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Influenza epidemics and pandemics are caused by influenza A virus. The cell surface protein of hemagglutinin and neuraminidase is responsible for viral infection and release of progeny virus on the host cell membrane. Now 18 hemagglutinin and 11 neuraminidase subtypes are identified. The avian influenza virus of H5N1 is an emergent threat to public health issues. To control the influenza viral infection it is necessary to develop antiviral inhibitors and vaccination. In the present investigation we carried out 50 ns Molecular Dynamics simulation on H5 hemagglutinin of Influenza A virus H5N1 complexed with fluorinated sialic acid by substituting fluorine atoms at any two hydroxyls of sialic acid by considering combinatorial combination...

PURPOSE: The aim of this study was to evaluate in vitro and in vivo the enhancement properties of experimental gadolinium (Gd)-based contrast agents (GBCAs) with different molecular weights and hydration numbers (P846 and gadopiclenol) compared with clinically approved low-molecular, extracellular agents (gadopentetate and gadoterate) at 9.4 T and to discuss influencing factors on r1 relaxivities. METHODS AND MATERIALS: All experiments were performed with a 9.4 T animal scanner (Bruker, Germany)...

Although essential for many cellular processes, the sequence of structural and molecular events during clathrin-mediated endocytosis remains elusive. While it was long believed that clathrin-coated pits grow with a constant curvature, it was recently suggested that clathrin first assembles to form flat structures that then bend while maintaining a constant surface area. Here, we combine correlative electron and light microscopy and mathematical growth laws to study the ultrastructural rearrangements of the clathrin coat during endocytosis in BSC-1 mammalian cells...

PURPOSE: The aim of the study is proposing a classification of different transoral lateral oropharyngectomy procedures in order to ensure better definitions of post-operative results. METHODS: The classification resulted from the consensus of the different authors and was based on anatomical-surgical principles. RESULTS: The classification comprises three types of lateral oropharyngectomy: type 1 is the resection of the palatine tonsil deep to the pharyngobasilar fascia; type 2 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle and the superior constrictor muscle; type 3 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle, the superior constrictor muscle, the buccopharyngeal fascia with extension to the pterygoid muscle and parapharyngeal space fat content...

1. We recently demonstrated that ginsenoside Rb1 (C54H92O23, molecular weight 1108) isolated from ginseng, when intravenously infused into rats with permanent middle cerebral artery occlusion, reduced cerebral infarct volume and ameliorated place navigation disability of the animals, through an anti-apoptotic action and possibly promotion of vascular regeneration. To investigate the ginsenoside Rb1-mediated vascular regeneration in vivo in a more easily accessible experimental systems, we made a burn wound on the backs of mice and topically applied either Vaseline (vehicle) alone or Vaseline containing low doses of ginsenoside Rb1 to the wound...

OBJECTIVE: The purposes of this article are to describe implementation of an abbreviated brain MRI protocol for use in children with primary headache and to present an experience with the adaptation of the protocol in practice, work flow integration, and effects on sedation use. CONCLUSION: The abbreviated brain MRI protocol reduced the need for sedation for 74% of the study sample. Use of this protocol in this particular patient population continues, but further validation is required before its use is expanded to other pediatric populations...

OBJECTIVE: To evaluate the relationship between quadriceps sensorimotor function (knee joint-position sense, quadriceps strength, and quadriceps onset of activity) and knee joint kinematics (knee flexion at initial contact and loading) during level walking and stair descent in a large cohort of 220 people with knee osteoarthritis. DESIGN: Cross-sectional correlational study. RESULTS: Joint-position sense correlated with knee flexion at initial contact during both tasks (r = -0...

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Technical advances in MRI have improved image quality and have led to expanding clinical indications for its use. However, long examination and interpretation times, as well as higher costs, still represent barriers to use of MRI. Abbreviated MRI protocols have emerged as an alternative to standard MRI protocols. These abbreviated MRI protocols seek to reduce longer MRI protocols by eliminating unnecessary or redundant sequences that negatively affect cost, MRI table time, patient comfort, image quality, and image interpretation time...

Membrane depolarization and intracellular Ca2+ promote activation of the large-conductance Ca2+ - and voltage-gated (Slo1) big potassium (BK) channel. We examined the physical interactions that stabilize the closed and open conformations of the ion conduction gate of the human Slo1 channel using electrophysiological and computational approaches. The results show that the closed conformation is stabilized by intersubunit ion-ion interactions involving negative residues (E321 and E324) and positive residues (329 RKK331 ) at the cytoplasmic ends of the transmembrane S6 segments ("RKK ring")...

Apicomplexan parasites invade host cells in an active process involving their ability to move by gliding motility. While the acto-myosin system of the parasite plays a crucial role in the formation and release of attachment sites during this process, there are still open questions regarding the involvement of other mechanisms in parasite motility. In many eukaryotes, a secretory-endocytic cycle leads to the recycling of receptors (integrins), necessary to form attachment sites, regulation of surface area during motility, and generation of retrograde membrane flow...

For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit. Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma...

OBJECTIVES: The aim of this study was to evaluate the pharmacokinetics, safety profile, and pharmacodynamics of gadopiclenol, a new high relaxivity macrocyclic gadolinium-based contrast agent, in healthy subjects and patients with brain lesions. MATERIALS AND METHODS: This was a single ascending dose phase I/IIa study. Phase I was double-blind, randomized, placebo-controlled and included 54 healthy subjects. In each dose group (0.025, 0.05, 0.075, 0.1, 0.2, and 0...

Breast MRI has been shown to be the most sensitive examination in the detection of breast cancer. However, given the high associated costs, its use in the screening setting has traditionally been limited to those who are at high-risk for breast cancer. Abbreviated protocol breast MRI is capable of reducing the traditional costs associated with breast MRI, while maintaining diagnostic accuracy and cancer detection, and therefore a potential future screening tool for breast cancer in a broader population of women than just those at high-risk...

The mouse double minute 4 (MDM4) is emerging from the shadow of its more famous relative MDM2 and is starting to steal the limelight, largely due to its therapeutic possibilities. MDM4 is a vital regulator of the tumor suppressor p53. It restricts p53 transcriptional activity and also, at least in development, facilitates MDM2's E3 ligase activity toward p53. These functions of MDM4 are critical for normal cell function and a proper response to stress. Their importance for proper cell maintenance and proliferation identifies them as a risk for deregulation associated with the uncontrolled growth of cancer...

In silico and in vitro studies have made progress in understanding protein-protein complex formation; however, the molecular mechanisms for their dissociation are unclear. Protein-protein complexes, lasting from microseconds to years, often involve induced-fit, challenging computational or kinetic analysis. Charybdotoxin (CTX), a peptide from the Leiurus scorpion venom, blocks voltage-gated K+ -channels in a unique example of binding/unbinding simplicity. CTX plugs the external mouth of K+ -channels pore, stopping K+ -ion conduction, without inducing conformational changes...

OBJECTIVE: Survival outcomes for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB). METHODS: We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan-Meir method...

A 28-year-old man with a history of mycosis fungoides presented for evaluation of multiple dark-brown macules and hyperpigmented dome-shaped papules on the distal tongue. A shave biopsy of the tongue revealed melanin pigment in the basal keratinocytes and melanophages in the lamina propria, consistent with pigmented fungiform papillae of the tongue. Relevant clinical and histologic features of this diagnosis are reviewed.

Civic honesty is essential to social capital and economic development but is often in conflict with material self-interest. We examine the trade-off between honesty and self-interest using field experiments in 355 cities spanning 40 countries around the globe. In these experiments, we turned in more than 17,000 lost wallets containing varying amounts of money at public and private institutions and measured whether recipients contacted the owners to return the wallets. In virtually all countries, citizens were more likely to return wallets that contained more money...

Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol)...