Salivary analysis in the diagnosis and treatment of breast cancer: a role for the general dentist

Saliva testing is an attractive area of research for the general dentist, as it offers a great opportunity to utilize an easily accessible fluid for the diagnosis of disease. Diseases that may be difficult to detect, such as breast cancer, are an area of particular interest. Breast cancer is the second leading cause of death among women in the U.S. and early detection is critical to patient survival. Frequent and inexpensive testing is the key to early detection. The general dentist is in the perfect position to take salivary samples from patients during routine checkups or procedures and to refer patients depending on the results.     

Brain‐dead donor heart conservation with a preservation solution supplemented by a conditioned medium from mesenchymal stem cells improves graft contractility after transplantation

Hearts are usually procured from brain‐dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD‐donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs‐derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon‐catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution‐supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD‐donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells and endonuclease G positive cells were increased in the BD‐group compared to sham. Preservation of BD‐donor hearts with CM resulted in a recovery of systolic graft function (dP/dt_max: BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase‐independent apoptosis.     

Influence of Hamstrings on Knee Moments During Loading Response of Gait in Individuals Following ACL Reconstruction

Biomechanical studies consistently report smaller knee extensor moments in the surgical limb during loading response (LR) of gait following ACL reconstruction (ACLr). However, this reduction in knee loading is quantified by net joint moments (NJM). As a result, in the presence of greater hamstring activity, the true contribution from the knee extensors may not be reduced. The purpose of this study is to compare hamstring activity and strength and knee joint moments between individuals post-ACLr and controls. Eighteen individuals 3 months post-ACLr and matched controls walked and net knee extensor moment peak and impulse and hamstring activity were identified during LR, as well as maximal hamstring strength. A hybrid musculoskeletal model estimated knee flexor moments from joint kinematics and hamstring electromyography. Flexor moments (SIMM) were scaled based on strength. Knee extensor moments were estimated from the sum of the net knee moment and estimated knee flexor moment; estimated extensor moment peaks and impulse were calculated during LR. Repeated measures analysis of variance compared groups and limbs. Smaller net knee extensor moment and greater hamstring activity, as well as deficits in maximal hamstring strength, were observed in the surgical limb (all p < 0.05). When accounting for the torque-producing capabilities of the knee flexors, estimated knee extensor moment peak and impulse were smaller in the surgical limb. These findings suggest that net knee moments accurately reflect smaller knee extensor loading post-ACLr. Statement of Clinical Significance: Rehabilitation programs should target increasing knee extensor loading to restore gait mechanics during early rehabilitation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:378-386, 2020     

Targeting the Complement Serine Protease MASP-2 as a Therapeutic Strategy for Coronavirus Infections

MASP-2, mannose-binding protein-associated serine protease 2, is a key enzyme in the lectin pathway of complement activation. Hyperactivation of this protein by human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 has been found to contribute to aberrant complement activation in patients, leading to aggravated lung injury with potentially fatal consequences. This hyperactivation is triggered in the lungs through a conserved, direct interaction between MASP-2 and coronavirus nucleocapsid (N) proteins. Blocking this interaction with monoclonal antibodies and interfering directly with the catalytic activity of MASP-2, have been found to alleviate coronavirus-induced lung injury both in vitro and in vivo. In this study, a virtual library of 8736 licensed drugs and clinical agents has been screened in silico according to two parallel strategies. The first strategy aims at identifying direct inhibitors of MASP-2 catalytic activity, while the second strategy focusses on finding protein-protein interaction inhibitors (PPIs) of MASP-2 and coronaviral N proteins. Such agents could represent promising support treatment options to prevent lung injury and reduce mortality rates of infections caused by both present and future-emerging coronaviruses. Forty-six drug repurposing candidates were purchased and, for the ones selected as potential direct inhibitors of MASP-2, a preliminary in vitro assay was conducted to assess their interference with the lectin pathway of complement activation. Some of the tested agents displayed a dose-response inhibitory activity of the lectin pathway, potentially providing the basis for a viable support strategy to prevent the severe complications of coronavirus infections.     

An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: results from a randomized trial

STUDY OBJECTIVE: Conventional emergency department testing strategies for patients with chest pain often do not provide unequivocal diagnosis of acute coronary syndromes. This study was conducted to determine whether the routine use of single photon emission computed tomography (SPECT) imaging at rest and early exercise stress testing to assess intermediate-risk patients with chest pain and no ECG evidence of acute ischemia will lead to earlier discharges, more discriminate use of coronary angiography, and an overall reduction in average costs of care with no adverse clinical outcomes. METHODS: All patients in this study had technetium 99m tetrofosmin SPECT imaging at rest and were randomly assigned to either a conventional (results of the imaging test blinded to the physician) or perfusion imaging-guided (results of the imaging test unblinded to the physician) strategy. Patients in the conventional arm were treated at their physician's discretion. Patients in the perfusion imaging-guided arm were treated according to a predefined protocol based on SPECT imaging test results: coronary angiography after a positive scan result and exercise treadmill testing after a negative scan result. Study endpoints consisted of total in-hospital costs and length of stay. Hospital costs were calculated using hospital department-specific Medicare cost/charge ratios. Length of stay was calculated as total hospital room days billed (regular and intensive care). RESULTS: We enrolled 46 patients, 9 with acute myocardial infarctions. Patients randomly assigned to the perfusion imaging-guided arm had $1,843 (95% confidence interval [CI] $431 to $6,171) lower median in-hospital costs and 2.0-day (95% CI 1.0 to 3.0 days) shorter median lengths of stay but similar rates of in-hospital and 30-day follow up events as patients in the conventional arm. CONCLUSION: An ED chest pain diagnostic strategy incorporating acute resting (99m)Tc tetrofosmin SPECT imaging and early exercise stress testing may lead to reduced in-hospital costs and decreased length of stay for patients with acute chest pain and nondiagnostic ECGs.     

Division of Labor in Families of Children and Adolescents with Autism Spectrum Disorder

Couples who have a child or adolescent with autism spectrum disorder (ASD) are faced with the difficult decision of how to divide child care responsibilities and paid employment. The authors examined the division of labor and its relation to parenting stress and marital adjustment in 73 married couples who have a child or adolescent with ASD. Mothers and fathers independently reported on their global level of parenting stress and marital adjustment and then completed a 7‐day online daily diary of time spent in child care, time spent in paid employment, and satisfaction with the time that one's spouse spent in child care. Overall, couples demonstrated a pattern of partial role specialization in which mothers engaged in more child care and fathers engaged in more paid employment. Child age was negatively related and degree of disability was positively related to role specialization. Time spent in paid employment and satisfaction with the time that one's spouse spent in child care had important associations with parenting stress and marital adjustment.     

Effects of Developmental Activation of the AhR on CD4+ T-Cell Responses to Influenza Virus Infection in Adult Mice

Background: Epidemiological and animal studies indicate that maternal exposure to pollutants that bind the aryl hydrocarbon receptor (AhR) correlates with poorer ability to combat respiratory infection and lower antibody levels in the offspring. These observations point to an impact on CD4⁺ T cells. Yet, the consequence of developmental exposure to AhR ligands on the activation and differentiation of CD4⁺ T cells has not been directly examined.Objectives: Our goal was to determine whether maternal exposure to an AhR ligand directly alters CD4⁺ T cell differentiation and function later in life.Methods: C57BL/6 mice were exposed to a prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in utero and via suckling. We then measured CD4⁺ T-cell activation and differentiation into distinct effector populations in adult offspring that were infected with influenza A virus (IAV). Reciprocal adoptive transfers were used to define whether modifications in CD4⁺ T-cell responses resulted from direct effects of developmental TCDD exposure on CD4⁺ T cells.Results: Developmental exposure skewed CD4⁺ T-cell responses to IAV infection. We observed fewer virus-specific, activated CD4⁺ T cells and a reduced frequency of conventional CD4⁺ effector-cell subsets. However, there was an increase in regulatory CD4⁺ T cells. Direct effects of AhR activation on CD4⁺ T cells resulted in impaired differentiation into conventional effector subsets; this defect was transferred to mice that had not been developmentally exposed to TCDD.Conclusions: Maternal exposure to TCDD resulted in durable changes in the responsive capacity and differentiation of CD4⁺ T cells in adult C57BL/6 mice.Citation: Boule LA, Winans B, Lawrence BP. 2014. Effects of developmental activation of the AhR on CD4⁺ T-cell responses to influenza virus infection in adult mice. Environ Health Perspect 122:1201–1208; http://dx.doi.org/10.1289/ehp.1408110