bluuebunny/crossref_metadata_2025 huggingface dataset:
Thoughts on the Bioethics of Estranged Biological Kin
Authors: Cassidy Lisa
Published: January 2012

This paper considers the bioethics of estranged biological kin, who are biologically related people not in contact with one another (due to adoption, abandonment, or other long‐term estrangement). Specifically, I am interested in what is owed to estranged biological kin in the event of medical need. A survey of current bioethics demonstrates that most analyses are not prepared to reckon with the complications of having or being estranged biological kin. For example, adoptees might wonder if a lack of contact with biological kin could someday affect their medical care (or affect the medical care of their biological relatives).

Estranged biological kin, such as adoptees, present us with a chance to think about human connection. After sketching several organ‐donation and adoption tropes, I argue that a feminist analysis of vulnerability and dependency is helpful for understanding the confusing ties of estranged biological kin. I conclude by proposing a medical registry that would put adoptees and others in touch with their estranged biological kin on a medically as‐needed basis.
Antiepileptic drug selection for people with HIV/AIDS: Evidence‐based guidelines from the ILAE and AAN
Authors: Birbeck Gretchen L. , French Jacqueline A. , Perucca Emilio , Simpson David M. , Fraimow Henry , George Jomy M. , Okulicz Jason F. , Clifford David B. , Hachad Houda , Levy for the Quality Standards subcommittee of the American René H.
Published: January 2012

A joint panel of the American Academy of Neurology (AAN) and the International League Against Epilepsy (ILAE) convened to develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED–ARV interactions. Key findings from this literature search included the following: AED–ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of approximately 50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of approximately 50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme‐inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors because pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C).
Intracranial extramedullary hematopoiesis in patients with thalassemia: a case report and review of the literature
Authors: Eskazan Ahmet Emre , Ar Muhlis Cem , Baslar Zafer
Published: January 2012

BACKGROUND: Extramedullary hematopoiesis (EH) is a compensatory phenomenon that results in the production of blood cell precursors outside the marrow in patients with chronic hemolytic anemia and ineffective erythropoiesis. EH usually involves the liver, spleen, and lymph nodes. It can also be found at paravertebral, intrathoracic, or pelvic locations. Intracranial EH is a rare entity and often asymptomatic but can sometimes lead to symptomatic tumor‐like masses. Treatment options are controversial and include hypertransfusion, surgical excision, radiotherapy, and hydroxyurea (HU).

STUDY DESIGN AND METHODS: Successful treatment of an intracranial EH mass with HU and blood transfusions in a beta‐thalassemia major patient was discussed along with a review of the published literature on intracranial EH in thalassemia.

RESULTS: In our patient, the extramedullary hematopoietic mass in the interhemispheric fissure showed a marked improvement after 6 months of HU and hypertransfusion therapy. In the English literature, there are a few cases with intracranial EH and thalassemia, which were treated with different treatment modalities, with different outcomes.

CONCLUSION: There is no standard treatment approach in patients with symptomatic EH. HU with hypertransfusion regimen is a reasonable first‐choice modality in treating intracranial EH masses.
Development and Validation of a Simple GC–MS Method for the Simultaneous Determination of 11 Anticholinesterase Pesticides in Blood—Clinical and Forensic Toxicology Applications
Authors: Papoutsis Ioannis , Mendonis Marcela , Nikolaou Panagiota , Athanaselis Sotirios , Pistos Constantinos , Maravelias Constantinos , Spiliopoulou Chara
Published: January 2012

Abstract:  Anticholinesterase pesticides are widely used, and as a result they are involved in numerous acute and even fatal poisonings. The aim of this study was the development, optimization, and validation of a simple, rapid, specific, and sensitive gas chromatography–mass spectrometry method for the determination of 11 anticholinesterase pesticides (aldicarb, azinphos methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, methamidophos, methidathion, methomyl, and terbufos) in blood. Only 500 μL of blood was used, and the recoveries after liquid–liquid extraction (toluene/chloroform, 4:1, v/v) were more than 65.6%. The calibration curves were linear (R2 ≥ 0.996). Limit of detections and limit of quantifications were found to be between 1.00–10.0 and 3.00–30.0 μg/L, respectively. Accuracy expressed as the %Er was found to be between −11.0 and 7.8%. Precision expressed as the percent relative standard deviation was found to be <9.4%. The developed method can be applied for the investigation of both forensic and clinical cases of accidental or suicidal poisoning with these pesticides.
Diclofenac and 2‐anilinophenylacetate degradation by combined activity of biogenic manganese oxides and silver
Authors: Meerburg Francis , Hennebel Tom , Vanhaecke Lynn , Verstraete Willy , Boon Nico
Published: January 2012

The occurrence of a range of recalcitrant organic micropollutants in our aquatic environment has led to the development of various tertiary wastewater treatment methods. In this study, biogenic manganese oxides (Bio‐MnOx), biogenic silver nanoparticles (Bio‐Ag0) and ionic silver were used for the oxidative removal of the frequently encountered drug diclofenac and its dechlorinated form, 2‐anilinophenylacetate (APA). Diclofenac was rapidly degraded during ongoing manganese oxidation by Pseudomonas putida MnB6. Furthermore, whereas preoxidized Bio‐MnOx, Bio‐Ag0 and Ag+ separately did not show any removal capacity for diclofenac, an enhanced removal occurred when Bio‐MnOx and silver species were combined. Similar results were obtained for APA. Finally, a slow removal of diclofenac but more rapid APA degradation was observed when silver was added to manganese‐free P. putida biomass. Combining these results, three mechanisms of diclofenac and APA removal could be distinguished: (i) a co‐metabolic removal during active Mn2+ oxidation by P. putida; (ii) a synergistic interaction between preoxidized Bio‐MnOx and silver species; and (iii) a (bio)chemical process by biomass enriched with silver catalysts. This paper demonstrates the use of P. putida for water treatment purposes and is the first report of the application of silver combined with biogenic manganese for the removal of organic water contaminants.
Design of Rotor for Internal Gear Pump Using Cycloid and Circular-Arc Curves
Authors: Choi T. H. , Kim M. S. , Lee G. S. , Jung S. Y. , Bae J. H. , Kim C.
Published: January 2012

In the case of internal gear pumps, the eccentricity of the outer rotor, which resembles a circular lobe, must be limited to a certain value in order to avoid the formation of cusps and loops; furthermore, the tip width of the inner rotor, which has a hypocycloid curve and an epicycloid curve, should not be allowed to exceed the limit value. In this study, we suggest that the tip width of the inner rotor be controlled by inserting a circular-arc curve between the hypocycloid and epicycloid curves. We also suggest that the outer rotor be designed using the closed-form equation for the inner rotor and the width correction coefficient. Thus, it is possible to design a gerotor for which there is no upper limit on the eccentricity, as in this case, undercut is prevented and there is no restriction on the tip width. We also develop an automated program for rotor design and calculation of the flow rate and flow rate irregularity. We demonstrate the superior performance of the gerotor developed in this study by analyzing the internal fluid flow using a commercial computational fluid dynamics (CFD)-code.
Analysis of NOX Formation in an Axially Staged Combustion System at Elevated Pressure Conditions
Authors: Prathap Chockalingam , Galeazzo Flavio C. C. , Kasabov Plamen , Habisreuther Peter , Zarzalis Nikolaos , Beck Christian , Krebs Werner , Wegner Bernhard
Published: January 2012

The objective of this investigation was to study the effect of axially staged injection of methane in the vitiated air cross flow in a two stage combustion chamber on the formation of NOX for different momentum flux ratios. The primary cylindrical combustor equipped with a low swirl air blast nozzle operating with Jet-A liquid fuel generates vitiated air in the temperature range of 1473–1673 K at pressures of 5–8 bars. A methane injector was flush mounted to the inner surface of the secondary combustor at an angle of 30 deg. Oil cooled movable and static gas probes were used to collect the gas samples. The mole fractions of NO, NO2, CO, CO2, and O2 in the collected exhaust gas samples were measured using gas analyzers. For all the investigated operating conditions, the change in the mole fraction of NOX due to the injection of methane (ΔNOX) corrected to 15% O2 and measured in dry mode was less than 15 ppm. The mole fraction of ΔNOX increased with an increase in mass flow rate of methane and it was not affected by a change in the momentum flux ratio. The penetration depth of the methane jet was estimated from the profiles of mole fraction of O2 obtained from the samples collected using the movable gas probe. For the investigated momentum flux ratios, the penetration depth observed was 15 mm at 5 bars and 5 mm at 6.5 and 8 bars. The results obtained from the simulations of the secondary combustor using a RANS turbulence model were also presented. Reaction modeling of the jet flame present in a vitiated air cross flow posed a significant challenge as it was embedded in a high turbulent flow and burns in partial premixed mode. The applicability of two different reaction models has been investigated. The first approach employed a combination of the eddy dissipation and the finite rate chemistry models to determine the reaction rate, while the presumed JPDF model was used in the further investigations. Predictions were in closer agreement to the measurements while employing the presumed JPDF model. This model was also able to predict some key features of the flow such as the change of penetration depth with the pressure.
An Analytical Model for a Piezoelectric Axially Driven Membrane Microcompressor for Optimum Scaled Down Design
Authors: Simon M. J. , Bright V. M. , Radebaugh R. , Lee Y. C.
Published: January 2012

A new and comprehensive analytical model for membrane microcompressors driven axially by a single lead zirconium titanate (PZT) stack actuator that incorporates assembly variation errors is presented. The model can be used as a future design aid, to predict dynamic device performance as a function of error severity and as microcompressor dimensions are scaled down from the macro to micro scale. The major conclusion of this work is that since micro compressors can be made adjustable to achieve maximum compression ratio another factor besides assembly variation error reduces the achievable compression ratio. An analytical method to predict the maximum pressure to within ∼5% of that experimentally measured is developed. Also, a numerical method to predict the maximum pressure to within ∼0.6% of that experimentally measured is defined. Moreover, an analytical method to predict the compression ratio degradation factor as a function of assembly variation error for adjustable and fixed devices is presented. It is shown that compression ratio is a function of this single net error parameter, and that this function is scale invariant. The model also outputs membrane moments, vertical shear forces, and stresses throughout actuation cycles.
How Do You Handle Your Antibodies?
Authors: Niewold Timothy B.
Published: January 2012

Genome-wide association study of a rare complex disease implicates an immunoglobulin receptor variant.
Sport category is an important determinant of cardiac adaptation: an MRI study
Authors: Luijkx Tim , Cramer Maarten J , Prakken Niek H J , Buckens Constantinus F , Mosterd Arend , Rienks Rienk , Backx Frank J G , Mali Willem P Th M , Velthuis Birgitta K
Published: January 2012

Background

Physiological cardiac adaptation in athletes is influenced by body surface area, gender, age, training intensity and sport type. This study assesses the influence of sport category and provides a physiological reference for sport category and gender.

Methods

Three hundred and eighty-one subjects (mean age 25±5 years, range 18 to 39 years; 61% men) underwent cardiac MRI and ECG: 114 healthy non-athletes (≤3 training h/week) and 267 healthy elite athletes (mean 17±6.6 training h/week). Athletes performed low-dynamic high-static (LD-HS, n=42), high-dynamic low-static (HD-LS, n=144) or high-dynamic high-static sports (HD-HS, n=81).

Results

Left ventricular (LV) end-diastolic volume (EDV) index (ml/m2) for non-athletes/LD-HS/HD-LS/HD-HS, respectively, was 101/107/122/129 in men and 90/103/106/111 in women. LV end-diastolic mass (EDM) index (g/m2) for non-athletes/LD-HS/HD-LS/HD-HS was, respectively, 47/49/57/69 for men and 34/38/42/51 for women. Left or right ventricular EDV ratios were alike in all groups. LV EDV/EDM ratios were similar in non-athletes/LD-HS/HD-LS athletes, and only lower in HD-HS athletes, disproving selective ventricular wall thickening in LD-HS athletes. Multivariate linear regression demonstrated HD-LS and HD-HS sport category coefficients (p<0.01) larger than those of training hours, gender and age (LV EDV/EDM coefficients for sport category LD-HS 6/0.75, HD-LS 16/7, HD-HS 21/17). ECG abnormalities were most frequent in HD-HS athletes and in male subjects.

Conclusions

This study demonstrates a balanced cardiac adaptation with preserved ratios of LV/right ventricular volume (in all sport categories) and LV volume/wall mass (in LD-HS and HD-LS sports). Sport category has a strong impact on cardiac adaptation. HD-HS sports show the largest changes, whereas LD-HS sports show dimensions similar to non-athletes.
Ideal Convergence ofk-Positive Linear Operators
Authors: Gadjiev Akif , Duman Oktay , Ghorbanalizadeh A. M.
Published: January 2012

We study some ideal convergence results ofk-positive linear operators defined on an appropriate subspace of the space of all analytic functions on a bounded simply connected domain in the complex plane. We also show that our approximation results with respect to ideal convergence are more general than the classical ones.
Improved production of biohydrogen in light-powered Escherichia coli by co-expression of proteorhodopsin and heterologous hydrogenase
Authors: Kim Jaoon YH , Jo ByungHoon , Jo Younghwa , Cha HyungJoon
Published: January 2012

Background

Solar energy is the ultimate energy source on the Earth. The conversion of solar energy into fuels and energy sources can be an ideal solution to address energy problems. The recent discovery of proteorhodopsin in uncultured marine γ-proteobacteria has made it possible to construct recombinant Escherichia coli with the function of light-driven proton pumps. Protons that translocate across membranes by proteorhodopsin generate a proton motive force for ATP synthesis by ATPase. Excess protons can also be substrates for hydrogen (H2) production by hydrogenase in the periplasmic space. In the present work, we investigated the effect of the co-expression of proteorhodopsin and hydrogenase on H2 production yield under light conditions.

Results

Recombinant E. coli BL21(DE3) co-expressing proteorhodopsin and [NiFe]-hydrogenase from Hydrogenovibrio marinus produced ~1.3-fold more H2 in the presence of exogenous retinal than in the absence of retinal under light conditions (70 μmole photon/(m2·s)). We also observed the synergistic effect of proteorhodopsin with endogenous retinal on H2 production (~1.3-fold more) with a dual plasmid system compared to the strain with a single plasmid for the sole expression of hydrogenase. The increase of light intensity from 70 to 130 μmole photon/(m2·s) led to an increase (~1.8-fold) in H2 production from 287.3 to 525.7 mL H2/L-culture in the culture of recombinant E. coli co-expressing hydrogenase and proteorhodopsin in conjunction with endogenous retinal. The conversion efficiency of light energy to H2 achieved in this study was ~3.4%.

Conclusion

Here, we report for the first time the potential application of proteorhodopsin for the production of biohydrogen, a promising alternative fuel. We showed that H2 production was enhanced by the co-expression of proteorhodopsin and [NiFe]-hydrogenase in recombinant E. coli BL21(DE3) in a light intensity-dependent manner. These results demonstrate that E. coli can be applied as light-powered cell factories for biohydrogen production by introducing proteorhodopsin.
FDA Advise-ERR: FDA Approves Hydromorphone Labeling Revisions to Reduce Medication Errors;Differentiating Penicillin from Penicillamine;Infusion Reconnected to the Wrong Patient;Spell Out Acetaminophen on Prescription Labels
Authors: Michael R. Cohen , Judy L. Smetzer
Published: January 2012

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.
Ticagrelor
Authors: Dennis J. Cada , Levien Terri L. , Danial E. Baker
Published: January 2012

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The January 2012 monograph topics are on clobazam, ruxolitinib, bupivacaine liposome injection suspension, ivacaftor, and teriflunomide. The DUE/MUE is on clobazam.
Recent Publications on Medications and Pharmacy
Authors: Flint Russett
Published: January 2012

Hospital Pharmacy presents this feature to keep pharmacists abreast of new publications in the medical/pharmacy literature. Articles of interest regarding a broad scope of topics are abstracted monthly.
Comprehensive Gene Expression Profiling in the Prefrontal Cortex Links Immune Activation and Neutrophil Infiltration to Antinociception
Authors: Poh Kay-Wee , Yeo Jin-Fei , Stohler Christian S. , Ong Wei-Yi
Published: January 2012

Functional neuroimaging studies have implicated the prefrontal cortex (PFCTX) in descending modulation of pain and the placebo effect. This study was performed to elucidate comprehensive PFCTX gene expression in an animal model of persistent trigeminal pain. Adult male C57BL/6J mice received facial carrageenan injection and showed sustained increase in nociceptive responses. Microarray analyses of differentially expressed genes in the PFCTX at 3 d after injection showed “immune system process” as the dominant ontology term and increased mRNA expression ofS100a8,S100a9,Lcn2,Il2rg,Fcgr1,Fcgr2b,C1qb,Ptprc,Ccl12, andCd52were verified by RT-PCR. Upregulation of S100A8, S100A9, and lipocalin 2 (LCN2) were confirmed by Western blots, and cells in the PFCTX were double immunolabeled with MPO, indicating they were neutrophils. Analyses of blood of facial carrageenan-injected mice also showed increased mRNA expression of these markers, suggesting transmigration of activated neutrophils into the brain. Other immune-related genes,Il2rg,Fcgr2b,C1qb,Ptprc, andCcl12were upregulated in the PFCTX but not blood. Approximately 70% of S100A9-positive cells in the PFCTX of carrageenan-injected mice were located in capillaries adherent to endothelial cells, whereas 30% were within the brain parenchyma. Carrageenan-injected mice showed significantly reduced nociceptive responses after injection of C terminus of murine S100A9 protein in the lateral ventricles and PFCTX but not somatosensory barrel cortex. Together, these findings demonstrate activation of immune-related genes in the PFCTX during inflammatory pain and highlight an exciting role of neutrophils in linking peripheral inflammation with immune activation of the PFCTX and antinociception.
Slit1b-Robo3 Signaling and N-Cadherin Regulate Apical Process Retraction in Developing Retinal Ganglion Cells
Authors: Wong Grace K. W. , Baudet Marie-Laure , Norden Caren , Leung Louis , Harris William A.
Published: January 2012

When neurons exit the cell cycle after their terminal mitosis, they detach from the apical surface of the neuroepithelium. Despite the fact that this detachment is crucial for further neurogenesis and neuronal migration, the underlying mechanisms are still not understood. Here, taking advantage of the genetics and imaging possibilities of the zebrafish retina as a model system, we show by knockdown experiments that the guidance molecule Slit1b and its receptor Robo3 are required for apical retraction of retinal ganglion cells (RGCs). In contrast, N-cadherin seems to be responsible for maintenance of apical attachment, as expression of dominant-negative N-cadherin causes RGCs to lose apical attachments prematurely and rescues retraction inslit1bmorphants. These results suggest that Slit-Robo signaling downregulates N-cadherin activity to allow apical retraction in newly generated RGCs.
Topographic Contribution of Early Visual Cortex to Short-Term Memory Consolidation: A Transcranial Magnetic Stimulation Study
Authors: van de Ven Vincent , Jacobs Christianne , Sack Alexander T.
Published: January 2012

The neural correlates for retention of visual information in visual short-term memory are considered separate from those of sensory encoding. However, recent findings suggest that sensory areas may play a role also in short-term memory. We investigated the functional relevance, spatial specificity, and temporal characteristics of human early visual cortex in the consolidation of capacity-limited topographic visual memory using transcranial magnetic stimulation (TMS). Topographically specific TMS pulses were delivered over lateralized occipital cortex at 100, 200, or 400 ms into the retention phase of a modified change detection task with low or high memory loads. For the high but not the low memory load, we found decreased memory performance for memory trials in the visual field contralateral, but not ipsilateral to the side of TMS, when pulses were delivered at 200 ms into the retention interval. A behavioral version of the TMS experiment, in which a distractor stimulus (memory mask) replaced the TMS pulses, further corroborated these findings. Our findings suggest that retinotopic visual cortex contributes to the short-term consolidation of topographic visual memory during early stages of the retention of visual information. Further, TMS-induced interference decreased the strength (amplitude) of the memory representation, which most strongly affected the high memory load trials.
Afadin, A Ras/Rap Effector That Controls Cadherin Function, Promotes Spine and Excitatory Synapse Density in the Hippocampus
Authors: Beaudoin Gerard M. J. , Schofield Claude M. , Nuwal Tulip , Zang Keling , Ullian Erik M. , Huang Bo , Reichardt Louis F.
Published: January 2012

Many molecules regulate synaptogenesis, but intracellular signaling pathways required for their functions are poorly understood. Afadin is a Rap-regulated, actin-binding protein that promotes cadherin complex assembly as well as binding many other cell adhesion molecules and receptors. To examine its role in mediating synaptogenesis, we deletedafadin(mllt1), using a conditional allele, in postmitotic hippocampal neurons. Consistent with its role in promoting cadherin recruitment,afadindeletion resulted in 70% fewer and less intense N-cadherin puncta with similar reductions of β-catenin and αN-catenin puncta densities and 35% reduction in EphB2 puncta density. Its absence also resulted in 40% decreases in spine and excitatory synapse densities in the stratum radiatum of CA1, as determined by morphology, apposition of presynaptic and postsynaptic markers, and synaptic transmission. The remaining synapses appeared to function normally. Thus, afadin is a key intracellular signaling molecule for cadherin recruitment and is necessary for spine and synapse formationin vivo.
Constitutive Activation of Ca2+/Calmodulin-Dependent Protein Kinase II during Development Impairs Central Cholinergic Transmission in a Circuit Underlying Escape Behavior inDrosophila
Authors: Kadas Dimitrios , Tzortzopoulos Athanasios , Skoulakis Efthimios M. C. , Consoulas Christos
Published: January 2012

Development of neural circuitry relies on precise matching between correct synaptic partners and appropriate synaptic strength tuning. Adaptive developmental adjustments may emerge from activity and calcium-dependent mechanisms. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been associated with developmental synaptic plasticity, but its varied roles in different synapses and developmental stages make mechanistic generalizations difficult. In contrast, we focused on synaptic development roles of CaMKII in a defined sensory-motor circuit. Thus, different forms of CaMKII were expressed with UAS-Gal4 in distinct components of the giant fiber system, the escape circuit ofDrosophila, consisting of photoreceptors, interneurons, motoneurons, and muscles.

The results demonstrate that the constitutively active CaMKII-T287D impairs development of cholinergic synapses in giant fiber dendrites and thoracic motoneurons, preventing light-induced escape behavior. The locus of the defects is postsynaptic as demonstrated by selective expression of transgenes in distinct components of the circuit. Furthermore, defects among these cholinergic synapses varied in severity, while the glutamatergic neuromuscular junctions appeared unaffected, demonstrating differential effects of CaMKII misregulation on distinct synapses of the same circuit. Limiting transgene expression to adult circuits had no effects, supporting the role of misregulated kinase activity in the development of the system rather than in acutely mediating escape responses. Overexpression of wild-type transgenes did not affect circuit development and function, suggesting but not proving that the CaMKII-T287D effects are not due to ectopic expression. Therefore, regulated CaMKII autophosphorylation appears essential in central synapse development, and particular cholinergic synapses are affected differentially, although they operate via the same nicotinic receptor.
The Regulation of Filamentous Growth in Yeast
Authors: Cullen Paul J , Sprague George F
Published: January 2012

Filamentous growth is a nutrient-regulated growth response that occurs in many fungal species. In pathogens, filamentous growth is critical for host–cell attachment, invasion into tissues, and virulence. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth, which provides a genetically tractable system to study the molecular basis of the response. Filamentous growth is regulated by evolutionarily conserved signaling pathways. One of these pathways is a mitogen activated protein kinase (MAPK) pathway. A remarkable feature of the filamentous growth MAPK pathway is that it is composed of factors that also function in other pathways. An intriguing challenge therefore has been to understand how pathways that share components establish and maintain their identity. Other canonical signaling pathways—rat sarcoma/protein kinase A (RAS/PKA), sucrose nonfermentable (SNF), and target of rapamycin (TOR)—also regulate filamentous growth, which raises the question of how signals from multiple pathways become integrated into a coordinated response. Together, these pathways regulate cell differentiation to the filamentous type, which is characterized by changes in cell adhesion, cell polarity, and cell shape. How these changes are accomplished is also discussed. High-throughput genomics approaches have recently uncovered new connections to filamentous growth regulation. These connections suggest that filamentous growth is a more complex and globally regulated behavior than is currently appreciated, which may help to pave the way for future investigations into this eukaryotic cell differentiation behavior.
Calculation of Expected Body Weight in Adolescents With Eating Disorders
Authors: Le Grange Daniel , Doyle Peter M. , Swanson Sonja A. , Ludwig Kali , Glunz Catherine , Kreipe Richard E.
Published: January 2012

OBJECTIVE:

To examine the agreement between three methods to calculate expected body weight (EBW) for adolescents with eating disorders: (1) BMI percentile, (2) McLaren, and (3) Moore methods.

METHODS:

The authors conducted a cross-sectional analysis of baseline information from adolescents seeking treatment of disordered eating at The University of Chicago. Adolescents (N = 373) aged 12 to 18 years (mean = 15.84, SD = 1.72), with anorexia nervosa (n = 130), bulimia nervosa (n = 59), or eating disorder not otherwise specified (n = 184). Concurrence between the BMI percentile, McLaren, and Moore methods was assessed for agreement above or below arbitrary cut points used in relation to hospitalization (75%), diagnosis (85%), and healthy weight (100%). Patterns of absolute discrepancies were examined by height, age, gender, and menstrual status. Limitations to some of these methods allowed comparison between all 3 methods in only 204 participants.

RESULTS:

Moderate agreement was seen between the 3 methods (κ values, 0.48–0.74), with pairwise total classification accuracy at each cut point ranging from 84% to 98%. The most discrepant calculations were observed among the tallest (>75th percentile) and shortest (<20th percentile) cases and older ages (>16 years). Many of the most discrepant cases fell above and below 85% EBW when comparing the BMI percentile and Moore methods, indicating disagreement on possible diagnosis of anorexia nervosa.

CONCLUSIONS:

These methods largely agree on percent EBW in terms of clinically significant cut points. However, the McLaren and Moore methods present with limitations, and a commonly agreed-upon method for EBW calculation such as the BMI percentile method is recommended for clinical and research purposes.
Modern pharmacological therapy of breast cancer
Authors: Láng István , Kahán Zsuzsanna , Hitre Erika , Dank Magdolna , Rubovszky Gábor , Horváth Zsolt , Kásler Miklós
Published: January 2012

Healthy lifestyle, population-based screening mammography and modern medical-oncological treatment in specialized breast cancer centers are the basic elements of the fight against breast cancer mortality. Treatment plan for the individual patient should be recommended by multidisciplinary oncoteam before initiating definitive therapy. Strategy of the medical-oncological therapy of breast cancer is determined by the biological features and stage of the tumor. The most important biological features are endocrine sensitivity, Human Epidermal Growth Factor Receptor 2 status and proliferative capability of the tumor. In this review the strategy of medical-oncological treatment (chemotherapy, endocrine therapy, targeted biological therapy) of breast cancer is presented, based on receptor status and proliferative capability of the tumor in various stages of the disease. Orv. Hetil., 2012, 153, 56–65.
Oscillations of difference equations with general advanced argument
Authors: Chatzarakis George , Stavroulakis Ioannis
Published: January 2012

Consider the first order linear difference equation with general advanced argument and variable coefficients of the form
$$\nabla x(n) - p(n)x(\tau (n)) = 0, n \geqslant 1,$$
where {p(n)} is a sequence of nonnegative real numbers, {τ(n)} is a sequence of positive integers such that
$$\tau (n) \geqslant n + 1, n \geqslant 1,$$
and ▿ denotes the backward difference operator ▿x(n) = x(n) − x(n − 1). Sufficient conditions which guarantee that all solutions oscillate are established. Examples illustrating the results are given.
Review of Ukrainian Species of the Genus Meliboeus (Coleoptera, Buprestidae, Agrilinae)
Authors: Prokhorov A.
Published: January 2012

Review of Ukrainian Species of the Genus Meliboeus (Coleoptera, Buprestidae, Agrilinae)

Five Ukrainian species of the genus Meliboeus are reviewed and keyed and the data on their distribution in the Palaearctic Region and Ukraine, examined material and larval host plants are given. A poorly known species Meliboeus morawitzi (Semenov, 1905) is redescribed.
Ingestion of a Foreign Body Unmasks an Asymptomatic Small Bowel Carcinoid Tumor
Authors: Wang Yi-Zarn , Greiffenstein Patrick
Published: January 2012

Bowel obstruction is a common surgical admission around the world. On the other hand, small intestinal tumors, such as midgut carcinoid, are uncommon neoplasms and an infrequent cause of intestinal obstruction leading to hospitalization. A foreign body is an extremely rare cause of intestinal obstruction and when ingested, foreign bodies most often lodge in the narrowest portion of the gastrointestinal tract. Narrowing of the small bowel due to a neoplasm can prohibit the passage of an accidentally ingested foreign object and produce an obstruction that neither the neoplasm nor the foreign body could have produced alone. We hereby report a case in which an accidentally ingested piece of foreign material leads to the finding of a small, early stage, asymptomatic, midgut carcinoid cancer in the proximal ileum that would have otherwise eluded detection for several years.
Additional Biological Therapies for Attention-Deficit Hyperactivity Disorder: Repetitive Transcranical Magnetic Stimulation of 1 Hz Helps to Reduce Methylphenidate
Authors: Niederhofer Helmut
Published: January 2012

Excessive hyperactivity, impulsiveness and attentional difficulties characterize attentiondeficit hyperactivity disorder (ADHD). The aim of this case report is to signal the possible therapeutic effectiveness of the repetitive transcranial magnetic stimulation (rTMS). Low frequency (1Hz, 1200 stim/die for five days) was applied on the impending scalp in the motor additional area of a patient suffering from combined type ADHD who received methylphenidate (MPH). We saw a significant improvement, especially according to criteria associated with hyperactivity. The improvement lasted for at least three weeks and suggested the final reduction in dosage of MPH.to 10 mg.
Abdominal Wall Metastasis in Scar after Open Resection of an Adrenocortical Carcinoma
Authors: Gupta Nikhil , Bansal Umesh , Mahajan Neha , Yadav Maha Singh
Published: January 2012

A 42-year-old man patient presented with progressively increasing, occasionally painful lump in the left upper and central abdomen. Investigations revealed well-defined capsulated left adrenocortical carcinoma. Tumor was resected successfully along with left kidney. Tumor recurred in the abdominal surgical scar 1.5 years after surgery. We are reporting this case because of rarity of metastatic recurrence of an adrenocortical carcinoma in the abdominal surgical scar 1.5 years after resection of primary tumor.
Lead‐Oriented Synthesis: A New Opportunity for Synthetic Chemistry
Authors: Nadin Alan , Hattotuwagama Channa , Churcher Ian
Published: January 2012

The pharmaceutical industry remains solely reliant on synthetic chemistry methodology to prepare compounds for small‐molecule drug discovery programmes. The importance of the physicochemical properties of these molecules in determining their success in drug development is now well understood but we present here data suggesting that much synthetic methodology is unintentionally predisposed to producing molecules with poorer drug‐like properties. This bias may have ramifications to the early hit‐ and lead‐finding phases of the drug discovery process when larger numbers of compounds from array techniques are prepared. To address this issue we describe for the first time the concept of lead‐oriented synthesis and the opportunity for its adoption to increase the range and quality of molecules used to develop new medicines.
Medial plica syndrome: A review of the literature
Authors: Bellary Sharath S. , Lynch Garret , Housman Brian , Esmaeili Ehsan , Gielecki Jerzy , Tubbs R. Shane , Loukas Marios
Published: January 2012

Knee pain is a very common complaint seen in the clinical setting. A torn medial meniscus, osteochondral defects, inflammation, or an irritated medial plica are some of the most common causes of medial knee pain. Plicae are synovial invaginations that are believed to be remnants of the embryological development of the knee. They have a potential to become inflamed and symptomatic. Diagnosis of medial plica syndrome involves physical exam and imaging studies, but the current gold standard is arthroscopy and therefore a definitive diagnosis cannot be made until surgery. As such, medial plicae are the most commonly missed diagnoses in the knee as it is purely a clinical diagnosis. Medial plica syndrome can be treated with physiotherapy, corticosteroid injections, or surgery. Overall, good outcomes have been seen following diagnosis and treatment of medial plica syndrome, with patients returning to their preferred levels of activity. This article reviews the topic of medial plica syndrome. Clin. Anat. 25:423–428, 2012. © 2011 Wiley Periodicals, Inc.
Arginine Mimetics Using α‐Guanidino Acids: Introduction of Functional Groups and Stereochemistry Adjacent to Recognition Guanidiniums in Peptides
Authors: Balakrishnan Shalini , Scheuermann Michael J. , Zondlo Neal J.
Published: December 2011

Arginine residues are broadly employed for specific biomolecular recognition, including in protein–protein, protein–DNA, and protein–RNA interactions. Arginine recognition commonly exploits the potential for bidentate electrostatic and hydrogen‐bonding interactions. However, in arginine residues, the guanidinium functional group is located at the terminus of a flexible hydrocarbon side chain, which lacks the functionality to contribute to specific arginine‐mediated recognition and may entropically disfavor binding. In order to enhance the potential for specificity and affinity in arginine‐mediated molecular recognition, we have developed an approach to the synthesis of peptides that incorporates an α‐guanidino acid as a novel arginine mimetic. α‐Guanidino acids, derived from α‐amino acids, with guanidinylation of the amino group, were incorporated stereospecifically into peptides on solid phase via coupling of an Fmoc amino acid to diaminopropionic acid (Dap), Fmoc deprotection, guanidinylation of the amine on solid phase, and deprotection, generating a peptide containing an α‐functionalized arginine mimetic. This approach was examined by incorporating arginine mimetics into ligands for the Src, Grb, and Crk SH3 domains at the site of the key recognition arginine. Protein binding was examined for peptides containing guanidino acids derived from Gly, L‐Val, L‐Phe, L‐Trp, D‐Val, D‐Phe, and D‐Trp. We demonstrate that paralogue specificity and target site affinity may be modulated with the use of α‐guanidino acid‐derived arginine mimetics, generating peptides that exhibit enhanced Src specificity by selection against Grb and peptides that reverse the specificity of the native peptide ligand, with enhancements in Src target specificity of up to 15‐fold (1.6 kcal mol−1).
Functionalization of Oxidases with Peroxidase Activity Creates Oxiperoxidases: A New Breed of Hybrid Enzyme Capable of Cascade Chemistry
Authors: Winter Remko T. , van den Berg Tomas E. , Colpa Dana I. , van Bloois Edwin , Fraaije Marco W.
Published: December 2011

The covalent flavoprotein alditol oxidase (AldO) from Streptomyces coelicolor A3(2) was endowed with an extra catalytic functionality by fusing it to a microperoxidase. Purification of the construct resulted in the isolation of a synthetic bifunctional enzyme that was both fully covalently flavinylated and heminylated: an oxiperoxidase. Characterization revealed that both oxidase and peroxidase functionalities were active, with the construct functioning as a single‐component xylitol biosensor. In an attempt to reduce the size of the oxidase–peroxidase fusion, we replaced portions of the native AldO sequence with the bacterial cytochrome c CXXCH heme‐binding motif. By mutating only three residues of the AldO protein we were able to create a functional oxidase–peroxidase hybrid.
An Efficient and Odorless Synthesis of Thioethers Using 2‐[Bis(alkylthio)methylene]‐3‐oxo‐N‐o‐tolylbutanamides as Thiol Equivalents
Authors: Yu Haifeng
Published: December 2011

Using 2‐[bis(alkylthio)methylene]‐3‐oxo‐N‐o‐tolylbutanamides 1 as odorless thiol equivalents, an efficient and odorless synthesis of thioethers has been developed. Promoted by NaOH in EtOH, the cleavage of 1 commences to generate thiolate anions, and the generated thiolate anions then react with halides to give various thioethers in good yield. It is noteworthy that only a very faint odor of thiols can be perceived during both the reaction and the workup.
Dynamic Changes of Sediment Discharge and the Influencing Factors in the Yellow River, China, for the Recent 90 Years
Authors: Mu Xingmin , Zhang Xiuqin , Shao Hongbo , Gao Peng , Wang Fei , Jiao Juying , Zhu Jingliang
Published: December 2011

The dynamic changes in the sediment discharge over 90 years from 1919 to 2008 in the Yellow River in China were assessed on the basis of annual rainfall series and annual sediment series in Shan County hydrological station. The key factors affecting sediment discharge, such as rainfall, and human activities were studied. Anomaly accumulation method and double mass curve were employed to test the stage changes of sediment discharge, and to determine the main factors of sediment decline. Results showed that the annual average sediment discharge under natural conditions was about 16 × 108 t, but the measured annual average sediment during 1919–2008 was 12.71 × 108 t. The highest annual average during the study period was 39.10 × 108 t in 1933 while the lowest was 1.77 × 108 t in 2008. Sediment discharge in the Yellow River experienced two low sediment stages (1924–1931 and 1979–2008) and a high sediment stage (1932–1971), respectively. Since 1979, there was a significant decreasing trend in the sediment discharge, and the main influencing factor was fierce human activities. Annual average sediment discharge in the post‐development period (1979–2008) was 69.7% lower than that in the pre‐development period (1919–1978), with average reduction of 81 and 19% caused by human activities and rainfall, respectively. These results provide important evidence for making protecting policy for water resources quality and environmental safety of the Yellow River.
A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low‐grade B‐cell lymphomas
Authors: Sinha Rajni , Kaufman Jonathan L. , Khoury Hanna Jean , King Nassoma , Shenoy Pareen J. , Lewis Carol , Bumpers Kevin , Hutchison‐Rzepka Amanda , Tighiouart Mourad , Heffner Leonard T. , Lechowicz Mary Jo , Lonial Sagar , Flowers Christopher R.
Published: January 2012

BACKGROUND:

Bortezomib has demonstrated efficacy in patients with relapsed B‐cell non‐Hodgkin lymphoma (NHL) both alone and in combination with other agents; however, limited data exist regarding its toxicity in combination with common frontline therapies for indolent NHL. A phase 1 study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone (R‐CHOP) was conducted in patients with untreated follicular lymphoma (FL) and other indolent NHLs.

METHODS:

Nineteen patients, including 10 patients with FL, were enrolled. The median patient age was 59 years (range, 29‐71 years). Seven patients had a FL International Prognostic Index score ≥3. R‐CHOP with the vincristine dose capped at 1.5 mg was administered on a 21‐day cycle for 6 to 8 cycles, and 1 of 3 dose levels of bortezomib (1.0 mg/m2 [n = 1], 1.3 mg/m2 [n = 6], or 1.6 mg/m2 [n = 12]) was administered on days 1 and 8 of each cycle using a Bayesian algorithm for dose escalation.

RESULTS:

The maximum tolerated dose (MTD) of bortezomib with modified R‐CHOP was reached at 1.6 mg/m2. Dose‐limiting toxicity was observed in 5 patients (1 patient at a bortezomib dose of 1.0 mg/m2, 1 patient at a bortezomib dose of 1.3 mg/m2, and 3 patients at a bortezomib dose of 1.6 mg/m2). Neuropathy occurred in 16 patients (84%), including 2 patients (11%) who experienced grade 3 sensory neuropathy. Grade 4 hematologic toxicity occurred in 4 patients. Of 19 evaluable patients, 100% responded, and the complete response rate was 68%. At a median follow‐up of 32 months, the 3‐year progression‐free survival rate was 89.5%.

CONCLUSIONS:

Bortezomib combined with modified R‐CHOP produced high response rates without substantial increases in toxicity. A phase 2 study of R‐CHOP and bortezomib given at this established MTD is currently ongoing. Cancer 2012;3538–3548. © 2012 American Cancer Society.