bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysregulation of Placental Endothelial Lipase in Obese Women With Gestational Diabetes Mellitus
Authors: Gauster Martin , Hiden Ursula , van Poppel Mireille , Frank Sasa , Wadsack Christian , Hauguel-de Mouzon Sylvie , Desoye Gernot
Published: August 2011

OBJECTIVE

This study addressed the hypothesis that placental endothelial lipase (EL) expression is affected by pregnancies complicated by obesity and gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

EL expression in placental tissues from pregnancies complicated by obesity, GDM, or obesity combined with GDM (obese-GDM) was analyzed by quantitative RT-PCR. Moreover, primary placental cells were isolated and treated with insulin, glucose, leptin, or tumor necrosis factor (TNF)-α, and EL expression was measured. Inhibitors of nuclear factor (NF)-κB or mitogen-activated protein kinase (MAPK) signaling were used to detect potential pathways of EL regulation in primary placental endothelial cells (ECs).

RESULTS

In placentas from obese-GDM pregnancies, EL expression was upregulated by 1.9-fold (P < 0.05) compared with lean pregnancies, whereas obesity or GDM alone had no significant effect. Analyses of metabolic parameters in maternal venous and umbilical venous plasma revealed significantly increased insulin and leptin as well as slightly increased glucose and TNF-α values in the obese and obese-GDM groups. Cell culture experiments identified TNF-α and leptin, but not glucose or insulin, as regulators of EL expression in ECs. Induction of EL expression by these mediators occurred in a para/endocrine manner, since only leptin and TNF-α receptors, but not the cytokines themselves, were expressed in ECs. Inhibitor experiments suggested that TNF-α and leptin-mediated upregulation of EL may occur via two different routes. Whereas TNF-α induced EL upregulation in ECs by activation of the NF-κB pathway, leptin did not stimulate NF-κB or MAPK signaling pathways in these cells.

CONCLUSIONS

Metabolic inflammation with high leptin and locally increased TNF-α concentrations at the fetal-placental interface regulates placental EL expression.
GLUT2 Accumulation in Enterocyte Apical and Intracellular Membranes
Authors: Ait-Omar Amal , Monteiro-Sepulveda Milena , Poitou Christine , Le Gall Maude , Cotillard Aurélie , Gilet Jules , Garbin Kevin , Houllier Anne , Château Danièle , Lacombe Amélie , Veyrie Nicolas , Hugol Danielle , Tordjman Joan , Magnan Christophe , Serradas Patricia , Clément Karine , Leturque Armelle , Brot-Laroche Edith
Published: August 2011

OBJECTIVE

In healthy rodents, intestinal sugar absorption in response to sugar-rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss of insulin action maintains apical GLUT2 location. In human enterocytes, apical GLUT2 location has not been reported but may be revealed under conditions of insulin resistance.

RESEARCH DESIGN AND METHODS

Subcellular location of GLUT2 in jejunal enterocytes was analyzed by confocal and electron microscopy imaging and Western blot in 62 well-phenotyped morbidly obese subjects and 7 lean human subjects. GLUT2 locations were assayed in ob/ob and ob/+ mice receiving oral metformin or in high-fat low-carbohydrate diet–fed C57Bl/6 mice. Glucose absorption and secretion were respectively estimated by oral glucose tolerance test and secretion of [U-14C]-3-O-methyl glucose into lumen.

RESULTS

In human enterocytes, GLUT2 was consistently located in basolateral membranes. Apical GLUT2 location was absent in lean subjects but was observed in 76% of obese subjects and correlated with insulin resistance and glycemia. In addition, intracellular accumulation of GLUT2 with early endosome antigen 1 (EEA1) was associated with reduced MGAT4a activity (glycosylation) in 39% of obese subjects on a low-carbohydrate/high-fat diet. Mice on a low-carbohydrate/high-fat diet for 12 months also exhibited endosomal GLUT2 accumulation and reduced glucose absorption. In ob/ob mice, metformin promoted apical GLUT2 and improved glucose homeostasis. Apical GLUT2 in fasting hyperglycemic ob/ob mice tripled glucose release into intestinal lumen.

CONCLUSIONS

In morbidly obese insulin-resistant subjects, GLUT2 was accumulated in apical and/or endosomal membranes of enterocytes. Functionally, apical GLUT2 favored and endosomal GLUT2 reduced glucose transepithelial exchanges. Thus, altered GLUT2 locations in enterocytes are a sign of intestinal adaptations to human metabolic pathology.
Nrf2 Represses FGF21 During Long-Term High-Fat Diet–Induced Obesity in Mice
Authors: Chartoumpekis Dionysios V. , Ziros Panos G. , Psyrogiannis Agathoklis I. , Papavassiliou Athanasios G. , Kyriazopoulou Venetsana E. , Sykiotis Gerasimos P. , Habeos Ioannis G.
Published: August 2011

OBJECTIVE

Obesity is characterized by chronic oxidative stress. Fibroblast growth factor 21 (FGF21) has recently been identified as a novel hormone that regulates metabolism. NFE2-related factor 2 (Nrf2) is a transcription factor that orchestrates the expression of a battery of antioxidant and detoxification genes under both basal and stress conditions. The current study investigated the role of Nrf2 in a mouse model of long-term high-fat diet (HFD)-induced obesity and characterized its crosstalk to FGF21 in this process.

RESEARCH DESIGN AND METHODS

Wild-type (WT) and Nrf2 knockout (Nrf2-KO) mice were fed an HFD for 180 days. During this period, food consumption and body weights were measured. Glucose metabolism was assessed by an intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Total RNA was prepared from liver and adipose tissue and was used for quantitative real-time RT-PCR. Fasting plasma was collected and analyzed for blood chemistries. The ST-2 cell line was used for transfection studies.

RESULTS

Nrf2-KO mice were partially protected from HFD-induced obesity and developed a less insulin-resistant phenotype. Importantly, Nrf2-KO mice had higher plasma FGF21 levels and higher FGF21 mRNA levels in liver and white adipose tissue than WT mice. Thus, the altered metabolic phenotype of Nrf2-KO mice under HFD was associated with higher expression and abundance of FGF21. Consistently, the overexpression of Nrf2 in ST-2 cells resulted in decreased FGF21 mRNA levels as well as in suppressed activity of a FGF21 promoter luciferase reporter.

CONCLUSIONS

The identification of Nrf2 as a novel regulator of FGF21 expands our understanding of the crosstalk between metabolism and stress defense.
Anti-inflammatory and Antioxidant Properties of HDLs Are Impaired in Type 2 Diabetes
Authors: Morgantini Cecilia , Natali Andrea , Boldrini Beatrice , Imaizumi Satoshi , Navab Mohamad , Fogelman Alan M. , Ferrannini Ele , Reddy Srinivasa T.
Published: August 2011

OBJECTIVE

In mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.

RESEARCH DESIGN AND METHODS

HDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography–tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.

RESULTS

The HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).

CONCLUSIONS

In patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired.
Low Bone Mineral Density and Its Predictors in Type 1 Diabetic Patients Evaluated by the Classic Statistics and Artificial Neural Network Analysis
Authors: Eller-Vainicher Cristina , Zhukouskaya Volha V. , Tolkachev Yury V. , Koritko Sergei S. , Cairoli Elisa , Grossi Enzo , Beck-Peccoz Paolo , Chiodini Iacopo , Shepelkevich Alla P.
Published: August 2011

OBJECTIVE

To investigate factors associated with bone mineral density (BMD) in type 1 diabetes by classic statistic and artificial neural networks.

RESEARCH DESIGN AND METHODS

A total of 175 eugonadal type 1 diabetic patients (age 32.8 ± 8.4 years) and 151 age- and BMI-matched control subjects (age 32.6 ± 4.5 years) were studied. In all subjects, BMI and BMD (as Z score) at the lumbar spine (LS-BMD) and femur (F-BMD) were measured. Daily insulin dose (DID), age at diagnosis, presence of complications, creatinine clearance (ClCr), and HbA1c were determined.

RESULTS

LS- and F-BMD levels were lower in patients (−0.11 ± 1.2 and −0.32 ± 1.4, respectively) than in control subjects (0.59 ± 1, P < 0.0001, and 0.63 ± 1, P < 0.0001, respectively). LS-BMD was independently associated with BMI and DID, whereas F-BMD was associated with BMI and ClCr. The cutoffs for predicting low BMD were as follows: BMI <23.5 kg/m2, DID >0.67 units/kg, and ClCr <88.8 mL/min. The presence of all of these risk factors had a positive predictive value, and their absence had a negative predictive value for low BMD of 62.9 and 84.2%, respectively. Data were also analyzed using the TWIST system in combination with supervised artificial neural networks and a semantic connectivity map. The TWIST system selected 11 and 12 variables for F-BMD and LS-BMD prediction, which discriminated between high and low BMD with 67 and 66% accuracy, respectively. The connectivity map showed that low BMD at both sites was indirectly connected with HbA1c through chronic diabetes complications.

CONCLUSIONS

In type 1 diabetes, low BMD is associated with low BMI and low ClCr and high DID. Chronic complications negatively influence BMD.
Quality of Medical Care in Diabetic Women Undergoing Fertility Treatment
Authors: Riskin-Mashiah Shlomit , Auslander Ron
Published: August 2011

OBJECTIVE

Diabetic women are at increased risk for adverse pregnancy outcomes that can be improved by preconception care. Our goal was to evaluate the quality of medical care in diabetic women who undergo fertility treatment and compare it with the quality of medical care in diabetic women with spontaneous pregnancies.

RESEARCH DESIGN AND METHODS

This retrospective study on reproductive-age women undergoing fertility treatment in Clalit Health Services (CHS) used data on fertility treatments, prescription fillings, HbA1c levels, and demographics extracted from CHS computerized systems. The control group comprised women with spontaneous pregnancy. Three quality measures in the periconception period were evaluated: folic acid prescription fillings, evaluation and level of HbA1c, and use of potentially hazardous drugs.

RESULTS

There were 230 fertility treatment cycles in 83 diabetic women, and 30 diabetic women had spontaneous pregnancy. Women in the fertility group were older and had fewer children. There were no significant differences in marital status or ethnicity. Regular folic acid use, HbA1c recording, and the percentage of women with HbA1c <7% was similar between women in fertility treatment and those with spontaneous pregnancy (23.9, 57.8, and 31.3% vs. 20.0, 73.3, and 40.0%, respectively). Several women in both groups continued the use of potentially hazardous medication.

CONCLUSIONS

The periconception medical care of diabetic women who undergo fertility treatment is suboptimal and no better than that of diabetic women with spontaneous pregnancies. More intensive and targeted counseling regarding the importance of folic acid and glycemic control is needed to optimize periconception care of these diabetic patients.
Prevalence and Characteristics of Painful Diabetic Neuropathy in a Large Community-Based Diabetic Population in the U.K.
Authors: Abbott Caroline A. , Malik Rayaz A. , van Ross Ernest R.E. , Kulkarni Jai , Boulton Andrew J.M.
Published: August 2011

OBJECTIVE

To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy.

RESEARCH DESIGN AND METHODS

Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS).

RESULTS

Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS >8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7–2.4], P < 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR = 1.5 [1.4–1.6], P < 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P < 0.0001).

CONCLUSIONS

One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN.
Smartness as a Cultural Practice in Schools
Authors: Hatt Beth
Published: August 2011

This study explores smartness as a cultural construct rather than a biological capacity. The cultural construction of smartness has broad consequences related to teacher expectations, student academic identity development, and schooling inequities. This study is based on a 1-year ethnography in a kindergarten classroom, and the author investigates smartness by first historicizing the concept of intelligence and then using the theoretical framework of figured worlds. Through the teachers’ disciplinary and pedagogical practices, students were taught and learned not just whether they were smart themselves, but how other student identities were constructed according to smartness as well. Analysis suggests smartness was used as a mechanism of control and social positioning along racial and class lines. Implications are discussed related to schooling practices and policy.
The macular edema
Authors: Malla OK
Published: August 2011

DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5259   Nepal J Ophthalmol 2011; 3(2): 99-101
Validation of performance of certified medical assistants in preschool vision screening examination
Authors: Adhikari S , Shrestha U
Published: August 2011

DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5264 Nepal J Ophthalmol 2011; 3(2): 128-133
Accommodation: Its relation to refractive errors, amblyopia and biometric parameters
Authors: Maheshwari R , Sukul RR , Gupta Y , Gupta M , Phougat A , Dey M , Jain R , Srivastava G , Bhardwaj U , Dikshit S
Published: August 2011

Aim: To study accommodation in relation to different refractive errors, amblyopia and to measure the anatomical changes in the accommodating eye Materials and methods: We studied the amplitude of accommodation (AA) in 150 patients in the age group 11 – 30 years which included emmetropes, myopes, hypermetropes and hypermetropic amblyopes using the Royal Air Force (RAF) rule. The anterior chamber depth (ACD), axial length (AxL) and lens thickness (LT) changes during accommodation were measured using an A-scan. Myopes and hypermetropes were further divided based on the amount of refractive error : < 2D, 2 -4D and > 4D. Results: Corrected low myopes had the highest accommodation amplitude (p < 0.05) followed by emmetropes. Corrected hypermetropes were found to have the lowest amplitude of accommodation (p < 0.05). The amblyopic eye had a significantly low AA compared to the non-amblyopic eye (p < 0.05). ACD decreased (p < 0.05) and LT increased (p < 0.05) during accommodation. The AxL increase was maximum in myopes (p < 0.05) followed by hypermetropes but the change was not significant in hypermetropes (p > 0.05). Conclusion: The amblyopic eye has low amplitudes of accommodation proving the benefit of near adds in amblyopic patients. Prolonged near work might induce myopia in susceptible eyes by increasing the axial length. Key words: accommodation, refractive error, amblyopia, biometric changes DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5267 Nepal J Ophthalmol 2011; 3(2): 146-150
Ocular manifestations in Herpes Zoster Ophthalmicus
Authors: Puri LR , Shrestha GB , Shah DN , Chaudhary M , Thakar A
Published: August 2011

Background: Ocular complications of herpes zoster ophthalmicus (HZO) may lead to substantial visual disability, severe post-herpetic neuralgia and rarely fatal cerebral complications. Aim: To identify the pattern of ocular manifestation in herpes zoster ophthalmicus. Materials and methods: A cross-sectional descriptive study was under taken including the clinically diagnosed cases of HZO. All of them underwent a complete ophthalmological evaluation. Results: Sixty-eight cases of HZO were examined, of which 37 (54.4 %) were male and 31 (45.6%) female. The mean age was 48.7 ± 18.5 years. Most of the patients (64.7 %) were above the age of 40 years. 77.94 % of the patients had some form of ocular involvement. Pain (77.9 %) was the commonest ocular complaint. In young patients less than 35 years, HIV was the most common risk factor (19.3 %).Visual status was good in the majority (73.5 %) of patients at presentation. Lid and adnexal findings (45.8 %) were most common ocular involvement followed by conjunctivitis (41.1 %). Corneal complication was seen in 38.2 % of cases, uveitis in 19.1 % and post-herpetic neuralgia (PHN) and secondary glaucoma each in 5.8 %. Conclusion: Eyelid and ocular adnexal involvement is most commonly found in patients with herpes zoster ophthalmicus followed by corneal complication and uveitis. There needs to be awareness of ocular involvement, which can be sight threatening, among the HZO patients and other medical departments and an increased emphasis on regular ophthalmic examination. Key words: herpes virus, herpes zoster, conjunctivitis, keratitis DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5271 Nepal J Ophthalmol 2011; 3(2): 165-171
Ocular morbidity among primary school children of Dhulikhel, Nepal
Authors: Sherpa D , Pant CR , Joshi N
Published: August 2011

Background: Knowledge of disease pattern in children can help design preventive and curative strategies. Objective: To study the pattern of ocular morbidity among the primary school children. Subjects and methods: All the children of randomly-selected five government primary schools of Dhulikhel were included in this study. A complete eye examination was done in all children including color vision, loupe examination, refraction and Schiotz tonometry. Funduscopy and automated perimetry were done in selected children. Results: A total of 466 primary school children were included in the study, of which 466 children 47 (10.08 %) had ocular morbidity. Refractive error was the commonest type of ocular morbidity in 11 (2.36 %). Hypermetropia was the commonest type of refractive error (0.84 %) in contrast to myopia (0.64 %). Conjunctivitis was the second common type of ocular morbidity (1.71 %). Glaucoma suspects accounted for 1.28 %, xexophthalmia 1.07 %, blephatitis 0.85 %, amblyopia 0.43 %, color blindness 0.43 %, conjunctival nevus 0.43 %, glaucoma 0.43 %, and strabismus 0.43 %, while congenital abnormalities were less common. Conclusion: Refractive error is the commonest form of ocular morbidity in primary school children. Key words: primary school children, refractive error DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5272 Nepal J Ophthalmol 2011; 3(2): 172-176
Cortical blindness and paraplegia following hypoxic ischemic encephalopathy as a complication of common krait bite
Authors: Samanta SK , Mahapatra NC , Fariduddin K , Mazumdar DB , Mandal K
Published: August 2011

Background: A case report of a successful recovery from paraplegia and cortical blindness following anti-venom injection for a snake bite by a common krait is reported here. Case: A 14-year old male patient was bitten by a common krait. On admission to a tertiary level hospital, he was started with antivenom serum. But the patient developed sudden respiratory distress following anaphylactic shock and he was kept on ventilation. The patient was discharged with paraplegia with loss of vision. He was diagnosed as a case of cortical blindness due to hypoxic ischemic encephalopathy. Subsequently, the patient recovered from paraplegia and regained visual acuity of 6/60 in both eyes (best corrected). The boy was reexamined after four years. Conclusion: Evaluation of victims of neurotoxic snake bite for early signs of respiratory depression and prompt respiratory assistance, even if anti-venom is not available, is most essential as a life saving measure. Key words: snake bite, common krait, anti-venom, hypoxic ischemic encephalopathy, cortical blindness DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5280 Nepal J Ophthalmol 2011; 3(2): 206-209
Challenges in the management of corneal ulcer
Authors: Sharma A
Published: August 2011

DOI: http://dx.doi.org/10.3126/nepjoph.v3i2.5283Nepal J Ophthalmol 2011; 3(2): 216-217
Alberta Nutrition Guidelines for Children and Youth: Awareness and Use in Schools
Authors: Downs Shauna M. , Farmer Anna , Quintanilha Maira , Berry Tanya R. , Mager Diana R. , Willows Noreen D. , McCargar Linda J.
Published: August 2011

Purpose: In June 2008, the Alberta government released the Alberta Nutrition Guidelines for Children and Youth. We evaluated the awareness of and intent to use the guidelines in Alberta schools, and sought to determine whether organizational characteristics were a factor in adoption of the guidelines.

Methods: Randomly selected schools from across Alberta completed a 19-question telephone survey, which included open- and closed-ended questions about the schools’ characteristics, the priority given to healthy eating, awareness of the guidelines, and the schools’ intent to use the guidelines. Of the 554 schools contacted, 357 (64%) completed the survey.

Results: Overall, 76.1% of schools were aware of the guidelines and 65% were in the process of adopting them. Fifty percent of schools identified healthy eating as a high priority and 65.9% reported making changes to improve the nutritional quality of foods offered in the past year. Schools that were larger, public, and urban, and had a school champion and healthy eating as a high priority were more likely to be adopting the guidelines.

Conclusions: Most schools were aware of the nutrition guidelines and many had begun the adoption process. Identifying a school champion may be an important first step for schools in terms of adopting health promotion initiatives.
Efficacy of facial nerve–sparing approach in patients with vestibular schwannomas
Authors: Haque Raqeeb , Wojtasiewicz Teresa J. , Gigante Paul R. , Attiah Mark A. , Huang Brendan , Isaacson Steven R. , Sisti Michael B.
Published: August 2011

Object

The goal of this article was to show that a combination of facial nerve–sparing microsurgical resection and Gamma Knife surgery (GKS) for expansion of any residual tumor can preserve good facial nerve function in patients with recurrent vestibular schwannoma (VS).

Methods

Records of individuals treated by a single surgeon with a facial nerve–sparing technique for a VS between 1998 and 2009 were retrospectively analyzed for tumor recurrence. Of the 383 patients treated for VS, 151 underwent microsurgical resection, and 20 (13.2%) of these patients required postoperative retreatment for a significant expansion of residual tumor after microsurgery. These 20 patients were re-treated with GKS.

Results

The rate of preservation of good facial nerve function (Grade I or II on the House-Brackmann scale) in patients treated with microsurgery for VS was 97%. Both subtotal and gross-total resection had excellent facial nerve preservation rates (97% vs 96%), although subtotal resection carried a higher risk that patients would require retreatment. In patients re-treated with GKS after microsurgery, the rate of facial nerve preservation was 95%.

Conclusions

In patients with tumors that cannot be managed with radiosurgery alone, a facial nerve–sparing resection followed by GKS for any significant regrowth provides excellent facial nerve preservation rates.
A meningioma and its consequences for American history and the rise of neurosurgery
Authors: Ansari Shaheryar F. , Gianaris Nicholas G. , Cohen-Gadol Aaron A.
Published: August 2011

The case of General Leonard Wood is notable both for its contribution to the field of neurosurgery and its historical significance. As one of Harvey Cushing's first successful brain tumor operations in 1910, Wood's surgery was part of the case series that culminated in Cushing's monograph Meningioma. This case was important to the rise of Cushing's career and his recognition as a member of the next generation of neurosurgeons who did not settle for mere bony decompression to taper intracranial tension but who dared to pursue intradural resections—operations that had been performed by surgeons for decades but were frowned upon because of the attendant risks.

Cushing's operation to remove a recurrent brain tumor ended Wood's life in 1927. The authors discuss the effects the tumor may have had on Wood's life and career, explore an alternate explanation for the cause of Wood's death, and provide a brief account of the life of General Wood, highlighting events in his military and administrative career juxtaposed against the progression of his illness. Furthermore, the case history of the General is reviewed, using information drawn from the original patient notes and recently discovered images from the Cushing Brain Tumor Registry that elucidate more details about General Wood's story, from the injury that caused his first tumor to his final surgery, leading to his demise.
Low-grade gliomas in adults
Authors: Sanai Nader , Chang Susan , Berger Mitchel S.
Published: August 2011

In recent years, advances in the understanding of low-grade glioma (LGG) biology have driven new paradigms in molecular markers, diagnostic imaging, operative techniques and technologies, and adjuvant therapies. Taken together, these developments are collectively pushing the envelope toward improved quality of life and survival. In this article, the authors evaluate the recent literature to synthesize a comprehensive review of LGGs in the modern neurosurgical era.
Immunoglobulin G4–related hypertrophic pachymeningitis involving cerebral parenchyma
Authors: Kim Eui Hyun , Kim Se Hoon , Cho Jin Mo , Ahn Jung Yong , Chang Jong Hee
Published: August 2011

The authors report a case of IgG4-related hypertrophic pachymeningitis that involved cerebral parenchyma. The mass was removed surgically. Histopathological studies showed diffuse infiltration of lymphoplasmacytic cells without evidence of Langerhans histiocytes or meningothelial cells. Immunoglobulin G4 was strongly positive on immunohistochemical staining. The Gd-enhanced lesion deep inside brain parenchyma was completely resolved after 3 months of oral corticosteroid medication. A nodular type of hypertrophic pachymeningitis that mimics a meningioma is rare. Nevertheless, preoperative presumption is very important, and immunohistochemical studies for IgG4 may be helpful in the differential diagnosis.
Increase of sensitivity to mechanical stimulus after transplantation of murine induced pluripotent stem cell–derived astrocytes in a rat spinal cord injury model
Authors: Hayashi Koichi , Hashimoto Masayuki , Koda Masao , Naito Atsuhiko T. , Murata Atsushi , Okawa Akihiko , Takahashi Kazuhisa , Yamazaki Masashi
Published: August 2011

Object

Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords.

Methods

Induced pluripotent stem cell–derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion–based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed.

Results

Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment.

Conclusions

Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI.
An L-2 burst fracture and cauda equina syndrome due to tetanus
Authors: Wilson Thomas J. , Orringer Daniel A. , Sullivan Stephen E. , Patil Parag G.
Published: August 2011

Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus.

This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine.

The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease.
Congenital atlantoaxial dislocation: a dynamic process and role of facets in irreducibility
Authors: Salunke Pravin , Sharma Manish , Sodhi Harsimrat Bir Singh , Mukherjee Kanchan K. , Khandelwal Niranjan K.
Published: August 2011

Object

Patient age at presentation with congenital atlantoaxial dislocation (CAAD) is variable. In addition, the factors determining irreducibility or reducibility in these patients remain unclear. The facets appear to contribute to the stability of the joint, albeit to an unknown extent. The objective of this paper was to study the characteristics of C1–2 facets in these patients and their bearing on the clinicoradiological presentation and management.

Methods

Twenty-four patients with CAAD were studied. Fifteen patients had irreducible CAAD (IrAAD); 3 of these patients experienced incomplete reduction after traction, and 9 had reducible CAAD (RAAD). The images (CT scans of the craniovertebral junction in a neutral position) obtained in the parasagittal, axial, and coronal planes were studied with respect to the C1–2 facets and were compared with 32 control scans. The inferior sagittal and coronal C-1 facet angles were measured. The lordosis of the cervical spine (cervical spine angle calculated on radiographs of the cervical spine, neutral view) in these patients was compared with normal. The management of these patients is described.

Results

The inferior sagittal C-1 facet angle and at least one coronal angle in patients with IrAAD were significantly acute compared with those in patients with RAAD and the control population. A significant correlation was found between age and the acuteness of the inferior sagittal C-1 facet angle (that is, the more acute the angle, the earlier the presentation). The lordosis of the cervical spine was exaggerated in patients with IrAAD. Three patients with IrAAD who had smaller acute angles experienced a partial reduction after traction and a complete reduction after intraoperative distraction of the facets, thereby avoiding a transoral procedure. An inferior sagittal C-1 facet angle of more than 150° in the sagittal plane predicted reducibility. Drilling a wedge off the facet in the sagittal plane to make the inferior sagittal C-1 facet angle 150° can reduce the C1–2 joint intraoperatively by posterior approach alone.

Conclusions

The acuteness of the inferior C-1 sagittal facet angles possibly determines the age at presentation and reducibility. The coronal angles determine the telescoping of C-2 within C-1. Patients with IrAAD can be treated using a posterior approach alone with the exception of those with extremely acute angles or a retroflexed dens. The exaggerated lordosis of the cervical spine in these patients is a compensatory phenomenon.
Genetics, genomics, and cancer risk assessment
Authors: Weitzel Jeffrey N. , Blazer Kathleen R. , MacDonald Deborah J. , Culver Julie O. , Offit Kenneth
Published: August 2011

Scientific and technologic advances are revolutionizing our approach to genetic cancer risk assessment, cancer screening and prevention, and targeted therapy, fulfilling the promise of personalized medicine. In this monograph, we review the evolution of scientific discovery in cancer genetics and genomics, and describe current approaches, benefits, and barriers to the translation of this information to the practice of preventive medicine. Summaries of known hereditary cancer syndromes and highly penetrant genes are provided and contrasted with recently discovered genomic variants associated with modest increases in cancer risk. We describe the scope of knowledge, tools, and expertise required for the translation of complex genetic and genomic test information into clinical practice. The challenges of genomic counseling include the need for genetics and genomics professional education and multidisciplinary team training, the need for evidence‐based information regarding the clinical utility of testing for genomic variants, the potential dangers posed by premature marketing of first‐generation genomic profiles, and the need for new clinical models to improve access to and responsible communication of complex disease risk information. We conclude that given the experiences and lessons learned in the genetics era, the multidisciplinary model of genetic cancer risk assessment and management will serve as a solid foundation to support the integration of personalized genomic information into the practice of cancer medicine. CA Cancer J Clin 2011. © 2011 American Cancer Society.
Modeling Smoke Plume-Rise and Dispersion from Southern United States Prescribed Burns with Daysmoke
Authors: Achtemeier Gary L. , Goodrick Scott A. , Liu Yongqiang , Garcia-Menendez Fernando , Hu Yongtao , Odman Mehmet Talat
Published: August 2011

We present Daysmoke, an empirical-statistical plume rise and dispersion model for simulating smoke from prescribed burns. Prescribed fires are characterized by complex plume structure including multiple-core updrafts which makes modeling with simple plume models difficult. Daysmoke accounts for plume structure in a three-dimensional veering/sheering atmospheric environment, multiple-core updrafts, and detrainment of particulate matter. The number of empirical coefficients appearing in the model theory is reduced through a sensitivity analysis with the Fourier Amplitude Sensitivity Test (FAST). Daysmoke simulations for “bent-over” plumes compare closely with Briggs theory although the two-thirds law is not explicit in Daysmoke. However, the solutions for the “highly-tilted” plume characterized by weak buoyancy, low initial vertical velocity, and large initial plume diameter depart considerably from Briggs theory. Results from a study of weak plumes from prescribed burns at Fort Benning GA showed simulated ground-level PM2.5 comparing favorably with observations taken within the first eight kilometers of eleven prescribed burns. Daysmoke placed plume tops near the lower end of the range of observed plume tops for six prescribed burns. Daysmoke provides the levels and amounts of smoke injected into regional scale air quality models. Results from CMAQ with and without an adaptive grid are presented.
Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer
Authors: Gao Xiaohua , Deeb Dorrah , Liu Yongbo , Arbab Ali S. , Divine George W. , Dulchavsky Scott A. , Gautam Subhash C.
Published: August 2011

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), a synthetic analog of oleanolic acid, and its C28 methyl ester derivative (CDDO-Me), have shown potent antitumorigenic activity against a wide range of cancer cell lines, including prostate cancer cells in vitro, and inhibited the development of liver and lung cancer in vivo. In the present study, we examined the efficacy of CDDO-Me in preventing the development and progression of prostate cancer in the transgenic adenocarinoma of the mouse prostate (TRAMP) model. CDDO-Me inhibited the growth of murine TRAMPC-1 prostate cancer cells by inducing apoptosis through the inhibition of antiapoptotic p-Akt, p-mTOR and NF-κB. Early intervention with CDDO-Me (7.5 mg/kg) initiated at five weeks of age for 20 wk inhibited the progression of the preneoplastic lesions (low-grade PIN and high-grade-PIN) to adenocarcinoma in the dorsolateral prostate (DLP) and ventral prostate (VP) lobes of TRAMP mice. Even delayed administration of CDDO-Me started at 12 wk of age for 12 wk inhibited the development of adenocarcimona of the prostate. Both early and late treatment with CDDO-Me inhibited the metastasis of tumor to the distant organs. Treatment with CDDO-Me inhibited the expression of prosurvival p-Akt and NF-κB in the prostate and knocking-down Akt in TRAMPC-1 tumor cells sensitized them to CDDO-Me. These findings indicated that Akt is a target for apoptoxicity in TRAMPC-1 cells in vitro and potentially a target of CDDO-Me for inhibition of prostate cancer in vivo.
Novel Antibody-Based Proteins for Cancer Immunotherapy
Authors: Fuenmayor Jaheli , Montaño Ramon F.
Published: August 2011

The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.
A Carbon Footprint of an Office Building
Authors: Airaksinen Miimu , Matilainen Pellervo
Published: August 2011

Current office buildings are becoming more and more energy efficient. In particular the importance of heating is decreasing, but the share of electricity use is increasing. When the CO2 equivalent emissions are considered, the CO2 emissions from embodied energy make up an important share of the total, indicating that the building materials have a high importance which is often ignored when only the energy efficiency of running the building is considered. This paper studies a new office building in design phase and offers different alternatives to influence building energy consumption, CO2 equivalent emissions from embodied energy from building materials and CO2 equivalent emissions from energy use and how their relationships should be treated. In addition this paper studies how we should weight the primary energy use and the CO2 equivalent emissions of different design options. The results showed that the reduction of energy use reduces both the primary energy use and CO2 equivalent emissions. Especially the reduction of electricity use has a high importance for both primary energy use and CO2 emissions when fossil fuels are used. The lowest CO2 equivalent emissions were achieved when bio-based, renewable energies or nuclear power was used to supply energy for the office building. Evidently then the share of CO2 equivalent emissions from the embodied energy of building materials and products became the dominant source of CO2 equivalent emissions. The lowest primary energy was achieved when bio-based local heating or renewable energies, in addition to district cooling, were used. The highest primary energy was for the nuclear power option.
Molecular Determinants of the Response of Tumor Cells to Boswellic Acids
Authors: Eichhorn Tolga , Greten Henry Johannes , Efferth Thomas
Published: August 2011

Frankincense (Boswellia serrata, B. carterii) is used as traditional remedy to treat inflammatory diseases. The molecular effects of the active ingredients, the boswellic acids, on the immune system have previously been studied and verified in several clinical studies. Boswellic acids also inhibit cancer cell growth in vitro and in vivo. The molecular basis of the cytotoxicity of boswellic acids is, however, not fully understood as yet. By mRNA-based microarray, COMPARE, and hierarchical cluster analyses, we identified a panel of genes from diverse functional groups, which were significantly associated with sensitivity or resistance of a- or b-boswellic acids, such as transcription factors, signal transducers, growth regulating genes, genes involved in RNA and protein metabolism and others. This indicates that boswellic acids exert profound cytotoxicity on cancer cells by a multiplicity of molecular mechanisms.
Theory-Guided Design of Organic Electro-Optic Materials and Devices
Authors: Dalton Larry , Benight Stephanie
Published: August 2011

Integrated (multi-scale) quantum and statistical mechanical theoretical methods have guided the nano-engineering of controlled intermolecular electrostatic interactions for the dramatic improvement of acentric order and thus electro-optic activity of melt-processable organic polymer and dendrimer electro-optic materials. New measurement techniques have permitted quantitative determination of the molecular order parameters, lattice dimensionality, and nanoscale viscoelasticity properties of these new soft matter materials and have facilitated comparison of theoretically-predicted structures and thermodynamic properties with experimentally-defined structures and properties. New processing protocols have permitted further enhancement of material properties and have facilitated the fabrication of complex device structures. The integration of organic electro-optic materials into silicon photonic, plasmonic, and metamaterial device architectures has led to impressive new performance metrics for a variety of technological applications.
Collective Sensing: Integrating Geospatial Technologies to Understand Urban Systems—An Overview
Authors: Blaschke Thomas , Hay Geoffrey J. , Weng Qihao , Resch Bernd
Published: August 2011

Cities are complex systems composed of numerous interacting components that evolve over multiple spatio-temporal scales. Consequently, no single data source is sufficient to satisfy the information needs required to map, monitor, model, and ultimately understand and manage our interaction within such urban systems. Remote sensing technology provides a key data source for mapping such environments, but is not sufficient for fully understanding them. In this article we provide a condensed urban perspective of critical geospatial technologies and techniques: (i) Remote Sensing; (ii) Geographic Information Systems; (iii) object-based image analysis; and (iv) sensor webs, and recommend a holistic integration of these technologies within the language of open geospatial consortium (OGC) standards in-order to more fully understand urban systems. We then discuss the potential of this integration and conclude that this extends the monitoring and mapping options beyond “hard infrastructure” by addressing “humans as sensors”, mobility and human-environment interactions, and future improvements to quality of life and of social infrastructures.
Fabrication and Characterization of Polyaniline/PVA Humidity Microsensors
Authors: Yang Ming-Zhi , Dai Ching-Liang , Lin Wei-Yi
Published: August 2011

This study presents the fabrication and characterization of a humidity microsensor that consists of interdigitated electrodes and a sensitive film. The area of the humidity microsensor is about 2 mm2. The sensitive film is polyaniline doping polyvinyl alcohol (PVA) that is prepared by the sol-gel method, and the film has nanofiber and porous structures that help increase the sensing reaction. The commercial 0.35 mm Complimentary Metal Oxide Semiconductor (CMOS) process is used to fabricate the humidity microsensor. The sensor needs a post-CMOS process to etch the sacrificial layer and to coat the sensitive film on the interdigitated electrodes. The sensor produces a change in resistance as the polyaniline/PVA film absorbs or desorbs vapor. Experimental results show that the sensitivity of the humidity sensor is about 12.6 kΩ/%RH at 25 °C.