bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Outcomes After Anterior Cruciate Ligament Reconstruction in Patients 60 Years and Older
Authors: Baker Champ L. , Jones Jaclyn C. , Zhang Jeff
Published: December 2014

Background:

Studies evaluating the benefit of surgical reconstruction of the anterior cruciate ligament (ACL) in middle-aged patients have shown promising results, but study populations were limited primarily to patients who were 40 to 60 years old. Some authors have suggested that surgery may benefit these older patients.

Hypothesis:

Patients aged ≥60 years with functional instability after ACL injury would benefit from ACL reconstruction.

Study Design:

Case series; Level of evidence, 4.

Methods:

Medical records from 1984 through 2010 were searched for patients aged ≥60 years who had undergone primary arthroscopic ACL reconstruction at a single institution. Fifteen patients (15 knees) were identified as meeting the above criteria. All patients were contacted for a telephone interview, and they completed Short Form–36 and modified Cincinnati Knee Score forms. One patient was deceased, and 1 had undergone revision to total knee arthroplasty. Among the remaining 13 patients, the mean age at surgery was 63.5 years (range, 60-73 years), and the mean patient age at the time of follow-up was 73 years (range, 65-85 years). Preoperative radiographs showed no obvious evidence of arthritis in 10 (77%) of the 13 patients; small osteophytes without loss of joint space were seen in 3 (23%) patients. The mean length of follow up was 115.7 months (range, 53-193 months).

Results:

At their last clinic visits, all 13 patients had regained full range of motion and returned to sports or exercise, such as tennis, golf, gym exercise, and yoga. Twelve patients reported no joint laxity.

Conclusion:

Patients aged ≥60 years with symptomatic instability from ACL injury can have good to excellent subjective outcomes with surgical reconstruction.

Clinical Relevance:

Physicians who treat active patients older than 60 years should not exclude ACL reconstruction based on the patient’s age alone.
Structural Properties of the Native Ligamentum Teres
Authors: Philippon Marc J. , Rasmussen Matthew T. , Turnbull Travis Lee , Trindade Christiano A.C. , Hamming Mark G. , Ellman Michael B. , Harris Matthew , LaPrade Robert F. , Wijdicks Coen A.
Published: December 2014

Background:

A majority of studies investigating the role of the ligamentum teres (LT) have focused primarily on anatomical and histological descriptions. To date, however, the structural properties of the LT have yet to be fully elucidated.

Purpose:

To investigate the structural properties of the native LT in a human cadaveric model.

Study Design:

Descriptive laboratory study.

Methods:

A total of 12 human cadaveric hemipelvises (mean age, 53.6 years; range, 34-63 years) were dissected free of all extra-articular soft tissues to isolate the LT and its acetabular and femoral attachments. A dynamic tensile testing machine distracted each femur in line with the fibers of the LT at a displacement-controlled rate of 0.5 mm/s. The anatomic dimensions, structural properties, and modes of failure were recorded.

Results:

The LT achieved a mean yield load of 75 N and ultimate failure load of 204 N. The LT had mean lengths of 38.0 and 53.0 mm at its yield and failure points, respectively. The most common (75% of specimens) mechanism of failure was tearing at the fovea capitis. On average, the LT had a linear stiffness of 16 N/mm and elastic modulus of 9.24 MPa. The mean initial length and cross-sectional area were 32 mm and 59 mm2, respectively.

Conclusion:

The human LT had a mean ultimate failure load of 204 N. Therefore, the results of this investigation, combined with recent biomechanical and outcomes studies, suggest that special consideration should be given to preserving the structural and corresponding biomechanical integrity of the LT during surgical intervention.

Clinical Relevance:

The LT may be more important as a static stabilizer of the hip joint than previously recognized. Further studies are recommended to investigate the appropriate indications to perform surgical repair or reconstruction of the LT for preservation of hip stability and function.
Responding to Hostility
Authors: Campbell Kim Sydow , Carmichael Pierson , Naidoo Jefrey S.
Published: December 2014

Hostile challenges to planned organization change are common and challenging to deal with effectively. Little research has explained successful responses to such stakeholder hostility. To address this gap, we use the concept of readiness to characterize the content of hostile challenges. We also use rhetorical strategies based on speech act theory to describe options for responding to those challenges. Because change agents must choose among multiple strategies, we continue a line of research investigating relative preferences among them. Ultimately, our aim is to offer six lessons for change agents who face hostile challenges based on evidence from research.
The Role of Motivational Values in the Construction of Change Messages
Authors: Cardon Peter W. , Philadelphia Marion
Published: December 2014

We examined how 106 early-career professionals constructed video change messages involving a ban on remote working. These professionals constructed three types of statements: vision statements, direct change statements, and indirect change statements. Professionals with higher assertive-directing motivational values tended to first construct vision statements and secondly construct direct change statements, whereas professionals higher in analytic-autonomizing motivational values tended to first construct indirect change statements and secondly construct direct change statements. Overall, early-career professionals displayed strong group orientation in their rationale for change and low directness in communicating change.
Cost-Effectiveness of a Low-Cost, Hospital-Based Primary Care Clinic
Authors: Agee Mark D. , Gates Zane , Reilly Patrick
Published: December 2014

This study assesses the cost-effectiveness of an insurance administration-free, hospital-based clinic designed to provide a full array of primary care services to low-income individuals at little or no cost. In addition to low/no-cost visits, individuals have the option to purchase a low-cost health insurance plan similar to any traditional health plan (eg, prescriptions, primary care, specialty care, durable medical equipment, radiology, laboratory test results). We used 3 years of data (2009-2012) on emergency department (ED) visits and inpatient hospital admissions from clinic patients and patients at the community’s 2 largest private physician groups to assess the cost-effectiveness of the hospital-based clinic in terms of ED and inpatient admission costs avoided and financial sustainability of the low-cost insurance plan. Estimated annual savings in hospital inpatient and ED costs were approximately 1.4 million. Insurance plan data indicated sound fiscal sustainability with modest provider reimbursement growth and zero annual premium growth.
US Primary Care Physicians’ Prostate Cancer Screening Practices
Authors: Rim Sun Hee , Hall Ingrid J. , Richards Thomas B. , Thompson Trevor D. , Richardson Lisa C. , Ross Louie E. , Plescia Marcus
Published: December 2014

Background:

Limited information exists on primary care physicians’ (PCPs) use of the prostate-specific antigen (PSA) test by patient risk category. We describe PCP responses to hypothetical patient scenario (PS) involving PSA testing among high-risk asymptomatic men.

Methods:

Data were from the 2007 to 2008 National Survey of Primary Care Physicians’ Practices Regarding Prostate Cancer Screening. PS#1: healthy 55-year-old white male with no family history of prostate cancer; PS#2: healthy 45-year-old African American male with no family history of prostate cancer; and PS#3: healthy 50-year-old male with a family history of prostate cancer. Data were analyzed in SAS/SUDAAN.

Results:

Most PCPs indicated that they generally discuss the possible benefits/risks of PSA testing with the patient and then recommend the test (PS#1-PS#3 range, 53.4%-68.7%; P < .001); only about 1% reported discussing and then recommending against the test. For PS#3, compared to PS#1 and #2, PCPs were more likely to discuss and recommend the test or attempt to persuade the patient who initially declines the test. For PS#3, all clinicians generally would order/discuss the PSA test and not rely on the patient to ask.

Conclusion:

Clinicians treat family history as an important reason to recommend, persuade, and initiate PSA testing.
The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations
Authors: Bodini Margherita , Ronchini Chiara , Giacò Luciano , Russo Anna , Melloni Giorgio E. M. , Luzi Lucilla , Sardella Domenico , Volorio Sara , Hasan Syed K. , Ottone Tiziana , Lavorgna Serena , Lo-Coco Francesco , Candoni Anna , Fanin Renato , Toffoletti Eleonora , Iacobucci Ilaria , Martinelli Giovanni , Cignetti Alessandro , Tarella Corrado , Bernard Loris , Pelicci Pier Giuseppe , Riva Laura
Published: December 2014

The analyses carried out using 2 different bioinformatics pipelines (SomaticSniper and MuTect) on the same set of genomic data from 133 acute myeloid leukemia (AML) patients, sequenced inside the Cancer Genome Atlas project, gave discrepant results. We subsequently tested these 2 variant-calling pipelines on 20 leukemia samples from our series (19 primary AMLs and 1 secondary AML). By validating many of the predicted somatic variants (variant allele frequencies ranging from 100% to 5%), we observed significantly different calling efficiencies. In particular, despite relatively high specificity, sensitivity was poor in both pipelines resulting in a high rate of false negatives. Our findings raise the possibility that landscapes of AML genomes might be more complex than previously reported and characterized by the presence of hundreds of genes mutated at low variant allele frequency, suggesting that the application of genome sequencing to the clinic requires a careful and critical evaluation. We think that improvements in technology and workflow standardization, through the generation of clear experimental and bioinformatics guidelines, are fundamental to translate the use of next-generation sequencing from research to the clinic and to transform genomic information into better diagnosis and outcomes for the patient.
Bone marrow skeletal stem/progenitor cell defects in dyskeratosis congenita and telomere biology disorders
Authors: Balakumaran Arun , Mishra Prasun J. , Pawelczyk Edyta , Yoshizawa Sayuri , Sworder Brian J. , Cherman Natasha , Kuznetsov Sergei A. , Bianco Paolo , Giri Neelam , Savage Sharon A. , Merlino Glenn , Dumitriu Bogdan , Dunbar Cynthia E. , Young Neal S. , Alter Blanche P. , Robey Pamela G.
Published: December 2014

Key Points

BMSCs from patients with TBDs are abnormal and unable to support hematopoiesis. Knockdown of TERC with siRNA recapitulates the TBD-BMSC phenotype.
CMV promotes recipient T-cell immunity following reduced-intensity T-cell–depleted HSCT, significantly modulating chimerism status
Authors: Sellar Rob S. , Vargas Frederick Arce , Henry Jake Y. , Verfuerth Stephanie , Charrot Sarah , Beaton Brendan , Chakraverty Ronjon , Quezada Sergio A. , Mackinnon Stephen , Thomson Kirsty J. , Peggs Karl S.
Published: December 2014

Key Points

CMV serostatus significantly influences chimerism levels after T-cell–depleted allogeneic transplantation. CMV-specific T cells are exclusively of recipient origin after R+/D− T-cell–depleted transplants and appear to provide protective immunity.
The effect of free-standing GaN substrate on carrier localization in ultraviolet InGaN light-emitting diodes
Authors: Tsai Ming-Ta , Chu Chung-Ming , Huang Che-Hsuan , Wu Yin-Hao , Chiu Ching-Hsueh , Li Zhen-Yu , Tu Po-Min , Lee Wei-I , Kuo Hao-Chung
Published: December 2014

In this study, we have grown 380-nm ultraviolet light-emitting diodes (UV-LEDs) based on InGaN/AlInGaN multiple quantum well (MQW) structures on free-standing GaN (FS-GaN) substrate by atmospheric pressure metal-organic chemical vapor deposition (AP-MOCVD), and investigated the relationship between carrier localization degree and FS-GaN. The micro-Raman shift peak mapping image shows low standard deviation (STD), indicating that the UV-LED epi-wafer of low curvature and MQWs of weak quantum-confined Stark effect (QCSE) were grown. High-resolution X-ray diffraction (HRXRD) analyses demonstrated high-order satellite peaks and clear fringes between them for the UV-LEDs grown on the FS-GaN substrate, from which the interface roughness (IRN) was estimated. The temperature-dependent photoluminescence (PL) measurement confirmed that the UV-LEDs grown on the FS-GaN substrate exhibited better carrier confinement. Besides, the high-resolution transmission electron microscopy (HRTEM) and energy-dispersive spectrometer (EDS) mapping images verified that the UV-LEDs on FS-GaN have fairly uniform distribution of indium and more ordered InGaN/AlInGaN MQW structure. Clearly, the FS-GaN can not only improve the light output power but also reduce the efficiency droop phenomenon at high injection current. Based on the results mentioned above, the FS-GaN can offer UV-LEDs based on InGaN/AlInGaN MQW structures with benefits, such as high crystal quality and small carrier localization degree, compared with the UV-LEDs on sapphire.
A stepwise loading method to magnetically responsive Pt-Fe3O4/MCNT catalysts for selective hydrogenation of 3-methylcrotonaldehyde
Authors: Song Shaofei , Yu Jianyan , Xiao Qiang , Ye Xiangrong , Zhong Yijun , Zhu Weidong
Published: December 2014

Pt-loaded multi-walled carbon nanotubes (Pt/MCNTs) and magnetically responsive Pt-Fe3O4/MCNT catalysts were prepared by a stepwise loading of preformed Pt and Fe3O4 nanoparticles onto multi-walled carbon nanotubes (MCNTs). The structure, composition, and magnetism of the catalysts were characterized by X-ray diffraction (XRD), TEM, H2-O2 titration, inductively coupling plasma-atomic emission spectroscopy (ICP-AES), and superconducting quantum interference device (SQUID) techniques. Ascribed to the well-controlled particle size in the preformed Pt colloids, Pt particles in the consequent Pt/MCNT and Pt-Fe3O4/MCNT catalysts are of high uniformity and dispersion. The prepared Pt catalysts show an excellent catalytic performance in the liquid phase hydrogenation of 3-methylcrotonaldehyde, one of typical α,β-unsaturated aldehydes. A very high selectivity to 3-methylcrotonalcohol of 98% at a conversion of about 80% was available on the magnetic Pt-Fe3O4/MCNT catalyst. The magnetic catalyst, with good superparamagnetism, can be easily recovered from the liquid phase system under the external magnetic field. Moreover, both the Pt/MCNT and magnetic Pt-Fe3O4/MCNT catalysts show a good recyclability, confirmed by five cycles of reusage.
Overexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine
Authors: Adema Auke D , Floor Karijn , Smid Kees , Honeywell Richard J , Scheffer George L , Jansen Gerrit , Peters Godefridus J
Published: December 2014

We aimed to determine whether the multidrug-resistance-proteins MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the antimetabolites cytarabine (Ara-C), gemcitabine (GEM), and the L-nucleoside analog troxacitabine. For this purpose we used HEK293 and the transfected HEK/MRP4 (59-fold increased MRP4) or HEK/MRP5i (991-fold increased MRP5) as model systems and tested the cells for drug sensitivity using a proliferation test. Drug accumulation was performed by using radioactive Ara-C, and for GEM and troxacitabine with HPLC with tandem-MS or UV detection. At 4-hr exposure HEK/MRP4 cells were 2-4-fold resistant to troxacitabine, ara-C and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), and HEK/MRP5i to ara-C and PMEA, but none to GEM. The inhibitors probenecid and indomethacin reversed resistance. After 4-hr exposure ara-C-nucleotides were 2-3-fold lower in MRP4/5 cells, in which they decreased more rapidly after washing with drug-free medium (DFM). Trocacitabine accumulation was similar in the 3 cell lines, but after the DFM period troxacitabine decreased 2-4-fold faster in MRP4/5 cells. Troxacitabine-nucleotides were about 25% lower in MRP4/5 cells and decreased rapidly in MRP4, but not in MRP5 cells. Accumulation of GEM-nucleotides was higher in the MRP4/5 cells. In conclusion: MRP4 and MRP5 overexpression confer resistance to troxacitabine and ara-C, but not to GEM, which was associated with a rapid decline of the ara-C and troxacitabine-nucleotides in HEK/MRP4-5 cells.
The impact of workforce redesign policies on role boundaries in ‘generalist’ podiatry practice: expert views within the professional body
Authors: Stressing Samantha J , Borthwick Alan M
Published: December 2014

Background

Demographic changes and a predicted rise in the prevalence of chronic illness have led to a range of health policies in the UK (and elsewhere) focused on workforce flexibility and extended roles for the allied health professions. Whilst much academic attention has been paid to extended specialised roles for allied health professionals such as podiatrists, little work has addressed the likely impact of these policy changes on non‐specialist, ‘generalist’ podiatry practice. This study aimed to explore expert professional views on the impact of role flexibility on generalist podiatry practice.

Methods

Expert podiatry practitioners drawn from within the professional body, the Society of Chiropodists and Podiatrists/College of Podiatry were recruited to 3 focus groups and 4 individual semi structured interviews and the data subject to a thematic analysis.

Results

Three key themes emerged, reflecting concerns about the future of generalist podiatry practice in the NHS, a perceived likelihood that generalist care will move inexorably towards private sector provision, and a growth in support worker grades undermining the position of generalist practice in the mainstream health division of labour. Up skilling generalist practitioners was viewed as the strongest defence against marginalisation.

Conclusions

An emphasis on enhanced and specialised roles in podiatry by NHS commissioners and profession alike may threaten the sustainability of generalist podiatry provision in the state funded NHS. Non‐specialist general podiatry may increasingly become the province of the private sector.
Asymmetries and relationships between dynamic loading, muscle strength, and proprioceptive acuity at the knees in symptomatic unilateral hip osteoarthritis
Authors: Shakoor Najia , Foucher Kharma C , Wimmer Markus A , Mikolaitis-Preuss Rachel A , Fogg Louis F , Block Joel A
Published: December 2014

Introduction

High joint loading, knee muscle weakness, and poor proprioceptive acuity are important factors that have been linked to knee osteoarthritis (OA). We previously reported that those with unilateral hip OA and bilateral asymptomatic knees are more predisposed to develop progressive OA in the contralateral knee relative to the ipsilateral knee. In the present study, we evaluate asymmetries in muscle strength and proprioception between the limbs and also evaluate relationships between these factors and joint loading that may be associated with the asymmetric evolution of OA in this group.

Methods

Sixty-two participants with symptomatic unilateral hip OA and asymptomatic knees were evaluated for muscle strength, joint position sense and dynamic joint loads at the knees. Muscle strength and proprioception were compared between limbs and correlations between these factors and dynamic joint loading were evaluated. Subgroup analyses were also performed in only those participants that fulfilled criteria for severe hip OA.

Results

Quadriceps muscle strength was 15% greater, and in the severe subgroup, proprioceptive acuity was 25% worse at the contralateral compared to ipsilateral knee of participants with unilateral hip OA (P <0.05). In addition, at the affected limb, there was an association between decreased proprioceptive acuity and higher knee loading (Spearman’s rho = 0.377, P = 0.007) and between decreased proprioceptive acuity and decreased muscle strength (Spearman’s rho = −0.328, P = 0.016).

Conclusions

This study demonstrated asymmetries in muscle strength and proprioception between the limbs in a unilateral hip OA population. Early alterations in these factors suggest their possible role in the future development of OA at the contralateral ‘OA-predisposed knee’ in this group. Furthermore, the significant association observed between proprioception, loading, and muscle strength at the affected hip limb suggests that these factors may be interrelated.
The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study
Authors: Roubille Camille , Raynauld Jean-Pierre , Abram François , Paiement Patrice , Dorais Marc , Delorme Philippe , Bessette Louis , Beaulieu André D , Martel-Pelletier Johanne , Pelletier Jean-Pierre
Published: December 2014

Introduction

Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP).

Methods

This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed.

Results

Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P <0.001), function (P <0.001), stiffness (P = 0.007) and total (P <0.001) scores as well as higher VAS pain score (P = 0.023), and PainDETECT scores. Although no difference was found in the cartilage volume between groups, the presence of meniscal extrusion in both medial (P = 0.006) and lateral (P = 0.023) compartments, and presence of meniscal tears in the lateral compartment (P = 0.011), were significantly associated with increasing PainDETECT score. Moreover, the presence of bone marrow lesions in the lateral plateau and the extent of the synovial membrane thickness in the lateral recess were associated with increasing PainDETECT scores (P = 0.032, P = 0.027, respectively).

Conclusions

In this study, meniscal lesions, particularly extrusion, were found to be among the strongest risk factors for NP in knee OA patients.

Trial registration

ClinicalTrials.gov NCT01733277. Registered 16 November 2012.
Insight on automated lesion delineation methods for PET data
Authors: Firouzian Azadeh , Kelly Matthew D , Declerck Jérôme M
Published: December 2014

Background

Defining tumour volume for treatment response and radiotherapy planning is challenging and prone to inter- and intra-observer variability. Various automated tumour delineation methods have been proposed in the literature, each having abilities and limitations. Therefore, there is a need to provide clinicians with practical information on delineation method selection.

Methods

Six different automated positron emission tomography (PET) delineation methods were evaluated and compared using National Electrical Manufacturer Association image quality (NEMA IQ) phantom data and three in-house synthetic phantoms with clinically relevant lesion shapes including spheres with necrotic core and irregular shapes. The impact of different contrast ratios, emission counts, realisations and reconstruction algorithms on delineation performance was also studied using similarity index (SI) and percentage volume error (%VE) as performance measures.

Results

With the NEMA IQ phantom, contrast thresholding (CT) performed best on average for all sphere sizes and parameter settings (SI = 0.83; %VE = 5.65% ± 24.34%). Adaptive thresholding at 40% (AT40) was the next best method and required no prior parameter tuning (SI = 0.78; %VE = 23.22% ± 70.83%). When using SUV harmonisation filtering prior to delineation (EQ.PET), AT40 remains the best method without prior parameter tuning (SI = 0.81; %VE = 11.39% ± 85.28%).

For necrotic core spheres and irregular shapes of the synthetic phantoms, CT remained the best performing method (SI = 0.83; %VE = 26.31% ± 38.26% and SI = 0.62; %VE = 24.52% ± 46.89%, respectively). The second best method was fuzzy locally adaptive Bayesian (FLAB) (SI = 0.83; %VE = 29.51% ± 81.79%) for necrotic core sphere and AT40 (SI = 0.58; %VE = 25.11% ± 32.41%) for irregular shapes. When using EQ.PET prior to delineation, AT40 was the best performing method without prior parameter tuning for both necrotic core (SI = 0.83; %VE = 27.98% ± 59.58%) and complex shapes phantoms (SI = 0.61; %VE = 14.83% ± 49.39%).

Conclusions

CT and AT40/AT50 are recommended for all lesion sizes and contrasts. Overall, considering background uptake information improves PET delineation accuracy. Applying EQ.PET prior to delineation improves accuracy and reduces coefficient of variation (CV) across different reconstructions and acquisitions.
A cross-sectional assessment to detect type 2 diabetes with endothelial and autonomic nervous system markers using a novel system
Authors: Lewis John E , Lantigua Laura , Atlas Steven E , Lopez Johanna , Mendez Armando , Goldberg Sharon , Medici Sacha , Konefal Janet , Woolger Judi M , Tiozzo Eduard , Aliffe Karyem H
Published: December 2014

Background

Type 2 diabetes mellitus is frequently unrecognized until complications appear. Diabetic autonomic neuropathy is one of the early complications of type 2 diabetes mellitus, resulting in autonomic nervous system (ANS) dysfunction. The purpose of this study was to determine the validity of ANS function indicators to screen for type 2 diabetes mellitus, as measured by the TM-Oxi and SudoPath system.

Methods

All enrolled participants completed a basic sociodemographic and medical history questionnaire including current medications. Healthy controls (n = 25) underwent a 2-hour oral glucose tolerance test (OGTT) to evaluate glucose, insulin, and insulin C-peptide. Patients with type 2 diabetes mellitus (n = 24) were assessed with fasting plasma glucose (FPG) and glycosylated hemoglobin. The TM-Oxi and SudoPath system evaluation was completed by all subjects. Data were analyzed using SPSS 22. Frequency and descriptive statistics were calculated on all variables. The criterion for statistical significance was α = 0.05.

Results

The twenty-five healthy controls had a mean age of 37.0 years. The twenty-four type 2 diabetes mellitus patients currently undergoing standard treatment had a mean age of 48.9 years. Based on the American Diabetes Association guidelines, we detected pre-diabetes in 4 subjects and diabetes in 1 subject, while all other subjects had normal FPG values. At 120 minutes, the correlations between the OGTT and cardiometabolic risk score (CMRS) were: r = 0.56 (p = 0.004) for glucose and r = 0.53 (p = 0.006) for insulin. At 120 minutes, the correlations between the OGTT and photoplethysmography index (PTGi) were: r = -0.56 (p = 0.003) for glucose and r = -0.41 (p = 0.04) for insulin. The CMRS, PTGi, and plethysmography total power index (PTGVLFi) differed significantly between the diabetes patients and healthy participants. The specificity and sensitivity for the CMRS, PTGi, and PTVLFi comparing the diabetes patients with healthy controls were high.

Conclusion

The TM-Oxi and SudoPath system shows promise as a valid, convenient, and non-invasive screening method for type 2 diabetes mellitus. The ANS function and CMR indicators measured by this system may be useful in guiding diabetes and cardiovascular health screening, treatment, and monitoring.
Disinfection of raw wastewater and activated sludge effluent using Fenton like reagent
Authors: Aslani Hassan , Nabizadeh Ramin , Alimohammadi Mahmood , Mesdaghinia Alireza , Nadafi Kazem , Nemati Reza , Ghani Maryam
Published: December 2014

Background and objectives

Water shortage problems have led to find either new water resources or improve wastewater treatment technologies in order to reuse. Due to less performance of previous units in microbial removal, disinfection has become a necessary step in wastewater treatment plants. In the present study performance of hydrogen peroxide (HP) and modified Fenton’s reagent (HP + Cu++) was considered for the disinfection of raw wastewater (RW) and activated sludge effluent (ASE).

Materials and methods

Plastic containers of 10-liter volume each were used for RW and ASE sampling. Microbiological analyses of the RW and ASE were performed in triplicate; before and after the disinfection process. Fecal coliforms were analyzed by the direct (without enrichment) multiple fermentation tube procedure.

Results

The results showed that using HP alone did not have any significant disinfection capability. In RW and ASE, the highest dose used in this study could reduce fecal coliforms (FC)s by only 1.54 and 1.16 log-inactivation, respectively. However, Maximum removal efficiency of modified Fenton in RW and ASE was 4.63 and 3.41 log-inactivation, respectively. The results suggested that Cu++ ions used in combination with H2O2 produced very rigorous synergistic effect, and HP disinfection capacity increased significantly.

Conclusion

Hydrogen peroxide, when applied alone, was not successful in disinfecting of either RW or ASE, and neither the WHO guideline nor the Iranian standard could be met. However, modified Fenton showed very significant disinfection potential and could reduce FCs under World Health Organization (WHO) guideline and Iranian national standard for agricultural irrigation.
Morphological, olfactory, and vocal development in big brown bats
Authors: Mayberry Heather W. , Faure Paul A.
Published: December 2014

Using a within subjects design, we documented morphological, bioacoustical and behavioral developmental changes in big brown bats. Eptesicus fuscus pups are born naked and blind but assume an adult-like appearance by post-natal day (PND) 45 and flight by PND 30. Adult females use spatial memory, acoustic and olfactory cues to reunite with offspring, but it is unclear if pups can recognize maternal scents. We tested the olfactory discrimination abilities of young E. fuscus pups and found they exhibited no odor preferences. Pups also emit distinct vocalizations called isolation calls (i-calls) that facilitate mother-offspring reunions, but how pups shift their vocalizations from i-calls to downward frequency modulated (FM) sweeps used in echolocation remains unclear. Between PND 0–9, pups emitted mainly long duration, tonal i-calls rich in harmonics, but after they switched to short duration, downward FM sweeps with fewer harmonics. Call maximum frequency and repetition rate showed minor changes across development. Signal duration, bandwidth, and number of harmonics decreased, whereas the maximum, minimum and bandwidth of the fundamental, and peak spectral frequency all increased. We recorded vocalizations during prolonged maternal separation and found that isolated pups called longer and at a faster rate, presumably to signal for maternal assistance. To assess how PND 13 pups alter their signals during interactions with humans we compared spontaneous and provoked vocalizations and found that provoked calls were spectrally and temporally more similar to those of younger bats suggesting that pups in distress emit signals that sound like younger bats to promote maternal assistance.
Computer simulations of the mouse spermatogenic cycle
Authors: Ray Debjit , Pitts Philip B. , Hogarth Cathryn A. , Whitmore Leanne S. , Griswold Michael D. , Ye Ping
Published: December 2014

The spermatogenic cycle describes the periodic development of germ cells in the testicular tissue. The temporal–spatial dynamics of the cycle highlight the unique, complex, and interdependent interaction between germ and somatic cells, and are the key to continual sperm production. Although understanding the spermatogenic cycle has important clinical relevance for male fertility and contraception, there are a number of experimental obstacles. For example, the lengthy process cannot be visualized through dynamic imaging, and the precise action of germ cells that leads to the emergence of testicular morphology remains uncharacterized. Here, we report an agent-based model that simulates the mouse spermatogenic cycle on a cross-section of the seminiferous tubule over a time scale of hours to years, while considering feedback regulation, mitotic and meiotic division, differentiation, apoptosis, and movement. The computer model is able to elaborate the germ cell dynamics in a time-lapse movie format, allowing us to trace individual cells as they change state and location. More importantly, the model provides mechanistic understanding of the fundamentals of male fertility, namely how testicular morphology and sperm production are achieved. By manipulating cellular behaviors either individually or collectively in silico, the model predicts causal events for the altered arrangement of germ cells upon genetic or environmental perturbations. This in silico platform can serve as an interactive tool to perform long-term simulation and to identify optimal approaches for infertility treatment and contraceptive development.
Influence of environmental information in natural scenes and the effects of motion adaptation on a fly motion-sensitive neuron during simulated flight
Authors: Ullrich Thomas W. , Kern Roland , Egelhaaf Martin
Published: December 2014

Gaining information about the spatial layout of natural scenes is a challenging task that flies need to solve, especially when moving at high velocities. A group of motion sensitive cells in the lobula plate of flies is supposed to represent information about self-motion as well as the environment. Relevant environmental features might be the nearness of structures, influencing retinal velocity during translational self-motion, and the brightness contrast. We recorded the responses of the H1 cell, an individually identifiable lobula plate tangential cell, during stimulation with image sequences, simulating translational motion through natural sceneries with a variety of differing depth structures. A correlation was found between the average nearness of environmental structures within large parts of the cell's receptive field and its response across a variety of scenes, but no correlation was found between the brightness contrast of the stimuli and the cell response. As a consequence of motion adaptation resulting from repeated translation through the environment, the time-dependent response modulations induced by the spatial structure of the environment were increased relatively to the background activity of the cell. These results support the hypothesis that some lobula plate tangential cells do not only serve as sensors of self-motion, but also as a part of a neural system that processes information about the spatial layout of natural scenes.
Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism
Authors: Cossette Stephanie M. , Gastonguay Adam J. , Bao Xiaoping , Lerch-Gaggl Alexandra , Zhong Ling , Harmann Leanne M. , Koceja Christopher , Miao Robert Q. , Vakeel Padmanabhan , Chun Changzoon , Li Keguo , Foeckler Jamie , Bordas Michelle , Weiler Hartmut , Strande Jennifer , Palecek Sean P. , Ramchandran Ramani
Published: December 2014

In this study, we have identified a novel member of the AMPK family, namely Sucrose non-fermenting related kinase (Snrk), that is responsible for maintaining cardiac metabolism in mammals. SNRK is expressed in the heart, and brain, and in cell types such as endothelial cells, smooth muscle cells and cardiomyocytes (CMs). Snrk knockout (KO) mice display enlarged hearts, and die at postnatal day 0. Microarray analysis of embryonic day 17.5 Snrk hearts, and blood profile of neonates display defect in lipid metabolic pathways. SNRK knockdown CMs showed altered phospho-acetyl-coA carboxylase and phospho-AMPK levels similar to global and endothelial conditional KO mouse. Finally, adult cardiac conditional KO mouse displays severe cardiac functional defects and lethality. Our results suggest that Snrk is essential for maintaining cardiac metabolic homeostasis, and shows an autonomous role for SNRK during mammalian development.
Testing avian compass calibration: comparative experiments with diurnal and nocturnal passerine migrants in South Sweden
Authors: Åkesson Susanne , Odin Catharina , Hegedüs Ramón , Ilieva Mihaela , Sjöholm Christoffer , Farkas Alexandra , Horváth Gábor
Published: December 2014

Cue-conflict experiments were performed to study the compass calibration of one predominantly diurnal migrant, the dunnock (Prunella modularis), and two species of nocturnal passerine migrants, the sedge warbler (Acrocephalus schoenobaenus), and the European robin (Erithacus rubecula) during autumn migration in South Sweden. The birds' orientation was recorded in circular cages under natural clear and simulated overcast skies in the local geomagnetic field, and thereafter the birds were exposed to a cue-conflict situation where the horizontal component of the magnetic field (mN) was shifted +90° or −90° at two occasions, one session starting shortly after sunrise and the other ca. 90 min before sunset and lasting for 60 min. The patterns of the degree and angle of skylight polarization were measured by full-sky imaging polarimetry during the cue-conflict exposures and orientation tests. All species showed orientation both under clear and overcast skies that correlated with the expected migratory orientation towards southwest to south. For the European robin the orientation under clear skies was significantly different from that recorded under overcast skies, showing a tendency that the orientation under clear skies was influenced by the position of the Sun at sunset resulting in more westerly orientation. This sun attraction was not observed for the sedge warbler and the dunnock, both orientating south. All species showed similar orientation after the cue-conflict as compared to the preferred orientation recorded before the cue-conflict, with the clearest results in the European robin and thus, the results did not support recalibration of the celestial nor the magnetic compasses as a result of the cue-conflict exposure.
Morphologic and physiologic retinal degeneration induced by intravenous delivery of vitamin A dimers in the leporid retina
Authors: Penn Jackie , Mihai Doina M. , Washington Ilyas
Published: December 2014

The eye uses vitamin A as a cofactor to sense light, during this process a fraction of vitamin A dimerizes forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD) and Stargardt disease, is the accumulation of these dimers in the retinal pigment epithelium (RPE) and Bruch's membrane (BM). However, it is not known whether dimers of vitamin A are merely secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E damaged photoreceptors and RPE cells, triggered inflammation, induced remolding of the choroidal vasculature, and triggered a decline in the retina's response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.
aPKC alters TGFβ response in NSCLC cells via both Smad-dependent and Smad-independent pathways
Authors: Gunaratne Adrian , Chan Eddie , El-Chabib Tarek H. , Carter David , Di Guglielmo Gianni M.
Published: December 2014

Transforming growth factor beta (TGFβ) signalling controls many cellular responses including proliferation, epithelial to mesenchymal transition, and apoptosis through the activation of canonical (Smad) as well as non-canonical (e.g., Par6) pathways. Previous studies from our lab demonstrated that aPKC inhibition regulates TGFβ receptor trafficking and signalling. Here we report that downstream TGFβ-dependent transcriptional responses in aPKC-silenced NSCLC cells were muted compared to control cells, despite an extension of Smad2 phosphorylation. We assessed SARA-Smad2-Smad4 association and observed that knockdown of aPKC increased SARA levels and SARA-Smad2 complex formation, increased cytoplasmic retention of Smad2, and reduced Smad2-Smad4 complex formation, which correlated with reduced Smad2 nuclear translocation. Interestingly, we also detected an increase in p38 MAPK phosphorylation and apoptosis in aPKC silenced cells, which were found to be TRAF6-dependent. Taken together our results suggest that aPKC isoforms regulate Smad and non-Smad TGFβ pathways and aPKC inhibition sensitizes NSCLC cells to undergo TGFβ-dependent apoptosis.
Focal adhesion kinase-related nonkinase (FRNK) negatively regulates IL-4-mediated inflammation
Authors: Sharma Ritu , Colarusso Pina , Zhang Hong , Stevens Kasia , Patel Kamala D.
Published: December 2014

Focal adhesion kinase (FAK)-related nonkinase (FRNK) is a cytoskeletal regulatory protein recently shown to dampen lung fibrosis, yet its role in inflammation is unknown. Here we show for the first time that expressing FRNK negatively regulates IL-4 inflammation using a human model of eosinophil recruitment. Mechanistically, FRNK blocked eosinophil accumulation, firm adhesion and transmigration by preventing transcription and protein expression of VCAM-1 and CCL26. IL-4 activates STAT6 to induce VCAM-1 and CCL26 transcription. We now show IL-4 also increases GATA6 to induce VCAM-1 expression. FRNK blocked IL-4-induced GATA6 transcription, but had little effect on GATA6 protein, and had no effect on STAT6 activation. FRNK can block FAK or Pyk2 signaling, thus we down-regulated these proteins with siRNA to determine if signaling from either protein was involved in regulating VCAM-1 and CCL26. Knocking down FAK, Pyk2 or both had no effect on VCAM-1 or CCL26 expression suggesting that FRNK acts independently of FAK and Pyk2 signaling. Finally, we found that IL-4 induces the late expression of endogenous FRNK. In summary, FRNK represents a novel mechanism for negatively regulating IL-4 inflammation.
A non-mitotic role for aurora kinase A as a direct activator of cell migration upon interaction with PLD, FAK and Src
Authors: Mahankali Madhu , Henkels Karen M. , Speranza Francis , Gomez-Cambronero Julian
Published: December 2014

Timely activation of Aurora Kinase A (AURA) is vital for centrosome formation and the progression of mitosis. Nonetheless, it is still unclear if and when other cellular functions are activated by AURA. We report here that Src phosphorylates and activates AURA at T288 and AURA also activates focal adhesion kinase (FAK), leading to initiation of cell movement. An additional and new way by which AURA is regulated, is by phospholipase D (PLD) that causes AURA activation. Conversely, AURA phosphorylates PLD, so both proteins engage in a positive reinforcement loop. AURA and PLD2 form a protein-protein complex and co-localize to cytoplasmic regions in cells. The reason why PLD activates AURA is because of the production of phosphatidic acid (PA) by the lipase that binds directly to AURA, with the region E171–E211 projected to be a PA binding pocket. Further, this direct interaction with PA enhances actin polymerization and cooperates synergistically with AURA, FAK and Src in yielding a fully effectual cellular migration. Thus, Src/FAK and PLD/PA are novel upstream regulators of AURA during the non-mitotic cellular function of cell migration.
Opposing roles for JNK and Aurora A in regulating WD40-Repeat Protein 62 association with spindle microtubules
Authors: Lim Nicholas R. , Yeap Yvonne Y. C. , Zhao Teresa T. , Yip Yan Y. , Wong Shu C. , Xu Dan , Ang Ching-Seng , Williamson Nicholas A. , Xu Zhiheng , Bogoyevitch Marie A. , Ng Dominic C. H.
Published: December 2014

WD40-Repeat protein 62 (WDR62) is a spindle pole protein required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly mutations lead to mitotic mislocalization highlighting a critical requirement for precise WDR62 spatiotemporal distribution although the regulatory mechanisms are unknown. Here we demonstrate that the WD40-repeat region of WDR62 is required for microtubule association while the disordered C-terminal region regulates cell-cycle dependent compartmentation. In agreement with a functional requirement for WDR62/JNK1 complex during neurogenesis, WDR62 specifically recruits JNK1, but not JNK2, to the spindle pole. However, JNK-mediated phosphorylation of WDR62 T1053 negatively regulated microtubule association and loss of JNK signalling resulted in constitutive WDR62 localization to microtubules irrespective of cell cycle stage. In contrast, we identified that Aurora A kinase (AURKA) and WDR62 were in complex and AURKA-mediated phosphorylation was required for spindle localization of WDR62 during mitosis. Our studies highlight complex regulation of WDR62 localization with opposing roles for JNK and AURKA in determining its spindle association.
LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism
Authors: Arranz Amaia M. , Delbroek Lore , Van Kolen Kristof , Guimarães Marco R. , Mandemakers Wim , Daneels Guy , Matta Samer , Calafate Sara , Shaban Hamdy , Baatsen Pieter , De Bock Pieter-Jan , Gevaert Kris , Vanden Berghe Pieter , Verstreken Patrik , De Strooper Bart , Moechars Diederik
Published: December 2014

Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, but the precise physiological function of the protein remains ill-defined. Recently, our group proposed a model in which LRRK2 kinase activity is part of an EndoA phosphorylation cycle that facilitates efficient vesicle formation at synapses in the Drosophila melanogaster neuromuscular junctions. Flies harbor only one LRRK gene that may encompass the functions of both mammalian LRRK1 and LRRK2. We therefore studied the role of LRRK2 in mammalian synaptic function and provide evidence that knockout or pharmacological inhibition of LRRK2 results in defects in synaptic vesicle endocytosis, altered synaptic morphology and impairments in neurotransmission. In addition, our data indicate that mammalian endophilin A1 (EndoA1) is phosphorylated by LRRK2 in vitro at T73 and S75, two residues in the BAR domain. Hence, our results indicate that LRRK2 kinase activity has an important role in the regulation of clathrin-mediated endocytosis of synaptic vesicles and subsequent neurotransmission at the synapse.