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US outlines effects of withdrawing land from oil drilling

The U.S. Interior Department's plan to withdraw hundreds of square miles in New Mexico from oil and gas production for the next 20 years is expected to result in only a few dozen wells not being drilled on federal land surrounding Chaco Culture National Historical Park. Land managers on Thursday released an environmental assessment of the plan first outlined by Interior Secretary Deb Haaland in 2021 in response to the concerns of Native American tribes in New Mexico and Arizona. Environmentalists say the agency needs to take a broader look at the cumulative effects of development if they want to preserve cultural sites and limit pollution from ongoing development beyond the proposed withdrawal zone.

The post US outlines effects of withdrawing land from oil drilling first appeared on Federal News Network.




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Pentagon chief says a six-month temporary budget bill will have devastating effects on the military

Defense Secretary Lloyd Austin says passage of a six-month temporary spending bill would have widespread and devastating effects on the department and the military. He wrote in a letter Sunday to key members of Congress that passing a continuing resolution that caps spending at 2024 levels, rather than taking action on the proposed 2025 budget will hurt thousands of defense programs, and damage military recruiting just as it is beginning to recover after the COVID-19 pandemic. Republican House Speaker Mike Johnson has teed up a vote this week on a bill that would keep the federal government funded for six more months.

The post Pentagon chief says a six-month temporary budget bill will have devastating effects on the military first appeared on Federal News Network.




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Brain Stimulation's Complex Emotional Effects

Mapping the emotional responses to deep brain stimulation




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Study proposal: The Effects of Mud Wrestling on the Female Urogenital Tract

How do women who mud wrestle or take regular mud baths (esp. naked, say at a spa) avoid getting mud in their, er, orifices—or do they avoid it? Would tampons be useful in preventing such an occurrence? Or is that even necessary?

And if mud is allowed into the vagina or anus, does that lead to an increased incidence of infection (whether by yeast or bacteria)? How would one go about (or, ladies, how have you gone about) preventing such resultant infections? And do spas have problems with the transmission of such infections in their mud baths?

I've found an abstract from a study in the Journal of the American Medical Association that found a greater incidence of pustular follicular dermatitis outbreaks among mud-wrestling college students (no joke) at the University of Washington in Seattle—but that doesn't speak to the question of vaginal, anal or urethral irritation stemming from prolonged mud exposure.

(And yes, this is a serious question, I promise—the topic came up during a conversation I was party to a while back about, well, vaginal irritation/infections. Fun stuff, huh?)




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Big oil firms knew of dire effects of fossil fuels as early as 1950s, memos show




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Trenbolone Side Effects

Side Effects
di: fantasynight




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How do psychedelics work? This brain region may explain their effects

The claustrum seems to act as a switchboard, telling different parts of the brain when to turn on and off. But what happens when the switchboard operator steps away?




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4 major effects of climate change in America

Warming temperatures are causing extreme weather patterns across the country. But communities are pushing back with solutions old and new.




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Current State of the Evidence: Examining the Effects of Orton-Gillingham Reading Interventions for Students With or at Risk for Word-Level Reading Disabilities

Over the past decade, parent advocacy groups led a grassroots movement resulting in most states adopting dyslexia-specific legislation, with many states mandating the use of the Orton-Gillingham (OG) approach to reading instruction. Orton-Gillingham is a direct, explicit, multisensory, structured, sequential, diagnostic, and prescriptive approach to reading for students with or at risk for word-level reading disabilities (WLRD). Evidence from a prior synthesis and What Works Clearinghouse reports yielded findings lacking support for the effectiveness of OG interventions.




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Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research




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Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews




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Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression

K Schoonjans
May 1, 1996; 37:907-925
Reviews




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Adiponectin forms a complex with atherogenic LDL and inhibits its downstream effects

Akemi Kakino
Nov 3, 2020; 0:jlr.RA120000767v1-jlr.RA120000767
Research Articles




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Adiponectin forms a complex with atherogenic LDL and inhibits its downstream effects [Research Articles]

Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL’s atherogenicity. L5, the most electronegative subfraction of LDL, induces atherogenic responses similarly to copper-oxidized LDL (oxLDL). Unlike native LDL endocytosed via the LDL receptor, L5 and oxLDL are internalized by cells via the lectin-like oxidized LDL receptor-1 (LOX-1). Using enzyme-linked immunosorbent assays (ELISAs), we showed that adiponectin preferentially bound oxLDL but not native LDL. In Chinese hamster ovary (CHO) cells transfected with LOX-1 or LDL receptor, adiponectin selectively inhibited the uptake of oxLDL but not of native LDL, respectively. Furthermore, adiponectin suppressed the internalization of oxLDL in human coronary artery endothelial cells (HCAECs) and THP-1–derived macrophages. Western blot analysis of human plasma showed that adiponectin was abundant in L5 but not in L1, the least electronegative subfraction of LDL. Sandwich ELISAs with anti-adiponectin and anti–apolipoprotein B antibodies confirmed the binding of adiponectin to L5 and oxLDL. In LOX-1–expressing CHO cells, adiponectin inhibited cellular responses to oxLDL and L5, including nuclear factor-B activation and ERK phosphorylation. In HCAECs, adiponectin inhibited oxLDL-induced endothelin-1 secretion and ERK phosphorylation. Conversely, oxLDL suppressed the adiponectin-induced activation of adenosine monophosphate–activated protein kinase in COS-7 cells expressing adiponectin receptor AdipoR1. Our findings suggest that adiponectin binds and inactivates atherogenic LDL, providing novel insight into the anti-atherogenic mechanisms of adiponectin.




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Solvent accessibility changes in a Na+-dependent C4-dicarboxylate transporter suggest differential substrate effects in a multistep mechanism [Membrane Biology]

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site–associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family.




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Thermal proteome profiling in zebrafish reveals effects of napabucasin on retinoic acid metabolism [Research]

Thermal proteome profiling (TPP) allows for the unbiased detection of drug – target protein engagements in vivo. Traditionally, one cell type is used for TPP studies, with the risk of missing important differentially expressed target proteins. The use of whole organisms would circumvent this problem. Zebrafish embryos are amenable to such an approach. Here, we used TPP on whole zebrafish embryo lysate to identify protein targets of napabucasin, a compound that may affect Signal transducer and activator of transcription 3 (Stat3) signaling through an ill-understood mechanism. In zebrafish embryos, napabucasin induced developmental defects consistent with inhibition of Stat3 signaling. TPP profiling showed no distinct shift in Stat3 upon napabucasin treatment, but effects were detected on the oxidoreductase, Pora, which might explain effects on Stat3 signaling. Interestingly, thermal stability of several aldehyde dehydrogenases (Aldhs) was affected. Moreover, napabucasin activated ALDH enzymatic activity in vitro. Aldhs have crucial roles in retinoic acid metabolism and functionally we validated napabucasin-mediated activation of the retinoic acid pathway in zebrafish in vivo. We conclude that TPP profiling in whole zebrafish embryo lysate is feasible and facilitates direct correlation of in vivo effects of small molecule drugs with their protein targets.




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Sacrificing the Human Psyche at the Altar of Social Media? 4 Concerning Ill-Effects to Know

Did you grow up in a world void of social media platforms? Then, you’re probably the last ‘lucky’ generation. A part of Generation Y and most of Generation Z have been raised alongside the internet and social media. Individuals belonging to the latter have practically been raised by such platforms, as they interact with strangers […]

The post Sacrificing the Human Psyche at the Altar of Social Media? 4 Concerning Ill-Effects to Know first appeared on What is Psychology?.




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The 'Ripple Effects' of Integrating Social-Emotional Learning into Elementary Learning

The principal of a school in Washington, DC, describes a shift toward equity, diversity, and inclusion.




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Cannabis and the Developing Brain: Insights into Its Long-Lasting Effects

Yasmin L. Hurd
Oct 16, 2019; 39:8250-8258
Symposium and Mini-Symposium




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Governor Carney Signs Package of Legislation to Combat Effects of Climate Change

WILMINGTON, Del. – Governor Carney joined Senator Stephanie Hansen, other members of the General Assembly and advocates on Thursday, September 5, to sign a package of bills that further Delaware’s efforts to protect the environment and support clean energy. Legislation included Senate Bill 265, House Bill 9, House Substitute 2 for House Bill 13, Senate Bill 237 and House […]



  • Department of Natural Resources and Environmental Control
  • Division of Climate
  • Coastal and Energy
  • Governor John Carney
  • News
  • Office of the Governor
  • climate change
  • legislation

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Can Technology Offset the Effects of Population Aging on Economic Growth? New Report from the Asian Development Bank

Can Technology Offset the Effects of Population Aging on Economic Growth? New Report from the Asian Development Bank Can Technology Offset the Effects of Population Aging on Economic Growth? New Report from the Asian Development Bank
Anonymous (not verified) Thu, 03/26/2020 - 16:59

East-West Wire

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News, Commentary, and Analysis
East-West Wire

The East-West Wire is a news, commentary, and analysis service provided by the East-West Center in Honolulu. Any part or all of the Wire content may be used by media with attribution to the East-West Center or the person quoted. To receive East-West Center Wire media releases via email, subscribe here.

For links to all East-West Center media programs, fellowships and services, see www.eastwestcenter.org/journalists.

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East-West Wire

Tagline
News, Commentary, and Analysis
East-West Wire

The East-West Wire is a news, commentary, and analysis service provided by the East-West Center in Honolulu. Any part or all of the Wire content may be used by media with attribution to the East-West Center or the person quoted. To receive East-West Center Wire media releases via email, subscribe here.

For links to all East-West Center media programs, fellowships and services, see www.eastwestcenter.org/journalists.

Explore




effects

Cuba’s Coastal Dwellers Mitigate the Effects of Climate Change



When the weather is bad, the residents of the Litoral neighborhood in Manzanillo, Cuba, are forced to evacuate their houses. When it’s calm, the sea penetrates the foundations of houses, leaving them vulnerable. Now the community is getting together to restore the mangroves and improve the environment to return their homes to safety.




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Fuzzy quantum effects have been seen on the largest scale yet

A weird quantum phenomenon called delocalisation has been measured for a 100-nanometre glass bead, helping reveal where the boundary lies between quantum and classical physics




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Certain quantum systems may be able to defy entropy's effects forever

A mathematical proof shows that some quantum states can resist nature’s tendency to disorder – but only under very specific conditions




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Breast Cancer Treatment Effects on Sex Life a Hidden Burden

Title: Breast Cancer Treatment Effects on Sex Life a Hidden Burden
Category: Health News
Created: 8/8/2022 12:00:00 AM
Last Editorial Review: 8/9/2022 12:00:00 AM




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How Does Melatonin Make You Feel, and Are There Side Effects?

Title: How Does Melatonin Make You Feel, and Are There Side Effects?
Category: Health and Living
Created: 7/15/2022 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM




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Judging When Alcohol's Effects Wear Off Not Easy, Study Finds

Title: Judging When Alcohol's Effects Wear Off Not Easy, Study Finds
Category: Health News
Created: 8/20/2010 4:10:00 PM
Last Editorial Review: 8/23/2010 12:00:00 AM




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Kids' Mild Brain Injury Can Have Long-Term Effects

Title: Kids' Mild Brain Injury Can Have Long-Term Effects
Category: Health News
Created: 8/24/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM




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Downstream Effects of Market Changes on Inhalers: Impacts on Individuals With Chronic Lung Disease

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24–$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005–March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease.




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Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation

BACKGROUD:Lung volume measurements are important for monitoring functional aeration and recruitment and may help guide adjustments in ventilator settings. The expiratory phase of airway pressure release ventilation (APRV) may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (expiratory time [TE]). We hypothesized that expiratory flow would correlate with estimated lung volume (ELV) as measured using a modified nitrogen washout/washin technique in a large-animal lung injury model.METHODS:Eight pigs (35.2 ± 1.0 kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration, which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15 mm Hg in normal and injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC INview tool. The expiratory flow-time slope and TE were measured from the expiratory flow profile.RESULTS:Lung elastance increased with induced lung injury from 29.3 ± 7.3 cm H2O/L to 39.9 ± 15.1cm H2O/L, and chest wall elastance increased with increasing intra-abdominal pressures (IAPs) from 15.3 ± 4.1 cm H2O/L to 25.7 ± 10.0 cm H2O/L in the normal lung and 15.8 ± 6.0 cm H2O/L to 33.0 ± 6.2 cm H2O/L in the injured lung (P = .39). ELV decreased from 1.90 ± 0.83 L in the injured lung to 0.67 ± 0.10 L by increasing IAP to 15 mm Hg. This had a significant correlation with a TE decrease from 2.3 ± 0.8 s to 1.0 ± 0.1 s in the injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29 ± 0.06 L/s2 to 0.63 ± 0.05 L/s2 (ρ = 0.78).CONCLUSIONS:Changes in ELV over time, and the TE and flow-time slope, could be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.




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Effects of Ultrasonic Use on Hearing Loss in Dental Hygienists: A matched pairs design study

Purpose Dental professionals are exposed to hazardous noise levels on a daily basis in clinical practice. The purpose of this study was to compare the hearing status of dental hygienists who utilize ultrasonic scalers in the workplace compared to age-matched control participants (non-dental hygienists) who were not exposed to ultrasonic noise.Methods A convenience sample of nineteen dental hygienists (experimental) and nineteen non-dental hygienists (control) was recruited for this study. A matched pairs design was utilized; participants in each group were matched based on age and gender to eliminate confounding variables. The testing procedure consisted of an audiologist performing a series of auditory tests including otoacoustic emissions test, pure-tone audiometry, and tympanometry on the experimental and control groups.Results In the right ear, there were notable differences from 1000 Hz – 10,000 Hz and in the left ear from 6000 Hz – 10,000 Hz, with higher hearing thresholds in the experimental group of dental hygienists. While 56% of the univariate tests conducted on how many days were worked per week showed statistical significance, the regression line slope indicated those that worked more days had better hearing statuses. The variables for years in practice for dental hygienists, how many of those years were full-time employment, and how many years the dental hygienist had used an ultrasonic scaling device, also had many significant univariate tests for the experimental group only. These variables were more likely to serve as proxies representing true noise exposure. The paired t-test between the groups demonstrated statistically significant differences between the experimental and control group at 9000 Hz in both ears.Conclusion While results from this study demonstrated various qualitative differences in hearing status of the control group (non-dental hygienists) and experimental group (dental hygienists), age was found to be the most critical variable. Furthermore, this data demonstrated differences in hearing status based on various frequencies between dental hygienists and age-matched controls that should be further explored with a larger population.




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Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats [Articles]

Compound probiotics have been widely used and commonly coadministered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (P450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin, and chlorzoxazone. Male Wistar rats were administered drinking water containing VSL#3 or not for 14 days and then intragastrically administered a P450 probe cocktail; this was done to investigate the host P450’s metabolic phenotype. Stool, liver/jejunum, and serum samples were collected for 16S ribosomal RNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both α and β diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1417 and 4004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of P450 genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum-conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug–processing gene expression, and intestinal structure in rats, which could be reasons for pharmacokinetic changes.

SIGNIFICANCE STATEMENT

This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of cytochrome P450 probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the present study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, combined here with the bile acid profile and histopathological analysis.




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Quantitatively Predicting Effects of Exercise on Pharmacokinetics of Drugs Using a Physiologically Based Pharmacokinetic Model [Articles]

Exercise significantly alters human physiological functions, such as increasing cardiac output and muscle blood flow and decreasing glomerular filtration rate (GFR) and liver blood flow, thereby altering the absorption, distribution, metabolism, and excretion of drugs. In this study, we aimed to establish a database of human physiological parameters during exercise and to construct equations for the relationship between changes in each physiological parameter and exercise intensity, including cardiac output, organ blood flow (e.g., muscle blood flow and kidney blood flow), oxygen uptake, plasma pH and GFR, etc. The polynomial equation P = aiHRi was used for illustrating the relationship between the physiological parameters (P) and heart rate (HR), which served as an index of exercise intensity. The pharmacokinetics of midazolam, quinidine, digoxin, and lidocaine during exercise were predicted by a whole-body physiologically based pharmacokinetic (WB-PBPK) model and the developed database of physiological parameters following administration to 100 virtual subjects. The WB-PBPK model simulation results showed that most of the observed plasma drug concentrations fell within the 5th–95th percentiles of the simulations, and the estimated peak concentrations (Cmax) and area under the curve (AUC) of drugs were also within 0.5–2.0 folds of observations. Sensitivity analysis showed that exercise intensity, exercise duration, medication time, and alterations in physiological parameters significantly affected drug pharmacokinetics and the net effect depending on drug characteristics and exercise conditions. In conclusion, the pharmacokinetics of drugs during exercise could be quantitatively predicted using the developed WB-PBPK model and database of physiological parameters.

SIGNIFICANCE STATEMENT

This study simulated real-time changes of human physiological parameters during exercise in the WB-PBPK model and comprehensively investigated pharmacokinetic changes during exercise following oral and intravenous administration. Furthermore, the factors affecting pharmacokinetics during exercise were also revealed.




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Effects of Dual Inhibition at Dopamine Transporter and {sigma} Receptors in the Discriminative-Stimulus Effects of Cocaine in Male Rats [Behavioral Pharmacology]

Previous studies demonstrated that sigma receptor (R) antagonists alone fail to alter cocaine self-administration despite blocking various other effects of cocaine. However, R antagonists when combined with dopamine transporter (DAT) inhibitors substantially decrease cocaine self-administration. To better understand the effects of this combination, the present study examined the effects of R antagonist and DAT inhibitor combinations in male rats discriminating cocaine (10 mg/kg, i.p.) from saline injections. The DAT inhibitors alone [(–)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate monohydrate (WIN 35,428) and methylphenidate] at low (0.1-mg/kg) doses that were minimally active failed to shift the dose-effect function for discriminative-stimulus effects of cocaine to the left more than 2-fold. At 0.32 mg/kg the DAT inhibitors alone shifted the cocaine dose-effect function leftward 24- or 6.6-fold, respectively. The R antagonists (BD1008, BD1047, and BD1063) failed to fully substitute for cocaine, although BD1008 and BD1047 substituted partially. At 10 mg/kg, BD1008, BD1047, or BD1063 alone shifted the cocaine dose-effect function leftward less than 6.0-fold. In combination with 0.1 mg/kg WIN 35,428, the 10 mg/kg doses of R antagonists shifted the cocaine dose-effect function from 12.3- to 36.7-fold leftward, and with 0.32 mg/kg WIN 35,428 from 14.3- to 440-fold leftward. In combination with 0.1 mg/kg methylphenidate, those R antagonist doses shifted the cocaine dose-effect function from 5.5- to 55.0-fold leftward, and with 0.32 mg/kg methylphenidate from 10.5- to 48.1-fold leftward. The present results suggest that dual DAT/R inhibition produces agonist-like subjective effects that may promote decreases in self-administration obtained in previous studies.

SIGNIFICANCE STATEMENT

There is currently no approved medication for treating stimulant abuse, although dopamine uptake inhibitors in combination with sigma receptor (R) antagonists decrease cocaine self-administration in laboratory animals. The present study assessed how this combination alters the discriminative-stimulus effects of cocaine in male rats. Results suggest that concurrent dopamine uptake inhibition and R antagonism together may promote decreases in self-administration, possibly by mimicking the subjective effects extant when subjects cease continued cocaine self-administration.




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Alternative Reinforcers Enhance the Effects of Opioid Antagonists, but Not Agonists, on Oxycodone Choice Self-Administration in Nonhuman Primates [Behavioral Pharmacology]

Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration–approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032–1.0 mg/kg), nalbuphine (0.32–10 mg/kg), buprenorphine (0.0032–0.032 mg/kg), methadone (0.32–1.0 mg/kg), or flumazenil (1–3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a μ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy μ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy μ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse–related behaviors.

SIGNIFICANCE STATEMENT

Clinical treatment programs for opioid use disorder use a combination of pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective have not been fully characterized. This study examined whether the effectiveness of μ-opioid medications to decrease oxycodone self-administration is altered in the presence of an alternative reinforcer. The results suggest that alternative reinforcers enhance the effects of antagonist or low-efficacy partial agonists, suggesting they may be a more effective strategy to curtail opioid use.




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Sex Differences in the Neural and Behavioral Effects of Acute High-Dose Edible Cannabis Consumption in Rats [Special Section: Cannabinoid Signaling in Human Health and Disease]

The consumption of 9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (six males, seven females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Rats were provided access to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg) for 10 minutes, during which they voluntarily consumed all of the provided Nutella and THC mixture. Cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24 hours after exposure. In another cohort (16 males, 15 females), we examined the effects of AHDECC on learning and prepulse inhibition and serum and brain THC and 11-hydroxy-THC concentrations. AHDECC resulted in higher brain and serum THC and 11-hydroxy-THC levels in female rats over 24 hours. AHDECC also produced: 1) Cg, dHipp, and NAc gamma power suppression, with the suppression being greater in female rats, in a time-dependent manner; 2) hypolocomotion, hypothermia, and antinociception in a time-dependent manner; and 3) learning and prepulse inhibition impairments. Additionally, most neural activity and behavior changes appear 2 hours after ingestion, suggesting that interventions around this time might be effective in reversing/reducing the effects of AHDECC.

SIGNIFICANCE STATEMENT

The effects of high-dose edible cannabis on behavior and neural circuitry are poorly understood. We found that the effects of acute high-dose edible cannabis consumption (AHDECC), which include decreased gamma power, hypothermia, hypolocomotion, analgesia, and learning and information processing impairments, are time and sex dependent. Moreover, these effects begin 2 hours after AHDECC and last for at least 24 hours, suggesting that treatments should target this time window in order to be effective.:




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Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice [Behavioral Pharmacology]

Low-efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO2 were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1 h. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics.

SIGNIFICANCE STATEMENT

This study used a novel set of mu opioid receptor (MOR)-selective opioids with graded MOR efficacies to examine the lower boundary of MOR efficacy sufficient to relieve pain-related behavioral depression in mice. Two novel low-efficacy opioids (JL-2-39, DC-1-76.1) produced effective antinociception with improved safety relative to higher- or lower-efficacy opioids, and results support further consideration of these and other low-efficacy opioids as candidate analgesics.




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Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons

A team of scientists from the Lunar and Planetary Laboratory at the University of Arizona, TU Delft, and Caltech has developed a new method to compute how tides affect the interiors of planets and moons in the Solar System.

The post Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons appeared first on Sci.News: Breaking Science News.




effects

How much should we worry about the health effects of microplastics?

A flurry of studies has found microplastics in nearly every organ in the human body, from the brain to the testicles. But very few have revealed whether these tiny bits of plastic impact our health





effects

Alemtuzumab: Its Effects on Cell Transplantation in Immune Deficient Asian Patients

Allogeneic hematopoietic cell transplantation (HCT) serves as a widely recognized curative treatment option for patients suffering from inborn errors of immunity (IEI).




effects

Why Do mRNA Vaccines Cause Side Effects?

Reasons why mRNA vaccines may cause side effects such as headaches and fevers have been finally identified by Australian researchers. This breakthrough




effects

Adverse Effects of Rheumatoid Arthritis Medicines on Pregnant Women and Fetus

Highlights: The study evaluated effects of Antirheumatic drugs on pregnant women diagnosed with rheumatoid arthriti




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Mental Health Parity and New Moms: Understanding the Effects

New research shows improved access to psychotherapy for pregnant and postpartum women struggling with depression and anxiety. Additionally, these women are now paying less out-of-pocket for treatment.




effects

Exploring the Effects of Likes on Young People's Mood

Young people are more sensitive to social media feedback than adults, with likes directly influencing their mood and engagement. This finding intensifies




effects

Iron Overload Effects on Mitochondrial DNA in - Thalassemia : Way Forward

Beta-thalassemia, also known as (and) #946;-thalassemia is a genetic disorder marked by reduced or absent beta chain synthesis of medlinkhemoglobin/medlink,




effects

Effects of Sit-Stand Desks on Health and Blood Pressure

Alternating between sitting and standing at work is effective in reducing medlinksedentary behavior/medlink, but it does not significantly lower medlinkblood




effects

PA cAARds! Initiative Combats Effects of Chronic Disease

PA cAARds! Initiative Combats Effects of Chronic Disease




effects

The Lingering Effects of Childhood BMI on Lung Health

In children abnormal BMI, whether too high or too low was found to be linked to impaired lung function. (!--ref1--) About 10 percent people suffer from poor lung function in childhood.




effects

Effects of Trans-Pacific Partnership on Pharmaceutical World

The Trans-Pacific Partnership (TPP) is a multi-national trade agreement now being considered by 12 countries. The ramifications of major components of