Blastocystis in Health and Disease: Are We Moving from a Clinical to a Public Health Perspective?

Blastocystis is a genus of common single-celled intestinal parasitic protists with an unsettled role in human health and disease. Being a stable component of intestinal microbiota, once established, the Blastocystis parasite appears more common in healthy individuals than in patients with infectious, functional, or inflammatory bowel disease. Recent data suggest that the parasite is associated with certain gut microbiota profiles and health indices. Convincing data and tools differentiating asymptomatic colonization from infection are yet to be demonstrated. Although the parasite may elicit disease under certain circumstances, the focus on Blastocystis may be shifting from a clinical to a public health perspective.     

Descriptive and risk factor analysis for choanal atresia: The National Birth Defects Prevention Study, 1997–2007

Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case–control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997 through 2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. The exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n = 117) and isolated choanal atresia cases (those without additional unrelated major defects; n = 61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CIs) were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR = 1.9; CI = 1.1,3.1), zinc (aOR = 1.7; CI = 1.0,3.1), and niacin (aOR = 1.8; CI = 1.0,3.1), and intake in the lowest quartile for methionine (aOR = 1.6; CI = 1.0,2.6) and vitamin D (aOR = 1.6; CI = 1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR = 2.6; CI = 1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR = 0.4; CI = 0.2,0.9) and fat (aOR = 0.5; 95% CI = 0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR = 2.3; CI = 1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR = 2.5; CI = 1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR = 4.0; CI = 1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies.     

Prevalence of Chronic Kidney Disease in Korea: the Korean National Health and Nutritional Examination Survey 2011–2013

Chronic kidney disease is a leading public health problem related to poor quality of life and premature death. As a resource for evidence-informed health policy-making, we evaluated the prevalence of chronic kidney disease using the data of non-institutionalized adults aged ≥ 20 years (n = 15,319) from the Korean National Health and Nutrition Examination Survey in 2011–2013. Chronic kidney disease was defined as a urine albumin-to-creatinine ratio ≥ 30 mg/g or an estimated glomerular filtration rate < 60 mL/min/1.73 m² using the Chronic Kidney Disease-Epidemiology Collaboration equation. The total prevalence estimate of chronic kidney disease for adults aged ≥ 20 years in Korea was 8.2%. By disease stage, the prevalence of chronic kidney disease was as follows: stage 1, 3.0%; stage 2, 2.7%; stage 3a, 1.9%; stage 3b, 0.4%; and stages 4–5, 0.2%. When grouped into three risk categories according to the 2012 Kidney Disease: Improving Global Outcomes guidelines, the proportions for the moderately increased risk, high risk, and very high risk categories were 6.5%, 1.2%, and 0.5%, respectively. Factors including older age, diabetes, hypertension, cardiovascular disease, body mass indexes of ≥ 25 kg/m² and < 18.5 kg/m², and rural residential area were independently associated with chronic kidney disease. Based on this comprehensive analysis, evidence-based screening strategies for chronic kidney disease in the Korean population should be developed to optimize prevention and early intervention of chronic kidney disease and its associated risk factors.     

The World of Microbes 2002: Scientific Advances and Challenges–Impressions and Highlights from the 12th Congress of Virology

Thousands of scientists participated in the World of Microbes Congress, which was organized by the International Union of the Microbiological Societies (IUMS) and took place in the Palais de Congres in Paris, France from 27 July to 1 August 2002. The attendees were members of the IUMS divisions of Bacteriology and Applied Microbiology, Mycology, and Virology. In addition to the symposia that were organized by each division, joined plenary symposia were held, which encompassed subjects of common interest to all microbiologists. The activities at the 12th Congress of Virology's plenary lectures, symposia, and poster sessions were organized to accommodate the presentation of over 1500 presentations. These brief comments are aimed to provide a sample of only a few presentations that dealt with subjects of emerging and re-emerging virus diseases, which are of general interest.     

Predictors of Default from Treatment for Tuberculosis: a Single Center Case–Control Study in Korea

Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case–control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (< 2,000 US dollars/month, 88.1% vs. 68.4%, P = 0.015), absence of TB stigma (4.3% vs. 61.3%, P < 0.001), treatment by a non-pulmonologist (74.1% vs. 25.9%, P < 0.001), history of previous treatment (37.0% vs. 19.0%, P = 0.019), former defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078–265.365, P < 0.001), treatment by a non-pulmonologist (aOR: 14.567, 95% CI: 3.260–65.089, P < 0.001), former defaulters (aOR: 33.226, 95% CI: 2.658–415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249–22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default.     

Habituation: The Foundation of Learning and Attention,International Workshop on Habituation,Vancouver, August 15–18, 2007

Antibodies can be used to identify tissue- and stage-specifically expressed genes. A monoclonal antibody MAB ab49 from a hybridoma library screened for immunohistochemical staining in the adult nervous system of Drosophila melanogaster was found to selectively bind to all neuropil regions and to synaptic boutons of motor neurons. In Western blots of homogenized brains the antibody recognizes two proteins of 32 and 34 kD. Using this antibody we have isolated seven cDNA clones that derive from two polyadeny-lated mRNA splice variants of a gene located at 79E1-2 on polytene chromosomes. The two mRNAs code for two inferred proteins of 249 and 223 amino acids, respectively, which are identical except for their C-terminals and a central deletion of 21 amino acids in the second protein. Both contain a contiguous string of 11 cysteine residues. In situ hybridization to frozen head sections detects expression of this gene in retina and neuronal perikarya. The 32 and 34 kD brain proteins that presumably are localized predominantly in synaptic terminals of photoreceptors and most if not all neurons may correspond to two variant cysteinestring proteins as they are of similar molecular weight and share an antigenic binding site for MAB ab49.     

The National Institutes of Health’s Biomedical Translational Research Information System (BTRIS): Design,contents, functionality and experience to date

The US National Institutes of Health (NIH) has developed the Biomedical Translational Research Information System (BTRIS) to support researchers’ access to translational and clinical data. BTRIS includes a data repository, a set of programs for loading data from NIH electronic health records and research data management systems, an ontology for coding the disparate data with a single terminology, and a set of user interface tools that provide access to identified data from individual research studies and data across all studies from which individually identifiable data have been removed. This paper reports on unique design elements of the system, progress to date and user experience after five years of development and operation.     

The association between major depressive disorder and obesity in US adolescents: results from the 2001–2004 National Health and Nutrition Examination Survey

The association between major depressive disorder (MDD) and obesity was assessed in 4,150 US adolescents aged 12–19 years from the 2001–2004 National Health and Nutrition Examination Survey. Weight and height were measured by health professionals and MDD was based on a structured diagnostic interview. The prevalence of MDD in the past year among US adolescents was 3.2% and 16.8% of US adolescents were obese. After adjustment for sex, age, race/ethnicity and poverty, MDD was not significantly associated with obesity among adolescents overall (adjusted odds ratio (adjOR) = 1.6, 95% confidence interval (CI) = 0.9–2.9), but an increased odds of obesity was observed among males (adjOR = 2.7, 95% CI = 1.1–7.1) and non-Hispanic blacks (adjOR = 3.1, 95% CI = 1.1–8.3) with MDD. Future research on strategies that might reduce the risk of obesity in males and non-Hispanic black adolescents with MDD may be warranted.     

The integration of size and weight cues for perception and action: evidence for a weight–size illusion

Humans routinely estimate the size and weight of objects. Yet, when lifting two objects of equal weight but different size, they often perceive the smaller object as being heavier. This size–weight illusion (SWI) is known to have a lesser effect on motor control of object lifting. How the nervous system combines “weight” and “size” cues with prior experience and whether these cues are differentially integrated for perception and sensorimotor action is still not fully understood. Therefore, we assessed not only whether the experience of size biases weight perception, but also if experience of weight biases the size perception of objects. Further, to investigate differences between perceptual and motor systems for cue-experience integration, participants haptically explored the weight of an object with one hand and then shaped the aperture of their other hand to indicate its perceived size. Results—First, next to a SWI, healthy adults (N = 21) perceived lighter objects as being smaller and heavier objects as being larger, demonstrating a weight–size illusion (WSI). Second, participants were more susceptible to either the SWI or WSI. Third, aperture of the non-exploring hand was scaled to perceived weight and not to physical size. Hand openings were consistently smaller than physical size, with SWI-sensitive participants being significantly more affected than WSI-sensitive subjects. We conclude: first, both size and weight perceptions are biased by prior experience. Weight perception is biased by expectations of size, while size perception is influenced by the expectancy of weight. Second, humans have the tendency to use one cue predominantly for both types of perception. Third, combining perceived weight with expected size influenced hand motor control, while online haptic feedback was largely ignored. Finally, we present a processing model underlying the size–weight cue integration for the perceptual and motor system.     

Serum C-reactive Protein Level and Distribution in Chronic Obstructive Pulmonary Disease Versus Healthy Controls: a Case–Control Study from Iran

Inflammation has a contributive role in the development and progression of chronic obstructive pulmonary disease (COPD).The present study was designed to determine the level and the distribution of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in COPD compared with controls. Ninety patients with COPD presented to an outpatient hospital clinic and 50 controls who were selected among personals of the same hospital entered the study. Serum high sensitive CRP (hs-CRP) was measured by immunoturbidimetric method and the ESR by Westergren method. Receiver operating characteristic curve was applied to determine a cutoff point for differentiation of the COPD and control group. In statistical analysis, the patients and controls were compared regarding levels and distribution of hs-CRP and ESR. Mean age of patients and controls was 67?±?11.6 and 51.3?±?6.7 years, respectively (p?=?0.001). Mean hs-CRP was significantly higher (4.76?±?5.6 vs 1.72?±?1.68 mg/L, p?=?0.001) but mean ESR was nonsignificantly higher (9.1?±?11.2 vs 7.2?±?7.4 m/h, p?=?0.95) in patients than control. Serum hs-CRP at 1.55 mg/L, differentiated patients and controls at sensitivity of 77.3 % and specificity of 60 %. Serum hs-CRP >3 mg/L was observed in 39 (44.3 %) patients and 9 (18 %) controls (p?=?0.001) and >6 mg/L in 22 (25 %) patients and 2 (4 %) controls (p?=?0.001).Serum hs-CRP was significantly correlated with ESR in patient but not in control group (Spearman correlation coefficient?=?0.516, p?=?0.001). Serum hs-CRP and ESR was not correlated with age, weigh, smoking, and the severity of COPD. The results of this study indicated a systemic inflammatory process in COPD. Since inflammation has an important contribution in development of future pulmonary and extrapulmonary complications, serum CRP assessment will provide additional information beyond that achieved by conventional method of pulmonary function test.     

Dietary Responses to a Hypertension Diagnosis: Evidence from the National Health and Nutrition Examination Survey (NHANES) 2007–2010

Dietary modification has been shown to substantially reduce blood pressure among people with hypertension. This article uses data from the 2007–2008 and 2009–2010 cross-sections of the National Health and Nutrition Examination Survey (NHANES) to examine the extent to which a hypertension diagnosis can influence individuals’ dietary choices. Several models were estimated to clarify the association of a hypertension diagnosis with dietary factors related to hypertension management. A comparison group of individuals at risk for developing hypertension was used. Results suggest that individuals who received a recent diagnosis of hypertension are more likely to have lower intakes of some dietary factors important in blood pressure management, including sodium. The results also highlight a discrepancy between added salt use and dietary sodium intake. While more recent hypertensive patients tended to consume lower levels of dietary sodium, patients diagnosed longer ago tended to use less added salt. Given that those diagnosed were more likely to have lower blood pressure profiles and improved diets, especially close to the time of diagnosis, the results of this study underscore the need for a prompt and accurate diagnosis of hypertension.     

Associations between the number of natural teeth in postmenopausal women and duration of lactation: The 2010–2012 Korea National Health and Nutrition Examination Survey

ObjectivesLactation is reported to be associated with changes in maternal calcium homeostasis. The relationship between lactation and long-term oral health remains to be revealed. This study was aimed to evaluate the relationship between lactation and the number of natural teeth in postmenopausal women using nationally representative data.MethodsThe data from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to 4211 respondents over 19 years old who had gone through menopause and had no missing values for the reproductive factors and outcome variables. The total number of natural teeth was then calculated after excluding third molars. Multiple logistic regression analyses were used to assess the associations of the number of natural teeth and lactation.ResultsAs the duration of total lactation increased, the number of natural teeth decreased. Average duration of lactation per child showed similar trends. The association between the total duration of lactation and the number of natural teeth showed an inverse relationship with a beta value of −0.0181 per day after adjustment, and the beta value of the average duration of lactation per child was −0.0287 after the adjustment. The odds ratios of the percentage of individuals with the number of teeth ≤27 tended to increase with increased duration of lactation. Adjusted odds ratios and 95% confidence intervals were 1.830 (1.009, 3.320); 1.142 (0.765, 1.704); 1.159 (0.807, 1.664); and 0.857 (0.563, 1.306) for lactation period of ≥25 months, 13–24 months, 7–12 months, ≤6 months, and no lactation, respectively.ConclusionsThis study investigated the relationship between the number of teeth and the total duration of lactation or an average duration of lactation per child using nationally representative data. Total duration of lactation and average duration of lactation per child were inversely related to the number of natural teeth. Lactation may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women.     

Proceedings from the National Cancer Institute’s Second International Workshop on the Biology,Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part III. Prevention and Treatment of Relapse after Allogeneic Transplantation

In the Second Annual National Cancer Institute’s Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Prevention and Treatment of Relapse after Allogeneic Transplantation highlighted progress in developing new therapeutic approaches since the first relapse workshop. Recent insights that might provide a basis for the development of novel, practical clinical trials were emphasized, including utilization of newer agents, optimization of donor lymphocyte infusion (DLI), and investigation of novel cellular therapies. Dr. de Lima discussed pre-emptive and maintenance strategies to prevent relapse after transplantation, for example, recent promising results suggestive of enhanced graft-versus-tumor activity with hypomethylating agents. Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy for relapse, including cytoreduction before DLI, combination of targeted agents with DLI, and considerations in use of second transplantations. Dr. Porter addressed strategies to enhance T cell function, including ex vivo activated T cells and T cell engineering, and immunomodulatory approaches to enhance T cell function in vivo, including exogenous cytokines and modulation of costimulatory pathways.     

The association between family history of asthma and the prevalence of asthma among US adults: National Health and Nutrition Examination Survey, 1999–2004

PurposeTo assess the overall prevalence of asthma and the association between family history of asthma and the prevalence of asthma among US adults.MethodsWe analyzed National Health and Nutrition Examination Survey data from 1999 to 2004 for 15,008 respondents aged 20 years or older with no history of emphysema. We divided respondents into three familial risk groups (high, moderate, and average) on the basis of the number and closeness of relatives, that they reported as having asthma and then assessed the asthma prevalence in each. We also assessed associations between asthma prevalence and age, sex, race/ethnicity, income, body mass index, smoking status, household smoking exposure, and physical activity.ResultsBy our definitions, 2.3% of respondents were at high, 13.0% at moderate, and 84.7% at average familial risk for asthma. The crude prevalence of self-reported lifetime asthma was 11.5% (95% confidence interval [CI]: 10.7–12.3%) among all respondents, and 37.6% (95% CI: 30.4–45.4%), 20.4% (95% CI: 18.2–22.7%), and 9.4% (95% CI: 8.7–10.2%) among those at high, moderate, and average familial risk, respectively. Among all risk factors we looked at, family history had the strongest association with lifetime asthma prevalence, and the association remained significant after adjustments for other risk factors. Compared with average familial risk, the adjusted odds ratios for lifetime asthma were 2.4 (95% CI: 2.0–2.8) for moderate and 4.8 (95% CI: 3.5–6.7) for high familial risk.ConclusionOur findings showed that a family history of asthma is an important risk factor for asthma and that familial risk assessments can help identify people at highest risk for developing asthma. Additional research is needed to assess how health care professionals can use family history information in the early detection and management of asthma.     

The brain renin–angiotensin system: a diversity of functions and implications for CNS diseases

The classic renin–angiotensin system (RAS) was initially described as a hormone system designed to mediate cardiovascular and body water regulation, with angiotensin II as its major effector. The discovery of an independent local brain RAS composed of the necessary functional components (angiotensinogen, peptidases, angiotensins, and specific receptor proteins) significantly expanded the possible physiological and pharmacological functions of this system. This review first describes the enzymatic pathways resulting in active angiotensin ligands and their interaction with AT₁, AT₂, and AT₄ receptor subtypes. Next, we discuss the classic physiologies and behaviors controlled by the RAS including cardiovascular, thirst, and sodium appetite. A final section summarizes non-classic functions and clinical conditions mediated by the brain RAS with focus on memory and Alzheimer’s disease. There is no doubt that the brain RAS is an important component in the development of dementia. It also appears to play a role in normal memory consolidation and retrieval. The presently available anti-dementia drugs are proving to be reasonably ineffective, thus alternative treatment approaches must be developed. At the same time, presently available drugs must be tested for their efficacy to treat newly identified syndromes and diseases connected with the RAS. The list of non-classic physiologies and behaviors is ever increasing in both number and scope, attesting to the multidimensional influences of the RAS. Such diversity in function presents a dilemma for both researchers and clinicians. Namely, the blunting of RAS subsystems in the hopes of combating one constellation of underlying causes and disease symptoms may be counter-balanced by unanticipated and unwanted consequences to another RAS subsystem. For example, the use of angiotensin-converting enzyme inhibitors and AT₁ and/or AT₂ receptor blockers have shown great promise in the treatment of cardiovascular related pathologies; however, their use could negate the cerebroprotective benefits offered by this system.     

Comparative Analysis of Calcineurin Inhibitor–Based Methotrexate and Mycophenolate Mofetil–Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.     

DeFries–Fulker Analysis of Twin Data with Skewed Distributions: Cautions and Recommendations from a Study of Children’s Use of Verb Inflections

DeFries-Fulker (DF) analysis is an adaptation of multiple regression that is used to estimate heritability of extreme scores (h²‰‰_g) on a dimension. Probands are identified as scoring below a cutoff that defines impairment, and one then uses regression to predict the scores of co-twins from the proband scores and a term that denotes the genetic relationship between twins (1.0 for MZ and 0.5 for DZ twins). This paper reports illustrative data and simulations for the situation where the dimensional variable shows substantial negative skew. Two types of simulation were conducted: in the first, an underlying polygenic liability dimension was normally distributed: skewing was introduced by transforming or truncating the liability distribution. In the second set of simulations, skewing arose because an infrequent defective gene impaired scores. In both sets of simulations DF analysis was robust in the face of severe skewing of the data. DF analysis can provide two pointers to major gene effects on extreme scores on a trait with a skewed distribution: first, group heritability estimates will be higher for the original skewed data than for normalised data; second, estimates of h²‰‰_g will increase as the cutoff to identify probands is made more stringent. Both these features were seen in data from a test of verb inflections given to174 6-year-old twin pairs, suggesting that a single major gene may be implicated in causing impaired grammatical development.