New Insights Into the Treatment of Hyperlipidemia: Pharmacological Updates and Emerging Treatments.

Cardiovascular diseases are the leading causes of global mortality and morbidity. Hyperlipidemia is a significant risk factor for atherosclerosis and subsequent cardiovascular diseases. Hyperlipidemia is characterized by imbalances in blood cholesterol levels, particularly elevated low-density lipoprotein cholesterol and triglycerides, and is influenced by genetic and environmental factors. Current management consists of lifestyle modifications and pharmacological interventions most commonly consisting of statins. This review paper explores pathophysiology, management strategies, and pharmacotherapies including commonly used well-established medications including statins, fibrates, and ezetimibe, exciting novel therapies including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and RNA interference therapies (inclisiran), lomitapide, and bempedoic acid, highlighting their mechanisms of action, clinical efficacy, and safety profiles. Additionally, emerging therapies under clinical trials including ApoC-III inhibitors, DGAT2 inhibitors, ACAT2 Inhibitors, and LPL gene therapies are examined for their potential to improve lipid homeostasis and cardiovascular outcomes. The evolving landscape of hyperlipidemia management underscores the importance of continued research into both established therapies and promising new candidates, offering hope for more effective treatment strategies in the future.

Triple Stentriever "Bouquet" Deployment with Zoom 88 Large-Bore Aspiration and Walrus Balloon-Guide Catheter for the Definitive Thrombectomy of a Carotid Free-Floating Thrombus.

Formation of a carotid free-floating thrombus (CFFT) is a rare and life-threatening condition without an optimal management plan. A 78-year-old woman with a history of prior right internal carotid artery (ICA) mechanical thrombectomy and antiplatelet noncompliance presented with transient ischemic attacks secondary to a recurrent CFFT in the right ICA. Given her symptoms and recurrent CFFT, endovascular mechanical thrombectomy was performed. A balloon guide-catheter (BGC) and a Zoom 88 distal access catheter were brought into the right distal common carotid artery and proximal ICA bulb, respectively. Three 0.021-inch microcatheters, each loaded with a unique stentriever, were navigated beyond the thrombus into the upper cervical ICA and deployed in a bouquet fashion. The BGC was inflated to achieve flow arrest, and the Zoom 88 aspiration catheter was tracked over the three bouquet stentrievers to ingest the thrombus. Follow-up angiography demonstrated recanalization of the proximal cervical ICA without evidence of residual thrombus. Twenty-four-hour postoperative computed tomography imaging did not reveal any evidence of new infarction. The patient was discharged home with an intact neurological examination, compliant on aspirin and apixaban. We demonstrate a novel technique utilizing a large-bore catheter with a triple stentriever "bouquet" to thrombectomize a CFFT.

Tunable plasmonic superchiral light for ultrasensitive detection of chiral molecules.

The accurate detection, classification, and separation of chiral molecules are pivotal for advancing pharmaceutical and biomolecular innovations. Engineered chiral light presents a promising avenue to enhance the interaction between light and matter, offering a noninvasive, high-resolution, and cost-effective method for distinguishing enantiomers. Here, we present a nanostructured platform for surface-enhanced infrared absorption-induced vibrational circular dichroism (VCD) based on an achiral plasmonic system. This platform enables precise measurement, differentiation, and quantification of enantiomeric mixtures, including concentration and enantiomeric excess determination. Our experimental results exhibit a 13 orders of magnitude higher detection sensitivity for chiral enantiomers compared to conventional VCD spectroscopic techniques, accounting for respective path lengths and concentrations. The tunable spectral characteristics of this achiral plasmonic system facilitate the detection of a diverse range of chiral compounds. The platform's simplicity, tunability, and exceptional sensitivity holds remarkable potential for enantiomer classification in drug design, pharmaceuticals, and biological applications.

A Rare Case of Cutaneous Metastasis of Unresectable Rectal Adenocarcinoma.

Colorectal cancer (CRC) is the third most common malignancy. Common metastatic sites for colorectal carcinoma are the lung and liver while cutaneous metastases are extremely rare. Skin metastasis may be an early manifestation of metastatic disease and represents a poor prognosis. Here we present a case of metachronous skin metastasis during chemoradiation treatment in a patient with locally advanced rectal cancer. A young boy aged 19 years presented to our hospital with radiological TNM staging of T3c N1 M0 with circumferential resection margin (CRM) involved. The treatment plan was defunctioning colostomy with neoadjuvant chemotherapy and radiotherapy with a later plan for surgery. Seven months later, there is a focal skin nodule in the nape of the neck. A core biopsy of this cutaneous nodule was done and proved metastatic. Surgery for the primary tumor and oligometastatic site was planned but due to extensive primary tumor, surgery was terminated and continues with chemotherapy and reassessment.

A low-dose thrombolytic infusion protocol for safe and successful treatment of left ventricular assist device thrombosis: a case series.

Background: Pump thrombosis is a serious complication of continuous-flow left ventricular assist device (CF-LVAD) therapy. In this study, we aim to report a novel protocol of an intermittent, low-dose, and slow infusion of tissue plasminogen activator (alteplase). Case summary: We treated seven LVAD pump thrombosis events (HeartMate® II and HeartWare) in four patients with a median age of 52 years (31-63), and all were female. The protocol was applied from January 2015 to December 2018, and it consisted of an intermittent, low-dose, and slow infusion of systemic thrombolytic therapy in the intensive care unit. This therapy resulted in successful resolution of pump thrombosis in six out of seven events. Bleeding complication occurred in one patient, which included a ruptured haemorrhagic ovarian cyst and a small cerebellar intra-parenchymal haemorrhage. All patients were discharged home in a stable condition, except one patient who died during hospitalization because of severe sepsis, pump thrombosis with subsequent pump exchange, and multi-organ failure. Discussion: A low-dose, prolonged, and systemic thrombolytic infusion protocol is an effective and relatively safe treatment that can lead to a sustained resolution of pump thrombosis with low bleeding complications and failure rates.

Ten-Fold Elevation of Chromogranin A Level Unrelated to a Neuroendocrine Tumor: A Case Report of the Diagnostic Interference of Proton Pump Inhibitors.

Chromogranin A (CgA) is a well-known biomarker for neuroendocrine tumors (NETs). However, due to its non-specificity, a proper assessment of CgA test results requires a detailed knowledge of the factors, conditions, and medications influencing its serum concentration. We describe a case of a 61-year-old patient presenting with a mass suspicious of a gastrointestinal NET and an exceedingly high level of serum CgA persistent after mass resection. Following a thorough review of patient's medical history and clinical presentation, along with radiographic and pathological findings, no evidence of a NET was detected. A trial of proton-pump inhibitor (PPI) withdrawal led to a dramatic normalization of CgA level, marking it as the culprit causing this tumor marker elevation. This case highlights the significant impact of PPI use on CgA level, and should incentivize clinicians to provide proper education to patients prior to testing.

Exploration of computational approaches to predict the structural features and recent trends in α-amylase production for industrial applications.

Amylases are biologically active enzymes that can hydrolyze starch to produce dextrin, glucose, maltose, and oligosaccharides. The amylases contribute approximately 30% to the global industrial enzyme market. The globally produced amylases are widely used in textile, biofuel, starch processing, food, bioremediation of environmental pollutants, pulp, and paper, clinical, and fermentation industries. The purpose of this review article is to summarize recent trends and aspects of α-amylases, classification, microbial production sources, biosynthesis and production methods, and its broad-spectrum applications for industrial purposes, which will depict the latest trends in α-amylases production. In the present article, we have comprehensively compared the biodiversity of α-amylases in different model organisms ranging from archaea to eukaryotes using in silico structural analysis tools. The detailed comparative analysis: regarding their structure, function, cofactor, signal peptide, and catalytic domain along with their catalytic residues of α-amylases in 16 model organisms were discussed in this paper. The comparative studies on alpha (α) amylases' secondary and tertiary structures, multiple sequence alignment, transmembrane helices, physiochemical properties, and their phylogenetic analysis in model organisms were briefly studied. This review has documented the recent trends and future perspectives of industrially important novel thermophilic α-amylases. In conclusion, this review sheds light on the current understanding and prospects of α-amylase research, highlighting its importance as a versatile enzyme with numerous applications and emphasizing the need for further exploration and innovation in this field.

Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older.

INTRODUCTION AND OBJECTIVES: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM). PATIENTS AND METHODS: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 µmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. RESULTS: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. CONCLUSIONS: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. CLINICAL TRIAL NUMBERS: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.

Ecosystem anthropogenic enrichments enhance Chroococcus abundance and suppress Anabaena during cyanobacterial-dominated spring blooms in the Pengxi River, Three Gorges Reservoir, China.

Taxa-specific responses to the increasing anthropogenic eutrophication offer promising insights for mitigating harmful algal blooms (HABs) in freshwaters. The present study evaluated the HABs species dynamics in response to the ecosystem anthropogenic enrichment during cyanobacterial-dominated spring HABs in the Pengxi River, Three Gorges Reservoir, China. Results show significant cyanobacterial dominance with a relative abundance (RA = 76.54 %). The ecosystem enrichments triggered shifts in the HABs community structure from Anabaena to Chroococcus, especially in the culture involving iron (Fe) addition (RA = 66.16 %). While P-alone enrichment caused a dramatic increase in the aggregate cell density (2.45 × 108 cells L-1), the multiple enrichment (NPFe) led to maximum biomass production (as chl-a = 39.62 ± 2.33 µgL-1), indicating that nutrient in conjunction with the HABs taxonomic characteristics e.g., tendency to possess high cell pigment contents rather than cell density can potentially determine massive biomass accumulations during HABs. The stimulation of growth as biomass production demonstrated by both P-alone and the multiple enrichments, NPFe indicates that although P exclusive control is feasible in the Pengxi ecosystem, it can only guarantee a short-term reduction in HABs magnitude and duration, thus a lasting HABs mitigation measure must consider a policy recommendation involving multiple nutrient management, especially N and P dual control strategy. The present study would adequately complement the concerted effort in developing a rational predictive framework for freshwater eutrophication management and HABs mitigations in the TGR and elsewhere with similar anthropogenic stressors.

The need of patients living with cancer for palliative care.

BACKGROUND: A comprehensive assessment of patients' problems and needs is essential for all patients with chronic diseases, including cancer. AIM: This study assesses the problems, unmet needs and requirement for palliative care (PC) among patients with cancer. METHOD: A descriptive cross-sectional design was employed using a valid self-reported questionnaire. RESULTS: On average, 62% of patients had problems that were unresolved. The need for patients to have more information about their health was identified (75.1%), followed by financial problems because of the illness and ability to afford healthcare (72.9%), and psychological issues, such as depression, anxiety and stress (67.1%). Patients stated that their spiritual needs were not being met (78.8%), and that they were experiencing psychological distress and problems with daily living that needed to be addressed through PC (78%, 75.1%, respectively). A chi-square test revealed that all problems are significantly associated with the need for PC (P<.001). CONCLUSION: Patients needed more assistance in psychological, spiritual, financial and physical domains, and this can be provided by palliative care. Palliative care in low-income countries is a human right for patients with cancer.

A case of spontaneous basal ganglia hemorrhage with contralateral extension utilizing the canal of Gratiolet.

BACKGROUND: Intracranial hemorrhage accounts for 10-20% of stroke etiologies annually. Basal ganglia is the most common site for intracranial hemorrhage accounting for 50% of all cases. Bilateral spontaneous basal ganglia hemorrhages (BGH) are rare with few reported cases. CASE PRESENTATION: We report an unusual case of a 69-year-old female who presented with a spontaneous bilateral basal ganglia hemorrhage secondary to a right BGH with contralateral extension through the anterior commissure (AC) utilizing the Canal of Gratiolet. Clinical course and imaging findings are discussed. CONCLUSIONS: To our knowledge, this is the first case to specifically detail the extension of spontaneous hemorrhage across the AC via the Canal of Gratiolet, and imaging findings provide a novel depiction of AC anatomy and fiber distribution in a clinical context. These findings may explain the mechanism behind this rare clinical entity.

Coexistence of a Heterozygous Caveolin-3 Deletion and a Novel Dystrophin Gene Mutation in a Duchenne Muscular Dystrophy Patient.

Inherited muscular abnormalities are debilitating disorders that greatly diminish the quality of life in affected individuals. Mutations in proteins such as dystrophin and caveolin, which together with other proteins form structural connections between the cytoskeleton and the extracellular matrix, are frequently the culprit of muscular dystrophies. In this case report, we describe a patient with a novel pathogenic dystrophin mutation co-existing with a caveolin-3 deletion. While genetically composed of this unique combination, the patient phenotypically presented with a primary clinical manifestation of Duchenne muscular dystrophy (DMD) in contrast to other cases of dual mutations in dystrophin and dystrophin-associated proteins.

A PRECEDE-PROCEED model-based educational intervention to promote healthy eating habits in middle school girls.

The present study was designed to develop Nutrition Education Program (NEP) based on PRECEDE-PROCEED model (PPM) to address healthy eating behavior among middle school girls aged between 4 and 12 years. For this, middle school girls from grade 1 to 8 (n = 900) were consulted for their eating behaviors, followed by the analysis of their health problems. From 15 different schools of three large cities (Faisalabad, Lahore, and Rawalpindi) of Pakistan, students were divided into two groups: control group (n = 30) and intervention group (n = 30) from each school. The data were collected through interview-based questionnaires according to the phases of PRECEDE Model and evaluated based on PROCEED model. Implementation of NEP was carried out through lectures. Lessons were prepared to enhance student's awareness about nutritious food and healthy lifestyle through educational pamphlets and influenced their attitude towards selection of food choices from My-Plate. Results showed that NEP was quite successful for long-term results. A significant increase in total caloric intake was observed after 8 weeks of NEP intervention (1694 ± 217 Kcal) as compared to before intervention (1329 ± 318 Kcal). Similarly, carbohydrate, protein, and fat content was also increased in daily diet. Conclusively, NEP based on PPM has great impact on healthy lifestyle of middle school girls. Significant difference was observed in score of health variables before and after NEP intervention.

Spatio-temporal numerical modeling of stochastic predator-prey model.

In this article, the ratio-dependent prey-predator system perturbed with time noise is numerically investigated. It relates to the population densities of the prey and predator in an ecological system. The initial prey-predator models only depend on the time and a couple of the differential equations. We are considering a model where the prey-predator interaction is influenced by both space and time and the need for a coupled nonlinear partial differential equation with the effect of the random behavior of the environment. The existence of the solutions is guaranteed by using Schauder's fixed point theorem. The computation of the underlying model is carried out by two schemes. The proposed stochastic forward Euler scheme is conditionally stable and consistent with the system of the equations. The proposed stochastic non-standard finite difference scheme is unconditionally stable and consistent with the system of the equations. The graphical behavior of a test problem for different values of the parameters is shown which depicts the efficacy of the schemes. Our numerical results will help the researchers to consider the effect of the noise on the prey-predator model.

Development of myocarditis and pericarditis after COVID-19 vaccination in children and adolescents: A systematic review.

Myocarditis and pericarditis have been reported after COVID-19 vaccine administration in children and adolescents, raising the concern about their possible association with these vaccines. The objective was to explore the incidence, clinical presentation, and association of myocarditis and pericarditis with COVID-19 vaccines in children and adolescents. We conducted a systematic literature search on three databases, that is, Cochrane, MEDLINE/PubMed, and EMBASE from inception till March 2022. A total of three case reports, four case series, and six observational studies were included in the review. For case reports and case series, the mean age of the patients was 17.4 years, with 96.9% being male. Chest pain (n = 31, 93.9%), fever (n = 18, 54.5%), myalgias (n = 15, 45.4%) and headache (n = 9, 27.2%) were the most common presentations. Out of 33 patients, 32 (96.9%) of patients received Pfizer-BioNTech whereas only one (3.03%) received Moderna (mRNA 1273). Clinical investigations revealed ST elevation (n = 32, 97%), and elevated CRP (n = 9, 27.2%) and cardiac troponin (n = 29, 87.8%). The pooled incidence of myocarditis and pericarditis from observational studies was (0.00063%) and (0.000074%) %, respectively. Myocarditis and pericarditis in children and adolescents after the COVID-19 vaccines were more prevalent among males and more commonly observed after the second dose of Pfizer. Though the overall incidence was low, however, the clinicians should consider myocarditis and pericarditis as probable diagnosis when encountering young patients, with a history of vaccine administration, presenting with suggestive findings.

Music to the Ears: An Unusual Case of Frontal Lobe Stroke With Complex Auditory Hallucinations.

Auditory hallucinations are defined as the perception of sensory auditory input in the absence of an external stimulus. It is a multifaceted pathology with a range of symptoms and an even wider range of possible underlying causes. Its lack of true distinctive clinical features along with overlapping symptoms makes distinguishing between etiologies difficult without appropriate workup. Here, we present an unusual case of left frontal lobe ischemic infarction, resulting in complex musical auditory hallucinations in the absence of behavioral changes.