Hematologic Findings in Children Exposed to A-Bomb Radiation In Utero in Hiroshima

1. Hematologic findings in in utero atomic bomb irradiated and nonirradiatedchildren of Hiroshima between the years 1950 to 1957 have been compared,and no changes peculiar to the irradiated group were found.

2. Despite several predisposing factors in Japan toward the development ofiron deficiency in children, overt anemia was rare and distribution of hemoglobin levels was only slightly lower than those reported in American andEuropean children.

3. Leukocyte levels, irrespective of age of the children, were found to beprogressively falling in the children of Hiroshima, whether or not exposure toirradiation had occurred. Thus, by 1957 the values were distinctly lower thanthose reported for normal children in Japan and the United States. No causefor this change was apparent.

Submitted on January 25, 1961 Accepted on February 17, 1961     

Risk of Autism Spectrum Disorders in Children Born to Mothers With Rheumatoid Arthritis: A Systematic Literature Review

Objective

There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASD s). We aimed to systematically review the risk of ASD s in children born to mothers with rheumatoid arthritis (RA ) compared to children born to mothers without RA .

Methods

We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science.

Results

Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case–control study found no difference in the prevalence of RA in mothers of children with ASD s versus control mothers. Another case–control study showed a statistically significant 8‐fold increase in autoimmune disorders, including RA , in mothers of offspring with ASD s compared to controls. Forty‐six percent of offspring with ASD s had a first‐degree relative with RA , compared to 26% of controls. And in a population‐based cohort study, investigators observed an increased risk of ASD s in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case–control study design.

Conclusion

Observational studies suggest a potentially increased risk of ASD s in children born to mothers with RA compared to children born to mothers without RA , although data are limited.

     

Disclosure of Parental HIV Infection to Children: A Systematic Review of Global Literature

This review examines the global empirical literature regarding disclosure of parental HIV infection to children. Thirty-eight articles published in English-language journals prior to 2011 were retrieved and reviewed regarding disclosure process, reasons for disclosure/non-disclosure and impacts of disclosure/non-disclosure. Disclosure rate was relatively low worldwide. The decision making of disclosure or non-disclosure was mainly affected by children’s development level, stigma, consideration of children’s benefits, and parenting practices. Unintentional and forced disclosures were common. Findings regarding the impacts of disclosure/non-disclosure were mixed but disclosure tended to have long-term positive impacts on the well-being of children, parents and family in general. This review underscores the importance of developing evidence-informed developmentally and culturally appropriate interventions to assist HIV-positive parents to disclose their HIV status to children, particularly in low-resource settings.     

Labor Migration and HIV Risk: A Systematic Review of the Literature

To inform the development of multilevel strategies for addressing HIV risk among labor migrants, 97 articles from the health and social science literatures were systematically reviewed. The study locations were Africa (23 %), the Americas (26 %), Europe (7 %), South East Asia (21 %), and Western Pacific (24 %). Among the studies meeting inclusion criteria, HIV risk was associated with multilevel determinants at the levels of policy, sociocultural context, health and mental health, and sexual practices. The policy determinants most often associated with HIV risk were: prolonged and/or frequent absence, financial status, and difficult working and housing conditions. The sociocultural context determinants most often associated with HIV risk were: cultural norms, family separation, and low social support. The health and mental health factors most often associated with HIV risk were: substance use, other STIs, mental health problems, no HIV testing, and needle use. The sexual practices most often associated with increased HIV risk were: limited condom use, multiple partnering, clients of sex workers, low HIV knowledge, and low perceived HIV risk. Magnitude of effects through multivariate statistics were demonstrated more for health and mental health and sexual practices, than for policy or sociocultural context. The consistency of these findings across multiple diverse global labor migration sites underlines the need for multilevel intervention strategies. However, to better inform the development, implementation, and evaluation of multilevel interventions, additional research is needed that overcomes prior methodological limitations and focuses on building new contextually tailored interventions and policies.     

Social Support and HIV-related Risk Behaviors: A Systematic Review of the Global Literature

Existing empirical evidence has well documented the role of social support in both physical and psychological well-being among various populations. In the context of HIV prevention, the rapid increase of studies on social support merits a systematic review to synthesize the current global literature on association between social support and HIV-related risk behaviors. The current review reveals a complex picture of this relationship across diverse populations. Existing studies indicate that higher levels of social support are related to fewer HIV-related risk behaviors among female sex workers and people living with HIV/AIDS and heterosexual adults in general. However, influences of social support on HIV-related risk behaviors are inconsistent within drug users, men who have sex with men and adolescents. These variations in findings may be attributed to different measurement of social support in different studies, specific context of social support for diverse population, or various characteristics of the social networks the study population obtained support from. Future studies are needed to explore the mechanism of how social support affects HIV-related risk behaviors. HIV prevention intervention efforts need to focus on the positive effect of social support for various vulnerable and at-risk populations. Future efforts also need to incorporate necessary structure change and utilize technical innovation in order to maximize the protective role of social support in HIV risk prevention or reduction.     

Physiological Factors Related to Aspiration Risk: A Systematic Review

Penetration–aspiration is considered the most serious component of oropharyngeal dysphagia. Clinicians regularly evaluate the pathophysiology of swallowing and postulate reasons or mechanisms behind penetration–aspiration. In this article we share the results of a two-stage literature review designed to elucidate the association between abnormalities in physiological measures of swallowing function and the occurrence of penetration–aspiration. In the first stage, a broad scoping review was undertaken using search terms for nine different structures involved in oropharyngeal swallowing. In the second stage, based on the results of the initial search, a more focused systematic review was undertaken which explored the association between aspiration and abnormalities in respiratory, tongue, hyoid, and laryngeal function in swallowing. A total of 37 articles underwent detailed quality review and data extraction in the systematic review. The results support measurement of tongue strength, anatomically normalized measures of hyoid movement, bolus dwell time in the pharynx while the larynx remains open, respiratory rate, and respiratory swallow phasing as parameters relevant to aspiration risk.     

Ganglioside GM1 Reduces Fetal Alcohol Effects in Rat Pups Exposed to Ethanol In Utero

We have investigated the effect of in utero ethanol exposure and ganglioside GM1 pretreatment on the endogenous ganglioside profile of the rat fetal brain. Prenatal ethanol exposure on gestation day (GD) 7 and GD8 and/or GD13 and GD14 leads to a very significant increase in the ganglioside GM1 content in at least 50% of the pup brains when assayed on GD20. This treatment protocol also results in significant decrease in the content of polysialogangliosides GD1a, GT1b, and GQ1b. GM1 treatment of pregnant dams before ethanol administration prevented this alteration in pup brain ganglioside profile. Ganglioside GM1 pretreatment appears to block the cellular membrane changes associated with fetal alcohol effects and thereby minimizes alterations in brain maturation and associated behavioral dysfunction.     

Hepatitis C Virus Infection and Coronary Artery Disease Risk: A Systematic Review of the Literature

Background and Aims

While hepatitis C virus (HCV) infection has been implicated in increasing the risk of coronary artery disease (CAD), conflicting reports exist regarding this association. We performed a systematic review to further investigate this association.

Methods

We conducted a PubMed search of original research articles from January 1, 1995 to June 30, 2013 to identify case–control and cohort studies evaluating the association between HCV and CAD using keyword terms [“hepatitis c” or “HCV”] and [“coronary artery disease” or “heart disease” or “atherosclerosis.”] The primary CAD-related endpoints included myocardial infarction, congestive heart failure, need for coronary artery bypass grafting, or transluminal percutaneous coronary angioplasty. Binary outcomes are reported as odds ratios (OR) with 95 % confidence interval (CI).

Results

We identified five studies (four cohort studies and one case–control study) that met our inclusion criteria. A significant association between HCV and CAD was demonstrated in one cohort study (adjusted HR 1.27; 95 % CI 1.22–1.31). One cohort study demonstrated a decreased risk of CAD associated with HCV (adjusted OR 0.74; 95 % CI 0.71–0.76). The remaining studies did not find a significant association between HCV and risk of CAD.

Conclusions

The current systematic review demonstrates that the association between HCV and CAD remains unclear. We need more large, long-term cohort studies with clear definitions of patient population and endpoints to better ascertain the association between HCV and CAD.     

Influence of Ethanol Consumption on Immune Competence of Adult Animals Exposed to Ethanol In Utero

Ethanol consumption results in significant changes in the immune system of experimental animals and humans. Previous work by ourselves and others has established that in utero exposure to ethanol results in alterations in the immune system of the offspring that persist into adult life. The present study was designed to determine if prenatal exposure to ethanol results in increased vulnerability to the immunosuppressive effects of ethanol consumption in adulthood. Male and female Sprague-Dawley offspring were selected in adulthood from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups, and given either an ethanol-containing liquid diet or were pair-fed an isocaloric liquid diet without ethanol for 30 days. At the end of the 30-day feeding period, lymphocyte responses to the mitogens concanavalin A (Con A) and lipopolysaccharide, and to interleukin-2 (IL-2) were tested using in vitro assays. The results of this study support and extend previous data demonstrating long-term adverse effects of prenatal ethanol exposure on T-cell responses to mitogens, and provide further evidence that deficits seem to be more robust in male than in female offspring. Prenatal E males showed reduced T-lymphocyte proliferation to Con A and T-lymphoblast proliferation to IL-2, compared with their prenatal PF and C counterparts, regardless of whether they were exposed to the ethanol or the control diet in adulthood. In addition, T-lymphoblast proliferation to IL-2 was suppressed in prenatal E, compared with prenatal C, females exposed to control diet in adulthood. This is the first report of a deficit in T-cell aspects of immunity in E females, although it appears that this deficit may have been partially mediated by nutritional effects. A second major finding in this study is that consumption of ethanol diet in adulthood in itself had significant immunosuppressive effects on T-cell responses in both males and females. However, contrary to our expectation, previous exposure to ethanol in utero did not exacerbate the changes in immune responsiveness that were observed after adult ethanol consumption.     

Technology Interventions to Curb Obesity: A Systematic Review of the Current Literature

Obesity is a public health crisis that has reached epidemic proportions. Although intensive behavioral interventions can produce clinically significant weight loss, their cost to implement, coupled with resource limitations, pose significant barriers to scalability. To overcome these challenges, researchers have made attempts to shift intervention content to the Internet and other mobile devices. This article systematically reviews the recent literature examining technology-supported interventions for weight loss and maintenance among overweight and obese adults. Thirteen studies were identified that satisfied our inclusion criteria (12 weight loss trials, 1 weight maintenance trial). Our findings suggest that technology interventions may be efficacious at producing weight loss. However, several studies are limited by methodologic shortcomings. There are insufficient data to evaluate their efficacy for weight maintenance. Further research is needed that employs state-of-the-art methodology, with careful attention being paid to adherence and fidelity to intervention protocols.     

Relationship-Based Predictors of Sexual Risk for HIV Among MSM Couples: A Systematic Review of the Literature

Behavioral and epidemiological studies report high risk for HIV among MSM couples. Over the last decade, studies have examined relationship dynamics associated with sexual risk for HIV. It is important to examine the impact this research has had on HIV prevention and what is still needed. We conducted a review of the literature focusing on relationship dynamics associated with sexual risk for HIV among MSM couples. Procedures used for this review were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses established to provide a framework for collecting, reviewing and reporting studies systematically (Mohler et al. in Ann Intern Med 151(4):264-269, 2009). We found that positive relationship dynamics are associated with less risk with partners outside the relationship, but were associated with greater odds of unprotected anal intercourse with primary partners. We also discuss other factors including sexual agreements about outside partners and make recommendations for next steps in HIV prevention research among MSM couples.     

Lipoprotein-Associated Phospholipase A2 as a Novel Risk Marker for Cardiovascular Disease: A Systematic Review of the Literature

We sought to critically assess the role of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) in the prediction of cardiovascular events in primary and secondary prevention settings. The inclusion criteria for our study included population-based epidemiologic studies and the presence of clinical outcomes of interest, including atherosclerotic disease, coronary events, stroke, and cardiovascular death. Studies that lacked clinical outcomes or that involved animals were excluded. We included primary and secondary prevention studies of subjects in all ethnic groups and of either sex, with no age limitation. We searched MEDLINE, Google Scholar, and the Cochrane Library for studies with publication dates from January 1970 through July 2009, and we searched major cardiology meeting abstracts from 2000 through 2009. From each study, we used predictive ability—including relative risk, hazard ratio, odds ratio, and prevalence of high Lp-PLA₂ levels, with adjustment—along with baseline population characteristics.Of 33 studies that met our inclusion criteria, 30 showed a significant association between Lp-PLA₂ and cardiovascular events. Most of the studies had been adjusted for major Framingham risk factors and other variables that might influence the effect under question. After multivariate adjustments in cohort and nested case-control studies, increased levels of Lp-PLA₂ remained a significant predictor of cardiovascular events. The available body of evidence suggests that Lp-PLA₂ is a reliable marker of risk for cardiovascular events.Key words: Atherosclerosis/prevention & control, biological markers/blood, case-control studies, cohort studies, C-reactive protein, epidemiology, inflammation, lipoprotein-associated phospholipase A2, phospholipases A2, treatment outcomeTraditional risk factors can predict the risk of cardiovascular (CV) disease in many, but not all, patients. About 10% to 20% of persons with coronary heart disease (CHD) have no identifiable risk factor,¹ and 35% of CHD deaths occur in patients who have total serum cholesterol levels of less than 200 mg/dL.²Current risk-prediction methods (such as the Framingham risk table) are not able to accurately pinpoint which patient will develop a CV event, or at what time. Exhaustive research is under way to improve our ability to determine individuals'' CV risks. Inflammation plays an important causal role in the development of atherosclerosis and its clinical complications³ (such as acute coronary syndrome [ACS], sudden cardiac death, acute myocardial infarction, unstable angina, and stroke). New diagnostic tests are being developed to identify individuals who are at high risk of inflammation.⁴ Several inflammatory markers, notably high-sensitivity C-reactive protein (hs-CRP)⁵ and white blood cells,⁶ have been studied as predictors of future CV events.Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a novel inflammatory marker that has been the recent focus of multiple epidemiologic studies involving primary and secondary prevention populations.⁷ A growing body of evidence suggests that Lp-PLA₂ is a CV risk marker independent of traditional risk factors like high-density-lipoprotein cholesterol (HDL-c), low-density-lipoprotein cholesterol (LDL-c), and hs-CRP. Lipoprotein-associated phospholipase A₂, a 45-kDa protein with 441 amino acids, was cloned in 1995.⁸ The gene for Lp-PLA₂ is located on chromosome 6p 21.2 to 12. Also known as platelet-activating factor acetylhydrolase (PAF-AH), Lp-PLA₂ hydrolyzes the short acyl group at the Sn-2 position of the phospholipids in oxidized LDL, which leads to production of the pro-inflammatory compounds lyso-phosphatidylcholine and oxidized nonesterified fatty acids.⁹ Lipoprotein-associated phospholipase A₂ is produced by several inflammatory cells (for example, monocytes, macrophages, T cells, hepatic Kupffer cells, and mast cells). In human plasma, it is associated mainly (70%–80%) with LDL particles, due to its affinity for the C-terminus of apolipoprotein B; the remaining 20%–30% is associated with HDL and other lipoproteins.¹⁰ Within LDL fractions, it shows more predilection for the denser LDL-4 and LDL-5, which are believed to be highly proatherogenic.¹¹ Studies have also shown that oxidized phospholipids are chemotactic and promote monocyte–endothelial-cell interaction.^12,13 A high level of circulating oxidized LDL has been shown to increase plaque vulnerability and mediate endothelial dysfunction, which can partly explain its higher levels in ACS patients.^14,15Recent reports suggest that human beings and rabbits with elevated Lp-PLA₂ have higher plaque burden in the coronary arteries.¹⁶ The reduction of atherosclerotic lesions in hyperlipidemic rabbits, by inhibiting Lp-PLA₂, supports the notion that Lp-PLA₂ enhances atherosclerosis.¹⁶ Lipoprotein-associated phospholipase A₂ is also expressed within the necrotic core and apoptotic macrophages of vulnerable and ruptured plaque in human coronary atheroma, which suggests its active role in acute coronary syndrome.¹⁷ Moreover, high levels of Lp-PLA₂ mRNA have been noted in carotid plaque.During myocardial ischemia, membrane phospholipids may undergo hydrolysis under stress, leading to accumulation of arachidonic acid and lysophophatidylcholine.^18,19 Lipoprotein-associated phospholipase A₂ levels are shown to be up-regulated by endotoxins.^20,21 The proatherogenic contribution of Lp-PLA₂ has been much studied; however, its anti-inflammatory and antiatherogenic potential should not go unnoticed.⁷Platelet-activating factor is prothrombotic and a mediator of inflammation; platelet-activating factor acetylhydrolase hydrolyzes PAF, thereby negating its proinflammatory and prothrombotic effects.²² The opposing actions of Lp-PLA₂ (PAF-AH) have led to a debate concerning which action is more potent and therefore warrants more attention. Initially, PAF-AH was thought to be atheroprotective by reducing platelet-activating factor.^23,24 However, subsequent studies have shown its role in inflammation: lysophosphatidyl choline stimulates macrophage proliferation, up--regulates cytokines and CD40 ligands, and increases the expression of vascular adhesion molecules.^25,26 This has led most researchers to believe that the proatherogenic effect of Lp-PLA₂ has a greater importance in CV disease prevention and management.Because of its low biologic fluctuation, high vascular specificity, and indication (at elevated levels) of plaque inflammation and endothelial dysfunction, Lp-PLA₂ is useful in identifying patients at high risk of CHD. A recent report²⁷ suggests that an Lp-PLA₂ level >235 ng/mL in healthy populations and >225 ng/mL in clinical populations is a high-risk marker for CV events, and that Lp-PLA₂ should be measured in patients who are at moderate to very high risk of CV events. An elevated Lp-PLA₂ level also predicts increased risk of myocardial infarction and stroke in population studies that are fully adjusted for other CV risk factors. More epidemiologic and clinical studies in the future can help clarify the effect of Lp-PLA₂ on atherosclerosis-related CV risk.

Secretory PLA₂

Secretory PLA₂ (sPLA₂)—another enzyme from the phospholipase A₂ family—has been the focus of many studies for its role in predicting coronary artery disease (CAD).²⁸ Secretory PLA₂ is an acute-phase reactant, the activity of which is up-regulated by other inflammatory markers.²⁶ Unlike Lp-PLA₂, its levels correlate with hs-CRP. Secretory PLA₂ is not widely used in clinical practice; one explanation for this could be its nonspecific predictive ability. However, ongoing and future studies will help shed more light on the predictive potential of sPLA₂ and its potential in comparison with Lp-PLA₂.The purpose of this particular review is to critically assess the role of Lp-PLA₂ in the prediction of CV events (with a focus on coronary heart disease) in primary and secondary prevention settings.     

Misdiagnosis of Heart Failure: A Systematic Review of the Literature

BackgroundHeart failure (HF) is a chronic disease associated with a significant burden to patients, families, and health services. The diagnosis of HF can be easily missed owing to similar symptoms with other conditions especially respiratory diseases.Methods and ResultsWe conducted a systematic review to determine the rates of HF and cardiomyopathy misdiagnosis and explored the potential causes. The included studies were narratively synthesized. Ten studies were identified including a total of 223,859 patients. There was a lack of definition of HF misdiagnosis in the studies and inconsistent diagnostic criteria were used. The rates of HF misdiagnosis ranged from 16.1% in hospital setting to 68.5% when general practitioner referred patients to specialist setting. The most common cause for misdiagnosis was chronic obstructive pulmonary disease (COPD). One study using a COPD cohort showed that HF was unrecognized in 20.5% of patients and 8.1% had misdiagnosis of HF as COPD. Another study suggests that anemia and chronic kidney disease are associated with an increase in the odds of unrecognized left ventricular systolic dysfunction. Other comorbidities such as obesity, old age, atrial fibrillation, and ischemic heart disease are prevalent in patients with a misdiagnosis of HF.ConclusionsThe misdiagnosis of HF is an unfortunate part of everyday clinical practice that occurs with a variable rate depending on the population studied. HF is frequently misdiagnosed as COPD. More research is needed to better understand the missed opportunities to correctly diagnose HF so that harm to patients can be avoided and effective treatments can be implemented.