👤 Shraddha Pandya

The statins remain the foundation of lipid management because they lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular events, and guidelines recommend stepwise intensification, often with ezetimibe first, when targets are not met or when intolerance limits dosing. This review introduces a mechanism-first, phenotype-guided framework that links add-on therapies to the dominant driver of residual risk, LDL-C, triglyceride-rich lipoproteins, elevated lipoprotein(a), or inherited dyslipidemia while integrating trial evidence with clinical practicality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies remain the best-validated add-on for very high-risk patients. FOURIER and ODYSSEY OUTCOMES demonstrated event reduction with evolocumab or alirocumab on background statin therapy. For patients who cannot tolerate adequate statin doses, bempedoic acid provides liver-selective inhibition of adenosine triphosphate (ATP)-citrate lyase, and CLEAR Outcomes showed fewer major cardiovascular events in statin-intolerant populations. Inclisiran extends PCSK9 pathway suppression through hepatic small interfering RNA (siRNA) and enables durable LDL-C reduction with twice-yearly maintenance dosing, offering an adherence-oriented alternative while outcomes data mature. Angiopoietin-like protein 3 (ANGPTL3)-directed therapies (evinacumab and investigational RNAi agents such as zodasiran) lower atherogenic lipoproteins through largely LDL receptor independent biology. They expand options for refractory disease, including homozygous familial hypercholesterolemia. Apolipoprotein C-III (ApoC-III) inhibitors (olezarsen and plozasiran) drive large triglyceride reductions that can be decisive in severe hypertriglyceridemia and pancreatitis-prone syndromes. Next-generation cholesteryl ester transfer protein (CETP) inhibition (notably obicetrapib) has re-emerged as an oral strategy with substantial lipid effects as outcomes programs progress. High-dose eicosapentaenoic acid (EPA) (icosapent ethyl) has the clearest triglyceride-focused outcomes signal; REDUCE-IT showed significant ischemic event reduction in statin-treated patients with persistent hypertriglyceridemia. Early Show less

Poly(ADP-ribose) (PAR) polymerase-1 (PARP1) has been implicated in DNA damage responses and neuroinflammation in Alzheimer's disease (AD), yet its role in amyloid-β (Aβ) pathology remains unclear. Here, we show that PARP1 activation drives Aβ pathology and neurodegeneration. Using a sensitive ELISA, we observed significantly elevated PAR levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD compared to controls. Show less

Identifying the microbial community and their functional potential from different stages of common effluent treatment plants (CETP) can enhance the efficiency of wastewater treatment systems. In this study, wastewater metagenomes from 8 stages of CETP were screened for microbial diversity and gene profiling along with their corresponding degradation activities. The microbial community displayed 98.46% of bacterial species, followed by Eukarya (0.10%) and Archaea 0.02%. At the Phylum level, Proteobacteria (28.8%) was dominant, followed by Bacteroidetes (16.1%), Firmicutes (11.7%), and Fusobacteria (6.9%) which are mainly capable of degrading the aromatic compounds. Klebsiella pneumoniae, Wolinella succinogenes, Pseudomonas stutzeri, Desulfovibrio vulgaris, and Clostridium sticklandii were the most prevalent species. The functional analysis further demonstrated the presence of enzymes linked with genes/pathways known to be involved in the degradation/metabolization of aromatic compounds like benzoate, bisphenol, 1,2-dichloroethane phenylalanine. This information was further validated with the whole genome analysis of the bacteria isolated from the CETP. We anticipate that integrating both shotgun and whole-genome analyses can reveal the rich reservoir for novel enzymes and genes present in CETP effluent that can contribute to designing efficient bioremediation strategies for the environment in general CETP system, in particular. Show less