Title: 'Synthetic Pot' Laced With Rat Poison Lands People in the ER
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM

Title: Concussions May Leave Former NFL Players With Another Issue: Impotence
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM

Title: Boom in Pot 'Concentrates' Could Pose Addiction Risk for Teens
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM

Title: Many Americans Eyeing CBD, Pot as Pain Relievers Without Knowing Risks
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM

Title: Jumps in Pot Use, Depression and Drinking Threaten Gains Against Smoking
Category: Health News
Created: 8/28/2019 12:00:00 AM
Last Editorial Review: 8/29/2019 12:00:00 AM

Title: Spotting the Signs of Deadly Melanoma Skin Cancers
Category: Health News
Created: 8/22/2021 12:00:00 AM
Last Editorial Review: 8/23/2021 12:00:00 AM

Title: Cheap, Same-Day Test Could Help Spot Miscarriage Risk
Category: Health News
Created: 8/18/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM

Title: Can Your Smartphone Spot a Narrowed Neck Artery?
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM

Title: How Long Do Potatoes Last? Raw, Cooked, and More
Category: Health and Living
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM

Title: Gene Tests Could Spot 1 Million Americans at Risk of High Cholesterol
Category: Health News
Created: 5/18/2022 12:00:00 AM
Last Editorial Review: 5/18/2022 12:00:00 AM

Title: Use of Pot, Hallucinogens Soaring Among Young Americans
Category: Health News
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: Major Gene Study Spots DNA Tied to Autism, Other Disorders
Category: Health News
Created: 8/19/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM

Title: Erectile Dysfunction (ED, Impotence)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 7/25/2022 12:00:00 AM

Title: CDC Panel Urges Seniors to Get New, More Potent Flu Shot This Fall
Category: Health News
Created: 6/23/2022 12:00:00 AM
Last Editorial Review: 6/23/2022 12:00:00 AM

Title: Pot Users Are Less Prone to Sinus Problems
Category: Health News
Created: 8/1/2022 12:00:00 AM
Last Editorial Review: 8/2/2022 12:00:00 AM

The rising obesity epidemic is a phenomenon that has gained increasing attention from health providers and health policy makers. This led to recognition of nonalcoholic fatty liver disease (MASLD). The standard for its assessment has been histologic, which is neither practical nor acceptable by patients. Subsequently, a number of noninvasive assessment methods have been developed. However, despite ease of implementation, their confounding variables do hinder their accuracy. Nonetheless, the development of the liver stiffness measurement (LSM) and incorporation of other biological parameters has minimized but not eliminated the need for liver biopsy. Imaging methods are useful in evaluation, estimation, and following the progression of steatosis and fibrosis with particular attention to controlled attenuation parameter (CAP) and MRI–Proton Density Fat Fraction (MRI-PDFF). The choices for the family physician are broad and rely on tests’ availability, cost, and patient acceptance. Great efforts have been undertaken to produce more robust and novel noninvasive markers that indicate fibrinogenesis directly in an implementable and cost-effective way.

Thermoregulation, responsible for maintaining a stable core temperature during wide fluctuations in external and internal thermal environments, is an iconic homeostatic process. However, we suggest that despite its fundamental physiological significance, the potential for required cool housing temperatures and thermoregulatory mechanisms to influence the interpretation of experimental data is not sufficiently appreciated. Moreover, although it is generally assumed that the major thermoregulatory pathways are well understood, here we discuss new research that suggests otherwise and reveals the emergence of a new wave of exciting ideas for this "old" field of research.

The CYP3A7 enzyme accounts for ~50% of the total cytochrome P450 (P450) content in fetal and neonatal livers and is the predominant P450 involved in neonatal xenobiotic metabolism. Additionally, it is a key player in healthy birth outcomes through the oxidation of dehydroepiandrosterone (DHEA) and DHEA-sulfate. The amount of the other hepatic CYP3A isoforms, CYP3A4 and CYP3A5, expressed in neonates is low but highly variable, and therefore the activity of individual CYP3A isoforms is difficult to differentiate due to their functional similarities. Consequently, a better understanding of the contribution of CYP3A7 to drug metabolism is essential to identify the risk that drugs may pose to neonates and developing infants. To distinguish CYP3A7 activity from CYP3A4/5, we sought to further characterize the selectivity of the specific CYP3A inhibitors CYP3cide, clobetasol, and azamulin. We used three substrate probes, dibenzylfluorescein, luciferin-PPXE, and midazolam, to determine the IC₅₀ and metabolism-dependent inhibition (MDI) properties of the CYP3A inhibitors. Probe selection had a significant effect on the IC₅₀ values and P450 inactivation across all inhibitory compounds and enzymes. CYP3cide and azamulin were both identified as MDIs and were most specific for CYP3A4. Contrary to previous reports, we found that clobetasol propionate (CP) was not an MDI of CYP3A5 but was more selective for CYP3A5 over CYP3A4/7. We further investigated CYP3cide and CP’s ability to differentiate CYP3A7 activity in an equal mixture of recombinant CYP3A4, CYP3A5, and CYP3A7, and our results provide confidence of CYP3cide’s and CP’s ability to distinguish CYP3A7 activity in the presence of the other CYP3A isoforms.

The -aminobutyric acid type A (GABA_A) receptor is modulated by a number of neuroactive steroids. Sulfated steroids and 3β-hydroxy steroids inhibit, while 3α-hydroxy steroids typically potentiate the receptor. Here, we have investigated inhibition of the α1β32L GABA_A receptor by the endogenous neurosteroid 3α-hydroxy-5β-pregnan-20-one (3α5βP) and the synthetic neuroactive steroid 3α-hydroxy-5α-androstane-17β-carbonitrile (ACN). The receptors were expressed in Xenopus oocytes. All experiments were done using two-electrode voltage-clamp electrophysiology. In the presence of low concentrations of GABA, 3α5βP and ACN potentiate the GABA_A receptor. To reveal inhibition, we conducted the experiments on receptors activated by the combination of a saturating concentration of GABA and propofol to fully activate the receptors and mask potentiation, or on mutant receptors in which potentiation is ablated. Under these conditions, both steroids inhibited the receptor with IC₅₀s of ~13 μM and maximal inhibitory effects of 70–90%. Receptor inhibition by 3α5βP was sensitive to substitution of the α1 transmembrane domain (TM) 2-2' residue, previously shown to ablate inhibition by pregnenolone sulfate. However, results of coapplication studies and the apparent lack of state dependence suggest that pregnenolone sulfate and 3α5βP inhibit the GABA_A receptor independently and through distinct mechanisms. Mutations to the neurosteroid binding sites in the α1 and β3 subunits statistically significantly, albeit weakly and incompletely, reduced inhibition by 3α5βP and ACN.

Despite a significant decrease in the number of prescriptions for opioids, the opioid crisis continues, fueled in large part by the availability of the phenylpiperidine mu opioid receptor (MOR) agonist fentanyl. In contrast, the number of prescriptions for and the off-label use of gabapentinoids (gabapentin and pregabalin) has increased dramatically, with gabapentinoids commonly detected in opioid overdose victims. Although gabapentinoids can decrease the potency of the opioid receptor antagonist naloxone to reverse heroin-induced hypoventilation in male rats, the specificity and nature of interaction between gabapentinoids and MOR agonists and any potential sex difference in those interactions are not well characterized. Gabapentinoids were studied in female and male rats discriminating fentanyl (0.0032 mg/kg, i.p.) or cocaine (3.2 mg/kg, i.p.). Alone, neither gabapentin nor pregabalin significantly increased fentanyl- or cocaine-appropriate responding. In rats discriminating fentanyl, each gabapentinoid dose-dependently shifted the fentanyl and heroin discrimination dose-effect functions to the left, whereas naloxone dose-dependently shifted the fentanyl and heroin discrimination dose-effect functions to the right. Each gabapentinoid (100 mg/kg) significantly decreased the potency of naloxone to antagonize the discriminative stimulus effect of fentanyl or heroin. In contrast, each gabapentinoid dose-dependently shifted the cocaine and d-methamphetamine discrimination dose-effect functions to the right. There were no significant sex differences in this study. These results suggest that gabapentinoids impact the misuse of opioids, the co-use of opioids and stimulant drugs, and the increasing number of overdose deaths in individuals using opioids, stimulant drugs, and gabapentinoids in mixtures.

Endocannabinoids, which are present throughout the central nervous system (CNS), can activate cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases. However, careful evaluation of abuse potential is necessary. This study evaluated the abuse potential of lenabasum, a selective CB2 receptor agonist in participants (n = 56) endorsing recreational cannabis use. Three doses of lenabasum (20, 60, and 120 mg) were compared with placebo and nabilone (3 and 6 mg). The primary endpoint was the peak effect (E_max) on a bipolar Drug Liking visual analog scale (VAS). Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. Lenabasum was safe and well tolerated. Compared with placebo, a 20-mg dose of lenabasum did not increase ratings of Drug Liking and had no distinguishable effect on other VAS endpoints. Dose-dependent increases in ratings of Drug Liking were observed with 60 and 120 mg lenabasum. Drug Liking and all other VAS outcomes were greatest for nabilone 3 mg and 6 mg, a medication currently approved by the US Food and Drug Administration (FDA). At a target therapeutic dose (20 mg), lenabasum did not elicit subjective ratings of Drug Liking. However, supratherapeutic doses of lenabasum (60 and 120 mg) did elicit subjective ratings of Drug Liking compared with placebo. Although both doses of lenabasum were associated with lower ratings of Drug Liking compared with 3 mg and 6 mg nabilone, lenabasum does have abuse potential and should be used cautiously in clinical settings.

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa. The two most abundant cannabinoids (⁹-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). Although the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC.

α-Synuclein (α-Syn) aggregation in Lewy bodies and Lewy neurites has emerged as a key pathogenetic feature in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Various factors, including posttranslational modifications (PTMs), can influence the propensity of α-Syn to misfold and aggregate. PTMs are biochemical modifications of a protein that occur during or after translation and are typically mediated by enzymes. PTMs modulate several characteristics of proteins including their structure, activity, localization, and stability. α-Syn undergoes various posttranslational modifications, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, O-GlcNAcylation, nitration, oxidation, polyamination, arginylation, and truncation. Different PTMs of a protein can physically interact with one another or work together to influence a particular physiological or pathological feature in a process known as PTMs crosstalk. The development of detection techniques for the cooccurrence of PTMs in recent years has uncovered previously unappreciated mechanisms of their crosstalk. This has led to the emergence of evidence supporting an association between α-Syn PTMs crosstalk and synucleinopathies. In this review, we provide a comprehensive evaluation of α-Syn PTMs, their impact on misfolding and pathogenicity, the pharmacological means of targeting them, and their potential as biomarkers of disease. We also highlight the importance of the crosstalk between these PTMs in α-Syn function and aggregation. Insight into these PTMS and the complexities of their crosstalk can improve our understanding of the pathogenesis of synucleinopathies and identify novel targets of therapeutic potential.

BACKGROUND AND PURPOSE:

Angioplasty and stent placement have been described as a bailout technique in individuals with failed thrombectomy. We aimed to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban before angioplasty and stent placement.

Tim Miller hopes Amazon's anthology series will help viewers appreciate the "blood, sweat, and tears" Firewalk Studios put into the scrapped game.

A new Nordic-style Open Kindergarten will be trialled in part of Scotland ahead of a potential roll-out across the country.

Chris just wants to ride a chocobo and get a headshot, but he's old and fingers hurt. Speaking of, Kelley's Digimon died of old age. Meanwhile, Josh five hours The Good Life and goes to fight a bear (as in rawr). And the whole cast travels to the world of Pinocchisouls.

The post RPG Cast – Episode 608: “Sentient Potatoes” appeared first on RPGamer.

News of the asteroid 2024 RW1 impacting near the Philippines may have come as a shock this week, but space agencies and astronomers around the world are keeping an eye out to protect us

Comet C/2023 A3, also known as Tsuchinshan–ATLAS, is expected to grace our skies from mid-October. Abigail Beall is hoping for a dazzling display

Gas bubbles on the surface of a star have been observed for the first time in detail outside our solar system, and they are 75 times the size of our sun

If you were standing on Mars as it was hit by charged particles from the sun, you might be able to see an aurora just like on Earth

Astronomers have detected an exoplanet around Barnard’s star, one of the sun’s closest neighbours, but it is too hot for liquid water or life

Complex carbon-based molecules crucial to life on Earth originated somewhere in space, but we didn't know where. Now, huge amounts of them have been spotted in a huge, cold cloud of gas

Many people enjoy the experience of using AIs like ChatGPT or voice assistants like Alexa to find out information, but it turns out doing so makes it less likely you will spot inaccurate information

It can be difficult to spot AI generated videos known as deepfakes, but there are ways to spot one if you know what to look for

Comet Nishimura (C/2023 P1) was discovered in August and is now whizzing by Earth, but finding it in the sky will be a challenge.

Kurt "CyberGuy" Knutsson presents the cities targeted most by robocalls, why this is happening and what you can do about it to protect your privacy.

I started work on it around a year ago on a whim because I was reading a lot of game design articles and couldn’t resist the idea of a small platform game. It’s really expanded a lot beyond that though! I’d like to start showing it to and discussing it with more people as I […]

Jacob Hando discusses why 'Harry Potter and the Goblet of Fire' has such an impactful front cover.

The annual Perseid meteor shower is set to peak on Sunday night into early Monday morning, giving stargazers the chance to see hundreds of meteors.

A stadium-sized asteroid is passing relatively close to Earth on Tuesday, NASA announced. Its distance from Earth and its massive size makes it a "potentially hazardous object."

Sedimentary mineral deposits found on the surface of Mars may have been left by an ancient sea 3.5 billion years ago.

The post Ancient Coastline Spotted in Martian Utopia Region appeared first on Sci.News: Breaking Science News.

This stunning new image from the NASA/ESA Hubble Space Telescope is one of the best ever views of a galaxy duo called MCG+05-31-045.

The post Hubble Spots Pair of Interacting Galaxies in Coma Cluster appeared first on Sci.News: Breaking Science News.

The European Commission has revealed the progress of potential European Union countries in areas including food safety. As part of the Enlargement Package, the EU Commission has assessed how prepared Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia, Serbia, Georgia, Moldova, Ukraine, and Turkey are as they work towards EU... Continue Reading

Sources say Harper’s name has been in the mix for at least 10 months

It's more of a desktop thing now, but it has picked up some new features.

The singer conveyed the richness of Bhojpuri and Maithili languages through her wide repertoire of songs

Mark Rylance is in talks to play Albus Dumbledore in Harry Potter TV series. Warner Bros. is yet to enter negotiations with the actor