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PURPOSE:

The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes.

PARTICIPANTS:

n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico.

FINDINGS TO DATE:

Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling.

FUTURE PLANS:

As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures.

Background:

The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear.

Purpose:

To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults.

Data Sources:

PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists.

Study Selection:

English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease.
Data Extraction:

Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.
Data Synthesis:

Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence).
Limitations:

Suboptimal quality and certainty of evidence.

Conclusion:

Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke.

Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer’s disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer’s patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1-42, a component of amyloid plaques. Further, gingipains were neurotoxic in vivo and in vitro, exerting detrimental effects on tau, a protein needed for normal neuronal function. To block this neurotoxicity, we designed and synthesized small-molecule inhibitors targeting gingipains. Gingipain inhibition reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus. These data suggest that gingipain inhibitors could be valuable for treating P. gingivalis brain colonization and neurodegeneration in Alzheimer’s disease.

Dental implants are often made of titanium alloys. Implant therapy currently promises a good long-term result without impacting health; however, its success depends on many factors. In this article, the authors focus on the most common risk factors associated with metallic surgical implants. Titanium-induced hypersensitivity can lead to symptoms of implant rejection. Corrosion and biofilm formation are additional situations in which these symptoms may occur. For medical purposes, it is important to define and discuss the characteristics of metals used in implantable devices and to ensure their biocompatibility. To avoid hypersensitivity reactions to metallic dental implants, precautionary principles for primary prevention should be established.

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus (GG) is the main upper airway dilator muscle. Currently, continuous positive airway pressure is the first-line treatment for OSA. Nevertheless, problems related to poor adherence have been described in some groups of patients. In recent years, new OSA treatment strategies have been developed to improve GG function. (A) Hypoglossal nerve electrical stimulation leads to significant improvements in objective (apnea-hypopnea index, or AHI) and subjective measurements of OSA severity, but its invasive nature limits its application. (B) A recently introduced combination of drugs administered orally before bedtime reduces AHI and improves the responsiveness of the GG. (C) Finally, myofunctional therapy also decreases AHI, and it might be considered in combination with other treatments. Our objective is to review these therapies in order to advance current understanding of the prospects for alternative OSA treatments.

Background:

The immune and bone systems are closely linked via cytokine cross-talk. This interdisciplinary field of research is referred to as osteoimmunology and pertains to inflammatory and osteoarticular diseases that feature the primary expression of tumor necrosis factor-alpha (TNF-α) and IL-6.

Objective:

Are there bone resorptive processes wherein chronic inflammatory conditions are not linked to TNF-α and IL-6 expression, but rather to the expression of other cytokines?
Materials and methods:

A comprehensive literature search was performed in PubMed Central.

Discussion:

Although all diseases with cytokines involved in bone resorption (TNF-α and IL-6) are at the forefront of destructive inflammatory processes, there is one exception in the literature: fatty oxide osteoporosis/osteolysis in the jawbone (FDOJ), which is associated with significant bone softening. However, it should be noted that TNF-α and IL-6 fall below the levels found in a healthy jawbone in this condition. Another conspicuous finding is that there is a nearly 35-fold overexpression of the chemokine RANTES/CCL5 (R/C) in all FDOJ cases studied thus far in the literature.

Conclusion:

FDOJ appears to represent a unique cytokine and inflammatory pattern from osteolysis in the body. R/C can be defined as the dominant carrier of a “maxillomandibular osteoimmunology”.

OBJECTIVES:

With a growing interest in the mother-infant dyad and the Developmental Origins of Health and Disease hypothesis among biological and medical anthropologists, this study set out to provide all the information required to evaluate if mineralization defects in dentine might be caused by vitamin D deficiency in the critical first 1000 days of life.

MATERIALS AND METHODS:

Information was compiled on dentine formation in utero to approximately 18 years, and a method for determining the location of the neonatal line in dentine was devised, allowing the assessment of the prenatal and early life period. Re-evaluation of previously analyzed teeth (n = 61) was undertaken with detailed examination of n = 5/22 first permanent molars forming in the prenatal and critical early life periods.

RESULTS:

First permanent molars and all deciduous teeth give information on intrauterine development and on the first 1000 days postnatally providing a direct window on maternal and fetal health. Three archaeological individuals had interglobular dentine that formed prenatally suggesting that their mothers experienced vitamin D deficiency at the time dentine was forming and all other individuals had a deficiency during the first 1000 days of life. Conditions that could cause systemic mineralization defects were determined, and in each, case they were found to be consistent with vitamin D deficiency.

DISCUSSION:

The neonatal line serves as a clear baseline for determining prenatal and postnatal events, particularly those related to vitamin D, calcium, and phosphate metabolism, and can be used to investigate the maternal-infant dyad for both past and present communities.