Burden of Uterine Fibroids: An African Perspective, A Call for Action and Opportunity for Intervention.

Black women carry the burden of uterine fibroids, (AKA uterine leiomyomas), at a much higher rate than their racial counterparts. Thus, increasing awareness and discovering a solution to an endemic problem that plagues Sub-Saharan Africa is of critical importance, not only for the region itself, but also for the medical community globally. A collaborative, patient oriented, cost effective, and culturally sensitive approach must be at the forefront of this endeavor. While the exact pathogenesis of uterine fibroid development remains elusive, the racial disparity is well documented. Moreover, in the developed world, women are able to seek treatment through surgical and non-surgical means; however, sub-Saharan regions face their own challenges that, if not addressed, can ultimately extinguish the lives of many suffering women. Unfortunately, the literature is scarce on how to prevent fibroid development, which may be critical for women who do not have access to effective interventions. Recent research from our group and others has shown that vitamin D deficiency plays an important role in fibroid development and may be a preventable risk factor. Daily vitamin D supplementation is a low cost, effective intervention that could be implemented throughout the Sub-Saharan region. Similarly, education and increased awareness as to the nature and symptoms of uterine fibroids could improve the quality of life, remove negative social stigma, and reduce morbidity and mortality rates in women who seek medical care with advanced uterine fibroids.

Testing the fading affect bias for healthy coping in the context of death.

Affect fades faster for unpleasant events than for pleasant events (e.g., Walker, Vogl, & Thompson, 1997 ), which is referred to as the fading affect bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003 ). Although research has generally shown that the FAB is a healthy coping mechanism, this same finding has not been demonstrated at a specific level of analysis accounting for particular event types and related individual differences (e.g., Gibbons et al., 2013 ). Given the strong unpleasant emotions associated with death (Rask, Kaunonen, & Paunonen-Ilmonen, 2002 ), the current study examined FAB in the context of death events and participant attitudes toward death. General healthy coping was shown by robust FAB across death and control (i.e., everyday) events and by a negative correlation between negative religious coping and FAB. Although healthy coping at a specific level of analysis was supported by increased FAB for participants who held accepting attitudes toward death when they recalled everyday events, it was not supported by decreased FAB for the same participants when they recalled death events. This effect was mediated by rehearsal ratings, not depression. Implications are discussed.

Recommendations for probiotic use-2011 update.

This study describes the consensus opinion of the participants of the third Yale Workshop on probiotic use. There were 10 experts participating. The recommendations update those of the first 2 meetings that were published in 2005 and 2008. The workshop presentations and papers in this supplement relate to the involvement of normal microbiota involved in intestinal microecology, how the microbes interact with the intestine to affect our immunologic responses, the stability and natural history of probiotic organisms, and the role of the intestinal microbatome with regard to affecting cardiac risk factors and obesity. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile diarrhea are reviewed. As in previous publications, the recommendations are given as A, B, or C ratings. The recent positive experiences with bacteriotherapy (fecal microbiome transplant) are also discussed in detail and a positive recommendation is made for use in severe resistant C. difficile diarrhea.

Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study.

OBJECTIVES: To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom. DESIGN: Open label, randomised, parallel group, phase II study. SETTING: Five UK centres (Oxford, Southampton, Bristol, Exeter, and London). PARTICIPANTS: Children aged 6 months to less than 13 years for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures were eligible. Those with laboratory confirmed pandemic H1N1 influenza or clinically diagnosed disease meriting antiviral treatment, allergy to egg or any other vaccine components, or coagulation defects, or who were severely immunocompromised or had recently received blood products were excluded. Children were grouped by age: 6 months-<3 years (younger group) and 3-<13 years (older group). Recruitment was by media advertising and direct mailing. Recruitment visits were attended by 949 participants, of whom 943 were enrolled and 937 included in the per protocol analysis. INTERVENTIONS: Participants were randomised 1:1 to receive AS03(B) (tocopherol based oil in water emulsion) adjuvanted split virion vaccine derived from egg culture or non-adjuvanted whole virion vaccine derived from cell culture. Both were given as two doses 21 days apart. Reactogenicity data were collected for one week after immunisation by diary card. Serum samples were collected at baseline and after the second dose. MAIN OUTCOME MEASURES: Primary reactogenicity end points were frequency and severity of fever, tenderness, swelling, and erythema after vaccination. Immunogenicity was measured by microneutralisation and haemagglutination inhibition assays. The primary immunogenicity objective was a comparison between vaccines of the percentage of participants showing seroconversion by the microneutralisation assay (fourfold rise to a titre of >or=1:40 from before vaccination to three weeks after the second dose). RESULTS: Seroconversion rates were higher after the adjuvanted split virion vaccine than after the whole virion vaccine, most notably in the youngest children (163 of 166 participants with paired serum samples (98.2%, 95% confidence interval 94.8% to 99.6%) v 157 of 196 (80.1%, 73.8% to 85.5%), P<0.001) in children under 3 years and 226 of 228 (99.1%, 96.9% to 99.9%) v 95.9%, 92.4% to 98.1%, P=0.03) in those over 3 years). The adjuvanted split virion vaccine was more reactogenic than the whole virion vaccine, with more frequent systemic reactions and severe local reactions in children aged over 5 years after dose one (13 (7.2%, 3.9% to 12%) v 2 (1.1%, 0.1% to 3.9%), P<0.001) and dose two (15 (8.5%, 4.8% to 13.7%) v 2 (1.1%, 0.1% to 4.1%), P<0.002) and after dose two in those under 5 years (15 (5.9%, 3.3% to 9.6%) v 0 (0.0%, 0% to 1.4%), P<0.001). Dose two of the adjuvanted split virion vaccine was more reactogenic than dose one, especially for fever >or=38 masculineC in those aged under 5 (24 (8.9%, 5.8% to 12.9%) v 57 (22.4%, 17.5% to 28.1%), P<0.001). CONCLUSIONS: In this first direct comparison of an AS03(B) adjuvanted split virion versus whole virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine, while more reactogenic, was more immunogenic and, importantly, achieved high seroconversion rates in children aged less than 3 years. This indicates the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION: Clinical trials.gov NCT00980850; ISRCTN89141709.

Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease largely affecting low birth weight, premature infants. Once acquired, NEC is accompanied by significant mortality and morbid sequelae. Our understanding of the pathophysiology of NEC continues to evolve, and the development of NEC is likely multifactorial with resultant bowel injury mediated through a final, common inflammatory pathway. The predisposition for NEC appears to involve the interplay between intestinal integrity and function, enteral feeding and bacterial colonization, and regulation of the gastrointestinal and systemic inflammatory response. Commensal organisms or probiotics have been shown to be crucial in the development and modulation of each of these factors within the intestinal epithelium. As a result, probiotic supplementation has been proposed as a promising new intervention for the prevention of NEC. To understand the potential utility of probiotics in NEC, we will discuss: the components of gut defense; the role of the intestinal ecosystem in modulating immunity and inflammation; bacterial colonization patterns in the preterm infant compared with patterns seen in the healthy, full-term infant; the evidence for probiotic use in other populations and diseases; and finally, the evidence of probiotic use specific to the preterm infant and NEC.

Probiotics and chronic disease.

In today's climate, changed lifestyles and the increased use of antibiotics are significant factors that affect the preservation of a healthy intestinal microflora. The concept of probiotics is to restore and maintain a microflora advantageous to the human body. Probiotics are found in a number of fermented dairy products, infant formula, and dietary supplements. Basic research on probiotics has suggested several modes of action beneficial for the human body and clinical research has proven its preventive and curative features in different intestinal and extraintestinal diseases. Chronic diseases cause considerable disablement in patients and represent a substantial economic burden on healthcare resources. Research has demonstrated a crucial role of nutrition in the prevention of chronic disease. Thus, positive, strain-specific effects of probiotics have been shown in diarrheal diseases, inflammatory bowel diseases, irritable bowel syndrome, and Helicobacter pylori-induced gastritis, and in atopic diseases and in the prevention of cancer. As the majority of probiotics naturally inhabit the human intestinal microflora, their use has been regarded as very safe. However, in view of the range of potential benefits on health that might be achieved by the use of some probiotic bacteria, major and thorough evaluation is still necessary. In conclusion, probiotics act as an adjuvant in the prevention and treatment of a wide variety of chronic diseases.

Probiotics as flourishing benefactors for the human body.

This article provides a comprehensive review of the beneficial effects of various strains of probiotics in preventing and treating certain diseases. Currently, changed lifestyles as well as the increased use of antibiotics are significant factors challenging the preservation of a healthy intestinal microflora. The concept of probiotics is to restore and uphold a microflora advantageous for the human body. Probiotics are found in a number of fermented dairy products, infant formula, and dietary supplements. In the presence of prebiotics, which are nondigestible food ingredients favorable for probiotic growth, their survival in the intestine is ameliorated.

The effect of protective nutrients on mucosal defense in the immature intestine.

Oral nutrition plays a dual role in the gut, providing nutrition to the body while affecting the function of the gastrointestinal tract. The exposure of the gut to food antigens, in the form of either beneficial or harmful nutritional substances, contributes to a vast array of physiological and pathologic gastrointestinal responses with secondary systemic implications. The immune system of the gastrointestinal tract is always involved in the first line of defense, and its actions are particularly important in the early period of life as maturation takes place. From maturation, a balance ensues in the regulatory mechanism of host defense, ultimately leading to either tolerance or immune reaction. This paper emphasizes how some nutrients may beneficially affect the gastrointestinal immune system's maturation in both term and especially premature neonates.

Probiotics and prebiotics: role in clinical disease states.

Parents of pediatric patients are seeking alternatives to conventional therapy in the prevention and treatment of gastrointestinal disease states because of therapeutic failures caused by the increased incidence of antibiotic resistance. One such alternative is the use of probiotics and prebiotics to stimulate health-promoting indigenous flora to affect pathogen colonization and expression of disease. Probiotics are live flora given in oral quantities that allow for colonization of the colon. Probiotics are given as functional foods or dietary supplements, and function to activate the mucosal immune system and prevent pathogen colonization and translocation by strengthening the mucosal barrier, interfering with pathogen colonization, and in some instances, producing secretory antibacterial substances. Prebiotics are nondigestible carbohydrates, principally oligosoccharides, that are fermented by colonic commensals, stimulating their proliferation and producing short-chain fatty acids. Both protective nutrients have been shown to reduce the incidence and severity of infantile diarrhea, particularly rotaviral gastroenteritis, prevent antibiotic-induced diarrhea, and prevent and treat intestinal food allergy. With additional multicenter clinical trial confirmations, these substances may become routine in the care of infants and young children.

The dynamic effects of breastfeeding on intestinal development and host defense.

In this review, evidence is provided to support the hypothesis that human milk provides a link between the mother and her newborn infant in the extrauterine environment in a manner similar to the placental link between mother and fetus in utero. In addition, breastfeeding helps prevent age-related diseases affecting the gastrointestinal tract during the newborn period. To provide evidence to support this hypothesis, anecdotal clinical studies are sited to suggest that human milk contains factors that may be missing in inherited diseases of inborn errors in metabolism and provide passive protective factors that lessen the expression of neonatal allergic and infectious diseases. In some instances, by providing the missing factor in an inherited disease, the newborn may be protected from serious damage to its developing brain. A second line of evidence to support this hypothesis is the observation that the composition of human milk varies with the infant's needs. To illustrate this principal, the composition of milk from mothers delivering prematurely and milk of mothers of full-term infants were compared, and the differences in trophic and protective factors in colostrum versus mature milk from mothers delivering full-term are cited. Finally, using observations from the laboratory that define the immaturities in neonatal and premature human intestinal defenses as the neonate's host defense deficiency, the specific effect that anti-inflammatory and maturational factors in human milk has on these immaturities is discussed. The active stimulus of maternal milk on the rapid development of host defenses is underscored. These cited examples of human milk effects in the newborn help support the stated hypothesis. Additional studies of human immature gut function along with translational and clinical studies are necessary to provide further objective evidence in support of breastfeeding for all neonates, particularly premature neonates.

Iron deficiency anemia in children with exstrophy of the cloaca.

The clinical records of twenty-five children with exstrophy of the cloaca (EC) were retrospectively reviewed to evaluate the prevalence and the clinical characteristics of iron deficiency anemia (IDA). Five of the 25 children with EC (20 %) exhibited IDA at some point. Their ages at the time of diagnosis were between 1.9 and 13.0 years. In the four cases where IDA was thought to be related to iron malabsorption secondary to short-bowel syndrome, its treatment required longer periods of iron supplementation to correct the anemia and to restore the total body iron stores. Physicians caring for children with EC should monitor for and treat IDA as part of a comprehensive management plan.

Nutritional impact of pre- and probiotics as protective gastrointestinal organisms.

The health benefits of pre- and probiotics have been the subject of increased research interests. These food supplements have been demonstrated to alter the pre-existing intestinal flora so as to provide an advantage to the host. This review focuses on the scientific evidence both for and against their role in promoting health and treating disease. Specific attention is turned to their effects on immunomodulation, lipid metabolism, cancer prevention, diarrhea, Helicobacter pylori, necrotizing enterocolitis, allergy, and inflammatory bowel disease.

Protective nutrients and functional foods for the gastrointestinal tract.

Epithelial and other cells of the gastrointestinal mucosa rely on both luminal and bloodstream sources for their nutrition. The term functional food is used to describe nutrients that have an effect on physiologic processes that is separate from their established nutritional function, and some of these nutrients are proposed to promote gastrointestinal mucosal integrity. We review the recent in vitro, animal, and clinical experiments that evaluated the role of several types of gastrointestinal functional foods, including the amino acids glutamine and arginine, the essential micronutrients vitamin A and zinc, and 2 classes of food additives, prebiotics and probiotics. Many of the data from preclinical studies support a strong role for enteral nutrients in gastrointestinal health; in comparison, the data from human studies are limited. In some cases, impressive data from in vitro and animal studies have not been replicated in human trials. Other clinical trials have shown positive health benefits, but some of those studies were plagued by flaws in study design or analysis. The methods available to detect important changes in human gastrointestinal function and structure are still limited, but with the development of more sensitive measures of gastrointestinal function, the effects of specific nutrients may be more easily detected. This may facilitate the development of phase 3 clinical trials designed to more rigorously evaluate the effects of a particular nutrient by focusing on valid and reliable outcome measures. Regulatory changes in the way in which health claims can be made for dietary supplements should also be encouraged.

PH changes at the surface of root dentin after intracanal dressing with calcium oxide and calcium hydroxide.

This study was designed to compare pH changes at the cervical and apical surfaces of root dentin after canal obturation with calcium oxide or calcium hydroxide pastes. The effect of the exposure to CO2 on the pH at the root surface also was assessed for both materials. Thirty-six extracted human canines were selected and instrumented. Wells 1 mm deep x 1.5 mm in diameter were drilled in the cervical and apical regions of the buccal root surface. The teeth were randomly divided into two groups and obturated with either calcium hydroxide or calcium oxide. pH was measured in the cervical and apical wells at varying time intervals until 48 days posttreatment. After pH measurement on day 48 the vials were flushed with CO2 and the pH measured again at days 53 and 68. The results indicated a similar pattern of pH increase after treatment with either calcium oxide or calcium hydroxide. pH dropped significantly after exposure to CO2 in both groups. This study demonstrated that hydroxyl ions produced when calcium oxide reacts with water diffuse through the dentinal tubules to the surface of the root in a manner similar to hydroxyl ions from calcium hydroxide.

Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer.

We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybridization specificity and sensitivity on parameters including oligonucleotide length, hybridization stringency, sequence identity, sample abundance, and sample preparation method. We find that 60-mer oligonucleotides reliably detect transcript ratios at one copy per cell in complex biological samples, and that ink-jet arrays are compatible with several different sample amplification and labeling techniques. Furthermore, results using only a single carefully selected oligonucleotide per gene correlate closely with those obtained using complementary DNA (cDNA) arrays. Most of the genes for which measurements differ are members of gene families that can only be distinguished by oligonucleotides. Because different oligonucleotide sequences can be specified for each array, we anticipate that ink-jet oligonucleotide array technology will be useful in a wide variety of DNA microarray applications.

Epidemiological evaluation of the outcomes of nonsurgical root canal treatment in a large cohort of insured dental patients.

Selected outcomes following initial nonsurgical root canal treatment (NSRCT) procedures were retrospectively assessed using an insurance company database of 110,766 nonsurgical root canal procedures that were completed by endodontists and their referring general dentists. A subset of 44,613 cases, with a minimum required follow-up time of 2 yr, showed incidences of extraction, retreatment and periradicular surgery equal to 5.56%, 2.47%, and 1.41%, respectively. The incidence of subsequent extraction increased with patient age. Teeth that were not restored after root canal therapy were significantly more likely to undergo extraction than restored teeth. Although the practice pattern for endodontists consisted of a significantly higher proportion of molars (48% more; p < 0.001) and a smaller proportion of anterior teeth (43% less; p < 0.001) than general dentists, both groups of providers had comparable rates of untoward events. These data strongly support the hypothesis that the specialist practice provides similar rates of clinical success compared with other providers, even when treating significantly more complex NSRCT cases. Overall, 94.44% of nonsurgical root canal treated teeth remained functional over an average follow-up time of 3.5 yr. These results are an important indication of the benefits of endodontic treatment when provided in an integrated health care delivery system of endodontists and their referring general dentists.