bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiographic Landmarks for Tunnel Positioning in Posterior Cruciate Ligament Reconstructions
Authors: Johannsen Adam M. , Anderson Colin J. , Wijdicks Coen A. , Engebretsen Lars , LaPrade Robert F.
Published: November 2012

Background:

Consistent radiographic guidelines for tunnel placement in single- or double-bundle posterior cruciate ligament (PCL) reconstructions are not well defined. Quantitative guidelines reporting the location of the individual PCL bundle attachments would aid in intraoperative tunnel placement and postoperative assessment of a PCL reconstruction.

Hypothesis:

Consistent and reproducible measurements in relation to radiographic landmarks for the entire PCL and its individual bundle attachments are achievable.

Study Design:

Controlled laboratory study.

Methods:

The femoral and tibial PCL bundle attachment centers of 20 nonpaired fresh-frozen cadaveric knees were labeled using radio-opaque spheres and the attachment areas were labeled using barium sulfate. Anteroposterior (AP) and lateral radiographs of the femur and tibia were obtained, and measurements of the distances between the PCL bundle centers and landmarks were acquired.

Results:

On the AP femur view, the anterolateral bundle (ALB) and posteromedial bundle (PMB) centers were 34.1 ± 3.0 mm and 29.2 ± 3.0 mm lateral to the most medial border of the medial femoral condyle, respectively. The lateral femur images revealed that the ALB center was 17.4 ± 1.7 mm and the PMB center was 23.9 ± 2.7 mm posteroproximal to a line perpendicular to the Blumensaat line that intersected the anterior margin of the medial femoral condyle cortex. Anteroposterior tibia images revealed that the ALB and PMB centers were located 0.2 ± 2.1 mm proximal and 4.9 ± 2.9 mm distal to the proximal joint line, respectively. The PCL attachment center was 1.6 ± 2.5 mm distal to the proximal joint line. On the lateral tibia view, the ALB center was 8.4 ± 1.8 mm, the PCL attachment center was 5.5 ± 1.7 mm, and the PMB center was 2.5 ± 1.5 mm superior to the champagne glass drop-off of the posterior tibia.

Conclusion:

Radiographic measurements from several clinically relevant views of the femur and tibia were reproducible with regard to the anatomic locations of the ALB and PMB centers. The measurements from the lateral femur and tibia views provided the most clinically pertinent radiographic measurements intraoperatively.

Clinical Relevance:

This study established a set of clinically relevant radiographic guidelines for anatomic reconstruction of the PCL. The parameters set forth in this study can be used in both the intraoperative and postoperative settings for both single- and double-bundle PCL reconstructions.
Anatomic Femoral Tunnels in Posterior Cruciate Ligament Reconstruction
Authors: Tompkins Marc , Keller Thomas C. , Milewski Matthew D. , Gaskin Cree M. , Brockmeier Stephen F. , Hart Joseph M. , Miller Mark D.
Published: November 2012

Background:

During posterior cruciate ligament (PCL) reconstruction, the placement and orientation of the femoral tunnel is critical to postoperative PCL function.

Purpose:

To compare the ability of outside-in (OI) versus inside-out (IO) femoral tunnel drilling in placing the femoral tunnel aperture within the anatomic femoral footprint of the PCL, and to evaluate the orientation of the tunnels within the medial femoral condyle.

Study Design:

Controlled laboratory study.

Methods:

Ten matched pairs of cadaver knees were randomized such that within each pair, 1 knee underwent arthroscopic OI drilling and the other underwent IO drilling. All knees underwent computed tomography (CT) both pre- and postoperatively with a technique optimized for ligament evaluation (80 keV with maximum mAs). Commercially available third-party software was used to fuse the pre- and postoperative CT scans, allowing comparison of the PCL footprint to the drilled tunnel. The percentage of tunnel aperture contained within the native footprint, as well as the distance from the center of the tunnel aperture to the center of the footprint, were measured. In addition, the orientation of the tunnels in the coronal and axial planes was evaluated.

Results:

The OI technique placed 70.4% ± 23.7% of the tunnel within the native femoral footprint compared with 79.8% ± 16.7% for the IO technique ( P = .32). The OI technique placed the center of the femoral tunnel 4.9 ± 2.2 mm from the center of the native footprint compared to 5.3 ± 2.0 mm for the IO technique ( P = .65). The femoral tunnel angle in the coronal plane was 21.0° ± 9.9° for the OI technique and 37.0° ± 10.3° for the IO technique ( P = .002). The tunnel angle in the axial plane was 27.3° ± 4.8° for the OI technique and 39.1° ± 11.5° for the IO technique ( P = .01).

Conclusion:

This study demonstrates no difference in the ability of the OI and IO techniques to place the femoral tunnel within the PCL femoral footprint during PCL reconstruction. With the technique parameters used in this study, the IO technique created femoral tunnels with a more vertical and anterior orientation than the OI technique.

Clinical Relevance:

Either technique can be used to place the femoral tunnel within the anatomic footprint. Consideration should be given to tunnel orientation following each technique, and what effect it has on graft bending angles, as these characteristics may affect graft strain and, ultimately, graft failure. In this regard, the IO technique likely produces gentler graft bending angles.
Sensitivity and Specificity of the Online Version of ImPACT in High School and Collegiate Athletes
Authors: Schatz Philip , Sandel Natalie
Published: November 2012

Background:

The utility of postconcussion neurocognitive testing versus symptom data has been debated. The sensitivity of the desktop version of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) tool has been documented, but psychometric properties of the recently released online version of ImPACT have yet to be fully established.

Purpose:

To document the sensitivity of the online ImPACT version in samples of (1) symptomatic concussed (high school and collegiate) athletes, and (2) asymptomatic concussed (high school and collegiate) athletes suspected of hiding their concussions.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

A total of 81 athletes observed to sustain a concussion by a certified athletic trainer or team physician, a finding that was confirmed with reported postconcussion symptoms, completed the ImPACT test within 3 days of injury. Data were compared with an independent sample of 81 athletes who completed preseason baseline cognitive assessments using ImPACT and who were matched (with concussed athletes) on the basis of sex, age, sport, concussion history, and absence of attention deficit hyperactivity disorder and learning disability. An independent group of 37 athletes who were also observed to sustain a concussion completed ImPACT within 3 days of injury. These athletes reported no postconcussion symptoms but were noted for suspected invalid response patterns on ImPACT (Impulse Control index >30 and Verbal Memory index <69%). The subscale data from the assessments (excluding those contributing to the aforementioned indices) were compared with a matched sample of 37 athletes who completed preseason baseline cognitive assessments in ImPACT (using the same criteria described above).

Results:

Data from the ImPACT online version yielded 91.4% sensitivity and 69.1% specificity. For asymptomatic athletes suspected of hiding their concussion, data from ImPACT yielded 94.6% sensitivity and 97.3% specificity.

Conclusion:

The online version of the ImPACT tool is a valid measure of neurocognitive performance at the acute stages of concussion, with high levels of sensitivity and specificity, even when athletes appear to be denying postconcussion symptoms.
Sexual Orientation and Occupational Attainment
Authors: Ueno Koji , Peña-Talamantes Abráham E. , Roach Teresa A.
Published: November 2012

Research shows that sexual minorities and heterosexuals differ in the level of success in educational and earnings attainment, but differences in occupational attainment have been unclear. To extend the literature, this article examines sexual orientation differences in young adulthood occupational status by analyzing the National Longitudinal Study of Adolescent Health Waves 1 to 4. Drawing from the life course literature, a theoretical framework is developed to explain how sexual orientation shifts opportunities and constraints in the occupational attainment process. The analysis shows that the association between sexual orientation and occupational status depends on gender, the type of sexual experience used to measure sexual orientation, and the timing of first sexual experience. Women who report their first same-sex attraction or sexual contact in young adulthood have lower occupational status than those without such experience, and men who report their first same-sex dating relationships in young adulthood tend to have higher occupational status than those without such relationships. These findings extend the existing knowledge on sexual development and status attainment, which has mainly focused on heterosexual development.
Research on Technological Innovation in Family Firms
Authors: De Massis Alfredo , Frattini Federico , Lichtenthaler Ulrich
Published: November 2012

The purpose of this article is to review and systematize prior work on technological innovation in family firms and to open up an agenda to guide future research into this promising area. The study shows that family involvement has direct effects on innovation inputs (e.g., R&D expenditures), activities (e.g., leadership in new product development projects), and outputs (e.g., number of new products), as well as moderating effects on the relationships between these steps of technological innovation. The article uses theories applied in family business research (e.g., agency theory) to discuss opportunities for extending technological innovation frameworks by considering family involvement.
The Prenatal Care at School Program
Authors: Griswold Carol H. , Nasso Jacqueline T. , Swider Susan , Ellison Brenda R. , Griswold Daniel L. , Brooks Marilyn
Published: November 2012

School absenteeism and poor compliance with prenatal appointments are concerns for pregnant teens. The Prenatal Care at School (PAS) program is a new model of prenatal care involving local health care providers and school personnel to reduce the need for students to leave school for prenatal care. The program combines prenatal care and education designed specifically for adolescents. Twenty-eight girls attended PAS in the fall of 2010. Program evaluation results showed a 14.2% increase in school attendance among students enrolled compared to peers enrolled the previous year, a 5.7% increase over a local teen clinic’s attendance to their group prenatal care program, and a 42% increase in pregnancy and childbirth knowledge. Satisfaction surveys indicated that participants all believed that PAS helped prepare them for labor and delivery and 92% felt encouraged to stay in school. This pilot program benefited pregnant teens by increasing school educational time, improving preparation for labor and delivery, and increasing participation with prenatal care.
Protective Effect of K201 on Isoproterenol-Induced and Ischemic–Reperfusion-Induced Ventricular Arrhythmias in the Rat
Authors: Otani Naoyuki , Matsuda Ryuko , Oda Kazuhiko , Nishino Setsu , Inoue Teruo , Kaneko Noboru
Published: November 2012

Aim:

Ventricular arrhythmia (VA) is a risk for sudden death. Polymorphic ventricular tachycardia (VT) degenerating to ventricular fibrillation occurs subsequent to the prolongation of the QT interval following administration of catecholamines under Ca2+ loading. Fatal VA also occurs in ischemia and ischemic–reperfusion. We compared the suppressive effect of K201 (JTV519), a multiple-channel blocker and cardiac ryanodine receptor-calcium release channel (RyR2) stabilizer, with that of diltiazem, a Ca2+ channel blocker, in 2 studies of isoproterenol-induced (n = 30) and ischemic–reperfusion-induced VAs (n = 38) in rats.

Methods:

Adult male Wistar rats were administered 12 mg/kg/min calcium chloride (CaCl2) for 20 minutes and then 6 μg/kg/min isoproterenol was infused with CaCl2 for a further 20 minutes. In other rats, the left coronary artery was ligated for 5 minutes followed by reperfusion for 20 minutes. K201 or diltiazem (both 1 mg/kg) was administered before infusion of the isoproterenol or induction of ischemia.

Results:

After administration of isoproterenol under Ca2+ loading, fatal VA frequently occurred in the vehicle (9 of 10 animals, 90%) and diltiazem (8 of 10, 80%) groups, and K201 significantly suppressed the incidences of arrhythmia and mortality (2 of 10, 20%). In the reperfusion study, the incidence and the time until occurrence of reperfusion-induced VA and mortality were significantly suppressed in the K201 (2 of 15 animals, 13%) and diltiazem (1 of 9 animals, 11%) groups compared to the vehicle group (8 of 14 animals, 57%).

Significance:

Induction of VA in an experimental model was achieved with a low dose of isoproterenol under Ca2+ loading. K201 markedly suppressed both the isoproterenol-induced and the reperfusion-induced VAs, whereas diltiazem did not suppress the isoproterenol-induced VA. The results suggest that both VAs are related to early after depolarization (EAD) and indicate that K201 has the potential to suppress EAD by stabilizing RyR2 to mediate Ca2+ release from the sarcoplasmic reticulum and acting as a multiple-channel blocker.
An Exploration of Crossover Sexual Offending
Authors: Kleban Holly , Chesin Megan S. , Jeglic Elizabeth L. , Mercado Cynthia Calkins
Published: November 2012

Studies have produced equivocal findings regarding whether sex offenders are stable in their choice of victims. Indeed, it remains unclear whether a sex offender’s subsequent victims are typically of the same gender, age range, and victim–perpetrator relationship as that of the initial victim. Although some differences may be attributed to methodological disparities, others are not. This study sought to clarify this question by examining the tendency of sex offenders to switch from one type of victim to another, both within an index offense and across offenses and all victims. Archival records of 789 incarcerated sex offenders were examined. Of those offenders who had multiple victims at the index offense ( n = 279), 13% had victims of both genders, 14% had victims in different age categories (child, adolescent, and adult), and 13% had varying relationships with the victims (i.e., family member, acquaintance, or stranger). When the records of those with past sexual convictions were examined ( n = 208), 20% of offenders had a prior victim of a different gender; 40% crossed over across age categories, and 48% of the repeat offenders had varying relationships with the victim across convictions. Offenders who had both male and female victims and offenders who had victims of varied relationship status across crimes had higher Static-99 risk scores than offenders who were more stable with regard to victim selection. These findings are compared to those of previous studies, focusing on how these results add clarity to a previous literature whose conclusions were challenged by the use of disparate sampling and research methodologies.
Parent Ratings of ADHD Symptoms in Chinese Urban Schoolchildren
Authors: Su Yi (Esther) , Wang Hong , Geng Yao-Guo , Sun Ling , Du Ya-Song , Fan Fang , Su Lin-Yan
Published: November 2012

Objective: The objective of this study was to assess the psychometric properties of the Chinese ADHD Rating Scale–IV (ADHD RS-IV): Home Version and to explore parent ratings of ADHD symptoms in a large sample of urban schoolchildren in China. Method: Parents of a representative sample of 1,616 schoolchildren (aged 6-17) in 12 Chinese cities completed the ADHD RS-IV: Home Version. Results: The Chinese ADHD RS-IV: Home Version demonstrated satisfactory internal consistency, test–retest reliability, parent–teacher correlation, discriminant validity, and convergent validity. Factor analysis revealed the DSM-IV two-factor model with “inattention” and “hyperactivity-impulsivity” dimensions, accounting for equal variances. Parent ratings revealed lower/similar scores for Chinese schoolchildren compared with the U.S. study. Conclusion: The ADHD RS-IV: Home Version is a reliable and valid ADHD rating scale in China. The factor structure is similar but not identical to the U.S. study. Normative data reveal cultural differences in some aspects of the parent ratings of ADHD.
Experimental and numerical investigations of oil film formation and friction in a piston ring–liner contact
Authors: Avan Emin Y , Spencer Andrew , Dwyer-Joyce Rob S , Almqvist Andreas , Larsson Roland
Published: November 2012

The piston ring–cylinder liner contact is a major source of the total parasitic losses in an internal combustion engine. The lubrication process of this contact highly influences the amount of friction, oil consumption and wear that occurs. In this work, a reciprocating test rig combined with an ultrasonic film thickness measurement system was developed and then used for tribological investigation of the piston ring–cylinder liner contact under idealised cold conditions. A special piston ring and cylinder liner holder were designed and five sensors were glued on to the back side of the liner specimen. Ultrasonic reflections captured by the sensors, used to obtain the film thickness, and friction were continuously recorded as the piston ring section reciprocated over the liner. Several experiments were performed at different speed and load conditions. Furthermore, a numerical model has been developed to predict film thickness and friction in all lubrication regimes. The experimentally measured film thickness and friction were compared with the output from the numerical model and good correlation was found. The parameters affecting the accuracy of the ultrasound measurements and numerical simulations of film thickness and friction are then discussed.
Association of all-trans retinoic acid treatment with the renin-angiotensin aldosterone system expression in glomerulosclerosis rats
Authors: Zhou Tian-Biao , Wu Wei-Feng , Qin Yuan-Han , Yin Sheng-Sheng
Published: November 2012

Background and objective:

All-trans retinoic acid (ATRA), a promising therapeutic agent, has been confirmed in animal experiments as playing a protective role against renal diseases. The renin-angiotensin aldosterone system (RAAS) plays a key role in the pathogenesis of renal diseases, and RAAS inhibitors can prevent the progression of kidney diseases. In our previous study, we found that ATRA could play a protective role against glomerulosclerosis (GS) lesions in rats, and its effect was similar to RAAS inhibitors. However, whether ATRA treatment was associated with RAAS expression was not clear.

Methods:

Six-week-old male Wistar rats were divided into three groups: sham operation group (SHO), glomerulosclerosis model group without treatment (GS) and GS model group treated with ATRA (GA). At the end of 13 weeks, the relevant samples were collected and analyzed.

Results:

The mRNA and protein expression of angiotensin-converting enzyme 1 (ACE1) in the GS group was notably higher when compared with the SHO group. However, mRNA and protein expression of ACE1 in the ATRA treatment group was markedly down-regulated when compared with the GS group. Angiotensin-converting enzyme 2 (ACE2) expression (mRNA or protein) in the GS group was reduced compared with that in the SHO group, and ATRA markedly increased the mRNA and protein expression of ACE2 compared with the GS group. The levels of protein expression of angiotensin I and angiotensin II were significantly up-regulated in the GS group compared with those in the SHO group, and ATRA reduced their expression in the GA group when compared with the GS group.

Conclusion:

ATRA is associated with RAAS expression in GS rats, but its detailed mechanism needs to be elucidated by further research.
Correlates of Moderate-to-Vigorous Physical Activity Participation in Adults With Intellectual Disabilities
Authors: Bodde Amy E. , Seo Dong-Chul , Frey Georgia C. , Van Puymbroeck Marieke , Lohrmann David K.
Published: November 2012

Adults with intellectual disabilities (ID) have low levels of physical activity and higher than average rates of related chronic health conditions. Understanding correlates of their physical activity participation may improve health promoting interventions. Forty-two adults with ID participated in a physical activity study. Physical activity knowledge and skills, awareness of recommendations and demographic characteristics were analyzed for their association with moderate-to-vigorous physical activity (MVPA) participation measured by accelerometers. Five variables were significantly correlated with MVPA. Body mass index was inversely correlated with MVPA, and gender, job location, job tasks, and place of residence were all significantly associated with MVPA. Understanding correlates of physical activity in this population will help inform disability service and health promotion professionals in future research and health intervention design.
Human Breast Adenocarcinoma Cytotoxicity and Modulation of 7,12-Dimethylbenz[a]anthracene-Induced Mammary Carcinoma in Balb/c Mice by Acacia catechu (L.f.) Wild Heartwood
Authors: Monga Jitender , Chauhan Chetan Singh , Sharma Manu
Published: November 2012

Objective. The chemopreventive potential of (+)-catechin-rich extract of Acacia catechu (L.f.) Willd. heartwood (AQCE) was evaluated against human breast adenocarcinoma cell line (MCF-7) and 7,12-dimethylbenz[ a]anthracene (DMBA)–induced mammary carcinoma in Balb/c mice. Methods. Cell cytotoxicity was investigated using different colorimetric assays. Apoptosis was observed using diphenylamine assay and fluorescent microscopy. AQCE was further evaluated for antitumor activity against DMBA-induced mammary carcinoma. The levels of tumor markers and oxidative stress were measured. Furthermore, level of transcription factors was measured by enzyme-linked immunosorbent assay. Results. The results showed that administration of AQCE showed a dose-dependent growth inhibition response and DNA fragmentation in MCF-7 cells. Tumor multiplicity was significantly decreased to 42.91% with AQCE when compared with DMBA-treated animals. The levels of tumor markers such as total sialic acid and lipid-associated sialic acid were substantially increased after DMBA treatment. However, AQCE treatment restored tumor markers level. AQCE also significantly reduced elevated levels of nitrite and malondialdehyde in DMBA-treated animals. Additionally, AQCE also increased the activities of antioxidant enzymes, viz., catalase, superoxide dismutase, total thiol, reduced glutathione, protein thiol, glutathione peroxidase, glutathione reductase, and glutathione- S-transferase in the mammary tissue and liver mitochondria of DMBA-administered animals. Significant increase in the protein levels of p53, c-jun, and p65 were observed in DMBA-treated mice, whereas less expression was observed in AQCE-treated animals. Eventually, AQCE also significantly improved body weight and maintained the mammary tissue architecture in normal range. Conclusions. The present data strongly suggest that anticancer potentiality of (+)-catechin-rich AQCE may be attributable to its ability to positively modulate tumor markers as well as the antioxidant system that could decompose the peroxides and, thereby, offer a protection against lipid peroxidation and linked to the expression of transcription factors during DMBA-induced mammary carcinoma.
Effect of Withania somnifera (Ashwagandha) on the Development of Chemotherapy-Induced Fatigue and Quality of Life in Breast Cancer Patients
Authors: Biswal Biswa Mohan , Sulaiman Siti Amrah , Ismail Hasanah Che , Zakaria Hasmat , Musa Kamarul Imran
Published: November 2012

Hypothesis. Withania somnifera is an herb with antioxidant, anti-inflammatory, anticancer, antistress, and adaptogenic properties. Previous studies have shown its antistress effects in animals. Traditional Indian medicine has used it for centuries to alleviate fatigue and improve general well-being. Methods. This is an open-label prospective nonrandomized comparative trial on 100 patients with breast cancer in all stages undergoing either a combination of chemotherapy with oral Withania somnifera or chemotherapy alone. The chemotherapy regimens were either taxotere, adriamycin, and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide. Withania somnifera root extract was administered to patients in the study group at a dose of 2 g every 8 hours, throughout the course of chemotherapy. The quality-of-life and fatigue scores were evaluated before, during, and on the last cycles of chemotherapy using the EORTC QLQ-C30 (Version 3), Piper Fatigue Scale (PFS), and Schwartz Cancer Fatigue Scale (SCFS-6). Results. The median age distributions in the study and control arm were 51 years (range = 36-70) and 50.5 years (range = 32-71), respectively. The majority (77%) of patients had stage II and III disease. Patients in the control arm experienced statistically significant higher estimated marginal means of fatigue score compared with the study group ( P < .001 PFS, P < .003 SCFS-6). Furthermore, various symptom scales of the EORTC QLQ-C30 were statistically significant in 7 out of 18 symptoms in the intervention group compared with the control group ( P < .001). The 24-month overall survival for all stages in study and control group patients were 72% versus 56%, respectively; however, the result was not significant ( P = .176), at a median follow-up duration of 26 months. Conclusions. Withania somnifera has potential against cancer-related fatigue, in addition to improving the quality of life. However, further study with a larger sample size in a randomized trial is warranted to validate our findings.
CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy
Authors: Nevo Yoram , Ben-Zeev Bruria , Tabib Adi , Straussberg Rachel , Anikster Yair , Shorer Zamir , Fattal-Valevski Aviva , Ta-Shma Asaf , Aharoni Sharon , Rabie Malcolm , Zenvirt Shamir , Goldshmidt Hanoch , Fellig Yakov , Shaag Avraham , Mevorach Dror , Elpeleg Orly
Published: November 2012

CD59 deficiency is a common finding in RBCs and WBCs in patients with chronic hemolysis suffering from paroxysmal nocturnal hemoglobinuria in which the acquired mutation in the PIGA gene leads to membrane loss of glycosylphosphatidylinositol-anchored membrane proteins, including CD59. The objective of the present study was to elucidate the molecular basis of childhood familial chronic Coombs-negative hemolysis and relapsing polyneuropathy presenting as chronic inflammatory demyelinating polyradiculoneuropathy in infants of North-African Jewish origin from 4 unrelated families. A founder mutation was searched for using homozygosity mapping followed by exome sequencing. The expression of CD59, CD55, and CD14 was examined in blood cells by flow cytometry followed by Western blot of the CD59 protein. A homozygous missense mutation, p.Cys89Tyr in CD59, was identified in all patients. The mutation segregated with the disease in the families and had a carrier rate of 1:66 among Jewish subjects of North-African origin. The mutated protein was present in the patients' cells in reduced amounts and was undetectable on the membrane surface. Based on the results of the present study, we conclude that the Cys89Tyr mutation in CD59 is associated with a failure of proper localization of the CD59 protein in the cell surface. This mutation is manifested clinically in infancy by chronic hemolysis and relapsing peripheral demyelinating disease.
Histone demethylase GASC1 - a potential prognostic and predictive marker in invasive breast cancer
Authors: Berdel Bozena , Nieminen Kaisa , Soini Ylermi , Tengström Maria , Malinen Marjo , Kosma Veli-Matti , Palvimo Jorma J , Mannermaa Arto
Published: November 2012

Background

The histone demethylase GASC1 (JMJD2C) is an epigenetic factor suspected of involvement in development of different cancers, including breast cancer. It is thought to be overexpressed in the more aggressive breast cancer types based on mRNA expression studies on cell lines and meta analysis of human breast cancer sets. This study aimed to evaluate the prognostic and predictive value of GASC1 for women with invasive breast cancer.

Methods

All the 355 cases were selected from a cohort enrolled in the Kuopio Breast Cancer Project between April 1990 and December 1995. The expression of GASC1 was studied by immunohistochemistry (IHC) on tissue microarrays. Additionally relativeGASC1mRNA expression was measured from available 57 cases.

Results

In our material, 56% of the cases were GASC1 negative and 44% positive in IHC staining. Women with GASC1 negative tumors had two years shorter breast cancer specific survival and time to relapse than the women with GASC1 positive tumors (p=0.017 and p=0.034 respectively). The majority of GASC1 negative tumors were ductal cases (72%) of higher histological grade (84% of grade II and III altogether). When we evaluated estrogen receptor negative and progesterone receptor negative cases separately, there was 2 times more GASC1 negative than GASC1 positive tumors in each group (chi2, p= 0.033 and 0.001 respectively). In the HER2 positive cases, there was 3 times more GASC1 negative cases than GASC1 positives (chi2, p= 0.029). Patients treated with radiotherapy (n=206) and hormonal treatment (n=62) had better breast cancer specific survival, when they were GASC1 positive (Cox regression: HR=0.49, p=0.007 and HR=0.33, p=0.015, respectively). The expression ofGASC1mRNA was in agreement with the protein analysis.

Conclusions

This study indicates that the GASC1 is both a prognostic and a predictive factor for women with invasive breast cancer. GASC1 negativity is associated with tumors of more aggressive histopathological types (ductal type, grade II and III, ER negative, PR negative). Patients with GASC1 positive tumors have better breast cancer specific survival and respond better to radiotherapy and hormonal treatment.
Total hip arthroplasty: leg length inequality impairs functional outcomes and patient satisfaction
Authors: Röder Christoph , Vogel Raphael , Burri Lukas , Dietrich Daniel , Staub Lukas P
Published: November 2012

Background

Leg length inequality (LLI) was identified as a problem of total hip arthroplasty soon after its introduction. Leg lengthening is the most common form of LLI. Possible consequences are limping, neuronal dysfunction and aseptic component loosening. LLI can result in an increased strain both on the contralateral hip joint and on the abductor muscles. We assessed the influence of leg lengthening and shortening on walking capacity, hip pain, limping and patient satisfaction at 2-year follow-up.

Methods

478 cases with postoperative lengthening and 275 with shortening were identified, and matched with three controls each. Rigorous adjustment for potential differences in baseline patient characteristics was performed by propensity-score matching of covariates. The arbitrarily defined desired outcomes were a walking capacity >60 minutes, no hip pain, no limping, and excellent patient satisfaction. Differences in not achieving the desired outcomes between the groups were expressed as odds ratios.

Results

In the lengthened case group, the odds ratio for not being able to walk for an hour was 1.70 (95% CI 1.28-2.26) for cases compared to controls, and the odds ratio for having hip pain at follow-up was 1.13 (95% CI 0.78-1.64). The odds ratio for limping was 2.08 (95% CI 1.55-2.80). The odds ratio for not achieving excellent patient satisfaction was 1.67 (95% CI 1.23-2.28). In the shortening case group, the odds ratio for not being able to walk for an hour was 1.23 (95% CI 0.84-1.81), and the odds ratio for having hip pain at follow-up was 1.60 (95% CI 1.05-2.44). The odds ratio for limping for cases was 2.61 (95% CI 1.78-3.21). The odds ratio for not achieving excellent patient satisfaction was 2.15 (95% CI 1.44-3.21).

Conclusions

Walking capacity, limping and patient satisfaction were all significantly associated with leg lengthening, whereas pain alleviation was not. In contrast, hip pain, limping and patient satisfaction were all significantly associated with leg shortening, whereas walking capacity was not.
Experts’ opinions on terminology for complementary and integrative medicine – a qualitative study with leading experts
Authors: Holmberg Christine , Brinkhaus Benno , Witt Claudia
Published: November 2012

Background

Integrative medicine (IM) is currently the most commonly used term to describe the integration of complementary and alternative medicine (CAM) into conventional medicine. In the definitions of IM the most important feature is the focus on evidence as crucial factor for therapeutic decision-making. However, there are discussions on the term “integrative medicine” with the most notable critique from within CAM that it describes the integration of complementary methods into conventional institutions and into a “conventional framework of thinking”. The aim of this qualitative study was to understand the thoughts of leading experts on IM and on the scientific debate in the field as well as their personal opinions about terminology in general.

Methods

We have conducted semi-standardized interviews with ten leading experts in the field of CAM and integrative medicine in the USA, England, and Germany, who have had leading positions at medical schools or the NIH in 2010 and 2011. Interviews were recorded, transcribed and analyzed using content analysis with the qualitative analysis software maxqda.

Results

Overall the current terminology was seen as a problem, although most experts agreed that the term “integrative medicine” (IM) described well what they do or they think is useful for medical care. The terminology debate was discussed from four perspectives: 1) from the perspective of medical practice, 2) from the perspective of research, 3) from the perspective of public relations, and 4) from the perspective of health care delivery. These perspectives may be used to evaluate the appropriateness of different terms in use in the field. When interviewees discussed the terminology question, they also discussed the type of health care system they envisioned. Such reflections led the interviewees to caution about too narrow a focus on the terminology question. The question of naming was one about influencing and changing medicine.

Conclusion

The discussion of the experts demonstrated that the discussion about terminology is an important debate about the shaping of medicine. The experts discussed terminology in the light of "how health care systems" should look like in the future.
The pressure/volume relationship during dobutamine stress echocardiography in transplanted heart: comparison with quality of life and coronary anatomy
Authors: Minardi Giovanni , Zampi Giordano , Pergolini Amedeo , Pulignano Giovanni , Scappaticci Massimiliano , Orsini Francesca Moschella , Pero Gaetano , Monica Paola Lilla Della , Cioffi Giovanni , Musumeci Francesco
Published: November 2012

Background

Cardiac allograft vasculopathy (CAV) is a major late complication in cardiac transplant recipients and has a relevant impact on outcome of these patients. Aims of this study: to compare, in cardiac transplant recipients patients, the diagnostic value of pressure/volume relationship (ESPVR) during dobutamine stress echocardiography (DSE) for coronary artery disease, assessed by Multislice Computed Tomography (MSCT), and by coronary angiography (CA). We also analyzed any possible relationship between ESPVR and the Health Related Quality of Life of the patients (HRQoL), evaluated by SF–36 questionnaire.

Methods

25 consecutive patients underwent DSE within 24 hours after MSCT coronary angiogram and then they underwent CA. The HRQoL questionnaire was administered to the patients in the settings of DSE. They were followed-up for 6 months.

Results

DSE has a sensitivity in detecting CAV of 67%, specificity of 95%, positive predictive value of 67% and negative predictive value of 95%; DSE with ESPVR has a sensitivity of 100%, specificity of 95%, positive predictive value of 75%, negative predictive value of 100%; MSCT has a sensitivity of 100%; specificity of 82%; positive predictive value of 43%; negative predictive value of 100%. Htx recipients with a flat-biphasic ESPVR, although asymptomatic, perceived a worst HRQoL compared with the up-sloping ESPVR population, and this is statistically significant for the general health (p 0.0004), the vitality (p 0.0013) and the mental health (p 0.021) SF-36 subscale.

Conclusions

Evaluation with DSE and ESPVR is accurate in the clinical control of heart transplant recipients reserving invasive evaluation only for patients with abnormal contractility indexes.
Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling
Authors: Li Qi , Zhu Qing-wen , Yuan Yong-yi , Huang Sha-sha , Han Dong-yi , Huang De-liang , Dai Pu
Published: November 2012

Background

Mutations in the SLC26A4 gene, which encodes the anion transporter, pendrin, are a major cause of autosomal recessive non-syndromic hearing loss (NSHL) in some Asian populations. SLC26A4 c.919-2A>G (IVS7-2A>G) is the most common mutation in East Asian deaf populations. To provide a basis for improving the clinical diagnosis of deaf patients, we evaluated 80 patients with the SLC26A4 c.919-2A>G monoallelic mutation from 1065 hearing-impaired subjects and reported the occurrence of a second mutant allele in these patients.

Methods

The occurrence of a second mutant allele in these 80 patients with a single c.919-2A>G mutation was investigated. Mutation screening was performed by bidirectional sequencing in SLC26A4 exons 2 to 6 and 9 to 21.

Results

We found that 47/80 patients carried another SLC26A4 c.919-2A>G compound mutation. The five most common mutations were: p.H723R, p.T410M, 15+5G>A (c.1705+5G>A), p.L676Q and p.N392Y. We found a Chinese-specific SLC26A4 mutation spectrum and an associated SLC26A4 contribution to deafness.

Conclusion

Our study illustrates that mutation analysis of other SLC26A4 exons should be undertaken in deaf patients with a single heterozygous SLC26A4 mutation. Moreover, a model of compound heterozygosity may partially explain the disease phenotype.
Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth
Authors: Enderling Heiko , Hlatky Lynn , Hahnfeldt Philip
Published: November 2012

Background

The role of the immune system in tumor progression has been a subject for discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression.

Methods

We implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression.

Results

A low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response.

Conclusions

Cancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step “immunoediting” concept – the modulation of tumor growth through inhibition, selection and promotion.
Effect of early anti-retroviral therapy on the pathogenic changes in mucosal tissues of SIV infected rhesus macaques
Authors: Malzahn Jessica , Shen Chengli , Caruso Lori , Ghosh Priyanka , Sankapal Soni Ramachandra , Barratt-Boyes Simon , Gupta Phalguni , Chen Yue
Published: November 2012

Background

The gastrointestinal tissue plays an important role in the pathogenesis of HIV/SIV infection and serves as a viral reservoir in infected individuals under antiretroviral therapy (ART). However, the effect of ART administration in the very early stage of infection on HIV/SIV replication and pathogenesis in gastrointestinal tissue has not been fully studied. In this current study, rhesus monkeys infected with SIV were treated with ART starting at day 7 post-infection. The effect of early ART on SIV replication and infection-related pathogenic changes in mucosal tissues of the infected monkeys was examined.

Methods

Nuclear acids were extracted from snap frozen ileum and colon tissues and mesentery lymph nodes from SIV infected monkeys with or without ART. SIV RNA and DNA loads as well as levels of CD3, CD4 and cytokine mRNA were measured by PCR and RT PCR from the isolated nuclear acids. Tissue sections were stained by immuno-fluorescence labeled antibodies for CD3 and CD4.

Results

Without ART treatment, these monkeys underwent a mild SIV infection with low viral loads and slightly decreased CD4+T cell counts in peripheral blood. In ART treated monkeys, SIV RNA loads were undetectable in blood with normal CD4+T cell counts, however, SIV RNA and DNA were detected in the intestinal tissues and mesentery lymph nodes although the levels were lower than those in untreated monkeys. The levels of CD3 and CD4 positive cells in the tissues were similar between the infected untreated monkeys and infected ART treated monkeys based on RT-PCR and immune-fluorescence staining of the tissue sections. Furthermore, compatible levels of IL-6, TNF-a, IL-1b and MyD88 mRNAs were detected in most of intestinal tissues and mesentery lymph nodes of infected ART treated and infected untreated monkeys.

Conclusions

These results suggest that early ART administration could not effectively inhibit SIV replication in intestinal tissues and mesentery lymph nodes and could not reduce the immune activation induced by SIV infection in the intestinal tissues.
Reliability and validity of the Wolfram Unified Rating Scale (WURS)
Authors: Nguyen Chau , Foster Erin R , Paciorkowski Alexander R , Viehoever Amy , Considine Colleen , Bondurant Aidena , Marshall Bess A , Hershey Tamara ,   Washington University Wolfram Study Group
Published: November 2012

Background

Wolfram syndrome (WFS) is a rare, neurodegenerative disease that typically presents with childhood onset insulin dependent diabetes mellitus, followed by optic atrophy, diabetes insipidus, deafness, and neurological and psychiatric dysfunction. There is no cure for the disease, but recent advances in research have improved understanding of the disease course. Measuring disease severity and progression with reliable and validated tools is a prerequisite for clinical trials of any new intervention for neurodegenerative conditions. To this end, we developed the Wolfram Unified Rating Scale (WURS) to measure the severity and individual variability of WFS symptoms. The aim of this study is to develop and test the reliability and validity of the Wolfram Unified Rating Scale (WURS).

Methods

A rating scale of disease severity in WFS was developed by modifying a standardized assessment for another neurodegenerative condition (Batten disease). WFS experts scored the representativeness of WURS items for the disease. The WURS was administered to 13 individuals with WFS (6-25 years of age). Motor, balance, mood and quality of life were also evaluated with standard instruments. Inter-rater reliability, internal consistency reliability, concurrent, predictive and content validity of the WURS were calculated.

Results

The WURS had high inter-rater reliability (ICCs>.93), moderate to high internal consistency reliability (Cronbach’s α = 0.78-0.91) and demonstrated good concurrent and predictive validity. There were significant correlations between the WURS Physical Assessment and motor and balance tests (rs>.67, p<.03), between the WURS Behavioral Scale and reports of mood and behavior (rs>.76, p<.04) and between WURS Total scores and quality of life (rs=-.86, p=.001). The WURS demonstrated acceptable content validity (Scale-Content Validity Index=0.83).

Conclusions

These preliminary findings demonstrate that the WURS has acceptable reliability and validity and captures individual differences in disease severity in children and young adults with WFS.
The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development
Authors: Torres-Poveda Kirvis , Burguete-García Ana I , Cruz Miguel , Martínez-Nava Gabriela A , Bahena-Román Margarita , Ortíz-Flores Esmeralda , Ramírez-González Abrahan , López-Estrada Guillermina , Delgado-Romero Karina , Madrid-Marina Vicente
Published: November 2012

Background

Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL).

Methods

Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL.

Results

No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A.

Conclusions

The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.