Panic in the Pandemic: Determinants of Vaccine Hesitancy and the Dilemma of Public Health Information Sharing during the COVID-19 Pandemic in Sri Lanka.

Vaccine hesitancy, a pressing global challenge in vaccination programs, was significantly amplified during the COVID-19 pandemic. The proliferation of misinformation, including false claims and rumours, and the influence of anti-vaccine movements fuelled hesitancy. This study aims to explore the socio-economic determinants that influenced vaccine hesitancy and the impact of public health information sharing in Sri Lanka during the pandemic.

Epidemic and Pandemic Preparedness and Response in a Multi-Hazard Context: COVID-19 Pandemic as a Point of Reference.

Infectious diseases manifesting in the form of epidemics or pandemics do not only cause devastating impacts on public health systems but also disrupt the functioning of the socio-economic structure. Further, risks associated with pandemics and epidemics become exacerbated with coincident compound hazards. This study aims to develop a framework that captures key elements and components of epidemic and pandemic preparedness and response systems, focusing on a multi-hazard context.

Frequency of Stroke and Factors Associated With It Among Old Age Hypertensive Patients in Karachi, Pakistan: A Cross-Sectional Study.

Introduction: Worldwide, stroke has become the major cause of mortality and morbidity among the old age population. Hypertension is one of the factors associated with stroke. Individuals with hypertension are at high risk of developing stroke.

Retraction: Determinants of Hypertension Among Patients With Type 2 Diabetes Mellitus in Karachi, Pakistan: A Cross-Sectional Study.

[This retracts the article DOI: 10.7759/cureus.22157.

Retraction: Comparison of High-Statin Therapy vs Moderate-Statin Therapy in Achieving Positive Low-Density Lipoprotein Change in Patients After Acute Coronary Syndrome: A Randomized-Control Trial.

[This retracts the article DOI: 10.7759/cureus.20710.

Determinants of Hypertension Among Patients With Type 2 Diabetes Mellitus in Karachi, Pakistan: A Cross-Sectional Study.

Introduction: Hypertension is the persistent rise of systemic arterial blood pressure. Among diabetic patients, hypertension is one of the important public health challenges. The frequency of hypertension among diabetic patients is almost twice than that of non-diabetic patients.

Comparison of High-Statin Therapy vs Moderate-Statin Therapy in Achieving Positive Low-Density Lipoprotein Change in Patients After Acute Coronary Syndrome: A Randomized-Control Trial.

Introduction: Statin use in secondary prevention after acute coronary syndrome (ACS) can play an important role in enhancing clinical outcomes, this has been proven in several randomized trials. This study was conducted to compare the efficacy of moderate-intensity and high-intensity statins in controlling low-density lipoprotein (LDL) after ACS.

Methodology: A randomized control trial was conducted at the Cardiology Department of Liaquat National Hospital, Karachi, Pakistan, from July 2020 to September 2021.

Inhibition of N-Methyl-D-aspartate-induced Retinal Neuronal Death by Polyarginine Peptides Is Linked to the Attenuation of Stress-induced Hyperpolarization of the Inner Mitochondrial Membrane Potential.

It is widely accepted that overactivation of NMDA receptors, resulting in calcium overload and consequent mitochondrial dysfunction in retinal ganglion neurons, plays a significant role in promoting neurodegenerative disorders such as glaucoma. Calcium has been shown to initiate a transient hyperpolarization of the mitochondrial membrane potential triggering a burst of reactive oxygen species leading to apoptosis. Strategies that enhance cell survival signaling pathways aimed at preventing this adverse hyperpolarization of the mitochondrial membrane potential may provide a novel therapeutic intervention in retinal disease.

A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death.

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation.

Modulating the dysregulated migration of pulmonary arterial hypertensive smooth muscle cells with motif mimicking cell permeable peptides.

Migration of vascular smooth muscle cells is a key element in remodeling during pulmonary arterial hypertension (PAH). We are observing key alterations in the migratory characteristics of human pulmonary artery smooth muscle cells (HPASMC) isolated from transplanted lungs of subjects with PAH. Using wound migration and barrier removal assays, we demonstrate that the PAH cells migrate under quiescent growth conditions and in the absence of pro-migratory factors such as platelet derived growth factor (PDGF).

Small-molecule inhibitors of JC polyomavirus infection.

The JC polyomavirus (JCPyV) infects approximately 50% of the human population. In healthy individuals, the infection remains dormant and asymptomatic, but in immuno-suppressed patients, it can cause progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease. Currently, there are no drugs against JCPyV infection nor for the treatment of PML.

Targeting receptor tyrosine kinases and their downstream signaling with cell-penetrating peptides in human pulmonary artery smooth muscle and endothelial cells.

Cell-penetrating peptide (CPP) intracellular delivery of receptor signaling motifs provides an opportunity to regulate specific receptor tyrosine kinase signal transductions. We targeted tyrosine residues Y740 and Y751 of the PDGF receptor β (PDGFRβ) and Y1175 of the VEGF receptor 2 (VEGFR2). The Y740 and Y751 motifs activated ERK and Akt, while the Y1175 motif activated ERK.

Gallic acid-based small-molecule inhibitors of JC and BK polyomaviral infection.

JCPyV and BKPyV are common human polyomaviruses that cause lifelong asymptomatic persistent infections in their hosts. In immunosuppressed individuals, increased replication of JCPyV and BKPyV cause significant disease. JCPyV causes a fatal and rapidly progressing demyelinating disease known as progressive multifocal leukoencephalopathy.

Spaser made of graphene and carbon nanotubes.

Spaser is a nanoscale source of surface plasmons comprising a plasmonic resonator and gain medium to replenish energy losses. Here we propose a carbon-based spaser design in which a graphene nanoflake (GNF) resonator is coupled to a carbon nanotube (CNT) gain element. We theoretically demonstrate that the optically excited CNT can nonradiatively transfer its energy to the localized plasmon modes of the GNF because of the near-field interaction between the modes and the CNT excitons.

A cell permeable peptide targeting the intracellular loop 2 of endothelin B receptor reduces pulmonary hypertension in a hypoxic rat model.

Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling motifs provides an opportunity to regulate specific receptor initiated signaling cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of antagonist therapies for individuals with pulmonary arterial hypertension (PAH).

killerFLIP: a novel lytic peptide specifically inducing cancer cell death.

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killerFLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein.

Design optimization of spasers considering the degeneracy of excited plasmon modes.

We model spaser as an n-level quantum system and study a spasing geometry comprising of a metal nanosphere resonantly coupled to a semiconductor quantum dot (QD). The localized surface plasmons are assumed to be generated at the nanosphere due to the energy relaxation of the optically excited electron-hole pairs inside the QD. We analyze the total system, which is formed by hybridizing spaser's electronic and plasmonic subsystems, using the density matrix formalism, and then derive an analytic expression for the plasmon excitation rate.

Selection of heptapeptides that bind helix 69 of bacterial 23S ribosomal RNA.

Helix 69 of Escherichia coli 23S rRNA has important roles in specific steps of translation, such as subunit association, translocation, and ribosome recycling. An M13 phage library was used to identify peptide ligands with affinity for helix 69. One selected sequence, NQVANHQ, was shown through a bead assay to interact with helix 69.

Enhancing and limiting endothelin-1 signaling with a cell-penetrating peptide mimicking the third intracellular loop of the ETB receptor.

TAT (a 13-mer derived from the HIV-1 Tat protein)-linked cell-permeable peptides deliver plasma membrane impermeable cargos into the cell. We investigated the effect of a TAT-linked intracellular third loop of the endothelin-1 type B receptor on endothelin-1 activation of ERK. The effect of this peptide on ERK activation was determined in ETB receptor cDNA-transfected Chinese hamster ovary cells and in ETA- and ETB-expressing human pulmonary artery smooth muscle cells obtained from a normal and a bone morphogenetic protein-2 receptor, exon 1-8 deletion subject, with pulmonary hypertension.

Chemically modified peptides targeting the PDZ domain of GIPC as a therapeutic approach for cancer.

GIPC (GAIP-interacting protein, C terminus) represents a new target class for the discovery of chemotherapeutics. While many of the current generation of anticancer agents function by directly binding to intracellular kinases or cell surface receptors, the disruption of cytosolic protein-protein interactions mediated by non-enzymatic domains is an underdeveloped avenue for inhibiting cancer growth. One such example is the PDZ domain of GIPC.

RGS-GAIP-interacting protein controls breast cancer progression.

Although the importance of RGS-GAIP-interacting protein (GIPC) in the biology of malignant cells is well known, the molecular mechanism of GIPC in the inhibition of tumor progression has not been identified. This study focused on elucidating the molecular role of GIPC in breast cancer progression. By using a human breast tumor specimen, an in vivo mouse model, and breast cancer cell lines, we showed for the first time that GIPC is involved in breast cancer progression through regulation of breast cancer cell proliferation, survival, and invasion.

A cyclic peptide targeted against PSD-95 blocks central sensitization and attenuates thermal hyperalgesia.

Post-synaptic density protein PSD-95 is emerging as a valid target for modulating nociception in animal studies. Based on the key role of PSD-95 in neuronal plasticity and the maintenance of pain behavior, we predicted that CN2097, a peptide-based macrocycle of nine residues that binds to the PSD-95 Discs large, Zona occludens 1 (PDZ) domains of PSD-95, would interfere with physiologic phenomena in the spinal cord related to central sensitization. Furthermore, we tested whether spinal intrathecal injection of CN2097 attenuates thermal hyperalgesia in a rat model of sciatic neuropathy.

Targeting GIPC/synectin in pancreatic cancer inhibits tumor growth.

Purpose: Various studies have shown the importance of the GAIP interacting protein, COOH-terminus (GIPC, also known as Synectin) as a central adaptor molecule in different signaling pathways and as an important mediator of receptor stability. GIPC/Synectin is associated with different growth-promoting receptors such as insulin-like growth factor receptor I (IGF-IR) and integrins. These interactions were mediated through its PDZ domain.

T7 phage display as a method of peptide ligand discovery for PDZ domain proteins.

The use of bacteriophage T7 is presented as a peptide display platform to identify short binding sequences for PDZ domain proteins. Two different domains are examined, the 10th PDZ domain (PDZ10) of the multi-PDZ domain protein 1 (MUPP1) and the third PDZ domain (PDZ3) of postsynaptic density-95 (PSD-95) protein. Using the T7Select 415-1b construct, which displays 415 peptides per phage particle, a random heptapeptide and focused octapeptide libraries were constructed and subjected to iterative selection-enrichment cycles against surface-immobilized PDZ3 and PDZ10 proteins.