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Background: Poorly controlled asthma leads to emergency department (ED) utilization and significant morbidity and mortality in pediatric patients with asthma. Inhaled corticosteroids (ICS) reduce asthma exacerbations, ED visits, and oral steroid courses for patients with poorly controlled persistent asthma. Current literature and national guidelines support the initiation of ICS for eligible patients in the ED. Approximately 21% of patients seen in our pediatric ED for asthma are eligible for ICS initiation, and 8% of that population are started on an ICS in the ED. Objective: To increase the proportion of eligible patients with …

Substance P is an undecapeptide affecting the gastrointestinal, cardiovascular, and urinary systems. In the central nervous system, substance P participates in the regulation of pain, learning, memory, and sexual homeostasis. In addition to these effects, previous papers provided solid evidence that substance P exhibits regulatory effects on growth. Indeed, our previous study revealed that growth hormone-releasing hormone (GHRH) neurons appear to be densely innervated by substance P fibers in humans. Since growth hormone secretion is regulated by the antagonistic actions of both GHRH and somatostatin, in the present paper we have examined the possibility that SP may also affect growth via the somatostatinergic system. Therefore, we have studied the putative presence of juxtapositions between the substance P-immunoreactive (IR) and somatostatinergic systems utilizing double label immunohistochemistry combined with high magnification light microscopy with oil immersion objective. In the present study, we have revealed a dense network of substance P-IR axonal varicosities contacting the majority of somatostatin-IR neurons in the human hypothalamus. Somatostatinergic perikarya are often covered by these fiber varicosities that frequently form basket-like encasements with multiple en passant type contacts, particularly in the infundibular nucleus/median eminence and in the basal periventricular area of the tuberal region. In addition, numerous substance-P-somatostatinergic juxtapositions can be found in the basal perifornical zone of the tuberal area. If these contacts are indeed functional synapses, they may represent the morphological substrate of the control of substance P on growth. Indeed, the frequency and density of these juxtapositions indicate that in addition to the regulatory action of substance P on GHRH secretion, substance P also influences growth by regulating hypothalamic somatostatinergic system via direct synaptic contacts.

The molecular modification of electrode surfaces enables synthesis of materials with atomic-level specificity. In order to fully realize the benefits of molecularly modified materials, immobilized molecules must maintain their solution-phase reactivity upon attachment to surfaces. We report the noncovalent immobilization of a pyrene-appended anthraquinone derivative onto indium tin oxide electrodes. X-ray photoelectron spectroscopy and cyclic voltammetry confirm the attachment of anthraquinone on the electrode surface. Cyclic voltammetry is reported between pH 5 and 9. The reduction potential of immobilized anthraquinone shifts cathodically with increasing pH by 60 mV/pH unit, consistent with proton-coupled electron transfer. The electron transfer rate constant also increases with increasing pH. Analogous electrochemical experiments performed using a water-soluble anthraquinone derivative freely diffusing in aqueous solution exhibit the same pH dependence in reduction potential. Thus, anthraquinone mainta...

Routine prophylaxis against venous thromboembolism is indicated following total joint arthroplasty. Prophylactic strategies differ in efficacy and safety, and variable risk exists among patients. Many strategies have been successfully used for chemoprophylaxis as well as mechanical prophylaxis with the use of pneumatic compression. Advances in battery technology and pump miniaturization have expanded the use of pneumatic compression in the post-discharge setting with mobile devices. Pneumatic compression is contraindicated in certain patients, and not all patients tolerate the devices. Mobile pneumatic compression is a valuable adjunct to venous thromboembolic risk mitigation strategies, but does not eliminate the need for pharmacologic agents.

Objective: To assess the application of a structured process to consolidate the number of medication administration times for residents of aged care facilities.Design A nonblinded, matched-pair, cluster randomized controlled trial. Setting and Participants: Permanent residents who were English-speaking and taking at least 1 regular medication, recruited from 8 South Australian residential aged care facilities (RACFs). Methods: The intervention involved a clinical pharmacist applying a validated 5-step tool to identify opportunities to reduce medication complexity (eg, by administering medications at the same time or through use of longer-acting or combination formulations). Residents in the comparison group received routine care. The primary outcome at 4-month follow-up was the number of administration times per day for medications charted regularly. Resident satisfaction and quality of life were secondary outcomes. Harms included falls, medication incidents, hospitalizations, and mortality. The association between the intervention and primary outcome was estimated using linear mixed models. Results: Overall, 99 residents participated in the intervention arm and 143 in the comparison arm. At baseline, the mean resident age was 86 years, 74% were female, and medications were taken an average of 4 times daily. Medication simplification was possible for 62 (65%) residents in the intervention arm, with 57 (62%) of 92 simplification recommendations implemented at follow-up. The mean number of administration times at follow-up was reduced in the intervention arm in comparison to usual care (−0.36, 95% confidence interval −0.63 to −0.09, P = .01). No significant changes in secondary outcomes or harms were observed. Conclusions and Implications: One-off application of a structured tool to reduce regimen complexity is a low-risk intervention to reduce the burden of medication administration in RACFs and may enable staff to shift time to other resident care activities. Refereed/Peer-reviewed

Purpose This radiation treatment planning study compares two approaches to designing a bolus for patients with head and neck cancer. Our current approach, based on clinical examination, is compared with an alternative approach, based on the patient's computed tomographic image data set, to investigate potential improvements in delivering the prescribed dose to the superficial regions of the clinical target volume (CTV) while limiting the dose to normal skin. Methods Twelve consecutive head and neck radiotherapy plans requiring a bolus were selected. A clinically placed bolus was designed by a radiation oncologist through physical examination of the patient. A virtual bolus was designed using an algorithm that configured it to overlay only the superficial CTV delineated on the patient's CT data set. These two approaches were compared on the basis of dose-volume histograms of normal skin and the superficial CTV, as well as the total bolus area. Results Of 12 patients, the virtual bolus plan resulted in a decrease in the bolus area of at least 4 cm 2 for nine patients, an increase in the bolus area of at least 30 cm 2 for three patients, and an improvement in the minimum dose to the superficial CTV in six patients. Of these six patients, half had a reduction in the bolus area with a corresponding modest 2% improvement in the minimum dose to the superficial CTV, whereas the other half had an increase in the bolus area with a corresponding dramatic 10%–57% improvement in the minimum dose to the superficial CTV. Conclusions Basing bolus design on computed tomography image data rather than on clinical examination reduced the area of normal skin under the bolus in 9 patients (75%) and improved dose coverage of the superficial CTV in 3 patients (25%). All plans benefited from the virtual bolus approach because it has been shown to be more appropriate for balancing skin sparing with target coverage.

Thyroid eye disease (TED) is a condition mainly associated with Graves' disease. We report a patient with moderate-tosevere TED who underwent a combination of intravenous and oral steroids and orbital radiotherapy that improved her visual acuity and colour vision drastically, and decreased upper lid oedema. We review the clinical features of this unusual condition, our patient's history and treatment, and the knowledge base from the current literature.

Human mesenchymal stem cells (hMSCs) are attractive candidates for tissue engineering and cell-based therapy because of their multipotentiality and availability in adult donors. However, in vitro expansion and differentiation of these cells is limited by replicative senescence. The proliferative capacity of hMSCs can be enhanced by ectopic expression of telomerase, allowing for long-term culture. However, hMSCs with constitutive telomerase expression demonstrate unregulated growth and even tumor formation. To address this problem, we used an inducible Tet-On gene expression system to create hMSCs in which ectopic telomerase expression can be induced selectively by the addition of doxycycline (i-hTERT hMSCs). i-hTERT hMSCs have inducible hTERT expression and telomerase activity, and are able to proliferate significantly longer than wild type hMSCs when hTERT expression is induced. They stop proliferating when hTERT expression is turned off and can be rescued when expression is re-induced. They retain multipotentiality in vitro even at an advanced age. We also used a selective inhibitor of telomere elongation to show that the mechanism driving immortalization of hMSCs by hTERT is dependent upon maintenance of telomere length. Thanks to their extended lifespan, preserved multipotentiality and controlled growth, i-hTERT hMSCs may prove to be a useful tool for the development and testing of novel stem cell therapies. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1879–1885, 2012

A series of allosteric kidney-type glutaminase (GLS) inhibitors were designed and synthesized using 1,4-di(5-amino-1,3,4-thiadiazol-2-yl)butane as a core scaffold. A variety of modified phenylacetyl groups were incorporated into the 5-amino group of the two thiadiazole rings in an attempt to facilitate additional binding interactions with the allosteric binding site of GLS. Among the newly synthesized compounds, 4-hydroxy-N-[5-[4-[5-[(2-phenylacetyl)amino]-1,3,4-thiadiazol-2-yl]butyl]-1,3,4-thiadiazol-2-yl]-benzeneacetamide, 2m, potently inhibited GLS with an IC50 value of 70 nM, although it did not exhibit time-dependency as seen with CB-839. Antiproliferative effects of 2m on human breast cancer lines will be also presented in comparison with those observed with CB-839.

99mTc-labeled bombesin analogues have shown promise for noninvasive detection of many tumors that express bombesin (BN)/gastrin-releasing peptide (GRP) receptors. 99mTc-labeled peptides, however, have a tendency to accumulate in the liver and intestines due to hepatobiliary clearance as a result of the lipophilicity of the 99mTc chelates. This makes the imaging of lesions in the abdominal area difficult. In this study, we have synthesized a new high affinity 99mTc-labeled BN analogue, [DTPA1, Lys3(99mTc-Pm-DADT), Tyr4]BN, having a built-in pharmacokinetic modifier, DTPA, and labeled with 99mTc using a hydrophilic diaminedithiol chelator (Pm-DADT) to effect low hepatobiliary clearance. In vitro binding studies using human prostate cancer PC-3 cell membranes showed that the inhibition constant (Ki) for [DTPA1, Lys3(99Tc-Pm-DADT), Tyr4]BN was 4.1 +/- 1.4 nM. Biodistribution studies of [DTPA1, Lys3(99mTc-Pm-DADT), Tyr4]BN in normal mice showed very low accumulation of radioactivity in the liver and intestines (1.32 +/- 0.13 and 4.58 +/- 0.50% ID, 4 h postinjection, respectively). There was significant uptake (7.71 +/- 1.37% ID/g, 1 h postinjection) in the pancreas which expresses BN/GRP receptors. The uptake in the pancreas could be blocked by BN, partially blocked by neuromedin B, but not affected by somatostatin, indicating that the in vivo binding was BN/GRP receptor specific. Scintigraphic images showed specific, high contrast delineation of prostate cancer PC-3 xenografts in SCID mice. Thus, the new peptide has a great potential for imaging BN/GRP receptor-positive cancers located even in the abdomen.

Periprosthetic infections of hip and knee joints are now treated by two-stage revision arthroplasty with an infection control rate of 91%. The present systematic review studied the reported incidence of acute kidney injury (AKI) and infection recurrence from January 1989 to June 2012 to assess the risk-benefit ratio of antibiotic spacer use. Ten observational studies (n=544 patients) with clinical outcomes showed an average incidence of AKI of 4.8%. The average reported persistence or recurrence rate of infection was 11% during a follow-up period that ranged from 13 to 108 months. The risk-benefit ratio presently favors treatment although there appears to be higher complication rates and incidence of AKI than previously reported. Marked heterogeneity in practice and lack of detail in reporting precluded more robust quantitative synthesis. Clinicians need to be aware of the potential risk of AKI, particularly in high-risk patients; practice patterns for the use of antibiotic spacers need to be standardized.

The bombesin (BN)/gastrin-releasing peptide (GRP) receptor is expressed in high density on the cell surface of a variety of tumors. This makes the receptors accessible as a molecular target for the detection of lesions in which they are expressed. In this study, we describe a high affinity hydrophilic (99m)Tc-labeled BN analogue, [DTPA(1), Lys(3)((99m)Tc-Hx-DADT), Tyr(4)]BN, having diethylenetriaminepentaacetic acid (DTPA), as a build-in pharmacokinetic modifier, to direct its excretion through the urinary system in order to lower abdominal background activity. In vitro binding studies using [(125)I-Tyr(4)]BN (K(d), 0.1 nM) and human prostate cancer PC-3 cell membranes showed that the inhibition constant (K(i)) of [DTPA(1), Lys(3)((99)Tc-Hx-DADT), Tyr(4)]BN was 19.9 +/- 8.0 nM. Biodistribution studies in normal mice showed fast blood clearance (0.15 +/- 0.01% ID/g, 4 h postinjection), low intestinal accumulation (9.16 +/- 2.35% ID/g, 4 h postinjection), and significant uptake in BN/GRP receptor rich tissues such as the pancreas (21.83 +/- 2.88% ID/g, 15 min postinjection). The pancreas/blood, pancreas/muscle, and pancreas/liver ratios were highest at 2 h postinjection at 23, 74, and 8.4, respectively. The uptake in the pancreas could be blocked by BN (11.96 +/- 1.17 vs 0.65 +/- 0.16% ID/g), partially blocked by neuromedin B (11.96 +/- 1.17 vs 6.66 +/- 0.51% ID/g), but not affected by somatostatin (11.96 +/- 1.17 vs 12.91 +/- 2.53% ID/g), indicating that the binding of [DTPA(1), Lys(3)((99m)Tc-Hx-DADT), Tyr(4)]BN to the receptors was specific. Scintigraphic imaging of human PC-3 prostate cancer xenografts in SCID mice gave a high target to nontarget ratio on the image. Thus, [DTPA(1), Lys(3)((99m)Tc-Hx-DADT), Tyr(4)]BN has the potential for imaging BN/GRP receptor-positive lesions.