Design, synthesis and biological evaluation of glucose metabolism inhibitors as anticancer agents.

Compared to normal cells, tumour cells exhibit an upregulation of glucose transporters and an increased rate of glycolytic activity. In previous research, we successfully identified a promising hit compound BH10 through a rigorous screening process, which demonstrates a potent capacity for inhibiting cancer cell proliferation by targeting glucose metabolism. In the current study, we identify Kelch-like ECH-associated protein 1 (Keap1) as a potential protein target of BH10via avidin pull-down assays with biotinylated-BH10. Subsequently, we present a comprehensive analysis of a series of BH10 analogues characterized by the incorporation of a naphthoimidazole scaffold and the introduction of a triazole ring with diverse terminal functional groups. Notably, compound 4d has emerged as the most potent candidate, exhibiting better anti-cancer activities against HEC1A cancer cells with an IC50 of 2.60 µM, an extended biological half-life, and an improved pharmacokinetic profile (compared to BH10) in mice.

Tranexamic Acid Reduces the Amount of Blood Transfused in Revision Total Hip Arthroplasty for Vancouver B2/B3 Periprosthetic Femur Fractures.

BACKGROUND: Periprosthetic fractures around total hip arthroplasty (THA) represent a significant source of morbidity and mortality. The use of tranexamic acid (TXA) in arthroplasty is well described, yet little literature supports its role in periprosthetic femur fractures (PFFs). This study investigated the effect of preoperative TXA administration on transfusion rate and volume, length of stay, and 90-day complication rates in patients undergoing revision THA for PFF. MATERIALS AND METHODS: All patients undergoing revision THA for PFF (Vancouver B2/B3) at our institution from August 2016 to June 2022 were identified. Routine TXA administration at surgical start was introduced in 2018. Patient demographics, operative time, blood product use, length of stay, and 90-day complications were collected. Patients were divided into those who received TXA preoperatively and those who did not. RESULTS: A total of 56 patients were included. There was no difference in age, sex, anesthetic type, fracture classification, or preoperative blood values between cohorts. TXA significantly lowered the amount of blood product required (2.3 units vs 3.2 units, P=.023). Preoperative TXA did not independently reduce length of stay; however, blood transfusion was associated with increased length of stay (7 days vs 4.7 days, P=.003). There were no differences in 90-day complications. CONCLUSION: Among patients who underwent revision THA for Vancouver B2/B3 PFF, TXA did not affect transfusion rates but did result in the use of fewer blood products without an increase in complications. We support routine use of TXA in this patient population. Future studies should assess earlier administration of TXA in the emergency department or once patients' conditions have been medically optimized. [Orthopedics. 202x;4x(x):xx-xx.].

Worsening of lymphopenia in patients with multiple sclerosis when switched from dimethyl fumarate to diroximel fumarate.

BACKGROUND: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are similar disease-modifying therapies (DMTs) that reduce disease activity in patients with relapsing-remitting multiple sclerosis (MS). We expect that patients on DRF would experience a similar incidence and severity of lymphopenia, given that it is a well-documented side effect of DMF treatment. METHODS: We utilized linear mixed-effects models to test for differences in white blood cell count (WBC), absolute lymphocyte count (ALC), absolute CD3+ count, absolute CD4+ count, and absolute CD8+ count over time in clinically stable patients with MS on DMF who switched to DRF. RESULTS: Twenty-two patients with MS who were clinically stable on DMF switched to DRF. Linear mixed-effects models showed a decrease in ALC when switching medications (ß = -225.70, p < 0.040). In addition, the models showed a decrease in absolute CD8+ counts after switches from DMF to DRF (ß = -85.59, p = 0.034). CONCLUSION: Patients with MS who are stable on DMF and switch to DRF may experience worsening of lymphopenia and lower absolute CD8+ counts, which may increase their risk of opportunistic infections. These findings indicate that close lymphocyte subset monitoring is clinically important when switching patients with MS from DMF to DRF.

Reassessment of pore occlusion in some diatom taxa with re-evaluation of Placoneis Mereschkowsky (Bacillariophyceae: Cymbellales) and description of two new genera.

In this article, the history and taxonomy of Placoneis gastrum, the type species of the genus Placoneis, was discussed. We investigated the structure of pore occlusions in Placoneis and related genera. As a result, we propose a new classification for tectulum-like types of pore occlusions. The new classification is congruent with previously-published and newly-constructed phylogenies based on molecular data. Based on the different structures of the pore occlusions, species of Placoneis are transferred to Witkowskia gen. nov. Hence, 168 new combinations are introduced. A new diatom species, with a similar morphology to Placoneis flabellata, was discovered in Bac Kan Province, Vietnam. It is described in this article as Chudaevia densistriata sp. nov. Placoneis flabellata is transferred to Chudaevia gen. nov. We also illustrate Placoneis flabellata herein and compare it to Chudaevia densistriata sp. nov. An unknown diatom, similar to Placoneis coloradensis, was discovered in Chukotka, Russia. It is introduced as Placoneis elinae sp. nov. below. Additionally, we discuss the distribution of some species of Witkowskia gen. nov. and Chudaevia gen. nov.

Cocconeiscrisscrossis sp. nov., a new monoraphid diatom (Bacillariophyta) from southern China.

A novel monoraphid diatom species, Cocconeiscrisscrossis You, Yu, Kociolek & Wang, sp. nov. is examined and described from the Qingyi River and Maolan Nature Reserve of southern China. The morphological description is based on light microscopy and scanning electron microscopy observations and the new species is compared with similar taxa in this genus. The characteristics unique to Cocconeiscrisscrossissp. nov. include its central area extending irregularly to both sides, it having closed valvocopulae with heavily silicified fimbriate margins and poles of the valvocopulae have 'sword-shaped' siliceous extensions. These features differentiate this new species from others in the genus. This new species was found in alkaline waterbodies, including streams, waterfall and ponds. It was usually found as an epiphyte on the stones; however, it was present on other substrates such as mosses.

Joint EANM-SNMMI guideline on the role of 2-[18F]FDG PET/CT in no special type breast cancer : (endorsed by the ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA).

INTRODUCTION: There is much literature about the role of 2-[18F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. PURPOSE: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). METHODS: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[18F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. RESULTS: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[18F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[18F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[18F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[18F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. CONCLUSION: 2-[18F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.

Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood-brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.

Increasing Body Mass Index Not Associated With Worse Patient-Reported Outcomes After Primary THA or TKA.

INTRODUCTION: As the US obesity epidemic continues to grow, so too does comorbid hip and knee arthritis. Strict body mass index (BMI) cutoffs for total hip and knee arthroplasty (THA and TKA) in the morbidly obese have been proposed and remain controversial, although current American Academy of Orthopaedic Surgeons guidelines recommend a BMI of less than 40 m/kg2 before surgery. This study sought to compare patient-reported outcomes and 30-day complication, readmission, and revision surgery rates after THA or TKA between morbidly obese patients and nonmorbidly obese control subjects. METHODS: All patients undergoing primary THA and TKA at our institution from May 2020 to July 2022 were identified. Patient demographics, surgical time, length of stay and 30-day readmission, revision surgery, and complication rates were prospectively collected. Preoperative and postoperative Hip and Knee Society (Hip Osteoarthritis Outcome Score [HOOS] and Knee Osteoarthritis Outcome Score [KOOS]) were collected. Patients were stratified by BMI as ideal weight (20 to 24.9), overweight (25 to 29.9), class I obese (30 to 34.9), class II obese (35 to 39.9), and morbidly obese (>40 m/kg2). RESULTS: A total of 1,423 patients were included for final analysis. No difference was observed in 30-day unplanned return to emergency department, readmission, or revision surgery in the morbidly obese cohort. Morbidly obese patients undergoing THA had lower preoperative HOOS (49.5 versus 54.5, P = 0.004); however, there was no difference in postoperative HOOS or KOOS at 12 months across all cohorts. DISCUSSION: No difference was observed in 30-day return to emergency department, readmission, or revision surgery in the morbidly obese cohort. Despite a lower preoperative HOOS, there was no difference in 12-month HOOS or KOOS when stratified by BMI. These findings suggest that such patients may achieve similar benefit from arthroplasty as their ideal weight counterparts.