An Integrated Machine Learning Approach for Congestive Heart Failure Prediction.

Congestive heart failure (CHF) is one of the primary sources of mortality and morbidity among the global population. Over 26 million individuals globally are affected by heart disease, and its prevalence is rising by 2% yearly. With advances in healthcare technologies, if we predict CHF in the early stages, one of the leading global mortality factors can be reduced. Therefore, the main objective of this study is to use machine learning applications to enhance the diagnosis of CHF and to reduce the cost of diagnosis by employing minimum features to forecast the possibility of a CHF occurring. We employ a deep neural network (DNN) classifier for CHF classification and compare the performance of DNN with various machine learning classifiers. In this research, we use a very challenging dataset, called the Cardiovascular Health Study (CHS) dataset, and a unique pre-processing technique by integrating C4.5 and K-nearest neighbor (KNN). While the C4.5 technique is used to find significant features and remove the outlier data from the dataset, the KNN algorithm is employed for missing data imputation. For classification, we compare six state-of-the-art machine learning (ML) algorithms (KNN, logistic regression (LR), naive Bayes (NB), random forest (RF), support vector machine (SVM), and decision tree (DT)) with DNN. To evaluate the performance, we use seven statistical measurements (i.e., accuracy, specificity, sensitivity, F1-score, precision, Matthew's correlation coefficient, and false positive rate). Overall, our results reflect our proposed integrated approach, which outperformed other machine learning algorithms in terms of CHF prediction, reducing patient expenses by reducing the number of medical tests. The proposed model obtained 97.03% F1-score, 95.30% accuracy, 96.49% sensitivity, and 97.58% precision.

Impact of Neighborhood Social Cohesion and Rodent Sightings on Mental Health among Residents of New York City During the COVID-19 Pandemic.

Common mental disorders such as depression and anxiety are prevalent globally, and rates are especially high in New York City (NYC) since the COVID-19 pandemic. Neighborhood social and physical environments have been found to influence mental health. We investigated the impact of neighborhood social cohesion and neighborhood rodent sightings (as an indicator of neighborhood cleanliness) on nonspecific serious psychological distress (NSPD) status using 2020 NYC Community Health Survey data from 8781 NYC residents. Multivariable logistic regression was used to evaluate the relationships among social cohesion, rodent sightings, and NSPD adjusted for confounders and complex sampling and weighted to the NYC population. Effect measure modification of rodent sightings on the effect of social cohesion on NSPD was evaluated on the multiplicative scale by adding the interaction term to the multivariable model and, if significant, stratifying on the effect modifier, and on the additive scale using the relative excess risk due to interaction (RERI). Social cohesion was found to decrease the odds of NSPD, and rodent sightings were found to increase the odds of NSPD. We found significant evidence of effect measure modification on the multiplicative scale. In the stratified models, there was a protective effect of social cohesion against NSPD among those not reporting rodent sightings, but no effect among those reporting rodent sightings. Our findings suggest that both neighborhood social cohesion and rodent sightings impact the mental health of New Yorkers and that rodent infestations may diminish the benefit of neighborhood social cohesion.

Relationship between the severity of pre-frailty and the degree of adaptation of Ninjin'yoeito (NYT) on pre-frailty.

With the global trend towards longer life expectancies, there's an increasing emphasis on not just living longer, but also maintaining health and wellbeing into older age. This study explores the efficacy of Ninjin'yoeito (NYT) in the early stages of frailty, a critical period for preventive interventions. Taking account of the knowledge gap regarding the association between early frailty and NYT, we use data from workplace health checkups to examine the relationship between pre-frailty severity and NYT adaption. The objective of our research is to enhance the comprehension of early treatments using NYT to prevent the progression of frailty. A total of 314 employees of the Kyoto Industrial Health Association who received workplace health checkups between November 2021 and March 2023 and consented to this study were included in the analysis. Information on gender, age, body mass index (BMI), NYT-specific symptoms assessment, the Japanese version of the General Health Questionnaire-12 (GHQ-12), and the Kihon Checklist (KCL) were obtained. The correlation analysis revealed that there was a strong positive correlation between the number of applicable NYT indications and the GHQ-12 score (r = 0.5992, p < 0.0001). Similarly, a moderate positive correlation was observed between the number of applicable NYT indications and the KCL score (r = 0.5030, p < 0.0001). In the multivariate analysis, both GHQ-12 (ß = 0.49, SE = 0.06, t = 7.66, 95% CI: 0.36 to 0.62, p = 0.000) and KCL (ß = 0.54, SE = 0.12, t = 4.29, 95% CI: 0.29 to 0.79, p = 0.000) showed significant positive associations with the variance in the number of applicable NYT indications, indicating that higher scores on these measures were related to a greater number of indications. NYT has the potential to be utilized not only as a therapeutic intervention for frailty, but also as a preventive measure.

Cryo-EM structure of human HCN3 channel and its regulation by cAMP.

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.

Application value of metagenomics next-generation sequencing in the diagnosis of respiratory virus infection after congenital heart surgery.

Background: Timely and accurate pathogen diagnosis can be challenging in children who contract a respiratory virus following congenital heart surgery (CHS). This often results in suboptimal drug use and treatment delays. Metagenomics next-generation sequencing (mNGS) is a swift, efficient, and unbiased method for obtaining microbial nucleic acid sequences. This technology holds promise as a comprehensive diagnostic tool, especially for pathogens undetectable by traditional methods. However, the efficacy of mNGS in the context of congenital heart disease infections remains uncertain. This study aimed to explore the diagnostic value of mNGS for respiratory virus infections post-CHS. Methods: We conducted a retrospective analysis of patients who developed respiratory tract infections post-CHS and were admitted to our cardiac center between July 2021 and December 2022. The patients were categorized into the following two groups based on the diagnostic method used: (I) the mNGS group (comprising 62 patients); and (II) the conventional microbiological test (CMT) group (comprising 70 patients). Bronchoalveolar lavage fluid (BALF) samples from these patients were tested to identify pathogens. Results: The mNGS group had significantly higher detection rates for both viral infections and mixed viral infections than the CMT group (56.45% vs. 17.14%, P<0.001, and 80.00% vs. 16.67%, P<0.001, respectively). In the mNGS group, 19.35% of the patients received antiviral therapy, and 61.29% received an anti-infective regimen adjustment. Conversely, in the CMT group, only 4.29% received antiviral therapy, and 28.57% received an anti-infective regimen adjustment. A higher percentage of patients showed improved respiratory symptoms in the mNGS group than the CMT group (74.19% vs. 44.29%, P=0.001). Additionally, the mNGS group had a shorter duration of mechanical ventilation and a reduced length of stay in the cardiac intensive care unit than the CMT group (P=0.012). Conclusions: Using mNGS for BALF enhances the detection of respiratory viral infections and coexisting viral infections post-CHS. This facilitates more precise treatment strategies and could potentially lead to improved patient outcomes.

Uncommon Carotid Artery Stenting Complications: A Series by Images.

AIMS: To describe through emblematic images rare but clinically relevant carotid artery stenting complications that occurred at two high-volume centres for carotid artery stenting (CAS). BACKGROUND: CAS is an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis in patients judged to be at high risk for CEA. CAS complications range between 1 and 9% and are higher in older patients complaining of neurological symptoms at the time of presentation. Besides periprocedural or early-after-procedure stroke, which remains the true Achilles' heel of CAS, other dramatic complications might compromise the clinical outcomes of this procedure. METHODS: Five infrequent complications, out of more than 1000 CAS performed in the years 2016-2021, have been described. RESULTS: Among CAS complications, acute carotid stent thrombosis, rescue retrieval of a disconnected distal cerebral embolic protection device, plaque prolapse after carotid stenting, cerebral hyperperfusion syndrome (CHS), and radial artery long sheath entrapment requiring surgical intervention were found to account for 0.3% of the total number of procedures performed by operators with high CAS volume. CONCLUSIONS: Unusual CAS complications may infrequently occur, even in hands of expert operators. To know how to deal with such complications might help interventionalists to improve CAS performance.

Effects of cell morphology, physiology, biochemistry and CHS genes on four flower colors of Impatiens uliginosa.

Introduction: Flower color is one of the important ornamental traits in the plants, which plays an active role in attracting pollinators to pollinate plants and reproduce their offspring. The flower color of Impatiens uliginosa is rich, there are four main flower colors in nature: deep red, red, pink, and white. However, it remains unclear whether on four different flower colors mechanism of I. uliginosa. Methods: We investigate colorimetric measurement, observation of epidermal cells, cellular pH determination, extraction and determination of total anthocyanins and flavonoid, semi-quantitative determination of pigment components, and gene cloning and qRT-PCR of CHS genes to study four flower colors of I. uliginosa. Results: The L* and b* values were the highest in white flower, while the a* values were the highest in pink flower. The same shape of epidermal cells was observed in different flower colors, which was all irregular flat polygons, and there were partial lignification. Their cellular pH values were weakly acidic, while the pH values of the deep red flower was the highest and the white flower was the lowest. The highest pigment content of the four flower colors was total anthocyanin content. And malvidin-3-galactosidechloride (C23H25ClO12), cyanidin-3-O-glucoside (C21H21O11) and delphinidin (C15H11O7) were the main pigment components affecting the color of four different flower colors. The anthocyanin synthesis gene IuCHS was expressed in four flowers, and all three copies of it had the highest expression level in pink flower and the lowest expression level in white flower. Discussion: These results revealed the influence of main internal factors on four different flower colors of I. uliginosa, and provided a basis for further understanding of the intracellular and molecular regulatory mechanisms of flower color variation, and laid a foundation for the improvement of flower color breeding of Impatiens.

Bimetallic FeOx-TiO2@Carbon hybrid structure materials with notable peroxidase enzyme mimics applied to one-step colorimetric detection of glucose.

FeOx-TiO2@Carbon hybrid structure materials (FeOx-TiO2@CHs) with high peroxidase (POD)-like activity have been prepared by one-pot hydrothermal method. Based on the excellent POD activity of FeOx-TiO2@CHs, one pot colorimetric detection for glucose was constructed by using TMB as substrate with the synergistic reaction of glucose oxidase; the linear range and the limit of detection (LOD) are 25 ~ 1000 and 1.77 µM, respectively. Using this method, the glucose in serum real samples was detected with satisfactory results, and the results are consistent with that of the glucometer method in the hospital. The recovery in diabetic and artificial urine samples was 95.71 ~ 104.67% and 99.01 ~ 103.16%, respectively. The mechanism of the catalytic colorimetric reaction was also investigated by multiple measurements, and the results indicated that superoxide anions (O2•-) between FeOx-TiO2@CHs and substrate play a main role, but a small quantity of hydroxyl radical •OH and singlet oxygen 1O2 is also generated simultaneously. The one-pot reaction method is simple and fast; the detection process only requires a simple mixing, which is suitable for application in special environment.

Genomic and Expression Analysis of Cassava (Manihot esculenta Crantz) Chalcone Synthase Genes in Defense against Tetranychus cinnabarinus Infestation.

Cassava is susceptible to mites, especially Tetranychus cinnabarinus. Secondary metabolism products such as flavonoids play an important role as antimicrobial metabolites protecting plants against biotic stressors including fungal, pathogen, bacterial, and pest defense. The chalcone synthase (CHS) is the initial step of the phenylpropanoid pathway for producing flavonoids and is the gatekeeper of the pathway. Until recently, the CHS genes family has not been systematically studied in cassava. Thirty-nine CHS genes were identified from the cassava genome database. Based on phylogenetic and sequence composition analysis, these CHSs were divided into 3 subfamilies. Within the same subfamily, the gene structure and motif compositions of these CHS genes were found to be quite conserved. Duplication events, particularly segmental duplication of the cassava CHS genes, were identified as one of the main driving force of its expansion. Various cis-elements contained in the promoter might regulate the gene expression patterns of MeCHS. Protein-protein interaction (PPI) network analysis showed that MeCHS1 and MeCHS10 protein are more closely related to other family members. The expression of MeCHS genes in young leaves was higher than that in other tissues, and their expression varies even within the same tissue. Coincidentally, these CHS genes of most LAP subclasses were highly expressed in young leaves. The verified MeCHS genes showed consistent with the real-time reverse transcription quantitative PCR (RT-qPCR) and proteomic expression in protected and affected leaves respectively, indicating that these MeCHS genes play crucial roles in the response to T. cinnabarinus. This study is the first to comprehensively expatiate the information on MeCHS family members. These data will further enhance our understanding both the molecular mechanisms and the effects of CHS genes. In addition, the results will help to further clarify the effects on T. cinnabarinus and provide a theoretical basis for the potential functions of the specific CHS gene in resistance to mites and other biotic stress.

Do the physical activity questions in the Japanese version of the Cardiovascular Health Study criteria truly reflect a decline in physical activity?

Older participants identified as having decreased physical activity according to the Japanese version of the Cardiovascular Health Study criteria did not show a significant reduction in accelerometer-measured physical activity. Despite its widespread use in Japanese studies, the Japanese version of the Cardiovascular Health Study physical activity questionnaire may not effectively capture declines in physical activity.

Coloration differences in three Camellia reticulata Lindl. cultivars: 'Tongzimian', 'Shizitou' and 'Damanao'.

Camellia reticulata Lindl., also known as Yunnan Camellia, is an important ornamental plant in China, especially for its large and stunning flowers. A comprehensive understanding of their coloration mechanisms can aid breeders in developing new cultivars and improving their ornamental value; however, it is still unclear in Yunnan Camellia, especially in mixed-color flowers. In this study, we conducted metabolic and transcriptomic comparison analyses to investigate the coloration differences in three Yunnan Camellia cultivars: C. reticulata 'Shizitou' (SZT), C. reticulata 'Damanao' (MN), and C. reticulata 'Tongzimian' (TZM). Our results revealed that the initial flowering stage may play a critical role in the color change of MN. Metabolome analysis demonstrated that cyanidin was the primary anthocyanin in SZT and MN's red region, while its content was low in TZM and MN's white region. According to the transcriptome analysis, the anthocyanins biosynthesis pathway was reconstructed in Yunnan Camellia, and the low expression of CHS was detected in TZM and MN's white region, while ANR maintained a high expression level, which may lead to the low content of cyanidin in them. Transcription factors MYBs, bHLH, and bZIP may play a key role in regulating anthocyanin-structural genes. The co-expression analysis showed that the meristem tissue may play a crucial role in the formation of the mixed white-red color in MN. Our study enriched the genetic basis of flower coloration differences in Yunnan Camellia which will be a valuable genomic resource to understanding the biology of coloration formation and for breeding the Camellia cultivars.

Structural dynamics and functional analysis of Saprolegnia parasitica chitin synthases 5 in a phospholipid bilayer.

Saprolegnia parasitica is an oomycete responsible for a fish disease called saprolegniosis, which poses an economic and environmental burden on aquaculture production. In Saprolegnia, CHS5 of S. parasitica (SpCHS5) contains an N-terminal domain, a catalytic domain of the glycosyltransferase -2 family containing a GT-A fold, and a C-terminal transmembrane domain. No three-dimensional structure of SpCHS5 is reported yet disclosing the structural details of this protein. We have developed a structural model of full-length SpCHS5 and validated it by molecular dynamics simulation technique. From the 1 microsecond simulations, we retrieved the stable RoseTTAFold model SpCHS5 protein to explain characteristics and structural features. Furthermore, from the analysis of the movement of chitin in the protein cavity, we assumed that ARG 482, GLN 527, PHE 529, PHE 530, LEU 540, SER 541, TYR 544, ASN 634, THR 641, TYR 645, THR 641, ASN 772 residues as a main cavity lining site. In SMD analysis, we investigated the opening of the transmembrane cavity required for chitin translocation. The pulling of chitin from the internal cavity to the extracellular region was observed through steered molecular dynamics simulations. A comparison of the initial and final structures of chitin complex showed that there's a transmembrane cavity opening in the simulations. Overall, this present work will help us understand the structural and functional basis of CHS5 and design inhibitors against SpCHS5.Communicated by Ramaswamy H. Sarma.

19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor.

For the A2A adenosine receptor (A2AAR), a class A G-protein-coupled receptor (GPCR), reconstituted in n-dodecyl-ß-D-maltoside (DDM)/|||||cholesteryl hemisuccinate (CHS) mixed micelles, previous 19F-NMR studies revealed the presence of multiple simultaneously populated conformational states. Here, we study the influence of a different detergent, lauryl maltose neopentyl glycol (LMNG) in mixed micelles with CHS, and of lipid bilayer nanodiscs on these conformational equilibria. The populations of locally different substates are pronouncedly different in DDM/|||||CHS and LMNG/|||||CHS micelles, whereas the A2AAR conformational manifold in LMNG/|||||CHS micelles is closely similar to that in the lipid bilayer nanodiscs. Considering that nanodiscs represent a closer match of the natural lipid bilayer membrane, these observations support that LMNG/|||||CHS micelles are a good choice for reconstitution trials of class A GPCRs for NMR studies in solution.

A role for ß-1,6- and ß-1,3-glucans in kinetochore function in Saccharomyces cerevisiae.

Chromosome segregation is crucial for the faithful inheritance of DNA to the daughter cells after DNA replication. For this, the kinetochore, a megadalton protein complex, assembles on centromeric chromatin containing the histone H3 variant CENP-A, and provides a physical connection to the microtubules. Here, we report an unanticipated role for enzymes required for ß-1,6- and ß-1,3-glucan biosynthesis in regulating kinetochore function in Saccharomyces cerevisiae. These carbohydrates are the major constituents of the yeast cell wall. We found that the deletion of KRE6, which encodes a glycosylhydrolase/ transglycosidase required for ß-1,6-glucan synthesis, suppressed the centromeric defect of mutations in components of the kinetochore, foremost the NDC80 components Spc24, Spc25, the MIND component Nsl1, and Okp1, a constitutive centromere-associated network protein. Similarly, the absence of Fks1, a ß-1,3-glucan synthase, and Kre11/Trs65, a TRAPPII component, suppressed a mutation in SPC25. Genetic analysis indicates that the reduction of intracellular ß-1,6- and ß-1,3-glucans, rather than the cell wall glucan content, regulates kinetochore function. Furthermore, we found a physical interaction between Kre6 and CENP-A/Cse4 in yeast, suggesting a potential function for Kre6 in glycosylating CENP-A/Cse4 or another kinetochore protein. This work shows a moonlighting function for selected cell wall synthesis proteins in regulating kinetochore assembly, which may provide a mechanism to connect the nutritional status of the cell to cell-cycle progression and chromosome segregation.

Ca-AlN MOFs-loaded chitosan/gelatin scaffolds; a dual-delivery system for bone tissue engineering applications.

Creating a scaffold for bone tissue engineering that is bioactive and capable of acting as a local-dual delivery system, releasing bioactive molecules and regulating the bone remodeling process to achieve balanced bone resorption and formation, is a significant challenge. The objective of this research is to create a composite scaffold using chitosan/gelatin (CHS/Gel) and the calcium (Ca)-alendronate (ALN) metal-organic frameworks (MOFs). The scaffold will act as a dual-delivery system, releasing Ca ions and ALN to regulate bone formation. Ca-ALN MOF nanoparticles (NPs) were prepared in mild conditions and studied by FTIR, XRD, FESEM, and TGA. Ca-ALN NPs-loaded CHS/Gel scaffolds were opportunely fabricated through freeze-drying approach. Physicochemical features of the scaffolds after incorporating NPs equated by CHS/Gel scaffold changed, therefore, the attendance of NPs caused a decreasing porosity, decreased swelling, and low rate of degradation. The release profile results showed that the NPs-loaded CHS/Gel scaffolds were able to simultaneously release ALN and Ca ions due to the decomposition of NPs. Additionally, the loading of NPs in the CHS/Gel scaffold led to an increment in alkaline phosphatase (ALP) activity and the quantity of deposited Ca along with osteogenesis gene markers. These findings suggest that the NPs-loaded CHS/Gel scaffold has the potential to enhance the differentiation of human adipose tissue-derived mesenchymal stem cells, making it a promising approach for bone repair.

MicroRNAs constitute an additional layer in plant response to simultaneous bio- and abiotic stresses as exemplified by UV-B radiation and flg22-treatment on Arabidopsis thaliana.

Plants are confronted with various environmental stresses and develop sophisticated adaptive mechanisms. Our previous work demonstrated that the crosstalk of flg22 and ultraviolet (UV)-B-induced signalling cascades reprograms the expression of flavonol pathway genes (FPGs), benefiting plant defence responses. Although several transcription factors have been identified to be involved in this crosstalk, the underlying mechanism is largely unclear. Here, we analyzed microRNAs (miRNAs) and identified 126, 129 and 113 miRNAs with altered abundances compared to untreated control in flg22-, UV-B- and flg22/UV-B-treated seedlings, respectively. Two distinct modules were identified: The first consists of 10 miRNAs repressed by UV-B but up-regulated by flg22, and the second with five miRNAs repressed by flg22 but up-regulated by UV-B. In Arabidopsis, the knockdown of miR858a, a representative of module I, increased the abundance of CHS (a marker gene for FPGs), whereas its overexpression reduced CHS. Conversely, knockout of miR164b from module II decreased CHS and its overexpression increased CHS transcript levels. These data suggest a decisive role of miRNAs in the crosstalk. In the next, we described the interaction between miR858a and its target MYB111 (a positive regulator of FPGs) from module I in detail. We showed that MYB111 was profoundly post-transcriptionally regulated by miR858a during the crosstalk, whose expression was specifically but antagonistically controlled by UVR8- and FLS2-mediated signallings. Moreover, transcriptional monitoring using the GUS reporter gene demonstrates that miRNA-mediated posttranscriptional regulation is the main driving force in reprogramming the expression of FPGs and regulates plant adaptation to multiple concurrent environmental stresses.

Advancing understanding of Ficus carica: a comprehensive genomic analysis reveals evolutionary patterns and metabolic pathway insights.

Ficus carica L. (dioecious), the most significant commercial species in the genus Ficus, which has been cultivated for more than 11,000 years and was one of the first species to be domesticated. Herein, we reported the most comprehensive F. carica genome currently. The contig N50 of the Orphan fig was 9.78 Mb, and genome size was 366.34 Mb with 13 chromosomes. Based on the high-quality genome, we discovered that F. carica diverged from Ficus microcarpa ~34 MYA, and a WGD event took place about 2─3 MYA. Throughout the evolutionary history of F. carica, chromosomes 2, 8, and 10 had experienced chromosome recombination, while chromosome 3 saw a fusion and fission. It is worth proposing that the chromosome 9 experienced both inversion and translocation, which facilitated the emergence of the F. carica as a new species. And the selections of F. carica for the genes of recombination chromosomal fragment are compatible with their goal of domestication. In addition, we found that the F. carica has the FhAG2 gene, but there are structural deletions and positional jumps. This gene is thought to replace the one needed for female common type F. carica to be pollinated. Subsequently, we conducted genomic, transcriptomic, and metabolomic analysis to demonstrate significant differences in the expression of CHS among different varieties of F. carica. The CHS playing an important role in the anthocyanin metabolism pathway of F. carica. Moreover, the CHS gene of F. carica has a different evolutionary trend compared to other Ficus species. These high-quality genome assembly, transcriptomic, and metabolomic resources further enrich F. carica genomics and provide insights for studying the chromosomes evolution, sexual system, and color characteristics of Ficus.

Cannabinoid Hyperemesis Encounters After Medical Legalization in Oklahoma.

Introduction Medical cannabis has recently become legal in Oklahoma. Cannabinoid hyperemesis syndrome (CHS) is severe nausea, vomiting, and often abdominal pain typically seen in heavy users of cannabis. The aim of this study is to determine whether emergency department (ED) diagnoses of CHS have increased after medical legalization. Methods We performed a retrospective chart review study of equivalent time periods prior to and after the first legal sales of medical cannabis in Oklahoma. Data were gathered from a single urban ED of adult patients with diagnosed or suspected CHS. We analyzed data using a chi-square analysis of CHS cases as a proportion of total ED visits. Results Diagnosed and suspected CHS visits increased from 43 cases in the eight months preceding the first legal sale to 62 cases in the eight months after legalization. This represents a statistically significant increase in ED visits for CHS (p = 0.026). Total ED encounters were 30,437 and 28,362, respectively, during those time periods. The proportion of visits for CHS was much higher (220/100000 vs 13.3/100000) than previously reported in the literature. The pre-legalization and post-legalization groups did not differ by age, sex, history of GI illness and diabetes, pregnancy, or other drug use. Conclusion We observed a statistically significant increase in ED visits for CHS after the first legal sales of medical cannabis in Oklahoma. Our high proportion of ED visits for CHS could be related to study design, increased provider awareness, high THC levels in Oklahoma's medical cannabis, or increased numbers of cannabis users after legalization. Increases in ED visits for CHS and other cannabinoid-related illnesses must be weighed against the positive effects for cannabis users by policymakers.

The Contributions of Nina Fedorovna Talyzina to Research Developed in Brazilian Postgraduate Programs.

Background: Nina Fedorovna Talyzina was a Russian psychologist, whose theories have been applied in educational research in many countries around the world, including Brazil. Her name is mainly connected to the Activity Theory of Learning (ATL), which has been dubbed the Galperin-Talyzina system of developmental didactics. Objective: Investigate how N.F. Talyzina's ideas are applied in dissertations and theses developed in postgraduate programs in Brazil. Design: Our research was a bibliographic review which used the state of the question method to examine how Talyzina's ideas are applied in Brazilian academic publications. Data were gathered from three responsible databases - the Brazilian Digital Library, the CAPES Catalogue, and the Institutional Repositories (1987-2022). The method of content analysis was used for data analysis, according to pre-determined categories. Results: We found a prevalence of research based on the methodology of formative experiments carried out at different educational levels. Skills, scientific concept- formation, and problem-solving were the objects of investigation in most of the studies. The ideas proposed by L.S. Vygotsky, A.N. Leontiev, P.Ya. Galperin, and V.V. Davidov were expressed through references to Talyzina's work as the theoretical basis of many studies, thus evidencing a crucial dialogue with the Cultural-Historical School (CHS). Conclusion: Our study points out the growing interest in Talyzina's ideas, specifically her Activity Theory of Learning, which can be attributed to comprehensive dialogues with the ideas of L.S. Vygotsky and A.N. Leontiev which predominate in Brazilian research.

RNAi-mediated CHS-2 silencing affects the synthesis of chitin and the formation of the peritrophic membrane in the midgut of Aedes albopictus larvae.

BACKGROUND: Mosquitoes are an important vector of viral transmission, and due to the complexity of the pathogens they transmit, vector control may be the most effective strategy to control mosquito-borne diseases. Chitin is required for insect growth and development and is absent in higher animals and plants, so regulating the chitin synthesis pathway can serve as a potentially effective means to control vector insects. Most of the current research on the chitin synthase (CHS) gene is focused on chitin synthase-1 (CHS-1), while relatively little is known about chitin synthase-2 (CHS-2). RESULTS: The CHS-2 gene of Ae. albopictus is highly conserved and closely related to that of Aedes aegypti. The expression of CHS-2 in the third-instar larvae and pupal stage of Ae. albopictus was relatively high, and CHS-2 expression in adult mosquitoes reached the highest value 24 h after blood-feeding. In the fourth-instar larvae of Ae. albopictus, CHS-2 expression was significantly higher in the midgut than in the epidermis. Silencing CHS-2 in Ae. albopictus larvae had no effect on larval survival and emergence. The expression of four genes related to chitin synthesis enzymes was significantly upregulated, the expression level of three genes was unchanged, and only the expression level of GFAT was significantly downregulated. The expression of chitin metabolism-related genes was also upregulated after silencing. The level of chitin in the midgut of Ae. albopictus larvae was significantly decreased, while the chitinase activity was unchanged. The epithelium of the midgut showed vacuolization, cell invagination and partial cell rupture, and the structure of the peritrophic membrane was destroyed or even absent. METHODS: The expression of CHS-2 in different developmental stages and tissues of Aedes albopictus was detected by real-time fluorescence quantitative PCR (qPCR). After silencing CHS-2 of the fourth-instar larvae of Ae. albopictus by RNA interference (RNAi), the expression levels of genes related to chitin metabolism, chitin content and chitinase activity in the larvae were detected. The structure of peritrophic membrane in the midgut of the fourth-instar larvae after silencing was observed by paraffin section and hematoxylin-eosin (HE) staining. CONCLUSION: CHS-2 can affect midgut chitin synthesis and breakdown by regulating chitin metabolic pathway-related genes and is involved in the formation of the midgut peritrophic membrane in Ae. albopictus, playing an important role in growth and development. It may be a potential target for enhancing other control methods.