The Role of Fatty Acid Synthase in the Vascular Smooth Muscle Cell to Foam Cell Transition.

Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells-lipid-laden, macrophage-like cells pivotal in atherosclerotic plaque formation. CHO uptake by VSMCs leads to two primary pathways: ABCA1-mediated efflux or storage in lipid droplets as cholesterol esters (CEs). CE formation, involving the condensation of free CHO and fatty acids, is catalyzed by sterol O-acyltransferase 1 (SOAT1). The necessary fatty acids are synthesized by the lipogenic enzyme fatty acid synthase (FASN), which we found to be upregulated in atherosclerotic human coronary arteries. This observation led us to hypothesize that FASN-mediated fatty acid biosynthesis is crucial in the transformation of VSMCs into foam cells. Our study reveals that CHO treatment upregulates FASN in human aortic SMCs, concurrent with increased expression of CD68 and upregulation of KLF4, markers associated with the foam cell transition. Crucially, downregulation of FASN inhibits the CHO-induced upregulation of CD68 and KLF4 in VSMCs. Additionally, FASN-deficient VSMCs exhibit hindered lipid accumulation and an impaired transition to the foam cell phenotype following CHO exposure, while the addition of the fatty acid palmitate, the main FASN product, exacerbates this transition. FASN-deficient cells also show decreased SOAT1 expression and elevated ABCA1. Notably, similar effects are observed in KLF4-deficient cells. Our findings demonstrate that FASN plays an essential role in the CHO-induced upregulation of KLF4 and the VSMC to foam cell transition and suggest that targeting FASN could be a novel therapeutic strategy to regulate VSMC phenotypic modulation.

Assessing Trustworthiness of Internet Pharmacies with an Internet Browser Extension.

Background: Many people are turning to online pharmacies for medication purchases leading to a growing number of legal and illegal online pharmacies (IOPs). With a growing number of IOPs, consumers are more likely to receive substandard or falsified medications when purchasing medications online. Objectives: This study aims to identify the number of verified, not recommended, and not verified pharmacy websites consumers see using different keywords and medications on an Internet browser based off the National Association Boards of Pharmacy's (NABP) list of verified and not recommended websites. It also aims to compare which keywords result in more not recommended pharmacy websites compared with verified pharmacy websites for consumers over time. Design and Methods: We created an Internet browser extension compatible with different Internet browsers to quickly identify which search results are verified, not recommended, and not verified based on NABP lists. We then utilized an application programming interface to automatically search different key terms and classify the search results as verified, not recommended, and not verified over a 4-week data collection period for analysis. Results: A total of 131 key terms were used for the search. There was an average signal determining the number of verified and not recommended search results compared with not verified results of 4.3% over the 4-week data collection period. There was about a 3:1 ratio of not recommended to verified search results noted. Top signal and not recommended search result producing keywords contained words such as "shipped" and "cheap." Conclusion: The Internet browser extension will aid in making it easier to identify which search results are safe and which are not safe when searching to purchase medications online. This study has set the premise on expanding how to use an Internet pharmacy extension to combat IOPs, improve patient safety, and increase safe access to medications.

A Comparison of Instructions for Use Documents and Manufacturer Produced Administration Videos for Biological Products.

OBJECTIVES: To compare Instructions for Use (IFU) and Manufacturer Produced Administration Videos (MPAV) for biological products to describe if they are highly similar or different. To identify differences between the two that may lead to medication errors and to point out possible solutions to optimize safety. METHODS: We screened 139 biological products having both an IFU and a MPAV. Differences between the IFU and MPAV of each biological product were noted and categorized by importance and how likely it would cause harm to patients. Strategies were discussed based on differences observed. RESULTS: Of the products screened, 51 had an IFU and a MPAV available for evaluation. They were primarily made to support the use of auto-injectors (n = 25) and pre-filled syringes (n = 19). Of this group, we found that 11 had no differences between the IFU and MPAV, while the other 40 had at least one or more identifiable differences. Differences were stratified into the following sub-categories from most to least prevalent: word choice differences, supplementary information, missing information, and unaligned directions. We looked at the distribution of differences per biological product and found an average of two differences per MPAV (IQR 1-3). CONCLUSION: We suggest that when sponsors create or update MPAVs, to focus on aligning critical content between the respective IFU and MPAV. We believe that it is possible for MPAVs to potentially reduce medication errors as a non-text-based media form and that care should be taken to avoid substantial differences in critical content between the IFU and MPAV.

Improving Safety by Evaluating the Impact of the Supply Chain and Drug Shortages on Health-Systems.

Background: The COVID-19 pandemic has shown how fragile our healthcare supply chain is with product delays, drug shortages, and labor shortages being exacerbated in recent years. Objective: This article reviews current threats to the healthcare supply chain that impact patient safety and highlights potential solutions for the future. Method: A review of the literature was conducted, and important up-to-date resources associated with drug shortages and supply chain were analyzed to build foundational knowledge. Potential supply chain threats and solutions were then explored through further literature analyses. Conclusions: The information provided in this article helps to brief pharmacy leaders on current supply chain issues and solutions that can be integrated throughout the healthcare supply chain in the future.

Pulmonary Adenocarcinoma Mimicking Pneumonia in a Young Adult.

Lung cancer is the third most common cancer in the United States. Lung adenocarcinoma is a subtype of non-small cell lung cancer. On computed tomography (CT) it can appear as ground glass nodules, consolidative opacity, or solid mass lesions located in the periphery. Because it can appear as a consolidation, it can sometimes be confused with an infectious process such as pneumonia. We present a case of a 27-year-old male initially diagnosed with pneumonia; however, three months later, when he presented to the hospital with worsening pleuritic chest pain, fever, and dyspnea after a bronchoscopy a week before admission, pathology was positive for adenocarcinoma.

Amoxicillin-Clavulanate Induced Liver Injury in a Young Female.

Amoxicillin-clavulanate (AC) is an antibiotic widely used for various infections. It has rarely been associated with drug-induced liver injury (DILI), mainly in males 55 or older with associated alcohol consumption or medications causing liver injury. Here we present an atypical case of a 22-year-old female with a past medical history of celiac disease and alopecia areata who was prescribed AC in urgent care for bilateral cervical lymphadenopathy, nausea, and chills. Her nausea and vomiting worsened after taking AC for three days, and she developed jaundice. On workup, she was found to have deranged liver functions, and pan-lobular hepatitis was confirmed on liver biopsy. She started to improve symptomatically after withdrawing AC, and her transaminases started showing a decreasing trend.

The predictability of expansion with Invisalign: A retrospective cohort study.

INTRODUCTION: Few studies have evaluated the predictability of expansion with Invisalign for the current SmartTrack material. METHODS: Pretreatment, predicted, and posttreatment digital models from Invisalign's ClinCheck software were obtained for 57 adult patients with a planned arch expansion of at least 3 mm. Arch width measurements were collected using a software measuring tool (MeshLab), Invisalign's arch width table, and the centroid of the clinical crown. Data for 30 patients were remeasured for each method to assess intrarater reliability. Predictability of expansion was calculated by comparing the amount of achieved expansion to predicted expansion. RESULTS: The predictability of expansion across centroids for the maxillary teeth was: 72.2% canines, 78.9% first premolars, 81.1% second premolars, 63.5% first molars, and 41.5% second molars. The predictability of expansion across centroids for the mandibular teeth was: 82.3% canines, 93.0% first premolars, 87.7% second premolars, 79.8% first molars, and 42.9% second molars. The average expansion was significantly different from that predicted for each type of tooth in both the maxilla and mandible. Both underexpansion and overexpansion were observed. Arch width measurement reliability for each employed method was as follows: MeshLab (average error 0.197 mm); calculated centroids (0.002 mm); ClinCheck arch width table (0.000 mm). CONCLUSIONS: On average, the amount of predicted expansion is not achieved with the Invisalign system and varies according to tooth type and arch. Discretion is required when overcorrecting to compensate for expansion inaccuracy. Both underexpansion and overexpansion were observed; further investigation into factors influencing underexpansion and overexpansion is required.

COVID-19 and Pregnancy.

It is of greatest concern how COVID-19 is affecting pregnancy, mothers, and babies. Scientists are studying the impact of COVID-19 on pregnant women and babies and are understanding a little more every day. Reports show that there is an increased risk in pregnant women compared to nonpregnant women to get more serious illness due to COVID-19. Researchers are also investigating COVID-19 and its potential impact on a fetus. There are exceedingly rare cases of COVID-19 transmission to the fetus, and newborns can pick up COVID-19 when exposed. Vaccines are proved to be safe for pregnant women and help prevent both mother and the fetus from getting COVID-19 and are also highly effective to prevent COVID-19 infection, critical sickness, and fatalities in general. There are specific guidelines for labor and delivery during the COVID-19 pandemic which are to be imposed and followed to achieve safer and healthier childbirth. In this article, the overall influence of COVID-19 in pregnancy, its pathophysiology, effects on placenta and neonates, maternal and perinatal features and outcomes, the role of vaccination, available treatment options, and the guidelines to be followed during the pandemic are discussed based on the available scientific evidence.

The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury.

BACKGROUND: Non-invasive, external low intensity focused ultrasound (liFUS) offers promise for treating neuropathic pain when applied to the dorsal root ganglion (DRG). OBJECTIVE: We examine how external liFUS treatment applied to the L5 DRG affects neuronal changes in single-unit activity from the primary somatosensory cortex (SI) and anterior cingulate cortex (ACC) in a common peroneal nerve injury (CPNI) rodent model. METHODS: Male Sprague Dawley rats were divided into two cohorts: CPNI liFUS and CPNI sham liFUS. Baseline single-unit activity (SUA) recordings were taken 20 min prior to treatment and for 4 h post treatment in 20 min intervals, then analyzed for frequency and compared to baseline. Recordings from the SI and ACC were separated into pyramidal and interneurons based on waveform and principal component analysis. RESULTS: Following CPNI surgery, all rats (n = 30) displayed a significant increase in mechanical sensitivity. In CPNI liFUS rats, there was a significant increase in pyramidal neuron spike frequency in the SI region compared to the CPNI sham liFUS animals beginning at 120 min following liFUS treatment (p < 0.05). In the ACC, liFUS significantly attenuated interneuron firing beginning at 80 min after liFUS treatment (p < 0.05). CONCLUSION: We demonstrate that liFUS changed neuronal spiking in the SI and ACC regions 80 and 120 min after treatment, respectively, which may in part correlate with improved sensory thresholds. This may represent a mechanism of action how liFUS attenuates neuropathic pain. Understanding the impact of liFUS on pain circuits will help advance the use of liFUS as a non-invasive neuromodulation option.

Disparities in colonoscopy utilization for lower gastrointestinal bleeding in rural vs urban settings in the United States.

BACKGROUND: Lower gastrointestinal bleeds (LGIB) is a very common inpatient condition in the United States. Gastrointestinal bleeds have a variety of presentations, from minor bleeding to severe hemorrhage and shock. Although previous studies investigated the efficacy of colonoscopy in hospitalized patients with LGIB, there is limited research that discusses disparities in colonoscopy utilization in patients with LGIB in urban and rural settings. AIM: To investigate the difference in utilization of colonoscopy in lower gastrointestinal bleeding between patients hospitalized in urban and rural hospitals. METHODS: This is a retrospective cohort study of 157748 patients using National Inpatient Sample data and the Healthcare Cost and Utilization Project provided by the Agency for Healthcare Research and Quality. It includes patients 18 years and older hospitalized with LGIB admitted between 2010 and 2016. This study does not differentiate between acute and chronic LGIB and both are included in this study. The primary outcome measure of this study was the utilization of colonoscopy among patients in rural and urban hospitals admitted for lower gastrointestinal bleeds; the secondary outcome measures were in-hospital mortality, length of stay, and costs involved in those receiving colonoscopy for LGIB. Statistical analyses were all performed using STATA software. Logistic regression was used to analyze the utilization of colonoscopy and mortality, and a generalized linear model was used to analyze the length of stay and cost. RESULTS: Our study found that 37.9% of LGIB patients at rural hospitals compared to approximately 45.1% at urban hospitals received colonoscopy, (OR = 0.730, 95%CI: 0.705-0.7, P > 0.0001). After controlling for covariates, colonoscopies were found to have a protective association with lower in-hospital mortality (OR = 0.498, 95%CI: 0.446-0.557, P < 0.0001), but a longer length of stay by 0.72 d (95%CI: 0.677-0.759 d, P < 0.0001) and approximately $2199 in increased costs. CONCLUSION: Although there was a lower percentage of LGIB patients that received colonoscopies in rural hospitals compared to urban hospitals, patients in both urban and rural hospitals with LGIB undergoing colonoscopy had decreased in-hospital mortality. In both settings, benefit came at a cost of extended stay, and higher total costs.

COVID-19 Vaccine-Related Arthritis: A Descriptive Study of Case Reports on a Rare Complication.

Large-scale coronavirus disease 2019 (COVID-19) vaccination programs have been rolled out worldwide. Vaccines that are widely used globally include mRNA vaccines, adenoviral vector vaccines, and inactivated whole-virus vaccines. COVID-19 vaccines can lead to varying side effects. Among the most common of these adverse effects are pain at the injection site, fatigue, and headaches. Some side effects, however, are not very well documented, and these include joint-related adverse effects. In this review, we assess the epidemiology and clinical features of post-COVID-19 vaccination joint-related adverse effects based on the analysis of 16 patient case reports. Based on our analysis, we found that females formed the majority of the cases, accounting for 62.5% of patients, while 37.5% of the cases were males. The mean age of presentation among the patients was 54.8 years, with a standard deviation (SD) of 17.49 years. In 37.5% of the cases, patients received the Sinovac vaccine. The proportion of patients who received other vaccines was as follows: the Pfizer vaccine: 31.25%; Sputnik V: 12.5%; Moderna, AstraZeneca, and Covaxin: 6.25% each. The characteristics of joint-related adverse effects following COVID-19 vaccination were analyzed in this study. We identified several key findings related to factors such as age, gender, type of vaccine, clinical features, and diagnosis modality. Our analysis showed that more cases were reported among individuals who received the Sinovac vaccine, as compared to the others. Further research is required to examine the underlying cause of this association.

A Case Report of Severe Posterior Reversible Encephalopathy Syndrome Due to Accelerated Hypertension in a Young Patient.

Posterior reversible encephalopathy syndrome (PRES) refers to white matter vasogenic edema primarily affecting the brain's posterior occipital and parietal lobes, causing acute neurological symptoms like headaches, visual symptoms, seizures, and altered mental status. We present the case of a 32-year-old male with uncontrolled hypertension, altered mental status, and left-sided weakness. He had a rapid neurological decline, and a computed tomography (CT) head showed blurring of gray-white matter interfaces in the right posterior parietal lobe, suggesting infarction or PRES. Magnetic resonance imaging (MRI) of the brain suggested worsening with acute-early subacute infarction involving the right temporal, parietal, and occipital lobes and diffuse cerebral edema causing compression of the right ventricle with diffuse sulcal effacement and central downward herniation. There were flair hyperintensities in the bifrontal, pons, and cerebellum. Given the history of uncontrolled hypertension, the right hemispheric infarction and edema were thought to be due to secondary complications of severe PRES. He underwent urgent bilateral craniectomies with dural augmentation and external ventricular drain placement to control the intracranial pressure the next day. His mental status, as well as neurologic function, showed gradual improvement in the next few months. A high index of suspicion and rapid treatment can pave the way for a quick recovery and help reduce morbidity and death.

Low Intensity Focused Ultrasound Increases Duration of Anti-Nociceptive Responses in Female Common Peroneal Nerve Injury Rats.

OBJECTIVE: Chronic pain affects 7%-10% of Americans, occurs more frequently and severely in females, and available treatments have been shown to have less efficacy in female patients. Preclinical models addressing sex-specific treatment differences in the treatment of chronic pain have been limited. Here we examine the sex-specific effects of low intensity focused ultrasound (liFUS) in a modified sciatic nerve injury (SNI) model. MATERIALS AND METHODS: A modified SNI performed by ligating the common peroneal nerve (CPN) was used to measure sensory, behavioral pain responses, and nerve conduction studies in female and male rats, following liFUS of the L5 dorsal root ganglion. RESULTS: Using the same dose of liFUS in females and males of the same weight, CPN latency immediately after treatment was increased for 50 min in females compared to 25 min in males (p < 0.001). Improvements in mechanical pain thresholds after liFUS lasted significantly longer in females (seven days; p < 0.05) compared to males (three days; p < 0.05). In females, there was a significant improvement in depression-like behavior as a result of liFUS (N = 5; p < 0.01); however, because males never developed depression-like behavior there was no change after liFUS treatment. CONCLUSIONS: Neuromodulation with liFUS has a greater effect in female rats on CPN latency, mechanical allodynia duration, and depression-like behavior. In order to customize neuromodulatory techniques for different patient phenotypes, it is essential to understand how they may alter sex-specific pathophysiologies.

COVID-19 Vaccine-Related Myocarditis: A Descriptive Study of 40 Case Reports.

After the surging rise in the Coronavirus disease 2019 (COVID-19) pandemic, the Food and Drug Administration (FDA) approved emergency approval of vaccinations to prevent life-threatening complications of COVID-19 infection. These vaccines are BNT162b2, mRNA-1273. Later, the FDA also approved JNJ-78436735. COVID-19 vaccination does not have major side effects, but there are some concerning adverse events reported right after vaccination. Myocarditis is one of them. Based on our analysis of 40 case reports, we are presenting the epidemiology and clinical picture of myocarditis related to the COVID-19 vaccine. Based on our analysis, we found that the majority of cases were seen in males with 90% predominance, and these cases were seen in the age group of 29.13 years old (mean, SD of 14.39 years). In 65% of cases, patients took the BNT162b2 vaccine; 30% of cases were reported with the mRNA-1273 vaccine; and 5% of cases with JNJ-78436735. Of all the cases, 80% of them are reported after the second dose of the vaccine with either Moderna or Pfizer. The characteristics of COVID-19 vaccine-related myocarditis were analyzed in this study. We identified several findings, ranging from age, gender, type of vaccination, presentation of symptoms, and diagnosis modality. This depicts the picture of COVID-19 vaccine-related myocarditis and what physicians should expect when dealing with the disease. Our analysis showed that more cases were reported after receiving the BNT162b2 vaccine compared to mRNA-1273 and JNJ-78436735 vaccines. Further research needs to be conducted to analyze the underlying cause of this association.

Chronic Steroid Use Causing Spinal Epidural Lipomatosis.

Chronic steroid use causes aberrant fat deposition in the epidural space, which may in rare cases result in spinal epidural lipomatosis (SEL). We discuss the case of a 79-year-old female who had been on steroids for a long time, initially for polymyalgia rheumatica (PMR), then for adrenal insufficiency. Her dose was raised with a few steroid stress doses to control the flare of adrenal insufficiency. The patient presented with complaints of intractable lumbosacral pain and was subsequently diagnosed with SEL and foraminal and spinal canal stenosis based on magnetic resonance imaging of the lumbar spine. She successfully underwent laminectomy.

Necrotizing Fasciitis: A Life-Threatening Infection Due to Clostridium Species.

Necrotizing fasciitis (NF), soft tissue infections, are rare but rapidly progressive and life-threatening infections with high morbidity and mortality rates. Early detection and intervention by physicians are paramount in mortality prevention. We present a case report of a 77-year-old female who presented with extensive NF due to a Clostridium septicum infection.

Rare Adverse Events Related to Nivolumab, an Immune Checkpoint Inhibitor: A Case Series.

Immune checkpoint inhibitors are a novel class of immunotherapy drugs that have improved the prognosis of melanoma, renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma, and various other solid tumors. Nivolumab is an immune checkpoint inhibitor that acts by inhibiting programmed death. Its use is associated with significant immune-related adverse events, such as pneumonitis, thyroiditis, hepatitis, pruritus, vitiligo, and diarrhea. However, adrenal insufficiency and checkpoint inhibitor-related autoimmune diabetes mellitus are extremely rare adverse events related to nivolumab treatment. Here, we are highlighting cases of adrenal insufficiency and diabetes inspidus as a result of nivolumab. These rare adverse events in our case series are to raise awareness that this medication also may be the cause for this illness among oncologists, endocrinologists, internists, and other clinicians.

A systematic review of acute telogen effluvium, a harrowing post-COVID-19 manifestation.

This systematic review focuses on the clinical features, physical examination findings, outcomes, and underlying pathology of acute telogen effluvium (TE), a type of diffuse hair loss, occurring in coronavirus disease 2019 (COVID-19) recovered patients. MEDLINE/PubMed and Embase databases were queried till October 2021 to identify studies reporting acute TE occurring after COVID-19 recovery. Data were obtained from 19 studies, which included 465 patients who were diagnosed with acute TE. The median age of these patients was 44 years and 67.5% were females. The most common trichoscopic findings were decreased hair density, the presence of empty follicles, or short regrowing hair. The mean duration from COVID-19 symptom onset to the appearance of acute TE was 74 days, which is earlier than classic acute TE. Most patients recovered from hair loss, while a few patients had persistent hair fall. Our results highlight the need to consider the possibility of post-COVID-19 acute TE in patients presenting with hair fall, with a history of COVID-19 infection, in the context of COVID-19 pandemic. Despite being a self-limiting condition, hair loss post-COVID-19 is a stressful manifestation. Identifying COVID-19 infection as a potential cause of acute TE will help the clinicians counsel the patients, relieving them from undue stress.

A Case Report of Sepsis Post Cardiac Catheterization.

Percutaneous coronary intervention (PCI) and cardiac catheterization are clean procedures done under aseptic precautions, but studies have shown transient bacteremia following the process, mostly involving Staphylococcus. This has many complications, from localized wounds at arterial access sites to endocarditis, mycotic aneurysm, and sepsis, and are associated with high mortality. These may require surgical intervention and prolonged antibiotic use. The risk of acquiring these infections is higher in femoral catheterization than in radial access. This risk also increases in patients with congestive cardiac failure, age 60 and above, and those with diabetes and obesity. Procedural hazards include multiple punctures and leaving the sheath for future access due to the needle tract's colonization. We present a case of sepsis presenting two days after PCI using single puncture radial access and a rapid downhill course.

The Epidemiology and Clinical Manifestations of Takayasu Arteritis: A Descriptive Study of Case Reports.

Takayasu's arteritis is a rare form of chronic inflammatory disorder involving large vessels, with an unclear etiology. Common early signs and symptoms are weakness, malaise, and fever. Takayasu's arteritis mainly involves the aorta and its branches as well as the subclavian and carotid arteries. While radiologic methods can identify diseased vessels, they can't tell the difference between active and chronic lesions. This study reviews the characteristics of Takayasu's arteritis to identify any possible changes in the prevalence of symptoms of the disease. We conducted a literature review of case reports on Takayasu arteritis from PubMed and Google Scholar. Variables of interest were age, gender, symptoms, blood pressure (BP) measurement, diminished pulses, and radiological findings. Data were transferred to an Excel spreadsheet (Microsoft Corporation, Redmond, WA), and mean, median, and standard deviation, frequencies, and proportions were calculated using R version 1.1.456 (RStudio: Integrated Development for R. RStudio, PBC, Boston, MA). There were 43 cases, and females accounted for 88.3% of the presentations. The average age was 25 years, SD 12.5 years. Fever was the most frequent symptom (20.93%), followed by chest pain (13.95%), claudication (13.95%), and headache (13.95%). Less frequent complaints included shortness of breath (11.62%), weight loss (9.30%), syncope (6.98%), and night sweats (4.65%). On the right side, the average BP was 142/87 mmHg, and the left-sided finding averaged 115/72 mmHg. Decreased pulses were primarily seen in the radial artery with 15 cases. Radiological findings showed narrowing of the vessels in the following order: aorta (22), carotid (11), renal (10), subclavian (9), celiac (2), mesenteric (2), axillary (2), and tibial (1). The characteristics of Takayasu's arteritis were analyzed in this study. It identified several findings, ranging from fever symptoms to the signs of claudication, as well as the involvement of major vessels, such as the aorta and its branches, and a summary of radiological findings. This depicts the picture of Takayasu's arteritis and what physicians should expect when dealing with the disease.