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To evaluate the biomechanical effects of different attachments' position for maxillary molar intrusion with clear aligner treatment by finite element analysis.

Cone-beam computed tomography images of a patient with supra-eruption of the maxillary second molars were selected to construct three-dimensional models of the maxilla, periodontal ligaments, dentition, and clear aligner. The models were divided into four groups depending on the attachment location on the first molar (1) no attachment (NA), (2) buccal attachment (BA), (3) palatal attachment (PA), and (4) bucco-palatal attachment (BPA). After applying an intrusion of 0.2mm on the second molar, displacements and stress distributions of the teeth, aligner, and periodontal ligament were analyzed with the finite element software.

All groups displayed equivalent movement patterns of aligners. The NA and BA groups showed buccal tipping of the second molar, while the PA group showed palatal tipping. The BPA group had the highest intruding value and the lowest buccal/palatal tipping value. All groups showed mesial tipping of the second molar. Stress distribution in the periodontal ligament strongly correlated with the attachment position. The BPA group showed the best stress distribution.

Combined BA and PA could effectively prevent buccal and palatal tipping and showed the best efficiency in intruding the second molar. The second molar showed an unavoidable tendency to tip mesially, regardless of the attachment position.
Combined BA and PA could effectively prevent buccal and palatal tipping and showed the best efficiency in intruding the second molar. The second molar showed an unavoidable tendency to tip mesially, regardless of the attachment position.While numerous targeted therapies have been recently adopted to improve the treatment of hematologic malignancies, acquired or intrinsic resistance poses a significant obstacle to their efficacy. Thus, there is increasing need to identify novel, targetable pathways to further improve therapy for these diseases. The integrated stress response is a signaling pathway activated in cancer cells in response to both dysregulated growth and metabolism, and also following exposure to many therapies that appears one such targetable pathway for improved treatment of these diseases. In this review, we discuss the role of the integrated stress response in the biology of hematologic malignancies, its critical involvement in the mechanism of action of targeted therapies, and as a target for pharmacologic modulation as a novel strategy for the treatment of hematologic malignancies.
The effectiveness of online classes is always a concern, and it can be overcome by opting for active learning strategies like team-based learning (TBL). This study was conducted to find out the effectiveness of online TBL as an active learning strategy. We also aimed to explore the satisfaction and perception of students toward TBL.

This is a mixed-method study conducted among 29 third-year Bachelor of Medicine and Bachelor of Surgery (MBBS) students of Gandaki Medical College using purposive sampling method in the duration of January to September 2021. Three two hours online TBL sessions were used for teaching introduction to medical ethics. The individual readiness assurance test (IRAT) scores were compared to the group readiness assurance test (GRAT) scores to evaluate the effect of TBL through cooperative learning. Learner reactions and satisfaction of students towards TBL were assessed using a validated questionnaire comprising of a five-point Likert scale. An open-ended question asking the participahics was effective as a teaching learning tool in our setting. The students were satisfied with the learning process and rated the learning strategy positively.
Online TBL in medical ethics was effective as a teaching learning tool in our setting. The students were satisfied with the learning process and rated the learning strategy positively.Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug conjugates through coupling the conventional chemotherapeutics to a carrier (such as antibody and peptide) provide an alternative strategy to improve therapeutic efficacy and simultaneously reduce the unspecific toxicities, by virtue of the advantages of highly specific targeting ability and potent killing effect. Although 14 antibody-drug conjugates (ADCs) have been approved worldwide and more are being investigated in clinical trials so far, several limitations have been disclosed during clinical application. Compared with ADCs, peptide-drug conjugates (PDCs) possess several advantages, including easy industrial synthesis, low cost, high tissue penetration and fast clearance. So far, only a handful of PDCs have been approved, highlighting tremendous development potential. Herein, we discuss the progress and pitfalls in the development of ADCs and underline what can learn from ADCs for the better construction of PDCs in the future.
Gut microbes were closely related to women's health. Previous studies reported that the gut microbes of premenopausal women were different from those of postmenopausal women. However, little was known about the relationship between gut microbiota dysbiosis and menopausal syndrome (MPS). PI3K inhibitor The aim of this study was to explore the relationship between MPS and gut microbes.

Patients with MPS (P group, n = 77) and healthy women (H group, n = 24) at menopause were recruited in this study. The stool specimen and clinical parameters (demographic data, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), et al) of participants' were collected. We evaluated the differences in gut microbes by 16S ribosomal RNA gene sequencing. We used LEfSe to identify gut microbes with varying abundances in different groups. The Spearman correlation coefficients of clinical parameters and gut microbes were calculated. PICRUSt was used to predict the potential KEGG Ortholog functional profiles of microbial cound.
There was gut microbiota dysbiosis in MPS, which is reflected in the deficiency of the abundance of Aggregatibacter segnis, Bifidobacterium animalis and Acinetobacter guillouiae related to the level of sex hormones. In MPS individuals, species with altered abundances and unique functional pathways were found.
Accumulating evidence implicates that gut fungi are associated with the pathogenesis of colorectal cancer (CRC). Our previous study has revealed that Candida tropicalis (C. tropicalis) promotes colorectal tumorigenesis by enhancing immunosuppressive function of myeloid-derived suppressor cells (MDSCs) and increasing accumulation of MDSCs, but the underlying mechanisms remain unestablished.

Bone marrow-derived MDSCs were stimulated with C. tropicalis. RNA-sequencing analysis was performed to screen the differentially expressed genes. Quantitative real-time PCR and western blot were used to measure the expression of related proteins. Co-culture assay of MDSCs and CD8
T cells was used to determine the immunosuppressive ability of MDSCs. Metabolomic analysis was conducted to detect metabolic reprogramming of MDSCs. Aerobic glycolysis of MDSCs was assessed by extracellular acidification rate (ECAR), glucose consumption and lactate production. A CAC mouse model was induced by AOM and DSS to determine the ther tropicalis-induced aerobic glycolysis of MDSCs. Blockade of PKM2 nuclear translocation attenuates C. tropicalis-mediated colorectal tumorigenesis. The high expression of PKM2, PKM2 (p-Y105) and iNOS in CRC-infiltrated MDSCs correlates with the development of human CRC.

C. tropicalis enhances immunosuppressive function of MDSCs via Syk-PKM2-HIF-1α-glycolysis signaling axis, which drives CRC. Therefore, we identify the Syk-PKM2-HIF-1α-glycolysis signaling axis as a potential therapeutic target for CRC.
C. tropicalis enhances immunosuppressive function of MDSCs via Syk-PKM2-HIF-1α-glycolysis signaling axis, which drives CRC. Therefore, we identify the Syk-PKM2-HIF-1α-glycolysis signaling axis as a potential therapeutic target for CRC.
Carbapenem-induced neurotoxicity is an unusual side effect, with seizure being the most commonly reported symptom. Among the carbapenems, imipenem-cilastin is classically associated with the most severe neurotoxicity side effects. Carbapenem is mainly excreted by the kidney and its half-life is significantly increased in patients with chronic kidney disease (CKD). Therefore, dose adjustment is necessary in such patients. Ertapenem-associated neurotoxicity is increasingly being reported in CKD patients, but rarely seen in patients with recommended dose adjustment.

We report a case of a 56-year-old male patient with chronic kidney disease 5 on dialysis(CKD 5D). The patient presented with a history of fever, chills and rigours during a session of haemodialysis (HD). He was diagnosed with Enterobacter cloacae catheter-related blood stream infection and was started on ertapenem. After 13days of ertapenem, he experienced an acute confusional state and progressed to having auditory and visual hallucinations. His blood investigations and imaging results revealed no other alternative diagnosis. Hence a diagnosis of ertapenem-induced neurotoxicity was made. He had complete resolution of symptoms after 10days' discontinuation of ertapenem.

Our case draws attention to the risk of potentially serious toxicity of the central nervous system in HD patients who receive the current recommended dose of ertapenem. It also highlights that renal dosing in CKD 5D patients' needs to be clinically studied to ensure antibiotic safety.
Our case draws attention to the risk of potentially serious toxicity of the central nervous system in HD patients who receive the current recommended dose of ertapenem. It also highlights that renal dosing in CKD 5D patients' needs to be clinically studied to ensure antibiotic safety.
To compare the surgical outcomes and postoperative complications with and without Ologen collagen matrix augmentation during XEN gel stent implantation.

We retrospectively analyzed patients who underwent XEN gel stent implantation with an ab externo technique. The amount of intraocular pressure (IOP) reduction, percentage of postoperative complications and additional management, and surgical success defined as IOP reduction greater than 20% compared with the preoperative IOP measurement were compared between Ologen-augmented and non-augmented groups. Groups of patients who underwent XEN gel stent implantation alone and combined with phacoemulsification were analyzed separately.

A total 103 eyes of 103 participants were included. Of those, 72 eyes underwent standalone XEN gel stent implantation 42 eyes with Ologen augmentation (Oloxen group) and 30 eyes without Ologen augmentation (Xen group). Thirty-one eyes underwent XEN gel stent implantation with phacoemulsification 19 eyes with Ologen augmentation (Phaco-Oloxen group) and 12 eyes without Ologen augmentation (PhacoXen group).
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