bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Follow-Up and Histopathology of the Temporal Bones in Nathalie Syndrome
Authors: de Heer Anne-Martine R. , Merchant Saumil N. , Kammeraad Janneke A.E. , Cruysberg Johannes R.M. , Huygen Patrick L.M. , Cremers Cor W.R.J.
Published: April 2012

The Nathalie syndrome (OMIM 255990) comprises a combination of features that do not resemble any other known syndrome and is as such an independent, rare entity. It is characterized by sensorineural hearing impairment, juvenile cataract, spinal muscular atrophy, skeletal abnormalities, retardation of growth, underdeveloped secondary gender characteristics and cardiomyopathy. Worldwide, only one family with this syndrome is known. An update of the clinical follow-up in this family and the results of autopsy are given. Audiometry showed a downsloping configuration that corresponded to the findings at histopathological examination of the cochlea: a diffuse atrophy of the organ of Corti, severe and diffuse atrophy of the stria vascularis and moderate loss of cochlear neurons in all turns. Another new striking feature is that individuals with the Nathalie syndrome have a shortened life expectancy with a risk of sudden death or death from heart failure resulting from (dilated) cardiomyopathy.
Recent Secular Trends in Pubertal Timing: Implications for Evaluation and Diagnosis of Precocious Puberty
Authors: Sørensen Kaspar , Mouritsen Annette , Aksglaede Lise , Hagen Casper P. , Mogensen Signe Sloth , Juul Anders
Published: April 2012

The decline in age at puberty in the general population has been paralleled by an increase in the number of girls referred for evaluation of precocious puberty (PP). In 1999, The Lawson Wilkins Pediatric Endocrine Society recommended a lowering of the age limit for evaluation of PP in girls. However, the limited evidence on which these recommendations were based led many experts to question these new suggestions. The emergence of new European pubertal timing data evaluated by robust clinical as well as biochemical markers has broadened our insight on how to interpret the recent pubertal changes. The recent pubertal trends have resulted in a concomitant lowering of the lower limit of normality of the pubertal onset. However, evidence suggests that age at the gonadotropin and sex steroid surges have not changed. Thus, it looks as if an increasing proportion of contemporary early pubertal girls may experience isolated gonadotropin-independent thelarche rather than central PP, which may not be discernible on pubertal examination alone. Thus, the population-based limits of normality should not be directly translated into revision of age limits for evaluation of PP due to the risk of misdiagnosing rapid progressive PP as well as intracranial and other underlying pathology.
Efficient Identification and Referral of Low-Income Women at High Risk for Hereditary Breast Cancer: A Practice-Based Approach
Authors: Joseph G. , Kaplan C. , Luce J. , Lee R. , Stewart S. , Guerra C. , Pasick R.
Published: April 2012

Background: Identification of low-income women with the rare but serious risk of hereditary cancer and their referral to appropriate services presents an important public health challenge. We report the results of formative research to reach thousands of women for efficient identification of those at high risk and expedient access to free genetic services. External validity is maximized by emphasizing intervention fit with the two end-user organizations who must connect to make this possible. This study phase informed the design of a subsequent randomized controlled trial. Methods: We conducted a randomized controlled pilot study (n = 38) to compare two intervention models for feasibility and impact. The main outcome was receipt of genetic counseling during a two-month intervention period. Model 1 was based on the usual outcall protocol of an academic hospital genetic risk program, and Model 2 drew on the screening and referral procedures of a statewide toll-free phone line through which large numbers of high-risk women can be identified. In Model 1, the risk program proactively calls patients to schedule genetic counseling; for Model 2, women are notified of their eligibility for counseling and make the call themselves. We also developed and pretested a family history screener for administration by phone to identify women appropriate for genetic counseling. Results: There was no statistically significant difference in receipt of genetic counseling between women randomized to Model 1 (3/18) compared with Model 2 (3/20) during the intervention period. However, when unresponsive women in Model 2 were called after 2 months, 7 more obtained counseling; 4 women from Model 1 were also counseled after the intervention. Thus, the intervention model that closely aligned with the risk program’s outcall to high-risk women was found to be feasible and brought more low-income women to free genetic counseling. Our screener was easy to administer by phone and appeared to identify high-risk callers effectively. The model and screener are now in use in the main trial to test the effectiveness of this screening and referral intervention. A validation analysis of the screener is also underway. Conclusion: Identification of intervention strategies and tools, and their systematic comparison for impact and efficiency in the context where they will ultimately be used are critical elements of practice-based research.
Role of Two Clusters of Male Alcoholics in Treatment Retention
Authors: Baltieri Danilo Antonio , Corrêa Filho João Maria
Published: April 2012

Aims: This study aimed to classify alcohol-dependent outpatients on the basis of clinical factors and to verify if the resulting types show different treatment retention. Methods: The sample comprised 332 alcoholics that were enrolled in three different pharmacological trials carried out at São Paulo University, Brazil. Based on four clinical factors – problem drinking onset age, familial alcoholism, alcohol dependence severity, and depression – K-means cluster analysis was performed by using the average silhouette width to determine the number of clusters. A direct logistic regression was performed to analyze the influence of clusters, medication groups, and Alcoholics Anonymous (AA) attendance in treatment retention. Results: Two clusters were delineated. The cluster characterized by earlier onset age, more familial alcoholism, higher alcoholism severity, and less depression symptoms showed a higher chance of discontinuing the treatment, independently of medications used and AA attendance. Participation in AA was significantly related to treatment retention. Discussion: Health services should broaden the scope of services offered to meet heterogeneous needs of clients, and identify treatment practices and therapists which improve retention. Information about patients’ characteristics linked to dropout should be used to make treatment programs more responsive and attractive, combining pharmacological agents with more intensive and diversified psychosocial interventions.
Genetics Blogs as a Public Health Tool: Assessing Credibility and Influence
Authors: Wagner L. , Paquin R. , Persky S.
Published: April 2012

The Internet is becoming an important source of information about genetics and holds promise for public health applications. However, the public has concerns about the credibility of online genetics information. We conducted a content analysis of genetics blogs (n = 94). Specifically, we assessed the prevalence of various genetics-related topics and perceived credibility indicators. The relationship between content indicators, credibility indicators, and blog influence, measured as links between blogs, was evaluated. Coverage of issues related to health or self-knowledge (31%) and life science (26%) was most common among genetics blogs. In terms of credibility indicators, most blogs disclosed authors’ full names (81%) and biographical information (67%). Many blog authors reported having genetics (67%) or life science expertise (59%). However, only 7% of blogs were affiliated with educational or medical institutions. Overall, blogs that focused on ancestry, that had authors with life science expertise, and that posted more frequently tended to be more influential. Findings suggest that life scientists and those who blog frequently may figure more centrally in shaping the genetics information available to the public via blogs. There is room for institutions that are likely to be perceived as credible sources of genetics information to assume a greater presence through blogs.
Experimental and Modeling Analysis of  Synechocystis sp. PCC 6803 Growth
Authors: Lopo Miguel , Montagud Arnau , Navarro Emilio , Cunha Isabel , Zille Andrea , de Córdoba Pedro Fernández , Moradas-Ferreira Pedro , Tamagnini Paula , Urchueguía Javier F.
Published: April 2012

Background/Aims: The influence of different parameters such as temperature, irradiance, nitrate concentration, pH, and an external carbon source on Synechocystis PCC 6803 growth was evaluated. Methods: 4.5-ml cuvettes containing 2 ml of culture, a high-throughput system equivalent to batch cultures, were used with gas exchange ensured by the use of a Parafilm™ cover. The effect of the different variables on maximum growth was assessed by a multi-way statistical analysis. Results: Temperature and pH were identified as the key factors. It was observed that Synechocystis cells have a strong influence on the external pH. The optimal growth temperature was 33°C while light-saturating conditions were reached at 40 µE·m–2·s–1. Conclusion: It was demonstrated that Synechocystis exhibits a marked difference in behavior between autotrophic and glucose-based mixotrophic conditions, and that nitrate concentrations did not have a significant influence, probably due to endogenous nitrogen reserves. Furthermore, a dynamic metabolic model of Synechocystis photosynthesis was developed to gain insights on the underlying mechanism enabling this cyanobacterium to control the levels of external pH. The model showed a coupled effect between the increase of the pH and ATP production which in turn allows a higher carbon fixation rate.
Endothelial Function, Oxidative Stress and Inflammatory Studies in Chronic Coronary Slow Flow Phenomenon Patients
Authors: Kopetz Victoria , Kennedy Jennifer , Heresztyn Tamila , Stafford Irene , Willoughby Scott R. , Beltrame John F.
Published: April 2012

The coronary slow flow phenomenon (CSFP) is associated with coronary microvascular dysfunction although the responsible mechanisms are unknown. This study compared endothelial function assessed by changes in augmentation index (AIx) following endothelium-independent (glyceryl trinitrate, GTN) and endothelium-dependent vasodilators (salbutamol), in 40 stable CSFP patients and 23 age-matched healthy controls. Plasma concentrations of inflammatory proteins (myeloperoxidase and high-sensitivity C-reactive protein), oxidative stress biomarkers (malondialdehyde and homocysteine), and asymmetric dimethylarginine levels were also determined. There were no differences between CSFP and controls in response to salbutamol (AIx: –2.28 ± 0.88% vs. –3.22 ± 0.70%, p = 0.4) or GTN (AIx: –11.30 ± 0.75% vs. –13.30 ± 1.00%, p = 0.12). Similarly, there were no differences in the measured biomarkers. Thus, alternate mechanisms to the assessed endothelial function, inflammatory and oxidative stress processes should be explored to explain the microvascular dysfunction in CSFP patients.
Human Biology of Weight Maintenance after Weight Loss
Authors: Mariman Edwin C.M.
Published: April 2012

One year after losing weight, most people have regained a significant part of the lost weight. As such, weight regain after weight loss has a negative impact on human health. The risk for weight regain is determined by psychosocial and behavioral factors as well as by various physiological and molecular parameters. Here, the latter intrinsic factors are reviewed and assembled into four functional modules, two related to the energy balance and two related to resistance against weight loss. Reported genetic factors do not reveal additional functional processes. The modules form nodes in a network describing the complex interactions of intrinsically determined weight maintenance. This network indicates that after an initial weight loss persons with a high baseline fat mass will most easily succeed in maintaining weight, because they can lose fat without raising stress in adipocytes and at the same time spare fat-free mass. However, continued weight loss and weight maintenance requires extra measures like increased physical activity, limited energy intake and a fat-free sparing composition of the diet. Eventually, this network may help to design novel therapeutic measures based on preventing the return effect of specific plasma factors or by preventing the accumulation of adipocyte cellular stress.
Probiotic Supplements (Lactobacillus reuteri DSM 17938 and ATCC PTA 5289) Do Not Affect Regrowth of Mutans Streptococci after Full-Mouth Disinfection with Chlorhexidine: A Randomized Controlled Multicenter Trial
Authors: Keller M.K. , Hasslöf P. , Dahlén G. , Stecksén-Blicks C. , Twetman S.
Published: April 2012

The aim of this study was to investigate the effectiveness of tablets containing two probiotic Lactobacillus reuteri strains in inhibiting regrowth of salivary mutans streptococci (MS) after full-mouth disinfection (FMD) with chlorhexidine. The null hypothesis was that the levels of MS would not differ in comparison with a placebo protocol. The study population was comprised of 62 young adults (mean age 23 years) with moderate or high counts of salivary MS who volunteered after informed consent. The study was a double-blinded randomized controlled trial with two parallel groups. After a 3-day chlorhexidine regimen, the subjects were randomly assigned to a test group (n = 32) with probiotic lozenges (2/day) or a placebo group (n = 30). The intervention period was 6 weeks, and stimulated whole saliva was collected at baseline and after 1, 6, and 12 weeks. The samples were processed for MS by a chair-side test and DNA-DNA hybridization as an estimate of 19 bacterial strains associated with oral health and disease. There was no significant difference between the groups at inclusion, and FMD reduced the salivary MS levels significantly in both groups. The MS suppression lasted less than 6 weeks and there were no statistical differences in salivary MS regrowth between the test and control groups at any of the follow-ups. Likewise, there were no major differences in the regrowth patterns of the checkerboard panel between the two groups. We conclude that daily oral administration of L. reuteri did not seem to affect or delay the regrowth of salivary MS after FMD with chlorhexidine.
Epithelial-Mesenchymal Transition: A Hallmark in Metastasis Formation Linking Circulating Tumor Cells and Cancer Stem Cells
Authors: Książkiewicz Magdalena , Markiewicz Aleksandra , Żaczek Anna J.
Published: April 2012

The occurrence of either regional or distant metastases is an indicator of poor prognosis for cancer patients. The mechanism of their formation has not yet been fully uncovered, which limits the possibility of developing new therapeutic strategies. Nevertheless, the discovery of circulating tumor cells (CTCs), which are responsible for tumor dissemination, and cancer stem cells (CSCs), required for tumor growth maintenance, shed light on the metastatic cascade. It seems that CTCs and CSCs are not necessarily separate populations of cancer cells, as CTCs generated in the process of epithelial-mesenchymal transition (EMT) can bear features characteristic of CSCs. This article describes the mechanisms of CTC and CSC formation and characterizes their molecular hallmarks. Moreover, we present different types of EMT occurring in physiological and pathological conditions, and we demonstrate its crucial role in providing CTCs with a CSC phenotype. The article delineates molecular changes acquired by cancer cells undergoing EMT that facilitate metastasis formation. Deeper understanding of those processes is of fundamental importance for the development of new strategies of early cancer detection and effective cancer treatment approaches that will be translated into clinical practice.
New Vessels after Stroke: Postischemic Neovascularization and Regeneration
Authors: Liman T.G. , Endres M.
Published: April 2012

The formation of new blood vessels after acute ischemic stroke is one of the most promising approaches to future therapies in the emerging field of stroke medicine. Angiogenesis and postnatal vasculogenesis are the underlying mechanisms of the formation of new blood vessels. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to play an important role in neovascularization and during the regenerative processes after a vascular injury as well as in the maintenance of endothelial integrity. This review summarizes possible mechanisms of angiogenesis, postischemic neovascularization and regeneration with a focus on the potential role of EPCs as a risk marker and as a therapeutic target in stroke medicine.
Remineralisation by Chewing Sugar-Free Gums in a Randomised, Controlled in situ Trial Including Dietary Intake and Gauze to Promote Plaque Formation
Authors: Cochrane N.J. , Shen P. , Byrne S.J. , Walker G.D. , Adams G.G. , Yuan Y. , Reynolds C. , Hoffmann B. , Dashper S.G. , Reynolds E.C.
Published: April 2012

Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not.
Hospitalised and Fatal Head Injuries in Viti Levu, Fiji: Findings from an Island-Wide Trauma Registry (TRIP 4)
Authors: Kool Bridget , Raj Naina , Wainiqolo Iris , Kafoa Berlin , McCaig Eddie , Ameratunga Shanthi
Published: April 2012

Background: Globally, head injury is a substantial cause of mortality and morbidity. A disproportionately greater burden is borne by low- and middle-income countries. The incidence and characteristics of fatal and hospitalised head injuries in Fiji are unknown. Methods: Using prospective data from the Fiji Injury Surveillance in Hospital system, the epidemiology of fatal and hospitalised head injuries was investigated (2004–2005). Results: In total, 226 hospital admissions and 50 fatalities (66% died prior to admission) with a principal diagnosis of head injury were identified (crude annual rates of 34.7 and 7.7/100,000, respectively). Males were more likely to die and be hospitalised as a result of head injury than females. The highest fatality rate was among those in the 30–44-year age group. Road traffic crashes were the leading causes of injuries resulting in death (70%), followed by ‘hit by person or object’ and falls (14% each). Among people admitted to hospital, road traffic crashes (34.5%) and falls (33.2%) were the leading causes of injury. The leading cause of head injuries in children was falls, in 15–29-year-olds road traffic crashes, and in adults aged 30–44 years or 45 years and older ‘hit by person or object’. Among the two major ethnic groups, Fijians had higher rates of falls and ‘hit by person or object’ and Indians higher rates for road traffic crashes. There were no statistically significant differences between the overall rates of head injuries or the fatal and non-fatal rates among Fijians or Indians by gender following age standardisation to the total Fijian national population. Conclusion: Despite underestimating the overall burden, this study identified head injury to be a major cause of death and hospitalisation in Fiji. The predominance of males and road traffic-related injuries is consistent with studies on head injuries conducted in other low- and middle-income countries. The high fatality rate among those aged 30–44 years in this study has not been noted previously. The high case fatality rate prior to admission to the hospital requires urgent attention.
The Release of a Troop of Rehabilitated Vervet Monkeys (Chlorocebus aethiops) in KwaZulu-Natal, South Africa: Outcomes and Assessment
Authors: Guy Amanda J. , Stone Olivia M.L. , Curnoe Darren
Published: April 2012

Rehabilitation and release have become central to the management and welfare of primate species in South Africa such as the vervet monkey(Chlorocebus aethiops). However, limited research means that it is unknown whether rehabilitation is a successful management strategy for this species. This study describes the release of a troop of rehabilitated vervet monkeys and evaluates the results of 1 year of post-release monitoring. The released animals exhibited wild behaviours and established a home range. Survival could not be adequately evaluated due to the high number of untraceable animals, and troop composition was significantly different from that of wild troops. Improvement may be gained by radio-collaring more animals using improved technology, ensuring that troop composition is comparable to wild troops, excluding ex-pets from re-introduction and a more detailed assessment of the release site.
Genetic and Environmental Factors Associated with Dental Caries in Children: The Iowa Fluoride Study
Authors: Wang X. , Willing M.C. , Marazita M.L. , Wendell S. , Warren J.J. , Broffitt B. , Smith B. , Busch T. , Lidral A.C. , Levy S.M.
Published: April 2012

Dental caries remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes and caries. In this analysis we tried to assess genetic and environmental factors contributing to childhood caries in the Iowa Fluoride Study. Environmental factors (age, sex, race, tooth-brushing frequencies and water fluoride level) and three dental caries scores (d2fs-total, d2fs-pit/fissure, and d2fs-smooth surface) were assessed in 575 unrelated children (mean age 5.2 years). Regression analyses were applied to assess environmental correlates. The Family-Based Association Test was used to test genetic associations for 23 single nucleotide polymorphism (SNP) markers in 7 caries candidate genes on 333 Caucasian parent-child trios. We evaluated the associations between caries status and the level of both single and multiple SNPs (haplotype) respectively. Permutation procedure was performed for correction of inflated type I errors due to multiple testing. Age, tooth-brushing frequency and water fluoride level were significantly correlated to at least one carious score. Caries on pit and fissure surfaces was substantially higher than on smooth surfaces (61 vs. 39%). SNPs in three genes (DSPP, KLK4 and AQP5) showed consistent associations with protection against caries. Of note, KLK4 and AQP5 were also highlighted by subsequent haplotype analysis. Our results support the concept that genes can modify the susceptibility of caries in children. Replication analysis in independent cohorts is highly needed in order to verify the validity of our findings.
Obesity, Diabetes, the Cardiorenal Syndrome, and Risk for Cancer
Authors: Forte Victoria , Pandey Abhishek , Abdelmessih Rita , Forte Giovanna , Whaley-Connell Adam , Sowers James R. , McFarlane Samy I.
Published: April 2012

Numerous epidemiological studies confirm that the prevalence of obesity and the cardiorenal metabolic syndrome (CRS) is extraordinarily high and that the rates have increased dramatically in the last three decades. In addition, epidemiological data demonstrate that obesity, the CRS, and diabetes are inextricably linked and are all associated with an increased incidence of a number of solid tissue cancers. The mechanisms for this association have been examined, including, but not limited to, higher levels of insulin and free levels of insulin-like growth factor and insulin resistance in obesity and the CRS. Mortality, morbidity, and the associated health care costs which are the link between obesity, the CRS, and diabetes are just beginning to be examined. In addition, we review the advantages of implementing lifestyle and surgical changes to modify obesity, lessening the development of the CRS, diabetes, and associated cancers. Epidemiological data regarding the general mechanisms of the pathogenesis of cancers associated with obesity, the CRS, and diabetes (specifically colon, pancreas, esophageal, liver, breast, prostate, thyroid, and renal carcinomas) are reviewed. The mechanisms by which obesity and other components of the CRS contribute to the pathogenesis of these cancers, such as hormone alterations and insulin- and insulin-like growth factor-dependent pathways of tumor pathogenesis, include the attending roles of inflammation and oxidative stress. Emphasis has been placed on obesity as a modifiable risk factor which, when addressed, provides a reduction in the rate of cancer deaths. In a second part to be published in the next issue of this journal, the relationship between diabetes and cancer will be reviewed in detail.
Association of HCV Core Antigen Seropositivity with Long-Term Mortality in Patients on Regular Hemodialysis
Authors: Kato Akihiko , Takita Takako , Furuhashi Mitsuyoshi , Fujimoto Taiki , Suzuki Hiroo , Maruyama Yukitaka , Sakao Yukitoshi , Miyajima Hiroaki
Published: April 2012

Anti-hepatitis C virus (HCV) antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD) patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg) seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2%) who had been positive for anti-HCV antibodies; 57 (69.5%) of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV) and non-CV mortalities in 376 patients. A total of 209 patients (55.6%) had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05–2.47, p < 0.05). HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27–5.45, p < 0.01). In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma) mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients.
Fluoride-Supplemented Milk Inhibits Acid Tolerance in Root Caries Biofilms
Authors: Neilands J. , Petersson L.G. , Beighton D. , Svensäter G.
Published: April 2012

In this study we investigated the effect of fluoride on plaque acid tolerance. The test group consumed 200 ml of milk supplemented with 5 mg F/l as NaF once a day, the milk control group drank 200 ml of unsupplemented milk, and the no-milk control group did not consume milk in this manner. Plaque samples were taken at baseline and after 15 months. The proportion of acid-tolerant bacteria in plaque was estimated using LIVE/DEAD® BacLight™ staining after exposure to pH 3.5 for 2 h. The fluoride group showed a statistically significant decrease in plaque acid tolerance compared to baseline. This study shows that daily intake of fluoride in milk reduces plaque acid tolerance.
Long-Term Follow-Up of Patients with Monoclonal Gammopathy of Undetermined Significance after Kidney Transplantation
Authors: Naina Harris V.K. , Harris Samar , Dispenzieri Angela , Cosio Fernando G. , Habermann Thomas M. , Stegall Mark D. , Dean Patrick G. , Prieto Mikel , Kyle Robert A. , Rajkumar S. Vincent , Leung Nelson
Published: April 2012

Introduction: Long-term data regarding kidney transplantation (KTx) patients with monoclonal gammopathy of undetermined significance (MGUS) are scarce. We evaluated the long-term outcomes of these patients in a single-center retrospective study from the Mayo Clinic, Rochester, Minn., USA. Methods: Patients who had an MGUS before transplant or developed one after KTx were selected. Monoclonal protein was screened as part of the KTx evaluation by serum protein electrophoresis. Screening for posttransplant lymphoproliferative disorder (PTLD) or MGUS after transplant was not required by protocol. Patients with multiple myeloma, dysproteinemia-related kidney disease or no pretransplant serum protein electrophoresis were excluded. Results: Between 1963 and 2006, 3,518 patients underwent KTx. MGUS was identified in 42 patients, with 23 before transplant and 19 after transplant. Median follow-up for these patients was 8.5 years (range 0.3–37). Four (17.4%) pretransplant MGUS patients developed a hematologic malignancy: 2 smoldering multiple myeloma and 2 PTLD – an Epstein-Barr virus-positive diffuse large cell lymphoma and a Hodgkin lymphoma. None of the 19 patients who developed an MGUS after transplant progressed to multiple myeloma, but 2 (10.5%) developed Epstein-Barr virus-negative T cell lymphoproliferative disorders at 16 and 26 years after transplant. Median survival was 26.1 and 28.0 years for the pretransplant and posttransplant MGUS groups, respectively. Conclusion: Progression from true MGUS to multiple myeloma is rare after KTx. KTx appears safe in true MGUS patients if the monoclonal gammopathy was not the cause of the kidney disease. None of the patients progressed to multiple myeloma, but 2 developed smoldering multiple myeloma and several developed PTLD. Further studies are needed to explain the relationship between MGUS and PTLD.
Gestational Diabetes and the Offspring: Implications in the Development of the Cardiorenal Metabolic Syndrome in Offspring
Authors: Garcia-Vargas Liliana , Addison Sonya S. , Nistala Ravi , Kurukulasuriya Damascene , Sowers James R.
Published: April 2012

The risk of developing type 2 diabetes and cardiovascular disease in women who had previously been diagnosed with gestational diabetes (GDM) is well established. There is increasing evidence that the offspring of women with GDM are at increased risk for the development of all components of the cardiorenal metabolic syndrome. Overall, it appears that these offspring have an increased risk for overweight/obesity, insulin resistance, higher blood pressure, renal disease, and type 2 diabetes. However, distinct differences in regional populations, lack of routine screening and treatment of GDM worldwide, and long follow-up periods for offspring represent a challenge in assessing the risk for development of these abnormalities in the offspring of women who have had GDM.
5/6 Nephrectomy as a Validated Rat Model Mimicking Human Warfarin-Related Nephropathy
Authors: Ozcan A. , Ware K. , Calomeni E. , Nadasdy T. , Forbes R. , Satoskar A.A. , Nadasdy G. , Rovin B.H. , Hebert L.A. , Brodsky S.V.
Published: April 2012

Background/Aims: We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN). We also previously reported that acute excessive anticoagulation with brodifacoum (superwarfarin) induces AKI in 5/6 nephrectomy (5/6NE) rats. Limitations of the brodifacoum model precluded a careful assessment of dose-response relationships. Methods: Warfarin treatment was used in 5/6NE. Results: Herein we report that warfarin treatment of 5/6NE rats resulted in a dose-dependent increase in serum creatinine (SC). The increase in SC following warfarin treatment was greater at 3 and 19 weeks after the ablative surgery, than that observed 8 weeks after the ablative surgery. The SC increase was correlated with the prothrombin time increase. Morphologically, 5/6NE, but not control rats, had acute tubular injury with RBC and RBC casts in the tubules. Treatment with vitamin K prevented SC increase and morphologic changes in the kidney associated with warfarin treatment. A single episode of WRN did not affect the progression of CKD in 5/6NE. Conclusion: (1) The 5/6NE model of CKD is an appropriate animal model to study the pathogenesis of WRN. (2) The pharmacokinetics of warfarin is better suited to the study of WRN than that of brodifacoum. (3) The more advanced stages of 5/6NE are more susceptible to WRN than the earlier stages. (4) Vitamin K treatment prevents WRN.
Hepatitis C Virus
Authors: Ye Jin
Published: April 2012

Hepatitis C virus (HCV) infects 3% of the world population and is the leading cause of liver failure in the United States. A unique feature of HCV is that the viral particles are integral to very low-density lipoprotein (VLDL)–derived lipoprotein particles. The virus is assembled into VLDL in hepatocytes and released out of the cells together with VLDL. The virus then infects more hepatocytes by entering the cells through the low-density lipoprotein receptor, which mediates uptake of majorities of VLDL-derived lipoprotein particles. These observations suggest that HCV may belong to a novel class of viruses that is associated with VLDL. Understanding the relationship between HCV and VLDL metabolism may reveal new strategies to treat HCV infection.
CIDE Proteins and Lipid Metabolism
Authors: Xu Li , Zhou Linkang , Li Peng
Published: April 2012

Lipid homeostasis is maintained through the coordination of lipid metabolism in various tissues, including adipose tissue and the liver. The disruption of lipid homeostasis often results in the development of metabolic disorders such as obesity, diabetes mellitus, liver steatosis, and cardiovascular diseases. Cell death–inducing DNA fragmentation factor 45-like effector family proteins, including Cidea, Cideb, and Fsp27 (Cidec), are emerging as important regulators of various lipid metabolic pathways and play pivotal roles in the development of metabolic disorders. This review summarizes the latest cell death–inducing DNA fragmentation factor 45-like effector protein discoveries related to the control of lipid metabolism, with emphasis on the role of these proteins in lipid droplet growth in adipocytes and in the regulation of very low-density lipoprotein lipidation and maturation in hepatocytes.
Biological Heart Rate Reduction Through Genetic Suppression of Gα
s
Protein in the Sinoatrial Node
Authors: Lugenbiel Patrick , Bauer Alexander , Kelemen Kamilla , Schweizer Patrick A. , Becker Rüdiger , Katus Hugo A. , Thomas Dierk
Published: April 2012

Background

Elevated heart rate represents an independent risk factor for cardiovascular outcome in patients with heart disease. In the sinoatrial node, rate increase is mediated by β
1
adrenoceptor mediated activation of the Gα
s
pathway. We hypothesized that genetic inactivation of the stimulatory Gα
s
protein in the sinoatrial node would provide sinus rate control and would prevent inappropriate heart rate acceleration during β‐adrenergic activation.

Methods and Results

Domestic pigs (
n
=10) were evenly assigned to receive either Ad‐small interfering RNA (siRNA)‐Gα
s
gene therapy to inactivate Gα
s
or adenovirus encoding for green fluorescent protein (Ad‐GFP) as control. Adenoviruses were applied through virus injection into the sinoatrial node followed by epicardial electroporation, and heart rates were evaluated for 7 days. Genetic inhibition of Gα
s
protein significantly reduced mean heart rates on day 7 by 16.5% compared with control animals (110±8.8 vs 131±9.4 beats per minute;
P
<0.01). On β‐adrenergic stimulation with isoproterenol, we observed a tendency toward diminished rate response in the Ad‐siRNA‐Gα
s
group (Ad‐siRNA‐Gα
s
, +79.3%; Ad‐GFP, +61.7%;
n
=3 animals per group;
P
= 0.294). Adverse effects of gene transfer on left ventricular ejection fraction (LVEF) were not detected following treatment (LVEF
Ad‐siRNA‐Gαs
, 66%; LVEF
Ad‐GFP
, 60%).

Conclusions

In this preclinical proof‐of‐concept study targeted Ad‐siRNA‐Gα
s
gene therapy reduced heart rates during normal sinus rhythm compared with Ad‐GFP treatment and prevented inappropriate rate increase after β‐adrenergic stimulation. Gene therapy may provide an additional therapeutic option for heart rate reduction in cardiac disease.

(
J Am Heart Assoc
. 2012;1:e000372 doi: 10.1161/JAHA.111.000372)
Carotid Intima‐Media Thickness Progression in HIV‐Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation
Authors: Hsue Priscilla Y. , Scherzer Rebecca , Hunt Peter W. , Schnell Amanda , Bolger Ann F. , Kalapus S.C. , Maka Kristinalisa , Martin Jeffrey N. , Ganz Peter , Deeks Steven G.
Published: April 2012

Background

Shear stress gradients and inflammation have been causally associated with atherosclerosis development in carotid bifurcation regions. The mechanism underlying higher levels of carotid intima‐media thickness observed among HIV‐infected individuals remains unknown.

Methods and Results

We measured carotid intima‐media thickness progression and development of plaque in the common carotid, bifurcation region, and internal carotid artery in 300 HIV‐infected persons and 47 controls. The median duration of follow‐up was 2.4 years. When all segments were included, the rate of intima‐media thickness progression was greater in HIV‐infected subjects compared with controls after adjustment for traditional risk factors (0.055 vs. 0.024 mm/year,
P
=0.016). Rate of progression was also greater in the bifurcation region (0.067 vs. 0.025 mm/year,
P
=0.042) whereas differences were smaller in the common and internal regions. HIV‐infected individuals had a greater incidence of plaque compared with controls in the internal (23% vs. 6.4%,
P
=0.0037) and bifurcation regions (34% vs. 17%,
P
=0.014). Among HIV‐infected individuals, the rate of progression in the bifurcation region was more rapid compared with the common carotid, internal, or mean intima‐media thickness; in contrast, progression rates among controls were similar at all sites. Baseline hsCRP was elevated in HIV‐infected persons and was a predictor of progression in the bifurcation region.

Conclusions

Atherosclerosis progresses preferentially in the carotid bifurcation region in HIV‐infected individuals. hsCRP, a marker of inflammation, is elevated in HIV and is associated with progression in the bifurcation region. These data are consistent with a model in which the interplay between hemodynamic shear stresses and HIV‐associated inflammation contribute to accelerated atherosclerosis.

(
J Am Heart Assoc
. 2012;1:jah3‐e000422 doi

:
10.1161/JAHA.111.000422
.)

Clinical Trial Registration

URL:
http://clinicaltrials.gov
. Unique identifier: NCT01519141
The Role of Norepinephrine and Estradiol in the Pathogenesis of Cardiac Wall Motion Abnormality Associated With Subarachnoid Hemorrhage
Authors: Sugimoto Keiko , Inamasu Joji , Hirose Yuichi , Kato Yoko , Ito Keisuke , Iwase Masatsugu , Sugimoto Kunihiko , Watanabe Eiichi , Takahashi Ayako , Ozaki Yukio
Published: April 2012

Background and Purpose—

The majority of patients with ventricular wall motion abnormality (WMA) associated with subarachnoid hemorrhage (SAH) are postmenopausal women. In addition to elevated catecholamine, the role of estrogen in the pathogenesis of WMA has recently been implicated. The objective of this study is to clarify the interrelation among catecholamine, estrogen, and WMA in patients with SAH.

Methods—

A retrospective analysis was performed on the medical records of 77 patients with SAH (23 men, 54 women) whose plasma levels of epinephrine, norepinephrine, and estradiol had been measured and echocardiograms had been obtained within 48 hours of SAH onset.

Results—

Twenty-four patients (31%) were found to sustain WMA on admission. Multivariate regression analysis revealed that decreased estradiol (
P
=0.018; OR, 0.902) and elevated norepinephrine levels (
P
=0.027; OR, 1.002) were associated with WMA. After quadrichotomization of 77 patients based on sex/WMA, plasma norepinephrine levels were markedly elevated in men with WMA, whereas estradiol levels were markedly decreased in women with WMA. Plasma norepinephrine and estradiol levels were not correlated. Fifty-four female patients with SAH were further quadrichotomized based on norepinephrine/estradiol levels with a threshold value of 1375 pg/mL for norepinephrine and 11 pg/mL for estradiol. The incidence of WMA in the high-norepinephrine/low-estradiol group was significantly higher than the low-norepinephrine/high-estradiol group.

Conclusions—

To our knowledge, this is the first study to evaluate the interrelation among catecholamine, estrogen, and SAH-induced WMA. Lack of estradiol in postmenopausal women may predispose them to develop WMA after poor-grade SAH. However, the precise role of multiple sex hormones in SAH-induced WMA should be evaluated in future prospective studies.
The Spectrum of Convectively Coupled Kelvin Waves and the Madden–Julian Oscillation in Regions of Low-Level Easterly and Westerly Background Flow
Authors: Roundy Paul E.
Published: April 2012

The zonal wavenumber–frequency power spectrum of outgoing longwave radiation in the global tropics suggests that power in convectively coupled Kelvin waves and the Madden–Julian oscillation (MJO) is organized into two distinct spectral peaks with a minimum in power in between. This work demonstrates that integration of wavelet power in the wavenumber–frequency domain over geographical regions of moderate trade winds yields a similar pronounced spectral gap between these peaks. In contrast, integration over regions of background low-level westerly wind yields a continuum of power with no gap between the MJO and Kelvin bands. Results further show that signals in tropical convection are redder in frequency in these low-level westerly wind zones, confirming that Kelvin waves tend to propagate more slowly eastward over the warm pool than other parts of the world. Results are consistent with the perspective that portions of disturbances labeled as Kelvin waves and the MJO that are proximate to Kelvin wave dispersion curves exist as a continuum over warm pool regions.
Physical Response of the Tropical–Subtropical North Atlantic Ocean to Decadal–Multidecadal Forcing by African Dust
Authors: Evan Amato T. , Foltz Gregory R. , Zhang Dongxiao
Published: April 2012

Dust storms are a persistent feature of the tropical North Atlantic and vary over a wide range of temporal scales. While it is well known that mineral aerosols alter the local radiative fluxes, far less is understood about the oceanic response to such forced changes to the radiative budget, particularly on long time scales. This study uses an observation-based climatology of dust surface forcing and an ocean general circulation model to examine the influence of anomalous atmospheric dust cover over the tropical North Atlantic on upper ocean temperature and circulation during 1955–2008. It is found that surface temperature anomalies from the model experiments are forced primarily by local radiation-induced changes to the surface heat budget. The subsurface temperature anomalies are additionally influenced by upper ocean circulation anomalies, which are the response to dust-forced steric changes in dynamic height. The results herein suggest that on decadal time scales dust-forced variability of ocean surface and subsurface temperatures are of a magnitude comparable to observed variability. On longer time scales dust-forced sea surface temperature anomalies vary in phase with the Atlantic multidecadal oscillation, implying that tropical North Atlantic multidecadal variability is related to changes in dust emissions from West Africa.
Restratification of the Upper Ocean after the Passage of a Tropical Cyclone: A Numerical Study
Authors: Mei Wei , Pasquero Claudia
Published: April 2012

The role of baroclinic instability in the restratification of the upper ocean after the passage of a tropical cyclone (TC) is determined by means of numerical simulations. Using a regional ocean model, the Regional Ocean Modeling System (ROMS), a high-resolution three-dimensional simulation that includes the process of baroclinic instability and is initialized with moderate-amplitude eddy structures reproduces the satellite-observed decay rate of the TC-induced sea surface temperature (SST) anomaly and is also in qualitative agreement with published observations after the passage of Hurricane Fabian in 2003 that showed decaying cold and warm anomalies located in the climatological mixed layer (CML) and upper thermocline, respectively. The model ocean is restratified after approximately one month with a net heat gain in the water column due to anomalous air–sea heat fluxes. The model shows, however, that vertical heat fluxes associated with baroclinic instability dominate over air–sea heat fluxes in restoring the CML heat content during the first month. A comparison with two-dimensional simulations that exclude baroclinic adjustment further highlights the importance of baroclinic instability: it can not only input a considerable amount of heat into the CML, but also establish strong stratification there, inhibiting the downward penetration of heat contributed by diabatic heating at the surface; both effects hasten the recovery of the SST.

Additional experiments were performed to examine the sensitivity of the model results to changes in Newtonian cooling rate, changes in the magnitude of the eddy structures used to initialize the simulation, and changes in poststorm wind strength; the results indicate that, although some of them may have a significant effect on the recovery time of the SST, their influence on the contribution of baroclinic instability to the recovery of the CML heat content is modest. However, the contribution of baroclinic instability exhibits pronounced positive dependence on the depth of the mixing layer relative to the CML depth and the relative size of the area with unperturbed water. Its dependence on the shape of the spatial variation of the mixing depth is relatively weak but in a more complicated manner. These dependencies are consistent with those predicted by a simple front adjustment model, whereas the latter also suggest that the contribution of baroclinic instability is independent of the prestorm stratification below the CML.

Overall, the idealized simulations in this study suggest that, for a typical situation in the real ocean, baroclinic instability can account for approximately 50% of the full recovery of the CML heat content, whereas under specific conditions the contribution can be significantly smaller. Those estimates provide a limit to the maximum net warming of the water column after the initial mixing event and thus have important implications regarding estimating the long-term effect of TCs on the upper-ocean heat budget.