Animal Studies Research Articles

The Fetal Alcohol Spectrum Disorders—An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions

Since the establishment of a clear link between maternal alcohol consumption during pregnancy and certain birth defects, the research into the treatment of FASD has become increasingly sophisticated. The field has begun to explore the possibility of intervening at different levels, and animal studies have provided valuable insights into the pathophysiology of the disease, forming the basis for implementing potential therapies with increasingly precise mechanisms. The recent reports suggest that compounds that reduce the severity of neurodevelopmental deficits, including glial cell function and myelination, and/or target oxidative stress and inflammation may be effective in treating FASD. Our goal in writing this article was to analyze and synthesize current experimental therapeutic interventions for FASD, elucidating their potential mechanisms of action, translational relevance, and implications for clinical application. This review exclusively focuses on animal models and the interventions used in these models to outline the current direction of research. We conclude that given the complexity of the underlying mechanisms, a multifactorial approach combining nutritional supplementation, pharmacotherapy, and behavioral techniques tailored to the stage and severity of the disease may be a promising avenue for further research in humans.

Docosahexaenoic Acid Supplementation for Neonatal Hyperbilirubinemia: A Double-Blind, Randomized Clinical Trial.

Docosahexaenoic acid (DHA) is an essential component for brain development during fetal and early postnatal life. Hyperbilirubinemia is characterized by abnormally high levels of bilirubin in the bloodstream, frequently leading to jaundice in newborns. In severe instances, this condition can progress to neurological damage or kernicterus, a form of brain damage. Initial cell-based experiments conducted by our research team revealed that DHA significantly enhances the survival rate of nerve cells treated with bilirubin and diminishes the oxidative stress indicated by reduced peroxide activity caused by unconjugated bilirubin (UCB). Further investigations through animal studies demonstrated that DHA effectively mitigates bilirubin-induced brain injury in neonatal rats. However, the potential of DHA to decrease the incidence of bilirubin-induced brain damage in clinical settings has not been previously explored or reported. Infants with neonatal hyperbilirubinemia (n = 30 per group) participated in a double-blind, randomized, placebo-controlled parallel study. They received either 100 mg/d DHA or placebo syrup immediately when they were diagnosed. The study found that the bilirubin level at 48 hours of treatment, serum neuron-specific enolase (NSE) levels, mean phototherapy duration, and abnormal rate of cranial magnetic resonance imaging (MRI) were lower in the DHA group than those in the control group (P < .05). These results suggested that DHA is effective as an adjuvant treatment for hyperbilirubinemia in children. It can reduce the incidence of neonatal hyperbilirubinemia brain injury and plays a certain protective role. Clinical study on protective effect of DHA on neonatal bilirubin injury is registered at Chinese Clinical Trial Registry as ChiCTR2300070250.

Chitin-glucan improves important pathophysiological features of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most frequent and debilitating conditions leading to gastroenterological referrals. However, recommended treatments remain limited, yielding only limited therapeutic gains. Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority. To provide an alternative approach to managing patients with IBS, we performed preclinical molecular, cellular, and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS. To evaluate the roles of CG in visceral analgesia, intestinal inflammation, barrier function, and to develop computational molecular models. Visceral pain was recorded through colorectal distension (CRD) in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS [15 milligrams (mg)/kilogram (kg)] in 33 Sprague-Dawley rats. Intracolonic pressure was regularly assessed during the 9 wk-experiment (weeks 0, 3, 5, and 7) in animals receiving CG (n = 14) at a human equivalent dose (HED) of 1.5 g/d or 3.0 g/d and compared to negative control (tap water, n = 11) and positive control (phloroglucinol at 1.5 g/d HED, n = 8) groups. The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate (DSS) administered in their drinking water during 14 d. HT-29 cells under basal conditions and after stimulation with lipopolysaccharide (LPS) were treated with CG to evaluate changes in pathways related to analgesia (µ-opioid receptor (MOR), cannabinoid receptor 2 (CB2), peroxisome proliferator-activated receptor alpha, inflammation [interleukin (IL)-10, IL-1b, and IL-8] and barrier function [mucin 2-5AC, claudin-2, zonula occludens (ZO)-1, ZO-2] using the real-time PCR method. Molecular modelling of CG, LPS, lipoteichoic acid (LTA), and phospholipomannan (PLM) was developed, and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations. Data were expressed as the mean ± SEM. Daily CG orally-administered to rats or mice was well tolerated without including diarrhea, visceral hypersensitivity, or inflammation, as evaluated at histological and molecular levels. In a model of CRD, CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14% after 2 wk of administration (P < 0.01) and reduced inflammation intensity by 50%, resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis. To better reproduce the characteristics of visceral pain in patients with IBS, we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity. CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20% five weeks after colitis induction (P < 0.01). When the CG dosage was increased to 3.0 g/d HED, this analgesic effect surpassed that of the spasmolytic agent phloroglucinol, manifesting more rapidly within 3 wk and leading to a 50% inhibition of pain perception (P < 0.0001). The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved, at least in part, a significant induction of MOR, CB2 receptor, and IL-10, as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8. CG also significantly upregulated barrier-related genes including muc5AC, claudin-2, and ZO-2. Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids, sequestering gram-negative LPS and gram-positive LTA bacterial toxins, as well as PLM in fungi at the lowesr energy conformations. CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.

A Review on the Potential Use of Medicinal Plants from the Apiaceae and the Rosaceae Families in Cardiovascular Diseases—Experimental Evidence and Traditional Applications

Cardiovascular diseases are the leading cause of mortality worldwide. The World Health Organization has presented alarming data stating that in 2019, 17.9 million people globally died due to cardiovascular diseases, constituting 32% of all deaths. Despite increasingly advanced pharmacological and procedural treatment methods for these diseases, there is still a quest for new therapeutic possibilities that promise even greater efficacy and safety. The overriding purpose of this study is to provide an insight into the traditional uses of species from the Apiaceae and Rosaceae families as well as to systematize knowledge regarding their scientifically proven cardiovascular activities (animal studies and clinical trials). The review is intended to indicate knowledge gaps for future studies concerning plants used in traditional medicine but without scientific research. As a result, various plant species from both Apiaceae and Rosaceae family have been collected and described based on their study that has proven their effectiveness and uses in cardiovascular diseases. Most of these plants have a hypotensive effect, followed by anti-hyperlipidemic, vasorelaxant, antithrombotic, and diuretic activity. These are the mechanisms that contribute to various cardiovascular diseases, such as heart attack, coronary heart disease, hypertension, and stroke.

Catheter-Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation.

Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, is developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non-survival and survival porcine experiments, successful PVE is achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug-resistant patient-derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth.

The Effects of Mkpuru Mmiri Consumption on Cognitive Performance and Brain Histology in an Animal Study

Mkpuru mmiri, popularly known as ice or methamphetamine (METH) is one of the illegal substances that young people in Nigeria abuse most frequently. The purpose of the study is to determine how methamphetamine affects the cognitive-motor behavior of Wistar rats. In the study, twenty-five Wistar rats weighing between 117 and 138 grams were split into five groups: group A had only rat feed and water, group B - D received doses of METH ranging from 5 mg/kg to 20 mg/kg, and group E received a dose of 5 mg/kg of diazepam. Neurobehavioral tools such as the navigator maze test, elevated plus maze and beam walk were used to assess the rats’ memory, anxiety-related behavior, balance, motor coordination, and working memory respectively. Two weeks after the injection, samples were taken and examined for oxidative stress markers (Malondialdehyde - MDA) and tissue antioxidant indicators (Superoxide dismutase - SOD, Glutathione - GSH, and Total Antioxidant Capacity - TAC). The data were analyzed using SPSS and post hoc LSD and the significance level was established at p&lt;0.05. The results showed that the test groups' body weight was significantly lower than the control groups' (p&lt;0.05). The test groups' relative brain weights increased significantly (p&lt;0.05) when compared to the control group. The data also showed a significantly (p&lt;0.05), level of antioxidant enzymes (SOD, GSH, and TAC levels) and a significantly (p&lt;0.05) greater level of MDA when compared to the control group. When comparing the test groups' cognitive abilities to the controls, the experimental rats' cognitive powers significantly declined. The study's conclusion demonstrated that chronic consumption of methamphetamine may deteriorate cognitive function.

Can current preclinical strategies for radiopharmaceutical development meet the needs of targeted alpha therapy?

Preclinical studies are essential for effectively evaluating TAT radiopharmaceuticals. Given the current suboptimal supply chain of these radionuclides, animal studies must be refined to produce the most translatable TAT agents with the greatest clinical potential. Vector design is pivotal, emphasizing harmonious physical and biological characteristics among the vector, target, and radionuclide. The scarcity of alpha-emitting radionuclides remains a significant consideration. Actinium-225 and lead-212 appear as the most readily available radionuclides at this stage. Available animal models for researchers encompass xenografts, allografts, and PDX (patient-derived xenograft) models. Emerging strategies for imaging alpha-emitters are also briefly explored. Ultimately, preclinical research must address two critical aspects: (1) offering valuable insights into balancing safety and efficacy, and (2) providing guidance on the optimal dosing of the TAT agent.

Разработка и реализация протокола поведенческого эксперимента для оценки когнитивных способностей и социального поведения мышей после стресса в раннем возрасте

&lt;p style="text-align: justify;"&gt;This manuscript presents a protocol designed for the comprehensive investigation of early life stress (ELS) outcomes and a feasibility study conducted with this protocol. ELS alters normal development by interfering at various levels: hormonal changes, brain cellular architecture, epigenome, and chromosomal structural elements. The protocol combines classic behavioral tests with advanced molecular techniques to obtain comprehensive data and thus uncover the underlying mechanisms of ELS. In this protocol, the main source of stress is maternal separation. Briefly, a group of C57Bl/6 mice undergoes maternal separation; then, mice perform the radial maze test and the resident-intruder test. As a control, another group of mice stays undisturbed and performs the same behavioral tests in the same timeframe. After the behavioral tests, biosamples are collected, including urine for corticosterone measurements, peripheral blood, hippocampus, amygdala, and prefrontal cortex tissues for DNA isolation and its downstream analyses (DNA methylation profiling and telomere length measuring), and whole brains for immunohistochemistry analysis of the glucocorticoid receptor density. This protocol was successfully tested as a feasibility study for a large-scale investigation that addresses potential flaws to establish a robust methodology. This paper reports on a comprehensive approach to examining multiple aspects of development that interrogates a holistic analysis of multilayer and multidimensional data and may contribute valuable insights for both animal and human studies.&lt;/p&gt;

Characterizations of White Mulberry, Sea-Buckthorn, Garlic, Lily of the Valley, Motherwort, and Hawthorn as Potential Candidates for Managing Cardiovascular Disease-In Vitro and Ex Vivo Animal Studies.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dysfunction. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, thromboembolism, and kidney and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta blockers, calcium inhibitors, ACE inhibitors, and anti-platelet drugs remains a second-line treatment after dietary interventions and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be effective and free from side effects, either taken together with or before the standard pharmacological intervention. Such herbal-originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea-buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (motherwort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and potential therapeutic option in the management of cardiovascular disorders.

Interdependence of placenta and fetal cardiac development.

The placenta and fetal heart undergo development concurrently during early pregnancy, and, while human studies have reported associations between placental abnormalities and congenital heart disease (CHD), the nature of this relationship remains incompletely understood. Evidence from animal studies suggests a plausible cause and effect connection between placental abnormalities and fetal CHD. Biomechanical models demonstrate the influence of mechanical forces on cardiac development, whereas genetic models highlight the role of confined placental mutations that can cause some forms of CHD. Similar definitive studies in humans are lacking; however, placental pathologies such as maternal and fetal vascular malperfusion and chronic deciduitis are frequently observed in pregnancies complicated by CHD. Moreover, maternal conditions such as diabetes and pre-eclampsia, which affect placental function, are associated with increased risk of CHD in offspring. Bridging the gap between animal models and human studies is crucial to understanding how placental abnormalities may contribute to human fetal CHD. The next steps will require new methodologies and multidisciplinary approaches combining innovative imaging modalities, comprehensive genomic testing, and histopathology. These studies may eventually lead to preventative strategies for some forms of CHD by targeting placental influences on fetal heart development.

Understanding changes in echocardiographic parameters at different ages following fetal growth restriction: a systematic review and meta-analysis.

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency-induced FGR offspring. We included 6 animal and 49 human studies. While unable to perform a meta-analysis of animal studies due to insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies mostly unclear. Echocardiographymay offer a non-invasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non-)imaging techniques for an improved risk estimation.

Probiotics in autism spectrum disorder: Recent insights from animal models.

Autism spectrum disorder is a neurodevelopmental disorder characterized by a wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism spectrum disorder, often proving ineffective and accompanied by a multitude of side effects. The gut microbiota is the reservoir of bacteria inhabiting our gastrointestinal tract. The gut microbial alterations observed in individuals with autism spectrum disorder, including elevated levels of Bacteroidetes, Firmicutes, and Proteobacteria, as well as reduced levels of Bifidobacterium, provide a basis for further investigation into the role of the gut microbiota in autism spectrum disorder. Recent preclinical studies have shown favorable outcomes with probiotic therapy, including improvements in oxidative stress, anti-inflammatory effects, regulation of neurotransmitters, and restoration of microbial balance. The aim of this review is to explore the potential of probiotics for the management and treatment of autism spectrum disorder, by investigating insights from recent studies in animals.

Alginate‐Coated Silicone Implants with Antisolvent‐Crystallized Paclitaxel to Prevent Breast Cancer Recurrence and Reduce Fibrosis

AbstractBreast cancer patients undergoing mastectomy receive silicone‐implant‐based breast reconstruction to mitigate the psychological distress of breast loss, typically in conjunction with adjuvant therapy. However, significant problems remain, such as systemic toxicity from chemotherapy and fibrosis that causes capsular contracture. Here, the development of a silicone implant coated with an alginate gel containing antisolvent‐crystallized paclitaxel (acPTX) is reported. By antisolvent crystallization, the compact formulation of acPTX ensures slow release for long‐term breast cancer recurrence prevention. The mixture of acPTX and the biodegradable alginate gel, which reduces fibrosis, is uniformly coated onto the silicone implant using 3D printed implant‐specific molds based on the shape obtained from 3D scanning. In a breast cancer recurrence mouse model, silicone implants coated with acPTX gel show a long‐term preventive effect compared to gel‐coated implants with commercially available PTX. Furthermore, animal studies using C57BL/6 mice show that alginate‐gel‐coated implants significantly reduce capsule thickness, collagen density, and the number of fibrosis‐related cells around the implant compared to silicone implants. The developed acPTX‐gel‐coated implant presents a promising approach for breast reconstruction in mastectomized breast cancer patients. It provides a novel platform for developing implants with long‐term drug release properties.

Polyphenols and Lactation: Molecular Evidence to Support the Use of Botanical Galactagogues.

Botanicals and herbal supplements contain a diverse array of polyphenols that may affect mammary gland function and promote galactagogue activity. This scoping review is conducted to identify scientific literature elucidating how polyphenols affect mammary gland biology and cellular mechanisms critical for lactation. A literature search of PubMed and Medline reviews relevant studies in dairy animals, rodent models, and cultured mammary epithelial cells that are published from January 2010 until July 2023, to ascertain effects of polyphenols on mechanisms regulating milk production and composition. The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review) strategy is applied and 80 studies on polyphenols and their implications on milk production and composition are included in this review. Limited information delineating effects of polyphenols on the molecular pathways that affect lactation are found, although available information suggests modulation of Stat5 signaling/differentiation, Stat3 signaling/remodeling, mTOR and insulin signaling/energy production, and nuclear factor kappa beta (NFκβ) signaling/oxidative stress and inflammation may play roles. A profound lack of mechanistic information underscores the critical need for further research to understand the impact of botanical supplements and polyphenols on milk production and composition in humans to establish maternal nutritional guidelines to support lactation and breastfeeding goals.

Cryopreservation and Rapid Recovery of Differentiated Intestinal Epithelial Barrier Cells at Complex Transwell Interfaces Is Enabled by Chemically Induced Ice Nucleation.

Cell-based models, such as organ-on-chips, can replace and inform in vivo (animal) studies for drug discovery, toxicology, and biomedical science, but most cannot be banked "ready to use" as they do not survive conventional cryopreservation with DMSO alone. Here, we demonstrate how macromolecular ice nucleators enable the successful cryopreservation of epithelial intestinal models supported upon the interface of transwells, allowing recovery of function in just 7 days post-thaw directly from the freezer, compared to 21 days from conventional suspension cryopreservation. Caco-2 cells and Caco-2/HT29-MTX cocultures are cryopreserved on transwell inserts, with chemically induced ice nucleation at warmer temperatures resulting in increased cell viability but crucially retaining the complex cellular adhesion on the transwell insert interfaces, which other cryoprotectants do not. Trans-epithelial electrical resistance measurements, confocal microscopy, histology, and whole-cell proteomics demonstrated the rapid recovery of differentiated cell function, including the formation of tight junctions. Lucifer yellow permeability assays confirmed that the barrier functions of the cells were intact. This work will help solve the long-standing problem of transwell tissue barrier model storage, facilitating access to advanced predictive cellular models. This is underpinned by precise control of the nucleation temperature, addressing a crucial biophysical mode of damage.

Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

A systematic review of animal and human data comparing the nasal potential difference test between cystic fibrosis and control

The nasal potential difference test (nPD) is an electrophysiological measurement which is altered in patients and animal models with cystic fibrosis (CF). Because protocols and outcomes vary substantially between laboratories, there are concerns over its validity and precision. We performed a systematic literature review (SR) of the nPD to answer the following review questions: A. Is the nasal potential difference similarly affected in CF patients and animal models?”, and B. “Is the nPD in human patients and animal models of CF similarly affected by various changes in the experimental set-up?”. The review protocol was preregistered on PROSPERO (CRD42021236047). We searched PubMed and Embase with comprehensive search strings. Two independent reviewers screened all references for inclusion and extracted all data. Included were studies about CF which described in vivo nPD measurements in separate CF and control groups. Risk of bias was assessed, and three meta-analyses were performed. We included 130 references describing nPD values for CF and control subjects, which confirmed substantial variation in the experimental design and nPD outcome between groups. The meta-analyses showed a clear difference in baseline nPD values between CF and control subjects, both in animals and in humans. However, baseline nPD values were, on average, lower in animal than in human studies. Reporting of experimental details was poor for both animal and human studies, and urgently needs to improve to ensure reproducibility of experiments within and between species.

Environmental Impacts on Cardiovascular Health and Biology: An Overview.

Environmental stressors associated with human activities (eg, air and noise pollution, light disturbance at night) and climate change (eg, heat, wildfires, extreme weather events) are increasingly recognized as contributing to cardiovascular morbidity and mortality. These harmful exposures have been shown to elicit changes in stress responses, circadian rhythms, immune cell activation, and oxidative stress, as well as traditional cardiovascular risk factors (eg, hypertension, diabetes, obesity) that promote cardiovascular diseases. In this overview, we summarize evidence from human and animal studies of the impacts of environmental exposures and climate change on cardiovascular health. In addition, we discuss strategies to reduce the impact of environmental risk factors on current and future cardiovascular disease burden, including urban planning, personal monitoring, and mitigation measures.

Dyslipidemia management in pregnant patients: a 2024 update

Abstract Over several decades the approach to treating dyslipidemias during pregnancy remains essentially unchanged. The lack of advancement in this field is mostly related to the fact that we lack clinical trials of pregnant patients both with available as well as new therapies. While there are numerous novel therapies developed for nonpregnant patients, there are still many limitations in dyslipidemia treatment during pregnancy. Besides pharmacotherapy and careful clinical assessment, the initiation of behavioral modifications as well as pre-conception management are very important. Among the various lipid-lowering medications, bile acid sequestrants are the only ones officially approved for treating dyslipidemia in pregnancy. Ezetimibe and fenofibrate can be considered if their benefits outweigh potential risks. Statins are still considered contraindicated, primarily due to animal studies and human case reports. However, recent systematic reviews and meta-analyses as well as data on familial hypercholesterolemia (FH) in pregnant patients have indicated that their use may not be harmful and could even be beneficial in certain selected cases. This is especially relevant for pregnant patients at very high cardiovascular risk, such as those who have already experienced an acute cardiovascular event or have homozygous or severe forms of heterozygous FH. In these cases, the decision to continue therapy during pregnancy should weigh the potential risks of discontinuation. Bempedoic acid, olezarsen, evinacumab, evolocumab and alirocumab, and inclisiran, are options to consider just before and after pregnancy is completed. In conclusion, decisions regarding lipid-lowering therapy for pregnant patients should be personalized. Despite the challenges in designing and conducting studies in pregnant women, there is a strong need to establish the safety and efficacy of dyslipidemia treatment during pregnancy.

Histologic Assessment of a Fast-Set Mineral Trioxide Aggregate (MTA) and Two Novel Antibacterial-Enhanced Fast-Set MTAs for Apexification and Periapical Healing of Teeth With Incomplete Root Formation in a Rat Model: An In Vivo Animal Study

Histologic Assessment of a Fast-Set Mineral Trioxide Aggregate (MTA) and Two Novel Antibacterial-Enhanced Fast-Set MTAs for Apexification and Periapical Healing of Teeth With Incomplete Root Formation in a Rat Model: An In Vivo Animal Study