bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Fingerprints of the Human Fecal Microbiota From 9 to 18 Months Old and the Effect of Fish Oil Supplementation
Authors: Andersen Anders Daniel , Mølbak Lars , Michaelsen Kim Fleischer , Lauritzen Lotte
Published: October 2011

Objectives:

The aim of this study was to monitor changes in the fecal microbiota from 9 to 18 months and to investigate the effect of increasing dietary n‐3 polyunsaturated fatty acids on the fecal microbiota.

Patients and Methods:

In a double‐blind controlled trial with random allocation to daily supplementation with 5 mL of fish oil (FO) or sunflower oil (SO) from 9 to 18 months of age, stool samples were collected from 132 healthy Danish infants. Molecular fingerprints of the bacterial DNA were obtained by terminal restriction fragment length polymorphism (T‐RFLP).

Results:

The T‐RFLP profiles indicated that a few T‐RFs became dominant with age (bp100 and 102, both presumed to be Bacteroidetes) concomitantly with an overall increase in the microbial diversity (P = 0.04). Breast‐feeding influenced both the T‐RFLP profiles at 9 months and the changes from 9 to 18 months, and breast‐feeding cessation during the trial modified the response to the dietary oils. In the FO group, the increase in bp102 was significantly reduced among children weaned before compared with those weaned during the trial (P = 0.027), whereas the increase in bp100 was reduced in the preweaned children of the SO group relative to those weaned during the trial (P = 0.004). This was supported by intervention group differences in the changes in bp102 and bp100 among the earlier weaned children (P = 0.06 and P = 0.09, respectively).

Conclusions:

Cessation of breast‐feeding played a dominant role relative to developmental changes in the fecal microbiota from 9 to 18 months. FO compared with SO supplementation affected changes in large bacterial groups, but only among children who had stopped breast‐feeding before 9 months of age.
Zinc Monotherapy From Time of Diagnosis for Young Pediatric Patients With Presymptomatic Wilson Disease
Authors: Mizuochi Tatsuki , Kimura Akihiko , Shimizu Norikazu , Nishiura Hiroshi , Matsushita Masami , Yoshino Makoto
Published: October 2011

In 4 young pediatric patients with presymptomatic Wilson disease, we found zinc monotherapy beginning at time of diagnosis to be safe and highly effective for follow‐up intervals between 1 and 2 years. Such maintenance therapy with zinc can maintain urinary copper excretion between 1 and 3 μg · kg−1 · day−1.
Septic Shock and Hypofibrinogenemia Predict a Fatal Outcome in Childhood Acute Acalculous Cholecystitis
Authors: Huang Shu‐Ching , Yang Yao‐Jong
Published: October 2011

Objectives:

The aim of the study was to investigate the etiology, clinical presentation, and risk factors for poor prognosis of acute acalculous cholecystitis (AAC) in children.

Patients and Methods:

Children younger than 18 years diagnosed as having AAC were analyzed retrospectively from 2000 to 2009. The demographic and clinical characteristics, etiology, and outcomes were recorded. AAC was defined as a gallbladder wall thickness of >3.5 mm in sonogram with a duration of symptoms <1 month. The severity of sonographic findings was scored, with 1 point each given for wall thickness >3.5 mm, gallbladder distention, sludge, and pericholecystic fluid.

Results:

A total of 109 children (boys:girls 1:2, median age 4.9 years) were diagnosed. The most common clinical presentation was fever (88%), followed by hepatomegaly (72%). The rates of elevated alanine aminotransferase and thrombocytopenia were 72% and 65%, respectively. The most common causative etiology was infectious diseases (74%). All of the patients were treated nonoperatively. Sixteen (15%) patients died. Children with mortality had a significantly higher rate of septic shock (P < 0.001), anemia (P = 0.01), thrombocytopenia (P = 0.04), hypofibrinogenemia (P = 0.002), the presence of pericholecystic fluid (P = 0.04), and higher sonographic scores (P = 0.04) than those with survival. Multiple logistic regression analysis confirmed that the presence of septic shock (P = 0.004) and hypofibrinogenemia (P = 0.014) were independent risk factors that predict mortality.

Conclusions:

Childhood AAC is usually secondary to a variety of etiologies, especially during the course of infectious diseases. The presence of septic shock and a low value of fibrinogen determine a fatal outcome in childhood AAC.
Liprotamase Long‐term Safety and Support of Nutritional Status in Pancreatic‐insufficient Cystic Fibrosis
Authors: Borowitz Drucy , Stevens Christopher , Brettman Lee R. , Campion Marilyn , Wilschanski Michael , Thompson Henry ,   Liprotamase 767 Study Group
Published: October 2011

Objectives:

Patients with cystic fibrosis (CF) who have exocrine pancreatic insufficiency (EPI) require treatment with pancreatic enzyme replacement therapy (PERT) to maintain adequate nutrition and age‐appropriate growth and weight gain. Liprotamase, a nonporcine, highly purified biotechnology‐derived PERT, has demonstrated significant efficacy in fat and protein malabsorption in patients with EPI compared to placebo. This study of liprotamase is the first ever long‐term trial of a PERT to evaluate safety and nutritional parameters.

Methods:

This phase III 12‐month open‐label trial assessed the safety, tolerability, and long‐term nutritional effects of liprotamase treatment in patients with CF and EPI 7 years and older. All of the patients were required to discontinue their long‐term use of porcine PERTs at the time of enrollment. Dosing started at 1 capsule of liprotamase (32,500 US Pharmacopoeia (USP) units crystallized cross‐linked lipase, 25,000 USP units crystallized protease, and 3,750 USP units amorphous amylase) per meal or snack; dose could be increased based on protocol‐defined parameters.

Results:

A total of 215 subjects were enrolled and 214 received at least 1 dose of liprotamase (mean 5.5 capsules per day). During the study period, height, weight, and body mass index z scores and lung function as measured by forced expiratory volume in 1 second were stable. There were no clinically meaningful changes in laboratory tests, including levels of fat‐soluble vitamins. Liprotamase was well tolerated without any significant safety concerns. Adverse events, primarily gastrointestinal, led to treatment discontinuation for 36 subjects (16.8%), most within the first 3 months.

Conclusions:

Treatment with a mean of 5.5 capsules of liprotamase per day, during meals and snacks, for up to 12 months was safe, well tolerated, and associated with age‐appropriate growth and weight gain or weight maintenance in subjects with CF‐related EPI.
Infant Stunting Is Associated With Short Maternal Stature
Authors: Hambidge K. Michael , Mazariegos Manolo , Kindem Mark , Wright Linda L. , Cristobal‐Perez Christina , Juárez‐García Lucrecia , Westcott Jamie E. , Goco Norman , Krebs Nancy F.
Published: October 2011

The objectives were to determine the range of maternal height associated with growth velocity of older infants and the magnitude of this association in an indigent population. Maternal height and infant length‐for‐age z scores (LAZ) were positively correlated at both 6 (n = 412, r = 0.324) and 12 (n = 388, r = 0.335) months (P < 0.0001) and for maternal heights from 131 to 164 cm. Maternal height is independently associated with infant LAZ and stunting (LAZ <−2) at both 6 and 12 months (P < 0.001) and with linear growth velocity from 6 to 12 months (P = 0.0023).
Human Milk Probiotic Lactobacillus fermentum CECT5716 Reduces the Incidence of Gastrointestinal and Upper Respiratory Tract Infections in Infants
Authors: Maldonado José , Cañabate Francisco , Sempere Luis , Vela Francisco , Sánchez Ana R. , Narbona Eduardo , López‐Huertas Eduardo , Geerlings Arjan , Valero Antonio D. , Olivares Mónica , Lara‐Villoslada Federico
Published: October 2011

Objectives:

The aim of the study was to examine the effects of a follow‐on formula containing Lactobacillus fermentum CECT5716 (L fermentum) on the incidence of infections in infants between the ages of 6 and 12 months.

Patients and Methods:

A randomized double‐blinded controlled study including infants at the age of 6 months was conducted. Infants were assigned randomly to either follow‐on formula supplemented with L fermentum plus galactooligosaccharide (experimental group, EG), or the same formula supplemented with only galactooligosaccharide (control group, CG). The main outcome was the incidence of infections for the 6‐month duration of the study.

Results:

The EG showed a significant 46% reduction in the incidence rate (IR) of gastrointestinal infections (EG: 0.196 ± 0.51, CG: 0.363 ± 0.53, IR ratio 0.54, 95% confidence interval [CI] 0.307–0.950, P = 0.032), 27% reduction in the incidence of upper respiratory tract infections (EG: 0.969 ± 0.96, CG: 1.330 ± 1.23, IR ratio 0.729, 95% CI 0.46–1.38, P = 0.026), and 30% reduction in the total number of infections (EG: 1.464 ± 1.15, CG: 2.077 ± 1.59, IR ratio 0.70, 95% CI 0.46–1.38, P = 0.003), at the end of the study period compared with CG.

Conclusions:

Administration of a follow‐on formula with L fermentum CECT5716 may be useful for the prevention of community‐acquired gastrointestinal and upper respiratory infections.
Prevalence and Outcome of Hepatobiliary Dysfunction in Neonatal Septicaemia
Authors: Khalil Sumaira , Shah Dheeraj , Faridi M.M.A. , Kumar Ashwani , Mishra Kiran
Published: October 2011

Background:

Cholestatic jaundice and liver enzyme abnormalities have been reported in neonatal septicaemia; the course, pattern, and outcome of such hepatobiliary dysfunction have not been described.

Methods:

One hundred fifty‐three neonates with blood culture–positive sepsis were recruited from the neonatal intensive care unit of an urban hospital. Liver function tests were done on day 3 and day 10 in all of the cases. In babies with abnormal results (direct bilirubin >20% of total with a minimum level of 2 mg/dL or alanine aminotransferase [ALT] >50 U/L), tests were repeated weekly for 1 month and then fortnightly for 3 months or until normalization of values. Anthropometry was recorded at all of these visits.

Results:

Klebsiella pneumoniaewas the commonest organism, isolated in 95.4% of subjects. Eighty‐three (54.2%) subjects had hepatobiliary dysfunction in the form of either cholestatic jaundice (n = 65 [42.5%]) or derangement in ALT (n = 57 [37.3%]). The onset of cholestasis was seen by day 3 of sepsis in 80% (n = 52), with maximum value of direct bilirubin seen by the 10th day in 90% (n = 58). Only 15% (n = 10) continued to have cholestatic jaundice beyond 30 days of onset of sepsis, and it resolved by 60 days. Hepatic enzyme abnormalities followed a more protracted course: onset by day 10 in 95%, peak value by day 38 in 90%, and normalisation by 60 days in 82% of subjects. The prevalence of any hepatobiliary dysfunction was found less frequently in babies who died as compared with survivors (43.4% vs 56.7%;P< 0.01). The weight, length, and head circumference during follow‐up visits were comparable between neonates with or without hepatobiliary dysfunction.

Conclusions:

Hepatobiliary dysfunction is common in Gram‐negative neonatal septicaemia. The onset of abnormalities is early in most cases but ultimately resolve within 2 to 3 months after sepsis. The presence of conjugated hyperbilirubinemia in neonatal sepsis may carry a better prognosis in terms of survival and has no significant effect on growth during early infancy.
Is Cow's Milk Harmful to a Child's Health?
Authors: Agostoni Carlo , Turck Dominique
Published: October 2011

Discussions and debates have recently emerged on the potential positive and negative effects of cow's milk in the paediatric community, also under the pressure of public opinion. The negative effects of cow's‐milk consumption seem to be limited to iron status up to 9 to 12 months; then no negative effects are observed, provided that cow's milk, up to a maximum daily intake of 500 mL, is adequately complemented with iron‐enriched foods. Lactose intolerance can be easily managed and up to 250 mL/day of milk can be consumed. Allergy to cow's‐milk proteins is usually transient. Atopic children may independently be at risk for poor growth, and the contribution of dairy nutrients to their diet should be considered. The connection of cow's milk to autistic spectrum disorders is lacking, and even a cause–effect relation with type 1 diabetes mellitus has not been established because many factors may concur. Although it is true that cow's milk stimulates insulin‐like growth factor‐1 and may affect linear growth, association with chronic degenerative, noncommunicable diseases has not been established. Finally, fat‐reduced milk, if needed, should be considered after 24 to 36 months. Cow's milk represents a major source of high nutritional quality protein as well as of calcium. Moreover, it has growth‐promoting effects independent of specific compounds. Its protein and fat composition, together with the micronutrient content, is suggestive of a functional food, whose positive effects are emphasised by regular consumption, particularly under conditions of diets poor in some limiting nutrients, although in industrialised countries cow's milk's optimal daily intake should be around 500 mL, adequately complemented with other relevant nutrients.
Serum and Tissue CD23, IL‐15, and FasL in Cow's‐Milk Protein–sensitive Enteropathy and in Coeliac Disease
Authors: Kokkonen Tuomo S. , Augustin Merja T. , Kokkonen Jorma , Karttunen Riitta , Karttunen Tuomo J.
Published: October 2011

Objectives:

The aim of the study was to explore pathogenesis and find new serum markers for cow's‐milk–sensitive enteropathy (CMSE) and coeliac disease (CD). We assessed the intestinal expression and serum concentration of CD23, IL‐15, and FasL. We hypothesised that the serum levels of CD23, a protein expressed in the lymphoid follicles, would be associated with lymphonodular hyperplasia (LNH), a feature characteristic of CMSE. We also presumed that interleukin (IL)‐15 and FasL, functionally connected with proliferation and apoptosis of the intraepithelial lymphocytes (IELs), would relate with the increased numbers of IELs present in both CMSE and CD.

Methods:

Twenty‐three children with CMSE, 20 with untreated CD, and 14 controls were studied for CD3, α/β‐ and γ/δ‐expressing IELs, and for duodenal and ileal expression of CD23, FasL, and IL‐15 by immunohistochemistry, and for serum concentration of sCD23, sFasL, and sIL‐15 by enzyme‐linked immunosorbent assay.

Results:

There was a trend for increase in sCD23 serum levels in untreated CMSE and in CD (P = 0.074; P = 0.077). CD23 was expressed in the mucosal germinal centres, but sCD23 was not related to presence of LNH. In CMSE, there was a trend for increase in serum sFasL (P = 0.07) and high levels associated with LNH (P = 0.025) and correlated with the IEL numbers (P < 0.05). Mucosal high endothelial venules adjacent to lymphoid follicles showed an intensive FasL expression.

Conclusions:

Serum sCD23 shows a trend of increment in CMSE and CD, and in the latter, sCD23 level may provide information about the severity of villous atrophy. In CMSE, high serum sFasL indicates both LNH and an increase of IELs, suggesting importance of FasL‐mediated mechanisms in the pathogenesis of these features characteristic of CMSE. Further studies are necessary to evaluate whether intensive FasL expression in mucosal high endothelial venules presents a regulatory element in mucosal immunity.
Lactose Malabsorption, Calcium Intake, and Bone Mass in Children and Adolescents
Authors: Medeiros Lilian C. da Silva , Lederman Henrique M. , de Morais Mauro B.
Published: October 2011

Objectives:

The objective of the present study was to evaluate the calcium intake and bone mass in children and early adolescents in accordance with their absorption capacity to lactose.

Patients and Methods:

A transversal study was conducted on a sample composed of 76 individuals. Lactose malabsorption status was determined with hydrogen breath test. The hydrogen breath test was applied using 2 g of lactose per kilogram of weight up to a maximum of 50 g. A hydrogen increment ≥20 ppm in relation to fasting was used to characterize lactose malabsorption. Two 24‐hour recalls were applied for the evaluation of food consumption. Bone mineral content and bone mineral density were evaluated in the lumbar spine by dual‐energy x‐ray absorptiometry.

Results:

The prevalence of lactose malabsorption was 61.8%. The participants were divided into 2 groups: lactose malabsorbers (n = 47) and lactose absorbers (n = 29). There was no statistically significant difference (P > 0.05) between the groups with respect to the intake of total calcium, milk calcium, milk, cheese, yogurt, ice cream, and calcium density of the diet. Additionally, there was no difference with respect to the bone mineral content and the bone mineral density of the lumbar spine. Independent from lactose absorption capacity, it was observed that the majority of the children and early adolescents showed calcium intake lower than the recommended value.

Conclusions:

There was no relation among lactose malabsorption and bone densities, bone mineral content, or calcium intake within the present study.
Proton Pump Inhibitor Use in Infants
Authors: Chen Ii‐Lun , Gao Wen‐Yi , Johnson Aisha P. , Niak Ali , Troiani John , Korvick Joyce , Snow Nancy , Estes Kristina , Taylor Amy , Griebel Donna
Published: October 2011

The Food and Drug Administration has completed its review of 4 clinical trials evaluating the use of proton pump inhibitors (PPIs) in infants (ages 1 month to <12 months) for the treatment of gastroesophageal reflux disease (GERD). An Advisory Committee meeting was held in November 2010 to discuss the potential reasons why PPI use in these trials failed to show a benefit in infants with GERD, and directions for future study. The present review summarizes the findings from the clinical trials. Potential mechanisms for the failed clinical trials are discussed. The safety of long‐term use is also discussed. As a result of our analysis and review, the authors agree with the Advisory Committee members that PPIs should not be administered to treat the symptoms of GERD in the otherwise healthy infant without the evidence of acid‐induced disease.
Resolution of the Acanthopagrus black seabream complex based on mitochondrial and amplified fragment‐length polymorphism analyses
Authors: Hsu T.‐H. , Guillén Madrid A. G. , Burridge C. P. , Cheng H.‐Y. , Gwo J.‐C.
Published: October 2011

In this study, DNA analyses were employed to verify the identity of six morphologically similar species that occur in the coastal waters of Taiwan: the black seabream complex (Acanthopagrus latus, Acanthopagrus schlegelii, Acanthopagrus sivicolus, Acanthopagrus taiwanensis, Acanthopagrus chinshira and Acanthopagrus pacificus). Amplified fragment‐length polymorphism (AFLP) analyses clearly distinguished the same six species that are morphologically diagnosable based on subtle differences in scale counts and anal‐fin colouration. In contrast, mitochondrial DNA analyses based on cytochrome b gene sequences did not distinguish individuals of A. schlegelii and A. sivicolus, reflecting either historical introgression or recent speciation and incomplete sorting of their mitochondrial lineages. Phylogenetic relationships among these six north‐west Pacific Ocean species of Acanthopagrus analysed using AFLP data were consistent with scale rows above the lateral line (TRac), sperm ultrastructure and geographical distribution. The study provides molecular tools for future research relevant to improved management of these resources, and an increased understanding of the evolutionary history of this radiation.
Quality of life and psychological status of patients with pemphigus vulgaris using Dermatology Life Quality Index and General Health Questionnaires
Authors: GHODSI S. Zahra , CHAMS‐DAVATCHI Cheyda , DANESHPAZHOOH Maryam , VALIKHANI Mahin , ESMAILI Nafiseh
Published: October 2011

Pemphigus vulgaris with painful chronic blisters and/or erosions on skin and mucosa can impair quality of life (QOL). Therapeutic modalities in the long run can have additional negative impact. There are few studies that have focused on QOL of such patients except in treated cases. The aim of this study was to describe the effect of the disease per se on QOL before receiving treatment and evaluation of psychological status of the patients and its effect on their QOL. A total of 61 patients with newly diagnosed non‐treated pemphigus vulgaris participated in the study. The Persian version of the Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate their QOL and the 28‐item General Health Questionnaire (GHQ‐28) for their psychological status. In this study, the mean DLQI score was 10.9 ± 6.9. QOL was worse in patients with nasal and pharynx involvement, with positive Nikolsky sign, patients with severe skin involvement and those who showed the symptom of itching. There was a negative correlation between DLQI score and duration of the disease. More than 77% of patients experienced anxiety and depression with more impaired QOL. In conclusion, pemphigus vulgaris is responsible for great alteration in QOL, especially in its severe form. The disease in its initial stage may have greater impact on the QOL. The high probability of anxiety and depression in these patients and its negative effect on QOL should be taken into account in the management of these patients right from the start of the treatment.
miR‐155 modulates microglia‐mediated immune response by down‐regulating SOCS‐1 and promoting cytokine and nitric oxide production
Authors: Cardoso Ana L. , Guedes Joana R. , Pereira de Almeida Luís , Pedroso de Lima Maria C.
Published: October 2011

Innate immunity constitutes the first line of defence against both external and endogenous threats in the brain, and microglia cells are considered key mediators of this process. Recent studies have shown that microRNAs (miRNAs) may play a determinant role in the regulation of gene expression during innate immune responses. The major goal of this work was to investigate the contribution of a specific miRNA – miR‐155 – to the modulation of the microglia‐mediated immune response. For this purpose, in vitro studies were performed in N9 microglia cells to evaluate changes in the levels of this miRNA following microglia activation. A strong up‐regulation of miR‐155 expression was observed following microglia exposure to lipopolysaccharide, which was consistent with a decrease in the levels of the suppressor of cytokine signalling 1 (SOCS‐1) protein, a key inhibitor of the inflammatory process and a predicted target of miR‐155. The miR‐155 knockdown by anti‐miRNA oligonucleotides up‐regulated SOCS‐1 mRNA and protein levels and significantly decreased the production of nitric oxide and the expression of inflammatory cytokines and inducible nitric oxide synthase. Finally, treatment of neuronal primary cultures with conditioned medium obtained from microglia cells, in which miR‐155 was inhibited before cell activation, decreased inflammatory‐mediated neuronal cell death. Overall, our results show that miR‐155 has a pro‐inflammatory role in microglia and is necessary for the progression of the immune response through the modulation of SOCS‐1, suggesting that, in a chronic inflammatory context, miR‐155 inhibition can have a neuroprotective effect.
Tropical tree seedling growth responses to nitrogen, phosphorus and potassium addition
Authors: Santiago Louis S. , Wright S. Joseph , Harms Kyle E. , Yavitt Joseph B. , Korine Carmi , Garcia Milton N. , Turner Benjamin L.
Published: October 2011

1. Nutrients are a critical resource for plant growth, but the elements limiting growth in tropical forests have rarely been determined.

2. We investigated the influence of nitrogen (N), phosphorus (P), potassium (K) and micronutrients on seedling biomass and nutrient allocation in a factorial nutrient fertilization experiment in lowland tropical forest at the Barro Colorado Nature Monument, Panama. We also measured 8 years of herbivory and growth for 1800 seedlings. We sought to determine the identity of limiting elements and possible nutrient interactions.

3. The five study species were Alseis blackiana, Desmopsis panamensis, Heisteria concinna, Sorocea affinis and Tetragastris panamensis. Plants grew in deeply shaded understorey with a mean canopy openness of 4.9% (±0.7%; 1 SE).

4. Tissue N concentration increased by 11% with N addition. Tissue P concentration increased by 16% with P addition. Tissue K increased by 4% with K addition. K addition reduced root‐to‐shoot biomass ratio. There was no significant effect of fertilization on specific leaf area or leaf area ratio.

5. The proportion of leaves damaged and the mean level of damage by herbivory increased with P and K addition and showed a significant P × K interaction.

6.7ensp;Across all species and years, relative growth rate of height increased with K addition and with N and P in combination. Relative growth rate of leaf count trended 8.5% higher with K addition (P = 0.076).

7. We also added micronutrients in a parallel experiment. There was no effect of micronutrient addition on any seedling parameter.

8. Synthesis. K addition affected seedlings by enhancing tissue nutrient concentration, increasing herbivory, reducing root‐to‐shoot biomass ratio and increasing height growth. Additional effects of N or P on tissue chemistry, herbivory and growth offer support for the multiple limiting resources hypothesis. Our results suggest that seedling growth is limited by nutrients, especially K, even under highly shaded conditions in this lowland tropical forest.
Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine
Authors: Chao C. , Klein N. P. , Velicer C. M. , Sy L. S. , Slezak J. M. , Takhar H. , Ackerson B. , Cheetham T. C. , Hansen J. , Deosaransingh K. , Emery M. , Liaw K.‐L. , Jacobsen S. J.
Published: October 2011

Abstract.  Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K‐L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012; 271: 193–203.

Objective.  An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance.

Design.  Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions.

Setting.  Two managed care organizations in California.

Subjects.  Number of 189 629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008.

Outcome.  Potential new‐onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12‐month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC).

Results.  Overall, 1014 potential new‐onset cases were electronically identified; 719 were eligible for case review; 31–40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto’s disease [IRR = 1.29, 95% confidence interval: 1.08–1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study.

Conclusions.  No autoimmune safety signal was found in women vaccinated with HPV4.
A detailed evaluation method to identify sources of quantitative resistance to Fusarium oxysporum f. sp. pisi race 2 within a Pisum spp. germplasm collection
Authors: Bani M. , Rubiales D. , Rispail N.
Published: October 2011

Fusarium oxysporum f. sp. pisi (Fop) is an important pathogen of field pea (Pisum sativum) worldwide. The constant evolution of the pathogen drives the necessity to broaden the genetic basis of resistance to Fop. To achieve this, it is important to have a large germplasm collection available and an accurate and efficient method for disease assessment. Here, a detailed evaluation method coupling disease incidence, disease rating over time and its related area under the disease progression curve (AUDPC) was established and used to screen a Pisum spp. germplasm collection against one isolate of Fop race 2. A large variation in the disease response of specific pea accessions ranging from highly resistant to susceptible was observed within the collection, indicating the quantitative expression of the resistance. The repetition of the inoculation experiments on a subset of 19 accessions, including two susceptible accessions, indicated that the scoring method was robust and reproducible and confirmed the highly resistant phenotypes of 11 accessions. To initiate the characterization of resistance mechanisms within these accessions, the external and internal stem symptoms were compared between these selected pea accessions, together with the extent of fungal colonization within plants. All these tests indicated that, in all resistant accessions, the resistance mechanisms efficiently stopped pathogen progression at the crown. Incorporation of these sources of resistance to breeding programmes will contribute to improved Fop resistance in pea cultivars.
Increased ethanol intake in prodynorphin knockout mice is associated to changes in opioid receptor function and dopamine transmission
Authors: Femenía Teresa , Manzanares Jorge
Published: October 2011

The purpose of this study was to examine the role of the prodynorphin gene in alcohol sensitivity, preference and vulnerability to alcohol consumption. Handling‐induced convulsion (HIC) associated to alcohol, alcohol‐induced loss of righting reflex (LORR), hypothermic effects in response to acute ethanol challenge, blood ethanol levels (BELs), conditioned place preference, voluntary ethanol consumption and preference, tyrosine hydroxylase (TH), dopamine transporter (DAT) and proenkephalin (PENK) gene expression, and µ‐, δ‐ and κ‐opioid agonist‐stimulated [S35]‐ guanosine 5′‐triphosphate‐binding autoradiography were studied in prodynorphin knockout (PDYN KO) and wild‐type (WT) mice. There were no differences in HIC, LORR or the decrease in body temperature in response to acute ethanol challenge between PDYN KO and WT mice. PDYN KO mice presented higher BEL, higher ethanol‐conditioned place preference and more ethanol consumption and preference in a two‐bottle choice paradigm than WT mice. These findings were associated with lower TH and higher DAT gene expression in the ventral tegmental area and substantia nigra, and with lower PENK gene expression in the caudate–putamen (CPu), accumbens core (AcbC) and accumbens shell (AcbSh) in PDYN KO. The functional activity of the µ‐opioid receptor was lower in the CPu, AcbC, AcbSh and cingulate cortex (Cg) of PDYN KO mice. In contrast, δ‐ and κ‐opioid receptor‐binding autoradiographies were increased in the CPu and Cg (δ), and in the CPu, AcbC and Cg (κ) of PDYN KO. These results suggest that deletion of the PDYN gene increased vulnerability for ethanol consumption by altering, at least in part, PENK, TH and DAT gene expression, and µ‐, δ‐ and κ‐opioid receptor functional activity in brain areas closely related to ethanol reinforcement.
Developmental and disease‐related influences on self‐management acquisition among pediatric liver transplant recipients
Authors: Piering Kristen , Arnon Ronen , Miloh Tamir A. , Florman Sander , Kerkar Nanda , Annunziato Rachel A.
Published: October 2011

Piering K, Arnon R, Miloh TA, Florman S, Kerkar N, Annunziato RA. Developmental and disease‐related influences on self‐management acquisition among pediatric liver transplant recipients. Pediatr Transplantation 2011: 15: 819–826. © 2011 John Wiley & Sons A/S.

Abstract:  Pediatric LT recipients are vulnerable to disruptions in their healthcare management and transitioning to self‐managed care. This study aimed to examine whether age at transplant and indication for transplant (acute vs. chronic liver disease) influence later self‐management skills. Sixty‐three LT recipients, aged 14 and older (M = 17.68, s.d. = 3.01), were recruited and asked to complete a healthcare management survey, the Developmentally Based Skills Checklist, adapted for transplant patients, listing 22 behaviors that medically ill adolescents should progressively master. While there were no significant differences between those who received an LT owing to an acute disease vs. those who received an LT owing to a chronic disease, the age at which patients received their transplant did yield significant results, although, overall, these findings were attenuated by current age. However, our findings indicated that males transplanted at a younger age struggled with mastery over their healthcare responsibilities relative to males transplanted later and females in both age groups. There are many possible reasons why the experience of transplant at a younger age could negatively affect or derail healthcare transitions. Future research is necessary to further untangle this relationship; yet, it seems as though longer time living with LT may make transition harder for families.
Nitric oxide as a critical factor for perception of UV‐B irradiation by microtubules in Arabidopsis
Authors: Krasylenko Yuliya A. , Yemets Alla I. , Sheremet Yarina A. , Blume Yaroslav B.
Published: October 2011

Influence of ultraviolet‐B (UV‐B) as an abiotic stress factor on plant microtubules (MTs) and involvement of nitric oxide (NO) as a secondary messenger mediating plant cell response to environmental stimuli were investigated in this study. Taking into account that endogenous NO content in plant cells has been shown to be increased under a broad range of abiotic stress factors, the effects of UV‐B irradiation and also the combined action of UV‐B and NO donor sodium nitroprusside (SNP) or NO scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (c‐PTIO) on the MTs organization in different root cells of Arabidopsis thaliana were tested. Subsequently, realization of the MT‐mediated processes such as root growth and development was studied under these conditions. Arabidopsis thaliana seedlings expressing the chimeric gene gfp‐map4 were exposed to the enhanced UV‐B with or without SNP or c‐PTIO pretreatment. The UV‐B irradiation alone led to a dose‐dependent root growth inhibition and to morphological alterations of the primary root manifested in their swelling and excessive root hair formation. Moreover, dose‐dependent randomization and depolymerization of MTs in both epidermal and cortical cells under the enhanced UV‐B were found. However, SNP pretreatment of the UV‐B irradiated A. thaliana seedlings recovered the UV‐B inhibited root growth as compared to c‐PTIO pretreatment. It has been shown that in 24 h after UV‐B irradiation the organization of MTs in root epidermal cells of SNP‐pretreated A. thaliana seedlings was partially recovered, whereas in c‐PTIO‐pretreated ones the organization of MTs has not been distinctly improved. Therefore, we suppose that the enhanced NO levels in plant cells can protect MTs organization as well as MT‐related processes of root growth and development against disrupting effects of UV‐B.
Benefit of transfusion‐related acute lung injury risk‐minimization measures – German haemovigilance data (2006–2010)
Authors: Funk M. B. , Guenay S. , Lohmann A. , Henseler O. , Heiden M. , Hanschmann K. M. O. , Keller‐Stanislawski B.
Published: October 2011

Objective  Based on the frequency of immune‐mediated and non‐immune‐mediated transfusion‐related acute lung injury (TRALI), the effect of risk‐minimization measures was evaluated during a period of 5 years (2006–2010). Risk‐minimization measures were implemented in 2008/2009, consisting of exclusion of female donors with a history of pregnancy or exclusion of female donors with human leucocyte antigen (HLA)/human neutrophil alloantigen (HNA) antibodies.

Methods  TRALI was confirmed according to the criteria of the International Haemovigilance Network. Based upon the results of donor testing of white‐blood‐cell antibodies (WBC‐Ab) against HLA or HNAs, confirmed cases were classified as immune‐ or non‐immune‐mediated TRALI. Reporting rates were calculated on the basis of the annually transfused blood components, and pre‐ and post‐implementation periods were compared.

Results  In total, 60 immune‐mediated (75%) and 20 non‐immune‐mediated (25%) TRALI reactions were confirmed. A total of 68 (64 women and four men) donors were involved: seven red‐blood‐cell concentrates donors (13%), six platelet concentrate donors (10%), and 48 fresh frozen plasma (FFP) donors (77%). The reporting rate of immune‐mediated TRALI caused by FFP decreased continuously; from 12·71 per million units in 2006/2007 to 6·81 per million units in 2008/2009 and no case in 2010.

Conclusion  The comparison of the pre‐ and the post‐implementation period demonstrated a significantly reduced risk of TRALI events comparing 2006/2007 with 2010 (P‐value: < 0·01). Furthermore, no case of TRALI‐induced fatality occurred after the implementation of risk‐minimization measures.
Male diet and age influence to inhibit female remating in Ceratitis capitata (Diptera: Tephritidae)
Authors: Costa A. M. , Anjos‐Duarte C. S. , Roriz A. K. P. , Dias V. S. , Joachim‐Bravo I. S.
Published: October 2011

This study evaluated the influence of age and adult nutritional status of Ceratitis capitata males on their ability to inhibit female remating. Their roles and that of copula duration on the amount of sperm transferred to female spermathecae were also analysed. After emergence, adults were kept in separate groups according to their diets (either high protein – 6.5 g of brewer’s yeast, or low protein – 3.5 g of brewer’s yeast) and their age at the time of use in experiments (4, 8, 12, 16 and 20 days old). The results demonstrated that: (i) male age was not a factor that influenced remating when females mated with well‐nourished males; however, the youngest males (4 days old) in the low‐protein group were less efficient in preventing female remating; (ii) 12‐ and 16‐day‐old males fed on a high‐protein diet transferred and produced more sperm than males of other groups; (iii) there was no correlation between copula duration and the amount of sperm transferred to the female; the longest copula durations were observed among low‐protein‐diet/20‐day‐old males. These results suggest that age and nutrition influence the ability of the males to inhibit female remating. The sterile insect technique is most effective when females do not remate after coupling with sterile males, and therefore, the capacity to inhibit female remating is an important characteristic of males released in the field.
Natural and human causes of earwig mortality during winter: temperature, parasitoids and soil tillage
Authors: Moerkens R. , Leirs H. , Peusens G. , Beliën T. , Gobin B.
Published: October 2011

Beneficial arthropods are often used for suppressing specific pest outbreaks in agricultural crop systems. The European earwig, Forficula auricularia L., (Dermaptera: Forficulidae), is an important natural enemy in fruit orchards. Recently, ecological studies were published describing earwig dispersal and survival during summer, hereby revealing clear differences between populations with a single brood (SBP) and two broods a year (DBP). In this article, we will describe three potential mortality factors of earwigs during the underground winter period, namely cold temperatures, parasitoids and soil tillage. This knowledge is essential for making efficient management strategies for increasing earwig abundance in fruit orchards. The effect of cold temperatures was checked during a 3‐year semi‐field experiment. Parasitism rates of Triarthria spp. (Fallén) and Ocytata pallipes (Fallén) (Diptera: Tachinidae) were obtained in a rearing experiment. The negative effect of soil tillage on the survival of earwigs nests was checked in a field experiment covering a 4‐year time period. A strong, negative relation between temperature [cooling day degrees (CDD)] and survival of female and male earwigs during winter was found. Male earwigs of SBP died very quickly, mimicking natural conditions. Between 60% and 90% of females do not survive winter. Survival of females in DBP was higher than in SBP. Parasitism rates vary a lot between species, generation, year and location (0–20%). During winter, we found a maximum mortality of 13%. There is a clear trend that soil tillage can reduce the number of nymphs in spring and summer by 50%. Implications for biocontrol are the following: (i) mortality owing to temperature can be predicted using CDD and if necessary preventive management actions can be undertaken to control pests; (ii) parasitism rates are negligible compared to high impact of temperature; and (iii) soil tillage can be timed more accurately using a recently developed day degree model.
Costa Rican soils contain highly insecticidal granulovirus strains against Phthorimaea operculella and Tecia solanivora
Authors: Gómez‐Bonilla Y. , López‐Ferber M. , Caballero P. , Léry X. , Muñoz D.
Published: October 2011

The aim of this work was to isolate and characterize novel Phthorimaea operculella granulovirus (PhopGV) strains from Costa Rican soils. Three novel strains, named PhopGV‐CR3, PhopGV‐CR4 and PhopGV‐CR5, were isolated from three locations in Costa Rica, Alvarado, Zarcero and Abangares, respectively, by means of soaking potato tubers with diluted soil samples. An additional strain, PhopGV‐CR2, was identified from diseased larvae from a Tecia solanivora laboratory culture. Restriction fragment length polymorphisms obtained for each isolate with six restriction endonucleases (RENs) allowed their identification as four distinct PhopGV strains. Both REN and Polymerase chain reaction analyses indicated the existence of an array of genotypic variants present in all isolates. Bioassays in P. operculella and T. solanivora showed that PhopGV‐CR3 was well adapted to the two coexisting hosts with high levels of pathogenicity against both pest species. The mean lethal dose values of this strain were 2.8 OBs/mm2 for P. operculella and less than 0.5 OBs/mm2 for T. solanivora. We conclude that PhopGV‐CR3 shows great promise for soil application against these pests in Costa Rican potato crops.
Treatment of seborrhoeic dermatitis of the scalp with a topical solution of urea, lactic acid, and propylene glycol (K301): results of two double‐blind, randomised, placebo‐controlled studies
Authors: Emtestam Lennart , Svensson Åke , Rensfeldt Kjell
Published: October 2011

Summary  Alternative treatments for seborrhoeic dermatitis are needed because of the increasing risk of anti‐fungal resistance to existing therapies. To investigate the efficacy, safety and tolerability of topical scalp treatment with K301 solution. Two multi‐centre, randomised, double‐blind studies were conducted. Study I: 4 weeks of once‐daily treatment with either one form of K301 (a or b) or placebo, followed by 4 weeks of maintenance treatment three times‐per‐week. Study II: 4 weeks of K301 (a) or placebo once‐daily. Study I: 98 patients enrolled (K301a + b, n = 51; placebo, n = 47) and 83 completed; 201 entered Study II (K301a, n = 136; placebo, n = 65) and 195 completed. Erythema and desquamation sum score at 4 weeks, mean (SD) values were 2.4 (2.0) for K301a + b and 3.2 (2.2) for placebo in Study I (P = 0.025) and 2.5 (1.9) for K301a and 3.2 (1.8) for placebo in Study II (not significant). In both studies, 4‐week desquamation scores were significantly improved for K301 vs. placebo (P < 0.05). Both studies showed significant improvements in symptomatic investigator and patient assessments for K301 over placebo after 4 weeks (P < 0.05). Treatment‐related adverse events were generally mild and included some smarting or burning upon application. The K301 was well tolerated and associated with clinically meaningful improvements in seborrhoeic dermatitis endpoints.
Alterations of acid–base balance, electrolyte concentrations, and osmolality caused by nonionic hyperosmolar contrast medium during pediatric cardiac catheterization
Authors: Dennhardt Nils , Schoof Stephan , Osthaus Wilhelm A. , Witt Lars , Bertram Harald , Sümpelmann Robert
Published: October 2011

Objective:  This prospective clinical observational study was conducted to investigate the effects of contrast medium on acid–base balance, electrolyte concentrations, and osmolality in children.

Background:  For pediatric cardiac catheterization, high doses of nonionic hyperosmolar contrast medium are widely used.

Methods:  Forty pediatric patients (age 0–16 years) undergoing cardiac angiography with more than 3 ml·kg−1 of nonionic hyperosmolar contrast medium (Iomeprol) were enrolled, and the total amount of the contrast agent given was documented. Before and after contrast medium administration, a blood sample was collected to analyze electrolytes, acid–base parameters, osmolality, hemoglobin, and hematocrit.

Results:  After cardiac catheterization, pH, hemoglobin, hematocrit, bicarbonate, base excess, sodium, chloride, calcium, anion gap and strong ion difference decreased, whereas osmolality increased significantly (base excess −1.8 ± 1.8 vs −3.4 ± 2.3, sodium 138 ± 2.9 vs 132 ± 4.1 mm, osmolality 284 ± 5.7 vs 294 ± 7.6 mosmol·kg−1, P < 0.01). Seventy‐eight percent of the children developed hyponatremia (sodium <135 mm). No changes were seen in pCO2, lactate, and potassium levels.

Conclusions:  Regarding the differential diagnosis of metabolic disturbances after pediatric cardiac catheterization, low‐anion gap metabolic acidosis and hyponatremia should be considered as a possible side effect of the administered contrast medium.