient (n = 1/17) and two households that neighbour patients' houses (n = 2/34). CONCLUSIONS: This study demonstrated the prevalence of C. neoformans VNI, which is a cause of cryptococcosis in patients with HIV/AIDS in the state of Amazonas, and revealed a greater diversity of molecular types affecting these patients in the region than in previous studies. In the studied group, a high mortality rate was observed, which reflects the importance of early diagnosis, and evidences cryptococcosis as an AIDS-defining disease and an important public health problem in the region. The home environment proved to be a potential source of infection/reinfection by C. neoformans VNI.

Investigation of fluconazole heteroresistance in clinical and environmental isolates of Cryptococcus neoformans complex and Cryptococcus gattii complex in the state of Amazonas, Brazil.

Heteroresistance, defined as the occurrence of apparently homogeneous subpopulations of microbial cells showing different levels of antimicrobial susceptibility is a problem that has been associated with therapeutical failure in cryptococcosis. The purpose of the study was an investigation on the level of heteroresistance to fluconazole (LHF) as observed in clinical and environmental C. neoformans/C. gattii complex species isolates from Amazonas State (AM), Brazil. A total of 45 isolates and 9 type strains were analyzed. The assessments comprised testing for minimal inhibitory concentrations (MICs), for LHFs, for the strains' capacity of adaptation to high fluconazole (FLC) concentrations above the LHF, and for the stability of the heteroresistance phenomenon. The mean MICs for clinical isolates of C. gattii (6.4 µg/ml) were higher than those observed for environmental C. gattii strains (1.7 µg/ml) and clinical (3.7 µg/ml) as well as environmental (1.5 µg/ml) C. neoformans isolates. The phenomenon of heteroresistance to FLC was recorded for all isolates. On average, the LHF (8-256 µg/ml) of the isolates was 16 times higher than the FLC MICs (0.5-16 µg/ml) and a proportion of 85% isolates showed LHFs ≥ 16 µg/ml, 40% even ≥ 32 µg/ml. According to the adaptation assay, a considerable number of isolates (58%) showed the capacity of adaptation to MICs even higher than the initially recorded LHF. After the adaptation experiment, the adaptative-LHF values (8-512 µg/ml) were about 60 times higher than the original MIC values. After nine subsequent passages in drug-free broth, the isolates had their adaptative-LHF reduced. However, the LHF did not revert to the initially measured level. Our findings challenge the clinical interpretation of the antifungal MIC testing and motivate future studies correlating the levels of heteroresistance and parameters like LHF and adaptative-LHF with cryptococcosis-associated morbidity and mortality. LAY SUMMARY: Cryptococcosis affects many people and is caused by fungi of the Cryptococcus neoformans/Cryptococcus gattii complexes. These agents appear to become more resistant to antifungals when exposed to increasing concentrations of antifungals due to a phenomenon called heteroresistance.

Mercury spatiality and mobilization in roadside soils adjacent to a savannah ecological reserve.

Mercury (Hg) is a persistent environmental pollutant of global concern. Recognized anthropic contributions to environmental Hg pollution include fuel fossil emissions, soil erosion, and industrial and mining activities. Environmental Hg that enters water bodies can be methylated before entering the food chain and contaminating man and wildlife. We used a kriging approach for sampling and X-ray crystallography to study the pressure of road-traffic Hg emissions on soil Hg concentrations in an ecological reserve (ESECAE) in Central Brazil' savannah. We took samples of organic (n = 144) and mineral (n = 144) layers from the road-side and from the undisturbed soils at 0.1, 1, and 2 km from traffic, inside the ESECAE. Overall, total mercury (THg) concentrations determined by atomic absorption spectrophotometry were significantly higher in the organic layer than in the mineral layer. The mean soil THg in the organic and mineral layers was highest at the roadside (respectively 19.77 ± 12.01 and 16.18 ± 11.54 µg g-1), gradually decreasing with the distance from the road. At 2 km, the mean soil THg was 0.09 ± 0.30 and 0.029 ± 0.03 µg g-1, respectively, for the organic and mineral layers. X-ray crystallography showed mineralogical similarity of the sampled soils, indicating Hg externality, i.e, it did not originate from existing soil minerals. Co-kriging analysis (n = 288) confirmed Hg hotspots on the roadsides and a faster mobilization occurring up to a distance of 1 km for both layers. The soil reception and retention of traffic Hg emissions are mainly in the organic layer and can impact subsoil and adjacent areas. Thus, traffic soil-Hg pollution is limited to the road proximities; THg concentrations are high up to 100 m with an inflection point at 1 km.

Satisfaction with oral health and associated factors among homeless people in Midwest Brazil.

BACKGROUND: Self-perceived oral health has been extensively investigated, but studies on homeless people are scarce, and there is currently no evidence from Latin America. OBJECTIVE: To investigate the prevalence and factors associated with satisfaction with the oral health of homeless individuals in one Brazilian capital of the Midwest region. SUBJECT AND METHODS: A cross-sectional study was carried out with 351 adult individuals attending a temporary public shelter who were interviewed about sociodemographic and psychosocial aspects, drugs use and oral health. The outcome was satisfaction with oral health (satisfied/dissatisfied). Pearson's chi-square test and Poisson regression with robust variance were used for statistical analysis. RESULTS: The prevalence of dissatisfaction with oral health was 68.9% (95% CI = 63.9-73.6). After adjusting for covariates, dissatisfaction was more frequent among individuals who were married/in a stable relationship (PR = 1.18; 95% CI = 1.02-1.36), with felt need for treatment (PR = 2.27; 95% CI = 1.23-4.17) or complete prosthesis (PR = 1.35; 95% CI = 1.18-1.55), and those who used illicit drugs in the past six months (PR = 1.22; 95% CI = 1.06-1.39). CONCLUSION: The prevalence of dissatisfaction with oral health in the homeless individuals studied was high and associated with their marital status, use of illicit drugs and self-reported need for dental treatment and complete prosthesis.

Identification of Potential Antiviral Inhibitors from Hydroxychloroquine and 1,2,4,5-Tetraoxanes Analogues and Investigation of the Mechanism of Action in SARS-CoV-2.

This study aimed to identify potential inhibitors and investigate the mechanism of action on SARS-CoV-2 ACE2 receptors using a molecular modeling study and theoretical determination of biological activity. Hydroxychloroquine was used as a pivot structure and antimalarial analogues of 1,2,4,5 tetraoxanes were used for the construction and evaluation of pharmacophoric models. The pharmacophore-based virtual screening was performed on the Molport® database (~7.9 million compounds) and obtained 313 structures. Additionally, a pharmacokinetic study was developed, obtaining 174 structures with 99% confidence for human intestinal absorption and penetration into the blood-brain barrier (BBB); posteriorly, a study of toxicological properties was realized. Toxicological predictions showed that the selected molecules do not present a risk of hepatotoxicity, carcinogenicity, mutagenicity, and skin irritation. Only 54 structures were selected for molecular docking studies, and five structures showed binding affinity (ΔG) values satisfactory for ACE2 receptors (PDB 6M0J), in which the molecule MolPort-007-913-111 had the best ΔG value of -8.540 Kcal/mol, followed by MolPort-002-693-933 with ΔG = -8.440 Kcal/mol. Theoretical determination of biological activity was realized for 54 structures, and five molecules showed potential protease inhibitors. Additionally, we investigated the Mpro receptor (6M0K) for the five structures via molecular docking, and we confirmed the possible interaction with the target. In parallel, we selected the TopsHits 9 with antiviral potential that evaluated synthetic accessibility for future synthesis studies and in vivo and in vitro tests.

Influence of vinification process over the composition of volatile compounds and sensorial characteristics of greek wines.

Wine is one of the most traditional consumed alcoholic beverages in the world. Millions of wine enthusiasts worldwide duly appreciate a wine of excellent quality in terms of physicochemical and sensorial properties. Different classes of wines have different volatile compositions and sensorial properties, which can be altered, depending on the vinification process and use of additives. Among the widely employed additives in wine production is sulfite (SO2). The popularity of sulfite lies in its ability to preserve the flavor and freshness of wine; however, depending on the quantity, sulfite can pose serious health risks to consumers and affect the quality of the drink. The present study evaluated and compared the compositions of volatile compounds and sensorial properties of sparkling and traditional wines (with and without SO2) produced from Greek grapes 'Grechetto', 'Greco bianco' and 'Greco di tufo'. The results obtained of the composition of volatile compounds in these wines pointed to differences between SO2-containing, SO2-free and sparkling wines, with different amounts of compounds such as alcohols, esters, fatty acids, phenols and differences in sensorial properties. The 'Grechetto' wine, prepared without SO2, exhibited greater quality, better volatile composition, and better sensorial properties compared to the wines produced with SO2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05160-y.

Transsylvian amygdalohippocampectomy for mesial temporal lobe epilepsy: Comparison of three different approaches.

OBJECTIVE: This study's objective was to compare the transinsular (TI-AH), transuncus (TU-AH), and temporopolar (TP-AH) amygdalohippocampectomy approaches regarding seizure control, temporal stem (TS) damage, and neurocognitive decline. METHODS: We included 114 consecutive patients with unilateral hippocampal sclerosis (HS) who underwent TI-AH, TU-AH, or TP-AH between 2002 and 2017. We evaluated seizure control using Engel classification. We used diffusion tensor imaging and postoperative Humphrey perimetry to assess the damage of the TS. We also performed pre- and postoperative memory performance and intelligence quotient (IQ). RESULTS: There were no significant differences in the proportion of patients free of disabling seizures (Engel IA+IB) among the three surgical approaches in the survival analysis. However, more patients were free of disabling seizures (Engel IA+IB) at 2 years of postsurgical follow-up with TP-AH (69.5%) and TI-AH (76.7%) as compared to the TU-AH (43.5%) approach (p = .03). The number of fibers of the inferior fronto-occipital fasciculus postoperatively was reduced in the TI-AH group compared with the TU-AH and TP-AH groups (p = .001). The rate of visual field defects was significantly higher with TI-AH (14/19, 74%) in comparison to the TU-AH (5/15, 33%) and TP-AH (13/40, 32.5%) approaches (p = .008). Finally, there was a significant postoperative decline in verbal memory in left-sided surgeries (p = .019) and delayed recall for both sides (p < .001) regardless of the surgical approach. However, TP-AH was the only group that showed a significant improvement in visual memory (p < .001) and IQ (p < .001) for both right- and left-sided surgeries. SIGNIFICANCE: The TP-AH group had better short-term seizure control than TU-AH, a lower rate of visual field defects than TI-AH, and improved visual memory and IQ compared to the other groups. Our findings suggest that TP-AH is a better surgical approach for temporal lobe epilepsy with HS than TI-AH and TU-AH.