bluuebunny/crossref_metadata_2025 huggingface dataset:
Falls following discharge after an in-hospital fall
Authors: Davenport Rick D , Vaidean Georgeta D , Jones Carol B , Chandler A Michelle , Kessler Lori A , Mion Lorraine C , Shorr Ronald I
Published: December 2009

Background

Falls are among the most common adverse events reported in hospitalized patients. While there is a growing body of literature on fall prevention in the hospital, the data examining the fall rate and risk factors for falls in the immediate post-hospitalization period has not been well described. The objectives of the present study were to determine the fall rate of in-hospital fallers at home and to explore the risk factors for falls during the immediate post-hospitalization period.

Methods

We identified patients who sustained a fall on one of 16 medical/surgical nursing units during an inpatient admission to an urban community teaching hospital. After discharge, falls were ascertained using weekly telephone surveillance for 4 weeks post-discharge. Patients were followed until death, loss to follow up or end of study (four weeks). Time spent rehospitalized or institutionalized was censored in rate calculations.

Results

Of 95 hospitalized patients who fell during recruitment, 65 (68%) met inclusion criteria and agreed to participate. These subjects contributed 1498 person-days to the study (mean duration of follow-up = 23 days). Seventy-five percent were African-American and 43% were women. Sixteen patients (25%) had multiple falls during hospitalization and 23 patients (35%) suffered a fall-related injury during hospitalization. Nineteen patients (29%) experienced 38 falls at their homes, yielding a fall rate of 25.4/1,000 person-days (95% CI: 17.3-33.4). Twenty-three patients (35%) were readmitted and 3(5%) died. One patient experienced a hip fracture. In exploratory univariate analysis, persons who were likely to fall at home were those who sustained multiple falls in the hospital (p = 0.008).

Conclusion

Patients who fall during hospitalization, especially on more than one occasion, are at high risk for falling at home following hospital discharge. Interventions to reduce falls would be appropriate to test in this high-risk population.
Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia
Authors: Zhou Li , Rua Rejane , Ng Thomas , Vongrad Valentina , Ho Yung S , Geczy Carolyn , Hsu Kenneth , Brew Bruce J , Saksena Nitin K
Published: December 2009

Background

HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.

Methods

To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.

Results

Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.

Conclusion

Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.
Ertapenem versus piperacillin/tazobactam for the treatment of complicated infections: a meta-analysis of randomized controlled trials
Authors: An Mao Mao , Zou Zui , Shen Hui , Zhang Jun Dong , Chen Meng Li , Liu Ping , Wang Rui , Jiang Yuan Ying
Published: December 2009

Background

Ertapenem, a new carbapenem with a favorable pharmacokinetic profile, has been approved for the treatment of complicated intra-abdominal Infections (cIAIs), acute pelvic infections (APIs) and complicated skin and skin-structure infections (cSSSIs). The aim of this study is to compare the efficacy and safety of ertapenem with piperacillin/tazobactam, which has been reported to possess good efficacy for the treatment of these complicated infections.

Methods

We performed a meta-analysis of randomized controlled trials identified in PubMed, Cochrane library and Embase that compared the efficacy and safety of ertapenem with piperacillin/tazobactam for the treatment of complicated infections including cIAIs, APIs, cSSSIs. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure visit. The primary safety outcome was drug related clinical and laboratory adverse events occurred during the treatment and the post-treatment period.

Result

Six RCTs, involving 3161 patients, were included in our meta-analysis. Ertapenem was associated similar clinical treatment success with piperacillin/tazobactam for complicated infections treatment (clinically evaluable population, 1937 patients, odds ratios: 1.15, 95% confidence intervals: 0.89-1.49; modified intention to treat population, 2855 patients, odds ratios: 1.03, 95% confidence intervals: 0.87-1.22). All of secondary efficacy outcomes analysis obtained similar findings with clinical treatment success. No difference was found about the incidence of drug related adverse events between ertapenem and piperacillin/tazobactam groups.

Conclusion

This meta-analysis provides evidence that ertapenem 1 g once a day can be used as effectively and safely as recommended dose of piperacillin/tazobactam, for the treatment of complicated infections, particularly of mild to moderate severity. It is an appealing option for the treatment of these complicated infections.
Analyses of associations between three positionally cloned asthma candidate genes and asthma or asthma-related phenotypes in a Chinese population
Authors: Zhou Huanyu , Hong Xiumei , Jiang Shanqun , Dong Hongxing , Xu Xiping , Xu Xin
Published: December 2009

Background

Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian populations such as Chinese and Japanese. However, for PHF11, DPP10, and HLA-G, none of the association studies have been conducted in Asian populations. Therefore, the aim of the present study is to test the associations between these three positionally cloned genes and asthma or asthma-related phenotypes in a Chinese population.

Methods

Two, five, and two single nucleotide polymorphisms (SNPs) in the identified top regions of PHF11, DPP10, and HLA-G, respectively, were genotyped in 1183 independent samples. The study samples were selected based on asthma affectation status and extreme values in at least one of the following three asthma-related phenotypes: total serum immunoglobulin E levels, bronchial responsiveness test, and skin prick test. Both single SNP and haplotype analyses were performed.

Results

We found that DPP10 was significantly associated with bronchial hyperresponsiveness (BHR) and BHR asthma after the adjustment for multiple testing; while the associations of PHF11 with positive skin reactions to antigens and the associations of HLA-G with BHR asthma were only nominally significant.

Conclusion

Our study is the first one to provide additional evidence that supports the roles of DPP10 in influencing asthma or BHR in a Chinese population.
End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study
Authors: Muntner Paul , Arshad Asghar , Morse Stephen A , Patel Dharmendrakumar A , Manapatra Pronabesh D , Reisin Efrain , Aguilar Erwin A , Chen Wei , Srinivasan Sathanur , Berenson Gerald S
Published: December 2009

Background

Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized.

Methods

The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988.

Results

Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m2 among ESRD cases and 18.6 kg/m2 and 18.9 kg/m2 among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD.

Conclusion

These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.
ACCISS study rationale and design: activating collaborative cancer information service support for cervical cancer screening
Authors: Cofta-Woerpel Ludmila , Randhawa Veenu , McFadden H Gene , Fought Angela , Bullard Emily , Spring Bonnie
Published: December 2009

Background

High-quality cancer information resources are available but underutilized by the public. Despite greater awareness of the National Cancer Institute's Cancer Information Service among low-income African Americans and Hispanics compared with Caucasians, actual Cancer Information Service usage is lower than expected, paralleling excess cancer-related morbidity and mortality for these subgroups. The proposed research examines how to connect the Cancer Information Service to low-income African-American and Hispanic women and their health care providers. The study will examine whether targeted physician mailing to women scheduled for colposcopy to follow up an abnormal Pap test can increase calls to the Cancer Information Service, enhance appropriate medical follow-up, and improve satisfaction with provider-patient communication.

Methods/Design

The study will be conducted in two clinics in ethnically diverse low-income communities in Chicago. During the formative phase, patients and providers will provide input regarding materials planned for use in the experimental phase of the study. The experimental phase will use a two-group prospective randomized controlled trial design. African American and Hispanic women with an abnormal Pap test will be randomized to Usual Care (routine colposcopy reminder letter) or Intervention (reminder plus provider recommendation to call the Cancer Information Service and sample questions to ask). Primary outcomes will be: 1) calls to the Cancer Information Service; 2) timely medical follow-up, operationalized by whether the patient keeps her colposcopy appointment within six months of the abnormal Pap; and 3) patient satisfaction with provider-patient communication at follow-up.

Discussion

The study examines the effectiveness of a feasible, sustainable, and culturally sensitive strategy to increase awareness and use of the Cancer Information Service among an underserved population. The goal of linking a public service (the Cancer Information Service) with real-life settings of practice (the clinics), and considering input from patients, providers, and Cancer Information Service staff, is to ensure that the intervention, if proven effective, can be incorporated into existing care systems and sustained. The approach to study design and planning is aimed at bridging the gap between research and practice/service.

Trial Registration

NCT00873288
Comparison of surveillance methods applied to a situation of low malaria prevalence at rural sites in The Gambia and Guinea Bissau
Authors: Satoguina Judith , Walther Brigitte , Drakeley Christopher , Nwakanma Davis , Oriero Eniyou C , Correa Simon , Corran Patrick , Conway David J , Walther Michael
Published: December 2009

Background

Health record-based observations from several parts of Africa indicate a major decline in malaria, but up-to-date information on parasite prevalence in West-Africa is sparse. This study aims to provide parasite prevalence data from three sites in the Gambia and Guinea Bissau, respectively, and compares the usefulness of PCR, rapid diagnostic tests (RDT), serology and slide-microscopy for surveillance.

Methods

Cross-sectional surveys in 12 villages at three rural sites were carried out in the Gambia and Guinea Bissau in January/February 2008, shortly following the annual transmission season.

Results

A surprisingly low microscopically detectable parasite prevalence was detected in the Gambia (Farafenni: 10.9%, CI95%: 8.7-13.1%; Basse: 9.0%, CI95%: 7.2-10.8%), and Guinea Bissau (Caio: 4%, CI95%: 2.6-5.4%), with low parasite densities (geometric mean: 104 parasites/μl, CI95%: 76-143/μl). In comparison, PCR detected a more than three times higher proportion of parasite carriers, indicating its usefulness to sensitively identify foci where malaria declines, whereas the RDT had very low sensitivity. Estimates of force of infection using age sero-conversion rates were equivalent to an EIR of approximately 1 infectious bite/person/year, significantly less than previous estimates. The sero-prevalence profiles suggest a gradual decline of malaria transmission, confirming their usefulness in providing information on longer term trends of transmission. A greater variability in parasite prevalence among villages within a site than between sites was observed with all methods. The fact that serology equally captured the inter-village variability, indicates that the observed heterogeneity represents a stable pattern.

Conclusion

PCR and serology may be used as complementary tools to survey malaria in areas of declining malaria prevalence such as the Gambia and Guinea Bissau.
A surveillance summary of smoking and review of tobacco control in Jordan
Authors: Belbeisi Adel , Al Nsour Mohannad , Batieha Anwar , Brown David W , Walke Henry T
Published: December 2009

The burden of smoking-related diseases in Jordan is increasingly evident. During 2006, chronic, noncommunicable diseases (NCDs) accounted for more than 50% of all deaths in Jordan. With this evidence in hand, we highlight the prevalence of smoking in Jordan among youth and adults and briefly review legislation that governs tobacco control in Jordan. The prevalence of smoking in Jordan remains unacceptably high with smoking and use of tobacco prevalences ranging from 15% to 30% among students aged 13-15 years and a current smoking prevalence near 50% among men. Opportunities exist to further reduce smoking among both youth and adults; however, combating tobacco use in Jordan will require partnerships and long-term commitments between both private and public institutions as well as within local communities.
Gamma motor neurons express distinct genetic markers at birth and require muscle spindle-derived GDNF for postnatal survival
Authors: Shneider Neil A , Brown Meghan N , Smith Courtney A , Pickel James , Alvarez Francisco J
Published: December 2009

Background

Gamma motor neurons (γ-MNs) selectively innervate muscle spindle intrafusal fibers and regulate their sensitivity to stretch. They constitute a distinct subpopulation that differs in morphology, physiology and connectivity from α-MNs, which innervate extrafusal muscle fibers and exert force. The mechanisms that control the differentiation of functionally distinct fusimotor neurons are unknown. Progress on this question has been limited by the absence of molecular markers to specifically distinguish and manipulate γ-MNs. Recently, it was reported that early embryonic γ-MN precursors are dependent on GDNF. Using this knowledge we characterized genetic strategies to label developing γ-MNs based on GDNF receptor expression, showed their strict dependence for survival on muscle spindle-derived GDNF and generated an animal model in which γ-MNs are selectively lost.

Results

In mice heterozygous for both the Hb9::GFP transgene and a tau-lacZ-labeled (TLZ) allele of the GDNF receptor Gfrα1, we demonstrated that small motor neurons with high Gfrα1-TLZ expression and lacking Hb9::GFP display structural and synaptic features of γ-MNs and are selectively lost in mutants lacking target muscle spindles. Loss of muscle spindles also results in the downregulation of Gfrα1 expression in some large diameter MNs, suggesting that spindle-derived factors may also influence populations of α-MNs with β-skeletofusimotor collaterals. These molecular markers can be used to identify γ-MNs from birth to the adult and to distinguish γ- from β-motor axons in the periphery. We also found that postnatal γ-MNs are also distinguished by low expression of the neuronal nuclear protein (NeuN). With these markers of γ-MN identity, we show after conditional elimination of GDNF from muscle spindles that the survival of γ-MNs is selectively dependent on spindle-derived GDNF during the first 2 weeks of postnatal development.

Conclusion

Neonatal γ-MNs display a unique molecular profile characterized by the differential expression of a series of markers - Gfrα1, Hb9::GFP and NeuN - and the selective dependence on muscle spindle-derived GDNF. Deletion of GDNF expression from muscle spindles results in the selective elimination of γ-MNs with preservation of the spindle and its sensory innervation. This provides a mouse model with which to explore the specific role of γ-fusimotor activity in motor behaviors.
Correlations between atazanavir Ctrough and hyperbilirubinemia: a case report
Authors: Uglietti Alessia , Novati Stefano , Gulminetti Roberto , Maserati Renato
Published: December 2009

Introduction

Hyperbilirubinemia is a common side effect of the antiretroviral agent atazanavir but is generally reversible upon discontinuation of treatment. We used therapeutic drug monitoring to investigate the occurrence of hyperbilirubinemia in a 49-year-old Hispanic man infected with HIV, following an overdose of ritonavir in ritonavir-boosted atazanavir therapy.

Case presentation

A 49-year-old Hispanic man with HIV who had received several highly active antiretroviral therapy regimens over a number of years including atazanavir-containing regimens, was diagnosed with hyperbilirubinemia. An inappropriate doubling of ritonavir boosting resulted in a high atazanavir Ctrough and an initial rise in bilirubin plasma levels. Bilirubin levels later decreased, probably as a consequence of enzyme induction, while atazanavir plasma concentrations remained elevated.

Conclusion

This article describes an occurrence of hyperbilirubinemia in a man infected with HIV and supports the importance of therapeutic drug monitoring in investigations of hyperbilirubinemia among patients receiving antiretroviral agents. That the patient tolerated exceptionally high atazanavir levels further strengthens the tolerability profile of this drug.
RETRACTED ARTICLE: Tuberous sclerosis with pulmonary lymphangioleiomyomatosis and renal angiomyolipomas. Computed tomographic findings: a case report
Authors: Vianna Flávia G , Marchiori Edson , Zanetti Gláucia , Mano Claudia M , Sarcinelli-Luz Branca , Carvalho Juliana F , Assed Carla , Santos Isabella G , Santos Alair ASMD , Vianna Alberto D
Published: December 2009

The authors describe a case of a 31-year-old female with tuberous sclerosis, a genetic, rare, variably expressed disease. Clinical symptoms were chest pain, and progressive dyspnea. Computed tomography scan of the chest showed bilateral, diffuse, small thin-walled cysts scattered throughout the lungs characteristic for pulmonary lymphangioleiomyomatosis. Computed tomography scan of the abdomen revealed enlarged, heterogeneous kidneys, with low density tumors corresponding to angiomyolipomas. Pulmonary lymphangioleiomyomatosis and bilateral renal angiomyolipomas are some presentations of tuberous sclerosis and the coexistence of both conditions may cause devastating morbidity and mortality.
High origin of dorsal branch of the ulnar nerve and variations in its branching pattern and distribution: a case report
Authors: Lama Polly , Potu Bhagath K , Bhat Kumar MR
Published: December 2009

Introduction

Ulnar nerve is a branch of the brachial plexus. In the front of the forearm, normally near the wrist joint, it gives a dorsal cutaneous branch which supplies the skin of the dorsum of the hand.

Case presentation

The present case reports a very rare finding, the dorsal branch of the ulnar nerve along with the main nerve trunk originated between the two heads of the flexor carpi ulnaris muscle, after descending along the medial border of the forearm extensor surface, on the dorsal aspect of the wrist it is divided into three branches, one medial and two lateral. The medial most division received a communicating branch from the superficial ramus of the ulnar nerve and continued as the medial proper digital nerve of the little finger. The lateral two divisions became cutaneous on the medial half of the dorsum of the hand along the medial three digits i.e. radial and ulnar side of little, ring and middle finger.

Conclusion

The site, extent of injury, variations and the delay in the treatment, significantly influences the outcome of ulnar nerve repair. Thus, an adequate knowledge of all possible variations in the ulnar nerve may be important for clinicians and may help to explain uncommon symptoms.
Plant polycistronic precursors containing non-homologous microRNAs target transcripts encoding functionally related proteins
Authors: Merchan Francisco , Boualem Adnane , Crespi Martin , Frugier Florian
Published: December 2009

Background

MicroRNAs (miRNAs) are endogenous single-stranded small RNAs that regulate the expression of specific mRNAs involved in diverse biological processes. In plants, miRNAs are generally encoded as a single species in independent transcriptional units, referred to as MIRNA genes, in contrast to animal miRNAs, which are frequently clustered.

Results

We performed a comparative genomic analysis in three model plants (rice, poplar and Arabidopsis) and characterized miRNA clusters containing two to eight miRNA species. These clusters usually encode miRNAs of the same family and certain share a common evolutionary origin across monocot and dicot lineages. In addition, we identified miRNA clusters harboring miRNAs with unrelated sequences that are usually not evolutionarily conserved. Strikingly, non-homologous miRNAs from the same cluster were predicted to target transcripts encoding related proteins. At least four Arabidopsis non-homologous clusters were expressed as single transcriptional units. Overexpression of one of these polycistronic precursors, producing Ath-miR859 and Ath-miR774, led to the DCL1-dependent accumulation of both miRNAs and down-regulation of their different mRNA targets encoding F-box proteins.

Conclusions

In addition to polycistronic precursors carrying related miRNAs, plants also contain precursors allowing coordinated expression of non-homologous miRNAs to co-regulate functionally related target transcripts. This mechanism paves the way for using polycistronic MIRNA precursors as a new molecular tool for plant biologists to simultaneously control the expression of different genes.
Tandem repeats modify the structure of human genes hosted in segmental duplications
Authors: De Grassi Anna , Ciccarelli Francesca D
Published: December 2009

Background

Recently duplicated genes are often subject to genomic rearrangements that can lead to the development of novel gene structures. Here we specifically investigated the effect of variations in internal tandem repeats (ITRs) on the gene structure of human paralogs located in segmental duplications.

Results

We found that around 7% of the primate-specific genes located within duplicated regions of the genome contain variable tandem repeats. These genes are members of large groups of recently duplicated paralogs that are often polymorphic in the human population. Half of the identified ITRs occur within coding exons and may be either kept or spliced out from the mature transcript. When ITRs reside within exons, they encode variable amino acid repeats. When located at exon-intron boundaries, ITRs can generate alternative splicing patterns through the formation of novel introns.

Conclusions

Our study shows that variation in the number of ITRs impacts on recently duplicated genes by modifying their coding sequence, splicing pattern, and tissue expression. The resulting effect is the production of a variety of primate-specific proteins, which mostly differ in number and sequence of amino acid repeats.
Lipid droplet formation in leprosy: Toll-like receptor-regulated organelles involved in eicosanoid formation and Mycobacterium leprae pathogenesis
Authors: Mattos Katherine A , D'Avila Heloisa , Rodrigues Luciana S , Oliveira Viviane G C , Sarno Euzenir N , Atella Georgia C , Pereira Geraldo M , Bozza Patricia T , Pessolani Maria Cristina V
Published: December 2009

Lipid droplets induced by Mycobacterium leprae in macrophages are Toll-like receptor-regulated organelles involved in eicosanoid formation and leprosy pathogenesis.

A hallmark of LL is the accumulation of Virchow's foamy macrophages. However, the origin and nature of these lipids, as well as their function and contribution to leprosy disease, remain unclear. We herein show that macrophages present in LL dermal lesions are highly positive for ADRP, suggesting that their foamy aspect is at least in part derived from LD (also known as lipid bodies) accumulation induced during ML infection. Indeed, the capacity of ML to induce LD formation was confirmed in vivo via an experimental model of mouse pleurisy and in in vitro studies with human peripheral monocytes and murine peritoneal macrophages. Furthermore, infected cells were shown to propagate LD induction to uninfected, neighboring cells by generating a paracrine signal, for which TLR2 and TLR6 were demonstrated to be essential. However, TLR2 and TLR6 deletions affected LD formation in bacterium-bearing cells only partially, suggesting the involvement of alternative receptors of the innate immune response besides TLR2/6 for ML recognition by macrophages. Finally, a direct correlation between LD formation and PGE2 production was observed, indicating that ML-induced LDs constitute intracellular sites for eicosanoid synthesis and that foamy cells may be critical regulators in subverting the immune response in leprosy.
Application of the finite-difference contrast-source inversion algorithm to seismic full-waveform data
Authors: Abubakar Aria , Hu Wenyi , Habashy Tarek M. , van den Berg Peter M.
Published: December 2009

We have applied the finite-difference contrast-source inversion (FDCSI) method to seismic full-waveform inversion problems. The FDCSI method is an iterative nonlinear inversion algorithm. However, unlike the nonlinear conjugate gradient method and the Gauss-Newton method, FDCSI does not solve any full forward problem explicitly in each iterative step of the inversion process. This feature makes the method very efficient in solving large-scale computational problems. It is shown that FDCSI, with a significant lower computation cost, can produce inversion results comparable in quality to those produced by the Gauss-Newton method and better than those produced by the nonlinear conjugate gradient method. Another attractive feature of the FDCSI method is that it is capable of employing an inhomogeneous background medium without any extra or special effort. This feature is useful when dealing with time-lapse inversion problems where the objective is to reconstruct changes between the baseline and the monitor model. By using the baseline model as the background medium in crosswell seismic monitoring problems, high quality time-lapse inversion results are obtained.
Increased Bone Volume and Correction of HYP Mouse Hypophosphatemia in the Klotho/HYP Mouse
Authors: Brownstein Catherine A. , Zhang Junhui , Stillman Althea , Ellis Bruce , Troiano Nancy , Adams Douglas J. , Gundberg Caren M. , Lifton Richard P. , Carpenter Thomas O.
Published: December 2009

Inactivating mutations of PHEX cause X-linked hypophosphatemia and result in increased circulating fibroblast growth factor 23 (FGF23). FGF23 action is dependent upon Klotho, which converts FGF receptor 1 into an FGF23-specific receptor. Disruption of Klotho results in a complex bone phenotype and hyperphosphatemia, the converse phenotype of X-linked hypophosphatemia. We examined effects of disrupting both Klotho and PHEX by creating a double-knockout (Klotho/HYP) mouse. The combined disruption corrected the hypophosphatemia in HYP mice, indicating that Klotho is epistatic to PHEX. FGF23 levels remained elevated in all groups except wild-type, indicating that Klotho is necessary for FGF23-dependent phosphaturic activity. 1,25-Dihydroxyvitamin D levels, reduced in HYP mice, were comparably elevated in Klotho and Klotho/HYP mice, demonstrating that Klotho is necessary for FGF23’s effect on vitamin D metabolism. Serum PTH levels were reduced in both Klotho and Klotho/HYP mice. Moreover, the Klotho null phenotype persisted in Klotho/HYP, maintaining the runty phenotype and decreased life span of Klotho null mice. Notably, microcomputed tomography analysis demonstrated greater trabecular bone volume fraction in Klotho/HYP mice than that in all other groups (Klotho/HYP, 56.2 ± 6.3%; Klotho, 32.5 ± 10.3%; HYP, 8.6 ± 7.7%; and wild type, 21.4 ± 3.4%; P < 0.004). Histomorphometric analysis confirmed the markedly increased trabecular bone density in Klotho/HYP mice and the well-established increase in osteoid volume in HYP mice. These observations suggest that with addition of Klotho loss of function, the overabundant osteoid typically produced in HYP mice (but fails to mineralize) is produced and mineralized in the double knockout, resulting in markedly enhanced trabecular bone density.
Estrogen Receptor-α as a Drug Target Candidate for Preventing Lung Inflammation
Authors: Vegeto Elisabetta , Cuzzocrea Salvatore , Crisafulli Concetta , Mazzon Emanuela , Sala Angelo , Krust Andreè , Maggi Adriana
Published: December 2009

Accumulating evidence shows that estrogens are protective factors in inflammatory lung diseases and are involved in the gender-related incidence of these pathologies. The aim of this study was to identify which estrogen receptor (ER), ER-α and/or ERβ, mediates hormone antiinflammatory effects in lung and how gender or aging modify this effect. Acute lung inflammation in wild type, ERα or ERβ knockout animals was induced by pleural injection of carrageenan; female mice were used and sham operated, ovariectomized, or ovariectomized and treated with 17β-estradiol (E2) before carrageenan. Our data show that ERα, and not ERβ, mediates E2-induced reduction of the inflammatory response. By real-time PCR and immunohistochemistry assays, we demonstrate ERα expression in the resident and infiltrated inflammatory cells of the lung, in which ERβ could not be detected. In these cells, E2-mediated reduction in the expression of inflammatory mediators was also due to ERα. In parallel, we observed that female mice were more prone to inflammation as compared with males, suggesting a gender-related difference in lung susceptibility to inflammatory stimuli, whereas the effect of E2 was similar in the two sexes. Interestingly, aging results in a strong increase in the inflammatory response in both sexes and in the disruption E2/ERα signaling pathway. In conclusion, our data reveal that E2 is able to regulate lung inflammation in a gender-unrelated, age-restricted manner. The specific involvement of ERα in hormone action opens new ways to identify drug targets that limit the inflammatory component of lung pathologies.
Mechanisms Regulating Repression of Haptoglobin Production by Peroxisome Proliferator-Activated Receptor-γ Ligands in Adipocytes
Authors: Vernochet Cecile , Davis Kathryn E. , Scherer Philipp E. , Farmer Stephen R.
Published: December 2009

Obesity leads to inflammation of white adipose tissue involving enhanced secretion of cytokines and acute-phase proteins in response in part to the accumulation of excess lipids in adipocytes. Haptoglobin is an acute-phase reactant secreted by white adipose tissue and induced by inflammatory cytokines such as TNFα. In this study, we investigated the mechanisms regulating haptoglobin expression in adipocytes. Peroxisome proliferator-activated receptor (PPAR)-γ agonists such as thiazolidinediones (TZDs) as well as non-TZD ligands can repress in vitro and in vivo haptoglobin expression in adipocytes and also prevent its induction by TNFα. This action requires direct involvement of PPARγ in regulating haptoglobin gene transcription because mutation of critical amino acids within helix 7 of the ligand-binding domain of PPARγ prevents repression of the haptoglobin gene by the synthetic ligands. Chromatin immunoprecipitation analysis shows active binding of PPARγ to a distal region of the haptoglobin promoter, which contains putative PPARγ binding sites. Additionally, PPARγ induces transcription of a luciferase reporter gene when driven by the distal promoter region of the haptoglobin gene, and TZD treatment significantly reduces the extent of this induction. Furthermore, the mutated PPARγ is incapable of enhancing luciferase activity in these in vitro reporter gene assays. In contrast to other adipokines repressed by TZDs such as resistin and chemerin, repression of haptoglobin does not require either CCAAT/enhancer-binding protein C/EBPα or the corepressors C-terminal binding protein 1 or 2. These data are consistent with a model in which synthetic PPARγ ligands selectively activate PPARγ bound to the haptoglobin gene promoter to arrest haptoglobin gene transcription.
Long-Range Transcriptional Control of Progesterone Receptor Gene Expression
Authors: Bonéy-Montoya Jamie , Ziegler Yvonne S. , Curtis Carol D. , Montoya Jonathan A. , Nardulli Ann M.
Published: December 2009

Estrogen receptor α (ERα) binds to specific target DNA sequences, estrogen response elements (EREs), to regulate estrogen-responsive gene expression. The progesterone receptor (PR) gene has been used extensively as a marker of estrogen responsiveness. Although we previously identified cis elements within 1 kb of the PR-B transcription start site that are associated with ERα and help to confer estrogen responsiveness, the identification of ERα binding sites far removed from the transcription start site suggested that long-range regulation of this gene may occur. We now show that eight regions of the PR gene from 311 kb upstream to 4 kb downstream of the PR-B transcription start site interact with ERα and that coactivator proteins and acetylated histones are selectively associated with these gene regions. Specific PR gene regions confer estrogen responsiveness to a heterologous reporter plasmid, and mutation of EREs within these regions diminishes estrogen-induced transactivation. Importantly, chromosome conformation capture assays reveal ERα- and ligand-dependent interactions between proximal and distal PR gene regions. Taken together, our studies suggest that distal regions of the PR gene participate in the dynamic regulation of this gene and that the coordinated action of proximal and distal PR gene regions allows cells to respond to changes in hormone levels with extraordinary versatility and sensitivity.
Dryden's “Vegetarian” Philosopher: Pythagoras
Authors: Corse Taylor
Published: December 2009

This essay examines the impassioned lecture on animal rights that John Dryden adapted from Ovid and included in Fables Ancient and Modern (1700). This lecture, which Dryden called “Of the Pythagorean Philosophy,” reflects many aspects of the contemporary debate about ethical eating and ethical killing that flourished in seventeenth-century England. Dryden joins the company of travel writers, pamphleteers, poets, scholars, and philosophers who were troubled by the pervasive mistreatment of animals in Western Europe.
The Thirtieth of January Sermon: Swift, Johnson, Sterne, and the Evolution of Culture the American Society for Eighteenth-Century Studies James L. Clifford Lecture, 2008
Authors: Weinbrot Howard D.
Published: December 2009

The stern royalist Act of 12 Car. 2, c.30 in 1662 reprobated the “abominable” regicide of Charles I on 30 January 1649 (n.s.). The act mandated that on every 30 January every Anglican church or chapel in every parish in British dominions should read a sermon deploring the murder and imploring God's forgiveness for so horrid a national crime. Such sermons soon indeed were heard in Britain's 10,000 parishes and generally were hostile to the ever guilty Dissenters waiting to repeat the act if given a chance. The (High) Church of England must support the monarch and be supported by him. No bishop no king. By at least as early as 1680, however, many were troubled by the “madding day” brutal sermons. Dissenters protested their loyalty. Lower-church Anglicans sought peace and comprehension, as in Gilbert Burnet's sermon in 1681 on Zacharia 8.19. Better to strike the thirtieth of January from the calendar than to continue thus. Let the mourning and rage end; let “joy and gladness” return. Such an attitude increased in spite of regular denigration. The High Church itself began to be vilified as the true traitor, as in the Atterbury treason trial of 1723; the Hanoverians promised stability and healthy and numerous heirs. The tone of the sermons gradually changed. For example, Swift's sermon in 1726 berates his parishioners for not fully understanding why they must reject any confession other than the Anglican. The regicide heirs have preserved their ancestral political and religious attitudes. Be careful or they will cut your throat. Samuel Johnson is more temperate in his undated sermon. The regicide was a sign of destructive envy, both in its own right and because it ignored alternatives, like legal restraint upon the crown. Swift places the regicide in a political and national context. Johnson places it in a psychological and human context. Sterne's comparably undated sermon regards regicide as “trespass,” almost as a property crime against general goodness. The British people should do better, but they are blessed in their government and good fortune. Sterne's visual rhetoric so like that in Tristram Shandy`s dash-laden pages, gives us a conversational and casual tone for a once ominous topic. The thirtieth of January sermons become markers in the evolution of culture. The sermon and the culture have evolved from rage, to rational and psychological discourse, and then almost to indifference.
Microtechnologies in neurosurgery
Authors: Di Ieva A
Published: December 2009

In the history of medicine, the understanding of the nervous system, both from an anatomical and a functional point of view, has always required new and more sophisticated tools. It has been widely demonstrated that engineering has helped towards this end. Incorporation of improved technical tools has expanded the available armamentarium to perform neurological surgery. Neurosurgery probably presents the most major challenges and always benefits from the introduction of sophisticated tools, from cranial trephination to the most modern robotics. This review examines the role of engineering to assist in neurosurgery.
Overhead line real-time rating estimation algorithm: Description and validation
Authors: Michiorri A , Taylor P C , Jupe S C E
Published: December 2009

This article describes research that aims to realize a real-time rating (RTR) system for power system components. The RTR technology is regarded with interest due to its potential to unlock network power transfer capacity, improve power flow congestion management flexibi-lity, and facilitate the connection of distributed generation. The solution described in this work involves the use of a limited number of meteorological stations and a series of analytical models for estimating component ratings. The effect of data uncertainty is taken into account by an estimation algorithm based on the Monte Carlo method. Estimations of conductor temperature and environmental conditions have been validated against measured data in five different network locations. Average errors of-2.2,-1.9,-1.2,-1.9, and 1.4 °C were found for the five different network locations over a period of 71 days when comparing estimates to measured results. Results analysis identified that the models used were the main source of error. The estimation of wind direction and solar radiation was the most sensitive to errors in the models. Therefore, suggestions are made regarding the improvement of these models and the RTR estimation system.
Identification of breaking events from the responses of a data buoy
Authors: Balaji R , Sannasiraj S A , Sundar V
Published: December 2009

Conventional data buoys record wave spectral parameters such as the significant height, peak period, and mean direction. Information about the existence of wave groups and breaking waves is also important for the design of ocean structures. To derive such information from data buoy measurements, understanding of the motion characteristics of data buoys under a variety of wave conditions is essential. In the present study, the motion characteristics of a scale-modelled discus data buoy were tested under the action of deep-water breaking waves of different intensities, covering spilling to steep plunging types. The laboratory generation of breaking waves was based on the constructive wave—wave interaction method. The buoy heave and pitch motions were measured using potentiometers and non-contact motion-capturing cameras. The measured time series of the breaking-wave surface elevation and the resulting buoy motions were analysed by continuous wavelet transformation and phase—time methods. A closer insight into the wavelet phases reveals that the breaking events leave a constant phase variation over a wider range of higher frequencies. Through appropriate filtering of the localized frequencies, the phase—time method could also be adopted to detect breaking events in the time histories of the measured wave elevation and motion response. The details of the model, instrumentation, testing conditions, and analysis are presented and discussed in this paper.
Apolipoproteins in diabetes dyslipidaemia in South Asians with young adult-onset diabetes: distribution, associations and patterns
Authors: Katulanda Gaya W , Katulanda Prasad , Adler A I , Peiris S R , Draisey I , Wijeratne S , Sheriff R , Matthews D R , Shine Brian
Published: December 2009

Background

Apolipoproteins B (apoB) and AI (apoAI) are strong predictors of cardiovascular disease (CVD). We describe apolipoprotein distributions and their associations with lipids and diabetes subtype in diabetic young adult South Asians.

Methods

In 995 subjects with diabetes, we measured fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG), apoB and apoAI, glycosylated haemoglobin (HbA1c) and glutamic acid decarboxylase antibodies (GADA). Low-density lipoprotein cholesterol (LDLC) and non-HDLC (NHDLC) were calculated. We compared values in subjects aged 15–50 y from the United States National Health and Nutrition Examination Survey (NHANES).

Results

Median age and duration of diabetes were 38 (range 14–45) and 4 (0–24) y. Men had significantly higher TC, TG, NHDLC, TC/HDLC, apoB/AI and NHDLC/apoB, and lower apoAI than women. Compared with the reference group, patients with type 1 diabetes had lower TG, apoB:apoAI and HDLC:apoAI, and higher HDLC and apoAI. Patients with type 2 diabetes had higher TG, TC, LDLC, NHDLC, TC:HDL, apoB, apoAI and apoB:apoAI, and lower HDLC, LDLC:apoB and HDLC:apoAI. Among patients with type 2 diabetes, 54% had high apoB (>1.2 g/L) and 33% also had high TG (>1.5 mmol/L). Measures of obesity (body mass index and waist circumference) were weakly correlated with lipid and apoprotein parameters, suggesting a modest contribution to dyslipidaemia.

Conclusions

A large proportion of young adult Sri Lankan patients with type 2 diabetes has a low LDLC:apoB and high apoB and/or TG, suggesting that these patients are at increased risk of CVD.
Complications and side-effects of foam sclerotherapy
Authors: Guex J-J
Published: December 2009

Aims

To describe and report incidence and frequency of side-effects and complications of sclerotherapy with foamed sclerosing agents. To explain, when possible, their pathophysiology and to indicate possible manoeuvres and techniques to limit them.

Methods

Review of current literature and personal research.

Results

Complications of foam sclerotherapy include complications of sclerotherapy in general and specific complications of foamed sclerosing agents. Side-effects related to the sclerosing compounds are also taken into account.

Conclusion

Complications and side-effects of careful foam sclerotherapy remain uncommon. However, more research is needed to understand them better and to further reduce their incidence. Their description to patients in the course of the informed consent is a prerequisite to any sclerosing treatment.
Revisiting the operational RNA code for amino acids: Ensemble attributes and their implications
Authors: Shaul Shaul , Berel Dror , Benjamini Yoav , Graur Dan
Published: December 2009

It has been suggested that tRNA acceptor stems specify an operational RNA code for amino acids. In the last 20 years several attributes of the putative code have been elucidated for a small number of model organisms. To gain insight about the ensemble attributes of the code, we analyzed 4925 tRNA sequences from 102 bacterial and 21 archaeal species. Here, we used a classification and regression tree (CART) methodology, and we found that the degrees of degeneracy or specificity of the RNA codes in both Archaea and Bacteria differ from those of the genetic code. We found instances of taxon-specific alternative codes, i.e., identical acceptor stem determinants encrypting different amino acids in different species, as well as instances of ambiguity, i.e., identical acceptor stem determinants encrypting two or more amino acids in the same species. When partitioning the data by class of synthetase, the degree of code ambiguity was significantly reduced. In cryptographic terms, a plausible interpretation of this result is that the class distinction in synthetases is an essential part of the decryption rules for resolving the subset of RNA code ambiguities enciphered by identical acceptor stem determinants of tRNAs acylated by enzymes belonging to the two classes. In evolutionary terms, our findings lend support to the notion that in the pre-DNA world, interactions between tRNA acceptor stems and synthetases formed the basis for the distinction between the two classes; hence, ambiguities in the ancient RNA code were pivotal for the fixation of these enzymes in the genomes of ancestral prokaryotes.