bluuebunny/crossref_metadata_2025 huggingface dataset:
Weight, height and eruption times of permanent teeth of children aged 4–15 years in Kampala, Uganda
Authors: Kutesa Annet , Nkamba Eriab Moses , Muwazi Louis , Buwembo William , Rwenyonyi Charles Mugisha
Published: March 2013

Background

Tooth eruption is a continuous biological process by which developing teeth emerge through the jaws and the overlying mucosa to enter into the oral cavity. Tooth eruption time and sequence are important factors in dental treatment planning, particularly in orthodontics, but also in forensic dentistry to estimate age of a child. Tooth eruption time is influenced by many factors. In this study we set out to determine the timing of eruption of permanent teeth and assess its association with the height and weight of school children aged 4–15 years in Kampala, Uganda.

Methods

This was a cross sectional study comprising of 1041 healthy Ugandan children: boys/girls (520/521) who were consecutively selected from two primary schools in Kampala. The children were clinically assessed for tooth emergency through the oral mucosa as well as measuring their weight and height. The mean and standard deviation of tooth eruption time was estimated for boys and girls. Bivariate analysis was used to assess any significant association between tooth eruption time and demographic variables. Pearson and partial correlation analyses were used to assess any significant association between the tooth eruption time and anthropometric measurements of the children.

Results

Generally, the mean eruption times for girls were lower compared to boys except for three teeth (#25, #32 and #42) which erupted earlier in boys. The average difference in mean eruption times of all teeth between boys and girls was found to be 0.8 (range, 0–1.5) years. In partial correlation analysis, mean tooth eruption times were positively, but not significantly associated with height while controlling for weight except for the mandibular left central incisor (#31). On the other hand, in partial correlation analysis, mean tooth eruption times were positively associated with weight while controlling for height except for tooth #11, #16, #26 and #41. The weight of the child was significantly correlated with mean eruption times in 50% of the teeth.

Conclusion

In the present study, the mean tooth eruption times for girls were lower compared to boys except for three teeth (#25, #32 and #42). The height of the child did not show any significant influence on the tooth eruption times while the influence of weight on tooth eruption times was non-conclusive.
Assessing the outcomes of implantable cardioverter defibrillator treatment in a real world setting: results from hospital record data
Authors: Ghislandi Simone , Torbica Aleksandra , Boriani Giuseppe
Published: March 2013

Background

A plethora of clinical studies have assessed the benefits of implantable cardioverter defibrillators (ICDs) and supported their use in clinical practice. However, evidence on the safety and efficacy of ICDs appears insufficient to support expansion of their use in clinical practice, and more information on their impact in real life settings is warranted. This paper aims to investigate the impact of ICDs using a large administrative dataset reflecting actual clinical practice.

Methods

Data were obtained from the hospital discharge database of the Friuli Venezia Giulia region in Italy containing patient-level information on 169,488 cases. Data on mortality outside hospital were obtained from regional sources. Exact matching method was used to estimate the outcomes associated with ICDs: mortality, length of stay, re-hospitalization and regional expenditure. The method was applied in two steps. First, patients with ICDs were matched with those without using the following: age class (by 5 years), gender, year of admission, type of admission (day hospital vs. ordinary) and primary diagnosis. In the second step, matching included also Charlson Comorbidities Index. Exact matching average treatment effect on the treated (ATT) was used as a main measure of impact.

Results

Compared with matched controls, treatment with ICDs was associated with lower mortality (absolute risk reduction 10.6% at 1 year and 8.3% at 2 and 8.4% at 3 years, p < 0.001 and hazard ratio 0.80, p < 0.001), greater regional expenditure at index hospitalization (ATT: €9459.64, p < 0.001) and during follow up (ATT: €1707.29, p < 0.001) and higher re-hospitalization rate (ATT: 0.53, p < 0.001). No significant difference was found for length of stay (9.07 vs. 8.86 days). The results were maintained after more restrictive matching was applied.

Conclusions

Assessing the impact of innovative, expensive medical technologies on the basis of real world data is warranted, especially when there are barriers to implementation. Hospital administrative datasets can be of great value when a technology such as the ICD is implemented in a relatively small sample of patients, to allow use of exact matching techniques.
Sex-specific induction of CYP6 cytochrome P450 genes in cadmium and lead tolerant Anopheles gambiae
Authors: Musasia Fauzia K , Isaac Alfred O , Masiga Daniel K , Omedo Irene A , Mwakubambanya Ramadhan , Ochieng Richard , Mireji Paul O
Published: March 2013

Background

Anopheles gambiae, one of the main Afro-tropical mosquito vector of malaria, has adapted to heavy metals in its natural habitat, and developed resistance to most conventional insecticides. Investigations were conducted to establish an association between tolerance to cadmium or lead-heavy metals, and expression of specific genes for cytochrome p450 enzymes associated with pyrethroid resistance in the mosquito.

Methods

Juvenile aquatic stages of the mosquito were selected for tolerance to cadmiun or lead through chronic exposure of the stages to maximum acceptable toxicant concentrations (MATCs) of the metals. Using real-time quantitative polymerase chain reaction (qPCR), three replicates each of male or female cadmium or lead-tolerant individuals and relevant controls were separately screened for expression of CYP6M2, CYP6P3 and CYP6Z1 genes. The variance in expression levels of the genes amongst the treatments was compared by ANOVA statistical tool.

Results

Expressions of all the genes were significantly lower (P <0.05) in females than in males. Within gender, there 1.3 - 2.3 or 3.1-4.2-fold reduction in expression of the genes in cadmium or lead selected than respective control populations. Expression of all the classes of gene was elevated in cadmium selected female populations relative to their respective controls.

Conclusion

These findings suggest that tolerance to cadmium or lead in the mosquito can influence response in cytochrome p450 genes associated with metabolism of pyrethroids in the mosquito in a sex-specific manner. This can, in turn, affect sensitivity of the mosquito to pyrethroids and other xenobiotics associated with these genes, with potential implications in mosquito vector control operations.
Malnutrition, a new inducer for arterial calcification in hemodialysis patients?
Authors: Zhang Kun , Cheng Gang , Cai Xue , Chen Jie , Jiang Ying , Wang Tong , Wang Jingfeng , Huang Hui
Published: March 2013

Background

Arterial calcification is a significant cardiovascular risk factor in hemodialysis patients. A series of factors are involved in the process of arterial calcification; however, the relationship between malnutrition and arterial calcification is still unclear.

Methods

68 hemodialysis patients were enrolled in this study. Nutrition status was evaluated using modified quantitative subjective global assessment (MQSGA). Related serum biochemical parameters were measured. And the radial artery samples were collected during the arteriovenous fistula surgeries. Hematoxylin/eosin stain was used to observe the arterial structures while Alizarin red stain to observe calcified depositions and classify calcified degree. The expressions of bone morphogenetic protein 2 (BMP2) and matrix Gla protein (MGP) were detected by immunohistochemistry and western blot methods.

Results

66.18% hemodialysis patients were malnutrition. In hemodialysis patients, the calcified depositions were mainly located in the medial layer of the radial arteries and the expressions of BMP2 and MGP were both increased in the calcified areas. The levels of serum albumin were negatively associated with calcification score and the expressions of BMP2 and MGP. While MQSGA score, serum phosphorus and calcium × phosphorus product showed positive relationships with calcification score and the expressions of BMP2 and MGP.

Conclusions

Malnutrition is prevalent in hemodialysis patients and is associated with arterial calcification and the expressions of BMP2 and MGP in calcified radial arteries. Malnutrition may be a new inducer candidate for arterial calcification in hemodialysis patients.
Association of estrogen receptor alpha gene polymorphism with age at onset, general psychopathology symptoms, and therapeutic effect of schizophrenia
Authors: Wang Shuai , Li Wenqiang , Zhao Jingyuan , Zhang Hongxing , Yang Yongfeng , Wang Xiujuan , Yang Ge , Lv Luxian
Published: March 2013

Background

Estrogen is believed to play an important role in the central nervous system (CNS) and exert a protective role against schizophrenia. Estrogen receptor alpha (ESRα) mediates the biological action of estrogen. Rs2234693 and rs9340799, single nucleotide polymorphisms of ESRα, may be related to many psychiatric disorders, while their association with schizophrenia has not been clarified.

Methods

Genotypes rs2234693 and rs9340799 were detected in 303 schizophrenic patients and 292 healthy controls in a Chinese population. The positive and negative syndrome scale (PANSS) was used to estimate symptoms and therapeutic effects. The association of these polymorphisms with schizophrenia and clinical characteristics was analyzed by the chi-square test, analysis of variance, and others.

Results

The distribution of genotypes and allele frequencies of rs2234693 and rs9340799 exhibited no significant differences between patients and controls, while haplotypes consisting of these polymorphisms had significant differences. For 2234693, T-allele carriers had an earlier age at onset. CC-homozygote carriers had a higher general psychopathology score and its percentage reduction in male and paranoid patients, respectively. CC-homozygote carriers had a higher tension (G4) and poor impulse control (G14) score, mainly in paranoid patients. Furthermore, patients with the CC homozygote had higher reductions of G4 and G14 scores when treated by aripirazole and risperidone, respectively.

Conclusions

Haplotypes consisting of these two polymorphisms in ESRα may be strongly associated with schizophrenia. The rs2234693 was related to age at onset, general psychopathology, G4 and G14 symptoms, even the therapeutic effect in different groups.
Profound hyperacute cardiac allograft rejection rescue with biventricular mechanical circulatory support and plasmapheresis, intravenous immunoglobulin, and rituximab therapy
Authors: Kaczorowski David J , Datta Jashodeep , Kamoun Malek , Dries Daniel L , Woo Y Joseph
Published: March 2013

Hyperacute rejection is a rare but potentially catastrophic complication after cardiac transplantation. We describe an unusual case of hyperacute rejection due to preformed anti-donor antibodies despite a negative preoperative panel-reactive antibody (PRA) screen. An excellent outcome was achieved in this case and our strategy involving the use of CentriMag ventricular assist devices (VADs) for biventricular support during treatment with rituximab, intravenous immunoglobulin (IVIG), and plasmapheresis is illustrated.
Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter Syndrome)
Authors: Sohn Young Bae , Cho Sung Yoon , Park Sung Won , Kim Su Jin , Ko Ah-Ra , Kwon Eun-Kyung , Han Sun Ju , Jin Dong-Kyu
Published: March 2013

Background

Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by the deficiency of iduronate-2-sulfatase (IDS). In affected patients, glycosaminoglycan (GAG) accumulates in the lysosomes of many organs and tissues contributing to the pathology associated with MPS II. The objective of this phase I/II clinical study was to evaluate the efficacy and safety of recombinant human iduronate-2-sulfatase (idursulfase beta, Hunterase®) in the treatment of MPS II.

Methods

Thirty-one MPS II patients between 6 and 35 years of age were enrolled in a randomized, single-blinded, active comparator-controlled phase I/II trial for 24 weeks. Patients were randomized to active comparator infusions (N=11), 0.5 mg/kg idursulfase beta infusions (N=10), or 1.0 mg/kg idursulfase beta infusions (N=10). The primary efficacy variable was the level of urinary GAG excretion. The secondary variables were changes in the distance walked in 6 minutes (6-minute walk test, 6MWT), echocardiographic findings, pulmonary function tests, and joint mobility.

Results

Patients in all three groups exhibited reduction in urine GAG and this reduced GAG level was maintained for 24 weeks. Urine GAG was also significantly reduced in the 0.5 mg/kg and 1.0 mg/kg idursulfase beta groups when compared to the active comparator group (P = 0.043, 0.002, respectively). Changes in 6MWT were significantly greater in the 0.5 mg/kg and 1.0 mg/kg idursulfase groups than in the active comparator group (p= 0.003, 0.015, respectively). Both idursulfase beta infusions were generally safe and well tolerated, and elicited no serious adverse drug reactions. The most frequent adverse events were urticaria and skin rash, which were easily controlled with administration of antihistamines.

Conclusions

This study indicates that idursulfase beta generates clinically significant reduction of urinary GAG, improvements in endurance as measured by 6MWT, and it has an acceptable safety profile for the treatment of MPS II.

Trial registration

ClinicalTrials.gov: NCT01301898
Acute tetraparesis secondary to bilateral precentral gyral cerebral ischemia: a case report
Authors: Geis Christian , Gunreben Ignaz , Kleinschnitz Christoph
Published: March 2013

Introduction

Sudden tetraparesis represents a neurological emergency and is most often caused by traumatic spinal cord injury, spinal epidural bleeding or brainstem ischemia and less frequently by medial disc herniation or spinal ischemia.

Case presentation

Here we report the rare case of an 82-year-old Caucasian man who developed severe tetraparesis four days after radical cystoprostatectomy. An emergency diagnostic study for spinal cord affection was normal. Brain magnetic resonance imaging revealed acute bilateral ischemic strokes in the precentral gyri as the underlying cause.

Conclusions

This case report underlines the need to also consider unusual causes of tetraparesis in an emergency situation apart from spinal cord or brain stem injury in order not to leave severe symptomatology unclear and possibly miss therapeutic options.
Investigation of VSX1 sequence variants in South Indian patients with sporadic cases of keratoconus
Authors: Verma Anshuman , Das Manoranjan , Srinivasan Muthiah , Prajna Namperumalsamy V , Sundaresan Periasamy
Published: March 2013

Background

The involvement of VSX1 gene for the genetic basis of keratoconus is unclear and controversial. The genetic screening of VSX1 from different ethnic populations can enlighten this subject. The aim of the present study is to investigate the role of VSX1 gene in patients with sporadic cases of keratoconus from South India.

Methods

The VSX1 gene coding regions, including exon-intron boundaries were screened by direct sequencing analysis in 117 sporadic cases of keratoconus. The identified variations were also analyzed in 108 ethnic matched healthy blood donors.

Results

In the VSX 1 gene screening, no pathogenic mutation was identified, whereas we could find the presence of four reported single nucleotide polymorphisms; c.546A>G (rs12480307), c.627+23G>A (rs6138482), c.627+84T>A (rs56157240) and c.504-24C>T (IVS3-24C). These variations were observed in similar frequency between cases and controls.

Conclusions

The lack of VSX1 pathogenic variations in a large number of unrelated sporadic keratoconus patients tend to omit its role, and corroborate the involvement of other genetic, environmental or behavioural factors in the development of this complex disorder.
Embryonic mammary signature subsets are activated in Brca1

-/-
and basal-like breast cancers
Authors: Zvelebil Marketa , Oliemuller Erik , Gao Qiong , Wansbury Olivia , Mackay Alan , Kendrick Howard , Smalley Matthew J , Reis-Filho Jorge S , Howard Beatrice A
Published: March 2013

Introduction

Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations. Embryonic mammary epithelial cells are an immature progenitor cell population, lacking differentiation markers, which is reflected in their very distinct genetic profiles when compared with those of their postnatal descendents.

Methods

We defined an embryonic mammary epithelial signature that incorporates the most highly expressed genes from embryonic mammary epithelium when compared with the postnatal mammary epithelial cells. We looked for activation of the embryonic mammary epithelial signature in mouse mammary tumors that formed in mice in which Brca1 had been conditionally deleted from the mammary epithelium and in human breast cancers to determine whether any genetic links exist between embryonic mammary cells and breast cancers.

Results

Small subsets of the embryonic mammary epithelial signature were consistently activated in mouse Brca1-/- tumors and human basal-like breast cancers, which encoded predominantly transcriptional regulators, cell-cycle, and actin cytoskeleton components. Other embryonic gene subsets were found activated in non-basal-like tumor subtypes and repressed in basal-like tumors, including regulators of neuronal differentiation, transcription, and cell biosynthesis. Several embryonic genes showed significant upregulation in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and/or grade 3 breast cancers. Among them, the transcription factor, SOX11, a progenitor cell and lineage regulator of nonmammary cell types, is found highly expressed in some Brca1
-/-
mammary tumors. By using RNA interference to silence SOX11 expression in breast cancer cells, we found evidence that SOX11 regulates breast cancer cell proliferation and cell survival.

Conclusions

Specific subsets of embryonic mammary genes, rather than the entire embryonic development transcriptomic program, are activated in tumorigenesis. Genes involved in embryonic mammary development are consistently upregulated in some breast cancers and warrant further investigation, potentially in drug-discovery research endeavors.
Vaccinia virus GLV-1h153 is a novel agent for detection and effective local control of positive surgical margins for breast cancer
Authors: Gholami Sepideh , Chen Chun-Hao , Belin Laurence J , Lou Emil , Fujisawa Sho , Antonacci Caroline , Carew Amanda , Chen Nanhai G , De Brot Marina , Zanzonico Pat B , Szalay Aladar A , Fong Yuman
Published: March 2013

Introduction

Surgery is currently the definitive treatment for early-stage breast cancer. However, the rate of positive surgical margins remains unacceptably high. The human sodium iodide symporter (hNIS) is a naturally occurring protein in human thyroid tissue, which enables cells to concentrate radionuclides. The hNIS has been exploited to image and treat thyroid cancer. We therefore investigated the potential of a novel oncolytic vaccinia virus GLV1h-153 engineered to express the hNIS gene for identifying positive surgical margins after tumor resection via positron emission tomography (PET). Furthermore, we studied its role as an adjuvant therapeutic agent in achieving local control of remaining tumors in an orthotopic breast cancer model.

Methods

GLV-1h153, a replication-competent vaccinia virus, was tested against breast cancer cell lines at various multiplicities of infection (MOIs). Cytotoxicity and viral replication were determined. Mammary fat pad tumors were generated in athymic nude mice. To determine the utility of GLV-1h153 in identifying positive surgical margins, 90% of the mammary fat pad tumors were surgically resected and subsequently injected with GLV-1h153 or phosphate buffered saline (PBS) in the surgical wound. Serial Focus 120 microPET images were obtained six hours post-tail vein injection of approximately 600 μCi of 124I-iodide.

Results

Viral infectivity, measured by green fluorescent protein (GFP) expression, was time- and concentration-dependent. All cell lines showed less than 10% of cell survival five days after treatment at an MOI of 5. GLV-1h153 replicated efficiently in all cell lines with a peak titer of 27 million viral plaque forming units (PFU) ( <10,000-fold increase from the initial viral dose ) by Day 4. Administration of GLV-1h153 into the surgical wound allowed positive surgical margins to be identified via PET scanning. In vivo, mean volume of infected surgically resected residual tumors four weeks after treatment was 14 mm3 versus 168 mm3 in untreated controls (P < 0.05).

Conclusions

This is the first study to our knowledge to demonstrate a novel vaccinia virus carrying hNIS as an imaging tool in identifying positive surgical margins of breast cancers in an orthotopic murine model. Moreover, our results suggest that GLV-1h153 is a promising therapeutic agent in achieving local control for positive surgical margins in resected breast tumors.
Predictive value of circulating interleukin-6 and heart-type fatty acid binding protein for three months clinical outcome in acute cerebral infarction: multiple blood markers profiling study
Authors: Park So-Young , Kim Jinkwon , Kim Ok-Joon , Kim Jin-Kyeoung , Song Jihwan , Shin Dong-Ah , Oh Seung-Hun
Published: March 2013

Introduction

There is no single blood marker for predicting the prognosis in ischemic stroke. A combination of multiple blood markers may enhance the ability to predict long-term outcome following ischemic stroke.

Methods

Blood concentrations of neuronal markers (neuron-specific enolase, visinin-like protein 1, heart type fatty acid binding protein (hFABP) and neuroglobin), astroglial markers (S100B and glial fibrillary acidic protein), inflammatory markers (IL-6, TNF-α, and C-reactive protein), blood-brain barrier marker (matrix metalloproteinase 9), and haemostatic markers (D-dimer and PAI-1) were measured within 24 hours after stroke onset. The discrimination and reclassification for favorable and poor outcome were compared after adding individual or a combination of blood markers to the clinical model of stroke outcome.

Results

In multivariate analysis, natural log-transformed (log) IL-6 (odds ratio (OR): 1.75, 95% CI: 1.25 to 2.25, P = 0.001) and loghFABP (OR: 3.23, 95% CI: 1.44 to 7.27, P = 0.005) were independently associated with poor outcome. The addition of a single blood marker to the clinical model did not improve the discriminating ability of the clinical model of stroke outcome. However, the addition of the combination of logIL-6 and loghFABP to the clinical model showed improved discrimination (area under receiver operating characteristic (AUROC) curve: 0.939 versus 0.910, P = 0.03) and reclassification performance (net reclassification improvement index: 0.18, P = 0.005).

Conclusions

A combination of circulating IL-6 and hFABP level has an additive clinical value for the prediction of stroke outcome.
Accuracy of blood-glucose measurements using glucose meters and arterial blood gas analyzers in critically ill adult patients: systematic review
Authors: Inoue Shigeaki , Egi Moritoki , Kotani Joji , Morita Kiyoshi
Published: March 2013

Introduction

Glucose control to prevent both hyperglycemia and hypoglycemia is important in an intensive care unit. Arterial blood gas analyzers and glucose meters are commonly used to measure blood-glucose concentration in an intensive care unit; however, their accuracies are still unclear.

Methods

We performed a systematic literature search (January 1, 2001, to August 31, 2012) to find clinical studies comparing blood-glucose values measured with glucose meters and/or arterial blood gas analyzers with those simultaneously measured with a central laboratory machine in critically ill adult patients.

Results

We reviewed 879 articles and found 21 studies in which the accuracy of blood-glucose monitoring by arterial blood gas analyzers and/or glucometers by using central laboratory methods as references was assessed in critically ill adult patients. Of those 21 studies, 11 studies in which International Organization for Standardization criteria, error-grid method, or percentage of values within 20% of the error of a reference were used were selected for evaluation. The accuracy of blood-glucose measurements by arterial blood gas analyzers and glucose meters by using arterial blood was significantly higher than that of measurements with glucose meters by using capillary blood (odds ratios for error: 0.04, P < 0.001; and 0.36, P < 0.001). The accuracy of blood-glucose measurements with arterial blood gas analyzers tended to be higher than that of measurements with glucose meters by using arterial blood (P = 0.20). In the hypoglycemic range (defined as < 81 mg/dl), the incidence of errors using these devices was higher than that in the nonhypoglycemic range (odds ratios for error: arterial blood gas analyzers, 1.86, P = 0.15; glucose meters with capillary blood, 1.84, P = 0.03; glucose meters with arterial blood, 2.33, P = 0.02). Unstable hemodynamics (edema and use of a vasopressor) and use of insulin were associated with increased error of blood glucose monitoring with glucose meters.

Conclusions

Our literature review showed that the accuracy of blood-glucose measurements with arterial blood gas analyzers was significantly higher than that of measurements with glucose meters by using capillary blood and tended to be higher than that of measurements with glucose meters by using arterial blood. These results should be interpreted with caution because of the large variation of accuracy among devices. Because blood-glucose monitoring was less accurate within or near the hypoglycemic range, especially in patients with unstable hemodynamics or receiving insulin infusion, we should be aware that current blood glucose-monitoring technology has not reached a high enough degree of accuracy and reliability to lead to appropriate glucose control in critically ill patients.
Prediction of invasive candidal infection in critically ill patients with severeacute pancreatitis
Authors: Hall Alison M , Poole Lee AL , Renton Bryan , Wozniak Alexa , Fisher Michael , Neal Timothy , Halloran Christopher M , Cox Trevor , Hampshire Peter A
Published: March 2013

Introduction

Patients with severe acute pancreatitis are at risk of candidal infectionscarrying the potential risk of an increase in mortality. Since early diagnosis isproblematic, several clinical risk scores have been developed to identify patientsat risk. Such patients may benefit from prophylactic antifungal therapy whilethose patients who have a low risk of infection may not benefit and may be harmed.The aim of this study was to assess the validity and discrimination of existingrisk scores for invasive candidal infections in patients with severe acutepancreatitis.

Methods

Patients admitted with severe acute pancreatitis to the intensive care unit wereanalysed. Outcomes and risk factors of admissions with and without candidalinfection were compared. Accuracy and discrimination of three existing risk scoresfor the development of invasive candidal infection (Candida score, CandidaColonisation Index Score and the Invasive Candidiasis Score) were assessed.

Results

A total of 101 patients were identified from 2003 to 2011 and 18 (17.8%) of thesedeveloped candidal infection. Thirty patients died, giving an overall hospitalmortality of 29.7%. Hospital mortality was significantly higher in patients withcandidal infection (55.6% compared to 24.1%, P = 0.02). Candida colonisation was associated with subsequent candidal infection onmultivariate analysis. The Candida Colonisation Index Score was the most accuratetest, with specificity of 0.79 (95% confidence interval [CI] 0.68 to 0.88),sensitivity of 0.67 (95% CI 0.41 to 0.87), negative predictive value of 0.91 (95%CI 0.82 to 0.97) and a positive likelihood ratio of 3.2 (95% CI 1.9 to 5.5). TheCandida Colonisation Index Score showed the best discrimination with area underthe receiver operating characteristic curve of 0.79 (95% CI 0.69 to 0.87).

Conclusions

In this study the Candida Colonisation Index Score was the most accurate anddiscriminative test at identifying which patients with severe acute pancreatitisare at risk of developing candidal infection. However its low sensitivity maylimit its clinical usefulness.
The influence of gender on the epidemiology of and outcome from severe sepsis
Authors: Sakr Yasser , Elia Cristina , Mascia Luciana , Barberis Bruno , Cardellino Silvano , Livigni Sergio , Fiore Gilberto , Filippini Claudia , Ranieri Vito Marco
Published: March 2013

Introduction

The impact of gender on outcome in critically ill patients is unclear. Weinvestigated the influence of gender on the epidemiology of severe sepsis andassociated morbidity and mortality in a large cohort of ICU patients in the regionof Piedmont in Italy.

Methods

This was a post-hoc analysis of data from a prospective, multicenter,observational study in which all patients admitted to one of 24 participatingmedical and/or surgical ICUs between 3 April 2006 and 29 September 2006 wereincluded.

Results

Of the 3,902 patients included in the study, 63.5% were male. Female patients weresignificantly older than male patients (66 ± 16 years vs. 63 ± 16 years,P < 0.001). Female patients were less likely to have severe sepsisand septic shock on admission to the ICU and to develop these syndromes during theICU stay. ICU mortality was similar in men and women in the whole cohort (20.1%vs. 19.8%, P = 0.834), but in patients with severe sepsis wassignificantly greater in women than in men (63.5% vs. 46.4%, P = 0.007).In multivariate logistic regression analysis with ICU outcome as the dependentvariable, female gender was independently associated with a higher risk of ICUdeath in patients with severe sepsis (odds ratio = 2.33, 95% confidence interval =1.23 to 4.39, P = 0.009) but not in the whole cohort (odds ratio = 1.07,95% confidence interval = 0.87 to 1.34).

Conclusion

In this large regional Italian cohort of ICU patients, there were more male thanfemale admissions. The prevalence of severe sepsis was lower in women than in men,but female gender was independently associated with a higher risk of death in theICU for patients with severe sepsis.
Macrophage phenotypes during tissue repair
Authors: Novak Margaret L , Koh Timothy J
Published: March 2013

Review on tissue repair and M1-like to M2a-like macrophages, exhibiting important differences from in vitro phenotypes.

Mp are crucial for tissue repair and regeneration but can also contribute to tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory “M1” phenotype, produced by exposure to IFN-γ and TNF-α, and an anti-inflammatory “M2a” phenotype, produced by IL-4 or IL-13. M2a Mp are frequently termed “wound healing” Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro-defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1- and M2-associated markers may be expressed simultaneously by actual tissue-repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.
Central and haematopoietic interleukin-1 both contribute to ischaemic brain injury in mice
Authors: Denes Adam , Wilkinson Fiona , Bigger Brian , Chu Michael , Rothwell Nancy J. , Allan Stuart. M.
Published: March 2013

Interleukin-1 (IL-1) is a key regulator of inflammation and ischaemic brain injury, but the contribution of central and peripheral sources of IL-1 to brain injury is not well understood. Here we show that haematopoietic-derived IL-1 is a key driver of ischaemic brain injury. Wild type (WT) mice transplanted with IL-1αβ-deficient bone marrow displayed a significant (40%) reduction in brain injury induced by focal cerebral ischaemia compared to WT mice transplanted with WT bone marrow. This was paralleled by improved neurological outcome and the almost complete absence of splenic-derived, but not liver-derived, IL-1α after stroke in WT mice lacking haematopoietic-derived IL-1. IL-1αβ knockout (KO) mice transplanted with IL-1αβ-deficient bone marrow showed a 60% reduction in brain injury compared to WT mice receiving WT bone marrow. Transplantation of WT bone marrow in IL-1αβ KO mice resulted in a similar level of blood-brain-barrier injury to that observed in WT mice receiving IL-1αβ-deficient bone marrow. Cerebral oedema after brain injury was reduced in IL-1αβ KO recipients irrespective of donor-derived IL-1, but a lack of haematopoetic IL-1 has also been associated with smaller brain oedema independently of recipient status. Thus, both central and haematopoietic-derived IL-1 are important contributors to brain injury after cerebral ischaemia. Identification of the cellular sources of IL-1 in the periphery could allow targeted interventions at these sites.
Erythropoietin attenuates cardiac dysfunction in experimental sepsis in mice via activation of the β-common receptor
Authors: Khan Areeg I. , Coldewey Sina M. , Patel Nimesh S. A. , Rogazzo Mara , Collino Massimo , Yaqoob Muhammed M. , Radermacher Peter , Kapoor Amar , Thiemermann Christoph
Published: March 2013

There is limited evidence that the tissue-protective effects of erythropoietin are mediated by a heterocomplex of the erythropoietin receptor and the β-common receptor (‘tissue-protective receptor’), which is pharmacologically distinct from the ‘classical’ erythropoietin receptor homodimer that is responsible for erythropoiesis. However, the role of the β-common receptor and/or erythropoietin in sepsis-induced cardiac dysfunction (a well known, serious complication of sepsis) is unknown. Here we report for the first time that the β-common receptor is essential for the improvements in the impaired systolic contractility afforded by erythropoietin in experimental sepsis. Cardiac function was assessed in vivo (echocardiography) and ex vivo (Langendorff-perfused heart) in wild-type and β-common receptor knockout mice, that were subjected to lipopolysaccharide (9 mg/kg body weight; young mice) for 16-18 hours or cecal ligation and puncture (aged mice) for 24 hours. Mice received erythropoietin (1000 IU/kg body weight) 1 hour after lipopolysaccharide or cecal ligation and puncture. Erythropoietin reduced the impaired systolic contractility (in vivo and ex vivo) caused by endotoxemia or sepsis in young as well as old wild-type mice in a β-common-receptor-dependent fashion. Activation by erythropoietin of the β-common receptor also resulted in the activation of well-known survival pathways (Akt and endothelial nitric oxide synthase) and inhibition of pro-inflammatory pathways (glycogen synthase kinase-3β, nuclear factor-κB and interleukin-1β). All the above pleiotropic effects of erythropoietin were lost in β-common receptor knockout mice. Erythropoietin attenuates the impaired systolic contractility associated with sepsis by activation of the β-common receptor, which, in turn, results in activation of survival pathways and inhibition of inflammation.
Mixing Enhancement Effect of Low-molecular-weight Organogelators for Thixotropic Organogel Creation
Authors: Ohsedo Yutaka , Watanabe Hisayuki , Oono Masashi , Tanaka Akihiro
Published: March 2013

In this study, we found that organogels composed of mixed alkylhydrazide derivatives with different alkyl chains as low-molecular-weight organogelators showed thixotropic properties, whereas organogels composed of a single alkylhydrazide component did not show such properties. With a two- or three-component system of alkylhydrazides, the transparency and mechanical properties of the resulting organogels were enhanced. This mixing enhancement for organogelators might be due to an improved network of closer and finer fibers compared to that in a one-component system.
Helix-sense-selective Polymerization of Substituted Acetylenes by Using an Isolated Rh Chiral Initiator with an Amino Acid Ligand
Authors: Zang Yu , Ohishi Tomoyuki , Aoki Toshiki , Teraguchi Masahiro , Kaneko Takashi
Published: March 2013

Helix-sense-selective polymerization (HSSP) of substituted acetylenes by using an isolated chiral Rh initiator with an amino acid ligand has been achieved. The sense of the helix of the main chain of the resulting polymer was controlled by the sign of the chirality of the ligand. The isolated initiator needed less of the chiral ligand and gave polymers having a higher [θ] value than the two component chiral initiator systems we reported previously. The resulting polymers had a higher Mw.
Selective Crystallization of W by Hydrothermal Treatment of Wastewater Containing W and Mo
Authors: Sasai Ryo , Hirata Koichiro
Published: March 2013

Tungsten was selectively recovered from wastewater containing W and Mo, as crystalline tungsten trioxide, by hydrothermal treatment. The optimal hydrothermal conditions for selective recovery of W involved treatment at 503 K for more than 8 h after adjusting the initial pH of the wastewater to 4.
Water-sliding Property of Polyacrylates with Different Fluoro Side Chains
Authors: Hirai Tomoyasu , Haraguchi Masayuki , Sakai Atsushi , Penaloza, Jr. David P , Ozawa Masaaki , Miyaji Katsuaki , Tanaka Keiji
Published: March 2013

The incorporation of fluoro-containing moieties into polymers can significantly change their surface properties. In this study, we synthesized two polyacrylates with different fluoro-containing side chains to give a better understanding of how the water-sliding property of polymers can be controlled.
Facile Synthesis of Thermally Stable Benzimidazolate-type Ionic Liquids
Authors: Tsuji Yuki , Ohno Hiroyuki
Published: March 2013

Novel azolate-type ionic liquids (ILs), alkyltributylphosphonium benzimidazolates (alkyl chain: methyl, butyl, and octyl), were prepared by neutralization of the corresponding alkyltributylphosphonium hydroxides with benzimidazole. All the azolate-type ILs prepared here showed high ionic conductivities above 10−3 S cm−1 at 80 °C, and good thermal stability over 300 °C. They are expected to be useful platforms for functional ILs having good thermal stabilities.
Synthesis of Silicon Quantum Dots Functionalized Chemically with Monosaccharides and Their Use in Biological Fluorescence Imaging
Authors: Nakahara Yoshio , Machiya Kazuki , Sato Toshiyuki , Nwe Ni Tar , Furuike Tetsuya , Tamura Hiroshi , Kimura Keiichi
Published: March 2013

Novel water-dispersible, pH-stable, and biocompatible quantum dots were synthesized through the surface modification of silicon quantum dots (SiQDs) with monosaccharides. The presence of the monosaccharide on the surface of the SiQDs was recognized by fluorescence measurements using its complementary lectin (concanavalin A). The fluorescence cell imaging was carried out by using SiQDs functionalized chemically with d-glucosamine, and it was shown that the SiQDs developed in this study are applicable as blue chromophores for biological fluorescence imaging.
Unequal Recombination and Evolution of the Mating-Type (MAT) Loci in the Pathogenic FungusGrosmannia clavigeraand Relatives
Authors: Tsui Clement K-M , DiGuistini Scott , Wang Ye , Feau Nicolas , Dhillon Braham , Bohlmann Jörg , Hamelin Richard C
Published: March 2013

Sexual reproduction in fungi is regulated by the mating-type (MAT) locus where recombination is suppressed. We investigated the evolution of MAT loci in eight fungal species belonging to Grosmannia and Ophiostoma (Sordariomycetes, Ascomycota) that include conifer pathogens and beetle symbionts. The MAT1-2 idiomorph/allele was identified from the assembled and annotated Grosmannia clavigera genome, and the MAT locus is flanked by genes coding for cytoskeleton protein (SLA) and DNA lyase. The synteny of these genes is conserved and consistent with other members in Ascomycota. Using sequences from SLA and flanking regions, we characterized the MAT1-1 idiomorph from other isolates of G. clavigera and performed dotplot analysis between the two idiomorphs. Unexpectedly, the MAT1-2 idiomorph contains a truncated MAT1-1-1 gene upstream of the MAT1-2-1 gene that bears the high-mobility-group domain. The nucleotide and amino acid sequence of the truncated MAT1-1-1 gene is similar to its homologous copy in the MAT1-1 idiomorph in the opposite mating-type isolate, except that positive selection is acting on the truncated gene and the alpha(α)-box that encodes the transcription factor has been deleted. The MAT idiomorphs sharing identical gene organization were present in seven additional species in the Ophiostomatales, suggesting that the presence of truncated MAT1-1-1 gene is a general pattern in this order. We propose that an ancient unequal recombination event resulted in the ancestral MAT1-1-1 gene integrated into the MAT1-2 idiomorph and surviving as the truncated MAT1-1-1 genes. The α-box domain of MAT1-1-1 gene, located at the same MAT locus adjacent to the MAT1-2-1 gene, could have been removed by deletion after recombination due to mating signal interference. Our data confirmed a 1:1 MAT/sex ratio in two pathogen populations, and showed that all members of the Ophiostomatales studied here including those that were previously deemed asexual have the potential to reproduce sexually. This ability can potentially increase genetic variability and can enhance fitness in new, ecological niches.
Strain Specific Genotype−Environment Interactions and Evolutionary Potential for Body Mass in Brook Charr (Salvelinus fontinalis)
Authors: Crespel Amélie , Bernatchez Louis , Audet Céline , Garant Dany
Published: March 2013

Discriminating between genetic and environmental causes of phenotypic variation is an essential requirement for understanding the evolutionary potential of populations. However, the extent to which genetic variation differs among conspecific groups and environments during ontogeny has rarely been investigated. In this study, the genetic basis of body mass was measured in three divergent strains of brook charr (Salvelinus fontinalis) in different rearing environments and at different time periods. The results indicate that body mass was a heritable trait in all strains but that the level of heritability greatly differed among strains. Moreover, heritability estimates of each strain varied differently according to environmental rearing conditions, and cross-environments correlations were all significantly lower than unity, indicating strain-specific patterns of genotype–environment interactions. Heritability estimates also varied throughout ontogeny and decreased by 50% from 9 to 21 months of age. This study highlights the divergence in genetic architecture and evolutionary potential among these strains and emphasizes the importance of considering the strain-specific potential of the response to selection according to environmental variation.
Distinct 3-O-Sulfated Heparan Sulfate Modification Patterns Are Required forkal-1−Dependent Neurite Branching in a Context-Dependent Manner inCaenorhabditis elegans
Authors: Tecle Eillen , Diaz-Balzac Carlos A , Bülow Hannes E
Published: March 2013

Heparan sulfate (HS) is an unbranched glycosaminoglycan exhibiting substantial molecular diversity due to multiple, nonuniformly introduced modifications, including sulfations, epimerization, and acetylation. HS modifications serve specific and instructive roles in neuronal development, leading to the hypothesis of a HS code that regulates nervous system patterning. Although the in vivo roles of many of the HS modifications have been investigated, very little is known about the function of HS 3-O-sulfation in vivo. By examining patterning of the Caenorhabditis elegans nervous system in loss of function mutants of the two 3-O-sulfotransferases, hst-3.1 and hst-3.2, we found HS 3-O-sulfation to be largely dispensable for overall neural development. However, generation of stereotypical neurite branches in hermaphroditic-specific neurons required hst-3.1, hst-3.2, as well as an extracellular cell adhesion molecule encoded by kal-1, the homolog of Kallmann Syndrome associated gene 1/anosmin-1. In contrast, kal-1−dependent neurite branching in AIY neurons required catalytic activity of hst-3.2 but not hst-3.1. The context-dependent requirement for hst-3.2 and hst-3.1 indicates that both enzymes generate distinct types of HS modification patterns in different cell types, which regulate kal-1 to promote neurite branching. We conclude that HS 3-O-sulfation does not play a general role in establishing the HS code in C. elegans but rather plays a specialized role in a context-dependent manner to establish defined aspects of neuronal circuits.
A Genomic Survey of Reb Homologs Suggests Widespread Occurrence of R-Bodies in Proteobacteria
Authors: Raymann Kasie , Bobay Louis-Marie , Doak Thomas G , Lynch Michael , Gribaldo Simonetta
Published: March 2013

Bacteria and eukaryotes are involved in many types of interaction in nature, with important ecological consequences. However, the diversity, occurrence, and mechanisms of these interactions often are not fully known. The obligate bacterial endosymbionts of Paramecium provide their hosts with the ability to kill sensitive Paramecium strains through the production of R-bodies, highly insoluble coiled protein ribbons. R-bodies have been observed in a number of free-living bacteria, where their function is unknown. We have performed an exhaustive survey of genes coding for homologs of Reb proteins (R-body components) in complete bacterial genomes. We found that reb genes are much more widespread than previously thought, being present in representatives of major Proteobacterial subdivisions, including many free-living taxa, as well as taxa known to be involved in various kinds of interactions with eukaryotes, from mutualistic associations to pathogenicity. Reb proteins display very good conservation at the sequence level, suggesting that they may produce functional R-bodies. Phylogenomic analysis indicates that reb genes underwent a complex evolutionary history and allowed the identification of candidates potentially involved in R-body assembly, functioning, regulation, or toxicity. Our results strongly suggest that the ability to produce R-bodies is likely widespread in Proteobacteria. The potential involvement of R-bodies in as yet unexplored interactions with eukaryotes and the consequent ecological implications are discussed.