Tyrosine Hydroxylase Knockdown at the Hypothalamic Supramammillary Nucleus Area Induces Obesity and Glucose Intolerance.

Introduction: The supramammillary nucleus (SuMN) exerts influences on a wide range of brain functions including feeding and feeding-independent fuel metabolism. However, which specific neuronal type(s) within the SuMN manifest this influence has not been delineated. This study investigated the effect of SuMN tyrosine hydroxylase (TH) (rate-limiting enzyme in dopamine synthesis) knockdown (THx) on peripheral fuel metabolism.

Brain Dopamine-Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects.

Despite enormous global efforts within clinical research and medical practice to reduce cardiovascular disease(s) (CVD), it still remains the leading cause of death worldwide. While genetic factors clearly contribute to CVD etiology, the preponderance of epidemiological data indicate that a major common denominator among diverse ethnic populations from around the world contributing to CVD is the composite of Western lifestyle cofactors, particularly Western diets (high saturated fat/simple sugar [particularly high fructose and sucrose and to a lesser extent glucose] diets), psychosocial stress, depression, and altered sleep/wake architecture. Such Western lifestyle cofactors are potent drivers for the increased risk of metabolic syndrome and its attendant downstream CVD.

Diagnostic Performance in Differentiating COVID-19 from Other Viral Pneumonias on CT Imaging: Multi-Reader Analysis Compared with an Artificial Intelligence-Based Model.

Growing evidence suggests that artificial intelligence tools could help radiologists in differentiating COVID-19 pneumonia from other types of viral (non-COVID-19) pneumonia. To test this hypothesis, an R-AI classifier capable of discriminating between COVID-19 and non-COVID-19 pneumonia was developed using CT chest scans of 1031 patients with positive swab for SARS-CoV-2 ( = 647) and other respiratory viruses ( = 384). The model was trained with 811 CT scans, while 220 CT scans ( = 151 COVID-19; = 69 non-COVID-19) were used for independent validation.

How the COVID-19 Pandemic Affected Attendance at a Tertiary Orthopedic Center Emergency Department: A Comparison between the First and Second Waves.

Italy was the first European country to face the SARS-CoV-2 virus (COVID-19) pandemic in 2020. The country quickly implemented strategies to contain contagions and re-organize medical resources. We evaluated the COVID-19 effects on the activity of a tertiary-level orthopedic emergency department (ED) during the first and second pandemic waves.

Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects.

Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic nervous system activity and central hypodopaminergic function has been demonstrated to potentiate an immune system pro-oxidative/pro-inflammatory condition and this immune phenotype is known to contribute significantly to the advancement of cardiovascular disease (CVD). Therefore, the possibility exists that bromocriptine-QR therapy may reduce adverse cardiovascular events in type 2 diabetes subjects via attenuation of this underlying chronic pro-oxidative/pro-inflammatory state.

Pterosaur melanosomes support signalling functions for early feathers.

Remarkably well-preserved soft tissues in Mesozoic fossils have yielded substantial insights into the evolution of feathers. New evidence of branched feathers in pterosaurs suggests that feathers originated in the avemetatarsalian ancestor of pterosaurs and dinosaurs in the Early Triassic, but the homology of these pterosaur structures with feathers is controversial. Reports of pterosaur feathers with homogeneous ovoid melanosome geometries suggest that they exhibited limited variation in colour, supporting hypotheses that early feathers functioned primarily in thermoregulation.

Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet.

The treatment of type 2 diabetes patients with bromocriptine-QR, a unique, quick release micronized formulation of bromocriptine, improves glycemic control and reduces adverse cardiovascular events. While the improvement of glycemic control is largely the result of improved postprandial hepatic glucose metabolism and insulin action, the mechanisms underlying the drug's cardioprotective effects are less well defined. Bromocriptine is a sympatholytic dopamine agonist and reduces the elevated sympathetic tone, characteristic of metabolic syndrome and type 2 diabetes, which potentiates elevations of vascular oxidative/nitrosative stress, known to precipitate cardiovascular disease.

CT radiomics-based machine learning classification of atypical cartilaginous tumours and appendicular chondrosarcomas.

Background: Clinical management ranges from surveillance or curettage to wide resection for atypical to higher-grade cartilaginous tumours, respectively. Our aim was to investigate the performance of computed tomography (CT) radiomics-based machine learning for classification of atypical cartilaginous tumours and higher-grade chondrosarcomas of long bones.

Methods: One-hundred-twenty patients with histology-proven lesions were retrospectively included.

Activation State of the Supramammillary Nucleus Regulates Body Composition and Peripheral Fuel Metabolism.

Whole body fuel metabolism and energy balance are controlled by an interactive brain neuronal circuitry involving multiple brain centers regulating cognition, circadian rhythms, reward, feeding and peripheral biochemical metabolism. The hypothalamic supramammillary nucleus (SuMN) comprises an integral node having connections with these metabolically relevant centers, and thus could be a key central coordination center for regulating peripheral energy balance. This study investigated the effect of chronically diminishing or increasing SuMN neuronal activity on body composition and peripheral fuel metabolism.

Experimental dopaminergic neuron lesion at the area of the biological clock pacemaker, suprachiasmatic nuclei (SCN) induces metabolic syndrome in rats.

Background: The daily peak in dopaminergic neuronal activity at the area of the biological clock (hypothalamic suprachiasmatic nuclei [SCN]) is diminished in obese/insulin resistant vs lean/insulin sensitive animals. The impact of targeted lesioning of dopamine (DA) neurons specifically at the area surrounding (and that communicate with) the SCN (but not within the SCN itself) upon glucose metabolism, adipose and liver lipid gene expression, and cardiovascular biology in normal laboratory animals has not been investigated and was the focus of this study.

Methods: Female Sprague-Dawley rats received either DA neuron neurotoxic lesion by bilateral intra-cannula injection of 6-hydroxydopamine (2-4 μg/side) or vehicle treatment at the area surrounding the SCN at 20 min post protriptyline ip injection (20 mg/kg) to protect against damage to noradrenergic and serotonergic neurons.

Circadian-timed dopamine agonist treatment reverses high-fat diet-induced diabetogenic shift in ventromedial hypothalamic glucose sensing.

Introduction: Within the ventromedial hypothalamus (VMH), glucose inhibitory (GI) neurons sense hypoglycaemia while glucose excitatory (GE) neurons sense hyperglycaemia to initiate counter control mechanisms under normal conditions. However, potential electrophysiological alterations of these two neuronal types in vivo in insulin-resistant states have never been simultaneously fully documented. Further, the anti-diabetic effect of dopamine agonism on this VMH system under insulin resistance has not been studied.

Bromocriptine mesylate improves glucose tolerance and disposal in a high-fat-fed canine model.

Bromocriptine mesylate treatment was examined in dogs fed a high fat diet (HFD) for 8 wk. After 4 wk on HFD, daily bromocriptine (Bromo; = 6) or vehicle (CTR; = 5) injections were administered. Oral glucose tolerance tests were performed before beginning HFD (OGTT1), 4 wk after HFD began (Bromo only), and after 7.

Circadian-timed quick-release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus.

Objective: Sympathetic nervous system (SNS) overactivity is a risk factor for insulin resistance and cardiovascular disease (CVD). We evaluated the impact of bromocriptine-QR, a dopamine-agonist antidiabetes medication, on elevated resting heart rate (RHR) (a marker of SNS overactivity in metabolic syndrome), blood pressure (BP) and the relationship between bromocriptine-QR's effects on RHR and HbA1c in type 2 diabetes subjects.

Design And Subjects: RHR and BP changes were evaluated in this post hoc analysis of data from a randomized controlled trial in 1014 type 2 diabetes subjects randomized to bromocriptine-QR vs placebo added to standard therapy (diet ± ≤2 oral antidiabetes medications) for 24 weeks without concomitant antihypertensive or antidiabetes medication changes, stratified by baseline RHR (bRHR).

The oldest freshwater crabs: claws on dinosaur bones.

With approximately 1,500 extant species, freshwater crabs (Decapoda: Brachyura) are among the most diverse decapod crustaceans. Nevertheless, their fossil record is extremely limited: only Potamidae, Potamonautidae and Trichodactylidae are reported up to the Eocene of the Neotropics so far. This work documents unusually large decapod claws from the Upper Cretaceous (Campanian) continental deposits of Velaux and vicinity (southern France), in close association with large vertebrate remains.

The rise of feathered dinosaurs: , the oldest dinosaur with 'feather-like' structures.

Diverse epidermal appendages including grouped filaments closely resembling primitive feathers in non-avian theropods, are associated with skeletal elements in the primitive ornithischian dinosaur from the Kulinda locality in south-eastern Siberia. This discovery suggests that "feather-like" structures did not evolve exclusively in theropod dinosaurs, but were instead potentially widespread in the whole dinosaur clade. The dating of the Kulinda locality is therefore particularly important for reconstructing the evolution of "feather-like" structures in dinosaurs within a chronostratigraphic framework.

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high-fat diet.

Among vertebrate species of the major vertebrate classes in the wild, a seasonal rhythm of whole body fuel metabolism, oscillating from a lean to obese condition, is a common biological phenomenon. This annual cycle is driven in part by annual changes in the circadian dopaminergic signalling at the suprachiasmatic nuclei (SCN), with diminution of circadian peak dopaminergic activity at the SCN facilitating development of the seasonal obese insulin-resistant condition. The present study investigated whether such an ancient circadian dopamine-SCN activity system for expression of the seasonal obese, insulin-resistant phenotype may be operative in animals made obese amd insulin resistant by high-fat feeding and, if so, whether reinstatement of the circadian dopaminergic peak at the SCN would be sufficient to reverse the adverse metabolic impact of the high-fat diet without any alteration of caloric intake.

Extreme tooth enlargement in a new Late Cretaceous rhabdodontid dinosaur from Southern France.

Rhabdodontidae is a successful clade of ornithopod dinosaurs, characteristic of Late Cretaceous continental faunas in Europe. A new rhabdodontid from the late Campanian, of southern France, Matheronodon provincialis gen. et sp.

A new Jurassic theropod from China documents a transitional step in the macrostructure of feathers.

Genuine fossils with exquisitely preserved plumage from the Late Jurassic and Early Cretaceous of northeastern China have recently revealed that bird-like theropod dinosaurs had long pennaceous feathers along their hindlimbs and may have used their four wings to glide or fly. Thus, it has been postulated that early bird flight might initially have involved four wings (Xu et al. Nature 421:335-340, 2003; Hu et al.

Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin.

Objective: The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin.

Impact of bromocriptine-QR therapy on cardiovascular outcomes in type 2 diabetes mellitus subjects on metformin.

Objectives: Type 2 diabetes mellitus (T2DM) is associated with a substantially increased risk of cardiovascular disease (CVD). Bromocriptine-QR (B-QR), a quick release sympatholytic dopamine D receptor agonist, is a FDA-approved therapy for T2DM which may provide CVD risk reduction. Metformin is considered to be an agent with a potential cardioprotective benefit.

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary.

An extended series of studies indicate that endogenous phase shifts in circadian neuronal input signaling to the biological clock system centered within the hypothalamic suprachiasmatic nucleus (SCN) facilitates shifts in metabolic status. In particular, a diminution of the circadian peak in dopaminergic input to the peri-SCN facilitates the onset of fattening, insulin resistance and glucose intolerance while reversal of low circadian peak dopaminergic activity to the peri-SCN via direct timed dopamine administration to this area normalizes the obese, insulin resistant, glucose intolerant state in high fat fed animals. Systemic circadian-timed daily administration of a potent dopamine D2 receptor agonist, bromocriptine, to increase diminished circadian peak dopaminergic hypothalamic activity across a wide variety of animal models of metabolic syndrome and type 2 diabetes mellitus (T2DM) results in improvements in the obese, insulin resistant, glucose intolerant condition by improving hypothalamic fuel sensing and reducing insulin resistance, elevated sympathetic tone, and leptin resistance.

Molecular composition and ultrastructure of Jurassic paravian feathers.

Feathers are amongst the most complex epidermal structures known, and they have a well-documented evolutionary trajectory across non-avian dinosaurs and basal birds. Moreover, melanosome-like microbodies preserved in association with fossil plumage have been used to reconstruct original colour, behaviour and physiology. However, these putative ancient melanosomes might alternatively represent microorganismal residues, a conflicting interpretation compounded by a lack of unambiguous chemical data.

Integrated Paleoenvironmental Reconstruction and Taphonomy of a Unique Upper Cretaceous Vertebrate-Bearing Locality (Velaux, Southeastern France).

The Velaux-La Bastide Neuve fossil-bearing site (Bouches-du-Rhône, France) has yielded a diverse vertebrate assemblage dominated by dinosaurs, including the titanosaur Atsinganosaurus velauciensis. We here provide a complete inventory of vertebrate fossils collected during two large-scale field campaigns. Numerous crocodilian teeth occur together with complete skulls.

Erratum: Neuroendocrine and metabolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats.

[This corrects the article DOI: 10.1186/1758-5996-6-104.].