Optimising thermochemical energy storage: a comprehensive analysis of CaCO3 composites with CaSiO3, CaTiO3, and CaZrO3.

With the increasing amount of renewable energy produced, many governments and industries are pushing for the installation of battery energy storage system (BESS) solutions. Thermal batteries are systems that store heat made from various energy sources, and can be used to produce electricity upon demand. These systems are easily scalable and can be installed in cities, homes and remote locations. Thermochemical energy storage (TCES) uses the enthalpy of a chemical reaction to store and release heat through endothermic and exothermic processes, respectively. CaCO3 has been identified as an ideal TCES material as it is cheap and abundant, but maximising long-term cyclability is key to ensure battery longevity. This article investigates the addition of CaSiO3, CaTiO3 and CaZrO3 to CaCO3 in a 1 : 1 ratio to ascertain the reaction properties and cyclic capacity over time. Cycling longevity and thermodynamic properties were determined using simultaneous differential scanning calorimetry and thermogravimetric analysis (DSC-TGA) along with the Sieverts technique, and their reaction pathway studied by powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The low cost of the CaCO3-CaSiO3 material of $1.8 USD per kW hth suggests that if a suitable particle refinement agent were to be employed to ensure cycling longevity this material would be an excellent TCES material. Despite the CO2 cycling capacity of the CaCO3-CaZrO3 system only reducing by 16 wt% over 100 cycles, the cost of ZrO2 brings the materials cost to $30.9 USD per kW hth, making this material currently unsuitable for application. The CaCO3-CaTiO3 system showed only a 17% drop in total CO2 uptake over 100 cycles, although the cost was $11.1 USD per kW hth.

Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways.

We have previously demonstrated that the glucocorticoid receptor ß (GRß) isoform induces hepatic steatosis in mice fed a normal chow diet. The GRß isoform inhibits the glucocorticoid-binding isoform GRα, reducing responsiveness and inducing glucocorticoid resistance. We hypothesized that GRß regulates lipids that cause metabolic dysfunction. To determine the effect of GRß on hepatic lipid classes and molecular species, we overexpressed GRß (GRß-Ad) and vector (Vec-Ad) using adenovirus delivery, as we previously described. We fed the mice a normal chow diet for 5 days and harvested the livers. We utilized liquid chromatography-mass spectrometry (LC-MS) analyses of the livers to determine the lipid species driven by GRß. The most significant changes in the lipidome were monoacylglycerides and cholesterol esters. There was also increased gene expression in the GRß-Ad mice for lipogenesis, eicosanoid synthesis, and inflammatory pathways. These indicate that GRß-induced glucocorticoid resistance may drive hepatic fat accumulation, providing new therapeutic advantages.

Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia.

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1-2 years, 1-2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.

Conditional deletion of CEACAM1 causes hepatic stellate cell activation.

Objectives: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with MASH. Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARγ on CEACAM1 transcriptoin and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation. Methods: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre+Cc1 fl/fl mutants with conditional Ceacam1 deletion in HSCs and characterized their MASH phenotype. Media transfer experiments were employed to examine whether media from mutant human and murine HSCs activate their wild-type counterparts. Results: LratCre+Cc1 fl/fl mutants displayed hepatic inflammation and fibrosis but without insulin resistance or hepatic steatosis. Their HSCs, like KD-LX2 cells, underwent myofibroblastic transformation and their media activated wild-type HDCs. This was inhibited by nicotinic acid treatment which stemmed the release of IL-6 and fatty acids, both of which activate the epidermal growth factor receptor (EGFR) tyrosine kinase. Gefitinib inhibition of EGFR and its downstream NF-κB/IL-6/STAT3 inflammatory and MAPK-proliferation pathways also blunted HSCs activation in the absence of CEACAM1. Conclusions: Loss of CEACAM1 in HSCs provoked their myofibroblastic transformation in the absence of insulin resistance and hepatic steatosis. This response is mediated by autocrine HSCs activation of the EGFR pathway that amplifies inflammation and proliferation.

Human soluble prorenin receptor expressed in mouse renal collecting duct shows sex-specific effect on cardiorenal function.

Soluble prorenin receptor (sPRR), a component of the renin-angiotensin system (RAS), has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. Despite studies showing that sPRR in the kidney is produced by tubular cells in the renal collecting duct (CD), its biological actions modulating cardiorenal function in physiological conditions remain unknown. Therefore, the objective of our study was to investigate whether CD-derived human sPRR (HsPRR) expression influences cardiorenal function and examine sex and circadian differences. Thus, we investigated the status of the intrarenal RAS, water and electrolyte balance, renal filtration capacity, and blood pressure (BP) regulation in CD-HsPRR and control (CTL) mice. CD-HsPRR mice were generated by breeding human sPRR-Myc-tag mice with Hoxb7/Cre mice. Renal sPRR expression increased in CD-HsPRR mice, but circulating sPRR and RAS levels were unchanged compared with CTL mice. Only female littermates expressing CD-HsPRR showed 1) increased 24-h BP, 2) an impaired BP response to an acute dose of losartan and attenuated angiotensin II (ANG II)-induced hypertension, 3) reduced angiotensin-converting enzyme activity and ANG II content in the renal cortex, and 4) decreased glomerular filtration rate, with no changes in natriuresis and kaliuresis despite upregulation of the ß-subunit of the epithelial Na+ channel in the renal cortex. These cardiorenal alterations were displayed only during the active phase of the day. Taken together, these data suggest that HsPRR could interact with ANG II type 1 receptors mediating sex-specific, ANG II-independent renal dysfunction and a prohypertensive phenotype in a sex-specific manner.NEW & NOTEWORTHY We successfully generated a humanized mouse model that expresses human sPRR in the collecting duct. Collecting duct-derived human sPRR did not change circulating sPRR and RAS levels but increased daytime BP in female mice while showing an attenuated angiotensin II-dependent pressor response. These findings may aid in elucidating the mechanisms by which women show uncontrolled BP in response to antihypertensive treatments targeting the RAS, improving approaches to reduce uncontrolled BP and chronic kidney disease incidences in women.

Population genomics of harbour seal Phoca vitulina from northern British Columbia through California and comparison to the Atlantic subspecies.

The harbour seal Phoca vitulina is a ubiquitous pinniped species found throughout coastal waters of the Northern Hemisphere. Harbour seal impacts on ecosystem dynamics may be significant due to their high abundance and food web position. Two subspecies exist in North America, P. v. richardii in the Pacific Ocean and P. v. vitulina in the Atlantic. Strong natal philopatry of harbour seals can result in fine-scale genetic structure and isolation by distance. Management of harbour seals is expected to benefit from improved resolution of seal population structure and dynamics. Here, we use genotyping-by-sequencing to genotype 146 harbour seals from the eastern Pacific Ocean (i.e. British Columbia (BC), Oregon and California) and the western Atlantic Ocean (i.e. Québec, Newfoundland and Labrador). Using 12,742 identified variants, we confirm the recently identified elevated genetic diversity in the eastern Pacific relative to the western Atlantic and greatest differentiation between the subspecies. Further, we demonstrate that this is independent of reference genome bias or other potential technical artefacts. Coast-specific analyses with 8933 and 3828 variants in Pacific and Atlantic subspecies, respectively, identify divergence between BC and Oregon-California, and between Québec and Newfoundland-Labrador. Unexpected PCA outlier clusters were observed in two populations due to cryptic relatedness of individuals; subsequently, closely related samples were removed. Admixture analysis indicates an isolation-by-distance signature where Oregon seals contained some of the BC signature, whereas California did not. Additional sampling is needed in the central and north coast of BC to determine whether a discrete separation of populations exists within the region.

Establishing ZIF-8 as a reference material for hydrogen cryoadsorption: An interlaboratory study.

Hydrogen storage by cryoadsorption on porous materials has the advantages of low material cost, safety, fast kinetics, and high cyclic stability. The further development of this technology requires reliable data on the H2 uptake of the adsorbents, however, even for activated carbons the values between different laboratories show sometimes large discrepancies. So far no reference material for hydrogen cryoadsorption is available. The metal-organic framework ZIF-8 is an ideal material possessing high thermal, chemical, and mechanical stability that reduces degradation during handling and activation. Here, we distributed ZIF-8 pellets synthesized by extrusion to 9 laboratories equipped with 15 different experimental setups including gravimetric and volumetric analyzers. The gravimetric H2 uptake of the pellets was measured at 77 K and up to 100 bar showing a high reproducibility between the different laboratories, with a small relative standard deviation of 3-4 % between pressures of 10-100 bar. The effect of operating variables like the amount of sample or analysis temperature was evaluated, remarking the calibration of devices and other correction procedures as the most significant deviation sources. Overall, the reproducible hydrogen cryoadsorption measurements indicate the robustness of the ZIF-8 pellets, which we want to propose as a reference material.

Delivering Multidisciplinary Rehabilitation Care in Parkinson's Disease: An International Consensus Statement.

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder impacting everyday function and quality of life. Rehabilitation plays a crucial role in improving symptoms, function, and quality of life and reducing disability, particularly given the lack of disease-modifying agents and limitations of medications and surgical therapies. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research and guidelines demonstrating its positive effects. Currently, there is a lack of consensus regarding fundamental topics related to rehabilitative services in PD. OBJECTIVE: The goal of the international Parkinson's Foundation Rehabilitation Medicine Task Force was to develop a consensus statement regarding the incorporation of rehabilitation in PD care. METHODS: The Task Force, comprised of international multidisciplinary experts in PD and rehabilitation and people directly affected by PD, met virtually to discuss topics such as rehabilitative services, existing therapy guidelines and rehabilitation literature in PD, and gaps and needs. A systematic, interactive, and iterative process was used to develop consensus-based statements on core components of PD rehabilitation and discipline-specific interventions. RESULTS: The expert-based consensus statement outlines key tenets of rehabilitative care including its multidisciplinary approach and discipline-specific guidance for occupational therapy, physical therapy, speech language pathology/therapy, and psychology/neuropsychology across all PD stages. CONCLUSIONS: Rehabilitative interventions should be an essential component in the comprehensive treatment of PD, from diagnosis to advanced disease. Greater education and awareness of the benefits of rehabilitative services for people with PD and their care partners, and further evidence-based and scientific study are encouraged.

Neuromorphometric associations with mood, cognition, and self-reported exercise levels in epilepsy and healthy individuals.

Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p < 0.001), poorer mood (p = 0.029), and lower MoCA scores (p = 0.027) than HCs. These group differences were associated with reduced volume, decreased gyrification, and altered surface topology (IGEs < HCs) in frontal, temporal and cerebellar regions involved in executive function, memory retrieval, and emotional regulation, respectively. These preliminary results support the notion that increased PEL may promote neuroplasticity in IGEs, thus emphasizing the role of physical activity in promoting brain health in people with epilepsy.

Prepulse inhibition and the call alert in emergency medical services.

In emergency medical services, paramedics are informed of an emergency call by a high-intensity acoustic alarm called the "call alert." Sudden, loud sounds like the call alert may cause a startle response and be experienced as aversive. Studies have identified an association between the call alert and adverse health effects in first responders; conceivably, these adverse health effects might be reduced by modifying the call alert to blunt its startling and aversive properties. Here, we assessed whether the call alert causes a startle response and whether its startling and aversive properties are reduced when the call alert is preceded by a weak acoustic "prepulse," a process referred to as "prepulse inhibition" (PPI). Paramedics (n = 50; 34M:13F:3 not reported; ages 20-68) were exposed to four call alerts (two with and two without a prepulse) in counterbalanced order. Responses were measured using electromyography (measuring blink amplitude), visual analog scales (quantifying perceived call alert intensity and aversiveness), and an electrocardiogram (assessing heart rate). Paramedics responded to the call alert with a startle reflex blink and an increased heart rate. Acoustic prepulses significantly reduced the amplitude of the call alert-induced startle blink, the perceived sound intensity, and the perceived "dislike" of the call alert. These findings confirm that the call alert is associated with an acoustic startle response in paramedics; adding a prepulse to the call alert can reduce its startling and aversive properties. Conceivably, such reductions might also diminish adverse health effects associated with the call alert in first responders.

FOXS1 is increased in liver fibrosis and regulates TGFß responsiveness and proliferation pathways in human hepatic stellate cells.

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFß) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFß induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFß to activate fibrotic pathways, and FOXS1 mRNA was significantly increased. To study TGFß-FOXS1 signaling, we developed human LX2 FOXS1 CRISPR KO and scrambled control HSCs. To determine differentially expressed gene transcripts controlled by TGFß-FOXS1, we performed RNA-seq in the FOXS1 KO and control cells and over 400 gene responses were attenuated in the FOXS1 KO HSCs with TGFß-activation. To validate the RNA-seq findings, we used our state-of-the-art PamGene PamStation kinase activity technology that measures hundreds of signaling pathways nonselectively in real time. Using our RNA-seq data, kinase activity data, and descriptive measurements, we found that FOXS1 controls pathways mediating TGFß responsiveness, protein translation, and proliferation. Our study is the first to identify that FOXS1 may serve as a biomarker for liver fibrosis and HSC activation, which may help with early detection of hepatic fibrosis or treatment options for end-stage liver disease.

Producing Alkali Metal Hydrides from Hydroxides.

In this study, a novel method for producing different alkali metal hydrides (NaH, KH, RbH, and CsH) from their corresponding metal hydroxides (NaOH, KOH, RbOH, and CsOH) is presented. For the production of NaH from NaOH, a variety of metallic reducing agents (Mg, Al, Si, CaH2, Cr, Mn, and Sr) were investigated. The reactions took place in an autoclave reactor with paraffin oil at 250 °C and 14 bar of H2 pressure. Splitting the process into two steps (metal formation and hydrogenation) simplified the separation and purification for the produced metal hydride. Moreover, the study explores the potential for this method of NaH production to be used for NaBH4 production and regeneration for hydrogen export applications. This approach offers an alternative, cost-effective method for producing NaH.

Soft robotic apparel to avert freezing of gait in Parkinson's disease.

Freezing of gait (FoG) is a profoundly disruptive gait disturbance in Parkinson's disease, causing unintended stops while walking. Therapies for FoG reveal modest and transient effects, resulting in a lack of effective treatments. Here we show proof of concept that FoG can be averted using soft robotic apparel that augments hip flexion. The wearable garment uses cable-driven actuators and sensors, generating assistive moments in concert with biological muscles. In this n-of-1 trial with five repeated measurements spanning 6 months, a 73-year-old male with Parkinson's disease and substantial FoG demonstrated a robust response to robotic apparel. With assistance, FoG was instantaneously eliminated during indoor walking (0% versus 39 ± 16% time spent freezing when unassisted), accompanied by 49 ± 11 m (+55%) farther walking compared to unassisted walking, faster speeds (+0.18 m s-1) and improved gait quality (-25% in gait variability). FoG-targeting effects were repeatable across multiple days, provoking conditions and environment contexts, demonstrating potential for community use. This study demonstrated that FoG was averted using soft robotic apparel in an individual with Parkinson's disease, serving as an impetus for technological advancements in response to this serious yet unmet need.

Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats.

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl "high," alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 µg/kg/infusion) or withdrawal to our knowledge. We established a rat model of xylazine/fentanyl co-SA and withdrawal and evaluated outcomes as a function of biological sex. When administered alone, chronic xylazine (2.5 mg/kg, intraperitoneal) induced unique sex-specific withdrawal symptomatology, whereby females showed delayed onset of signs and a possible enhancement of sensitivity to the motor-suppressing effects of xylazine. Xylazine reduced fentanyl consumption in both male and female rats regardless of whether it was experimenter-administered or added to the intravenous fentanyl product (0.05, 0.10, and 0.5 mg/kg/infusion) when compared to fentanyl SA alone. Interestingly, this effect was dose-dependent when self-administered intravenously. Naloxone (0.1 mg/kg, subcutaneous injection) did not increase somatic signs of fentanyl withdrawal, regardless of the inclusion of xylazine in the fentanyl infusion in either sex; however, somatic signs of withdrawal were higher across time points in females after xylazine/fentanyl co-SA regardless of naloxone exposure as compared to females following fentanyl SA alone. Together, these results indicate that xylazine/fentanyl co-SA dose-dependently suppressed fentanyl intake in both sexes and induced a unique withdrawal syndrome in females that was not altered by acute naloxone treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Single Long-Incision Minimally Invasive Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of this study is to determine differences in outcomes in patients with adolescent idiopathic scoliosis undergoing spinal deformity correction surgery using a posterior spinal fusion (PSF) approach versus single and triple-incision minimally invasive surgery (MIS). SUMMARY OF BACKGROUND DATA: MIS increased in popularity as surgeons' focus moved towards soft tissue preservation, but it carries technical demands and increased surgical time compared with PSF. PATIENTS AND METHODS: Surgeries performed from 2016 to 2020 were included. Cohorts were formed based on surgical approach: PSF versus single long-incision MIS (SLIM) versus traditional MIS [3-incision MIS (3MIS)]. There were a total of 7 subanalyses. Demographic, radiographic, and perioperative data were collected for the 3 groups. Kruskal-Wallis and χ 2 tests were used for continuous and categorical variables, respectively. RESULTS: Five hundred thirty-two patients met our inclusion criteria, 294 PSF, 179 3MIS, and 59 SLIM.Estimated blood loss (mL) ( P < 0.00001) and length of stay (LOS) ( P < 0.00001) was significantly higher in PSF than in SLIM and 3MIS. Surgical time was significantly higher in 3MIS than in PSF and SLIM ( P = 0.0012).Patients who underwent PSF had significantly lower postoperative T5 to T12 kyphosis ( P < 0.00001) and percentage kyphosis change ( P < 0.00001). Morphine equivalence was significantly higher in the PSF group during total hospital stay ( P = 0.0042).Patients who underwent SLIM and 3MIS were more likely to return to noncontact ( P = 0.0096) and contact sports ( P = 0.0095) within 6 months and reported lower pain scores ( P < 0.001) at 6 months postoperation. CONCLUSION: SLIM has a similar operative time to PSF and is technically similar to PSF while maintaining the surgical and postoperative outcome advantages of 3MIS.

Tobacco withdrawal-induced changes in sensorimotor filtering as a predictor of smoking lapse in trauma-exposed individuals.

Prepulse inhibition (PPI) is a measure of sensorimotor filtering thought to shield the processing of initial weaker auditory stimuli from interruption by a later startle response. Previous studies have shown smoking withdrawal to have a negative impact on sensorimotor filtering, particularly in individuals with psychopathology. Because tobacco use may alleviate sensory and sensorimotor filtering deficits, we examined whether smoking withdrawal-induced changes in PPI were associated with maintenance of smoking abstinence in trauma-exposed individuals with and without PTSD who were attempting to quit smoking. Thirty-eight individuals (n = 24 with current or past PTSD; 14 trauma-exposed healthy controls) made an acute biochemically-verified smoking cessation attempt supported by 8 days of contingency management (CM) and cognitive behavioral therapy (CBT) for smoking. Participants completed a PPI task at the pre-quit baseline, 2 days post-quit, and 5 days post-quit. Post-quit changes in PPI were compared between those who remained abstinent for the first 8-days of the quit attempt and those who lapsed back to smoking. PPI changes induced by biochemically-verified smoking abstinence were associated with maintenance of abstinence across the 8-day CM/CBT-supported quit attempt. As compared to those who maintained tobacco abstinence, participants who lapsed to smoking had significantly lower PPI at 2 and 5 days post-quit relative to baseline. Thus, among trauma-exposed individuals, decreases in PPI during acute smoking cessation supported by CM/CBT are associated with lapse back to smoking. Interventions that improve PPI during early smoking abstinence may facilitate smoking cessation among such individuals who are at high risk for chronic, refractory tobacco use.

Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine.

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.

Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.

The normal stress response in humans is governed by the hypothalamic-pituitary-adrenal (HPA) axis through heightened mechanisms during stress, raising blood levels of the glucocorticoid hormone cortisol. Glucocorticoids are quintessential compounds that balance the proper functioning of numerous systems in the mammalian body. They are also generated synthetically and are the preeminent therapy for inflammatory diseases. They act by binding to the nuclear receptor transcription factor glucocorticoid receptor (GR), which has two main isoforms (GRα and GRß). Our classical understanding of glucocorticoid signaling is from the GRα isoform, which binds the hormone, whereas GRß has no known ligands. With glucocorticoids being involved in many physiological and cellular processes, even small disruptions in their release via the HPA axis, or changes in GR isoform expression, can have dire ramifications on health. Long-term chronic glucocorticoid therapy can lead to a glucocorticoid-resistant state, and we deliberate how this impacts disease treatment. Chronic glucocorticoid treatment can lead to noticeable side effects such as weight gain, adiposity, diabetes, and others that we discuss in detail. There are sexually dimorphic responses to glucocorticoids, and women tend to have a more hyperresponsive HPA axis than men. This review summarizes our understanding of glucocorticoids and critically analyzes the GR isoforms and their beneficial and deleterious mechanisms and the sexual differences that cause a dichotomy in responses. We also discuss the future of glucocorticoid therapy and propose a new concept of dual GR isoform agonist and postulate why activating both isoforms may prevent glucocorticoid resistance.

Feeding Ractopamine Improves the Growth Performance and Carcass Characteristics of the Lard-Type Mangalica Pig.

Mangalica pigs are gaining popularity within the U.S. as a niche breed, given their reputation for superior-quality pork. However, slow growth rates, a poor lean yield, and excessive adiposity limit the widespread adoption of Mangalica. To determine if feeding the metabolic modifier, ractopamine hydrochloride (RAC), would improve growth performance without impairing pork quality in the Mangalica, pigs were fed either 0 or 20 mg per kg RAC for 21 days. At 24 h postharvest, pork quality and carcass composition measurements were recorded; then, primal cuts were fabricated and assessed. RAC increased ADG (p < 0.04) and gain efficiency (p < 0.03) by 24% and 21%, respectively. RAC increased Loin Eye Area (p < 0.0001) by 21% but did not impact the 10th rib fat depth (p > 0.90) or marbling score (p > 0.77). RAC failed to alter any primal cut weights. Feeding RAC lowered b* values (p < 0.04) and tended to lower L* values (p < 0.08) while not affecting a* values (p > 0.30), suggesting RAC darkened loin color. Finally, RAC decreased cook yield percentage (p < 0.02) by 11% without impacting Warner-Bratzler Shear Force (p > 0.31). These data support the hypothesis that feeding RAC to Mangalica improves growth performance without impairing pork quality in this breed.

Stannaborates: tuning the ion conductivity of dodecaborate salts with tin substitution.

Metal substituted dodecaborate anions can be coupled with alkali metal cations to have great potential as solid-state ion conductors for battery applications. A tin atom can replace a B-H unit within an unsubstituted dodecaborate cage to produce a stable, polar divalent anion. The chemical and structural change in forming a stannaborate results in a modified crystal structure of respective group 1 metal salts, and as a result, improves the material's ion conductivity. Li2B11H11Sn shows high ion conductivity of ∼8 mS cm-1 at 130 °C, similar to the state-of-the-art LiCB11H12 at these temperatures, however, obtaining high ion conductivity at room temperature is not possible with pristine alkali metal stannaborates.