Pharmacological Treatment Research Articles

Abstract 4136786: Prediabetes increases platelet activation and thrombotic susceptibility via mitochondrial oxidants

Recent studies suggest that prediabetes is not only a prelude to diabetes, but also is an independent risk factor for cardiovascular thrombotic events in young and aged people. However, the mechanisms that may promote platelet activation and thrombosis during prediabetes have not been studied. We hypothesized that in prediabetes, dysregulation of electron transfer and accumulation of mitochondrial oxidants promotes platelet activation and thrombosis, and that aging exacerbates the phenotype. We recruited young (18-50 year) and middle-aged (51-64 year) Veterans with prediabetes and age- and BMI- matched healthy Veterans. Compared to healthy cohort, platelets from prediabetes exhibited enhanced agonist induced platelet activation, mitochondrial oxidants, membrane potential and thrombus formation ex vivo in both young and middle-aged cohorts to a similar extent. Preincubation of platelets with either a mitochondria targetable superoxide dismutase (SOD) mimetic or MitoQ (transfers electrons from Complex I/II to complex III to lower superoxide generation within mitochondria), rescued the prothrombotic phenotype. We confirmed these platelet phenotypes in C57BL6/J mice fed high fat (HF) diet for 2 weeks (model of early diabetes). Importantly, HF-fed mice showed increased susceptibility to carotid artery and pulmonary thrombosis in vivo . Pharmacological treatment of HF-fed mice with SOD-mimetic or MitoQ, or genetic overexpression of catalase within mitochondria, rescued the prothrombotic state. This is the first report showing platelet hyperactivity and enhanced thrombotic susceptibility in prediabetes. Further, our findings suggest that enhanced mitochondrial oxidants due to the premature electron escape contribute to the phenotype. Our data imply a therapeutic potential of SOD-mimetic and MitoQ in lowering thrombotic burden in prediabetes.

Managing emotional and physical stress in sickle cell anemia: a review of effective strategies and approaches

Sickle cell anemia (SCA) is a genetic blood disorder characterized by recurrent pain episodes, chronic complications, and significant emotional and physical stress. This review article explores effective strategies for managing both the emotional and physical aspects of stress in SCA patients. A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar, using keywords such as “sickle cell anemia,” “stress management,” “psychological support,” and “pain management.” Emotional stress in SCA arises from chronic pain, frequent hospitalizations, and disease uncertainty, leading to conditions such as anxiety and depression. Effective management of emotional stress involves a combination of psychological counseling, cognitive-behavioral therapy (CBT), and support groups, which help patients develop coping strategies and address the mental health challenges of living with a chronic illness. This review evaluates various psychological interventions and their impact on patient outcomes, emphasizing the need for integrated mental health support in the management of SCA. Physical stress in SCA is primarily due to acute vaso-occlusive crises and chronic pain, which require effective pain management and preventive measures. The review explores pharmacological treatments, such as opioids and hydroxyurea, as well as non-pharmacological approaches, including physical therapy and lifestyle modifications. Additionally, the article discusses innovative therapies like gene therapy and stem cell transplantation, which hold promise for long-term disease management.

Hard-to-treat autoimmune hepatitis and primary biliary cholangitis: The dawn of a new era of pharmacological treatment.

Patients with hard-to-treat autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC) are defined a posteriori as those who do not show a sufficient response or are intolerant to pharmacological treatments, thus not achieving biochemical surrogate endpoints that are associated with long-term liver-related-event-free survival. The absence of a recently harmonized definition of 'complete biochemical response within 6 months (CBR≤6M)', which is defined as the normalization of serum transaminase and IgG levels below the upper limit of normal (ULN) at ≤6 months after treatment initiation is regarded as hard-to-treat AIH. The implementation of CBR≤6M, in turn, has been facilitating clinical trials, e.g., between azathioprine and mycophenolate mofetil, to reconsider appropriate first-line steroid sparing agents, leading to a reduction in the number of hard-to-treat AIH cases. Regarding PBC, one of the disseminated definitions of hard-to-treat patients is the absence of POISE criteria, which are evaluated at 12 months with serum alkaline phosphatase and bilirubin levels, after the introduction of ursodeoxycholic acid. Hard-to-treat PBC not meeting the POISE criteria has very recently been the target population for the U.S. FDA-approved second-line drugs, elafibranor and seladelpar. In future pharmacological treatment of AIH and PBC, the primary objective for AIH is likely to focus on lowering the number of hard-to-treat patients with personalized steroid sparing treatment regimens. A challenging goal in PBC treatment is the further optimization of treatment surrogate endpoints, even to the stricter ALP normalization, with which an indication of second- or later-line drugs might be expanded, but could ultimately lengthen patients' long-term survival.

Pharmacological management of pediatric metabolic dysfunction-associated steatotic liver disease.

Pediatric obesity, characterized by a body mass index (BMI) at or above the 95th percentile for age, affects a substantial number of children and adolescents worldwide. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, represents a prominent hepatic manifestation of obesity and metabolic syndrome, emerging as the most prevalent hepatic disorder among pediatric patients and a significant contributor to liver transplantation in adults. The escalating prevalence of pediatric MASLD mirrors the alarming rise in childhood obesity rates over recent decades. While lifestyle modifications focusing on dietary changes and increased physical activity constitute the cornerstone of MASLD management, achieving and maintaining significant weight reduction remains challenging. Moreover, disease progression often persists despite standard-of-care interventions, warranting exploration into alternative therapeutic strategies. Pharmacological interventions, particularly, glucagon-like peptide-1 receptor agonists (GLP-1RA), have shown promise in addressing pediatric obesity and its associated comorbidities, including MASLD. Recent studies have demonstrated the efficacy of GLP-1RA in inducing weight loss and improving liver enzyme levels, suggesting a potential role in halting disease progression, and reducing the risk of major adverse liver outcomes. This review provides a comprehensive overview of the current pharmacotherapy landscape for pediatric MASLD, with a focus on novel agents such as GLP-1RA. Furthermore, the manuscript proposes a practical algorithm to assist in integrating GLP-1RA into the clinical management of pediatric patients with obesity and MASLD. Despite promising results, further research is warranted to elucidate the long-term efficacy and safety of GLP-1RA in pediatric populations.

Study to Evaluate the Comparative Efficacy of Medhya Rasayana (Pharmacological) Versus Nonpharmacological Interventions in Management of Gadget Addiction in Children: Protocol for Parallel, Triple-Arm, Randomized Clinical Trial.

Gadget addiction is a common behavioral problem among children. It is known to hamper social and academic life as well as adversely affect the lives of children. Ayurveda offers many therapeutic modalities and Ayurvedic medicines that can be used in the management of gadget addiction in children. The purpose of this study is to evaluate and compare the effectiveness of nonpharmacological therapies and the pharmaceutical intervention Medhya Rasayana in treating childhood gadget addiction. This study aims to provide a detailed description of the study methodology that will be used to compare the efficacy of nonpharmacological versus pharmaceutical interventions in the treatment of children's gadget addiction. A randomized, parallel, triple-arm interventional study will be conducted on diagnosed participants of gadget addiction with an age group of 6- to 16-year-old children, which will be selected and equally distributed in 2 groups. Group P will be given Medhya Rasayana (pharmacological intervention), group N will be nonpharmacological Ayurveda intervention, and group C (cognitive behavioral therapy) will be an external group. The Study duration is 180 days with assessment at baseline, midpoint, and endpoint Appropriate statistical techniques, such as ANOVA and regression analysis, will be used to examine the data and evaluate the efficacy of the 3 groups' interventions. We will perform subgroup analysis according to initial addiction severity, gender, and age. Primary outcome measures include a reduction in gadget addiction and changes in the psychosocial well-being of participants. Standardized questionnaires and instruments will be used to collect data. In December 2023, the randomized controlled study got underway. Since participants may begin at any time, our goal is for everyone to be finished by December 2024. This research will provide crucial new information about the relative effectiveness of Ayurveda nonpharmacological therapies and Medhya Rasayana in treating children's gadget addiction. The results will guide evidence-based treatments aimed at reducing the negative impact of excessive gadget use on this susceptible population's psychosocial development. In the end, the findings are meant to help policy makers and medical professionals create sensible plans to deal with the rising issue of childhood gadget addiction. PRR1-10.2196/51833.

Dietary patterns as predictors of adverse antidiabetics reactions - A cross-sectional study of polish diabetes sufferers

Background: Diabetes mellitus (DM) is a multifaceted problem. There is a need to coordinate the diet with pharmacological interventions, because of the possible interaction between the two. The present study aimed to identify the factors related to the dietary habits of people suffering with diabetes that may increase the risk of adverse reactions to anti-diabetic medication. Methods: Between 2019 and 2020, patients with DM (N=203), aged 18-65, were enrolled for analysis. A quantitative and cross-sectional survey was applied. The study employed a Dietary Habits and Nutrition Beliefs Questionnaire devised in Poland for people aged 15–65 years (KomPAN) and a self-designed questionnaire as research tools. Results: The majority of the patients with DM studied confirmed the use of a low carbohydrate diet in relation to their disease (87.7%). The mean pHDI-10 score for the study group was 22.55±8.67 points and the mean nHDI-14 score was 15.00±9.88 points. The place of residence, education and general financial situation of the subjects had a statistically significant effect on the results (p<0.05). The majority of subjects reported regular use of anti-diabetic medication (77.8%). Of those treated with oral medication, 61.1% had experienced adverse effects and 49.3% had been hospitalized as a result. Of those treated with insulin, 40.9% reported adverse effects. Conclusions: Health professionals should be proactive in giving people with DM, particularly those who are less educated, financially disadvantaged, aged 41-55 and are working, adequate counseling about dietary recommendations from the very onset of their illness.

HUBUNGAN PEMBERIAN JENIS ASUPAN NUTRISI DAN PEMILIHAN TERAPI DENGAN LAMA PERAWATAN PADA BBLR DENGAN IKTERUS NEONATORUM DI RSUD KANJURUHAN MALANG

Infants born weighing less than 2500 grams can be classified into the Low Birth Weight (LBW) category. This classification is not based on gestational age, which makes LBW infants particularly vulnerable because their bodies are not fully prepared to face the extrauterine environment. There are several impacts associated with LBW, one of which is the incidence of neonatal jaundice. This condition occurs especially in LBW infants, leading to longer hospital stays. During the treatment period, the reduction in serum bilirubin levels must be supported by adequate nutritional intake and appropriate therapy. Nutritional intake may include exclusive breastfeeding, predominant breastfeeding, or a combination of both, while therapies include phototherapy, exchange transfusion, and pharmacological treatments. Providing nutrition as early as possible can help reduce bilirubin levels more quickly. Therefore, the purpose of this study was to determine the relationship between types of nutritional intake, therapy selection, and the length of stay in LBW infants with neonatal jaundice at Kanjuruhan Kepanjen Hospital, Malang Regency. The study used an observational analytic design with a cross-sectional approach and included 56 samples selected through purposive sampling. Data were collected using a form based on secondary data and analyzed using the Eta Test, with a correlation value of η = 0.438. The results indicate a moderate relationship between the type of nutritional intake and the length of stay in LBW infants with neonatal jaundice. This study also reported a significant difference in the average length of stay based on the type of nutritional intake, with an ANOVA test yielding a p-value of 0.004. This suggests a significant difference in the length of stay based on nutritional intake. These findings should be of particular concern to healthcare workers when providing nutritional care for LBW infants with neonatal jaundice. Keywords: LBW, neonatal jaundice, infant nutrition, therapy selection, hospitalization.

Renal Artery Stenosis and Mid-Aortic Syndrome in Children—A Review

Background: Renal artery stenosis (RAS) and mid-aortic syndrome (MAS) are significant yet under-recognized causes of pediatric hypertension. RAS is characterized by the narrowing of the renal arteries, while MAS involves the stenosis of the abdominal aorta along with its associated vessels. The etiologies of RAS and MAS often involve genetic factors and acquired conditions such as fibromuscular dysplasia and Takayasu arteritis, contributing to their complex clinical presentations. Despite advancements in diagnostic imaging, challenges remain in effectively identifying these conditions. Pharmacological treatment can achieve partial blood pressure control, but it usually does not lead to complete recovery. Treatment options range from angioplasty to more definitive surgical interventions such as renal artery reimplantation and aorto-aortic bypass, tailored according to the specific pathology and extent of the disease. Methods: This review explores the diagnosis and management of RAS and MAS in children, highlighting the necessity for early detection and showcasing the evolving landscape of treatment. Conclusions: We advocate for a multidisciplinary approach that includes advanced imaging for effective diagnosis and tailored therapy. By integrating the latest research and clinical practices, this article provides valuable insights into managing complex vascular conditions in the pediatric population, ultimately aiming to enhance the quality of life for affected individuals.

Post-COVID condition: a focus on psychiatric symptoms and diagnoses in patients with cognitive complaints.

Cognitive and psychiatric symptoms are frequently reported after SARS-CoV-2 infection, but their interplay has been only partially explored. We investigated frequency and severity of psychiatric symptoms in patients with persistent cognitive complaints after COVID-19. We conducted a cross-sectional study. Neurologists assessed 101 patients reporting cognitive symptoms after COVID-19. Patients were invited to fill a screening battery with self-reported psychometric scales (Depression Anxiety Stress Scales-21, Impact of Event Scale-Revised, Insomnia Severity Index). Patients scoring above validated cut-offs in ≥1 scale were referred to psychiatrists who administered the Mini-International Neuropsychiatric Interview (M.I.N.I.), Hamilton Anxiety (HAM-A), and Hamilton Depression (HAM-D) rating scales and asked to complete the Personality Inventory for DSM-5-Brief Form (PID-5-BF). Out of the 57 referred patients, 38 (64.4%) accepted to undergo the psychiatric examination. Among these, 18 (47.4%) were diagnosed with adjustment disorder (23.7%), anxiety disorder (10.5%), major depressive disorder (7.9%), and post-traumatic stress disorder (2.6%). Pharmacologic treatment before post-COVID condition (present in 12 patients, 31.6%) was associated with a score above cut-off on the HAM-A and HAM-D scales. A longer duration of untreated psychiatric illness after COVID-19 was associated with worse scores on the same scales. Patients with a higher PID-5-BF total score had a higher probability of receiving a psychiatric diagnosis. Almost half of patients with post-COVID-19 conditions reporting cognitive symptoms were found to suffer from a psychiatric condition after psychiatric evaluation. The application of a psychiatric screening in a population suffering from long-term effects of COVID-19 can lead to early diagnosis and timely treatment.

Sodium Chloride Cotransporter in Hypertension

The sodium chloride cotransporter (NCC) is essential for electrolyte balance, blood pressure regulation, and pathophysiology of hypertension as it mediates the reabsorption of ultrafiltered sodium in the renal distal convoluted tubule. Given its pivotal role in the maintenance of extracellular fluid volume, the NCC is regulated by a complex network of cellular pathways, which eventually results in either its phosphorylation, enhancing sodium and chloride ion absorption from urines, or dephosphorylation and ubiquitination, which conversely decrease NCC activity. Several factors could influence NCC function, including genetic alterations, hormonal stimuli, and pharmacological treatments. The NCC’s central role is also highlighted by several abnormalities resulting from genetic mutations in its gene and consequently in its structure, leading to dysregulation of blood pressure control. In the last decade, among other improvements, the acquisition of knowledge on the NCC and other renal ion channels has been favored by studies on extracellular vesicles (EVs). Dietary sodium and potassium intake are also implicated in the tuning of NCC activity. In this narrative review, we present the main cornerstones and recent evidence related to NCC control, focusing on the context of blood pressure pathophysiology, and promising new therapeutical approaches.

RBIO-09. EFFECTS OF RADIATION ON THE HIPPOCAMPUS AND HIPPOCAMPAL NEUROGENESIS: A SYSTEMATIC REVIEW OF INJURY MECHANISMS AND INTERVENTION STRATEGIES

Abstract PURPOSE To understand how radiation affects the hippocampus and hippocampal neurogenesis. Radiotherapy is a common modality in the treatment of brain tumors that targets malignant cells with radiation. However, unintended iatrogenic injury may extend to adjacent healthy cells. The hippocampus is a particular area of concern, given its vital role in memory and learning and capacity for neurogenesis. METHODS We searched the PubMed, Embase, and Web of Science databases for studies assessing the effects of radiation on the hippocampus and hippocampal neurogenesis, adhering to PRISMA guidelines. Animal studies were evaluated according to the ARRIVE guidelines for pre-clinical studies. The SYRCLE risk of bias tool was utilized to examine potential bias among studies. Study characteristics, including study design, sample size, experimental methods, radiation dose, and results were collected and synthesized. RESULTS Ninety-two studies met inclusion criteria, and the majority of studies investigated rat and/or mouse models (n = 91, 98.9%). Across studies, cranial irradiation was consistently found to be associated with detrimental effects on hippocampal function and structure through molecular alterations to gene and protein expression, neuronal cell apoptosis, disruption of dendritic spines, and initiation of pro-inflammatory processes. The consequences for neurogenesis were mostly focused on the dentate gyrus of the hippocampus. These effects manifested as cognitive deficits in hippocampus-dependent tasks such as memory and learning. Behavioral (e.g., running) and pharmacological (e.g., PPARα agonists) interventions against the deleterious effects of radiation suggest the potential to address radiation-induced hippocampal disruption and cognitive deficits. The majority of studies were found to have an unclear risk of bias. CONCLUSIONS This systematic review highlights the effects of cranial radiation on hippocampal neurogenesis and their association with disruptions in memory and learning. Future research should continue to focus on delivering radiotherapy that spares susceptible regions in the brain, preserving patients’ cognitive function and quality of life.

Acromegaly in Speckle Tracking Echocardiography—A New Cardiac Hypertrophy Phenotype? Case Report and Review

Background: This study aims to provide a comprehensive overview of speckle tracking echocardiography (STE) findings in patients diagnosed with acromegaly, exploring a potential application for the differential diagnosis of cardiac hypertrophy and guiding clinicians in patient management. To our knowledge, this is the first review showcasing changes in the bull’s-eye pattern in myocardial function after acromegaly treatment, suggesting a possible pattern in this aetiology of left ventricular hypertrophy. Methods: A review of PubMed articles using the search term “speckle tracking echocardiography acromegaly” yielded 11 relevant papers published between 2017 and 2023. The final analysis evaluated each paper’s substantial value and summarised pertinent information. A clinical case of myocardial strain changes before and after pharmacological and neurosurgical treatment is also described. Results: The 11 analysed papers, with patient groups ranging from 19 to 50 individuals, revealed varying results in STE parameters between acromegalic and control groups. Left ventricular strain parameters were commonly assessed, showing discrepancies in different studies. Notably, the MAGYAR-Path Study emphasised left ventricular twist and radial strain abnormalities in acromegaly patients. Furthermore, the interplay between acromegaly and diabetes influenced myocardial function. Drug treatment with somatostatin receptor ligands demonstrated a favourable impact on left ventricular systolic function. The case study we describe in this manuscript showed changes in the posterior basal LV segment, which may be a specific pattern of acromegaly remodelling. Somatostatin therapy and neurosurgery led to the normalisation of global longitudinal strain (GLS) and improvement in myocardial work, as well as improved diastolic function, including enhanced left atrial strain (LAS) as well as a visible elastic recoil sign (ERS). Conclusions: While the available literature on STE in acromegaly is limited, our analysis suggests potential applications in differentiating hypertrophy aetiologies and monitoring cardiac function post-treatment. The results underscore the need for more interdisciplinary research to optimise patient management. The bull’s-eye pattern with posterior basal segment strain impairment we describe may be used to differentiate this entity.

Epileptiform Electrographic Patterns After Cardiac Arrest: Give Up or Treat?

This Viewpoint challenges conventional clinical practice that eschews pharmacological intervention for comatose patients with epileptiform abnormalities after cardiac arrest using evidence from the Treatment of Electroencephalographic Status Epilepticus after Cardiopulmonary Resuscitation (TELSTAR) trial.

In Vitro Models of Diabetes: Focus on Diabetic Retinopathy

Diabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators. In addition to pharmacological interventions for controlling the blood glycaemic level, the main strategies for treating diabetic retinopathy are the intravitreal injections of drugs, surgical treatments, and vitrectomies. The complexity of diabetic retinopathy is due to its close interactions with different cell types (endothelial cells, astrocytes, and Müller cells). The evaluation of the efficacy of novel pharmacological strategies is mainly performed through in vivo models. However, the use of different animal species leads to heterogenic results and ethical concerns. For these reasons, the development of new and reliable in vitro models, such as cell co-cultures and eye organoids, represents an urgent need in this area of research. This review features an overview of the in vitro models used to date and highlights the advances in technology used to study this pathology.

Peptidergic G-Protein-Coupled Receptor Signaling Systems in Cancer: Examination of Receptor Structure and Signaling to Foster Innovative Pharmacological Solutions

Background. Peptidergic GPCR systems are broadly distributed in the human body and regulate numerous physiological processes by activating complex networks of intracellular biochemical events responsible for cell regulation and survival. Excessive stimulation, ill-function, or blockade of GPCRs produces cell disturbances that may cause disease should compensatory mechanisms not suffice. Methods and Results. Revision of updated experimental research provided an evident relationship associating peptidergic GPCR malfunction with tumor formation and maintenance resulting from uncontrolled cell proliferation and migration, colonization, inhibition of apoptosis or altered metabolism, and increased angiogenesis in tumoral tissues. Conclusion. Determination of the implication of GPCR peptide signaling in specific neoplasia is crucial to designing tailored pharmacological treatments to counteract or dismantle the origin of the signaling circuitry causing cellular disruption. In some cases, particular ligands for these receptors may serve as concomitant treatments to aid other pharmacological or physical approaches to eradicate neoplasias.

Topic modeling and content analysis of people's anxiety-related concerns raised on a computer-mediated health platform.

About one in four Chinese people might suffer or have already suffered from anxiety conditions, with a lifetime prevalence rate of 4.8%. However, many of those who could have benefited from psychological or pharmacological treatments fail to be recognized or treated due to the lack of timely recognition and accurate diagnosis. This study used a topic modeling approach to explore people's anxiety-related concerns raised on a computer-mediated Chinese health platform, YOU WEN BI DA (questioning and answering), to provide implications for accurate diagnosis, targeted education, tailored intervention, and informed policy-making in the course of addressing this condition of public concern. First, we extracted data from YOU WEN BI DA between May 2022 and February 2023. After cleaning the extracted data both using the Python text processing tool spaCy and manually, we ascertained the optimal number of topics by drawing on the coherence scores and used latent Dirichlet allocation (LDA) topic modeling to generate the most salient topics and related terms. We then categorized the topics ascertained into different classes of themes by plotting them onto a 2D plane via multidimensional scaling using the pyLDAvis visualization tool. Finally, we analyzed these topics and themes qualitatively to better understand people's anxiety-related concerns. 5 topics with different overall prevalence were ascertained through data analysis. Topic 2 (tinnitus phobia-incurred concerns, n = 639) is the most popular dominant topic, occurring in 25.1% of the 2545 collected concerns, closely followed by Topics 1 (neurosis-incurred concerns, n = 512;) and 3 (sleep, dyskinesia, bipolar, cognitive, and somatic disorders-incurred concerns, n = 619), which appeared in 20.1% and 24.3% of the 2545 concerns respectively. Topic 5 (social phobia-incurred concerns, n = 428) ranks as the fourth most popular dominant topic, showing up in 16.8% of the 2545 concerns. Topic 4 (autonomic nerve dysfunction-incurred concerns, n = 347) accounts for 13.6% of the 2545 concerns. The t-distributed Stochastic Neighbor Embedding analysis reveals partial similarities between Topics 2 and 5 as well as between Topics 4 and 5 because many concerns involved in Topics 2 and 5 pertain to people's psychological status of fear and anxiety and the relief and dispelling of such symptoms through medication, and many concerns involved in Topics 4 and 5 relate to people's worries about the negative impact on their nerves and the adjustment and conditioning of such effects through medication. This was the first study that investigated Chinese people's anxiety-related concerns raised on YOU WEN BI DA using the topic modeling technique. The automatic text analysis and complementary manual interpretation of the collected data allowed for the discovery of the dominant topics hidden in the data and the categorization of these topics into different themes to reveal the overall status of people's anxiety-related concerns. The research findings can provide some practice implications for health and medical educators, practitioners, and policy-makers to make joint efforts to address this common public concern effectively and efficiently.

Viscosity regulates cell spreading and cell-extracellular matrix interactions.

Fluid viscosity and osmolarity are among some of the underappreciated mechanical stimuli that cells can detect. Abnormal changes of multiple fluidic factors such as viscosity and osmolarity have been linked with diseases such as cystic fibrosis, cancer, and coronary heart disease. Changes in viscosity have been recently suggested as a regulator of cell locomotion. These novel studies focus on cell migration and spreading on glass substrates and through microchannels, and it remains a question whether viscosity impacts the cellular remodeling of extracellular matrices (ECMs). Here, we demonstrate that elevated viscosity induces cellular remodeling of collagen substrates and enhances cell spreading on ECM-mimetic substrates. Our results expand on recent work showing that viscosity induces increased cellular forces and demonstrates that viscosity can drive local ECM densification. Our data further show that microtubules, Ras-related C3 botulinum toxin substrate 1 (Rac1), actin-related protein 2/3 (Arp2/3) complex, Rho-associated protein kinase 1 (ROCK), and myosin are important regulators of viscosity-induced ECM remodeling. In the context of viscosity-induced cell spreading, cells cultured on glass and collagen substrates exhibit markedly different responses to pharmacological treatments, indicating that microtubules, Rac1, and Arp2/3 play distinct roles in regulating cellular spreading depending on the substrate. In addition, our results demonstrate that high osmotic pressures override viscosity-induced cell spreading by suppressing membrane ruffling. Our results demonstrate viscosity as a regulator of ECM remodeling and cell spreading in a fibrillar microenvironment. We also reveal a complex interplay between viscosity and osmolarity. We anticipate that our research can pave the way for future investigations into the crucial roles played by viscosity in both physiological and pathological conditions.

Evaluation of pitolisant, sodium oxybate, solriamfetol, and modafinil for the management of narcolepsy: a retrospective analysis of the FAERS database

ObjectiveNarcolepsy, a rare neurological disorder believed to have an autoimmune etiology, necessitates lifelong management. This study aimed to provide evidence supporting the safety of pharmacological treatment for narcolepsy.MethodsFive-year data on pitolisant, sodium oxybate, solriamfetol, and modafinil were extracted from the FDA Adverse Event Reporting System (FAERS) self-reporting database for the period spanning from 2019 to 2023. Various statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network analysis (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to quantify the signals. Finally, a comparative analysis was conducted between demographic data, outcomes, and inherent associations among the medications and the signals.ResultsAfter data analysis, we obtained 50 signals (a cumulative count of 762 cases) for pitolisant, 640 signals (corresponding to 46,962 cases) for sodium oxybate, 40 signals (equivalent to 1,228 cases) for solriamfetol, and finally, 72 signals (representing 632 cases) for modafinil. The majority of these patients were female. Psychiatric and nervous system disorders were identified as the predominant adverse drug events (ADEs). For sodium oxybate, it is crucial to consider psychiatric disorders (such as suicidal ideation), respiratory disorders (including sleep apnea syndrome and respiratory depression), and signs of pregnancy and congenital familial diseases. For solriamfetol, noteworthy new ADEs include drug inefficacy, suicidal ideation, restless legs syndrome, and somnambulism. Furthermore, a relationship has been observed between modafinil use and restricted fetal growth, spontaneous abortion, cognitive disorders, and drug inefficacy and abuse.ConclusionThe majority of observed adverse reactions in this study were consistent with those listed in the product instructions. However, potential novel or notable ADE signals were identified through real-world pharmacovigilance analysis. It is anticipated that this paper will offer additional information regarding safe and rational medication for narcolepsy.

A Systematic Review of Dietary Lifestyle Interventions for Neuropathic Pain

Background/Objectives: Chronic severe neuropathic pain (NP) affects one in 10 individuals over the age of 30 in North America. Standard pharmacological interventions are associated with significant side effects and have limited effectiveness. Diets seeking to improve physiological health, support gut barrier integrity, and decrease systemic inflammation have recently emerged as powerful tools conferring neuroprotective and anti-inflammatory effects, potentially reducing the overall morbidity and mortality of multiple neurological and metabolic diseases. This systematic review aimed to synthesize the literature around NP outcomes following dietary interventions compared to routine standard of care. Methods: Following PRISMA guidelines, an initial search yielded 15,387 records after deduplication. Six interventional trials specifically assessing dietary interventions for neuropathic pain were included and analyzed. The dietary lifestyle interventions included low-fat plant-based, plant-based fasting-mimicking, low-calorie, potassium-reduced, gluten-free, and intermittent high-protein/Mediterranean diets. Results: The included studies described some statistically significant improvements in pain severity on objective quantitative sensory testing, electrophysiology, imaging, and subjective questionnaires. The overall risk of bias was moderate, with only one trial demonstrating a low risk of bias across all assessed domains. No serious adverse events were identified, and dietary interventions were generally well tolerated. Conclusions: The data collected and synthesized in this systematic review indicate that dietary lifestyle interventions may offer a low-risk, low-cost, low-tech option for chronic neuropathic pain management, potentially improving quality of life and reducing overall morbidity. However, given substantial variability across studies and a moderate risk of bias, further research is warranted to substantiate these findings.

Drug Interaction-Informed Approaches to Inflammatory Bowel Disease Management

Inflammatory bowel disease (IBD) is a complex and chronic condition that requires the use of various pharmacological agents for its management. Despite advancements in IBD research, the multifaceted mechanisms involved continue to pose significant challenges for strategic prevention. Therefore, it is crucial to prioritize safe and effective treatment strategies using the currently available pharmacological agents. Given that patients with IBD often require multiple medications due to combination therapy or other underlying conditions, a comprehensive understanding of drug interactions is essential for optimizing treatment regimens. In this review, we examined the pharmacological treatment options recommended in the current IBD management guidelines and provided a comprehensive analysis of the known pharmacokinetic interactions associated with these medications. In particular, this review includes recent research results for the impact of anti-drug antibodies (ADAs) on the concentrations of biological agents used in IBD treatment. By leveraging detailed interaction data and employing personalized dosing strategies, healthcare providers can improve therapeutic outcomes and minimize adverse effects, ultimately improving the quality of care for patients with IBD.