Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey

Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.     

The quality of cardiovascular disease care for adolescents with kidney disease: a Midwest Pediatric Nephrology Consortium study

Background

Cardiovascular disease is the leading cause of increased mortality for adolescents with advanced kidney disease. The quality of preventive cardiovascular care may impact long-term outcomes for these patients.

Methods

We reviewed the records of 196 consecutive adolescents from eight centers with pre-dialysis chronic kidney disease, on dialysis or with a kidney transplant, who transferred to adult-focused providers. We compared cardiovascular risk assessment and therapy within and across centers. Predictors of care were assessed using multilevel models.

Results

Overall, 58 % (range 44–86 %; p?=?0.08 for variance) of five recommended cardiovascular risk assessments were documented. Recommended therapy for six modifiable cardiovascular risk factors was documented 57 % (26–76 %; p?=?0.09) of the time. Of these patients, 30 % (n?=?59) were reported to go through formal transition which was independently associated with a 21 % increase in composite cardiovascular risk assessment (p?<?0.001). Transfer after 2006 and kidney transplant status were also associated with increased cardiovascular risk assessment (p?<?0.01 and p?=?0.045, respectively).

Conclusions

Adolescents with kidney disease receive suboptimal preventive cardiovascular care, that may contribute to their high risk of future cardiovascular mortality. A great opportunity exists to improve outcomes for children with kidney disease by improving the reliability of preventive care that may include formal transition programs.     

Hypertension favors the inflammatory process in rats with experimentally induced periodontitis

Bonato CF, do‐Amaral CCF, Belini L, Salzedas LMP, Oliveira SHP. Hypertension favors the inflammatory process in rats with experimentally induced periodontitis. J Periodont Res 2012; 47: 783–792. © 2012 John Wiley & Sons A/S Background and Objective: Cardiovascular diseases are significantly correlated with chronic periodontitis. The aim of this study was to evaluate bone‐loss level, neutrophil migration, CXCL2/CINC‐2α, CXCL5/LIX, CCL20/MIP‐3α and tumor necrosis factor‐α (TNF‐α) production, inducible nitric oxide synthase (iNOS) expression and C‐reactive protein (CRP) release in spontaneously hypertensive rats (SHRs) and normotensive (WTK) rats after experimental induction of periodontal disease. Material and Methods: Periodontitis was induced by placement of silk yarn ligatures around the first molar counterparts. The levels of CRP, CCL20/MIP‐3α and CXCL5/LIX were evaluated in the peripheral blood, and bone‐loss level, neutrophil recruitment, the production of myeloperoxidase, CXCL2, CXCL5, CCL20 and TNF‐α, and the expression of iNOS were evaluated in the gingival tissue. Histological sections were taken to evaluate and measure bone resorption and neutrophil recruitment in the furcation region. Results: Rats with periodontitis had alveolar bone resorption. SHRs with periodontitis showed marked bone loss and increased neutrophil infiltration in comparison with WTK rats. SHRs with periodontitis showed increased levels of TNF‐α and CXCL2, and a slight tendency for increased levels of CXCL5, in the gingival tissue but no increase in the level of CCL20. In SHRs, even without periodontitis, the levels of TNF‐α, CXCL2, CXCL5 and CCL20 showed a slight tendency to increase. In the WTK rats, TNF‐α, CXCL2 and CXCL5 levels were increased with periodontitis, but the level of CCL20 was not. iNOS was expressed in the gingival tissue of WTK rats and SHRs with periodontitis; however, SHRs appeared to express a higher level of iNOS than did WKT rats. The CRP level was elevated in both types of rats with periodontitis; however, the CRP level was higher in SHRs with periodontitis than in WTK rats with periodontitis. Conclusion: In SHRs, the hypertensive condition per se seems to favor the inflammatory processes that become potentiated with periodontitis, when compared with WKT rats.     

Factors associated with unintended pregnancy in Brazil: cross-sectional results from the Birth in Brazil National Survey, 2011/2012

Background

Unintended pregnancy, a pregnancy that have been either unwanted or mistimed, is a serious public health issue in Brazil. It is reported for more than half of women who gave birth in the country, but the characteristics of women who conceive unintentionally are rarely documented. The aim of this study is to analyse the prevalence and the association between unintended pregnancy and a set of sociodemographic characteristics, individual-level variables and history of obstetric outcomes.

Methods

Birth in Brazil is a cross-sectional study with countrywide representation that interviewed 23,894 women after birth. The information about intendedness of pregnancy was obtained after birth at the hospital and classified into three categories: intended, mistimed or unwanted. Multinomial regression analysis was used to estimate the associations between intendedness of a pregnancy, and sociodemographic and obstetric variables, calculating odds ratios and 95 % confidence intervals. All significant variables in the bivariate analysis were included in the multinomial multivariate model and the final model retaining variables that remained significant at the 5 % level.

Results

Unintended pregnancy was reported by 55.4 % of postpartum women. The following variables maintained positive and significant statistical associations with mistimed pregnancy: maternal age?<?20 years (OR?=?1.89, 95 % CI: 1.68–2.14); brown (OR?=?1.15, 95 % CI: 1.04–1.27) or yellow skin color (OR?=?1.56, 95 % CI: 1.05–2.32); having no partner (OR?=?2.32, 95 % CI: 1.99–2.71); having no paid job (OR?=?1.15, 95 % CI: 1.04–1.27); alcohol abuse with risk of alcoholism (OR?=?1.25, 95 % CI: 1.04–1.50) and having had three or more births (OR?=?2.01, 95 % CI: 1.63–2.47). The same factors were associated with unwanted pregnancy, though the strength of the associations was generally stronger. Women with three or more births were 14 times more likely to have an unwanted pregnancy, and complication in the previous pregnancies and preterm birth were 40 % and 19 % higher, respectively. Previous neonatal death was a protective factor for both mistimed (OR?=?0.61, 95 % CI: 0.44–0.85) and unwanted pregnancy (OR?=?0.44, 95 % CI: 0.34–0.57).

Conclusions

This study confirms findings from previous research about the influence of socioeconomic and individual risk factors on unintended pregnancy. It takes a new approach to the problem by showing the importance of previous neonatal death, preterm birth and complication during pregnancy as risk factors for unintended pregnancy.

     

The role of macrophage migration inhibitory factor in the cascade of events leading to reperfusion-induced inflammatory injury and lethality

Ischemia and reperfusion (I/R) injury is associated with a systemic inflammatory response, characterized by intense tumor necrosis factor (TNF)-alpha production and TNF-alpha-dependent tissue injury. Macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine that may induce TNF-alpha release and play an important role in innate immune and inflammatory responses. The aim of this work was to assess whether MIF was involved the inflammatory cascade and injury that follows intestinal I/R. To this end, wild-type (WT) and MIF-deficient (MIF(-/-)) mice underwent 60 minutes of ischemia followed by 60 minutes of reperfusion, after which they were culled for the assessment of inflammatory parameters. I/R was accompanied by an increase in circulating levels of MIF and an increase of vascular permeability, hemorrhage, and production of TNF-alpha in the intestine and lungs. The latter parameters were markedly suppressed in reperfused MIF(-/-) mice, and this was associated with decreased lethality (80% in WT versus 20% in MIF(-/-) mice). Interestingly, the reperfusion-associated neutrophil accumulation in the intestine and lungs was similar in WT and MIF(-/-) mice. Leukocytes isolated from lungs of MIF(-/-) mice were less activated, as assessed by their response to zymosan in a luminol-enhanced chemiluminescence assay. In conclusion, our results suggest that MIF plays an important role in the cascade of events leading to TNF-alpha production and reperfusion-induced tissue injury and lethality in mice.     

Bond strength of acrylic teeth to denture base resin after various surface conditioning methods before and after thermocycling

This study aimed to evaluate the durability of adhesion between acrylic teeth and denture base acrylic resin. The base surfaces of 24 acrylic teeth were flatted and submitted to 4 surface treatment methods: SM1 (control): No SM; SM2: application of a methyl methacrylate-based bonding agent (Vitacol); SM3: air abrasion with 30-microm silicone oxide plus silane; SM4: SM3 plus SM2. A heat-polymerized acrylic resin was applied to the teeth. Thereafter, bar specimens were produced for the microtensile test at dry and thermocyled conditions (60 days water storage followed by 12,000 cycles). The results showed that bond strength was significantly affected by the SM (P < .0001) (SM4 = SM2 > SM3 > SM1) and storage regimens (P < .0001) (dry > thermocycled). The methyl methacrylate-based adhesive showed the highest bond strength.     

Need of vascular surgeon and comparison of value for anterior lumbar interbody fusion (ALIF) in lateral decubitus: Delphi consensus

European Spine Journal - Anterior lumbar approaches are recommended for clinical conditions that require interbody stability, spinal deformity corrections or a large fusion area. Anterior lumbar...     

Design Method of a Foldable Ventricular Assist Device for Minimally Invasive Implantation

To date, ventricular assist devices (VADs) have become accepted as a therapeutic solution for end‐stage heart failure patients when a donor heart is not available. Newer generation VADs allow for a significant reduction in size and an improvement in reliability. However, the invasive implantation still limits this technology to critically ill patients. Recently, expandable/deployable devices have been investigated as a potential solution for minimally invasive insertion. Such a device can be inserted percutaneously via peripheral vessels in a collapsed form and operated in an expanded form at the desired location. A common structure of such foldable pumps comprises a memory alloy skeleton covered by flexible polyurethane material. The material properties allow elastic deformation to achieve the folded position and withstand the hydrodynamic forces during operation; however, determining the optimal geometry for such a structure is a complex challenge. The numerical finite element method (FEM) is widely used and provides accurate structural analysis, but computation time is considerably high during the initial design stage where various geometries need to be examined. This article details a simplified two‐dimensional analytical method to estimate the mechanical stress and deformation of memory alloy skeletons. The method was applied in design examples including two popular types of blade skeletons of a foldable VAD. Furthermore, three force distributions were simulated to evaluate the strength of the structures under different loading conditions experienced during pump operation. The results were verified with FEM simulations. The proposed two‐dimensional method gives a close stress and deformation estimation compared with three‐dimensional FEM simulations. The results confirm the feasibility of such a simplified analytical approach to reveal priorities for structural optimization before time‐consuming FEM simulations, providing an effective tool in the initial structural design stage of foldable minimally invasive VADs.