Development,optimization and characterization of glycyrrhetinic acid–chitosan nanoparticles of atorvastatin for liver targeting

Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.     

Maternal di-(2-ethylhexyl)-phthalate exposure influences essential fatty acid homeostasis in rat placenta

Maintaining essential fatty acid (EFA) homeostasis during pregnancy is critical for fetal development. As the organ that controls the maternal-to-fetal supply of nutrients, the placenta plays a significant role in guiding EFA transfer to the fetus. Many EFA homeostasis proteins are regulated by peroxisome proliferator-activated receptors (PPARs). The metabolites of di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous environmental contaminant, might influence EFA homeostasis via trans-activation of PPARs with subsequent downstream effects on EFA transporters and enzymes. To investigate DEHP's effect on placental/fetal EFA homeostasis, female Sprague-Dawley rats were orally gavaged with either vehicle or DEHP at 750 or 1500 mg/kg/day from gestational day (GD) 0 to GD 19. Changes in the expression of several EFA homeostasis regulating proteins were determined in the junctional (JXN) and labyrinthine (LAB) zones of the placenta, including PPAR isoforms (alpha, beta and gamma), fatty acid translocase (FAT/CD36), fatty acid transport protein 1 (FATP1), plasma membrane fatty acid binding protein (FABPpm), heart cytoplasmic fatty acid binding protein (HFABP), cytochrome P450 (CYP) 4A1, and cyclooxygenase (COX)-1 and -2. Additionally, effects of DEHP maternal exposure on the placental transfer and fetal distribution of representative EFAs, arachidonic acid (AA) and docosahexaenoic acid (DHA), and the placental production of prostaglandins (PGs) were investigated. Expression of PPARalpha, PPARgamma, FAT/CD36, FATP1, HFABP and CYP4A1 was up-regulated in JXN and/or LAB while COX-2 was down-regulated in JXN. PPARbeta, FABPpm, and COX-1 demonstrated variable expression. Reduced directional maternal-to-fetal placental transfer and altered fetal distribution of AA and DHA were observed in concordance with a decreased total placental PG production. These results correlate with previous in vitro data, suggesting that DEHP could influence placental EFA homeostasis with potential downstream effects in the developing fetus.     

Utility of prolonged bedside amplitude-integrated encephalogram in encephalopathic infants

We hypothesized that prolonged bedside limited-channel amplitude-integrated electroencephalogram (aEEG) monitoring following a standard 1-hour conventional electroencephalogram (cEEG) would increase the detection of subclinical seizures and allow continuous evaluation of the background EEG in neonatal encephalopathy. This may identify complementary roles for these EEG technologies in neonatal units where continuous cEEG monitoring may not be readily available. We prospectively recruited 25 term neonates with a diagnosis of neonatal seizures or encephalopathy. All infants underwent a standard 1-hour cEEG followed by 12 to 24 hours of aEEG monitoring. Data from the aEEG (plus the raw signal) were analyzed by an epileptologist and compared with information obtained from the clinical report of the cEEG. aEEG and cEEG data were available for 24 infants. Results from magnetic resonance imaging (MRI) performed at 7 to 10 days of life were available in 23/24 infants. Background classification on cEEG and aEEG was similar in 83% of patients. Five of 24 infants had normal background on cEEG. Prolonged aEEG detected evolution of background from initially normal to moderately abnormal in an additional four infants. It also detected more subclinical seizures than the 1-hour cEEG in 8/14 infants. Normal background on aEEG and cEEG was associated with normal MRI results, and severe background abnormality (5/24) on both aEEG and cEEG was associated with abnormal MRI results. Data obtained from prolonged aEEG (plus raw EEG) provide similar background activity, enhance seizure detection, and complement standard cEEG in predicting short-term outcomes, based on MRI, in term neonates with seizures or encephalopathy. Limited-channel aEEG technology may provide a pragmatic alternative for longitudinal monitoring of newborn infants with encephalopathy in neonatal units where prolonged video EEG monitoring is not feasible.     

Primiparity, assisted reproduction, and preterm birth in twin pregnancies: a population based study

Objective To determine the prevalence of pregnancy complications among primiparous patients with twin gestation in our population and to investigate the association between the increased rates of assisted reproduction (ART) in twin gestation and preterm birth (PTD). Material and methods A retrospective population based cohort study was designed, including all twin deliveries after 24 weeks gestation (n = 2,601). The study group included 666 primiparous women and the comparison group 1,935 multiparous women. Maternal characteristics and perinatal outcome were evaluated. Women with fetal malformations were excluded. A multiple logistic regressions analysis for independent risk factors was performed including factors that were significantly different between the study groups in the univariate analysis. Patient’s data were obtained from computerized database and analyzed using SPSS statistical package. Results Primiparous women had a significantly higher rate of preeclampsia, chronic hypertension, ART, prelabor rupture of membranes (PROM) preterm deliveries (PTD), labor dystocia, cesarean section (CS) and vacuum extraction of the first twin than the multiparous group. Primiparous patients had a significantly lower gestational age at delivery and neonatal birth weight of the first and second twin. In multiple logistic regressions analysis primiparity and ART were independent risk factors for PTD, (OR 1.45, 95% CI 1.18–1.78; OR 1.36, 95% CI 1.09–1.71, respectively). Conclusions (1) Primiparous patients with twin gestation represent a unique population with high rate of infertility and underlying diseases such as chronic hypertension in comparison to the multiparous women with twin gestation; (2) primiparity is an independent risk factor for prematurity in twin gestations; and (3) although primiparous women had an increased maternal complications, neonatal mortality rates were not significantly different from multiparous women.     

Evaluation of endothelial function in women with polycystic ovary syndrome

Objectives

Previous studies have suggested that vascular reactivity may be altered in women with polycystic ovary syndrome (PCOS). We sought to evaluate the vascular reactivity specifically the endothelial function (EF) in women with PCOS and to study the effect of metformin on their EF.

Study design

Thirty-one women diagnosed with PCOS and 33 healthy controls underwent evaluation of EF using a post-ischemia reactive hyperemia technique (Endo-PAT). EF was quantitatively determined as the ratio between the arterial pulse wave amplitude following a 5 min arterial occlusion in the forearm to the pre-occlusion value. Oral metformin 850 mg bid was administered to PCOS patients. After 3 months of treatment EF was reassessed using the same technique.

Results

The average endothelial function was 1.48 ± 0.32 in the PCOS group versus 2.00 ± 0.51 in the controls (P < 0.001). There were no significant changes in the EF among the 18 patients who were treated with metformin, EF index pre- and post-treatment was 1.42 versus 1.43, respectively.

Conclusions

Endothelial dysfunction is more likely to occur among PCOS patients than in healthy controls. These preliminary results suggest that metformin treatment for 3 months in PCOS patients does not improve endothelial function.     

Factors Associated with Macular Staphyloma Area on Ultra-widefield Fundus Images

PurposeTo assess the feasibility of applying ultra-widefield fundus (UWF) images for macular staphyloma area (MSA) measurement and investigate the associated factors with MSA.MethodsThis is a retrospective study. MSA was measured by UWF imaging. Central foveal thickness, subfoveal choroidal thickness, subfoveal scleral thickness were measured on spectral domain optical coherence tomography. Intraclass correlation coefficients of MSA measurement would be evaluated. Multiple linear regression analysis was used to analyze the associated factors with MSA.ResultsIn total, 135 eyes of 92 patients were enrolled. The mean age was 64.73 ± 10.84 years. Mean MSA on UWF image was 279.67 ± 71.70 mm². Intraclass correlation coefficients of MSA measurement was 0.965 (95% confidence interval [CI], 0.946 to 0.977; p < 0.001). In the multiple linear regression analysis, after adjusting for subfoveal choroidal thickness, best-corrected visual acuity, central foveal thickness, and subfoveal scleral thickness, the factors independently related to MSA were axial length (β = 8.352; 95% CI, 3.306 to 13.398; p = 0.001), sex (β = −26.673; 95% CI, −51.759 to −1.586; p = 0.037), age (β = 1.184; 95% CI, 0.020 to 2.348; p = 0.046).ConclusionsIt is feasible to measure MSA on UWF image. Female, longer axial length, and older age may indicate larger MSA.     

Reimagining Undergraduate Medical Education in a Post-COVID-19 Landscape

Online education due to the COVID-19 pandemic caused many medical schools to increasingly employ asynchronous and virtual learning that favored student independence and flexibility. At the same time, the COVID-19 pandemic highlighted existing shortcomings of the healthcare field in providing for marginalized and underserved communities. This perspective piece details the authors’ opinions as medical students and medical educators on how to leverage the aspects of pandemic medical education to train physicians who can better address these needs.KEY WORDS: undergraduate medical education, social determinants of health, virtual learning

“American medical education needed a revolution,” writes Professor Jon M. Barry in The Great Influenza: The Story of the Deadliest Pandemic in History¹. He described a different era of medical education, a time in the late 1800s when medical students graduated without having ever touched a patient. The revolution began at Johns Hopkins Hospital with William Osler’s teaching hospital model for postgraduate training, a model that spread across the nation and has formed the foundation for modern medical education². A few decades later, the Flexner Report commissioned by the American Medical Association codified recommendations for standardized curriculum based on Osler’s program at Hopkins, giving rise to the biomedical model of medical education^{3, 4}. In the same decade, the 1918 influenza pandemic, one of the deadliest pandemics in the history of humankind, infected approximately one-third of the world’s population, causing an estimated 50 million deaths⁵. Clearly, as Barry describes, it was a time of great crisis, ripe for great change.The Flexner Report and 1918 pandemic thus led to many medical schools adopting the biomedical model and overhauling their curricula. Since then, shortcomings of the Flexner Report, such as limiting the opportunities of Black physicians and excluding social determinants of health from the medical model^{4, 6}, have been acknowledged and medical education has increasingly prioritized diversity and inclusion and public health education to better serve the diverse health needs of society^7–9. The biopsychosocial model of medicine has largely supplanted the biomedical model^{7, 8}, and many medical schools have modified their biomedical curricula to incorporate systems-based learning and social determinants of health.Yet healthcare is far from perfect today, with issues of cost, access, and systemic inequality still plaguing patients. As medical students and medical educators, we strive for a medical education that will better prepare the next generation of physicians to address these failures of the profession. We also have experienced how the current COVID-19 pandemic, similar to the 1918 influenza pandemic, has caused great crises in healthcare and changes in medical education^10–12. As vaccines have made a post-COVID era more tangible, we believe the medical field is once again ripe for revolution. In this perspective piece, we detail how we can leverage the current flux in medical education, capitalizing on asynchronous and virtual learning with a focus on social determinants and disparities, to better train physicians who will be prepared to serve the public health in a post-COVID era.     

Exploring the Barriers and Motivators to Dietary Adherence among Caregivers of Children with Disorders of Amino Acid Metabolism (AAMDs): A Qualitative Study

Dietary intervention is generally accepted as the mainstay of treatment for patients with disorders of amino acid metabolism (AAMDs). However, dietary adherence to a low-protein diet is always reported as a common challenge among these patients. This study explored the perception of barriers and motivators to dietary adherence among caregivers of AAMD patients in Malaysia. Twenty caregivers of children with AAMDs receiving ongoing treatment at the genetic clinic participated in an online focus group discussion from November to December 2021. Findings showed a total of five interrelated main themes identified from focus group discussion (FGD) exploring parents’ experiences related to the management of their child’s daily diet. The barriers to dietary adherence were burden of dietary treatment, diet and dietary behavior, parenting challenges, limited knowledge related to dietary treatment, and challenges in healthcare system delivery. Key factors facilitating good dietary adherence include good knowledge of dietary treatment, parental coping strategies, social coping, and dietary behavior. In conclusion, despite the existence of several barriers to the implementation of dietary treatment, caregivers managed to use a wide range of coping strategies to overcome some, if not all, of the challenges. The important next step is to develop, in conjunction with multidisciplinary healthcare professionals, feasible implementation strategies that could address these barriers and at the same time improve the quality of life of caregivers.     

Adult extracardiac rhabdomyomas presenting as a slowly growing neck mass

Rhabdomyomas are rare benign tumors arising from skeletal muscle cells, most common cardiac in origin and usually seen in pediatric age group, often associated with neurophakomatosis like tuberous sclerosis. Extracardiac tumors are rare and are classified based on histology into adult, fetal and genital forms. The adult form of extracardiac rhabdomyoma are seen in the head and neck region in vast majority of cases. These can occur within the pharyngeal or laryngeal compartments along with other neck spaces and the orbits. In this case report, we describe the findings of adult extracardiac rhabdomyoma and discuss the striking similarity with lymphomas on imaging.