LLC

Prostate cancer is a leading diagnosis and major cause of cancer-related deaths in men worldwide. As a typical hormone-responsive disease, prostate cancer is commonly managed with androgen deprivation therapy (ADT) to curb its progression and potential metastasis. Unfortunately, progression to castration-resistant prostate cancer (CRPC), a notably more aggressive phase of the disease, occurs within a timeframe of 2-3 years following ADT. Enzalutamide, a recognized androgen receptor (AR) antagonist, has been employed as a standard of care for men with metastatic castration-resistant prostate cancer (mCRPC) since it was first approved in 2012, due to its ability to prolong survival...

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) is a widespread contaminant of emerging concern resulting from oxidation of 6PPD, which is an antidegradant substance added to tires. The recent identification of 6PPD-quinone as the cause of acute mortality in coho salmon has quickly motivated studies on 6PPD-quinone toxicity to other species. Subsequent findings have shown that 6PPD-quinone toxicity is highly species specific. Closely related species can differ widely in response to 6PPD-quinone from extremely sensitive to tolerant...

For plant protection products applied as seed treatments, the risk to birds and mammals possibly feeding on such treated seeds needs to be addressed in the EU, in order to register these products for commercial use. For this purpose, the European Food Safety Food Authority (EFSA) has provided guidance on how to execute such a risk assessment. The risk assessment follows a tiered approach. In the Tier 1 risk assessment of the EFSA guidance (2023), it is assumed that birds or mammals have ad libitum access to treated seeds and exclusively feed on treated seeds...

BACKGROUND: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. OBJECTIVE: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. METHODS: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years...

Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread but also to prevent physical and social complications and reduce the disease burden. Objectives The study aims to evaluate the factors that lead to a delayed leprosy diagnosis. Methods This study was conducted in the outpatient departments of Leprosy Control Institute and Hospital, Dhaka, Bangladesh, and at Medical College for Women and Hospital, Dhaka, Bangladesh, from March 2023 to June 2023...

Indentation testing is the most common approach to quantify mechanical brain tissue properties. Despite a myriad of studies conducted already, reported stiffness values vary extensively and continue to be subject of study. Moreover, the growing interest in the relationship between the brain's spatially heterogeneous microstructure and local tissue stiffness warrants the development of standardized measurement protocols to enable comparability between studies and assess repeatability of reported data. Here, we present three individual protocols that outline (1) sample preparation of a 1000-µm thick coronal slice, (2) a comprehensive list of experimental parameters associated with the FemtoTools FT-MTA03 Micromechanical Testing System for spherical indentation, and (3) two different approaches to derive the elastic modulus from raw force-displacement data...

Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. This practice is necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging, for instance), and providing intra- and post-procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research...

Proteomics and phosphoproteomics play crucial roles in elucidating the dynamics of post-transcriptional processes. While experimental methods and workflows have been established in this field, a persistent challenge arises when dealing with small samples containing a limited amount of protein. This limitation can significantly impact the recovery of peptides and phosphopeptides. In response to this challenge, we have developed a comprehensive experimental workflow tailored specifically for small-scale samples, with a special emphasis on neuronal tissues like the trigeminal ganglion...

BACKGROUND: The evidence in the effectiveness of deep brain stimulation in children with medication-refractory non-degenerative monogenic dystonia is heterogeneous and long-term results are sparse. OBJECTIVES: The objective is to describe long-term outcomes in a single-center cohort and compare our results with a meta-analysis cohort form literature. METHODS: We performed a retrospective single-center cohort study including consecutive pediatric patients with non-degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual-patient data meta-analysis with the same inclusion criteria...

Objectives Root canal treatments aim to eliminate biofilms effectively. Considering the limitations of chemical irrigants, there is growing interest in natural alternatives like periostracum due to their antibacterial and fouling-resistant properties. This study aimed to assess periostracum's toxicity as a root canal irrigant by investigating its effects on zebrafish embryos' heart rate, survival rate, and hatching rate, as well as inflammation studies using neutral red assays comparing it to standard irrigants like ethylenediaminetetraacetic acid (EDTA), chlorhexidine (CHX), and sodium hypochlorite (NaOCl)...

BACKGROUND: Medical tapes can lead to skin damage upon removal in susceptible patients with fragile skin and at higher risk of developing tissue injury. PURPOSE: We compared the effect of medical tapes with silicone-based versus acrylate-based adhesives on the back or volar forearm stratum corneum using analytical techniques to assess skin condition and potential damage post product removal on 88 healthy volunteers. METHODS: Two studies were conducted in separate facilities (Study 1: 3M In-house Clinical Facility, St...

BACKGROUND: The dentate nuclei of the cerebellum are key sites of neuropathology in Friedreich ataxia (FRDA). Reduced dentate nucleus volume and increased mean magnetic susceptibility, a proxy of iron concentration, have been reported by magnetic resonance imaging studies in people with FRDA. Here, we investigate whether these changes are regionally heterogeneous. METHODS: Quantitative susceptibility mapping data were acquired from 49 people with FRDA and 46 healthy controls...

BACKGROUND AND OBJECTIVE: The Levodopa in EArly Parkinson's disease study showed no effect of earlier versus later levodopa initiation on Parkinson's disease (PD) progression over 80 weeks. We now report the effects over 5 years. METHODS: The Levodopa in EArly Parkinson's disease study randomly assigned patients to levodopa/carbidopa 300/75 mg daily for 80 weeks (early start) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed start)...

BACKGROUND: Invasive treatments like radiofrequency stereotactic lesioning or deep brain stimulation of the globus pallidus internus can resolve drug-resistant status dystonicus (SD). However, these open procedures are not always feasible in patients with SD. OBJECTIVE: The aim was to report the safety and efficacy of simultaneous asleep bilateral transcranial magnetic resonance-guided focused ultrasound (MRgFUS) pallidotomy for life-threatening SD. METHODS: We performed bilateral simultaneous MRgFUS pallidotomy under general anesthesia in 2 young patients with pantothenate kinase-associated neurodegeneration and GNAO1 encephalopathy...

INTRODUCTION: Noninvasive continuous blood pressure monitoring has the potential to improve patient treatment in the hospital setting. Such noninvasive devices can be applied earlier in the treatment process to empower nurses and clinicians to react more quickly to patient deterioration with the added benefit of eliminating the risks associated with invasive monitoring. However, emerging technologies must be capable of reproducing current clinical measures for medical decision making...

Indigenous peoples in Canada are disproportionately exposed to environmental contaminants and may face elevated health risks related to their unique cultural, spiritual, and economic relationships with the land, including the use of traditional food systems. However, to date, institutionalized approaches to assess risks to human and ecological health from contaminants have not been well developed or implemented with Indigenous community contexts in mind. There is regulatory interest in developing new approach methods for risk assessment, and thus an opportunity to increase their relevance to Indigenous communities in which they will be ultimately applied...

Cancer immunotherapy has greatly improved the prognosis of tumor-bearing patients. Nevertheless, cancer patients exhibit low response rates to current immunotherapy drugs, such as PD1 and PDL1 antibodies. Cyclic dinucleotide analogs are a promising class of immunotherapeutic agents. In this study, in situ autologous tumor vaccines, composed of Bis-2'-F-cGS AS MP phosphonothioate isomers (FGA-di-pS-2 or FGA-di-pS-4) and cytidinyl/cationic lipids (Mix), were constructed. Intravenous (i.v.) and intratumoral (i...

BACKGROUND: IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells. METHODS: Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay...

Aquatic risk assessment is essential to guarantee the sustainable use of pesticides and the conservation of water resources near agricultural fields. This article discusses a proposal for a tiered regulatory framework for the aquatic risk assessment of pesticides in Brazil. The first step is problem formulation, which includes establishing general and specific protection goals. In the exposure assessment, the Estimated Environmental Concentrations in water should be calculated based on realistic worst-case assumptions regarding application rate and frequency, the entry into the edge-of-field water body, and fate in the water body, using scenario-dependent models suggested by the Brazilian Environmental Agency...

BACKGROUND: Early contraceptive implant removal without intentions to conceive predisposes women to unintended pregnancies.. Some of the unintended pregnancies end in unsafe abortions which further increases the risk of maternal mortality and morbidity. Therefore, we assessed the proportion of women who had early contraceptive implant removal. We also explored the reasons for early contraceptive implant removalamong women at Mbale Regional Referral Hospital in eastern Uganda. METHODS: We conducted a sequential explanatory mixed methods study at Mbale Regional Referral Hospital between November 2022 to December 2022...