Generation of Multispecies Oral Bacteria Biofilm Models.

It is well-recognized that oral biofilms that occur in health and disease have a polymicrobial composition, though these are poorly reflected in the literature, with many studies focussing on simple mono-species biofilm model systems. The utility of polymicrobial biofilm model systems is that they more accurately reflect the oral cavity and allow researchers to ask relevant questions in basic science studies, pharmaceutical screening, and investigating inflammatory interactions. Here we describe the detailed methodology of how to sequentially construct and maintain polymicrobial biofilm models pertinent to caries, periodontal disease, and denture stomatitis.

Hot off the press.

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as chlorfortunone A from .

A phase III, multi-arm multi-stage covariate-adjusted response-adaptive randomized trial to determine optimal early mobility training after stroke (AVERT DOSE).

Rationale: The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary.

Aim: To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity.

Hypotheses: Compared with a prespecified reference arm, the optimal dose regimen(s) will result in more participants experiencing little or no disability (mRS 0-2) at 3 months post-stroke (primary), fewer deaths at 3 months, fewer and less severe complications during the intervention period, faster recovery of unassisted walking, and better quality of life at 3 months (secondary).

Clinical Outcomes After Combined ACL and Anterolateral Ligament Reconstruction Versus Isolated ACL Reconstruction With Bone-Patellar Tendon-Bone Grafts: A Matched-Pair Analysis of 2018 Patients From the SANTI Study Group.

Background: Bone-patellar tendon-bone (BPTB) autografts are widely considered the standard for anterior cruciate ligament reconstruction (ACLR).

Purpose/hypothesis: The aims of this study were to compare the clinical outcomes after ACLR with gold standard BPTB autografts versus combined ACLR + anterolateral ligament reconstruction (ALLR) with hamstring tendon (HT) autografts at medium-term follow-up in a large series of propensity-matched patients. The hypothesis was that combined ACLR + ALLR with HT autografts would result in lower graft rupture rates and non-graft rupture-related reoperation rates.

Cryo-EM structures of light-harvesting 2 complexes from reveal the molecular origin of absorption tuning.

The genomes of some purple photosynthetic bacteria contain a multigene family encoding a series of α- and β-polypeptides that together form a heterogeneous antenna of light-harvesting 2 (LH2) complexes. To unravel this complexity, we generated four sets of deletion mutants in , each encoding a single type of gene pair and enabling the purification of complexes designated as PucA-LH2, PucB-LH2, PucD-LH2, and PucE-LH2. The structures of all four purified LH2 complexes were determined by cryogenic electron microscopy (cryo-EM) at resolutions ranging from 2.

A new network for the synergistic translation of mouse research.

Over the past 20 years, the UK has become a leading force in the generation and use of complex mouse models in the precise investigation of human disease. Nevertheless, there remains a great challenge in improving how research in animals is translated to clinical benefits. Developing and expanding connections between basic scientists and clinicians to ensure that animal models accurately recapitulate human disease will be key to this effort.

Risk Factors for Anterior Cruciate Ligament Graft Failure in Professional Athletes: An Analysis of 342 Patients With a Mean Follow-up of 100 Months From the SANTI Study Group.

Background: Anterior cruciate ligament (ACL) injuries are among the most common knee injuries sustained in elite sport, and athletes generally undergo ACL reconstruction (ACLR) to facilitate their return to sport. ACL graft rupture is a career-threatening event for elite athletes.

Purpose/hypothesis: The purpose of this study was to determine the risk factors for graft failure in professional athletes undergoing ACLR.

Pattern of pterygomaxillary disarticulation associated with Le Fort I maxillary osteotomy.

Pterygomaxillary disarticulation (PMD) contributes to surgical complications of Le Fort 1 osteotomy and is associated with undesirable fractures of the pterygoid plates. The aim of this paper was to investigate the patterns of PMD in Le Fort I osteotomies using Rowe's disimpaction forceps, and to evaluate correlations with age and anatomical measurements. Cone-beam computed tomography (CBCT) scans of 70 consecutive orthognathic patients were retrospectively evaluated to study four patterns of PMD: Type 1 - PMD at, or anterior to, the pterygomaxillary junction (PMJ); Type 2 - PMD posterior to the PMJ; Type 3 - PMJ separation with comminuted fracture of the pterygoid plates; Type 4 - disarticulation of the maxilla involving the pterygoid plates above the level of the osteotomy line.

TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT receptor agonist SEP-383856.

SEP-383856 (SEP-856) is a novel antipsychotic under clinical development. It displays a unique pattern of receptor interaction, with only weak (partial agonist) activity at dopamine D receptors, yet more potent agonist activity at the trace amine associated receptor (TAAR1) and 5-hydroxytryptamine 1 A receptor (5-HT). Nonetheless, these observations await independent confirmation and more detailed characterization of the in vitro and in vivo actions of SEP-856 at TAAR1 and 5-HT receptors would be instructive.

Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides.

Excess brain cholesterol is strongly implicated in the pathogenesis of Alzheimer's disease (AD). Here we evaluated how the presence of a cholesterol-binding site (CBS) in the transmembrane and juxtamembrane regions of the amyloid precursor protein (APP) regulates its processing. We generated nine point mutations in the APP gene, changing the charge and/or hydrophobicity of the amino-acids which were previously shown as part of the CBS.

Surgery-first approach for correction of class III dentofacial deformity with Le Fort I osteotomy; is it advantageous?

The surgery-first approach (SFA) to orthognathic treatment aims to reduce its duration without compromising the outcome. However, the objective assessment of the achieved occlusion has been limited. This study was designed to assess the treatment duration, outpatient appointment number, and quality of occlusal outcomes for two groups of patients; one treated with the SFA and the other with an orthodontics-first approach (OFA).

Translational framework for implementation evaluation and research: Protocol for a qualitative systematic review of studies informed by Normalization Process Theory (NPT) [version 1; peer review: 2 approved].

Background: Normalization Process Theory (NPT) identifies mechanisms that have been demonstrated to play an important role in implementation processes. It is now widely used to inform feasibility, process evaluation, and implementation studies in healthcare and other areas of work. This qualitative synthesis of NPT studies aims to better understand how NPT explains observed and reported implementation processes, and to explore the ways in which its constructs explain the implementability, enacting and sustainment of complex healthcare interventions.

Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension.

Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing's syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics.

Investigating Dual-Species and Staphylococcal Biofilm Antiseptic Challenge.

can persistently colonize human skin, alongside a diverse bacterial microbiome. In this study we aimed to investigate the efficacy of antiseptic activities on dual-species interkingdom biofilms containing staphylococci to determine if antiseptic tolerance was negatively impacted by dual-species biofilms. Chlorhexidine, povidone iodine, and hydrogen peroxide (HO), were able to significantly reduce biofilm viable cell counts following exposure at 2%, 10%, and 3%, respectively.

Palliation of head and neck cancer: a review of the unique difficulties.

Each year, there are 11 900 new diagnoses of head and neck cancers in the UK, with around 4000 deaths. Survival rates are higher for those diagnosed earlier, however, patients are often diagnosed later, with 20% palliative at the time of diagnosis. There is a scarcity of head and neck cancer palliative care literature available.

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action.

Unlabelled: Generalized anxiety disorder (GAD), the most frequently diagnosed form of anxiety, is usually treated by cognitive-behavioural approaches or medication; in particular, benzodiazepines (acutely) and serotonin or serotonin/noradrenaline reuptake inhibitors (long term). Efficacy, compliance, and acceptability are, however, far from ideal, reinforcing interest in alternative options. Agomelatine, clinically employed in the treatment of major depression, expresses anxiolytic properties in rodents and was effective in the treatment of GAD (including severely ill patients) in several double-blind, short-term (12 weeks) and relapse-prevention (6 months) studies.

Developmental Neuropathology and Neurodegeneration of Down Syndrome: Current Knowledge in Humans.

Individuals with Down syndrome (DS) suffer from developmental delay, intellectual disability, and an early-onset of neurodegeneration, Alzheimer's-like disease, or precocious dementia due to an extra chromosome 21. Studying the changes in anatomical, cellular, and molecular levels involved may help to understand the pathogenesis and develop target treatments, not just medical, but also surgical, cell and gene therapy, etc., for individuals with DS.

Cell Viability Assays for Candida auris.

Cell viability assays are useful for assessing the efficacy of antifungal therapeutics and disinfection strategies in vitro. In recent years these assays have been fundamental for the testing of conventional and novel therapies against the nosocomial fungal pathogen Candida auris. Here we provide detailed descriptions of methods for assessing cellular viability of Candida auris in vitro, such as metabolic assays (XTT and resazurin), colony-forming unit counting, live/dead quantitative PCR, and fluorescent staining for microscopic analyses.

Perfusate Composition and Duration of Normothermic Perfusion in Kidney Transplantation: A Systematic Review.

normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions prior to transplantation. The optimal perfusate composition and duration, however, remain undefined. A systematic literature search (Embase; Medline; Scopus; and BIOSIS Previews) was conducted.

SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to Ca.

Post-translational modification of the myofilament protein troponin I by phosphorylation is known to trigger functional changes that support enhanced contraction and relaxation of the heart. We report for the first time that human troponin I can also be modified by SUMOylation at lysine 177. Functionally, TnI SUMOylation is not a factor in the development of passive and maximal force generation in response to calcium, however this modification seems to act indirectly by preventing SUMOylation of other myofilament proteins to alter calcium sensitivity and cooperativity of myofilaments.

Protein import in mitochondria biogenesis: guided by targeting signals and sustained by dedicated chaperones.

Mitochondria have a central role in cellular metabolism; they are responsible for the biosynthesis of amino acids, lipids, iron-sulphur clusters and regulate apoptosis. About 99% of mitochondrial proteins are encoded by nuclear genes, so the biogenesis of mitochondria heavily depends on protein import pathways into the organelle. An intricate system of well-studied import machinery facilitates the import of mitochondrial proteins.