Effects of prenatal cigarette smoke exposure on neurobehavioral outcomes in 10-year-old children of adolescent mothers

In this prospective study, adolescent mothers (mean age = 16; range = 12-18; 70% African-American) were interviewed about their tobacco use during pregnancy. When their children were ten, mothers reported on their child's behavior and the children completed a neuropsychological battery. We examined the association between prenatal cigarette smoke exposure (PCSE) and offspring neurobehavioral outcomes on data from the 10-year phase (n = 330). Multivariate regression analyses were conducted to test if PCSE predicted neurobehavioral outcomes, adjusting for demographic characteristics, maternal psychological characteristics, prenatal exposure to other substances, and exposure to environmental tobacco smoke. Independent effects of PCSE were found. Exposed offspring had more delinquent, aggressive, and externalizing behaviors (CBCL). They were more active (Routh, EAS, and SNAP) and impulsive (SNAP) and had more problems with peers (SNAP). On the Stroop test, deficits were observed on the more complex interference task that requires both selective attention and response inhibition. The significant effects of PCSE on neurobehavioral outcomes were found for exposure to as few as 10 cigarettes per day. Most effects were found from first trimester PCSE exposure. These results are consistent with results from an earlier assessment when the children were age 6, demonstrating that the effects of prenatal tobacco exposure can be identified early and are consistent through middle childhood.     

Motivational and mindfulness intervention for young adult female marijuana users

This pilot study tested the efficacy of a brief intervention using motivational interviewing (MI) plus mindfulness meditation (MM) to reduce marijuana use among young adult females. Thirty-four female marijuana users between the ages of 18 and 29 were randomized to either the intervention group (n = 22), consisting of two sessions of MI-MM, or an assessment-only control group (n = 12). The participants' marijuana use was assessed at baseline and at 1, 2, and 3 months posttreatment. Fixed-effects regression modeling was used to analyze treatment effects. Participants randomized to the intervention group were found to use marijuana on 6.15 (z = −2.42, p = .015), 7.81 (z = −2.78, p = .005), and 6.83 (z = −2.23, p = .026) fewer days at Months 1, 2, and 3, respectively, than controls. Findings from this pilot study provide preliminary evidence for the feasibility and effectiveness of a brief MI-MM for young adult female marijuana users.     

Engineering extracellular matrix structure in 3D multiphase tissues

In native tissues, microscale variations in the extracellular matrix (ECM) structure can drive different cellular behaviors. Although control over ECM structure could prove useful in tissue engineering and in studies of cellular behavior, isotropic 3D matrices poorly replicate variations in local microenvironments. In this paper, we demonstrate a method to engineer local variations in the density and size of collagen fibers throughout 3D tissues. The results showed that, in engineered multiphase tissues, the structures of collagen fibers in both the bulk ECM phases (as measured by mesh size and width of fibers) as well as at tissue interfaces (as measured by density of fibers and thickness of tissue interfaces) could be modulated by varying the collagen concentrations and gelling temperatures. As the method makes use of a previously published technique for tissue bonding, we also confirmed that significant adhesion strength at tissue interfaces was achieved under all conditions tested. Hence, this study demonstrates how collagen fiber structures can be engineered within all regions of a multiphase tissue scaffold by exploiting knowledge of collagen assembly, and presents an approach to engineer local collagen structure that complements methods such as flow alignment and electrospinning.     

Complementary targeting of liposomes to IL-1α and TNF-α activated endothelial cells via the transient expression of VCAM1 and E-selectin

Inflammation is in part defined by the transient upregulation of cell adhesion molecules on the surface of endothelial cells (ECs) in response to cytokines. We hypothesized that liposomes with a complementary surface presentation of antibodies to the pattern of molecules on the EC surface may enhance targeting. We quantified the expression of vascular cell adhesion molecule-1 (VCAM1) and endothelial leukocyte cell adhesion molecule-1 (E-selectin) on ECs upon exposure to either tumor necrosis factor-α (TNF-α) or interleukin-1α (IL-1α) as a function of time. Liposomes, composed of 95 mol% dioleoyl phosphatidylcholine (DOPC) and 5 mol% dodecanyl phosphatidylethanolamine (N-dod-PE), were prepared by conjugating different molar ratios of antibodies against VCAM1 (aVCAM1) and E-selectin (aE-selectin). Increased binding was observed when immunoliposomes complemented the presentation of VCAM1:E-selectin expressed on TNF-α activated ECs. The 1:1 aVCAM1:aE-selectin liposomes had maximal binding at both 6 and 24 h on IL-1α activated ECs due to differences in molecular organization. The results demonstrate that liposomes targeting to inflamed endothelium may be optimized by exploiting the dynamic expression of VCAM1 and E-selectin on the EC surface.     

Short tandem repeat and human leukocyte antigen mutations or losses confound engraftment and typing analysis in hematopoietic stem cell transplants

Clonal chromosomal abnormalities are often found in the tumor cells of patients with malignancies. These abnormalities can cause downregulation of human leukocyte antigen (HLA) and instability of short tandem repeat (STR) DNA sequences, confounding HLA typing and/or engraftment analysis in hematopoietic stem cell transplants (HSCT). We describe here the abnormalities observed during testing of 600 HSCT patients. HLA molecular typing was performed by reference strand conformational analyses and/or sequence-based typing. STR testing was performed with 10 to 16 STR primer sets, following 1 to 4 informative loci in each patient. Eight patients exhibited either loss of heterozygosity (4 STR, 3 HLA) or STR length mutation (n = 1), and 5 of the 8 exhibited correlative cytogenetic abnormalities. Diagnoses were acute myelogenous leukemia (AML; n = 7) or myelofibrosis (MFIB: n = 1), yielding an 11% incidence of these chromosomal abnormalities among the subset of 72 AML/MFIB HSCT patients. These results highlight some of the problems encountered and the possibility for interpretive errors that can arise when analyzing molecular typing and engraftment data, particularly among AML/MFIB patients.     

Patient-physician social concordance, medical visit communication and patients' perceptions of health care quality

Social characteristics (e.g. race, gender, age, education) are associated with health care disparities. We introduce social concordance, a composite measure of shared social characteristics between patients and physicians.

Objective

To determine whether social concordance predicts differences in medical visit communication and patients’ perceptions of care.

Methods

Regression analyses were used to determine the association of patient-provider social concordance with medical visit communication and patients’ perceptions of care using data from two observational studies involving 64 primary care physicians and 489 of their patients from the Baltimore, MD/Washington, DC/Northern Virginia area.

Results

Lower patient-physician social concordance was associated with less positive patient perceptions of care and lower positive patient affect. Patient-physician dyads with low vs. high social concordance reported lower ratings of global satisfaction with office visits (OR = 0.64 vs. OR = 1.37, p = 0.036) and were less likely to recommend their physician to a friend (OR = 0.61 vs. OR = 1.37, p = 0.035). A graded-response was observed for social concordance with patient positive affect and patient perceptions of care.

Conclusion

Patient-physician concordance across multiple social characteristics may have cumulative effects on patient-physician communication and perceptions of care.

Practice implications

Research should move beyond one-dimensional measures of patient-physician concordance to understand how multiple social characteristics influence health care quality.     

Prolonged Infusion of Angiotensin II in apoE?/? Mice Promotes Macrophage Recruitment with Continued Expansion of Abdominal Aortic Aneurysm

Angiotensin II (AngII) infusion initiates abdominal aortic aneurysm (AAA) development due to medial disruption and results in luminal dilation and thrombus formation. The objective of this study was to determine whether AAA progressed during protracted AngII infusion. Male apoE^−/− mice were infused with AngII using miniosmotic pumps. On day 27, suprarenal aortic luminal diameters were ultrasonically measured to identify mice exhibiting AAAs. Mice were designated to three groups with similar mean luminal dilation. Group 1 mice were sacrificed on day 28. Group 2 and 3 mice were subsequently infused with saline or AngII, respectively, for an additional 56 days. In Group 2, saline infusion—after the initial 28 days of AngII infusion—led to an immediate decrease in systolic blood pressure. Over the subsequent 56 days of saline infusion, there were no aneurysm-related deaths or significant changes in luminal diameter. In contrast, continuous AngII infusion in Group 3 maintained persistently increased systolic blood pressure, with aneurysmal rupture–associated deaths, increased luminal diameters, and tissue remodeling. Aortic aneurysmal segments that expanded during continuous AngII infusion exhibited macrophage accumulation in regions of medial disruption, predominantly on the adventitial aspect. Macrophages immunostained for CD206 more than for iNOS, consistent with an M2 phenotype. In conclusion, prolonged AngII infusion promotes AAA expansion, and is associated with enhanced rupture rates and increased macrophage infiltration.Infusion of angiotensin II (AngII) into mice promotes rapid formation of abdominal aortic aneurysms (AAAs) within 14 days.^1–11 Initiation of AngII-induced AAA is associated with medial disruption leading to a localized thrombus.¹² There is a rapid luminal dilation between days 3 and 8 of AngII infusion with subsequent, gradual luminal expansion.¹² Although many laboratories have demonstrated that AngII consistently initiates AAA development in both hyper- and normocholesterolemic mice,^13–16 its role in aneurysmal progression, expansion, and rupture has not been defined in prospective human studies. However, there are conflicting data from retrospective analyses on AAA expansion and rupture in humans.^17–19Many factors have been associated with the development of AAAs in animal models.²⁰ Most of these studies have invoked mechanisms that prevent the initiation phase of AAAs. However, pharmacological treatment of AAAs in humans would be initiated in aortas with established disease. Currently, it is unknown whether pharmacological approaches that suppress initiation of disease would also inhibit progression of established aneurysms. Therefore, there is a need to determine mechanisms of AAA progression, expansion, and rupture since these may differ from disease initiation.The purpose of this current study was to determine whether chronic AngII infusion led to AAA expansion and rupture. This was accomplished by prolonged infusion of AngII for 84 days with sequential luminal diameter measurements and histological characterization of aortas at termination. This group was compared to one in which AAAs were initiated by AngII infusion, but were subsequently implanted with miniosmotic pumps infusing saline. The data demonstrate that continuous AngII infusion increased aortic dilation and aneurysmal rupture. Sequential sectioning of aneurysmal tissues demonstrated morphological heterogeneity, and increased macrophage recruitment localized to regions of medial disruption.     

Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function

Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix. These results clarify how FLG mutations impair epidermal permeability barrier function.