bluuebunny/crossref_metadata_2025 huggingface dataset:
The Glucagon-Like Peptide 1 Receptor Agonist Exenatide Inhibits Small Intestinal Motility, Flow, Transit, and Absorption of Glucose in Healthy Subjects and Patients With Type 2 Diabetes: A Randomized Controlled Trial
Authors: Thazhath Sony S. , Marathe Chinmay S. , Wu Tongzhi , Chang Jessica , Khoo Joan , Kuo Paul , Checklin Helen L. , Bound Michelle J. , Rigda Rachael S. , Crouch Benjamin , Jones Karen L. , Horowitz Michael , Rayner Christopher K.
Published: October 2015

The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 μg) or saline (−30 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq 99mTc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0–60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia.
Mitochondrial Calpain-1 Disrupts ATP Synthase and Induces Superoxide Generation in Type 1 Diabetic Hearts: A Novel Mechanism Contributing to Diabetic Cardiomyopathy
Authors: Ni Rui , Zheng Dong , Xiong Sidong , Hill David J. , Sun Tao , Gardiner Richard B. , Fan Guo-Chang , Lu Yanrong , Abel E. Dale , Greer Peter A. , Peng Tianqing
Published: October 2015

Calpain plays a critical role in cardiomyopathic changes in type 1 diabetes (T1D). This study investigated how calpain regulates mitochondrial reactive oxygen species (ROS) generation in the development of diabetic cardiomyopathy. T1D was induced in transgenic mice overexpressing calpastatin, in mice with cardiomyocyte-specific capn4 deletion, or in their wild-type littermates by injection of streptozotocin. Calpain-1 protein and activity in mitochondria were elevated in diabetic mouse hearts. The increased mitochondrial calpain-1 was associated with an increase in mitochondrial ROS generation and oxidative damage and a reduction in ATP synthase-α (ATP5A1) protein and ATP synthase activity. Genetic inhibition of calpain or upregulation of ATP5A1 increased ATP5A1 and ATP synthase activity, prevented mitochondrial ROS generation and oxidative damage, and reduced cardiomyopathic changes in diabetic mice. High glucose concentration induced ATP synthase disruption, mitochondrial superoxide generation, and cell death in cardiomyocytes, all of which were prevented by overexpression of mitochondria-targeted calpastatin or ATP5A1. Moreover, upregulation of calpain-1 specifically in mitochondria induced the cleavage of ATP5A1, superoxide generation, and apoptosis in cardiomyocytes. In summary, calpain-1 accumulation in mitochondria disrupts ATP synthase and induces ROS generation, which promotes diabetic cardiomyopathy. These findings suggest a novel mechanism for and may have significant implications in diabetic cardiac complications.
Managing Diabetes in Pregnancy Using Cell Phone/Internet Technology
Authors: Bartholomew Marguerite Lisa , Soules Karen , Church Kacy , Shaha Steve , Burlingame Janet , Graham George , Sauvage Lynnae , Zalud Ivica
Published: October 2015

In Brief For pregnant women with diabetes, using cell phone/Internet technology to track and report self-monitoring of blood glucose results improves compliance and satisfaction compared to using the more traditional methods of log books, telephone calls, and voicemail messages.
Self-Reported Gastrointestinal Symptoms in Type 2 Diabetes Improve With an Intensive Lifestyle Intervention: Results From the Action for Health in Diabetes (Look AHEAD) Clinical Trial
Authors: Neiberg Rebecca H. , Rejeski Jared J. , Applegate William B. , Clark Jeanne M. , Knowler William C. , Bray George A. , Espeland Mark A. , Cheskin Lawrence J.
Published: October 2015

In Brief This article reports on an investigation of whether an intensive lifestyle intervention (ILI) would reduce gastrointestinal symptoms over 4 years of follow-up for participants in the Action for Health in Diabetes (Look AHEAD) trial compared to a diabetes support and education (DSE) group. Look AHEAD is a randomized, multicenter trial comparing overweight and obese adults with type 2 diabetes treated with ILI versus DSE. ILI, and weight loss in general, had beneficial effects on gastrointestinal (GI) symptoms, with some variability in the strength of the effect depending on the specific symptom and time course. Potential modifiers were analyzed, yet ILI retained an association with improvement in GI symptoms.
Event Prestige as a Mediator between Sport Involvement and Intent to Continue Participation
Authors: Kim Seungmo , Liu Jing Dong , Love Adam
Published: October 2015

The current study examined perceived event prestige as a mediator between sport involvement and sport participation behavioral intent. A total of 455 participants ( M age = 28.6 yr., SD = 9.1) were recruited at the 2013 Standard Chartered Hong Kong Marathon. The findings indicated that a model in which perceived event prestige partially mediated the relationship between sport involvement and intent to return to the event was most representative of the data. While individuals with higher sport involvement were more likely to indicate an interest in continued participation, this relationship was strongest among those who perceived the event to be particularly prestigious. Thus, those who market mass participation sporting events should use strategies designed to emphasize the prestigious stature of the event and should employ measures to increase sport involvement among participants.
Delayed Positive Effects of an Acute Bout of Coordinative Exercise on Children's Attention
Authors: Schmidt Mirko , Egger Fabienne , Conzelmann Achim
Published: October 2015

Since attention is an important prerequisite for learning, it is particularly worthwhile to promote it in schools, through specific interventions. The present study examined the effects of an acute bout of coordinative exercise in physical education on the attention of primary school children. A total of 90 fifth grade primary school children (41 boys, 49 girls; M = 11.0 yr., SD = 0.6) participated in the study and were randomly assigned to either the experimental or the control group. The experimental group received a cognitively demanding physical education lesson consisting of different coordinative exercises; the control group attended a normal sedentary school lesson. Before, immediately after, and 90 min. after each experimental condition, the children's attentional performance was tested using the revised version of the d2 Test of Attention (d2–R). Results of the repeated-measures analysis of variance (ANOVA) revealed that children's attentional performance increased through the specifically designed physical education lesson, not immediately but 90 min. after cessation. The results are discussed in terms of mechanisms explaining the relationship between acute physical exercise, and immediate and delayed effects on attention.
The Effects on Driving Speed of a Head-Up Display of Road Warnings
Authors: Huang Cheng-Hung , Chao Chun-Wen
Published: October 2015

This study investigated the superimposition of the projected markings on the road with head-up display, as well as their effects on the driver's speed. Two experiments were conducted. In Exp. 1, driving operations were simulated with a desktop computer to assess 18 deceleration markings (from the factors position, shape, and color) and determined the factors and levels influencing driving speeds. Based on the results of Exp. 1, six deceleration markings (from the factors shape and color) were selected in the driving simulator for conducting Exp. 2. The results of Exp. 1 showed that markings at the sides were better than the markings in the center. In Exp. 2, there was no significant difference between the effects of the arrangement of markings and the change of shape and color on driving stability. Yellow and white colors had no significant effect on speed; however, bar markings were better than zigzag markings. The results indicated that the projection of markings on a head-up display was helpful for indicating necessary deceleration.
Antiallergic Effects of Anti-Interleukin-33 are Associated with Suppression of Immunoglobulin Light Chain and Inducible Nitric Oxide Synthase
Authors: Park Chang-Shin , Jang Tae Young , Heo Min-Jeong , Jung Ah-Yeoun , Kim Young Hyo
Published: October 2015

Objective

We aimed to find novel genes that are significantly induced in allergic mice and that are significantly downregulated with anti-interleukin (IL) 33 treatment.

Methods

Thirty-six mice were allocated into each of group A (intraperitoneal [i.p.]) sensitized and intranasally challenged to saline solution), group B (sensitized and challenged to ovalbumin), group C (sensitized and challenged with ovalbumin, and null treatment with i.p. saline solution), and group D (sensitized and challenged with ovalbumin, and treatment with anti-IL-33 i.p. injection). We counted the number of nose-scratching in 10 minutes, serum ovalbumin-specific immunoglobulin E (IgE), and titers of cytokines (IL-1, IL-4, IL-5, IL-10, IL-13) in bronchoalveolar lavage fluid. By using one whole lung from each mouse, we performed microarray analysis and real-time polymerase chain reaction.

Results

Group D showed a significantly reduced nose-scratching events and lower serum ovalbumin-specific IgE compared with groups B and C. All the cytokines in the bronchoalveolar lavage fluid were significantly decreased after anti-IL-33 treatment. Microarray analysis revealed that group B (immunoglobulin free light chain [IgFLC], 89.1 times; nitric oxide synthase [NOS] 2,11.5 times) and group C (IgFLC, 141.6 times; NOS2,11.7 times) had significantly increased expression of IgFLC and NOS2 genes compared with group A. After anti-IL-33 treatment, group D showed significantly decreased expression of both IgFLC (49.3 times) and NOS2 (6.5 times). In real-time polymerase chain reaction, groups B and C had significantly increased expression of these genes (IgFLC, 10.4 times and 29 times, respectively; NOS2, 3.8 times and 4.5 times, respectively). After treatment, group D showed significantly decreased expression of IgFLC (5.0 times) and NOS2 (2.5 times).

Conclusion

The antiallergic effect of anti-IL-33 can be explained by suppression of IgFLC and NOS2 in a murine model of allergic rhinitis.
Soft Tissue Mobilization to Resolve Chronic Pain and Dysfunction Associated With Postoperative Abdominal and Pelvic Adhesions: A Case Report
Authors: Wong Yui Y. , Smith Ryan W. , Koppenhaver Shane
Published: October 2015

Study Design

Case report.

Background

Common complications from abdominal and pelvic surgery include adhesions and chronic pain. Laparoscopic adhesiolysis is sometimes used to reduce adhesions and related pain. Physical therapy interventions, such as soft tissue mobilization (STM), may be used for this condition; however, evidence to support its effectiveness is lacking.

Case Description

A 28-year-old woman with a history of 5 abdominal/pelvic surgeries presented with right-sided lower abdominal and anterior hip pain, which had been present since she had undergone a laparoscopic appendectomy with a right ovarian cystectomy surgery 1 year earlier. As an active-duty member in the US Navy, due to pain and weakness, she was unable to perform required curl-ups for her fitness test. Though she had been previously treated both surgically with laparoscopic adhesiolysis and nonsurgically with physical therapy consisting of stretching and strengthening exercises, her pain and function did not improve. She was again evaluated and treated with physical therapy and, based on the examination findings, STM was used to address her pain and dysfunction, which were thought to be related to intra-abdominal adhesions.

Outcomes

Following 5 sessions of physical therapy over a 3-week period that included STM and therapeutic exercises, followed by 5 additional sessions over a 4-week period that focused on therapeutic exercises, the patient reported substantially decreased pain, improved function, and a full return to previous level of activity, including unrestricted physical training in a military setting.

Discussion

The outcomes for this patient suggest that STM may be effective as a conservative treatment option for pain and dysfunction related to intra-abdominal adhesions from abdominal/pelvic surgery. Studies with a higher level of evidence, including potential comparison between STM and traditional laparoscopic adhesiolysis, are needed to further determine benefits of nonsurgical care for this condition.

Level of Evidence

Therapy, level 4. J Orthop Sports Phys Ther 2015;45(12):1006–1016. Epub 15 Oct 2015. doi:10.2519/jospt.2015.5766
Effects of Neuromuscular Fatigue on Quadriceps Strength and Activation and Knee Biomechanics in Individuals Post–Anterior Cruciate Ligament Reconstruction and Healthy Adults
Authors: Thomas Abbey C. , Lepley Lindsey K. , Wojtys Edward M. , McLean Scott G. , Palmieri-Smith Riann M.
Published: October 2015

Study Design

Laboratory-based experiment using a pretest/posttest design.

Objectives

To determine the effects of neuromuscular fatigue on quadriceps strength and activation and sagittal and frontal plane knee biomechanics during dynamic landing following anterior cruciate ligament reconstruction (ACLR).

Background

Impaired quadriceps central activation occurs post-ACLR, likely altering lower extremity biomechanics. Neuromuscular fatigue similarly reduces volitional muscle activation and impairs neuromuscular control. Upon return to full activity post-ACLR, individuals likely concurrently experience quadriceps central activation deficits and neuromuscular fatigue, though the effects of fatigue on muscle strength and activation and biomechanics post-ACLR are unknown.

Methods

Seventeen individuals 7 to 10 months post-ACLR and 16 controls participated. Quadriceps strength and central activation ratio were recorded prefatigue and postfatigue, which was induced via sets of double-leg squats. Knee biomechanics were recorded during a dynamic landing activity prefatigue and postfatigue.

Results

Both groups demonstrated smaller knee flexion (initial contact, P = .017; peak, P = .004) and abduction (initial contact, P = .005; peak, P = .009) angles postfatigue. The ACLR group had smaller peak knee flexion angles (P<.001) prefatigue and postfatigue than controls. Knee flexion moment was smaller in those post-ACLR than controls prefatigue (P<.001), but not postfatigue (P = .103). Controls had smaller knee flexion moments postfatigue (P = .001). Knee abduction moment was smaller in both groups postfatigue (P = .003). All participants demonstrated significantly lower strength (P<.001) and activation (P = .003) postfatigue.

Conclusion

Impaired strength, central activation, and biomechanics were present postfatigue in both groups, suggesting that neuromuscular fatigue may increase noncontact ACL injury risk. However, these changes were not exaggerated in those post-ACLR, likely because they already demonstrated a stiff-legged landing strategy prefatigue. J Orthop Sports Phys Ther 2015;45(12):1042–1050. Epub 15 Oct 2015. doi:10.2519/jospt.2015.5785
Effects of Cooling During Exercise on Thermoregulatory Responses of Men With Paraplegia
Authors: Bongers Coen C.W.G. , Eijsvogels Thijs M.H. , van Nes Ilse J.W. , Hopman Maria T.E. , Thijssen Dick H.J.
Published: October 2015

Background

People with spinal cord injury (SCI) have an altered afferent input to the thermoregulatory center, resulting in a reduced efferent response (vasomotor control and sweating capacity) below the level of the lesion. Consequently, core body temperature rises more rapidly during exercise in individuals with SCI compared with people who are able-bodied. Cooling strategies may reduce the thermophysiological strain in SCI.

Objective

The aim of this study was to examine the effects of a cooling vest on the core body temperature response of people with a thoracic SCI during submaximal exercise.

Methods

Ten men (mean age=44 years, SD=11) with a thoracic lesion (T4–T5 or below) participated in this randomized crossover study. Participants performed two 45-minute exercise bouts at 50% maximal workload (ambient temperature 25°C), with participants randomized to a group wearing a cooling vest or a group wearing no vest (separate days). Core body temperature and skin temperature were continuously measured, and thermal sensation was assessed every 3 minutes.

Results

Exercise resulted in an increased core body temperature, skin temperature, and thermal sensation, whereas cooling did not affect core body temperature. The cooling vest effectively decreased skin temperature, increased the core-to-trunk skin temperature gradient, and tended to lower thermal sensation compared with the control condition.

Limitations

The lack of differences in core body temperature among conditions may be a result of the relative moderate ambient temperature in which the exercise was performed.

Conclusions

Despite effectively lowering skin temperature and increasing the core-to-trunk skin temperature gradient, there was no impact of the cooling vest on the exercise-induced increase in core body temperature in men with low thoracic SCI.
Factor Rotation and Standard Errors in Exploratory Factor Analysis
Authors: Zhang Guangjian , Preacher Kristopher J.
Published: October 2015

In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical exploration method. The results are (a) CF-varimax, CF-quartimax, CF-equamax, and CF-parsimax produced similar asymptotic standard errors when the factor loading matrix is an independent cluster solution and (b) the four rotation methods produced different asymptotic standard errors when the factor loading matrix has a more complex structure. In addition, properties of the CF family are explored with a full range of κ values.
The natural history of cerebral cavernous malformations in children
Authors: Gross Bradley A. , Du Rose , Orbach Darren B. , Scott R. Michael , Smith Edward R.
Published: October 2015

OBJECT

Cerebral cavernous malformations (CMs) are a source of neurological morbidity from seizures and focal neurological deficits due to mass effect and hemorrhage. Although several natural history reports exist for adults with CMs, similar data for pediatric patients are limited.

METHODS

The authors reviewed hospital databases to identify children with CMs who had not been treated surgically and who had clinical and radiological follow-up. Annual hemorrhage rates were calculated in lesion-years, and risk factors were assessed using the Cox proportional hazards model.

RESULTS

In a cohort of 167 patients with 222 CMs, the mean patient age at the time of diagnosis was 10.1 years old (SD 6.0). Ninety patients (54%) were male. One hundred four patients (62%) presented with hemorrhage from at least 1 CM, 58 (35%) with seizures with or without CM hemorrhage, and 43 (26%) with incidental lesions. Twenty-five patients (15%) had multiple CMs, 17 (10%) had a family history of CMs, and 33 (20%) had radiologically apparent developmental venous anomalies (DVAs). The overall annual hemorrhage rate was 3.3%. Permanent neurological morbidity was 29% per hemorrhage, increasing to 45% for brainstem, thalamic, or basal ganglia CM and decreasing to 15% for supratentorial lobar or cerebellar lesions. The annual hemorrhage rate for incidental CMs was 0.5%; for hemorrhagic CMs, it was 11.3%, increasing to 18.2% within the first 3 years. Hemorrhage clustering within 3 years was statistically significant (HR 6.1, 95% CI 1.72–21.7, p = 0.005). On multivariate analysis, hemorrhagic presentation (HR 4.63, 95% CI 1.53–14.1, p = 0.007), brainstem location (HR 4.42, 95% CI 1.57–12.4, p = 0.005), and an associated radiologically apparent DVA (HR 2.91, 95% CI 1.04–8.09, p = 0.04) emerged as significant risk factors for hemorrhage, whereas age, sex, CM multiplicity, and CM family history did not.

CONCLUSIONS

Prior hemorrhage, brainstem location, and associated DVAs are significant risk factors for symptomatic hemorrhage in children with CMs. Hemorrhage clustering within the first 3 years of a bleed can occur, a potentially important factor in patient management and counseling.
On resident duty hour restrictions and neurosurgical training: review of the literature
Authors: Bina Robert W. , Lemole G. Michael , Dumont Travis M.
Published: October 2015

Within neurosurgery, the national mandate of the 2003 duty hour restrictions (DHR) by the Accreditation Council for Graduate Medical Education (ACGME) has been controversial. Ensuring the proper education and psychological well-being of residents while fulfilling the primary purpose of patient care has generated much debate. Most medical disciplines have developed strategies that address service needs while meeting educational goals. Additionally, there are numerous studies from those disciplines; however, they are not specifically relevant to the needs of a neurosurgical residency. The recent implementation of the 2011 DHR specifically aimed at limiting interns to 16-hourduty shifts has proven controversial and challenging across the nation for neurosurgical residencies—again bringing education and service needs into conflict.

In this report the current literature on DHR is reviewed, with special attention paid to neurosurgical residencies, discussing resident fatigue, technical training, and patient safety. Where appropriate, other specialty studies have been included. The authors believe that a one-size-fits-all approach to residency training mandated by the ACGME is not appropriate for the training of neurosurgical residents. In the authors’ opinion, an arbitrary timeline designed to limit resident fatigue limits patient care and technical training, and has not improved patient safety.
A combinatorial radiographic phenotype may stratify patient survival and be associated with invasion and proliferation characteristics in glioblastoma
Authors: Rao Arvind , Rao Ganesh , Gutman David A. , Flanders Adam E. , Hwang Scott N. , Rubin Daniel L. , Colen Rivka R. , Zinn Pascal O. , Jain Rajan , Wintermark Max , Kirby Justin S. , Jaffe C. Carl , Freymann John , _ _
Published: October 2015

OBJECT

Individual MRI characteristics (e.g., volume) are routinely used to identify survival-associated phenotypes for glioblastoma (GBM). This study investigated whether combinations of MRI features can also stratify survival. Furthermore, the molecular differences between phenotype-induced groups were investigated.

METHODS

Ninety-two patients with imaging, molecular, and survival data from the TCGA (The Cancer Genome Atlas)-GBM collection were included in this study. For combinatorial phenotype analysis, hierarchical clustering was used. Groups were defined based on a cutpoint obtained via tree-based partitioning. Furthermore, differential expression analysis of microRNA (miRNA) and mRNA expression data was performed using GenePattern Suite. Functional analysis of the resulting genes and miRNAs was performed using Ingenuity Pathway Analysis. Pathway analysis was performed using Gene Set Enrichment Analysis.

RESULTS

Clustering analysis reveals that image-based grouping of the patients is driven by 3 features: volume-class, hemorrhage, and T1/FLAIR-envelope ratio. A combination of these features stratifies survival in a statistically significant manner. A cutpoint analysis yields a significant survival difference in the training set (median survival difference: 12 months, p = 0.004) as well as a validation set (p = 0.0001). Specifically, a low value for any of these 3 features indicates favorable survival characteristics. Differential expression analysis between cutpoint-induced groups suggests that several immune-associated (natural killer cell activity, T-cell lymphocyte differentiation) and metabolism-associated (mitochondrial activity, oxidative phosphorylation) pathways underlie the transition of this phenotype. Integrating data for mRNA and miRNA suggests the roles of several genes regulating proliferation and invasion.

CONCLUSIONS

A 3-way combination of MRI phenotypes may be capable of stratifying survival in GBM. Examination of molecular processes associated with groups created by this combinatorial phenotype suggests the role of biological processes associated with growth and invasion characteristics.
The fate of cranial neuropathy after flow diversion for carotid aneurysms
Authors: Brown Benjamin L. , Lopes Demetrius , Miller David A. , Tawk Rabih G. , Brasiliense Leonardo B. C. , Ringer Andrew , Sauvageau Eric , Powers Ciarán J. , Arthur Adam , Hoit Daniel , Snyder Kenneth , Siddiqui Adnan , Levy Elad , Hopkins L. Nelson , Cuellar Hugo , Rodriguez-Mercado Rafael , Veznedaroglu Erol , Binning Mandy , Mocco J , Aguilar-Salinas Pedro , Boulos Alan , Yamamoto Junichi , Hanel Ricardo A.
Published: October 2015

OBJECT

The authors sought to determine whether flow diversion with the Pipeline Embolization Device (PED) can approximate microsurgical decompression in restoring function after cranial neuropathy following carotid artery aneurysms.

METHODS

This multiinstitutional retrospective study involved 45 patients treated with PED across the United States. All patients included presented between November 2009 and October 2013 with cranial neuropathy (cranial nerves [CNs] II, III, IV, and VI) due to intracranial aneurysm. Outcome analysis included clinical and procedural variables at the time of treatment as well as at the latest clinical and radiographic follow-up.

RESULTS

Twenty-six aneurysms (57.8%) were located in the cavernous segment, while 6 (13.3%) were in the clinoid segment, and 13 (28.9%) were in the ophthalmic segment of the internal carotid artery. The average aneurysm size was 18.6 mm (range 4–35 mm), and the average number of flow diverters placed per patient was 1.2. Thirty-eight patients had available information regarding duration of cranial neuropathy prior to treatment. Eleven patients (28.9%) were treated within 1 month of symptom onset, while 27 (71.1%) were treated after 1 month of symptoms. The overall rate of cranial neuropathy improvement for all patients was 66.7%. The CN deficits resolved in 19 patients (42.2%), improved in 11 (24.4%), were unchanged in 14 (31.1%), and worsened in 1 (2.2%). Overtime, the rate of cranial neuropathy improvement was 33.3% (15/45), 68.8% (22/32), and 81.0% (17/21) at less than 6, 6, and 12 months, respectively. At last follow-up, 60% of patients in the isolated CN II group had improvement, while in the CN III, IV, or VI group, 85.7% had improved. Moreover, 100% (11/11) of patients experienced improvement if they were treated within 1 month of symptom onset, whereas 44.4% (12/27) experienced improvement if they treated after 1 month of symptom onset; 70.4% (19/27) of those with partial deficits improved compared with 30% (3/10) of those with complete deficits.

CONCLUSIONS

Cranial neuropathy caused by cerebral aneurysm responds similarly when the aneurysm is treated with the PED compared with open surgery and coil embolization. Lower morbidity and higher occlusion rates obtained with the PED may suggest it as treatment of choice for some of these lesions. Time to treatment is an important consideration regardless of treatment modality.
Screening for intracranial aneurysms? Prevalence of unruptured intracranial aneurysms in Hong Kong Chinese
Authors: Chan David Y. C. , Abrigo Jill M. , Cheung Tom C. Y. , Siu Deyond Y. W. , Poon Wai S. , Ahuja Anil T. , Wong George K. C.
Published: October 2015

OBJECT

The objective of this study was to generate data on the local prevalence of unruptured intracranial aneurysms (UIAs) in asymptomatic Hong Kong Chinese individuals. First-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH) were recruited as surrogates of the general population and to explore the potential role of screening in this locality.

METHODS

The authors identified first-degree relatives of consecutive patients with subarachnoid hemorrhage from a ruptured aneurysm who were admitted to a university hospital in Hong Kong from June 2008 to December 2010. Magnetic resonance angiography (MRA) was the imaging modality used to screen the cerebral vasculature of these asymptomatic individuals. If MRA showed abnormal findings, CT angiography was performed to confirm the MRA findings.

RESULTS

In total, 7 UIAs were identified from the 305 MR angiograms obtained. The prevalence of UIAs in first-degree relatives of patients with aSAH in the Hong Kong Chinese population was 2.30% (95% CI1.02%–4.76%). This percentage was lower than the prevalence rate of 3.2% from a meta-analysis of the literature. The sizes of the UIAs detected ranged from 1.4 mm to 7.5 mm; 85.7% of the UIAs detected in this study were < 5 mm, in contrast to 66% noted in the literature. One of the UIAs identified underwent endovascular stent placement with a flow diverter. None of the UIAs identified ruptured or became symptomatic during a median follow-up period of 3.5 years.

CONCLUSIONS

The prevalence of UIAs in first-degree relatives of patients with aSAH in the Hong Kong Chinese population was lower than that in Caucasians. At the same time, most of the UIAs detected in this study were small (85.7% were < 5 mm, vs 66% in a meta-analysis). With a similar incidence of aSAH in Hong Kong (7.5 per 100,000 person-years) as compared with data cited in the literature, the hypothesis that UIA rupture risk size threshold is different in Chinese patients should be further investigated.
Extensive traumatic anterior skull base fractures with cerebrospinal fluid leak: classification and repair techniques using combined vascularized tissue flaps
Authors: Archer Jacob B. , Sun Hai , Bonney Phillip A. , Zhao Yan Daniel , Hiebert Jared C. , Sanclement Jose A. , Little Andrew S. , Sughrue Michael E. , Theodore Nicholas , James Jeffrey , Safavi-Abbasi Sam
Published: October 2015

OBJECT

This article introduces a classification scheme for extensive traumatic anterior skull base fracture to help stratify surgical treatment options. The authors describe their multilayer repair technique for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture using a combination of laterally pediculated temporalis fascial-pericranial, nasoseptal-pericranial, and anterior pericranial flaps.

METHODS

Retrospective chart review identified patients treated surgically between January 2004 and May 2014 for anterior skull base fractures with CSF fistulas. All patients were treated with bifrontal craniotomy and received pedicled tissue flaps. Cases were classified according to the extent of fracture: Class I (frontal bone/sinus involvement only); Class II (extent of involvement to ethmoid cribriform plate); and Class III (extent of involvement to sphenoid bone/sinus). Surgical repair techniques were tailored to the types of fractures. Patients were assessed for CSF leak at follow-up. The Fisher exact test was applied to investigate whether the repair techniques were associated with persistent postoperative CSF leak.

RESULTS

Forty-three patients were identified in this series. Thirty-seven (86%) were male. The patients’ mean age was 33 years (range 11–79 years). The mean overall length of follow-up was 14 months (range 5–45 months). Six fractures were classified as Class I, 8 as Class II, and 29 as Class III. The anterior pericranial flap alone was used in 33 patients (77%). Multiple flaps were used in 10 patients (3 salvage) (28%)—1 with Class II and 9 with Class III fractures. Five (17%) of the 30 patients with Class II or III fractures who received only a single anterior pericranial flap had persistent CSF leak (p < 0.31). No CSF leak was found in patients who received multiple flaps. Although postoperative CSF leak occurred only in high-grade fractures with single anterior flap repair, this finding was not significant.

CONCLUSIONS

Extensive anterior skull base fractures often require aggressive treatment to provide the greatest long-term functional and cosmetic benefits. Several vascularized tissue flaps can be used, either alone or in combination. Vascularized flaps are an ideal substrate for cranial base repair. Dual and triple flap techniques that combine the use of various anterior, lateral, and nasoseptal flaps allow for a comprehensive arsenal in multilayered skull base repair and salvage therapy for extensive and severe fractures.
Endoscopic transnasal external fistulation in recurrent cystic subdiaphragmatic craniopharyngioma: a novel technique
Authors: Solanki Sandeep P. , Sama Anshul , Robertson Iain J.
Published: October 2015

The authors present a technique for the persistent external drainage of intractable subdiaphragmatic cystic recurrences with the creation of a fistula between the cyst wall epithelium and epithelium on the nasal cavity, using a pedicled nasoseptal flap as a conduit. The long-term efficacy of endoscopic transnasal external fistulation (ETEF) in controlling cystic recurrences in this patient group is addressed through a retrospective observational review of 3 male patients aged 8, 22, and 45 years with the diagnosis of recurrent cystic subdiaphragmatic craniopharyngioma who underwent the ETEF procedure between 2006 and 2009. Clinical presentation, neuroimaging, surgical interventions, and follow-up were recorded. The main outcome measure was cyst reaccumulation on MRI.

Patients had a mean follow-up of 76 months (range 5–8 years) with no incidence of cystic recurrence. Follow-up imaging revealed sustained cyst involution contrary to the usual recurrent enlargement commonly seen in this patient group. Symptoms of headache and visual field defects improved post-ETEF. Long-term theoretical complications of a persistent fistula such as intracranial abscess, meningitis, or CSF leak were not observed. ETEF promotes nasalization of cystic recurrences in subdiaphragmatic craniopharyngioma. It is safe and effective, causing long-term involution of cysts and can be considered a definitive procedure.
Malignant brainstem tumors in children, excluding diffuse intrinsic pontine gliomas
Authors: Klimo Paul , Nesvick Cody L. , Broniscer Alberto , Orr Brent A. , Choudhri Asim F.
Published: October 2015

OBJECT

Malignant tumors of the brainstem, excluding classic diffuse intrinsic pontine gliomas (DIPGs), are a very rare, heterogeneous group of neoplasms that have been infrequently described in the literature. In this paper, the authors present their experiences with treating these unique cancers.

METHODS

A retrospective chart review was conducted to identify eligible cases over a 15-year period. All tumors involving the pons were, by consensus, felt not to be DIPGs based on their neuroimaging features. Demographic information, pathological specimens, neuroimaging characteristics, surgical and nonsurgical management plans, and survival data were gathered for analysis.

RESULTS

Between January 2000 and December 2014, 29 patients were identified. The mean age at diagnosis was 8.4 years (range 2 months to 25 years), and 17 (59%) patients were male. The most common presenting signs and symptoms were cranial neuropathies (n = 24; 83%), hemiparesis (n = 12; 41%), and ataxia or gait disturbance (n = 10; 34%). There were 18 glial and 11 embryonal tumors. Of the glial tumors, 5 were radiation-induced and 1 was a malignant transformation of a previously known low-grade tumor. Surgical intervention consisted of biopsy alone in 12 patients and some degree of resection in another 15 patients. Two tumors were diagnosed postmortem. The median overall survival for all patients was 196 days (range 15 to 3999 days). There are currently 5 (17%) patients who are still alive: 1 with an anaplastic astrocytoma and the remaining with embryonal tumors.

CONCLUSIONS

In general, malignant non-DIPG tumors of the brainstem carry a poor prognosis. However, maximal cytoreductive surgery may be an option for select patients with focal tumors. Long-term survival is possible in patients with nonmetastatic embryonal tumors after multimodal treatment, most importantly maximal resection.
Series Arc Fault Detection Algorithm Based on Autoregressive Bispectrum Analysis
Authors: Yang Kai , Zhang Rencheng , Chen Shouhong , Zhang Fujiang , Yang Jianhong , Zhang Xingbin
Published: October 2015

Arc fault is one of the most critical reasons for electrical fires. Due to the diversity, randomness and concealment of arc faults in low-voltage circuits, it is difficult for general methods to protect all loads from series arc faults. From the analysis of many series arc faults, a large number of high frequency signals generated in circuits are found. These signals are easily affected by Gaussian noise which is difficult to be eliminated as a result of frequency aliasing. Thus, a novel detection algorithm is developed to accurately detect series arc faults in this paper. Initially, an autoregressive model of the mixed high frequency signals is modelled. Then, autoregressive bispectrum analysis is introduced to analyze common series arc fault features. The phase information of arc fault signal is preserved using this method. The influence of Gaussian noise is restrained effectively. Afterwards, several features including characteristic frequency, fluctuation of phase angles, diffused distribution and incremental numbers of bispectrum peaks are extracted for recognizing arc faults. Finally, least squares support vector machine is used to accurately identify series arc faults from the load states based on these frequency features of bispectrum. The validity of the algorithm is experimentally verified obtaining arc fault detection rate above 97%.
Nonprofit Governance, Organizational Purposiveness and Design
Authors: Wagner Antonin
Published: October 2015

The final article published in this Special Issue on nonprofit governance provides a platform for myself as the guest editor in two ways: both to reflect in a Postscript on the editorial process in which I became involved since posting a call for papers, as well as to write this Foreword that helps readers to become engaged in a meaningful discourse with the contributing authors. Incongruous as it may appear to be, I begin with the Postscript, as the Introductory Note to the Special Issue is not meant to integrate the articles published into a consistent concluding argument, but rather to evaluate my role ex post and at the same time to reveal to readers ex ante the premises based on which as guest-editor I selected articles for this Special Issue on nonprofit governance. [...]
Hsp90: A New Player in DNA Repair?
Authors: Pennisi Rosa , Ascenzi Paolo , Di Masi Alessandra
Published: October 2015

Heat shock protein 90 (Hsp90) is an evolutionary conserved molecular chaperone that, together with Hsp70 and co-chaperones makes up the Hsp90 chaperone machinery, stabilizing and activating more than 200 proteins, involved in protein homeostasis (i.e., proteostasis), transcriptional regulation, chromatin remodeling, and DNA repair. Cells respond to DNA damage by activating complex DNA damage response (DDR) pathways that include: (i) cell cycle arrest; (ii) transcriptional and post-translational activation of a subset of genes, including those associated with DNA repair; and (iii) triggering of programmed cell death. The efficacy of the DDR pathways is influenced by the nuclear levels of DNA repair proteins, which are regulated by balancing between protein synthesis and degradation as well as by nuclear import and export. The inability to respond properly to either DNA damage or to DNA repair leads to genetic instability, which in turn may enhance the rate of cancer development. Multiple components of the DNA double strand breaks repair machinery, including BRCA1, BRCA2, CHK1, DNA-PKcs, FANCA, and the MRE11/RAD50/NBN complex, have been described to be client proteins of Hsp90, which acts as a regulator of the diverse DDR pathways. Inhibition of Hsp90 actions leads to the altered localization and stabilization of DDR proteins after DNA damage and may represent a cell-specific and tumor-selective radiosensibilizer. Here, the role of Hsp90-dependent molecular mechanisms involved in cancer onset and in the maintenance of the genome integrity is discussed and highlighted.
A Mechanistic Review of Mitophagy and Its Role in Protection against Alcoholic Liver Disease
Authors: Williams Jessica , Ding Wen-Xing
Published: October 2015

Alcoholic liver disease (ALD) is a major health problem worldwide, and alcohol is well-known to cause mitochondrial damage, which exacerbates alcohol-induced liver injury and steatosis. No successful treatments are currently available for treating ALD. Therefore, a better understanding of mechanisms involved in regulation of mitochondrial homeostasis in the liver and how these mechanisms may protect against alcohol-induced liver disease is needed for future development of better therapeutic options for ALD. Mitophagy is a key mechanism for maintaining mitochondrial homeostasis by removing damaged mitochondria, and mitophagy protects against alcohol-induced liver injury. Parkin, an E3 ubiquitin ligase, is well-known to induce mitophagy in in vitro models although Parkin-independent mechanisms for mitophagy induction also exist. In this review, we discuss the roles of Parkin and mitophagy in protection against alcohol-induced liver injury and steatosis. We also discuss Parkin-independent mechanisms for mitophagy induction, which have not yet been evaluated in the liver but may also potentially have a protective role against ALD. In addition to mitophagy, mitochondrial spheroid formation may also provide a novel mechanism of protection against ALD, but the role of mitochondrial spheroids in protection against ALD progression needs to be further explored. Targeting removal of damaged mitochondria by mitophagy or inducing formation of mitochondrial spheroids may be promising therapeutic options for treatment of ALD.
Αlpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson’s Disease
Authors: Bobela Wojciech , Aebischer Patrick , Schneider Bernard
Published: October 2015

Accumulation and misfolding of the alpha-synuclein protein are core mechanisms in the pathogenesis of Parkinson’s disease. While the normal function of alpha-synuclein is mainly related to the control of vesicular neurotransmission, its pathogenic effects are linked to various cellular functions, which include mitochondrial activity, as well as proteasome and autophagic degradation of proteins. Remarkably, these functions are also affected when the renewal of macromolecules and organelles becomes impaired during the normal aging process. As aging is considered a major risk factor for Parkinson’s disease, it is critical to explore its molecular and cellular implications in the context of the alpha-synuclein pathology. Here, we discuss similarities and differences between normal brain aging and Parkinson’s disease, with a particular emphasis on the nigral dopaminergic neurons, which appear to be selectively vulnerable to the combined effects of alpha-synuclein and aging.
The La-Related Proteins, a Family with Connections to Cancer
Authors: Stavraka Chara , Blagden Sarah
Published: October 2015

The evolutionarily-conserved La-related protein (LARP) family currently comprises Genuine La, LARP1, LARP1b, LARP4, LARP4b, LARP6 and LARP7. Emerging evidence suggests each LARP has a distinct role in transcription and/or mRNA translation that is attributable to subtle sequence variations within their La modules and specific C-terminal domains. As emerging research uncovers the function of each LARP, it is evident that La, LARP1, LARP6, LARP7 and possibly LARP4a and 4b are dysregulated in cancer. Of these, LARP1 is the first to be demonstrated to drive oncogenesis. Here, we review the role of each LARP and the evidence linking it to malignancy. We discuss a future strategy of targeting members of this protein family as cancer therapy.
Assessing Embodied Energy and Greenhouse Gas Emissions in Infrastructure Projects
Authors: Krantz Jan , Larsson Johan , Lu Weizhuo , Olofsson Thomas
Published: October 2015

Greenhouse gas (GHG) emissions from construction processes are a serious concern globally. Of the several approaches taken to assess emissions, Life Cycle Assessment (LCA) based methods do not just take into account the construction phase, but consider all phases of the life cycle of the construction. However, many current LCA approaches make general assumptions regarding location and effects, which do not do justice to the inherent dynamics of normal construction projects. This study presents a model to assess the embodied energy and associated GHG emissions, which is specifically adapted to address the dynamics of infrastructure construction projects. The use of the model is demonstrated on the superstructure of a prefabricated bridge. The findings indicate that Building Information Models/Modeling (BIM) and Discrete Event Simulation (DES) can be used to efficiently generate project-specific data, which is needed for estimating the embodied energy and associated GHG emissions in construction settings. This study has implications for the advancement of LCA-based methods (as well as project management) as a way of assessing embodied energy and associated GHG emissions related to construction.
Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1
Authors: Arnason Terra , Harkness Troy
Published: October 2015

Early detection and improved therapies for many cancers are enhancing survival rates. Although many cytotoxic therapies are approved for aggressive or metastatic cancer; response rates are low and acquisition of de novo resistance is virtually universal. For decades; chemotherapeutic treatments for cancer have included anthracyclines such as Doxorubicin (DOX); and its use in aggressive tumors appears to remain a viable option; but drug resistance arises against DOX; as for all other classes of compounds. Our recent work suggests the anticoagulant protein Tissue Factor Pathway Inhibitor 1α (TFPI1α) plays a role in driving the development of multiple drug resistance (MDR); but not maintenance; of the MDR state. Other factors; such as the ABC transporter drug efflux pumps MDR-1/P-gp (ABCB1) and BCRP (ABCG2); are required for MDR maintenance; as well as development. The patient population struggling with therapeutic resistance specifically requires novel treatment options to resensitize these tumor cells to therapy. In this review we discuss the development, maintenance, and reversal of MDR as three distinct phases of cancer biology. Possible means to exploit these stages to reverse MDR will be explored. Early molecular detection of MDRcancers before clinical failure has the potential to offer new approaches to fighting MDRcancer.