Therapeutic potential of Capparis spinosa in experimental model of acute acetic acid-induced colitis: Anti-inflammatory and antioxidant effects.

Introduction: This study examined the anti-inflammatory and antioxidant properties of Capparis spinosa L. (caper) in order to determine its medicinal potential in the treatment of acute colitis. Method: Sixty male rats were divided into six groups. After the experimental period, distal colonic extension was collected for determination of colonic damage, oxidative stress markers, along with antioxidant markers. The impact of altered levels of inflammatory cytokines in colon tissues on the underlying mechanisms examined. Results: The results showed that administering different doses of caper led to significant decreases in TNF-α and IL-6 levels when compared to the control colitis group (p < 0.001). Caper treatment effectively lowered elevated oxidative stress factors (MDA, NO, and MPO) compared to the control colitis group (p < 0.001). Caper treatment resulted in a significant increase in antioxidant factors (CAT, SOD, and GSH) compared with the control colitis group (p < 0.001).Significant improvements in tissue repair were observed in caper-treated groups compared to positives and control colitis (p < 0.001). Conclusion: The study highlights caper may be useful in the treatment of acute colitis due to its ameliorative effects on inflammation, oxidative stress, and tissue repair.

Role of orphan G-protein coupled receptors in tissue ischemia: A comprehensive review.

Ischemic events lead to many diseases and deaths worldwide. Ischemia/reperfusion (I/R) occurs due to reduced blood circulation in tissues followed by blood reflow. Reoxygenation of ischemic tissues is characterized by oxidative stress, inflammation, energy distress, and endoplasmic reticulum stress. There are still no adequate clinical protocols or pharmacological approaches to address the consequences of I/R damage. G protein-coupled receptors (GPCRs) are important therapeutic targets. They compose a large family of seven transmembrane-spanning proteins that are involved in many biological functions. Orphan GPCRs are a large subgroup of these receptors expressed in different organs. In the present review, we summarized the literature regarding the role of orphan GPCRs in I/R in different organs. We focused on the effect of these receptors on modulating cellular and molecular processes underlying ischemia including apoptosis, inflammation, and autophagy. The study showed that GPR3, GPR4, GPR17, GPR30, GPR31, GPR35, GPR37, GPR39, GPR55, GPR65, GPR68, GPR75, GPR81, and GPR91 are involved in ischemic events, mainly in the brain and heart. These receptors offer new possibilities for treating I/R injuries in the body.

Anxiety, a significant risk factor for coronary artery disease: what is the best index.

BACKGROUND: Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders that substantially impact global health. Iran ranks among the countries with a high incidence of CAD and anxiety disorders. Therefore, the present study aims to determine the potential association and epidemiological aspects of anxiety and CAD within the population of Mashhad, the second most popoulos city in Iran. METHODS: The present study is based on extracted data from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study which is a 10-year prospective cohort study intended to assess the effects of various CAD risk factors among Mashhad city residents. Anxiety scores were assessed at the baseline using Beck Anxiety Inventory and individuals were classified based on the BAI 4-factor structure model which included autonomic, cognitive, panic, and neuromotor components. Accordingly, the association between baseline anxiety scores and the BAI four-factor model with the risk of CAD events was analyzed using SPSS software version 21. RESULTS: Based on the results, 60.4% of the sample were female, and 5.6% were classified as having severe forms of anxiety. Moreover, severe anxiety was more prevalent in females. Results showed a 1.7% risk of CAD (p-value < 0.001) over 10 years with one unit increase in anxiety score. Based on the 4-factor model structure, we found that only panic disorder could significantly increase the risk of CAD by 1.1% over the 10-year follow-up (p-value < 0.001). CONCLUSION: Anxiety symptoms, particularly panic disorder, are independently and significantly associated with an increased overall risk of developing CAD over a 10-year period. Therefore, further studies are warranted to investigate the mechanisms through which anxiety may cause CAD, as well as possible interventions to mitigate these processes.

Recent Advances in the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a complex, multifaceted, progressive, and yet incurable complication that can cause irreversible damage to the individual, family, and society. In recent years strategies for the management and rehabilitation of SCI besides axonal regeneration, remyelination, and neuronal plasticity of the injured spinal cord have significantly improved. Although most of the current research and therapeutic advances have been made in animal models, so far, no specific and complete treatment has been reported for SCI in humans. The failure to treat this complication has been due to the inherent neurological complexity and the structural, cellular, molecular, and biochemical characteristics of spinal cord injury. In this review, in addition to elucidating the causes of spinal cord injury from a molecular and pathophysiological perspective, the complexity and drawbacks of neural regeneration that lead to the failure in SCI treatment are described. Also, recent advances and cutting-edge strategies in most areas of SCI treatment are presented.

Evaluation of Melatonin and its Nanostructures Effects on Skin Disorders Focused on Wound Healing.

Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin's effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.

Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial.

BACKGROUND: Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. METHOD: Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. RESULTS: The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS. CONCLUSION: Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.

Evaluating the Protective Effects of Thymoquinone on Methamphetamine-induced Toxicity in an In Vitro Model Based on Differentiated PC12 Cells.

Methamphetamine (Meth) is a highly addictive stimulant. Its potential neurotoxic effects are mediated through various mechanisms, including oxidative stress and the initiation of the apoptotic process. Thymoquinone (TQ), obtained from Nigella sativa seed oil, has extensive antioxidant and anti-apoptotic properties. This study aimed to investigate the potential protective effects of TQ against Meth-induced toxicity by using an in vitro model based on nerve growth factor-differentiated PC12 cells. Cell differentiation was assessed by detecting the presence of a neuronal marker with flow cytometry. The effects of Meth exposure were evaluated in the in vitro neuronal cell-based model via the determination of cell viability (in an MTT assay) and apoptosis (by annexin/propidium iodide staining). The generation of reactive oxygen species (ROS), as well as the levels of glutathione (GSH) and dopamine, were also determined. The model was used to determine the protective effects of 0.5, 1 and 2 µM TQ against Meth-induced toxicity (at 1 mM). The results showed that TQ reduced Meth-induced neurotoxicity, possibly through the inhibition of ROS generation and apoptosis, and by helping to maintain GSH and dopamine levels. Thus, the impact of TQ treatment on Meth-induced neurotoxicity could warrant further investigation.

Buprenorphine induced opioid withdrawal syndrome relieved by adjunctive Magnesium: A clinical trial.

INTRODUCTION: Precipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO4) as an NMDA receptor antagonist on OWS. MATERIALS AND METHODS: The study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups. The control group received conventional therapies, including clonidine 0.1 mg tablet each hour, intravenous infusion of 10 mg diazepam every 30 min, and IV paracetamol (Acetaminophen) 1 g, while the intervention group received 3 g of MGSO4 in 20 min and then 10 mg/kg/h up to 2 h, in addition to the conventional treatment. The clinical opiate withdrawal scale (COWS) evaluated OWS at the start of the treatment, 30 min, and 2 h later. RESULTS: Both groups had similar demographic, opiate types, and COWS severity at the start of the intervention. COWS was lower in the intervention than the control group at 30 min (11.20 ± 2.86 and 14.65 ± 2.36, respectively, P = 0.002) and at 2 h (3.2 ± 1.61 and 11.25 ± 3.27, respectively, P < 0.001) after treatment. The intervention group received lesser doses of clonidine (0.12 ± 0.51 and 0.17 ± 0.45 mg, P = 0.003) and Diazepam (13.50 ± 5.87, 24.0 ± 6.80 mg, P = 0.001) than the control group. Serum magnesium levels raised from 1.71 ± 0.13 mmol/L to 2.73 ± 0.13 mmol/L in the intervention group. CONCLUSION: Magnesium can significantly reduce the severity of OWS. Additional studies are required to confirm these results.

Treatment of high dose of intravenous midazolam abuse: a case report.

This study reports a rare case of high-dose midazolam abuse and Munchausen Syndrome. A 48-year-old female physician was referred by a psychiatrist to the Toxicology Department of Imam Reza Hospital for abstaining from 300 mg/day of parenteral midazolam. She had mimicked the symptoms of Crohn's disease; therefore, she had undergone 15 colonoscopies and 40 times MRI or CT scan, all of which were normal. Six months earlier, she had switched oral methadone to 30 mg/day of intravenous midazolam. She also had several skin lesions on injection sites that she considered pyoderma gangrenosum. When the total daily dose of intravenous midazolam was switched to oral bioequivalence of clonazepam, she could not tolerate withdrawal (Clinical Institute Withdrawal Assessment Scale-Benzodiazepines = 68). Therefore, she received midazolam again as a continuous intravenous infusion. Within 7 days, the whole dose was replaced by the bioequivalence oral dose of clonazepam. She was also treated with carbamazepine and cognitive behavior therapy. Afterward, she was transferred to the psychiatric ward for further psychiatric treatment. Dependency on a high dose of midazolam could be treated by tapering off the long-acting benzodiazepine.

White blood cell and platelet distribution widths are associated with hypertension: data mining approaches.

In this paper, we are going to investigate the association between Hypertension (HTN) and routine hematologic indices in a cohort of Iranian adults. The data were obtained from a total population of 9704 who were aged 35-65 years, a prospective study was designed. The association between hematologic factors and HTN was assessed using logistic regression (LR) analysis and a decision tree (DT) algorithm. A total of 9704 complete datasets were analyzed in this cohort study (N = 3070 with HTN [female 62.47% and male 37.52%], N = 6634 without HTN [female 58.90% and male 41.09%]). Several variables were significantly different between the two groups, including age, smoking status, BMI, diabetes millitus, high sensitivity C-reactive protein (hs-CRP), uric acid, FBS, total cholesterol, HGB, LYM, WBC, PDW, RDW, RBC, sex, PLT, MCV, SBP, DBP, BUN, and HCT (P < 0.05). For unit odds ratio (OR) interpretation, females are more likely to have HTN (OR = 1.837, 95% CI = (1.620, 2.081)). Among the analyzed variables, age and WBC had the most significant associations with HTN OR = 1.087, 95% CI = (1.081, 1.094) and OR = 1.096, 95% CI = (1.061, 1.133), respectively (P-value < 0.05). In the DT model, age, followed by WBC, sex, and PDW, has the most significant impact on the HTN risk. Ninety-eight percent of patients had HTN in the subgroup with older age (≥58), high PDW (≥17.3), and low RDW (<46). Finally, we found that elevated WBC and PDW are the most associated factor with the severity of HTN in the Mashhad general population as well as female gender and older age.

Crosslinked hydrogel loaded with chitosan-supported iron oxide and silver nanoparticles as burn wound dressing.

Burns can result in infection, disability, psychosocial and economic issues. Advanced wound dressings like hydrogel absorb exudate and maintain moisture. Considering the antimicrobial properties of silver nanoparticles and iron oxide nanoparticles, the efficiency of cross-linked hydrogel loaded with chitosan-supported iron oxide and silver nanoparticles for burn wounds repair was investigated in animal model. Cellulose hydrogel dressing made from carboxymethylcellulose and hydroxyethylcellulose crosslinked with different concentrations of citric acid (10, 15, 20, and 30%) was produced. The physicochemical characteristics of the synthetized hydrogels including Fourier-Transform Infrared spectroscopy, Thermal behavior, Swelling properties, and Scanning Electron Microscope (SEM) were evaluated. The silver nanoparticles and iron nanoparticles were produced and the characteristics, cytotoxicity, antimicrobial activities and their synergistic effect were investigated. After adding nanoparticles to hydrogels, the effects of the prepared wound dressings were investigated in a 14-day animal model of burn wound. The results showed that the mixture comprising 12.5 ppm AgNps, and IONPs at a concentration ≤100 ppm was non-cytotoxic. Moreover, the formulations with 20% CA had a swelling ratio of almost 250, 340, and 500 g/g at pHs of 5, 6.2, and 7.4 after one hour, which are lower than those of formulations with 5 and 10% CA. The total mass loss (59.31%) and the exothermic degradation happened in the range of 273-335 °C and its Tm was observed at 318.52 °C for hydrogels with 20% CA. Thus, the dressing comprising 20% CA which was loaded with 12.5 ppm silver nanoparticles (AgNPs) and 100 ppm iron oxide nanoparticles (IONPs) indicated better physicochemical, microbial and non-cytotoxic characteristics, and accelerated the process of wound healing after 14 days. It was concluded that the crosslinked hydrogel loaded with 12.5 ppm AgNPs and 100 ppm IONPs possesses great wound healing activity and could be regarded as an effective topical burn wound healing treatment.

Longitudinal Recovery Following Repetitive Traumatic Brain Injury.

Importance: One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited. Objective: To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years. Design, Setting, and Participants: This cohort study included participants presenting to emergency departments enrolled within 24 hours of TBI in the prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years, February 2014 to July 2020). Participants who completed outcome assessments at 1 year and 3 to 7 years were included. Data were analyzed from September 2022 to August 2023. Exposures: Postindex TBI(s). Main Outcomes and Measures: Demographic and clinical factors, prior TBI (ie, preindex TBI), and functional (Glasgow Outcome Scale-Extended [GOSE]), postconcussive (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]), psychological distress (Brief Symptom Inventory-18 [BSI-18]), depressive (Patient Health Questionnaire-9 [PHQ-9]), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 [PCL-5]), and health-related quality-of-life (Quality of Life After Brain Injury-Overall Scale [QOLIBRI-OS]) outcomes were assessed. Adjusted mean differences (aMDs) and adjusted relative risks are reported with 95% CIs. Results: Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%] male; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. A total of 50 (3.2%) and 132 (12.2%) reported 1 or more postindex TBIs at 1 year and 3 to 7 years, respectively. Risk factors for postindex TBI were psychiatric history, preindex TBI, and extracranial injury severity. At 1 year, compared with those without postindex TBI, participants with postindex TBI had worse functional recovery (GOSE score of 8: adjusted relative risk, 0.57; 95% CI, 0.34-0.96) and health-related quality of life (QOLIBRI-OS: aMD, -15.9; 95% CI, -22.6 to -9.1), and greater postconcussive symptoms (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress symptoms (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), depression symptoms (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4), and PTSD symptoms (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4). At 3 to 7 years, these associations remained statistically significant. Multiple (2 or more) postindex TBIs were associated with poorer outcomes across all domains. Conclusions and Relevance: In this cohort study of patients with acute TBI, postindex TBI was associated with worse symptomatology across outcome domains at 1 year and 3 to 7 years postinjury, and there was a dose-dependent response with multiple postindex TBIs. These results underscore the critical need to provide TBI prevention, education, counseling, and follow-up care to at-risk patients.

Effects of multiple doses of montmorillonite, alone and in combination with activated charcoal, on the toxicokinetics of a single dose of digoxin in rats.

Objectives: A narrow margin between the therapeutic and toxic doses of digoxin can result in an increased incidence of toxicity. Since digoxin has an enterohepatic cycle, multiple oral doses of absorbents like montmorillonite may be useful in the treatment of digoxin toxicity. Materials and Methods: In this study, 4 groups of 6 rats received intraperitoneal digoxin (1 mg/kg), and half an hour later, distilled water (DW) or oral adsorbents, including montmorillonite (1 g/kg), activated charcoal (1 g/kg) (AC) alone or in combination in the ratio of 70:30. Half of the mentioned doses were also gavaged at 3 and 5.5 hr after digoxin injection. The serum level of digoxin, biochemical factors, and activity score were assessed during the experiment. Three control groups only received DW, montmorillonite, or AC. Results: All adsorbents were able to significantly decrease the serum level of digoxin compared to the digoxin+DW group (P<0.01). Only montmorillonite reversed the digoxin-induced hyperkalemia (P<0.05). Multiple dose administration of adsorbents also significantly reduced the digoxin area under the curve and half-life and increased digoxin clearance (P<0.05). However, there was no significant difference in the kinetic parameters between groups that received digoxin plus adsorbents. Conclusion: Multiple-dose of montmorillonite reversed digoxin toxicity and reduced serum digoxin levels by increasing the excretion and reducing the half-life. Montmorillonite has also corrected digoxin-induced hyperkalemia. Based on the findings, a multiple-dose regimen of oral montmorillonite could be a suitable candidate for reducing the toxicity issue associated with drugs like digoxin that undergo some degree of enterohepatic circulation.

Efficacy of orally administered montmorillonite in myoglobinuric acute renal failure model in male rats.

Objectives: Acute kidney injury can be associated with serious consequences and therefore early treatment is critical to decreasing mortality and morbidity rate. We evaluated the effect of montmorillonite, the clay with strong cation exchange capacity, on the AKI model in rats. Materials and Methods: Glycerol (50% solution, 10 ml/kg) was injected in the rat hind limbs to induce AKI. 24 hr after induction of acute kidney injury, the rats received oral doses of montmorillonite (0.5 g/kg or 1 g/kg), or sodium polystyrene sulfonate (1 g/kg) for three consecutive days. Results: Glycine induced acute kidney injury in rats with high levels of urea (336.60± 28.19 mg/dl), creatinine (4.10± 0.21 mg/dl), potassium (6.15 ± 0.28 mEq/L), and calcium (11.52 ± 0.19 mg/dl). Both doses of montmorillonite (0.5 and 1 g/kg) improved the serum urea (222.66± 10.02 and 170.20±8.06, P<0.05), creatinine (1.86±0.1, 2.05± 0.11, P<0.05), potassium (4.68 ± 0.4, 4.73 ± 0.34, P<0.001) and calcium (11.15 ± 0.17, 10.75 ± 0.25, P<0.01) levels. Treatment with montmorillonite especially at a high dose reduced the kidney pathological findings including, tubular necrosis, amorphous protein aggregation, and cell shedding into the distal and proximal tubule lumen. However, administration of SPS could not significantly decrease the severity of damages. Conclusion: According to the results of this study, as well as the physicochemical properties of montmorillonite, such as high ion exchange capacity and low side effects, montmorillonite can be a low-cost and effective treatment option to reduce and improve the complications of acute kidney injury. However, the efficacy of this compound in human and clinical studies needs to be investigated.

Effect of citalopram and sertraline on the expression of miRNA- 124, 132, and 16 and their protein targets in patients with depression.

Objectives: This study aimed to evaluate the effect of SSRIs on the expression of miRNAs and their protein targets. Materials and Methods: In a 100 day open-label study of citalopram (n=25) and sertraline (n=25), levels of miRNA 16, 132, and 124 and glucocorticoid receptor (GR), Brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) protein expression were measured by QRT-PCR and western blot in healthy control (n=20), patients with depression at the baseline, and same patients after 100 days of treatment. Results: Expression levels of GR and BDNF proteins were lower in the depressed group before treatment as compared with the healthy group (P<0.0001). The SERT level was higher among the depressed group before treatment in comparison with the healthy group (P<0.0001). The level of GR and BDNF significantly increased, and SERT expression decreased after receiving sertraline (P<0.05). When the depressed group received citalopram, only SERT and GR were altered (P<0.05). Among the microRNAs' expression investigated, mir-124 and mir-132 were higher, and mir-16 was lower among the depressed compared with the healthy group (P<0.0001). Individuals receiving citalopram only showed an increase in the expression of mir-16 while administration of sertraline led to a significant increase in the expression of mir-16 and a decrease in mir-124 and mir-132 (P<0.05). Conclusion: This elucidated the relationship between antidepressant treatment and the expression of different microRNA that control gene expression in various pathways involved in depressed patients. Receiving SSRI can affect the level of these proteins and their relevant microRNAs.

The role of the ATP-Binding Cassette A1 (ABCA1) in neurological disorders: a mechanistic review.

INTRODUCTION: Cholesterol homeostasis is critical for normal brain function. It is tightly controlled by various biological elements. ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that effluxes cholesterol from cells, particularly astrocytes, into the extracellular space. The recent studies pertaining to ABCA1's role in CNS disorders were included in this study. AREAS COVERED: In this comprehensive literature review, preclinical and human studies showed that ABCA1 has a significant role in the following diseases or disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, neuropathy, anxiety, depression, psychosis, epilepsy, stroke, and brain ischemia and trauma. EXPERT OPINION: ABCA1 via modulating normal and aberrant brain functions such as apoptosis, phagocytosis, BBB leakage, neuroinflammation, amyloid ß efflux, myelination, synaptogenesis, neurite outgrowth, and neurotransmission promotes beneficial effects in aforementioned diseases. ABCA1 is a key molecule in the CNS. By boosting its expression or function, some CNS disorders may be resolved. In preclinical studies, liver X receptor agonists have shown promise in treating CNS disorders via ABCA1 and apoE enhancement.

An overview on nanoplatforms for statins delivery: Perspectives for safe and effective therapy.

Statins are the most widely used pharmacological agents for reducing blood cholesterol levels and treating atherosclerotic cardiovascular diseases. Most of the statins' derivatives have been limited by water solubility, bioavailability, and oral absorption, which has led to adverse effects on several organs, especially at high doses. As an approach to reducing statin intolerance, achieving a stable formulation with improved efficacy and bioavailability at low doses has been suggested. Nanotechnology-based formulations may provide a therapeutic benefit over traditional formulations in terms of potency and biosafety. Nanocarriers can provide tailored delivery platforms for statins, thereby enhancing the localized biological effects and lowering the risk of undesired side effects while boosting statin's therapeutic index. Furthermore, tailored nanoparticles can deliver the active cargo to the desired site, which culminates in reducing off-targeting and toxicity. Nanomedicine could also provide opportunities for therapeutic methods by personalized medicine. This review delves into the existing data on the potential improvement of statin therapy using nano-formulations.

Mucocutaneous alterations and complications in amphetamine abusers: a narrative review.

Amphetamines are the second most commonly used illicit drug worldwide. Amphetamine use can result in significant cutaneous morbidity. This review highlights the dermatological manifestations of amphetamine abuse.

Socioeconomic and clinical factors associated with prolonged hospital length of stay after traumatic brain injury.

BACKGROUND: Hospital length of stay (HLOS) after traumatic brain injury (TBI) is a metric of injury severity, resource utilization, and access to services. This study aimed to evaluate socioeconomic and clinical factors associated with prolonged HLOS after TBI. METHODS: Retrospective data from adult hospitalized patients diagnosed with acute TBI at a US Level 1 trauma center between August 1, 2019 - April 1, 2022 were extracted from the electronic health record. HLOS was stratified by Tier (1: 1-74th percentile; 2: 75-84th; 3: 85-94th; 4: 95-99th). Demographic, socioeconomic, injury severity, and level-of-care factors were compared by HLOS. Multivariable logistic regressions evaluated associations between socioeconomic and clinical variables and prolonged HLOS, using multivariable odds ratios (mOR) and [95% confidence intervals]. Estimated daily charges were calculated for a subset of medically-stable inpatients awaiting placement. Statistical significance was assessed at p < 0.05. RESULTS: In 1443 patients, median HLOS was 4 days (interquartile range 2-8; range 0-145). HLOS Tiers were 0-7, 8-13, 14-27, and ≥28 days (Tiers 1-4, respectively). Patients with Tier 4 HLOS differed significantly from others, with increased Medicaid insurance (53.4% vs. 30.3-33.1%, p = 0.003), severe TBI (Glasgow Coma Scale 3-8: 38.4% vs. 8.7-18.2%, p < 0.001), younger age (mean 52.3-years vs. 61.1-63.7-years, p = 0.003), low socioeconomic status (53.4% vs. 32.0-33.9%, p = 0.003), and need for post-acute care (60.3% vs. 11.2-39.7%, p < 0.001). Independent factors associated with prolonged (Tier 4) HLOS were Medicaid (mOR = 1.99 [1.08-3.68], vs. Medicare/commercial), moderate and severe TBI (mOR = 3.48 [1.61-7.56]; mOR = 4.43 [2.18-8.99], respectively, vs. mild TBI), and need for post-acute placement (mOR = 10.68 [5.74-19.89], while age was protective (per-year mOR = 0.98 [0.97-0.99]). Estimated daily charges for a medically-stable inpatient was $17126. CONCLUSIONS: Medicaid insurance, moderate/severe TBI, and need for post-acute care were independently associated with prolonged HLOS ≥28 days. Medically-stable inpatients awaiting placement accrue immense daily healthcare costs. At-risk patients should be identified early, receive care transitions resources, and be prioritized for discharge coordination pathways.

A qualitative assessment of factors contributing to Spanish-speaking federally qualified health center patients' chronic pain experiences.

People of Hispanic or Latino ethnicity (Latinx people) experience pain diagnosis, treatment, and care disparities relative to non-Latinx Whites. Those whose preferred language is Spanish may experience additional disparities when receiving care in a language-discordant environment. In order to better understand medically underserved Spanish-speaking Latinx patients' pain care experience in primary care, we conducted semi-structured qualitative interviews with federally qualified health center staff members (n = 9) and Spanish-speaking adult Latinx patients with chronic pain (n = 12) to capture data on their perspectives. Interview data were mapped to the individual (microsystem), interpersonal (mesosystem), organizational (exosystem), and environmental (macrosystem) levels of Bronfenbrenner's Ecological Systems Theory and analyzed using thematic content analysis informed by the Framework Method. Findings suggest that Spanish-speaking patients and English-speaking care team members may interpret information about pain state and severity differently, may have misaligned expectations about care, treatment methodologies, and treatment goals, and may experience difficulty forming a mutual understanding during health care encounters due to cross-linguistic and cross-cultural miscommunication. Patients preferred to describe their pain in words rather than with numbers or standardized scales, and both patients and frontline care team members expressed frustration with medical interpretation services, which added time and complexity to visits. Patients and health center staff emphasized the diversity of experiences among Spanish-speaking Latinx people, and the need to account for both linguistic and cultural differences during care encounters. Both groups supported hiring more Spanish-speaking, Latinx healthcare personnel who better resemble the patient population, which has the potential to improve linguistic and cultural concordance and competence, with the aim of improving care outcomes and patient satisfaction. Further study is warranted to examine how linguistic and cultural communication barriers impact pain assessment and treatment in primary care, the extent to which patients feel understood by their care teams, and their confidence in their ability to understand and interpret treatment recommendations.