Prognostic impact of the ankle–brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study

Aims/hypothesis

The prognostic importance of the ankle–brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes.

Methods

The ABI was measured at baseline in 668 individuals with type 2 diabetes, and the individuals were followed-up for a median of 10 years. Multivariate Cox analysis was used to examine associations between the ABI and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration and peripheral neuropathy) and macrovascular (total cardiovascular events, major adverse cardiovascular events [MACE] and cardiovascular mortality) complications, and all-cause mortality. The improvement in risk stratification was assessed using the C statistic and the integrated discrimination improvement (IDI) index.

Results

During follow-up, 168 individuals had a cardiovascular event (140 MACE) and 191 individuals died (92 cardiovascular deaths); 156 individuals newly developed or experienced worsening diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly developed microalbuminuria and 93 with deteriorating renal function) and 95 newly developed or experienced worsening peripheral neuropathy. The ABI, either analysed as a continuous or as a categorical variable, was significantly associated with all macrovascular and mortality outcomes, except for non-cardiovascular mortality. Individuals with a baseline ABI of ≤0.90 had a 2.1-fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p?=?0.004), a 2.7-fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p?=?0.004) and a 2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p?=?0.001). The ABI improved risk discrimination over classical risk factors, with relative IDIs ranging from 6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In addition, an ABI of ≤0.90 was associated with the development or worsening of peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p?=?0.033), but not with retinopathy or renal outcomes.

Conclusions/interpretation

A low ABI is associated with excess risk of adverse cardiovascular outcomes, mortality and peripheral neuropathy development or worsening, and improves cardiovascular risk stratification. The ABI should therefore be routinely evaluated in individuals with type 2 diabetes.

     

Effects of interactions between ApoE polymorphisms,alcohol consumption and obesity on age-related trends of blood pressure levels in postmenopausal women: The Bambuì cohort study of aging (1997–2008)

Objectives

To evaluate the effects of interactions between ApoE genotypes, alcohol consumption and obesity on the age-related trends of blood pressure (BP) levels in postmenopausal women.

Study design

A population-based prospective cohort study of all residents in Bambuì, south-eastern Brazil, aged 60 years or older. Repeated BP measurements were obtained in four waves from 851 women who underwent ApoE genotyping at baseline (88.3% of those enrolled), and multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. The few measurements (2.1%) made during hormone replacement therapy were excluded from the analysis.

Results

Alcohol consumption was associated with high levels of systolic and diastolic BP in an age × genotype-dependent manner only in the non-obese women (BMI < 27 kg/m²). Among those with the ?3/3 genotype, the differences in systolic and diastolic levels between drinkers and non-drinkers estimated at the age of 60 years were respectively 13.7 mmHg (p = 0.022) and 10.7 mmHg (p = 0.002), and disappeared in the older age groups, in which drinking was associated with systolic/diastolic hypertension if the non-obese women were ?4 carriers.

Conclusion

In non-obese postmenopausal women, alcohol consumption is associated with systolic and diastolic hypertension early in those with the ?3/3 ApoE genotype, and late in ?4 carriers. We hypothesize the mediation of androgen hormones and the influence of ApoE genotypes on age at natural menopause. A better understanding of these mechanisms may guide better preventive choices.     

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis

Circulating T_FH (cT_FH) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT_FH1, cT_FH2, cT_FH17, and cT_FR cells, respectively. This CD4⁺T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT_FH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cT_FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T_FH cells derived from naïve CD4⁺T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T_FH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10⁺T_FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT_FH and B cell subsets.     

Artificial Intelligence for Fast and Accurate 3-Dimensional Tooth Segmentation on Cone-beam Computed Tomography

IntroductionTooth segmentation on cone-beam computed tomographic (CBCT) imaging is a labor-intensive task considering the limited contrast resolution and potential disturbance by various artifacts. Fully automated tooth segmentation cannot be achieved by merely relying on CBCT intensity variations. This study aimed to develop and validate an artificial intelligence (AI)-driven tool for automated tooth segmentation on CBCT imaging.MethodsA total of 433 Digital Imaging and Communications in Medicine images of single- and double-rooted teeth randomly selected from 314 anonymized CBCT scans were imported and manually segmented. An AI-driven tooth segmentation algorithm based on a feature pyramid network was developed to automatically detect and segment teeth, replacing manual user contour placement. The AI-driven tool was evaluated based on volume comparison, intersection over union, the Dice score coefficient, morphologic surface deviation, and total segmentation time.ResultsOverall, AI-driven and clinical reference segmentations resulted in very similar segmentation volumes. The mean intersection over union for full-tooth segmentation was 0.87 (±0.03) and 0.88 (±0.03) for semiautomated (SA) (clinical reference) versus fully automated AI-driven (F-AI) and refined AI-driven (R-AI) tooth segmentation, respectively. R-AI and F-AI segmentation showed an average median surface deviation from SA segmentation of 9.96 μm (±59.33 μm) and 7.85 μm (±69.55 μm), respectively. SA segmentations of single- and double-rooted teeth had a mean total time of 6.6 minutes (±76.15 seconds), F-AI segmentation of 0.5 minutes (±8.64 seconds, 12 times faster), and R-AI segmentation of 1.2 minutes (±33.02 seconds, 6 times faster).ConclusionsThis study showed a unique fast and accurate approach for AI-driven automated tooth segmentation on CBCT imaging. These results may open doors for AI-driven applications in surgical and treatment planning in oral health care.     

Synergistic potential of 1α,25-dihydroxyvitamin D3 and calcium–aluminate–chitosan scaffolds with dental pulp cells

Clinical Oral Investigations - This study aimed to develop a porous chitosan–calcium–aluminate scaffold (CH-AlCa) in combination with a bioactive dosage of 1α,25-dihydroxyvitamin...     

Postpartum depression: A systematic review of the genetics involved

Postpartum depression is one of the most prevalent psychopathologies. Its prevalence is estimated to be between 10% and 15%. Despite its multifactorial etiology, it is known that genetics play an important role in the genesis of this disorder. This paper reviews epidemiological evidence supporting the role of genetics in postpartum depression (PPD). The main objectives of this review are to determine which genes and polymorphisms are associated with PPD and discuss how this association may occur. In addition, this paper explores whether these genes are somehow related to or even the same as those linked to Major Depression (MD). To identify gaps in the current knowledge that require investigation, a systematic review was conducted in the electronic databases PubMed, LILACS and SciELO using the index terms “postpartum depression” and “genetics”. Literature searches for articles in peer-reviewed journals were made until April 2014. PPD was indexed 56 times with genetics. The inclusion criteria were articles in Portuguese, Spanish or English that were available by institutional means or sent by authors upon request; this search resulted in 20 papers. Genes and polymorphisms traditionally related to MD, which are those involved in the serotonin, catecholamine, brain-derived neurotrophic factor and tryptophan metabolism, have been the most studied, and some have been related to PPD. The results are conflicting and some depend on epigenetics, which makes the data incipient. Further studies are required to determine the genes that are involved in PPD and establish the nature of the relationship between these genes and PPD.     

Effect of testosterone on bone mineralization of the hypophosphataemic rat.

Clinical observations in patients with X-linked hypophosphataemic rickets, that bone changes can be corrected during puberty, suggest that androgen can participate actively in the process of bone mineralization. In the present study we investigated the role of testosterone on the bone mineralization of male rats placed on a low phosphorus and vitamin D diet and kept in complete darkness after weaning. After 15 days the animals presented hypophosphataemia, rickets and osteomalacia, as assessed by histomorphometry of the tibia and seventh caudal vertebra calcification fronts respectively. Testosterone propionate administration for five days, while the animals were kept on the same rachitogenic diet, induced an improvement in the bone mineralization process of the hypophosphataemic rat independently of serum phosphate levels. Testosterone-treated rats were cured of rickets but not of osteomalacia, despite the reduction in osteoid seam area.