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γ-Hydroxybutyric acid (GHB) is an endogenous short chain fatty acid that acts as a neurotransmitter and neuromodulator in the mammalian brain. It has often been illegally abused or misused due to its strong anesthetic effect, particularly in drug-facilitated crimes worldwide. However, proving its ingestion is not straightforward because of the difficulty in distinguishing between endogenous and exogenous GHB, as well as its rapid metabolism. Metabolomics and metabolism studies have recently been used to identify potential biomarkers of GHB exposure. This mini-review provides an overview of GHB-associated metabolic alterations and explores the potential of metabolites for application as biomarkers of GHB exposure. For this, we discuss the biosynthesis and metabolism of GHB, analytical issues of GHB in biological samples, alterations in metabolic pathways, and changes in the levels of GHB conjugates in biological samples from animal and human studies. Metabolic alterations in organic acids, amino acids, and polyamines in urine enable discrimination between GHB-ingested animals or humans and controls. The potential of GHB conjugates has been investigated in a variety of clinical settings. anti-PD-L1 antibody Despite the recent growth in the application of metabolomics and metabolism studies associated with GHB exposure, it remains challenging to distinguish between endogenous and exogenous GHB. This review highlights the significance of further metabolomics and metabolism studies for the discovery of practical peripheral biomarkers of GHB exposure.Bone metastases from prostate cancer (PCa) often show an increase in density on computed tomography (CT) after successful androgen deprivation therapy (ADT). Density may be reduced, however, as the disease progresses or, contrarily, when disease is no longer active. The current study investigated the role of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in differentiating between these two conditions.

The study cohort included 15 PCa patients with sclerotic/blastic bone metastasis in whom reduction in bone density of metastasis was noted on follow-up 68Ga-PSMA-11 PET/CT after ADT. Each patient had two PET/CT scans. Prior to the first scan, six patients were castration naïve and nine patients were already treated. All patients had ADT between the two PET/CT scans. PET parameters (SUVmax and tumor-to-background ratio), and CT parameters (HUmax) were determined and compared for each lesion on both scans. Patient's response was based on prostate-specific antigen (PSA) levels and appearanger showed an increased uptake, new lesions were detected in the eighth patient.

A decrease in density of bone lesions may reflect clinical progression, or contrarily, a response to therapy in patients with PCa and skeletal involvement treated with ADT. Uptake of 68Ga-PSMA-11 may separate between these two vastly opposing conditions.

A decrease in density of bone lesions may reflect clinical progression, or contrarily, a response to therapy in patients with PCa and skeletal involvement treated with ADT. Uptake of 68Ga-PSMA-11 may separate between these two vastly opposing conditions.Sleep and functioning are associated with a risk of early workforce exit. However, patterns of change in sleep and functioning through time have not been investigated using person-oriented approaches to show what features of sleep and functioning are associated with an early exit. We examined the pattern of interactions between sleep and health functioning characterizing homogenous subgroups of employees and their associations with premature work exit. An additional aim was to provide a tutorial providing detailed description on how to apply these models, compared to traditional variable based risk factors. We analyzed data from 5148 midlife employees of the City of Helsinki, Finland, surveyed over three phases (2000-02, 2007, and 2012). Using repeated measures latent class analyses (RMLCA) we classified people into groups based on their trajectories in sleep and functioning. We identified four longitudinal groups (1) Stable good sleep and functioning (reference), (2) Persistent sleep problems and good or moderate functioning, (3) Poor functioning with good sleep, and (4) Problematic sleep and health functioning. Compared to group 1, elevated risk was found in all classes with group 4 being the worst. In conclusion, focusing on person-orientated patterns of interactions between sleep and functioning helped produce qualitatively different and quantitatively stronger predictions than using conventional risk factor methodology. Thus, longitudinal person-oriented approaches may be a more powerful method for quantifying the role of sleep and health functioning as risks for premature exit from work.This paper presents the results of experimental tests carried out on an electromagnetic shaker where the excited element was a specimen with additional weight attached to the slip table. The load was random with a different kurtosis parameter value, i.e., it was performed for non-Gaussian loads. The experiment was accompanied by basic fatigue calculations in the frequency domain and their verification with experimental results. A significant decrease in fatigue life was found to take place with an increase in kurtosis and the maintenance of the same standard deviation of the specimen load. The fatigue effect, caused by the deviation from the normal distribution that was described by the kurtosis parameter, on the fatigue life of aluminum alloy 6082 was presented. An analysis revealed the different amplitude probability distributions for the loading signal and the recorded deformation signal. It was concluded that there was a lack of sensitivity of the numerical model to the change in the kurtosis parameter of the distribution of random loads.Marine sponges (porifera) have proved to be a prolific source of unique bioactive secondary metabolites, among which the alkaloids occupy a special place in terms of unprecedented structures and outstanding biological activities. Identification of active cytotoxic alkaloids extracted from marine animals, particularly sponges, is an important strive, due to lack of knowledge on traditional experiential and ethnopharmacology investigations. In this report, a comprehensive survey of demospongian bioactive alkaloids in the range 1987-2020 had been performed with a special emphasis on the potent cytotoxic activity. Different resources and databases had been investigated, including Scifinder (database for the chemical literature) CAS (Chemical Abstract Service) search, web of science, Marin Lit (marine natural products research) database. More than 230 representatives of different classes of alkaloids had been reviewed and classified, different genera belonging to the phylum porifera had been shown to be a prolific source of alkaloidal molecules, including Agelas sp.

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