Air powder waterjet technology using erythritol or glycine powders in periodontal or peri-implant prophylaxis and therapy: A consensus report of an expert meeting.

Objectives: To attain a collective expert opinion on the use of air powder waterjet technology (APWT) with erythritol and glycine powders in the prophylaxis and therapy of periodontal and peri-implant diseases.

Material And Methods: In the first step, a modified one-round online Delphi survey including 44 five-point Likert scale questions was conducted among a group of 10 expert clinicians and researchers with thorough knowledge and experience in this topic. In the second step, the single questions and the survey results were discussed during a meeting, and consensus statements were formulated, respectively.

A telepathology based screening tool for COVID-19 by leveraging morphological changes related to leukocytes in peripheral blood smears.

As we approach the aftermath of a global pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2), the importance of quickly developing rapid screening tests has become very clear from the point of view of containment and also saving lives. Here, we present an explorative study to develop a telepathology-based screening tool using peripheral blood smears (PBS) to identify Coronavirus Disease (COVID-19)-positive cases from a group of 138 patients with flu-like symptoms, consisting of 82 positive and 56 negative samples. Stained blood smear slides were imaged using an automated slide scanner (AI 100) and the images uploaded to the cloud were analyzed by a pathologist to generate semi-quantitative leukocyte morphology-related data.

Selective expansion of regulatory T cells by NKTR-358 in healthy volunteers and patients with systemic lupus erythematosus.

Objective: To evaluate NKTR-358, a polyethylene glycol-interleukin-2 conjugate composition designed to selectively induce regulatory T cells (Tregs), in first-in-human studies.

Methods: Healthy volunteers and patients with systemic lupus erythematosus (SLE) received single- or multiple-dose (biweekly) NKTR-358 or placebo in two sequential, randomized, phase 1 studies (single ascending dose [SAD; NCT04133116] and multiple ascending dose [MAD; NCT03556007]). Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics (PK) and immune effects of NKTR-358; exploratory objectives included effects on SLE disease activity.

Twin boundary migration mechanisms in quasi-statically compressed and plate-impacted Mg single crystals.

Twinning is a prominent deformation mode that accommodates plasticity in many materials. This study elucidates the role of deformation rate on the atomic-scale mechanisms that govern twin boundary migration. Examination of Mg single crystals deformed under quasi-static compression was compared with crystals deformed via plate impact.

NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases.

Impaired interleukin-2 (IL-2) production and regulatory T-cell dysfunction have been implicated as immunological mechanisms central to the pathogenesis of multiple autoimmune and inflammatory diseases. NKTR-358, a novel regulatory T-cell stimulator, is an investigational therapeutic that selectively restores regulatory T-cell homeostasis in these diseases. We investigated NKTR-358's selectivity for regulatory T-cells, receptor-binding properties, vo and pharmacodynamics, ability to suppress conventional T-cell proliferation in mice and non-human primates, and functional activity in a murine model of systemic lupus erythematosus.

Streptolysin O Rapidly Impairs Neutrophil Oxidative Burst and Antibacterial Responses to Group A Streptococcus.

Group A Streptococcus (GAS) causes a wide range of human infections, ranging from simple pharyngitis to life-threatening necrotizing fasciitis and toxic shock syndrome. A globally disseminated clone of M1T1 GAS has been associated with an increase in severe, invasive GAS infections in recent decades. The secreted GAS pore-forming toxin streptolysin O (SLO), which induces eukaryotic cell lysis in a cholesterol-dependent manner, is highly upregulated in the GAS M1T1 clone during bloodstream dissemination.

Crosstalk among IL-23 and DNAX activating protein of 12 kDa-dependent pathways promotes osteoclastogenesis.

IL-23 has been well studied in the context of T cell differentiation; however, its role in the differentiation of myeloid progenitors is less clear. In this paper, we describe a novel role of IL-23 in myeloid cell differentiation. Specifically, we have identified that in human PBMCs, IL-23 induces the expression of MDL-1, a PU.

Leukotriene B4 activates intracellular calcium and augments human osteoclastogenesis.

Introduction: Bone erosion in inflammatory arthritis depends on the recruitment and activation of bone resorbing cells, the osteoclasts. Interleukin-23 (IL-23) has been primarily implicated in mediating inflammatory bone loss via the differentiation of Th17 receptor activator of nuclear factor κB ligand (RANKL)-producing cells. In this article, we describe a new role of IL-23 in activating the synthesis and production of leukotriene B4 (LTB4) in innate immune cells.

A novel in vivo gene transfer technique and in vitro cell based assays for the study of bone loss in musculoskeletal disorders.

Differentiation and activation of osteoclasts play a key role in the development of musculoskeletal diseases as these cells are primarily involved in bone resorption. Osteoclasts can be generated in vitro from monocyte/macrophage precursor cells in the presence of certain cytokines, which promote survival and differentiation. Here, both in vivo and in vitro techniques are demonstrated, which allow scientists to study different cytokine contributions towards osteoclast differentiation, signaling, and activation.

GFAP out-performs S100β in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions.

Both glial fibrillary acidic protein (GFAP) and S100β are found in glial cells and are released into serum following a traumatic brain injury (TBI), however, the clinical utility of S100β as a biomarker has been questioned because of its release from bone. This study examined the ability of GFAP and S100β to detect intracranial lesions on computed tomography (CT) in trauma patients and also assessed biomarker performance in patients with fractures and extracranial injuries on head CT. This prospective cohort study enrolled a convenience sample of adult trauma patients at a Level I trauma center with and without mild or moderate traumatic brain injury (MMTBI).

Detection of bidirectional signaling during integrin activation and neutrophil adhesion.

Neutrophil arrest and migration on inflamed endothelium is dependent upon a conformational shift in CD11a/CD18 (LFA-1) from a low to high affinity and clustered state which determines the strength and lifetime of bond formation with intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal adaptor proteins kindlin-3 and talin-1 anchor clustered LFA-1 to the cytoskeleton and support the transition from neutrophil rolling to arrest. We employ microfluidic flow channels and total internal reflection fluorescence microscopy to evaluate the spatiotemporal regulation of LFA-1 affinity and bond formation that facilitate the transition from neutrophil rolling to arrest.

Leukocyte function antigen-1, kindlin-3, and calcium flux orchestrate neutrophil recruitment during inflammation.

Neutrophil arrest and migration on inflamed endothelium involves a conformational shift in CD11a/CD18 (leukocyte function antigen-1; LFA-1) to a high-affinity and clustered state that determines the strength and lifetime of bond formation with ICAM-1. Cytoskeletal adapter proteins Kindlin-3 and Talin-1 anchor clustered LFA-1 to the cytoskeleton and facilitate the transition from neutrophil rolling to arrest. We recently reported that tensile force acts on LFA-1 bonds inducing their colocalization with Orai1, the predominant membrane store operated Ca(2+) channel that cooperates with the endoplasmic reticulum to elicit cytosolic flux.

Chemokines, selectins and intracellular calcium flux: temporal and spatial cues for leukocyte arrest.

Leukocyte trafficking to acute sites of injury or infection requires spatial and temporal cues that fine tune precise sites of firm adhesion and guide migration to endothelial junctions where they undergo diapedesis to sites of insult. Many detailed studies on the location and gradient of chemokines such as IL-8 and other CXCR ligands reveal that their recognition shortly after selectin-mediated capture and rolling exerts acute effects on integrin activation and subsequent binding to their ligands on the endothelium, which directs firm adhesion, adhesion strengthening, and downstream migration. In this process, G-protein coupled receptor (GPCR) signaling has been found to play an integral role in activating and mobilizing intracellular stores of calcium, GTPases such as Rap-1 and Rho and cytokeletal proteins such as Talin and F-actin to facilitate cell polarity and directional pseudopod formation.

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention.

Study Objective: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention.

Methods: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury.

Migrational guidance of neutrophils is mechanotransduced via high-affinity LFA-1 and calcium flux.

Acute inflammation triggers the innate immune response of neutrophils that efficiently traffic from the bloodstream to concentrate at high numbers at the site of tissue infection or wounding. A gatekeeper in this process is activation of β(2) integrins, which form bond clusters with ICAM-1 on the endothelial surface. These bond clusters serve dual functions of providing adhesive strength to anchor neutrophils under the shear forces of blood flow and directional guidance for cell polarization and subsequent transmigration on inflamed endothelium.

Operating characteristics of executive functioning tests following traumatic brain injury.

The primary purposes of this study were to determine if controls, and mild and moderate/severe traumatic brain injury (TBI) patients performed differently on a battery of executive functioning (EF) tests, and to identify the operating characteristics of EF tests in this population. Participants consisted of 46 brain-injured individuals and 24 healthy controls. All participants completed an extensive battery of EF tests.

Cardiac resynchronization therapy: a pilot study examining cognitive change in patients before and after treatment.

Background: Cardiovascular patients with reduced cardiovascular output and capacity such as those with congestive heart failure (CHF) have demonstrated cognitive-related dysfunction. The use of cardiac resynchronization therapy (CRT) is considered standard care for CHF patients who do not improve despite optimal medical therapy. Cardiac resynchronization therapy may improve neurocognitive and psychosocial functioning in patients by increasing cardiac output and cerebral perfusion.

Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow.

Orai1 was reported to function as a calcium channel subunit that facilitates store operated calcium entry (SOCE) in T cells and is necessary for formation of the immune synapse. We reasoned that SOCE via Orai1 might regulate PMNs activation during recruitment to inflamed endothelium. Orai1 function was assessed by real-time imaging of calcium transients as PMNs were stimulated to roll, arrest, and migrate on E-selectin and ICAM-1 in shear flow.

Transmigration of neutrophils across inflamed endothelium is signaled through LFA-1 and Src family kinase.

Leukocyte capture on inflamed endothelium is facilitated by a shift in LFA-1 from low to high affinity that supports binding to ICAM-1. LFA-1 bonds help anchor polymorphonuclear leukocytes (PMN) to inflamed endothelium in shear flow, and their redistribution to the leading edge guides pseudopod formation, migration, and extravasation. These events can be disrupted at the plasma membrane by stabilizing LFA-1 in a low- or intermediate-affinity state with allosteric small molecules.

Healthcare utilization among veterans undergoing chemotherapy: the impact of a cancer care coordination/home-telehealth program.

The 2001 Institute of Medicine report indicted that the US healthcare system fails to provide high-quality care, and offered 6 aims of improvement that would redesign the delivery of care for the 21st century. This study compared the use of Department of Veterans Affairs (VA) inpatient and outpatient services of cancer patients enrolled in a Cancer Care Coordination/Home-Telehealth (CCHT) program that involved remote management of symptoms (eg, emotional distress, pain) via home-telehealth technologies to a control group of cancer patients receiving standard VA care. Using a matched case-control design, 2 control patients per case were selected, matched by tumor type and cancer stage.

Measurement of patient fears about implantable cardioverter defibrillator shock: an initial evaluation of the Florida Shock Anxiety Scale.

Background: Psychological distress is both a precipitant and a consequence of ICD shock. Therefore, the assessment of patient anxiety and concerns related to receiving an ICD shock may prompt appropriate psychological referrals and treatment.

Methods: The purpose of this study is to assess the initial validity and clinical utility of the Florida Shock Anxiety Scale (FSAS).

Parametric manipulation of working memory load in traumatic brain injury: behavioral and neural correlates.

Traumatic brain injury (TBI) is often associated with enduring impairments in high-level cognitive functioning, including working memory (WM). We examined WM function in predominantly chronic patients with mild, moderate and severe TBI and healthy comparison subjects behaviorally and, in a small subset of moderate-to-severe TBI patients, with event-related functional magnetic resonance imaging (fMRI), using a visual n-back task that parametrically varied WM load. TBI patients showed severity-dependent and load-related WM deficits in performance accuracy, but not reaction time.

Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia.

Background: Schizophrenic patients show deficits in working memory (WM) and inhibition of prepotent responses. We examined brain activity while subjects performed tasks that placed demands on WM and overriding prepotent response tendencies, testing predictions that both processes engage overlapping prefrontal cortical (PFC) regions and that schizophrenic patients show reduced PFC activity and performance deficits reflecting both processes.

Methods: Functional magnetic resonance imaging data were acquired while 16 schizophrenic and 15 healthy subjects performed the N-Back task that varied WM load and a version of the AX-CPT that required overriding a prepotent response tendency.