bluuebunny/crossref_metadata_2025 huggingface dataset:
Nerve Growth Factor Eye Drop Administration Improves Visual Function in a Patient With Optic Glioma
Authors: Chiaretti Antonio , Falsini Benedetto , Servidei Serenella , Marangoni Dario , Pierri Filomena , Riccardi Riccardo
Published: February 2011

Background. Spontaneous visual improvement in people with an optic glioma (OG) of the anterior or retrochiasmatic optic pathways is rare. Objective. To evaluate the effects on visual function of nerve growth factor (NGF) eye drop administration in a patient with severe visual impairment due to a low-grade OG. Methods. A 45-year-old woman with OG and long-standing optic nerve atrophy was assessed before and after 2 NGF treatment courses. The drug used was 2.5S murine NGF. One milligram of NGF, diluted in saline solution, was administered onto the conjunctiva of both eyes for 10 consecutive days 3 times a day for each treatment. The follow-up was performed by clinical, neuroradiologic, and electrophysiological tests (electroretinogram and visual evoked potentials [VEPs]) at the end of each treatment and 30 and 60 days later. Results. A repeated subjective and objective improvement of visual function (>3 lines visual acuity; >40° visual field; >50% VEP amplitude increase, Wilcoxon test P < .01) was recorded after NGF treatment. These measures tended to deteriorate toward baseline values 60 days from the end of each NGF treatment. No ocular or systemic side effects were observed throughout treatment. Conclusions. Conjunctival NGF may be a beneficial adjunct therapy for visual loss in patients with OG, possibly exerting its effects on residual viable optic pathways.
Efficacy of Using a Novel Endoscopic Lens Cleaning Device: A Prospective Randomized Controlled Trial
Authors: Cassera Maria A. , Goers Trudie A. , Spaun Georg O. , Swanström Lee L.
Published: February 2011

Introduction. Clear visualization of the surgical field is critical in laparoscopic surgery. The authors evaluated a device that does not necessitate an external cleaning process for the laparoscope. It was hypothesized that it will minimize the interruption in operative workflow. Methods. A total of 40 advanced laparoscopy patients were randomized to either the control or device group. Demographic data, procedural data, length of stay, frequency and duration of lens cleaning, and lens clarity scores (LCS) were recorded. Independent samples t test and Fisher’s exact test were performed. Results . No significant difference was found between the device and control groups in demographic data, procedure time ( P = .922) or LCS ( P = .124). Laparoscope cleaning in the device group was significantly shorter than in the control group ( P < .001). No complications were observed. Conclusion. An intra-abdominal laparoscopic cleaning device can effectively clean the laparoscopic lens and lead to less workflow interruption. Although not documented in this study, it may also lead to shorter operative times.
Teaching Medical Students About Obesity: A Pilot Program to Address an Unmet Need Through Longitudinal Relationships With Bariatric Surgery Patients
Authors: Roberts David H. , Kane Erin M. , Jones Daniel B. , Almeida Jacqueline M. , Bell Sigall K. , Weinstein Amy R. , Schwartzstein Richard M.
Published: February 2011

Background. Despite obesity’s relevance and impact, curricula addressing obesity are underrepresented in clinical medical education. A novel pilot program to begin teaching medical students about care of the obese patient was developed and student attitudes toward obesity and bariatric surgery were assessed. Methods.The authors paired third-year students with obese patients undergoing bariatric surgery. Students established a longitudinal patient relationship, received faculty mentorship, and kept a reflections journal. An attitude assessment survey was administered before and after third year. Reflections were analyzed for common themes. Results. Baseline student responses differed from those previously reported for practicing physicians on many survey statements, including more strongly agreeing with the relationship between obesity and serious medical conditions ( P < .001), the need to educate patients about obesity risks ( P < .001), and willingness to recommend bariatric surgery evaluation ( P = .004). These differences were maintained after clinical clerkships. Reflection themes included recognition of obesity stereotypes, improved estimation of body mass index, and awareness of physicians’ attitudes about obesity. Conclusion. Development and assessment of a novel pilot program to teach third-year medical students about obesity and bariatric surgery suggests a potential impact on student attitudes and understanding of obesity and obesity surgery. Students today may have different attitudes toward obesity than those reflected in prior data for physicians in practice, and programs such as this may help maintain positive attitudes.
Shifting priorities in multimorbidity: a longitudinal qualitative study of patient’s prioritization of multiple conditions
Authors: Morris Rebecca L , Sanders Caroline , Kennedy Anne P , Rogers Anne
Published: February 2011

Objective: To examine what influences self-management priorities for individuals with multiple long-term conditions and how this changes over time.

Methods: A longitudinal qualitative study using semi-structured interviews completed with 21 participants with more than one chronic condition.

Results: The study demonstrates the impact of multiple conditions on many aspects of people’s illness management. Narratives illuminated how individual’s condition priorities changed at pivotal points and altered their engagement with self-management practices. This is influenced by contact with health professionals and how people framed illness and lifestyle changes. Medication management was a central point where individuals took control of their conditions. Additional conditions were more readily accommodated if people established a cognitive link between existing management practices. Thus, multiple conditions were not inevitably experienced as an increasing burden but subject to considerable flux and change.

Discussion: Prioritizing one condition over another at a particular time together with a transfer and amalgamation of practices appears to facilitate accommodation of multiple conditions and ease the burden of everyday management. These findings have implications for how we understand the variable nature of multimorbidity experience and management for patients. Clinicians might usefully engage with patients’ understanding to reduce complexity, and enhance engagement of condition management.
Clinical approach to optic neuritis: pitfalls, red flags and differential diagnosis
Authors: Voss Elke , Raab Peter , Trebst Corinna , Stangel Martin
Published: February 2011

Demyelinating optic neuritis (ON) is the most common cause of optic neuropathy typically presenting with a subacute painful visual loss. In 20% of patients with multiple sclerosis (MS), ON is the presenting symptom and half of the patients with isolated ON develop MS within 15 years. The diagnosis of ON plays an important role in neurological practice. A correct and early diagnosis is necessary to ensure optimal further investigations and treatment. Other causes of optic neuropathies such as connective tissue disorders, infectious diseases, tumours or ischaemic neuropathies are less frequent but clinical and therapeutic management can differ dramatically. We present five patients admitted to our hospital with suspected demyelinating ON, but the clinical work up revealed different causes of optic neuropathy. We discuss the differential diagnosis of ON and clinical red flags that require careful diagnostic assessment of other diseases. A workflow for the diagnosis of optic neuropathies is presented.
Estimating Cashflow-at-Risk (CFaR)
Authors: Jang SooCheong (Shawn) , Park Kwangmin , Lee Ji-eun
Published: February 2011

Of the many risks faced by restaurants, a shortage of cashflow is among the most damaging. This study introduces an effective tool to estimate the cashflow risk of restaurants, so that firms can be ready to address the potential risks. Using a comparables approach to Cashflow-at-Risk (CFaR), the study analyzes cashflow data from publicly listed U.S. restaurant firms from 1988 to 2007. The study found that estimated cashflow shortfalls were larger for small and medium-size firms than for large firms. Also, full-service restaurants’ cashflow shortfalls were larger than those of limited-service restaurants, suggesting relative cashflow risk positions for different restaurant segments. This study provides nonfinancial firms such as restaurant firms with a practical tool to estimate cashflow risk, which could mitigate the probability of financial distress and improve the financial health of firms.
A Taxonomy for Resorts
Authors: Brey Eric T.
Published: February 2011

Resort classification methods have so far struggled in creating mutually exclusive categories that are based on a solid definition of resort. This article proposes a resort classification system that allows industry comparisons across typologies and geographic limitations. Through multiple interviews with more than sixty resort professionals, this study develops a definition stating minimum qualifications for a resort and proposes a classification system based on range and scope of amenities. Emphasizing resorts’ leisure orientation, while taking into consideration the growth of conventions and business meetings, the definition sets minimum qualifications that include size, variety of amenities, food and beverage outlets, and specific lodging qualifications. The definition and classification differentiates resorts from resort-like properties. The taxonomy of four categories includes rules that address specific issues surrounding resort classification.
The replication rate of human hematopoietic stem cells in vivo
Authors: Catlin Sandra N. , Busque Lambert , Gale Rosemary E. , Guttorp Peter , Abkowitz Janis L.
Published: February 2011

Hematopoietic stem cells (HSCs) replicate (self-renew) to create 2 daughter cells with capabilities equivalent to their parent, as well as differentiate, and thus can both maintain and restore blood cell production. Cell labeling with division-sensitive markers and competitive transplantation studies have been used to estimate the replication rate of murine HSCs in vivo. However, these methods are not feasible in humans and surrogate assays are required. In this report, we analyze the changing ratio with age of maternal/paternal X-chromosome phenotypes in blood cells from females and infer that human HSCs replicate on average once every 40 weeks (range, 25-50 weeks). We then confirm this estimate with 2 independent approaches, use the estimate to simulate human hematopoiesis, and show that the simulations accurately reproduce marrow transplantation data. Our simulations also provide evidence that the number of human HSCs increases from birth until adolescence and then plateaus, and that the ratio of contributing to quiescent HSCs in humans significantly differs from mouse. In addition, they suggest that human marrow failure, such as the marrow failure that occurs after umbilical cord blood transplantation and with aplastic anemia, results from insufficient numbers of early progenitor cells, and not the absence of HSCs.
Genome-wide analysis of target genes regulated by HoxB4 in hematopoietic stem and progenitor cells developing from embryonic stem cells
Authors: Oshima Motohiko , Endoh Mitsuhiro , Endo Takaho A. , Toyoda Tetsuro , Nakajima-Takagi Yaeko , Sugiyama Fumihiro , Koseki Haruhiko , Kyba Michael , Iwama Atsushi , Osawa Mitsujiro
Published: February 2011

Forced expression of the transcription factor HoxB4 has been shown to enhance the self-renewal capacity of mouse bone marrow hematopoietic stem cells (HSCs) and confer a long-term repopulating capacity to yolk sac and embryonic stem (ES) cell–derived hematopoietic precursors. The fact that ES cell–derived precursors do not repopulate bone marrow without HoxB4 underscores an important role for HoxB4 in the maturation of ES-derived hematopoietic precursors into long-term repopulating HSCs. However, the precise molecular mechanism underlying this process is barely understood. In this study, we performed a genome-wide analysis of HoxB4 using ES cell–derived hematopoietic stem/progenitor cells. The results revealed many of the genes essential for HSC development to be direct targets of HoxB4, such as Runx1, Scl/Tal1, Gata2, and Gfi1. The expression profiling also showed that HoxB4 indirectly affects the expression of several important genes, such as Lmo2, Erg, Meis1, Pbx1, Nov, AhR, and Hemgn. HoxB4 tended to activate the transcription, but the down-regulation of a significant portion of direct targets suggested its function to be context-dependent. These findings indicate that HoxB4 reprograms a set of key regulator genes to facilitate the maturation of developing HSCs into repopulating cells. Our list of HoxB4 targets also provides novel candidate regulators for HSCs.
The influence of environmental calcium concentrations on calcium flux, compensatory drinking and epithelial calcium channel expression in a freshwater cartilaginous fish
Authors: Allen Peter J. , Weihrauch Dirk , Grandmaison Vanessa , Dasiewicz Patricia , Peake Stephan J. , Anderson W. Gary
Published: February 2011

Calcium metabolism and mRNA levels of the epithelial calcium channel (ECaC) were examined in a freshwater cartilaginous fish, the lake sturgeon Acipenser fulvescens. Lake sturgeon were acclimated for ≥2 weeks to 0.1 (low), 0.4 (normal) or 3.3 (high) mmol l–1 environmental calcium. Whole-body calcium flux was examined using 45Ca as a radioactive marker. Net calcium flux was inward in all treatment groups; however, calcium influx was greatest in the low calcium environment and lowest in the high calcium environment, whereas efflux had the opposite relationship. A significant difference in the concentration of 45Ca in the gastrointestinal tract (GIT) of fish in the low calcium environment led to the examination of drinking rate and calcium flux across the anterior-middle (mid) intestine. Drinking rate was not different between treatments; however, calcium influx across the mid-intestine in the low calcium treatment was significantly greater than that in both the normal and high calcium treatments. The lake sturgeon ECaC was 2831 bp in length, with a predicted protein sequence of 683 amino acids that shared a 66% identity with the closest sequenced ECaCs from the vertebrate phyla. ECaC mRNA levels were examined in the gills, kidney, pyloric caeca, mid-intestine and spiral intestine. Expression levels were highest in the gills, then the kidneys, and were orders of magnitude lower in the GIT. Contrary to existing models for calcium uptake in the teleost gill, ECaC expression was greatest in high calcium conditions and kidney ECaC expression was lowest in low calcium conditions, suggesting that cellular transport mechanisms for calcium may be distinctly different in these freshwater cartilaginous fishes.
Temperature gradients in the flight muscles ofManduca sextaimply a spatial gradient in muscle force and energy output
Authors: George Nicole T. , Daniel Tom L.
Published: February 2011

There is a significant dorso-ventral temperature gradient in the dominant flight muscles [dorsolongitudinal muscles (DLM1)] of the hawkmoth Manduca sexta during tethered flight. The mean temperature difference was 5.6°C (range=3.8–6.9°C) between the warmer, ventral-most subunits and the cooler, dorsal-most subunits. As force generation in muscle depends on temperature, the mechanical energy output of more dorsal subunits will differ from that of deeper and warmer muscle subunits. To test this hypothesis, we isolated the dorsal subunits and the ventral subunits and recorded both single and 25 Hz (wingbeat frequency) isometric contractions at a range of temperatures. Our data show that the contractile dynamics of the various regions of the DLM1 are similarly affected by temperature, with higher temperatures leading to reduced contraction times. Furthermore, using standard electromyography, we showed that the different regions are activated nearly simultaneously (mean time difference=0.22 ms). These observations suggest that the existence of a temperature gradient will necessarily produce a mechanical energy gradient in the DLM1 in M. sexta.
Neural circuit activity in freely behaving zebrafish (Danio rerio)
Authors: Issa Fadi A. , O'Brien Georgeann , Kettunen Petronella , Sagasti Alvaro , Glanzman David L. , Papazian Diane M.
Published: February 2011

Examining neuronal network activity in freely behaving animals is advantageous for probing the function of the vertebrate central nervous system. Here, we describe a simple, robust technique for monitoring the activity of neural circuits in unfettered, freely behaving zebrafish (Danio rerio). Zebrafish respond to unexpected tactile stimuli with short- or long-latency escape behaviors, which are mediated by distinct neural circuits. Using dipole electrodes immersed in the aquarium, we measured electric field potentials generated in muscle during short- and long-latency escapes. We found that activation of the underlying neural circuits produced unique field potential signatures that are easily recognized and can be repeatedly monitored. In conjunction with behavioral analysis, we used this technique to track changes in the pattern of circuit activation during the first week of development in animals whose trigeminal sensory neurons were unilaterally ablated. One day post-ablation, the frequency of short- and long-latency responses was significantly lower on the ablated side than on the intact side. Three days post-ablation, a significant fraction of escapes evoked by stimuli on the ablated side was improperly executed, with the animal turning towards rather than away from the stimulus. However, the overall response rate remained low. Seven days post-ablation, the frequency of escapes increased dramatically and the percentage of improperly executed escapes declined. Our results demonstrate that trigeminal ablation results in rapid reconfiguration of the escape circuitry, with reinnervation by new sensory neurons and adaptive changes in behavior. This technique is valuable for probing the activity, development, plasticity and regeneration of neural circuits under natural conditions.
Identification of erythroid progenitors induced by erythropoietic activity inXenopus laevis
Authors: Nogawa-Kosaka Nami , Sugai Tatsuhisa , Nagasawa Kazumichi , Tanizaki Yuta , Meguro Mizue , Aizawa Youichi , Maekawa Shun , Adachi Motoyasu , Kuroki Ryota , Kato Takashi
Published: February 2011

Oxygen is essential for the survival of animals. Red blood cells in the circulation, i.e. peripheral erythrocytes, are responsible for transporting oxygen to tissues. The regulation of erythropoiesis in vertebrates other than mammals is yet to be elucidated. Recently we identified erythropoietin, a primary regulator of erythropoiesis, in Xenopus laevis, which should enable us to identify target cells, including erythroid progenitors, and to investigate the production and development of erythroid cells in amphibians. Here, we established a semi-solid colony-forming assay in Xenopus laevis to clarify the existence of colony-forming unit-erythroid cells, the functional erythroid progenitors identified in vitro. Using this assay, we showed that recombinant xlEPO induces erythroid colony formation in vitro and detected an increased level of erythropoietin activity in blood serum during acute anemic stress. In addition, our study demonstrated the possible presence of multiple, non-xlEPO, factors in anemic serum supportive of erythroid colony formation. These results indicate that erythropoiesis mediated by erythropoietin is present in amphibian species and, furthermore, that the regulatory mechanisms controlling peripheral erythrocyte number may vary among vertebrates.
Burrow extension with a proboscis: mechanics of burrowing by the glycerid Hemipodus simplex
Authors: Murphy Elizabeth A. K. , Dorgan Kelly M.
Published: February 2011

Burrowing marine infauna are morphologically diverse and ecologically important as ecosystem engineers. The polychaetes Nereis virens and Cirriformia moorei extend their burrows by crack propagation. Nereis virens does so by everting its pharynx and C. moorei, lacking an eversible pharynx or proboscis, uses its hydrostatic skeleton to expand its anterior. Both behaviors apply stress to the burrow wall that is amplified at the tip of the crack, which extends by fracture. That two species with such distinct morphologies and life histories both burrow by fracturing sediment suggests that this mechanism may be widespread among burrowers. We tested this hypothesis with the glycerid polychaete Hemipodus simplex, which has an eversible proboscis that is much longer and everts more rapidly than the pharynx of N. virens. When the proboscis is fully everted, the tip flares out wider than the rest of the proboscis, creating a shape and applying a stress distribution similar to that of N. virens and resulting in relatively large forces near the tip of the crack. These forces are larger than necessary to extend the crack by fracture and are surprisingly uncorrelated with the resulting stress amplification at the crack tip, which is also larger than necessary to extend the burrow by fracture. These large forces may plastically deform the mud, allowing the worm to build a semi-permanent burrow. Our results illustrate that similar mechanisms of burrowing are used by morphologically different burrowers.
The Sources and Popularity of Online Drug Information: An Analysis of Top Search Engine Results and Web Page Views
Authors: Law Michael R , Mintzes Barbara , Morgan Steven G
Published: February 2011

Background:

The Internet has become a popular source of health information. However, there is little information on what drug information and which Web sites are being searched.

Objective:

To investigate the sources of online information about prescription drugs by assessing the most common Web sites returned in online drug searches and to assess the comparative popularity of Web pages for particular drugs.

Methods:

This was a cross-sectional study of search results for the most commonly dispensed drugs in the US (n = 278 active ingredients) on 4 popular search engines: Bing, Google (both US and Canada), and Yahoo. We determined the number of times a Web site appeared as the first result. A linked retrospective analysis counted Wikipedia page hits for each of these drugs In 2008 and 2009.

Results:

About three quarters of the first result on Google USA for both brand and generic names linked to the National Library of Medicine. In contrast, Wikipedia was the first result for approximately 80% of generic name searches on the other 3 sites. On these other sites, over two thirds of brand name searches led to industry-sponsored sites. The Wikipedia pages with the highest number of hits were mainly for opiates, benzodiazepines, antibiotics, and antidepressants.

Conclusions:

Wikipedia and the National Library of Medicine rank highly In online drug searches. Further, our results suggest that patients most often seek information on drugs with the potential for dependence, for stigmatized conditions, that have received media attention, and for episodic treatments. Quality improvement efforts should focus on these drugs.
Azathioprine-lnduced Fever in Sarcoidosis
Authors: McBane Sarah , Rojas Carlos
Published: February 2011

Objective:

To report a case of drug-induced fever associated with azathioprine treatment in a patient with sarcoidosis.

Case Summary:

A 52-year-old man with pulmonary sarcoidosis presented to the emergency department with a 1 -day history of fever (temperature 39.9 °C), chills, nausea, and vomiting. One week earlier, azathioprine 50 mg/day had been started for worsening dyspnea. The patient was admitted and evaluated for acute infectious processes. All of his home medications (hydroxychloroquine, prednisone, fluticasone/salmeterol, lovastatin, pantoprazole, Zolpidem, ibandronate, albuterol), except prednisone, were held. Results of chest X-ray, viral cultures, and urine and blood cultures revealed no source of infection. The patient's temperature returned to normal within 30 hours after discontinuation of azathioprine; rechallenge was not performed.

Discussion:

Fever as an adverse drug reaction is often unrecognized, particularly in medically complex patients. Azathioprine has been reported to cause drug fever in patients with inflammatory bowel disease and in those with rheumatoid arthritis; to our knowledge, there have been no previous reports documenting azathioprine-induced fever in patients with sarcoidosis. The chronological course of febrile response and defervescence is highly suggestive of drug-induced fever.

Conclusions:

The rapid resolution of fever after discontinuation of azathioprine suggests that it was the likely source of fever in this patient. If azathioprine is increasingly prescribed in patients with sarcoidosis, fever as an adverse reaction may become more common.
Metal nanoparticle-enhanced radiative transitions: Giving singlet oxygen emission a boost
Authors: Toftegaard Rasmus , Arnbjerg Jacob , Cong Huaiping , Agheli Hossein , Sutherland Duncan S. , Ogilby Peter R.
Published: February 2011

The fabrication and use of metal nanoparticles to influence electronic transitions in a given molecule is of growing interest; there is much to be gained by developing and exploiting methods to enhance weak optical signals. Singlet molecular oxygen, O2(a1∆g), which is an important intermediate in many oxidation reactions, particularly in biological systems, is ideally monitored by the 1275-nm O2(a1∆g) → O2(X3Σg–) phosphorescent transition. Unfortunately, the latter is highly forbidden and, as such, often presents a severe limitation in the application of this optical probe. In this paper, we describe how this weak phosphorescent transition can be enhanced by using localized surface plasmons (LSPs) from specially engineered gold nanostructures. In an attempt to elucidate the mechanism of this process, data were recorded from samples in which we decoupled the component of the plasmon resonance that absorbs incident light from the component that scatters incident light. We find that the latter appears to be the feature of significance in the process through which singlet oxygen phosphorescence is enhanced. In this work, we also illustrate how the singlet oxygen system provides an ideal model for a general study of metal-enhanced radiative rate constants.
Supramolecular complexation and photocyclodimerization of methyl 3-methoxy-2-naphthoate with modified γ-cyclodextrins
Authors: Liang Wenting , Zhang Hui-Hui , Wang Jing-Jing , Peng Yuan , Chen Bin , Yang Cheng , Tung Chen-Ho , Wu Li-Zhu , Fukuhara Gaku , Mori Tadashi , Inoue Yoshihisa
Published: February 2011

A series of modified γ-cyclodextrins (CDs) were prepared as chiral host for catalyzing the enantiodifferentiating photocyclodimerization of methyl 3-methoxy-2-naphthoate (NA). The complexation behavior of NA with modified γ-CDs was studied by UV–vis, fluorescence, and circular dichroism spectroscopies. All of the modified γ-CDs formed stable 1:2 host–guest complex with NA, and binding affinities for two-step complexation critically depended on the structure of modified γ-CDs. The enantioselectivity of NA photocyclodimerization was also significantly affected by the modification of γ-CD. The secondary rim-modification considerably reduced the enantioselectivity, for which the interrupted hydrogen-bonding network, leading to a flexible CD skeleton, is most probably responsible.
Upregulation of thyroid transcription factor-1 and human leukocyte antigen class I in Hashimoto's disease providing a clinical evidence for possible triggering autoimmune reaction
Authors: Huang Huibin , Li Xisheng , Lin Ling , Shi Yaxiong , Lin Xiahong , Li Liangyi , Xu Dongming
Published: February 2011

Objective

An increase in the expression of autoantigens and their presenting molecules human leukocyte antigen (HLA) class I has been demonstrated to be responsible for autoimmune diseases. Thyroid transcription factor-1 (TTF-1 or NKX2-1) synchronously upregulates both HLA class I and thyroid-specific autoantigen, which may be involved in the pathological process of autoimmune thyroiditis. In this study, the expressions and potential role of TTF-1 and HLA class I in Hashimoto's disease (HT) were examined.

Patients

In this study, 22 resection specimens clinically and histopathologically confirmed to have Hashimoto's disease and 30 normal thyroid specimens from adjacent tissues of thyroid adenoma were used.

Measurement

Western blot, real-time PCR, and immunohistochemistry were performed to assay TTF-1 and HLA class I in the thyrocytes of Hashimoto's disease as well as in the normal thyroid from adjacent tissues of thyroid adenoma.

Results

The TTF-1 and HLA class I in Hashimoto's disease were significantly higher than those in the controls.

Conclusion

Upregulation of TTF-1 and HLA class I in Hashimoto's disease provide a clinical evidence for possible triggering of autoimmune reaction.
Tumor Biology and Prognostic Factors in Renal Cell Carcinoma
Authors: Finley David S. , Pantuck Allan J. , Belldegrun Arie S.
Published: February 2011

In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed.
Targeted Therapies for the Treatment of Metastatic Renal Cell Carcinoma: Clinical Evidence
Authors: Hutson Thomas E.
Published: February 2011

Although systemic therapy for patients with metastatic renal cell carcinoma (mRCC) was once limited to the cytokines interleukin-2 and interferon (IFN)-α, in recent years several targeted therapies have become available for first- and second-line use. These include sorafenib, sunitinib, bevacizumab (plus IFN-α), temsirolimus, everolimus, and, most recently, pazopanib. This expanded list of treatment options arose from molecular biological research that revealed aberrant signal transduction activities in RCC, enabling the identification of specific molecular targets for therapy. Molecular-targeted therapies have better efficacy and tolerability than cytokine therapy, and many are administered orally. The superior outcomes achieved with molecular-targeted agents are prompting investigators to reconsider overall survival as a primary endpoint in clinical trials, given the inherent complications of a required long duration of follow-up, a required large population, and confounding caused by crossover trial designs or effects of subsequent therapy after progression on the agent of interest. In mRCC trials, progression-free survival has become a popular primary endpoint and has served as the basis of approval for several targeted therapies. In addition to the identification of new agents, current research is focused on the evaluation of combination therapy with targeted agents. As more information regarding mechanisms of disease and drug resistance becomes available, new targets, new targeted agents, and new combinations will be studied with the goal of providing maximal efficacy with minimal toxicity. This article reviews the clinical evidence supporting the benefits of targeted agents in mRCC treatment, discusses survival endpoints used in their pivotal clinical trials, and outlines future research directions.
Treatment-Associated Adverse Event Management in the Advanced Renal Cell Carcinoma Patient Treated with Targeted Therapies
Authors: Ravaud Alain
Published: February 2011

Targeted therapy for advanced renal cell carcinoma (RCC) has recently expanded the available treatment options for patients with these malignancies. The rapid introduction of novel treatment options into clinical practice within a relatively short time frame has created some new challenges pertaining to adverse event (AE) management in patients with advanced RCC. Accumulating safety data from the pivotal phase III clinical trials of the anti–vascular endothelial growth factor (VEGF) antibody bevacizumab plus interferon, VEGF receptor tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), and mammalian target of rapamycin inhibitors (temsirolimus and everolimus) have served to characterize the toxicity profiles of these novel agents. Overall, it is evident that RCC-directed targeted therapy differs from immunotherapy and cytotoxic chemotherapy in terms of a number of unique nonhematologic AEs (some of which have not been traditionally encountered in oncology practice) and that there are distinctions within and across the various classes of agents with respect to the most prominent AEs and the risk for less common but serious complications. Although treatment-associated AEs are common, the majority of AEs reported during clinical trial experiences were grade 1 or 2 in severity and manageable with intervention in the form of supportive measures and/or dosage modification. Therefore, despite the relatively complex AE profiles of RCC-directed targeted therapy, patient education, consistent monitoring with a focus on early detection by health care providers (oncologists, general physicians, nurses), and the application of emerging AE management strategies may allow for prolonged treatment in most patients with advanced RCC.
Clinical Practice Guidelines for the Treatment of Metastatic Renal Cell Carcinoma: Today and Tomorrow
Authors: Molina Ana M. , Motzer Robert J.
Published: February 2011

In the U.S. and Europe, clinical practice guidelines for metastatic renal cell carcinoma have undergone several revisions as a result of the introduction of molecular-targeted therapies. Recently, the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU) published updated guidelines to reflect these new treatment approaches that provide greater efficacy and better tolerability than the previous standard of care, cytokine therapy with interleukin-2 or interferon-α. Recommendations are classified by line of therapy, Memorial Sloan-Kettering Cancer Center risk level for survival, and level of evidence. Although many similarities exist, levels of evidence between the NCCN and EAU guidelines have differing designations and definitions, and timing of updates varies. New research developments, such as identification of effective combinations of targeted agents, optimal regimens for sequential therapy, newly designed targeted agents, benefits in special populations, and identification of additional prognostic factors and biomarkers, will prompt continued updates and refinements of today's clinical practice guidelines, with the goal of providing physicians with the most up-to-date clinical consensus upon which to base treatment decisions. Because clinical trial populations may not represent real-life patient populations, recommendations should serve only as a guide and must be tailored to the needs of each patient.
The Political and Economic Context of Home Care Work in California
Authors: Delp Linda , Muntaner Carles
Published: February 2011

California's primarily female, ethnically diverse home care workforce is at the intersection of the public and private spheres of work and at the front line of recurring policy and budget debates targeting government-funded long-term care services. The convening of a Home Care Research Working Group in 2001 has led to collaborative action research initiatives and advocacy for policies to improve working conditions and home care services. The study reported here demonstrates that: 1) current long-term care policy is inadequate to ameliorate home care stressors such as physical and emotional demands, schedule conflicts, financial strain, and job insecurity; 2) workers' experience of home care differs by gender and by race or ethnic group; and 3) a union that actively engages workers is a viable avenue to provide individual support and empowerment as well as collective advocacy for home care services, critical in an era of attacks against health and social service programs.
Housework and Recovery from Work among Nursing Teams: A Gender Perspective
Authors: Rotenberg Lúcia , Griep Rosane Harter , Pessanha Joseane , Gomes Luciana , Portela Luciana Fernandes , Fonseca Maria de Jesus Mendes
Published: February 2011

The impact on health of work carried out within the household is recognized by several authors in the occupational health field. The purpose of this article is to verify whether and to what extent the need for recovery is related to professional work hours and to housework duties in female nursing workers. Workers ( N = 1122) completed a questionnaire with data on household chores and professional work, as well as the Need for Recovery from Work scale. Regression analysis showed that the odds for reporting poor recovery were significantly higher for workers showing long domestic work hours, high total work load (professional plus domestic work hours), and housework overload. No association was found for professional work hours per se. Findings highlight the potential detrimental effects of housework, either by itself or in combination with professional work for the group studied, and can generate discussion on gender equality in both the public and private domains.
Gender-Based Political Harassment and Violence: Effects on the Political Work and Public Roles of Women
Authors: Valverde María Eugenia Rojas
Published: February 2011

This article shows the significance of the problems of political harassment and violence against women in positions of political responsibility in Bolivia. This phenomenon is seen in both rural and urban areas and transcends borders. It has been shown that these attacks constitute a violation of women's civil and political rights and a threat to the physical and mental health of women leaders in Bolivia. Furthermore, there is no punishment of guilty parties, reparation, or moral or material compensation for the women who are affected. In Bolivia, gender-based harassment and violence is a fundamental barrier to women's political participation. However, this phenomenon is still not addressed by government programs and is not part of the public discourse and debate. In spite of the measures taken to promote women's political participation, several different administrations have been unable to guarantee women the capacity to occupy positions of responsibility without being threatened or harassed. The results of our research led to a bill addressing this problem. Subsequently, Ecuador took this bill as an example and replicated it in a legislative initiative. These results show the importance of research by organizations that represent women in preventing unjust situations and health problems.
Immunohistochemical Analysis Reveals an Influx of Regulatory T Cells and Focal Trophoblastic STAT-1 Phosphorylation in Chronic Villitis of Unknown Etiology
Authors: Katzman Philip J. , Murphy Shawn P. , Oble Darryl A.
Published: February 2011

Maternal T cells and fetal macrophages constitute the primary infiltrate of chronic villitis of unknown etiology (CVUE), but the role of CD25+/FOXP3+ regulatory T (Treg) cells in CVUE has not been examined. Moreover, little is known about the expression of immune markers, such as the major histocompatibility complex (MHC) class II antigen, human leukocyte antigen–DR (HLA-DR), in trophoblasts in this disease. We, therefore, examined CVUE placentas for the presence of Treg cells and aberrant activation of HLA-DR in trophoblasts. Sequential formalin-fixed, paraffin-embedded tissue sections from 8 CVUE placentas and 10 control placentas were stained by immunohistochemistry with antibodies for CD3, CD4, CD8, CD20, CD25, FOXP3, CD56, CD68, HLA-DR, STAT-1, and phosphorylated STAT-1 [P-(Y701)-STAT-1]. T cells and histiocytes were confirmed as the inflammatory infiltrate in CVUE. In areas of CVUE, histiocytes strongly expressed HLA-DR and nuclear P-(Y701)-STAT-1, and the relative numbers of CD25+/FOXP3+ Treg cells were increased, compared with control placentas. In 5 of 8 CVUE cases, there was patchy nuclear expression of P-(Y701)-STAT-1 in syncytiotrophoblast most extensively involved by villitis, but no other marker examined was detected in the trophoblast cell layer. We confirmed the influx of T cells and histiocytes in CVUE. Our results are the 1st, to our knowledge, to identify increased numbers of Treg cells in CVUE vs noninflamed placentas. However, we were unable to verify HLA-DR expression in trophoblasts of placentas with CVUE, suggesting that this does not contribute to the influx of T cells. Our observation that P-(Y701)-STAT-1 expression in a syncytiotrophoblast is restricted to regions of inflammation suggests that the JAK–STAT-1 pathway is aberrantly activated in these cells.
An in vitro microbial model associated with sucrose to produce dentin caries lesions
Authors: Steiner-Oliveira Carolina , Rodrigues Lidiany , Zanin Iriana , Carvalho Carolina , Kamiya Regianne , Hara Anderson , Nobre-dos-Santos Marinês
Published: February 2011

The complexity of the oral environment and ethical issues have prompted the development of an in vitro bacterial model to evaluate the effect of frequency of sucrose exposure on dentin caries formation, biofilm composition, and pH changes. In the experiment, dentin specimens (n=45) were randomly divided into four groups: control (C), negative control (0S), 3S (three sucrose baths), and 6S (six sucrose baths). The specimens then were inoculated with Streptococcus mutans and treated according to the protocol described below. Dentin demineralization and lesion depth were assessed by transverse microradiography. Extracellular polysaccharides that formed in the biofilm were analyzed and counts of microorganisms in the carious dentin were measured. After a 7-day period of growth, the biofilm pH was assessed before and after sucrose baths (n=5). The addition of sucrose led to dentin caries development regardless of the number of sucrose baths performed. The number of colony forming units (cfu) from the carious dentin did not differ among the treatment groups, though the extracellular polysaccharides from both 3S and 6S differed from 0S. The pH decreased immediately after the sucrose bath but increased again after 5 min. We demonstrate here that the in vitro microbial model for the study of dentin caries formation is reproducible and able to produce dentin caries, irrespective of the frequency of sucrose exposure.
Polar constituents of Ligustrum vulgare L. and their effect on lipoxygenase activity
Authors: Mučaji Pavel , Nagy Milan , Záhradníková Anna , Holková Ivana , Bezáková Lýdia , Švajdlenka Emil , Liptaj Tibor , Prónayová Nadežda
Published: February 2011

The present work summarizes results of isolation and identification of polar constituents of the methanolic extract of Ligustrum vulgare L. leaves and of the evaluation of inhibiting activity of selected isolates on rat lung cytosol fraction lipoxygenase. Six different compounds were isolated from the ethylacetate and butanol portions of the methanolic extract (hydroxytyrosol and its glucoside, ligustroflavon, oleuropein, acteoside, echinacoside). The inhibitory activity of oleuropein, echinacoside and the water infusion of Ligustrum vulgare leaves tested on LOX was expressed as IC50. Kinetic parameters (K M, V max) and type of inhibition were determined. As the most effective in competitive inhibition of LOX, oleuropein was proved.
Engineering patient-specific drill templates and bioabsorbable posterior cervical plates: a feasibility study
Authors: Ryken Timothy C. , Kim John , Owen Brent D. , Christensen Gary E. , Reinhardt Joseph M.
Published: February 2011

Object

The authors describe a method of using computer models to generate customized cervical implants. A promising yet challenging technique in cervical spine surgery involves the use of pedicle screws to assist with posterior instrumentation. Surrounding anatomical structures such as the vertebral arteries and cervical nerve roots present challenges for safe screw placement; however, the use of computer-generated templates seems to be a promising method to assist with placement. In this study, the authors explore the use of computer-generated templates and introduce their methods for creating custom, bioabsorbable posterior cervical implants.

Methods

The cervical spines (C2–T1) from 4 cadavers were scanned with volumetric CT. Using commercially available software, the authors generated volumetric models of a cervical drill template and the mold for a cervical plate spanning a desired number of vertebrae. The computer generated models of the cervical drill template and cervical plate mold were converted into physical models using a rapid prototyping machine. The biopolymer polylactic acid resin was heated to 250°C and resolidified to form thin ~ 5-mm-thick plates. The newly formed plates were reheated to 60°C and cast on the cervical mold.

Results

The resulting translucent plates were found on visual inspection to have a secure lock-and-key fit on the original cadaver spine, and the techniques used were robust and reproducible. The process described in this brief report provides the background to proceed with development and testing of these patient-absorbable templates.

Conclusions

The creation and use of patient-specific bioabsorbable posterior cervical plates in conjunction with multilevel drill templates appear promising. Additional feasibility studies are planned, and in vitro studies are required to determine the safety and efficacy of using patient-specific drill templates and converting them into bioabsorbable implants.
Thoracolumbar spine trauma classification: the Thoracolumbar Injury Classification and Severity Score system and case examples
Authors: Patel Alpesh A. , Dailey Andrew , Brodke Darrel S. , Daubs Michael , Harrop James , Whang Peter G. , Vaccaro Alexander R. , _ _
Published: February 2011

Object

The aim of this study was to review the Thoracolumbar Injury Classification and Severity Score (TLICS) and to demonstrate its application through a series of spine trauma cases.

Methods

The Spine Trauma Study Group collaborated to create and report the TLICS system. The TLICS system is reviewed and applied to 3 cases of thoracolumbar spine trauma.

Results

The TLICS system identifies 3 major injury characteristics to describe thoracolumbar spine injuries: injury morphology, posterior ligamentous complex integrity, and neurological status. In addition, minor injury characteristics such as injury level, confounding variables (such as ankylosing spondylitis), multiple injuries, and chest wall injuries are also identified. Each major characteristic is assigned a numerical score, weighted by severity of injury, which is then summated to yield the injury severity score. The TLICS system has demonstrated initial success and its use is increasing. Limitations of the TLICS system exist and, in some instances, have yet to be addressed. Despite these limitations, the severity score may provide a basis to judge spinal stability and the need for surgical intervention.

Conclusions

By addressing both the posterior ligamentous integrity and the patient's neurological status, the TLICS system attempts to overcome the limitations of prior thoracolumbar classification systems. The TLICS system has demonstrated both validity and reliability and has also been shown to be readily learned and incorporated into clinical practice.