bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote monitoring of pain and symptoms using wireless technology in children and adolescents with sickle cell disease
Authors: Jacob Eufemia , Duran Joana , Stinson Jennifer , Lewis Mary Ann , Zeltzer Lonnie
Published: July 2012

Purpose

The purpose of this study was to examine (a) symptoms, (b) pain characteristics (intensity, location, quality), (c) pain medications and nonpharmacological strategies used for pain, (d) thoughts and feelings, and (e) healthcare visits. We also examined the relationship between pain and sleep.

Data sources

Pain and symptoms were entered on an electronic e‐Diary using a smartphone and were remotely monitored by an advanced practice registered nurse (APRN). Sixty‐seven children and adolescents (10–17 years) reported mild to severe pain at home that did not require healthcare visits. Symptoms reported were (a) general symptoms such as tiredness/fatigue (34.7%), headache (20.8%), yellowing of the eyes (28.4%); (b) respiratory symptoms such as sniffling (32.9%), coughing (19.1%), changes in breathing (10.0%); and (c) musculoskeletal symptoms such as stiffness in joints (15.8%). A significant negative correlation was found between pain and sleep (r = −.387, p = .024). Factors that predict pain included previous history of sickle cell disease (SCD) related events, symptoms, and negative thoughts.

Conclusion

Pain and multiple symptoms entered on a web‐based e‐Diary were remotely monitored by an APRN and prompted communications, further evaluation, and recommendations.

Implications for practice

Remote monitoring using wireless technology may facilitate timely management of pain and symptoms and minimize negative consequences in SCD.
Spatio‐temporal shifts of the dynamic Cape fur seal population in southern Africa, based on aerial censuses (1972–2009)
Authors: Kirkman Steve P. , Yemane D. , Oosthuizen W. H. , Meÿer M. A. , Kotze P. G. H. , Skrypzeck H. , Vaz Velho F. , Underhill L. G.
Published: July 2012

Abstract

A time series of aerial censuses of Cape fur seal colonies, spanning four decades (1972–2009) and three countries (South Africa, Namibia, and Angola), was analyzed to assess spatio‐temporal changes in population numbers. A weighted quantile regression approach was used to estimate trends in pup counts that were used as proxies for numbers of older animals at breeding colonies. There was a 74% increase in the number of breeding colonies over the study period, from 23 in 1973 to 40 in 2009. There was also a significant northward shift in the distribution of the breeding population. This was largely attributable to events in the northern part of the population's range coinciding with Namibia, where seal numbers declined at most colonies in the south of Namibia while several new breeding colonies developed in the northern part of Namibia and one in southern Angola. Despite range expansion and the development of new colonies, the overall size of the population in 2009 was similar to that of the early 1990s, according to the pup count models. Potential mechanisms for the observed changes, and their management implications, are discussed.
Kunjin flaviviral encephalomyelitis in an Arabian gelding in New South Wales, Australia
Authors: Tee SY , Horadagoda N , Mogg TD
Published: July 2012

Flaviviruses, including Kunjin virus, are arboviruses that cause encephalomyelitis in humans and horses. This case report describes an Arabian gelding exhibiting neurological signs of flavivirus encephalomyelitis, the diagnostic investigation and confirmation of an unreported case of Kunjin virus equine encephalomyelitis in Australia.
Comparative approach to understanding traumatic injury in the immature, postnatal brain of domestic animals
Authors: Finnie JW
Published: July 2012

Traumatic brain injury (TBI) is a frequent occurrence in veterinary medicine, but the mechanisms leading to brain damage after a head impact are incompletely understood, particularly in the postnatal immature and still developing nervous system. This paper reviews neurotrauma studies, largely in paediatric humans and experimental animal models, in order to outline the pathophysiological and biomechanical events likely to be operative in head trauma involving domestic animal species in the postnatal period, as there is almost no other information available in the veterinary literature. Predicting the outcome of TBI is particularly difficult at this developmental time, in large part because recovery is influenced by the stage of brain maturation and neuroplasticity. An important part of the clinical management of TBI is the differentiation of primary brain damage, which occurs at the moment of head impact and is largely refractory to treatment, from the cascade of secondary events, which evolve over time and are potentially preventable and amenable to therapeutic intervention. An understanding of the causes and consequences of secondary brain damage such as hypoxia–ischaemia, brain swelling, elevated intracranial pressure, and infection is critical to limiting the resulting brain injury.
Haematology and biochemistry of warru (Petrogale lateralisMacDonnell Ranges race) in captivity and the wild
Authors: Ruykys L , Rich B , McCarthy P
Published: July 2012

Objective

Use haematology, biochemistry and protein electrophoresis analyses to establish reference values for, and describe the health status of, wild and captive colonies of critically endangered warru (black‐footed rock‐wallaby: Petrogale lateralis MacDonnell Ranges race).

Methods

Blood samples were taken from warru in three wild colonies (Alalka, Kalka, New Well) in the A
nangu Pitjantjatjara Yankunytjatjara Lands in north‐west South Australia (SA) and from captive animals at Monarto Zoo, SA. General haematology, serum biochemistry and protein electrophoresis analyses were conducted and results used to establish reference ranges. For the parameters that are indicative of a population's health, comparisons among the study sites were completed using analysis of variance.

Results

General haematology results suggested that warru were not experiencing chronic anaemia and the protein electrophoresis values indicated that colonies were not suffering from population‐wide disease. However, the lower superoxide dismutase, retinol, total carotenoids and ascorbic acid values for New Well warru suggested those animals had a lower plane of nutrition than those at Kalka and Alalka. Higher urea concentrations in New Well and Alalka warru could be a reflection of the absence of reliable free water at these sites.

Conclusion

The results have implications for the management of in situ colonies, including potentially using supplementary feeding to improve nutrition, and suggested that these animals were not suffering from disease. The study presents the first blood reference values for P. lateralis and, potentially, a methodology for other threatened species recovery programs to follow to establish the health of their populations.
Impact of xerostomia on oral health and quality of life among adults infected with HIV‐1
Authors: Jeganathan Sarangapany , Carey Helen , Purnomo Julianita
Published: July 2012

The study investigated the impact of xerostomia on oral health and quality of life (QoL) among patients infected with human immunodeficiency virus (HIV) who were attending for routine HIV monitoring in Australia. This cross‐sectional, self‐administered questionnaire survey and oral screening (OS) included 100 subjects who were HIV positive. The OS was conducted by a dentist blinded to the subject's survey responses. Xerostomia was determined by asking the subjects a single question. Subjects with xerostomia were found to have increased caries activity and poorer QoL, especially in the psychological dimensions of the oral health impact profile. Age and duration of HIV infection were associated with xerostomia. Early diagnosis of xerostomia and intervention with preventive dental care would potentially reduce caries and improve QoL among patients infected with HIV‐1. Ongoing chronic inflammation of salivary glands despite the beneficial effects of antiretroviral therapy may play a role in the etiology of xerostomia in patients infected with HIV and requires further study.
A novel prosthodontic alternative for patients who are edentulous and have microstomia: a case report
Authors: Egan John Gerard , Swindells Stephen Andrew
Published: July 2012

Excision of squamous cell carcinoma from the lower lip of a patient can result in limited mouth opening (microstomia). For any patients who have this condition, routine or general dentistry and prosthetic treatment is challenging. Traditional denture techniques tend to be unsatisfactory, due to the patients’ reduced ability to open their mouth. The use of sectional and modified dentures and those with a small degree of flexibility has been reported to be useful for patients needing complete dentures.

This case report presents a flexible denture base material that can be manipulated on insertion into a smaller shape that is half the original size and is completely flexible for insertion into a mouth that has limited opening. Once seated on the maxillary and mandibular residual ridges, the denture regains its original form and becomes firm and strong to allow the patient to function. This procedure offers a prosthodontic treatment option for a patient with microstomia.
Comparison of patient satisfaction, quality of life, and bite force between elderly edentulous patients wearing mandibular two implant‐supported overdentures and conventional complete dentures after 4 years
Authors: Geckili Onur , Bilhan Hakan , Mumcu Emre , Dayan Cagatay , Yabul Ali , Tuncer Necat
Published: July 2012

This study compared two groups of patients who were elderly and edentulous, one group included subjects who had mandibular overdentures supported by two implants (Group I); the other groups wore conventional complete dentures (Group II). This retrospective study included 100 edentulous patients (50 from each group) with an average age of 67.86 years, who had been followed for 4 years. The groups were compared in terms of patient satisfaction, quality of life (QOL), and bite force. The bite force and patient satisfaction scores of Group I were found to be statistically significantly higher than Group II (p < .05). However, no statistically significant difference was found between the two groups’ QOL scores (p > .05) except on the physical pain subscale (p = .013). Based on these results, it can be concluded that after 4 years of function, subjects wearing mandibular overdentures supported by two implants had higher values for bite force and patient satisfaction scores, but similar QOL scores when compared to conventional complete denture‐wearers.
Impact of oral health in patients with multiple sclerosis and epilepsy: A survey in a neurology clinic
Authors: Koffman Boyd M. , Khuder Sadik , Mutgi Sunil , Crooks Ryan , Herial Nabeel
Published: July 2012

This study investigated the impact of oral health on neurological disorders using the Oral Health Impact Profile (OHIP). A total of 460 subjects completed the OHIP, including 141 control subjects who did not have any neurological conditions. Of the 319 subjects with a neurological diagnosis who were enrolled in the study, 31% had multiple sclerosis (MS), 34% had epilepsy, and 34% had other neurological conditions. Compared to the control group, mean age (p = .001), education (p = .003), and household income levels (p ≤ .001) were statistically significantly lower among subjects with epilepsy than in the other two groups. The majority of the study populations were Caucasian and the percentage was highest in those with MS (87%). Patients with any neurologic diagnosis had greater physical pain and disability than controls. Adjusting for demographic variables, the impact of physical disability was statistically significantly higher in patients with any neurological diagnosis (including MS and epilepsy) (OR = 4.49). In multinomial regression, the strongest association of physical disability impact was noted in patients with epilepsy (OR = 5.17). The physical disability domain of the OHIP is more commonly associated with a neurological diagnosis, including MS, and the association is strongest in patients with diagnosis of epilepsy.
Facial morphology and occlusion of a patient with fibrodysplasia ossificans progressiva (FOP): a case report
Authors: Susami Takafumi , Mori Yoshiyuki , Tamura Kazumi , Ohkubo Kazumi , Nagahama Kouhei , Takahashi Naoko , Uchino Natsuko , Uwatoko Kiwako , Haga Nobuhiko , Takato Tsuyoshi
Published: July 2012

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by postnatal heterotopic ossification (HO). When HO affects the masticatory muscles, mouth opening becomes restricted. This paper presents the changes in facial morphology and occlusion of a patient with FOP who was followed from the age of 8 to age 21. At the initial examination, he had a severely protruded maxilla and Angle Class II Division 1 malocclusion. His mouth opening was restricted (5.0 mm). He had a large overjet and this enabled him to clean his teeth and to eat. Orthodontic correction was not planned, and his facial growth was closely followed with attention to his oral hygiene. The maxillary protrusion and a low mandibular plane angle became more prominent as the patient aged. His mandible rotated in a counterclockwise direction. His molars had delayed eruption or were impacted and seven were extracted. His mouth opening increased slightly and his oral hygiene improved to excellent.
Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial with an open‐label, long‐term extension study
Authors: Seino Yutaka , Hiroi Shinzo , Hirayama Masashi , Kaku Kohei
Published: July 2012

Aims/Introduction

To evaluate the efficacy and safety of alogliptin added to treatment with glimepiride.

Materials and Methods

This multicenter, randomized, double‐blind, parallel‐group, 24‐week (12‐week observation and 12‐week treatment) study compared alogliptin 12.5 or 25 mg in combination with glimepiride (1–4 mg/day) vs placebo added to glimepiride monotherapy in Japanese patients with type 2 diabetes who had poor glycemic control despite treatment with diet and exercise plus a sulfonylurea. The primary end‐point was a change in glycated hemoglobin (HbA
1c) from baseline. A 40‐week open‐label extension study evaluated the long‐term safety and efficacy of the combination.

Results

Alogliptin 12.5 or 25 mg in combination with glimepiride significantly decreased HbA
1c compared with glimepiride monotherapy after 12 weeks' treatment (−0.59, −0.65 and 0.35%, respectively; P < 0.0001 for both combination groups vs glimepiride monotherapy). Alogliptin 12.5 and 25 mg combination therapy was also associated with significantly higher responder rates (HbA
1c <6.9%: 9.6% and 7.7%, HbA
1c <7.4%: 29.8% and 34.6%) compared with glimepiride monotherapy (HbA
1c <6.9%: 0%, HbA
1c <7.4%: 3.9%). The incidence of adverse events was comparable between glimepiride monotherapy and alogliptin combination treatment, with most reported adverse events being mild in severity. In the extension study, the incidence of adverse events was comparable between the combination groups, with the majority of adverse events being mild.

Conclusions

Once‐daily alogliptin was effective and generally well tolerated when given as add‐on therapy to glimepiride in Japanese patients with type 2 diabetes who had inadequate glycemic control on sulfonylurea plus lifestyle measures. Clinical benefits were maintained for 52 weeks. This trial was registered with ClinicalTrials.gov (double‐blind study no. NCT01318083; long‐term study no. NCT01318135).
Management of cases suffering from atypical myopathy: Interpretations of descriptive, epidemiological and pathophysiological findings. Part 1: First aid, cardiovascular, nutritional and digestive care
Authors: van Galen G. , Votion D.‐M.
Published: July 2012

Atypical myopathy is highly fatal, but about a quarter of affected horses survive. This highlights the need for provision of supportive treatment for these cases. This review is a practical guideline for equine practitioners and includes suggestions for close monitoring of involved organ systems and discusses options of supportive treatment based on current knowledge of the condition.
A pilot study on the corneal curvatures and ocular dimensions of horses less than one year of age
Authors: TOWNSEND W. M. , WASSERMAN N. , JACOBI S.
Published: July 2012

Intraocular lenses (IOLs) have been implanted in adult equine eyes after cataract surgery. Foals and weanlings comprise a large proportion of those horses undergoing cataract surgery. Due to potential differences in the size and corneal curvature of the juvenile eye, it is not currently known whether implantation of adult IOLs is appropriate in foals and weanlings. The objective of the study was to measure the anterior chamber depth (ACD), central lens thickness (CLT), vitreous chamber depth (VCD), axial globe length (AGL) and corneal curvature of horses less than one year of age. The axial dimensions from one eye of 10 foals were measured using simultaneous A and B scan ultrasonography. The corneal curvature from one eye of 7 weanlings was determined using a modified photokeratometer. Ultrasonography revealed a mean ACD of 4.94 mm, mean CLT of 9.38 mm, mean VCD of 18.96 mm and mean AGL of 33.32 mm for the foals. The mean corneal curvature was 15.4 diopters (D). The mean ACD, CLT, VCD and AGL of the foals were less than the measurements reported in the literature for adult horses. The mean corneal curvature was similar to the values reported by some authors for adult horses. Due to the differences in axial dimensions between adult and juvenile eyes, an IOL that corrects vision in an adult horse might not adequately correct vision in a horse less than one year of age.
Hepatoencephalopathy syndrome due to Cassia occidentalis (Leguminosae, Caesalpinioideae) seed ingestion in horses
Authors: OLIVEIRA‐FILHO J. P. , CAGNINI D. Q. , BADIAL P. R. , PESSOA M. A. , DEL PIERO F. , BORGES A. S.
Published: July 2012

Cassia occidentalis is a bush from the Leguminosae family, subfamily Caesalpinoideae, and is a toxic plant of veterinary interest due to the occasional contamination of animal rations. This report describes the clinical and histopathological findings of an outbreak of C. occidentalis poisoning in horses. Twenty mares were poisoned after consuming ground corn contaminated with 8% of C. occidentalis seeds. Of the 20 animals affected, 12 died: 8 mares were found dead, 2 died 6 h after the onset of clinical signs compatible with hepatic encephalopathy and the 2 other animals were subjected to euthanasia 12 h after the onset of the clinical signs. The remaining 8 mares presented with mild depression and decreased appetite, but improved with treatment and no clinical sequelae were observed. In 6 animals that underwent a necropsy, an enhanced hepatic lobular pattern was noted and within the large intestine, a large number of seeds were consistently observed. Hepatocellular pericentrolobular necrosis and cerebral oedema were the main histological findings. In one mare, there was mild multifocal semimembranosus rhabdomyocytic necrosis and haemorrhage. Seeds collected from intestinal contents and sifted from the culpable feedstuff were planted. Examination of the leaves, flowers, fruits and seeds of the resultant plants identified C. occidentalis. Horses poisoned by C. occidentalis seeds demonstrate clinical signs associated with hepatoencephalopathy and frequently die suddenly. Lesions primarily involve the liver and secondarily, the central nervous system. Cassia occidentalis poisoning should be considered a differential diagnosis in horses with hepatoencephalopathy and special caution should be taken with horse rations to avoid contamination with seeds of this toxic plant.
A preliminary study into the correlation of stiffness of the laminar junction of the equine hoof with the length density of its secondary lamellae
Authors: KOCHOVÁ P. , WITTER K. , CIMRMAN R. , MEZEROVÁ J. , TONAR Z.
Published: July 2012

Reason for performing study: The relationship between mechanical behaviour and microscopic structure of the laminar junction of equine hooves under testing conditions requires elucidation.

Objectives: To determine mechanical parameters and 2D length density of profiles of secondary lamellae of the laminar junction in the dermal region and to assess possible correlations.

Methods: Specimens (25 samples in total) of the laminar junction were taken from front, quarter and heel parts from 3 equine hooves and exposed to a uniaxial tensile test until rupture to obtain Young's moduli of elasticity, ultimate stress and strain. Neighbouring specimens to those used for the biomechanical experiment were processed histologically to assess the length density of laminar junction basement membrane using stereological grids.

Results: The estimated median (interquartile range) length density of the laminar junction basement membrane was 0.024 (0.020–0.027)/µm. Young's modulus of elasticity was 0.15 (0.11–0.35) MPa in the small deformation region, and 7.58 (6.14–8.68) MPa in the linear region was. The ultimate stress was 1.67 (1.41–2.67) MPa, and the ultimate strain was 0.50 (0.38–0.70). The Young's modulus of elasticity in the region of small deformations has a moderate correlation with the length density of the laminar junction basement membrane.

Conclusions: As with most soft biological tissues, the laminar junction has a nonlinear mechanical behaviour. Within the range of small deformations, which correspond to physiological loading of the laminar junction, a higher length density of the laminar junction basement membrane is correlated with a higher resistance of the laminar junction against high stresses transmitted from the distal phalanx to the hoof wall.

Potential relevance: The condition of the laminar junction apparatus may be easily quantified as the length density of profiles of secondary dermal lamellae. This quantification provides a simple tool that could be used for comparing the proneness of the various parts of the laminar junction to initial stages of laminitis.
Occurrence of Immunoglobulin M Antibodies against Several Bacterial and Viral Pathogens in Acute Hantavirus Infection
Authors: Wellinghausen Nele , Goetz Andrea , Weber Ursula
Published: July 2012

Elevated levels of immunoglobulin M antibodies against various pathogens, most frequently Epstein-Barr-virus and
Coxiella burnetii
, were detected by immunoassay in 15 of 48 patients (31.3%) with acute Puumala virus infections. Although the mechanisms leading to this IgM response are not clear yet, polyspecific immunoglobulin M antibodies have to be taken into account to avoid misinterpretation of serological results in acute hantavirus infection.
Enhanced Priming of Adaptive Immunity by Mycobacterium smegmatis Mutants with High-Level Protein Secretion
Authors: Taylor Natalie , Bahunde Faith , Thompson Afton , Yu Jae-Sung , Jacobs William R. , Letvin Norm L. , Haynes Barton F. , Lee Sunhee
Published: July 2012

Mycobacteria have features that make them attractive as potential vaccine vectors. The nonpathogenic and rapidly growing
Mycobacterium smegmatis
can express both
Mycobacterium tuberculosis
antigens and heterologous antigens from other pathogens, and it has been used as a viable vector for the development of live vaccines. In order to further improve antigen-specific immunogenicity of
M. smegmatis
, we screened a random transposon mutant library for mutants displaying enhanced efficiency of protein secretion (“high secretors”) and isolated 61 mutants showing enhanced endogenic and transgenic protein secretion. Sequence analysis identified a total of 54 genes involved in optimal secretion of insert proteins, as well as multiple independent transposon insertions localized within the same genomic loci and operons. The majority of transposon insertions occurred in genes that have no known protein secretion function. These transposon mutants were shown to prime antigen-specific CD8
+
T cell responses better than the parental strain. Specifically, upon introducing the simian immunodeficiency virus (SIV)
gag
gene into these transposon mutant strains, we observed that they primed SIV Gag-specific CD8
+
T cell responses significantly better than the control prime immunization in a heterologous prime/boost regimen. Our results reveal a dependence on bacterial secretion of mycobacterial and foreign antigens for the induction of antigen-specific CD8
+
T cells
in vivo
. The data also suggest that these
M. smegmatis
transposon mutants could be used as novel live attenuated vaccine strains to express foreign antigens, such as those of human immunodeficiency virus type 1 (HIV-1), and induce strong antigen-specific T cell responses.
IgG Antibody Response to Toxins A and B in Patients with Clostridium difficile Infection
Authors: Wullt M. , Norén T. , Ljungh Å. , Åkerlund T.
Published: July 2012

IgG antibodies against
Clostridium difficile
toxins A and B were followed in controls and in patients with an initial
C. difficile
infection (CDI). Of the 50 CDI patients, 38 were cured and 12 developed recurrence. Compared to controls, patients had significantly lower anti-toxin A and B IgGs at inclusion, but the subsequent levels rose slightly regardless of clinical outcome. The results imply that the general serum reactivity against toxins A and B in the population reduces the risk of CDI, which suggests implications for vaccine strategies.
Two-Component Cluster Analysis of a Large Serodiagnostic Database for Specificity of Increases of IgG Antibodies against Pertussis Toxin in Paired Serum Samples and of Absolute Values in Single Serum Samples
Authors: de Greeff Sabine C. , Teunis Peter , de Melker Hester E. , Mooi Frits R. , Notermans Daan W. , Elvers Bert , Schellekens Joop F. P.
Published: July 2012

Measuring IgG antibodies against pertussis toxin (IgG-Ptx) with an enzyme-linked immunosorbent assay (ELISA) can be used to diagnose pertussis infection; however, the cutoff points are not unanimously defined. To determine the diagnostic specificity of increases of IgG-Ptx in paired sera and of absolute values in single serum samples, we applied a two-component cluster analysis to serum samples of patients suspected for pertussis, whose sera had been submitted to a routine diagnostic laboratory between 2003 and 2009, and had been assayed with an in-house IgG-Ptx ELISA calibrated with the international FDA lot 3 IgG-Ptx reference serum. Children eligible for the acellular pertussis vaccination were excluded to avoid interference from a vaccine-induced IgG-Ptx rise. Binary distribution mixtures were fitted to the data. Receiver operating characteristic (ROC) curves were calculated for absolute values in single samples (
n
= 14,452) and increases in paired samples (
n
= 2,455). For both parameters, two subpopulations could be identified: a population with high reactivity (persons with pertussis infection) and a population with low reactivity (persons without pertussis infection). For absolute values in single samples, the area under the curve (AUC) of the ROC curve was 0.993 and the optimum cutoff (with the highest cumulative value of specificity plus sensitivity) was 67.7 IU/ml (95% confidence interval, 63.9 to 74.1; sensitivity, 96.4%; specificity, 95.7%). A previously determined diagnostic cutoff of 125 IU/ml was associated with a sensitivity of 88.1% and a specificity of 98.8%. For increases in paired sera, the AUC was 0.999 and the optimum cutoff was 3.1-fold (95% CI, 2.8 to 3.4; sensitivity, 99.6%; specificity, 99.2%). Given the methodology of this study, estimates of sensitivity probably are overrated (because pertussis patients without IgG-Ptx response are not detected), but estimates of specificities can be considered very accurate.
Memory CD8+T Cells Are Sufficient To Alleviate Impaired Host Resistance to Influenza A Virus Infection Caused by Neonatal Oxygen Supplementation
Authors: Giannandrea Matthew , Yee Min , O'Reilly Michael A. , Lawrence B. Paige
Published: July 2012

Supplemental oxygen administered to preterm infants is an important clinical intervention, but it is associated with life-long changes in lung development and increased sensitivity to respiratory viral infections. The precise immunological changes caused by neonatal oxygen treatment remain poorly understood. We previously reported that adult mice exposed to supplemental oxygen as neonates display persistent pulmonary inflammation and enhanced mortality after a sublethal influenza A virus infection. These changes suggest that neonatal hyperoxia impairs the cytotoxic CD8+T cell response required to clear the virus. In this study, we show that although host resistance to several different strains of influenza A virus is reduced by neonatal hyperoxia, this treatment does not impair viral clearance, nor does it alter the magnitude of the virus-specific CD8+T cell response to primary infection. Moreover, memory T cells are sufficient to ameliorate the increased morbidity and mortality and alleviate the excessive lung damage observed in mice exposed to high oxygen levels as neonates, and we attribute this sufficiency principally to virus-specific memory CD8+T cells. Thus, we show that neonatal hyperoxia reduces host resistance to influenza virus infection without diminishing the function of cytotoxic T lymphocytes or the generation of virus-specific memory T cells and that CD8+memory T cells are sufficient to provide protection from negative consequences of this important life-saving intervention. Our findings suggest that vaccines that generate robust T cell memory may be efficacious at reducing the increased sensitivity to respiratory viral infections in people born prematurely.
Detection of Antibodies against Orientia tsutsugamushi Sca Proteins in Scrub Typhus Patients and Genetic Variation of
sca
Genes of Different Strains
Authors: Ha Na-Young , Kim Yuri , Choi Ji-Hye , Choi Myung-Sik , Kim Ik-Sang , Kim Yeon-Sook , Cho Nam-Hyuk
Published: July 2012

Scrub typhus, caused by
Orientia tsutsugamushi
infection, is one of the main causes of acute febrile illness in the Asian-Pacific region. Although early diagnosis and immediate antibiotic treatment are critical for reducing disease severity and mortality, current diagnostic methods using serological and molecular approaches have some limitations in sensitivity and applicability in clinical laboratories. In this study, we identified and characterized
O. tsutsugamushi
surface cell antigen (
sca
) family genes encoding autotransporter proteins in order to test them as novel diagnostic targets. We evaluated antibody responses against the Sca proteins in scrub typhus patient sera and examined the genetic diversity of these genes in different strains after PCR amplification. Specific antibody responses against ScaA and ScaC were observed in patients with high indirect immunofluorescence assay titers (≥1:640), whereas specific responses against ScaB and ScaE were relatively low. Genetic analysis using genomic DNAs revealed the
sca
genes to be quite variable among the different strains. In contrast to
scaA
,
scaC
, and
scaD
, which were detected in all of the tested strains,
scaB
and
scaE
were amplified differentially from the different strains, suggesting a differential presence of the genes in the genomes. Among the members of the gene family, the sequence of
scaC
is the most highly conserved between the different strains, and the size of
scaD
is the most variable due to the presence of different numbers of internal repeat sequences. These results suggest that the
sca
genes of
O. tsutsugamushi
may be valuable targets for use in combination with classical assay methods for scrub typhus diagnosis.
Nocardia neocaldoniensis as a Cause of Skin and Soft Tissue Infection
Authors: McGhie Travea , Fader Robert , Carpenter John , Brown-Elliott Barbara A. , Vasireddy Ravikiran , Wallace Richard J.
Published: July 2012

Nocardia neocaledoniensis
was introduced as a new environmental species of
Nocardia
in 2004. We present the first case of human skin and soft tissue infection caused by this species in a patient with rheumatoid arthritis receiving prednisone and methotrexate therapy.
Barcode Identifiers as a Practical Tool for Reliable Species Assignment of Medically Important Black Yeast Species
Authors: Heinrichs Guido , de Hoog G. Sybren , Haase Gerhard
Published: July 2012

Herpotrichiellaceous black yeasts and relatives comprise severe pathogens flanked by nonpathogenic environmental siblings. Reliable identification by conventional methods is notoriously difficult. Molecular identification is hampered by the sequence variability in the internal transcribed spacer (ITS) domain caused by difficult-to-sequence homopolymeric regions and by poor taxonomic attribution of sequences deposited in GenBank. Here, we present a potential solution using short barcode identifiers (27 to 50 bp) based on ITS2 ribosomal DNA (rDNA), which allows unambiguous definition of species-specific fragments. Starting from proven sequences of ex-type and authentic strains, we were able to describe 103 identifiers. Multiple BLAST searches of these proposed barcode identifiers in GenBank revealed uniqueness for 100 taxonomic entities, whereas the three remaining identifiers each matched with two entities, but the species of these identifiers could easily be discriminated by differences in the remaining ITS regions. Using the proposed barcode identifiers, a 4.1-fold increase of 100% matches in GenBank was achieved in comparison to the classical approach using the complete ITS sequences. The proposed barcode identifiers will be made accessible for the diagnostic laboratory in a permanently updated online database, thereby providing a highly practical, reliable, and cost-effective tool for identification of clinically important black yeasts and relatives.
Investigation of False-Positive Results Given by the QuantiFERON-TB Gold In-Tube Assay
Authors: Slater Madeline , Parsonnet Julie , Banaei Niaz
Published: July 2012

We investigated a sudden increase in the rate of positive QuantiFERON-TB Gold In-Tube results from 10% to 31% at a U.S. academic institution. Direct comparison of the TB antigen tubes with tubes from a different lot number identified that a potential problem with the TB antigen vials in a certain tube lot was the likely cause of the elevated positive rate. The underlying defect remains unknown. This finding warrants refinement of quality control programs by the manufacturer and users.
A Multilocus Sequence Typing Scheme Implies Population Structure and Reveals Several Putative Novel Achromobacter Species
Authors: Spilker Theodore , Vandamme Peter , LiPuma John J.
Published: July 2012

The genus
Achromobacter
currently is comprised of seven species, including
Achromobacter xylosoxidans
, an opportunistic and nosocomial pathogen that displays broad-spectrum antimicrobial resistance and is recognized as causing chronic respiratory tract infection in persons with cystic fibrosis (CF). To enable strain typing for global epidemiologic investigations, to clarify the taxonomy of “
Achromobacter
-like” strains, and to elucidate the population structure of this genus, we developed a genus-level multilocus sequence typing (MLST) scheme. We employed
in silico
analyses of whole-genome sequences of several phylogenetically related genera, including
Bordetella
,
Burkholderia
,
Cupriavidus
,
Herminiimonas
,
Janthinobacterium
,
Methylibium
, and
Ralstonia
, for selecting loci and designing PCR primers. Using this MLST scheme, we analyzed 107 genetically diverse
Achromobacter
isolates cultured from biologic specimens from CF and non-CF patients, 1 isolate recovered from sludge, and an additional 39 strains obtained from culture collections. Sequence data from these 147 strains, plus three recently genome-sequenced
Achromobacter
strains, were assigned to 129 sequence types based on seven loci. Calculation of the nucleotide divergence of concatenated locus sequences within and between MLST clusters confirmed the seven previously named
Achromobacter
species and revealed 14 additional genogroups. Indices of association showed significant linkage disequilibrium in all of the species/genogroups able to be tested, indicating that each group has a clonal population structure. No clear segregation of species/genogroups between CF and non-CF sources was found.
Diversity of the Cronobacter Genus as Revealed by Multilocus Sequence Typing
Authors: Joseph S. , Sonbol H. , Hariri S. , Desai P. , McClelland M. , Forsythe S. J.
Published: July 2012

Cronobacter
(previously known as
Enterobacter sakazakii
) is a diverse bacterial genus consisting of seven species:
C. sakazakii
,
C. malonaticus
,
C. turicensis
,
C. universalis
,
C. muytjensii
,
C. dublinensis
, and
C. condimenti
. In this study, we have used a multilocus sequence typing (MLST) approach employing the alleles of 7 genes (
atpD
,
fusA
,
glnS
,
gltB
,
gyrB
,
infB
, and
ppsA
; total length, 3,036 bp) to investigate the phylogenetic relationship of 325
Cronobacter
species isolates. Strains were chosen on the basis of their species, geographic and temporal distribution, source, and clinical outcome. The earliest strain was isolated from milk powder in 1950, and the earliest clinical strain was isolated in 1953. The existence of seven species was supported by MLST. Intraspecific variation ranged from low diversity in
C. sakazakii
to extensive diversity within some species, such as
C. muytjensii
and
C. dublinensis
, including evidence of gene conversion between species. The predominant species from clinical sources was found to be
C. sakazakii. C. sakazakii
sequence type 4 (ST4) was the predominant sequence type of cerebral spinal fluid isolates from cases of meningitis.
Unrecognized Norovirus Infections in Health Care Institutions and Their Clinical Impact
Authors: Beersma Matthias F. C. , Sukhrie Faizel H. A. , Bogerman Jolanda , Verhoef Linda , Mde Melo Mariana , Vonk Alieke G. , Koopmans Marion
Published: July 2012

Noroviruses (NoVs) have emerged as the leading cause of acute viral gastroenteritis (GE) in humans. Although diagnostic facilities have greatly improved, significant underdiagnosis of NoV in hospitals may still occur, thereby increasing clinical burden and nosocomial spread. We evaluated the underdiagnosis of sporadic NoV infections in a tertiary care hospital and estimated its clinical impact. From December 2008 until July 2009, fecal samples specifically referred for bacterial but not viral examination were retrospectively tested for NoV by real-time PCR. The clinical and virological data from patients with undiagnosed NoV infection (missed patients) were evaluated and compared with those from patients with recognized NoV. During the study period, 45 patients with undiagnosed NoV were detected, whereas 50 patients were regularly diagnosed. The missed NoV cases were more frequently adults than children (80% versus 46%;
P
< 0.001). The viral load levels did not differ between the diagnosed and missed patients, but missed patients more frequently presented without diarrhea (20% versus 4%;
P
< 0.07). The newly admitted missed NoV cases with GE underwent more diagnostic imaging (24% versus 4%;
P
< 0.01) and tended to be hospitalized longer. When missed-NoV patients were included, the number of nosocomial clusters doubled and missed patients were index cases in 5 of the 6 clusters. These data indicate that NoV infections are frequently missed despite routine laboratory testing and demonstrate that underdiagnosis of NoV patients is associated with costly abdominal imaging and nosocomial clustering. Awareness of NoV infection in adult patients and education about the importance of viral GE should be increased.
Detection of Carbapenemases in Enterobacteriaceae by a Commercial Multiplex PCR
Authors: Kaase Martin , Szabados Florian , Wassill Lars , Gatermann Sören G.
Published: July 2012

A commercial multiplex PCR (hyplex SuperBug ID) was tested with a collection of 132 clinical
Enterobacteriaceae
strains producing different carbapenemases. The sensitivity for the detection of KPC-, VIM-, NDM-, and OXA-48-encoding genes was 100%, whereas two IMP variants were missed.
Hepatitis B Virus DNA Splicing in Lebanese Blood Donors and Genotype A to E Strains: Implications for Hepatitis B Virus DNA Quantification and Infectivity
Authors: El Chaar Mira , El Jisr Tamima , Allain Jean-Pierre
Published: July 2012

Hepatitis B virus (HBV) is one of the major viruses transmissible by blood that causes chronic infection in immunocompromised individuals. The study of 61 HBV carrier blood donors from Lebanon revealed multiple patterns of spliced HBV DNA. HBV DNA splicing was examined and quantified in samples of five genotypes and in seroconversion panels. The Lebanese sample median viral load was 1.5 ×102IU/ml. All strains were genotype D, serotype ayw; 35 clustered as subgenotype D1 and 7 clustered as subgenotype D2. Three splice variants (SP1, SP1A, and Pol/S) were observed in 12 high-viral-load samples. Twenty samples of each genotype, A to E, were tested for the presence of HBV spliced DNA and SP1-specific splice variant. An unspliced HBV genome was dominant, but 100% of strains with a viral load of ≥105copies/ml contained various proportions of spliced DNA. SP1 was detected in 56/100 (56%) samples in levels that correlated with the overall viral load. HBV DNA quantification with S (unspliced) and X (total DNA) regions provided different levels of viral load, with the difference corresponding to spliced DNA. During the highly infectious window period, the SP1 variant became detectable shortly after the hepatitis B surface antigen (HBsAg), suggesting a correlation between the initiation of splicing and the production of detectable levels of HBsAg. The quantification of HBV DNA with primers located outside and inside the spliced region might provide different estimations of viral load and differentiate between infectious and defective viral genomes. The role of splicing neoproteins in HBV replication and interaction with the host remains to be determined.
Genotyping of 353 Staphylococcus aureus Bloodstream Isolates Collected between 2004 and 2009 at a Norwegian University Hospital and Potential Associations with Clinical Parameters
Authors: Aamot Hege Vangstein , Blomfeldt Anita , Eskesen Arne N.
Published: July 2012

We analyzed 353
Staphylococcus aureus
bloodstream isolates from 2004 to 2009 to identify dominant genotypes, changes over time, and associations between genotype, phenotype, and clinical parameters. The isolates were genotyped with regard to
spa
type and presence of Panton-Valentine leukocidin and toxic shock syndrome toxin 1-encoding genes. A high level of genetic diversity was detected. All but three isolates were methicillin sensitive. Interestingly,
spa
clonal complex 021 showed a weak association with higher all-cause hospital mortality.
Comparison of a High-Resolution Melting Assay to Next-Generation Sequencing for Analysis of HIV Diversity
Authors: Cousins Matthew M. , Ou San-San , Wawer Maria J. , Munshaw Supriya , Swan David , Magaret Craig A. , Mullis Caroline E. , Serwadda David , Porcella Stephen F. , Gray Ronald H. , Quinn Thomas C. , Donnell Deborah , Eshleman Susan H. , Redd Andrew D.
Published: July 2012

Next-generation sequencing (NGS) has recently been used for analysis of HIV diversity, but this method is labor-intensive, costly, and requires complex protocols for data analysis. We compared diversity measures obtained using NGS data to those obtained using a diversity assay based on high-resolution melting (HRM) of DNA duplexes. The HRM diversity assay provides a single numeric score that reflects the level of diversity in the region analyzed. HIV
gag
and
env
from individuals in Rakai, Uganda, were analyzed in a previous study using NGS (
n
= 220 samples from 110 individuals). Three sequence-based diversity measures were calculated from the NGS sequence data (percent diversity, percent complexity, and Shannon entropy). The amplicon pools used for NGS were analyzed with the HRM diversity assay. HRM scores were significantly associated with sequence-based measures of HIV diversity for both
gag
and
env
(
P
< 0.001 for all measures). The level of diversity measured by the HRM diversity assay and NGS increased over time in both regions analyzed (
P
< 0.001 for all measures except for percent complexity in
gag
), and similar amounts of diversification were observed with both methods (
P
< 0.001 for all measures except for percent complexity in
gag
). Diversity measures obtained using the HRM diversity assay were significantly associated with those from NGS, and similar increases in diversity over time were detected by both methods. The HRM diversity assay is faster and less expensive than NGS, facilitating rapid analysis of large studies of HIV diversity and evolution.
A Member of a New Picornaviridae Genus Is Shed in Pig Feces
Authors: Sauvage Virginie , Ar Gouilh Meriadeg , Cheval Justine , Muth Erika , Pariente Kevin , Burguiere Ana , Caro Valérie , Manuguerra Jean-Claude , Eloit Marc
Published: July 2012

During a study of the fecal microbiomes from two healthy piglets using high-throughput sequencing (HTS), we identified a viral genome containing an open reading frame encoding a predicted polyprotein of 2,133 amino acids. This novel viral genome displayed the typical organization of picornaviruses, containing three structural proteins (VP0, VP3, and VP1), followed by seven nonstructural proteins (2A, 2B, 2C, 3A, 3B, 3C
pro
, and 3D
pol
). Given its particular relationship with
Parechovirus
, we propose to name it “Pasivirus” for
Pa
recho
si
ster clade virus, with “Swine pasivirus 1” (SPaV1) as the type species. Fecal samples collected at an industrial farm from healthy sows and piglets from the same herd (25 and 75, respectively) with ages ranging from 4 to 28 weeks were analyzed for the presence of SPaV1 by one-step reverse transcription (RT)-PCR targeting a 3D region of 151 bp. SPaV1 was detected in fecal samples from 51/75 healthy piglets (68% of the animals) and in none of the 25 fecal samples from healthy sows, indicating that SPaV1 circulates through enteric infection of healthy piglets. We propose that SPaV1 represents the first member of a novel
Picornaviridae
genus related to parechoviruses.
The NS1 Protein of Influenza A Virus Blocks RIG-I-Mediated Activation of the Noncanonical NF-κB Pathway and p52/RelB-Dependent Gene Expression in Lung Epithelial Cells
Authors: Rückle Andrea , Haasbach Emanuel , Julkunen Ilkka , Planz Oliver , Ehrhardt Christina , Ludwig Stephan
Published: July 2012

Influenza A virus (IAV) infection of epithelial cells activates NF-κB transcription factors via the canonical NF-κB signaling pathway, which modulates both the antiviral immune response and viral replication. Since almost nothing is known so far about a function of noncanonical NF-κB signaling after IAV infection, we tested infected cells for activation of p52 and RelB. We show that the viral NS1 protein strongly inhibits RIG-I-mediated noncanonical NF-κB activation and expression of the noncanonical target gene CCL19.
CCR5 Mutations Distinguish N-Terminal Modifications of RANTES (CCL5) with Agonist versus Antagonist Activity
Authors: Choi Won-Tak , Nedellec Rebecca , Coetzer Mia , Colin Philippe , Lagane Bernard , Offord Robin E. , Hartley Oliver , Mosier Donald E.
Published: July 2012

CCR5 is the major HIV-1 entry coreceptor. RANTES/CCL5 analogs are more potent inhibitors of infection than native chemokines; one class activates and internalizes CCR5, one neither activates nor internalizes, and a third partially internalizes without activation. Here we show that mutations in CCR5 transmembrane domains differentially impact the activity of these three inhibitor classes, suggesting that the transmembrane region of CCR5, a key interaction site for inhibitors, is a sensitive molecular switch, modulating receptor activity.