Identification of Toxoplasma gondii adhesins through a machine learning approach.

Toxoplasma gondii, as other apicomplexa, employs adhesins transmembrane proteins for binding and invasion to host cells. Search and characterization of adhesins is pivotal in understanding Apicomplexa invasion mechanisms and targeting new druggable candidates. This work developed a machine learning software called ApiPredictor UniQE V2.0, based on two approaches: support vector machines and multilayer perceptron, to predict adhesins proteins from amino acid sequences. By using ApiPredictor UniQE V2.0, five SAG-Related Sequences (SRSs) were identified within the Toxoplasma gondii proteome. One of those candidates, TgSRS12B, was cloned in plasmid pEXP5-CT/TOPO and expressed in E. coli BL21 DE3. The resulting recombinant protein was purified via affinity chromatography. Co-precipitation assays in CaCo and Muller cells showed interactions between TgSRS12B-His-tagged and the membrane fractions from both human cell lines. In conclusion, we demonstrated that ApiPredictor UniQE V2.0, a bioinformatic free software, was able to identify TgSRS12B as a new adhesin protein.

Novel Sesquiterpenoid Skeletons by Wagner-Meerwein Rearrangements of Longipinane-9,13-diol-1-one Derivatives.

The partial or total hydrolysis of (3R,4S,5S,6S,9R,10R,11R)-9,13-diangeloyloxylongipinan-1-one (1), isolated from the roots of Stevia viscida, gave alcohols 2 or 3, respectively, which were subjected to molecular rearrangements with boron trifluoride etherate. Compound 2 afforded (3R,4R,5R,6S,9R,10S,11S)-11,13-oxyneomorelian-1-one (10) and (4S,5R,6S,8S,10R)-10,13-oxyneojiquilp-2-en-1-one (11), both possessing novel sesquiterpenoid skeletons. In turn, 3 provided (3R,4R,5S,6S,9R,11R)-13-hydroxymoreli-10(14)-en-1-one (7) and 10. Acetylation of 3 gave 4, thus allowing reduction of the C-1 carbonyl group to yield 5, which was rearranged to (1S,3R,4S,5S,6S,9R,10R,11R)-13-acetoxy-9,11-epoxyjiquilpane (6), while an attempt to mesylate 3 directly gave rearranged (3R,4R,5S,6S,9R,11R)-13-mesyloxymoreli-10(14)-en-1-one (8) through expulsion of the C-9 mesylate group by the antiperiplanar C-4-C-10 bond migration to C-4-C-9. In addition, treatment of 1 with boron trifluoride etherate generated (3R,4R,5S,6S,9R,11R)-13-angeloyloxymoreli-10(14)-en-1-one (9). The structures of 2-11 were elucidated by 1D and 2D NMR experiments and those of 2, 3, 8, 10, and 11 were confirmed by single-crystal X-ray diffraction analysis.

Novel Sesquiterpene Skeletons by Multiple Wagner-Meerwein Rearrangements of a Longipinane-1,9-diol Derivative.

The tricyclic sesquiterpene (1R,3R,4S,5S,7S,8S,9S,10R,11R)-7,8-diangeloyloxylongipinan-1,9-diol, or rasteviol (7), underwent multiple Wagner-Meerwein molecular rearrangements and several hydride shifts when treated with Et2O-BF3 to generate the six new compounds (1R,3R,4S,5R,7S,8S,9S,10R,11S)-7,8-diangeloyloxy-1,9-epoxyjiquilpane (8), (1R,3R,4S,5R,7R,8S,9S,11S)-8-angeloyloxy-1,7-epoxyzamor-10(14)-ene (11), (2S,3R,4R,5R,6R,7R,8S,9S,10S)-7,8-diangeloyloxy-6,9-epoxyjanitziane (14), (4R,5R,7S,8S,9S,10S,11S)-7,8-diangeloyloxy-9-hydroxyjiquilp-3(15)-ene (16), (2S,3S,5R,7S,8R,10S,11R)-7,8-diangeloyloxyiratzian-9-one (18), and (2S,3S,5R,10S,11R)-8-angeloyloxyiratzi-7-en-9-one (22), of which 8, 11, 14, and 18 possess new hydrocarbon skeletons. Their structures were determined by 1D and 2D NMR in combination with single-crystal X-ray diffraction analyses of derivatives 10, 15, 20, and 21, which allowed confirmation of their absolute configurations by means of the Flack and Hooft parameters. In addition, some reaction mechanism information was gained from deuterium labeling experiments.

Absolute configuration of phomactatriene diterpenoids obtained by Wagner-Meerwein rearrangement of epimeric verticillols.

The epimeric diterpenes (+)-(1S,3E,7E,11S,12S)-verticilla-3,7-dien-12-ol (1), isolated from Bursera suntui, and (+)-(1S,3E,7E,11S,12R)-verticilla-3,7-dien-12-ol (2), isolated from Bursera kerberi, gave the same Wagner-Meerwein rearrangement product (-)-(1E,4Z,8Z,11S,12R)-phomacta-1,(15)4,8-triene (3). The Et2 O:BF3 -induced transformations evidence that verticillenes and phomactanes, both containing the bicyclo[9.3.1]pentadecane skeleton, are biogenetically related through the verticillen-12-yl cation (A+ ), which also is a key intermediate in the biosynthetic pathways to generate antitumor taxanes. Molecular modeling using the Monte Carlo protocol, followed by density functional theory (DFT) geometry optimization employing the hybrid functionals B3LYP and B3PW91, both with the DGDZVP basis set, secured the configuration of 3 as followed from the good agreement between the calculated and experimental vibrational circular dichroism spectra. Similar DFT calculations allowed determining the absolute configuration of (+)-(1R,4R,5R,8S,9S,11S,12R,15R)-1,15:4,5:8,9-triepoxyphomactane (9), which surprisingly derives from epoxidation of the second minimum energy conformer of 3.

Laparoscopic repair of a lumbar hernia: report of a case and extensive review of the literature.

Lumbar hernias are a protrusion of intra-abdominal contents through a weakness or rupture in the posterior abdominal wall. They are considered to be a rare entity with approximately 300 cases reported in the literature since it was first described by Barbette in 1672. Petit described the inferior lumbar triangle in 1783 and Grynfeltt described the superior lumbar triangle in 1866; both are anatomical boundaries where 95% of lumbar hernias occur, whereas the other 5% are considered to be diffuse. Twenty percent of lumbar hernias are congenital and the other 80% are acquired; the acquired lumbar hernias can be further classified into either primary (spontaneous) or secondary. The typical presentation of lumbar hernias is a patient with a protruding semispherical bulge in the back with a slow growth. However, they may present with an incarcerated or strangulated bowel, so it is recommended that all lumbar hernias must be repaired as soon as they are diagnosed. The "gold standard" for diagnosing a lumbar hernia is a CT scan, because it is able to delineate muscular and fascial layers, detect a defect in one or more of these layers, evaluate the presence of herniated contents, differentiate muscle atrophy from a real hernia, and serve as a useful tool in the differential diagnosis, such as tumors. Recent studies have demonstrated the advantages of a laparoscopic repair instead of the classic open approach as the ideal treatment option for lumbar hernias. We report a case of a spontaneous lumbar hernia initially diagnosed as a lipoma and corrected with the open approach, but after relapsing 2 years later it was corrected using a laparoscopic approach. It is followed by an extensive review of lumbar hernias literature regarding history, anatomy, and surgical techniques.

Multiple Distinct Neoplasms in a North African Hedgehog (Atelerix algirus).

This paper describes the clinical and pathological features of 4 different tumors, located in the integumentary, digestive, and endocrine systems, presenting in a North African hedgehog (Atelerix algirus). A 3.5-year-old female hedgehog was presented with a cutaneous mass on the right flank. The lesion consisted of a well-differentiated dermal mast cell tumor with no recurrence and metastasis after complete surgical excision. Six months later, the hedgehog developed a mass in the left lower jaw, lethargy, anorexia, and progressive weight loss. Clinical and radiographic evaluations revealed swelling, ulceration, displacement, and destruction of subjacent bone tissue, and the animal died 1 month after the onset of clinical signs. At necropsy, 2 neoplasms in the oral cavity (squamous cell carcinoma and histiocytic sarcoma) and multiple myelolipomas in the adrenal glands were detected. Metastasis of the oral squamous cell carcinoma was observed in the lungs. Although neoplasms are frequent in this species, and more than 1 type of tumor in a single individual has been occasionally reported, this is the first description of both myelolipoma and multiple concurrent neoplasms involving various organs and different cellular origins in a hedgehog.

Control of the Growth of Listeria monocytogenes in Cooked Ham through Combinations of Natural Ingredients.

In the ready-to-eat food industry, Listeria control is mandatory to ensure the food safety of the products since its presence could cause a disease called listeriosis. The objective of the present study was to carry out a challenge test to verify the efficiency of different combinations of natural antimicrobial ingredients against Listeria monocytogenes to be used in ready-to-eat foods. Six different formulations of cooked ham were prepared: a control formulation and five different formulations. An initial inoculation of 2 log cycles was used in the different products, and the growth of Listeria was monitored at different temperatures and times (4 °C for 17 w and 7 °C for 12 w). Control samples showed a progressive growth, reaching 5-6 log after 3 or 4 weeks. The rest of the samples showed constant counts of Listeria during the entire study. Only samples containing 100 ppm nitrite + 250 PPM ascorbic acid + 0.7% PRS-DV-5 did not control the growth of Listeria at 7 °C after 7 w of storage. The results obtained allowed us to classify the cooked ham prepared using natural ingredient combinations as a "Ready-to-eat food unable to support the growth of L. monocytogenes other than those intended for infants and for special medical purposes".

Corrigendum: Ring attractor bio-inspired neural network for social robot navigation.

[This corrects the article DOI: 10.3389/fnbot.2023.1211570.].

Ring attractor bio-inspired neural network for social robot navigation.

Introduction: We introduce a bio-inspired navigation system for a robot to guide a social agent to a target location while avoiding static and dynamic obstacles. Robot navigation can be accomplished through a model of ring attractor neural networks. This connectivity pattern between neurons enables the generation of stable activity patterns that can represent continuous variables such as heading direction or position. The integration of sensory representation, decision-making, and motor control through ring attractor networks offers a biologically-inspired approach to navigation in complex environments. Methods: The navigation system is divided into perception, planning, and control stages. Our approach is compared to the widely-used Social Force Model and Rapidly Exploring Random Tree Star methods using the Social Individual Index and Relative Motion Index as metrics in simulated experiments. We created a virtual scenario of a pedestrian area with various obstacles and dynamic agents. Results: The results obtained in our experiments demonstrate the effectiveness of this architecture in guiding a social agent while avoiding obstacles, and the metrics used for evaluating the system indicate that our proposal outperforms the widely used Social Force Model. Discussion: Our approach points to improving safety and comfort specifically for human-robot interactions. By integrating the Social Individual Index and Relative Motion Index, this approach considers both social comfort and collision avoidance features, resulting in better human-robot interactions in a crowded environment.

Intermediate risk of choledocholithiasis: are we on the right path?

The risk of choledocholithiasis should be assessed in every patient undergoing cholecystectomy to define the next step. The American Society for Gastrointestinal Endoscopy proposed a stratified predictor scale of choledocholithiasis. Therefore, we aimed to describe our experience managing patients with an intermediate risk of choledocholithiasis according to the American Society for Gastrointestinal Endoscopy guidelines and the actual presence of bile duct stones in magnetic resonance cholangiopancreatography. Methods: A retrospective observational study with a prospective database was conducted. The analysis included sociodemographic data, laboratory values, and imaging. Bivariate, multivariate, and receiver operating characteristic analysis were performed. Results: Three hundred twenty-seven patients had an intermediate risk for choledocholithiasis. Half the patients were at least 65 years old. 24.77% were diagnosed with choledocholithiasis. Bile duct dilation was documented in only 3.06% of cases. Diagnosis of choledocholithiasis is associated with an age odds ratio (OR): 1.87 (P 0.02), alkaline phosphatase OR: 2.44 (P 0.02), and bile duct dilation greater than 6 mm OR: 14.65 (P 0.00). Conclusions: High variability in the accuracy of imaging techniques results in a large number of patients classified as intermediate risk without choledocholithiasis in cholangioresonance. Therefore, enhancing the criteria to define intermediate risk for patients in order to optimize resources is of paramount importance.

CD8+ T-cell Exhaustion Phenotype in Human Asymptomatic and Ocular Toxoplasmosis.

This work analyzed exhaustion markers in CD8+ T-cell subpopulations in 21 samples of peripheral blood mononuclear cells (PBMCs) from individuals with ocular toxoplasmosis (n = 9), chronic asymptomatic toxoplasmosis (n = 7), and non-infected people (n = 5) by using RT-qPCR and flow cytometry techniques. The study found that gene expression of PD-1 and CD244, but not LAG-3, was higher in individuals with ocular toxoplasmosis versus individuals with asymptomatic infection or uninfected. Expression of PD1 in CD8+ central memory (CM) cells was higher in nine individuals with toxoplasmosis versus five uninfected individuals (p = .003). After ex vivo stimulation, an inverse correlation was found between the exhaustion markers and quantitative clinical characteristics (lesion size, recurrence index, and number of lesions). A total exhaustion phenotype was found in 55.5% (5/9) of individuals with ocular toxoplasmosis. Our results suggest that the CD8+ exhaustion phenotype is involved in the pathogenesis of ocular toxoplasmosis.

Hill Modified, a Novel Approach: Technique Description and Experience in Patients with Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease among patients with obesity, with an associated prevalence of 39 to 61% between the population who attends a bariatric surgery evaluation. Laparoscopic sleeve gastrectomy (LSG) has become a popular and valid option for obesity treatment, even though the literature is ambivalent regarding the increase or decrease in GERD after this surgery. Thus, it is necessary to propose new surgical techniques as a solution to GERD in patients with a concomitant LSG or with a history of it. Therefore, we present a modified technique based on Hill's gastropexy described originally in 1967. OBJECTIVE: Describe and propose a surgical procedure for GERD management based on the Hill technique that can be applied in all patients who undergo an LSG or with a history of it. METHODS: Retrospective observational study with a prospective database in which we described, Hill modified technique in a group of 16 patients with GERD who underwent this procedure concomitantly with an LSG or who presented with GERD after LSG with a 3-year follow-up. The surgical technique is based on an intra-abdominal esophageal length of a minimum of 3 cm and posterior fixation of the gastroesophageal junction to the crus. RESULTS: Postoperative controls have shown satisfactory results in the control and management of GERD symptoms in this group of patients, with very few to no complications associated with the procedure and without reintervention or medication out of the standard protocol. CONCLUSION: Hill modified technique can be used and presented as an option for GERD control in patients with LSG.

Academic paediatric surgery and work-life balance: Insights from Mexico.

Academic pediatric surgery in Mexico has many challenges and opportunities. Work life balance, health service delivery and committements to our many students and residents must be tailored to goals and aspirations respecting talent at every opportunity when we encounter it. This article offers a perspective on the landscape and how we can shape the future in our nation to embrace new leadership in academic pediatric surgery.

In vitro cytotoxic potential of extracts from Aristolochia foetida Kunth against MCF-7 and bMECs cell lines.

The aim of this study was to evaluate the cytotoxic potential of Aristolochia foetida Kunth. Stems and leaves of A. foetida Kunth (Aristolochiaceae) have never been investigated pharmacologically. Recent studies of species of the Aristolochiaceae family found significant cytotoxic activities. Hexane, dichloromethane, ethyl acetate and methanol extracts were analyzed by 1H NMR and GC-MS to know the metabolites in each extract. In GC-MS analysis, the main compounds were methyl hexadecanoate (3); hexadecanoic acid (4); 2-butoxyethyl dodecanoate (9); ethyl hexadecanoate (20); methyl octadeca-9,12,15-trienoate (28) and (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid (40). The results showed a significant reduction in cell viability of the MCF-7 (breast cancer) cell line caused by organic extracts in a dose-dependent manner. The cytotoxicity activity of the dichloromethane extract from the stems (DSE) showed IC50 values of 45.9 µg/mL and the dichloromethane extract of the leaves (DLE) showed IC50 values of 47.3 µg/mL. DSE and DLE had the highest cytotoxic potential in an in vitro study against the MCF-7 cell line and non-tumor cells obtained from the bovine mammary epithelial (bMECs). DSE and DLE induced a loss in mitochondrial membrane potential (ΔΨm) and can cause cell death by apoptosis through the intrinsic pathway in the MCF-7 cell line. DSE and DLE are cytotoxic in cancer cells and cause late apoptosis. Higher concentrations of DSE and DLE are required to induce a cytotoxic effect in healthy mammary epithelial cells. This is the first report of the dichloromethane extract of A. foetida Kunth that induces late apoptosis in MCF-7 cancer cells and may be a candidate for pharmacological study against breast cancer.

Antifeedant and cytotoxic activity of longipinane derivatives.

The polyoxygenated longipinane derivatives 1- 8 were tested as antifeedant compounds against the herbivorous insects Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae. Compounds 1-3 and 8 exhibited significant antifeedant activity against S. littoralis and M. persicae. The antifeedant activity against S. littoralis increased moderately after the C-8 hydroxy group in 3 was removed to afford 1 and increased strongly after the remaining two hydroxy groups were acetylated to afford 2. Compound 1 was active on M. persicae. Compounds 1, 3, and 4, with an unsaturated six-membered ring, exhibited an increase in post-ingestive effects on S. littoralis ranging from antifeedant in the case of 1 to toxic for compounds 3 and 4. These compounds did not have any phytotoxic effect on Lactuca sativa. When tested on a panel of tumoral cells, compounds 2 and 6 exhibited moderate selective cytotoxic effects on the p53 null lung carcinoma cells H1299, which were not affected by the drug paclitaxel. In addition, vibrational circular dichroism (VCD) was applied to the representative longipinene derivative 2 to verify its absolute configuration, and the sensitivity of the VCD methodology was evaluated by comparing spectra of the three diastereoisomers (4 R,5 S,7 R,9 R,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one (2), (4 R,5 S,7 S,9 R,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one, and (4 R,5 S,7 R,9 S,10 R,11 R)-7,9-diacetyloxylongipin-2-en-1-one.

Oxygenated verticillene derivatives from Bursera suntui.

Medium polarity fractions of the hexane extracts of the stems of Bursera suntui afforded six previously known (1-6) and four hitherto unknown verticillane derivatives: (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol (7), (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol 20-acetate (8), (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol (9), and (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 20-acetate (10). Acetylation of 9 and 10 yielded (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 7,20-diacetate (11), while hydrolysis of 8 gave 7. The structures and stereochemistry of 7-11 were established by spectroscopic analyses, particularly by 1D and 2D NMR spectra and HRESIMS. The conformational preferences of 7-11 were studied by molecular mechanics modelling employing the Monte Carlo protocol followed by B3LYP/DGDZVP DFT calculation, thus supporting the observed (1)H NMR NOESY cross peaks.

Ultrastructural characteristics of blood cells in the Yellow-Bellied Slider Turtle (Trachemys scripta scripta).

BACKGROUND: The classification of blood cells from the Yellow-Bellied Slider Turtle (Trachemys scripta scripta) is relevant due to their increasing importance as pets and as object of study in clinical settings and research projects. However, no previous ultrastructural characterization of blood cells from turtles of the genus Trachemys has been reported. OBJECTIVES: The objective of this study was to provide an ultrastructural characterization of blood cells of the Yellow-Bellied Slider Turtle. METHODS: Blood samples from 10 healthy adult turtles (5 males and 5 females) were obtained and processed for transmission electron microscopy using standard methods. RESULTS: Some erythrocytes had intracytoplasmic inclusions compatible with hemoglobin precipitates; mitochondria and ribosomes in the cytoplasm of erythrocytes were also observed. Five types of white blood cells were ultrastructurally identified: heterophils, eosinophils, basophils, lymphocytes, and monocytes. Heterophils were similar to those described from Sea Turtles, with only one morphologic variation of this cell. Eosinophils were homogeneous in size and had intracytoplasmic granules without crystalline structures. Basophils were ultrastructurally described for the first time for a turtle and had heterogeneous intracytoplasmic granules. Lymphocytes and monocytes were similar to those described from other chelonians. Some thrombocytes had an irregularly lobulated nucleus and intracytoplasmic canalicular structures. CONCLUSION: This study provides the first ultrastructural classification of blood cells in Trachemys scripta scripta, as a baseline for further hematologic studies in this species.

Absolute configuration of the alpha-methylbutyryl residue in longipinene derivatives from Stevia pilosa.

The absolute configuration of the alpha-methylbutyryl residue in (4R,5S,7S,8S,9S,10R,11R,2''S)-7-angeloyloxy-9-hydroxy-8-(alpha-methylbutyryloxy)-longipin-2-en-L-one and (4R,5S,7S,8R,10R,11R,2''S)-7-angeloyloxy-8-(alpha-methylbutyryloxy)- longipin-2-en-L-one was determined by chemical correlation with (S)-(+)-benzyl alpha-methylbutyrate prepared from authentic (S)-(+)-alpha-methylbutyric acid. Both compounds were isolated from the hexane extracts of roots of Stevia pilosa Lag. together with four other longipinene derivatives. The developed correlation method is useful to ascertain the chirality of natural alpha-methylbutyryl esters found in nature and to reinforce the hypotheses on the biogenetic origin of these residues.

Primary cricotracheal resection with thyrotracheal anastomosis for the treatment of severe subglottic stenosis in children and adolescents.

Severe subglottic stenosis in children is best managed by laryngotracheal reconstruction or cricotracheal resection (CTR). We describe clinical outcomes with CTR and end-to-end anastomosis in pediatric patients with severe subglottic stenosis in a tertiary-care pediatric teaching hospital in Mexico City. We prospectively followed up all consecutive patients younger than 18 years of age with a Myer-Cotton grade 3 or 4 subglottic stenosis who underwent CTR between May 1, 2000, and March 31, 2003. The frequency of each clinical outcome was calculated. Twenty-two patients (16 boys [72.7%] and 6 girls [27.3%]) were included. The mean age at operation was 4.6 years (range, 11 months to 16 years). Eighteen patients (81.8%) required primary CTR, and 4 (18.2%) required extended CTR. Seventeen (77.3%) had grade 3 stenosis, and 5 (22.7%) had grade 4 stenosis. Six (27.3%) had associated clinical conditions, and 3 (13.6%) had associated vocal cord mobility defects. All were tracheostomy-dependent at presentation, and none had undergone previous airway surgery. Ten (45.5%) underwent one-stage surgery, and 12 (54.5%) had a concomitant temporary tracheotomy. No intraoperative complications occurred. Seventeen patients (77.3%) developed postoperative granulation tissue requiring endoscopic resection. The mean follow-up was 1.2 years (range, 2 months to 2.8 years). No deaths occurred. Fifteen children (88.2%) with grade 3 stenosis and 5 (100%) with grade 4 stenosis were decannulated, for an overall decannulation rate of 90.9%. Partial cricoid resection with end-to-end anastomosis has been a feasible procedure with reproducible successful results among our patients. We conclude that CTR performed as a primary procedure is an effective treatment for the management of severe subglottic stenosis in children.