BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve ...obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by 18F-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).
Acute compartment syndrome is an emergent condition characterized by increased pressure in a noncompliant fascial compartment, resulting in ischemia of the muscles and nerves. It is most commonly ...caused by a traumatic etiology but rarely can be caused by an atraumatic etiology, resulting in a confusing clinical scenario. We present a case of a 15-year-old sedentary teenager diagnosed with acute exertional medial compartment syndrome of the foot, initially diagnosed with MRI, following two days of rugby practice.
Diffusion-weighted imaging (DWI) has become an increasingly used tool in abdominal and pelvic magnetic resonance imaging (MRI), primarily in the oncologic setting. DWI sequences are being added to ...routine MRI protocols at many institutions, and as its use has spread, more non-oncologic applications have been explored. The purpose of this article is to provide a review of DWI applications in inflammatory, infectious, autoimmune-mediated, and ischemic processes affecting the genitourinary system.
IgG4-RD has the ability to mimic other pathologic conditions, requiring that health care professionals have a high index of suspicion to make a proper diagnosis.
Fossil apes and human evolution Almécija, Sergio; Hammond, Ashley S; Thompson, Nathan E ...
Science,
05/2021, Letnik:
372, Številka:
6542
Journal Article
Recenzirano
Odprti dostop
Humans diverged from apes (chimpanzees, specifically) toward the end of the Miocene ~9.3 million to 6.5 million years ago. Understanding the origins of the human lineage (hominins) requires ...reconstructing the morphology, behavior, and environment of the chimpanzee-human last common ancestor. Modern hominoids (that is, humans and apes) share multiple features (for example, an orthograde body plan facilitating upright positional behaviors). However, the fossil record indicates that living hominoids constitute narrow representatives of an ancient radiation of more widely distributed, diverse species, none of which exhibit the entire suite of locomotor adaptations present in the extant relatives. Hence, some modern ape similarities might have evolved in parallel in response to similar selection pressures. Current evidence suggests that hominins originated in Africa from Miocene ape ancestors unlike any living species.
Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand‐metal bonds. Inspired by the success of Auranofin and other gold complexes ...as antitumor agents, we have studied the cytotoxicity of bis‐ and mono‐CAAC‐gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov‐3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non‐specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC‐gold complexes in biological environments, which may result in more specific drug‐target interactions and decreased side effects.
Analogous to Auranofin, CAAC‐supported gold complexes show promising results as antitumoral agents as shown by their cytotoxicity against four cancer cell lines. Noticeably, this study includes the probing of their Ic50, their ability to bind and inhibit their biological target (TrxR), non‐specific binding toward non‐tumor associated proteins, their cell‐death mechanism and determination of morphological changes using Transmission Electron Microscopy.
Some reports of supernova (SN) discoveries turn out not to be true core-collapse explosions. One such case was SN 2009ip, which was recognized to be the eruption of a luminous blue variable (LBV) ...star. This source had a massive (50-80 M), hot progenitor star identified in pre-explosion data; it had documented evidence of pre-outburst variability and it was subsequently discovered to have a second outburst in 2010. In 2012, the source entered its third known outburst. Initial spectra showed the same narrow-line profiles as before, suggesting another LBV-like eruption. We present new photometry and spectroscopy of SN 2009ip, indicating that the 2012 outburst transitioned into a genuine SN explosion. The most striking aspect of these data is that unlike any previous episodes, the spectrum developed Balmer lines with very broad P-Cygni profiles characteristic of normal Type II supernovae (SNe II), in addition to overlying narrow emission components. The emission lines exhibit unprecedented (for any known non-terminal LBV-like eruption) full width at half-maximum intensity values of ∼8000 km s−1, while the absorption components seen just before the main brightening had blue wings extending out to −13 000 km s−1. These velocities are typical of core-collapse SN explosions, but have never been associated with emission lines from a non-terminal LBV-like eruption. SN 2009ip is the first object to have both a known massive blue progenitor star and LBV-like eruptions with accompanying spectra observed a few years prior to becoming a SN. Immediately after the broad lines first appeared, the peak absolute magnitude of M
V
−14.5 was fainter than that of normal SNe II. However, after a brief period of fading, the source quickly brightened again to M
R
= −17.5 mag in ∼2 d, suggesting a causal link to the prior emergence of the broad-line spectrum. Once the bright phase began, the broad lines mostly disappeared, and the spectrum resembled the early optically thick phases of luminous SNe IIn. The source reached a peak brightness of −18 mag about 2 weeks later, after which broad emission lines again developed in the spectrum as the source faded. We conclude that the most recent 2012 outburst of SN 2009ip was the result of a true core-collapse SN IIn that occurred when the progenitor star was in an LBV-like outburst phase, and where the SN was initially faint and then rapidly brightened due to interaction with circumstellar material. The pulsational pair instability, LBV-like eruptions or other instabilities due to late nuclear burning phases in massive stars may have caused the multiple pre-SN eruptions.
PDF
