bluuebunny/crossref_metadata_2025 huggingface dataset:
Arginine68 is an essential residue for the C-terminal cleavage of human Atg8 family proteins
Authors: Liu Chao , Ma Haijie , Wu Jiaxue , Huang Qiang , Liu Jun O , Yu Long
Published: May 2013

Background

Autophagy is a conserved cellular process that degrades and recycles cytoplasmic components via a lysosomal pathway. The phosphatidylethanolamine (PE)-conjugation of the Atg8 protein plays an important role in the yeast autophagy process. In humans, six Atg8 homologs, including MAP1LC3A, MAP1LC3B, MAP1LC3C (refer to LC3A, LC3B, and LC3C hereafter), GABARAP, GABARAPL1, and GABARAPL2 have been reported. All of them can be conjugated to PE through a ubiquitin-like conjugation system, and be located to autophagosomes.

Results

In this study, we found 3 new alternative splicing isoforms in LC3B, GABARAP, and GABARAPL1, (designated as LC3B-a, GABARAP-a and GABARAPL1-a, respectively). None of them can go through the PE-conjugation process and be located to autophagosomes. Interestingly, compared with LC3B, LC3B-a has a single amino acid (Arg68) deletion due to the NAGNAG alternative splicing in intron 3. Through structural simulations, we found that the C-terminal tail of LC3B-a is less mobile than that of LC3B, thus affecting its C-terminal cleavage by human ATG4 family proteins. Furthermore, we found that Arg68 is an essential residue facilitating the interaction between human Atg8 family proteins and ATG4B by forming a salt bridge with Asp171 of ATG4B. Depletion of this salt bridge reduces autophagosomes formation and autophagic flux under both normal and nutrition starvation conditions.

Conclusions

These results suggest Arg68 is an essential residue for the C-terminal cleavage of Atg8 family proteins during the autophagy process.
Enzymatically active Rho and Rac small-GTPases are involved in the establishment of the vacuolar membrane after Toxoplasma gondii invasion of host cells
Authors: Na Ren-Hua , Zhu Guo-Hui , Luo Ji-Xuan , Meng Xiao-Jing , Cui Liwang , Peng Hong-Juan , Chen Xiao-guang , Gomez-Cambronero Julian
Published: May 2013

Background

GTPases are the family of hydrolases that bind and hydrolyze guanosine triphosphate. The large Immunity-related GTPases and the small GTPase ADP-ribosylation factor-6 in host cells are known to accumulate on the parasitophorous vacuole membrane (PVM) of Toxoplasma gondii and play critical roles in this parasite infection, but these GTPases cannot explain the full extent of infection.

Results

In this research, RhoA and Rac1 GTPases from the host cell were found to accumulate on the PVM regardless of the virulence of the T. gondii strains after T. gondii invasion, and this accumulation was dependent on their GTPase activity. The real-time micrography of T. gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA showed that this GTPase was recruited to the PVM at the very beginning of the invasion through the host cell membrane or from the cytosol. Host cell RhoA and Rac1 were also activated after T. gondii tachyzoites invasion, which was needed for host cell cytoskeleton reorganization to facilitate intracellular pathogens invasion. The decisive domains for the RhoA accumulation on the PVM included the GTP/Mg2+ binding site, the mDia effector interaction site, the G1 box, the G2 box and the G5 box, respectively, which were related to the binding of GTP for enzymatic activity and mDia for the regulation of microtubules. The recruited CFP-RhoA on the PVM could not be activated by epithelial growth factor (EGF) and no translocation was observed, unlike the unassociated RhoA in the host cell cytosol that migrated to the cell membrane towards the EGF activation spot. This result supported the hypothesis that the recruited RhoA or Rac1 on the PVM were in the GTP-bound active form. Wild-type RhoA or Rac1 overexpressed cells had almost the same infection rates by T. gondii as the mock-treated cells, while RhoA-N19 or Rac1-N17 transfected cells and RhoA, Rac1 or RhoA + Rac1 siRNA-treated cells showed significantly diminished infection rates compared to mock cells.

Conclusions

The accumulation of the RhoA and Rac1 on the PVM and the requisite of their normal GTPase activity for efficient invasion implied their involvement and function in T. gondii invasion.
Simultaneous molecular formula determinations of natural compounds in a plant extract using 15 T Fourier transform ion cyclotron resonance mass spectrometry
Authors: Park Kyu Hwan , Kim Min Sun , Baek Sun Jong , Bae Ik Hyun , Seo Sang-Wan , Kim Jongjin , Shin Yong Kook , Lee Yong-Moon , Kim Hyun Sik
Published: May 2013

Background

Plant extracts are a reservoir of pharmacologically active substances; however, conventional analytical methods can analyze only a small portion of an extract. Here, we report a high-throughput analytical method capable of determining most phytochemicals in a plant extract and of providing their molecular formulae from a single experiment using ultra-high-resolution electrospray ionization mass spectrometry (UHR ESI MS). UHR mass profiling was used to analyze natural compounds in a 70% ethanol ginseng extract, which was directly infused into a 15 T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer for less than 10 min without a separation process.

Results

The UHR FT-ICR MS yielded a mass accuracy of 0.5 ppm and a mass resolving power (m/Δm) of 1,000,000–270,000 for the range m/z 290–1,100. The mass resolution was sufficient to resolve the isotopic fine structure (IFS) of many compounds in the extract. After noise removal from 1,552 peaks, 405 compounds were detected. The molecular formulae of 123 compounds, including 33 ginsenosides, were determined using the observed IFS, exact monoisotopic mass, and exact mass difference. Liquid chromatography (LC)/FT-ICR MS of the extract was performed to compare the high-throughput performance of UHR ESI FT-ICR MS. The LC/FT-ICR MS detected only 129 compounds, including 19 ginsenosides. The result showed that UHR ESI FT-ICR MS identified three times more compounds than LC/FT-ICR MS and in a relatively shorter time. The molecular formula determination by UHR FT-ICR MS was validated by LC and tandem MS analyses of three known ginsenosides.

Conclusions

UHR mass profiling of a plant extract by 15 T FT-ICR MS showed that multiple compounds were simultaneously detected and their molecular formulae were decisively determined by a single experiment with ultra-high mass resolution and mass accuracy. Simultaneous molecular determination of multiple natural products by UHR ESI FT-ICR MS would be a powerful method to profile a wide range of natural compounds.
Survival following gamma knife radiosurgery for brain metastasis from breast cancer
Authors: Jaboin Jerry J , Ferraro Daniel J , DeWees Todd A , Rich Keith M , Chicoine Michael R , Dowling Joshua L , Mansur David B , Drzymala Robert E , Simpson Joseph R , Magnuson William J , Patel Anushka H , Zoberi Imran
Published: May 2013

Background

Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes.

Methods

A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis.

Results

Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival.

The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival.

Conclusion

Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival.
Methicillin-resistant Staphylococcus aureus risk profiling: who are we missing?
Authors: Pasricha Janet , Harbarth Stephan , Koessler Thibaud , Camus Veronique , Schrenzel Jacques , Cohen Gilles , Pittet Didier , Perrier Arnaud , Iten Anne
Published: May 2013

Background

Targeted screening of patients at high risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage is an important component of MRSA control programs, which rely on prediction tools to identify those high-risk patients. Most previous risk studies reported a substantial rate of patients who are eligible for screening, but failed to be enrolled. The characteristics of these missed patients are seldom described. We aimed to determine the rate and characteristics of patients who were missed by a MRSA screening programme at our institution to see how the failure to include these patients might impact the accuracy of clinical prediction tools.

Findings

From March-June 2010 all patients admitted to 13 internal medicine wards at the University of Geneva Hospital (HUG) were prospectively screened for MRSA carriage. Of 1968 patients admitted to the ward, 267 patients (13.6%) failed to undergo appropriate MRSA screening. Forty-one (2.4%) screened patients were MRSA carriers at admission. On multivariate regression, patients who were missed by screening were more likely to be aged < 50 years (OR 2.4 [1.4-3.9]), transferred to internal medicine from another ward in the hospital (OR 2.8 [1.1-7.1]), and have a history of malignancy (OR 3.2[2.1-5.1]). There was no significant difference in the rate of previous MRSA carriage between screened and unscreened patients.

Conclusions

Our findings highlight the potential bias that “missed” patients may introduce into MRSA risk scores. Reporting on the proportions and characteristics of missed patients is essential for accurate interpretation of MRSA prediction tools.
Editorial: A missing link? Monocyte activation by uremic toxins in cardiorenal syndrome
Authors: Armstrong Ehrin J , Granick Jennifer L , Simon Scott I
Published: May 2013

Discussion on the effects of the uremic toxin, indoxyl sulfate, on monocyte activation as a link between chronic kidney disease and atherosclerosis.
Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals
Authors: Moon Hyun-Seuk , Dalamaga Maria , Kim Sang-Yong , Polyzos Stergios A. , Hamnvik Ole-Petter , Magkos Faidon , Paruthi Jason , Mantzoros Christos S.
Published: May 2013

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.
Msx1andTbx2antagonistically regulateBmp4expression during the bud-to-cap stage transition in tooth development
Authors: Saadi Irfan , Das Pragnya , Zhao Minglian , Raj Lakshmi , Ruspita Intan , Xia Yan , Papaioannou Virginia E. , Bei Marianna
Published: May 2013

Bmp4 expression is tightly regulated during embryonic tooth development, with early expression in the dental epithelial placode leading to later expression in the dental mesenchyme. Msx1 is among several transcription factors that are induced by epithelial Bmp4 and that, in turn, are necessary for the induction and maintenance of dental mesenchymal Bmp4 expression. Thus, Msx1-/- teeth arrest at early bud stage and show loss of Bmp4 expression in the mesenchyme. Ectopic expression of Bmp4 rescues this bud stage arrest. We have identified Tbx2 expression in the dental mesenchyme at bud stage and show that this can be induced by epithelial Bmp4. We also show that endogenous Tbx2 and Msx1 can physically interact in mouse C3H10T1/2 cells. In order to ascertain a functional relationship between Msx1 and Tbx2 in tooth development, we crossed Tbx2 and Msx1 mutant mice. Our data show that the bud stage tooth arrest in Msx1-/- mice is partially rescued in Msx1-/-;Tbx2+/- compound mutants. This rescue is accompanied by formation of the enamel knot (EK) and by restoration of mesenchymal Bmp4 expression. Finally, knockdown of Tbx2 in C3H10T1/2 cells results in an increase in Bmp4 expression. Together, these data identify a novel role for Tbx2 in tooth development and suggest that, following their induction by epithelial Bmp4, Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity that leads to EK formation and to mesenchymal Bmp4 expression at the key bud-to-cap stage transition.
The Maf factor Traffic jam both enables and inhibits collective cell migration inDrosophilaoogenesis
Authors: Gunawan Felix , Arandjelovic Mimi , Godt Dorothea
Published: May 2013

Border cell cluster (BCC) migration in the Drosophila ovary is an excellent system to study the gene regulatory network that enables collective cell migration. Here, we identify the large Maf transcription factor Traffic jam (Tj) as an important regulator of BCC migration. Tj has a multifaceted impact on the known core cascade that enables BCC motility, consisting of the Jak/Stat signaling pathway, the C/EBP factor Slow border cells (Slbo), and the downstream effector DE-cadherin (DEcad). The initiation of BCC migration coincides with a Slbo-dependent decrease in Tj expression. This reduction of Tj is required for normal BCC motility, as high Tj expression strongly impedes migration. At high concentration, Tj has a tripartite negative effect on the core pathway: a decrease in Slbo, an increase in the Jak/Stat inhibitor Socs36E, and a Slbo-independent reduction of DEcad. However, maintenance of a low expression level of Tj in the BCC during migration is equally important, as loss of tj function also results in a significant delay in migration concomitant with a reduction of Slbo and consequently of DEcad. Taken together, we conclude that the regulatory feedback loop between Tj and Slbo is necessary for achieving the correct activity levels of migration-regulating factors to ensure proper BCC motility.
The expanding role of fish models in understanding non-alcoholic fatty liver disease
Authors: Asaoka Yoichi , Terai Shuji , Sakaida Isao , Nishina Hiroshi
Published: May 2013

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC). NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio) and medaka (Oryzias latipes). Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this review, we summarize aspects of NAFLD (specifically focusing on NASH) pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.
notch3is essential for oligodendrocyte development and vascular integrity in zebrafish
Authors: Zaucker Andreas , Mercurio Sara , Sternheim Nitzan , Talbot William S. , Marlow Florence L.
Published: May 2013

Mutations in the human NOTCH3 gene cause CADASIL syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). CADASIL is an inherited small vessel disease characterized by diverse clinical manifestations including vasculopathy, neurodegeneration and dementia. Here we report two mutations in the zebrafish notch3 gene, one identified in a previous screen for mutations with reduced expression of myelin basic protein (mbp) and another caused by a retroviral insertion. Reduced mbp expression in notch3 mutant embryos is associated with fewer oligodendrocyte precursor cells (OPCs). Despite an early neurogenic phenotype, mbp expression recovered at later developmental stages and some notch3 homozygous mutants survived to adulthood. These mutants, as well as adult zebrafish carrying both mutant alleles together, displayed a striking stress-associated accumulation of blood in the head and fins. Histological analysis of mutant vessels revealed vasculopathy, including: an enlargement (dilation) of vessels in the telencephalon and fin, disorganization of the normal stereotyped arrangement of vessels in the fin, and an apparent loss of arterial morphological structure. Expression of hey1, a well-known transcriptional target of Notch signaling, was greatly reduced in notch3 mutant fins, suggesting that Notch3 acts via a canonical Notch signaling pathway to promote normal vessel structure. Ultrastructural analysis confirmed the presence of dilated vessels in notch3 mutant fins and revealed that the vessel walls of presumed arteries showed signs of deterioration. Gaps evident in the arterial wall and the presence of blood cells outside of vessels in mutants indicated that compromised vessel structure led to hemorrhage. In notch3 heterozygotes, we found elevated expression of both notch3 itself and target genes, indicating that specific alterations in gene expression caused by a partial loss of Notch3 function might contribute to the abnormalities observed in heterozygous larvae and adults. Our analysis of zebrafish notch3 mutants indicates that Notch3 regulates OPC development and mbp gene expression in larvae, and maintains vascular integrity in adults.
Efficient Synthesis of Various 4-Tosyloxy-2-substituted Phenols Using Pyridinium Salt-supported [Hydroxy(tosyloxy)iodo]benzene Reagent
Authors: Yang Bing , Zhang Jizhen , Zhao Dejian , Wang Yazhen , Jia Hongbin
Published: May 2013

A novel pyridinium salt-supported [hydroxy(tosyloxy)iodo]benzene (HTIB) reagent (N-{4-[hydroxy(tosyloxy)iodo]phenyl}pyridinium hexafluorophosphate) was prepared via Zincke’s reaction. The conjugated HTIB was an effective reagent for tosyloxylation of phenolic aromatic rings with an electron-withdrawing substitute at the ortho-position. The reagent can be easily regenerated in high yield and reused three times without any decrease in activity.
Controlled longitudinal bone growth by temporary tension band plating
Authors: Gottliebsen M. , Møller-Madsen B. , Stødkilde-Jørgensen H. , Rahbek O.
Published: May 2013

Permanent growth arrest of the longer bone is an option in the treatment of minor leg-length discrepancies. The use of a tension band plating technique to produce a temporary epiphysiodesis is appealing as it avoids the need for accurate timing of the procedure in relation to remaining growth. We performed an animal study to establish if control of growth in a long bone is possible with tension band plating. Animals (pigs) were randomised to temporary epiphysiodesis on either the right or left tibia. Implants were removed after ten weeks. Both tibiae were examined using MRI at baseline, and after ten and 15 weeks. The median interphyseal distance was significantly shorter on the treated tibiae after both ten weeks (p = 0.04) and 15 weeks (p = 0.04). On T1-weighted images the metaphyseal water content was significantly reduced after ten weeks on the treated side (p = 0.04) but returned to values comparable with the untreated side at 15 weeks (p = 0.14). Return of growth was observed in all animals after removal of implants.

Temporary epiphysiodesis can be obtained using tension band plating. The technique is not yet in common clinical practice but might avoid the need for the accurate timing of epiphysiodesis.

Cite this article: Bone Joint J 2013;95-B:855–60.
The surgical anatomy of the piriformis tendon, with particular reference to total hip replacement
Authors: Roche J. J. W. , Jones C. D. S. , Khan R. J. K. , Yates P. J.
Published: May 2013

The piriformis muscle is an important landmark in the surgical anatomy of the hip, particularly the posterior approach for total hip replacement (THR). Standard orthopaedic teaching dictates that the tendon must be cut in to allow adequate access to the superior part of the acetabulum and the femoral medullary canal. However, in our experience a routine THR can be performed through a posterior approach without sacrificing this tendon.

We dissected the proximal femora of 15 cadavers in order to clarify the morphological anatomy of the piriformis tendon. We confirmed that the tendon attaches on the crest of the greater trochanter, in a position superior to the trochanteric fossa, away from the entry point for broaching the intramedullary canal during THR. The tendon attachment site encompassed the summit and medial aspect of the greater trochanter as well as a variable attachment to the fibrous capsule of the hip joint. In addition we dissected seven cadavers resecting all posterior attachments except the piriformis muscle and tendon in order to study their relations to the hip joint, as the joint was flexed. At flexion of 90° the piriformis muscle lay directly posterior to the hip joint.

The piriform fossa is a term used by orthopaedic surgeons to refer the trochanteric fossa and normally has no relation to the attachment site of the piriformis tendon. In hip flexion the piriformis lies directly behind the hip joint and might reasonably be considered to contribute to the stability of the joint.

We conclude that the anatomy of the piriformis muscle is often inaccurately described in the current surgical literature and terms are used and interchanged inappropriately.

Cite this article: Bone Joint J 2013;95-B:764–9.
Is greater than 145° of deep knee flexion under weight-bearing conditions safe after total knee arthroplasty?
Authors: Niki Y. , Takeda Y. , Udagawa K. , Enomoto H. , Toyama Y. , Suda Y.
Published: May 2013

We investigated the characteristics of patients who achieved Japanese-style deep flexion (seiza-sitting) after total knee replacement (TKR) and measured three-dimensional positioning and the contact positions of the femoral and tibial components. Seiza-sitting was achieved after surgery by 23 patients (29 knees) of a series of 463 TKRs in 341 patients. Pre-operatively most of these patients were capable of seiza-sitting, had a lower body mass index and a favourable attitude towards the Japanese lifestyle (27 of 29 knees). According to two-/three-dimensional image registration analysis in the seiza-sitting position, flexion, varus and internal rotation angles of the tibial component relative to the femoral component had means of 148° (sd 8.0), 1.9° (sd 3.2) and 13.4° (sd 5.9), respectively. Femoral surface contact positions tended to be close to the posterior edge of the tibial polyethylene insert, particularly in the lateral compartment, but only 8.3% (two of 24) of knees showed femoral subluxation over the posterior edge. The mean contact positions of the femoral cam on the tibial post were located 7.8 mm (sd 1.5) proximal to the lowest point of the polyethylene surface and 5.5 mm (sd 0.9) medial to the centre of the post, indicating that the post-cam contact position translated medially during seiza-sitting, but not proximally. Collectively, the seiza-sitting position seems safe against component dislocation, but the risks of posterior edge loading and breakage of the tibial polyethylene post remain.

Cite this article: Bone Joint J 2013;95-B:782–7.
Slipped capital femoral epiphysis associated with vitamin D deficiency
Authors: Madhuri V. , Arora S. K. , Dutt V.
Published: May 2013

Slipped capital femoral epiphysis (SCFE) is uncommon in India and we routinely look for associated metabolic or endocrine abnormalities. In this study we investigated a possible association between vitamin D deficiency and SCFE. All children presenting with SCFE during the study period had their 25-hydroxyvitamin D levels measured as part of an overall metabolic, renal and endocrine status evaluation, which included measurement of body mass index (BMI). Vitamin D status was compared with age-, gender- and habitat-matched controls with acute trauma or sepsis presenting to our emergency department.

A total of 15 children (12 boys and three girls) with a mean age of 13 years (sd 1.81; 10 to 16) presented for treatment for SCFE during a two-year period beginning in January 2010. Renal and thyroid function was within the normal range in all cases. The mean BMI was 24.9 kg/m2(17.0 to 33.8), which was significantly higher than that of the controls (p = 0.006). There was a statistically significant difference between the mean values of 25-hydroxyvitamin D in the children with SCFE and the controls (11.78 ng/ml (sd 5.4) versus 27.06 ng/ml (sd 5.53), respectively; p < 0.001). We concluded that, along with high BMI, there is a significant association of vitamin D deficiency and SCFE in India.

Cite this article: Bone Joint J 2013;95-B:851–4.
Giant cell tumours of the small bones of the hands and feet
Authors: Oliveira V. C. , van der Heijden L. , van der Geest I. C. M. , Campanacci D. A. , Gibbons C. L. M. H. , van de Sande M. A. J. , Dijkstra P. D. S.
Published: May 2013

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation.

We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome.

At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet.

Cite this article: Bone Joint J 2013;95-B:838–45.
Inadequate ‘three-point’ proximal fixation predicts failure of the Gamma nail
Authors: Abram S. G. F. , Pollard T. C. B. , Andrade A. J. M. D.
Published: May 2013

The Gamma nail is frequently used in unstable peri-trochanteric hip fractures. We hypothesised that mechanical failure of the Gamma nail was associated with inadequate proximal three-point fixation. We identified a consecutive series of 299 Gamma nails implanted in 299 patients over a five-year period, 223 of whom fulfilled our inclusion criteria for investigation. The series included 61 men and 162 women with a mean age of 81 years (20 to 101). Their fractures were classified according to the Modified Evans’ classification and the quality of fracture reduction was graded. The technical adequacy of three points of proximal fixation was recorded from intra-operative fluoroscopic images, and technical inadequacy for each point was defined. All patients were followed to final follow-up and mechanical failures were identified. A multivariate statistical analysis was performed, adjusting for confounders. A total of 16 failures (7.2%) were identified. The position of the lag screw relative to the lateral cortex was the most important point of proximal fixation, and when inadequate the failure rate was 25.8% (eight of 31: odds ratio 7.5 (95% confidence interval 2.5 to 22.7), p < 0.001).

Mechanical failure of the Gamma nail in peri-trochanteric femoral fractures is rare (< 1%) when three-point proximal fixation is achieved. However, when proximal fixation is inadequate, failure rates increase. The strongest predictor of failure is positioning the lateral end of the lag screw short of the lateral cortex. Adherence to simple technical points minimises the risk of fixation failure in this vulnerable patient group.

Cite this article: Bone Joint J 2013;95-B:825–30.
Tretinoin Confused with Isotretinoin; Death from Intravenous Nimodipine; Incorrect Medication Names Selected during Order Entry; Reduce Ambien Dose in Order Sets; Confusion between Levothyroxine and Liothyronine
Authors: Cohen Michael R. , Smetzer Judy L.
Published: May 2013

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Optimizing the Customized Residency Plan
Authors: Phillips Holly , Wilkinson Samaneh T. , Buck Brian
Published: May 2013

Residents and residency program directors (RPDs) understand that the goal of the residency year is to earn a residency certificate through achievement of established goals and objectives. The customized residency plan provides a map for the resident and RPD to follow throughout the course of the residency year, helping to keep everyone on track to accomplish the established goals and objectives of the program. It also provides information that allows preceptors to take the individual resident's plan into consideration when customizing a learning experience. This article will focus on the process for developing a customized residency plan and implementing it over the course of the residency year.
Hidden Sources of Grapefruit in Beverages: Potential Interactions with Immunosuppressant Medications
Authors: Auten Ashley A. , Beauchamp Lauren N. , Joshua Taylor  , Hardinger Karen L.
Published: May 2013

Purpose

The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions.

Methods

A careful review of the ingredients of the 3 largest US beverage manufacturer's product lines was conducted through manufacturer correspondence, product labeling examination, and online nutrition database research. Focus was placed on citrus-flavored soft drinks, teas, and juice products and their impact on a patient's immunosuppressant regimens.

Results

Twenty-three beverages were identified that contained grapefruit. Five did not contain the word “grapefruit” in the product name. In addition to the confirmed grapefruit-containing products, 17 products were identified as possibly containing grapefruit juice or grapefruit extract.

Conclusion

A greater emphasis should be placed upon properly educating patients regarding hidden sources of grapefruit in popular US beverages and the potential for food-drug interactions.
Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals
Authors: Baker Danial E.
Published: May 2013

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at bakerdan@wsu.edu .
The Incentive Effect of Equalization Grants on Tax Collection
Authors: Rodríguez Javiera Bravo
Published: May 2013

Equalization grants that are inversely related to collected revenue increase the marginal cost of collecting because they tax the collection itself. The main finding is evidence for Chilean municipalities that equalization grants have this incentive effect on local revenue. In order to identify this effect, we exploit that today’s collected revenue could affect grants received 2, 3, or 4 years later, as determined by the equalization grant’gs distribution formula. This formula has undergone changes in the 1990-2006 period. We find a negative relationship between the equalization grant’s implicit tax and collected local revenue, and this effect is greater when the period of time between collection and the corresponding distribution of grants is shorter and when the political coalition to which the incumbent mayor belongs has a high likelihood of winning the next election and therefore paying this implicit tax in the coming years.
Dependence and Uniqueness in Bayesian Games
Authors: Beggs Alan W.
Published: May 2013

Abstract: This paper studies uniqueness of equilibrium in symmetric Bayesian games. It shows that if signals are highly but not perfectly dependent, then players play their risk-dominant actions for all but a vanishing set of signal realizations. In contrast to the literature on global games, noise is not assumed to be additive. Dependence is modeled using the theory of copulas.
Productive argument selection: Is lexical semantics enough?
Authors: Zeldes Amir
Published: May 2013

This paper is concerned with the ability of lexical semantic classes to predict the behavior of argument structures in productively selecting novel lexical material. It will be argued that while lexical semantic classes can explain a great deal about the spectrum of potential arguments and resulting entailments for those arguments, constructions which are synonymous from a formal semantic perspective exhibit significant differences in their empirically observed propensity for argument realization. Using corpus data and methods from Baayen's morphological productivity paradigm, I will show that such differences are not restricted to lexicalized, collocational preferences, but also extend to the readiness with which different constructions admit novel arguments.
An update on the constitutive androstane receptor (CAR)
Authors: Molnár Ferdinand , Küblbeck Jenni , Jyrkkärinne Johanna , Prantner Viktória , Honkakoski Paavo
Published: May 2013

The constitutive androstane receptor (CAR; NR1I3) has emerged as one of the main drug- and xenobiotic-sensitive transcriptional regulators. It has a major effect on the expression of several oxidative and conjugative enzymes and transporters, and hence, CAR can contribute to drug/drug interactions. Novel functions for CAR are also emerging: it is able to modulate the metabolic fate of glucose, lipids, and bile acids, and it is also involved in cell-cell communication, regulation of the cell cycle, and chemical carcinogenesis. Here, we will review the recent information available on CAR and its target gene expression, its interactions with partner proteins and mechanisms of action, interindividual and species variation, and current advances in CAR ligand selectivity and methods used in interrogation of its ligands.
Better Quality of Care or Healthier Patients? Hospital Utilization by Medicare Advantage and Fee-for-Service Enrollees
Authors: Nicholas Lauren Hersch
Published: May 2013

Do differences in rates of use among managed care and Fee-for-Service Medicare beneficiaries reflect selection bias or successful care management by insurers? I demonstrate a new method to estimate the treatment effect of insurance status on health care utilization. Using clinical information and risk-adjustment techniques on data on acute admission that are unrelated to recent medical care, I create a proxy measure of unobserved health status. I find that positive selection accounts for between one-quarter and one-third of the risk-adjusted differences in rates of hospitalization for ambulatory care sensitive conditions and elective procedures among Medicare managed care and Fee-for-Service enrollees in 7 years of Healthcare Cost and Utilization Project State Inpatient Databases from Arizona, Florida, New Jersey and New York matched to Medicare enrollment data. Beyond selection effects, I find that managed care plans reduce rates of potentially preventable hospitalizations by 12.5 per 1000 enrollees (compared to mean of 46 per 1000) and reduce annual rates of elective admissions by 4 per 1000 enrollees (mean 18.6 per 1000).
BV functions in a Gelfand triple
for differentiable measure and its applications
Authors: Röckner Michael , Zhu Rongchan , Zhu Xiangchan
Published: May 2013

In this paper, we introduce a definition of BV functions for (non-Gaussian) differentiable measure in a Gelfand triple which is an extension of the definition of BV functions in [Ann. Probab. 40 (2012), 1759–1794], using Dirichlet form theory. By this definition, we can analyze the reflected stochastic quantization problem associated with a self-adjoint operator A and a cylindrical Wiener process on a convex set Γ in a Banach space E. We prove the existence of a martingale solution of this problem if Γ is a regular convex set.
The natural pseudo-distance as a
quotient pseudo-metric, and applications
Authors: Cagliari Francesca , Di Fabio Barbara , Landi Claudia
Published: May 2013

The natural pseudo-distance is a similarity measure conceived for
the purpose of comparing shapes. In this paper we revisit this
pseudo-metric from the point of view of quotients. In particular,
we show that the natural pseudo-distance coincides with the
quotient pseudo-metric on the space of continuous functions on a
compact manifold, endowed with the uniform convergence metric,
modulo self-homeomorphisms of the manifold. As applications of
this result, the natural pseudo-distance is shown to be actually a
metric on a number of function subspaces such as the space of
topological embeddings, of isometries, and of simple Morse
functions on surfaces.
Modification of hemicelluloses with polycarboxylic acids
Authors: Zoldners Juris , Kiseleva Tatiana
Published: May 2013

Polycarboxylic acids (PCAs) aroused interest as crosslinking agents for natural polymers, such as cellulose, starch, chitosan, and hemicelluloses (HC), for improving their water resistance and imparting them new properties. Here, PCAs were studied for the crosslinking of HC films. HCs were isolated from gray alder (Alnus incana L.) wood as a water-soluble fraction by sawdust extraction with 7% potassium hydroxide. Citric acid (CA), maleic acid (MA), and butane tetracarboxylic acid (BTCA) served as crosslinking agents in the presence of sodium hypophosphite as a catalyst. The crosslinking reaction was followed by the analysis of free and esterified COOH groups in HC films. At temperatures below 100–110°C, the HC esterification process with BTCA proceeded very slowly. At 140°C, most of the acids’ COOH groups reacted with HC during 1–1.5 h. BTCA had a higher esterification activity than CA and MA. The obtained films retained their form on immersing in water and subsequent drying in the open air. The water retention value of films followed the reaction kinetics, that is, decreased with increasing reaction time. Water-resistant films were obtained with no <10–11% of BTCA and 20% of CA based on the weight of HC. The water vapor sorption capacity of the films after modification with 10% BTCA decreased approximately twice in the whole range of the relative humidity of air compared with the case of unmodified HC films.
Polyoxometalate (POM)-aided modification of lignin from wheat straw biorefinery
Authors: Dizhbite Tatiana , Jashina Lilija , Dobele Galina , Andersone Anna , Evtuguin Dmitry , Bikovens Oskar , Telysheva Galina
Published: May 2013

The oxidative modification of Biolignin (BL) has been investigated to make it more suitable as an adsorbent for transition/heavy metals. BL is a by-product of a wheat straw organosolv process for the production of pulp, ethanol, and pentoses (CIMV S.A. pilot plant, Levallois Perret, France). It was subjected to oxidation by a polyoxometalate (POM) H3[PMo12O40], aiming at the increment of oxygen-containing adsorption-active sites. The POM oxidation of BL was performed under moderate conditions (1 bar, 60–90°C, and 200°C) with the co-oxidants O2 or H2O2. The resulting lignin functionality and structure was evaluated by pyrolysis-gas chromatography/mass spectrometry, solid-state 13C nuclear magnetic resonance, Fourier transform infrared, and chemical analysis. The condensation degree of BL and its COOH and aliphatic OH group contents increased significantly, whereas the polymer structure was maintained. Under optimal conditions with POM/H2O2, the sorption capacity of lignins toward Cd(II) and Pb(II) was increased threefold and twofold, respectively.
Adipose circadian clocks: coordination of metabolic rhythms by clock genes, steroid hormones, and PPARs
Authors: Krueger Katherine C. , Feldman Brian J.
Published: May 2013

A central clock consisting of interconnected positive and negative feedback gene loops operates in the brain, tying rhythmic activity to the 24-h day. The central clock entrains similar feedback loops present in most peripheral tissues to coordinate metabolic gene expression among organs and with feeding activity for more efficient utilization of resources. Recent studies are beginning to elucidate the intricate feedback mechanisms among central and peripheral clocks and their roles in activity and metabolic homeostasis. Adipose tissue serves as a major energy storage organ and releases paracrine and endocrine hormones to signal energy status to other organs. Within the adipose tissue, the transcriptional feedback regulation between clock genes and nuclear hormone receptors, together with direct protein associations among these molecules, ensures the expression of metabolic genes at the appropriate time. This review will summarize the important components and mechanisms of adipose clock entrainment, particularly highlighting instructive studies carried out in mice. This research not only illustrates the intricate connections between clocks and metabolism but also provides potential mechanisms to correct abnormalities induced by disrupted sleep or poor diet.
Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents
Authors: Björkqvist Jenny , Lecher Bernd , Maas Coen , Renné Thomas
Published: May 2013

Contact to polyanions induces autoactivation of the serine protease factor XII that triggers the kallikrei-kinin system. Recent studies indicate that polysaccharide-induced autoactivation of factor XII has a role in allergy-related vascular leakage, and angioedema. Here, we characterize in vivo effects of the synthetic polysaccharide dextran sulfate in human plasma and in rodent models. Minute amounts of high-molecular-weight dextran sulfate-initiated factor XII-autoactivation and triggered formation of the inflammatory mediator bradykinin via plasma kallikrein-mediated cleavage of high-molecular-weight kininogen. High-molecular-weight kininogen fragments, containing the HKH20 sequence in domain D5H, blocked dextran sulfate-initiated bradykinin-generation by depleting plasma Zn2+ ions. Topical application of high molecular weight dextran sulfate increased leakage in murine skin microvessels, in a bradykinin-dependent manner. Intravital laser scanning microscopy showed a greater than two-fold elevated and accelerated fluid extravasation in C1 esterase inhibitor deficient mice that lack the major inhibitor of factor XII, compared to wild-type controls. Intra-arterial infusion of dextran sulfate induced a rapid transient drop in arterial blood pressure in rats and preinjection of kinin B2 receptor antagonists or HKH20 peptide blunted dextran sulfate-triggered hypotensive reactions. The data characterize dextran sulfate as a potent in vivo activator of factor XII with implications for bradykinin-mediated vascular permeability and blood pressure control.