Immunomodulatory Effects of Dietary Polyphenols

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.     

Examining consent within the patient-doctor relationship

The notion of consent which rose to the forefront in biomedical ethics as an attempt to safeguard patients' autonomy, is relatively new. The notion itself requires qualification, for it precludes neither duress nor ignorance. More seriously, I argue here that consent is redundant except in situations where paternalism prevails. Paradoxically, these are the very situations where it may be difficult to uphold or to verify voluntary consent. I suggest that a request-based relationship has the potential to overcome these difficulties. It enhances patients' participation in decision making, requires that the patients remain in command and avoids their subordination. Request is also more conducive to treatments that are representative of patients' own values and perceptions. In practice, what one wants and what one agrees to, often concur. But these are not conceptually identical issues, and they carry important differences of emphasis.     

The prevalence of Type 2 Diabetes Mellitus in the United Arab Emirates: justification for the establishment of the Emirates Family Registry

To study the prevalence of Type 2 Diabetes Mellitus (T2DM) in a population of United Arab Emirates (UAE) residents through the creation of the ??Emirates Family Registry?? (EFR). Major hospitals and diabetes centres in the UAE were contacted to establish a bio-banking facility referred to as the EFR. Through assistance made available by the Ministry of Health and collaborators of this network, demographic data of T2DM patients were collected and collated in a database for analysis and longitudinal studies. Clinical specimens were collected for biochemical profiling (such as; glucose, lipids, HbA_1c levels). In the first 24?months of the operation the EFR recruited 23,064 adult volunteers from three major hospitals and nine primary care centres throughout the UAE. Within this cohort, 88% were patients classified as T2DM patients from the medical records. The cohort was divided into age categories with 59% of T2DM patients aged between 40 and 59?years old. UAE nationals comprised 30% of the database of which 21% were diagnosed with T2DM. However the percentage of adults with T2DM was higher in other ethnic groups effecting almost 33% of the Indians who live in the UAE. A total of 741 UAE Nationals consented to donate blood; in phase I of the study; for biochemical testing after which 23% were diagnosed with T2DM, 30% with pre-T2DM and 47% were healthy. This study is consistent with the previously reported high prevalence of T2DM in the UAE. Furthermore, analyses of the factors that predispose to the disease have revealed that obesity, a large waist circumference, consanguineous marriage, family history, lack of physical activity, unhealthy dietary practices, high total cholesterol, and high triglycerides levels were more prevalent in T2DM patients. The classification of these features will contribute to defining more effective and specific plans to screen for and manage diabetes and its complications in UAE and other developing countries.     

Smoking in pregnancy affects the fetal heart: possible links to future cardiovascular disease

Objectives: To investigate effects of maternal smoking on the fetal heart rate (FHR) in ambulatory patients using a portable fetal electrocardiogram recording device.

Methods: A prospective cohort study of 43 pregnant smokers and 43 non-smoking gestation-matched controls with uncomplicated singleton pregnancies. Smokers were divided into light (1–10) and moderate (11–20 cigarettes/d). The FHR was recorded for 16?h with smokers smoking at will, using an event button to record when they lit a cigarette. Fifty recordings were made in the patients’ homes with 36 in ambulatory inpatients. Three consecutive 30-min epochs (before, during and after smoking) were compared with the controls.

Results: Basal FHR was significantly lower before smoking in the foetuses of smokers compared with non-smokers (p?=?0.048). During smoking, there was a significant dose-dependent fall in short-, long-term and true beat-to-beat variabilities (p?=?0.004, p?<?0.0001 and p?=?0.024, respectively).

Conclusion: Maternal smoking leads to reversible changes in FHR variability that mimic those associated with an increased incidence of adverse cardiovascular events in adults. As heart rate and variability reflect the autonomic control of the heart, our findings suggest that maternal smoking interferes with the autonomic control of the FHR.     

Trabecular bone in domestic dogs and wolves: Implications for understanding human self-domestication

The process of domestication is complex and results in significant morphological, cognitive, and physiological changes. In canids, some of the traits indicative of domestication of domestic dogs compared to their wild counterparts the wolves are prosociality toward humans, reduced stress hormone levels, and reduced cranial capacity. Research suggests that selection for prosociality among dogs resulted in morphological changes such as reduction in cranial capacity, juvenilization of the face, and overall gracile morphology. Interestingly, similar features have been described in modern humans compared to extinct species of Homo, for example, Neanderthals. Therefore, the human self-domestication hypothesis has been proposed to partially explain the gracile modern human skeleton. Specifically, that as modern humans settled in communities, there was increased selection for prosociality (intergroup cooperation); and one of the by-products of this selection was the evolution of a gracile skeleton, including a slight reduction in cranial capacity, reduced brow ridge and tooth size, and low trabecular bone fraction (TBF). However, TBF variation has not been tested between domestic dogs and wolves, who underwent self-domestication. Thus, this study tests the hypothesis that dogs have low TBF as a consequence of domestication compared to their wild counterparts, the wolves, by comparing TBF in the hindlimbs—proximal femur and distal tibia- of the two species. Wilcoxon rank sum tests show that dogs have lower TBF values than wolves in both elements. These preliminary results add to the literature documenting changes in self-domesticated species and provide a potential analog to further the understanding of self-domestication.     

Displacement of the Hip Center of Rotation After Arthroplasty of Crowe III and IV Dysplasia: A Radiological and Biomechanical Study

To study the direction and biomechanical consequences of hip center of rotation (HCOR) migration in Crowe type III and VI hips after total hip arthroplasty, post-operative radiographs and CT scans of several unilaterally affected hips were evaluated. Using a three-dimensional model of the human hip, the HCOR was moved in all directions, and joint reaction force (JRF) and abductor muscle force (AMF) were calculated for single-leg stance configuration. Comparing to the normal side, HCOR had displaced medially and inferiorly by an average of 23.4% and 20.8%, respectively, of the normal femoral head diameter. Significant decreases in JRF (13%) and AMF (46.13%) were observed in a presumptive case with that amount of displacement. Isolated inferior displacement had a small, increasing effect on these forces. In Crowe type III and IV hips, the HCOR migrates inferiorly and medially after THA, resulting in a decrease in JRF, AMF, and abductor muscle contraction force.     

Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21) gene. To determine the mutational spectrum in the Tunisian CAH population, the CYP21 active gene was analyzed in 51 unrelated patients using our cascade strategy (digestion by restriction enzyme, sequencing). All patients had a classical form of 21-hydroxylase deficiency. Mutations were detected in over 94% of the chromosomes examined. The most frequent mutation in the Tunisian CAH population was found to be Q318X, with large prevalence (35.3%), in contrast to 0.5-13.8% described in other series. Incidence of other mutations does not differ, as previously described: large deletions (19.6%), mutation in intron 2 (17.6%), and I172N (10.8%). Four novel mutations were found in four patients with the salt-wasting form. These four novel mutations include three point mutations that have not been reported to occur in the CYP21P pseudogene: R483W, W19X, 2669insC, and one small conversion of DNA sequence from exon 5 to exon 8. Our results have shown a good genotype/phenotype correlation in the case of most mutations. This is the first report of screening for mutations of 21-hydroxylase gene in the Tunisian population and even in the Arab population.