Clinical significance of BPI-ANCA in patients with cystic fibrosis: a single center prospective study.

Recurrent pulmonary exacerbation due to infection and inflammation remain the major cause of mortality and morbidity in patients with cystic fibrosis (CF). Increased levels of BPI-ANCA have been linked to Pseudomonas colonization and pulmonary exacerbations in patients with CF. The majority of these studies were done in Europe, and it is unclear whether similar findings are true in CF patients who lives in United States. In our single center study of 47 patients with CF, the prevalence of BPI-ANCA was 19% at baseline and 15% at annual follow-up visit. Overall, there were no statistical differences noted in FEV1 and frequency of pulmonary exacerbations in CF patients who were positive for BPI-ANCA compared to those who were negative for BPI-ANCA. The role of BPI-ANCA in patients with CF still remains unclear.

Structure and Performance of Benzoxazine Composites for Space Radiation Shielding.

Innovative multifunctional materials that combine structural functionality with other spacecraft subsystem functions have been identified as a key enabling technology for future deep space missions. In this work, we report the structure and performance of multifunctional polymer matrix composites developed for aerospace applications that require both structural functionality and space radiation shielding. Composites comprised of ultra-high molecular weight polyethylene (UHMWPE) fiber reinforcement and a hydrogen-rich polybenzoxazine matrix are prepared using a low-pressure vacuum bagging process. The polybenzoxazine matrix is derived from a novel benzoxazine resin that possesses a unique combination of attributes: high hydrogen concentration for shielding against galactic cosmic rays (GCR), low polymerization temperature to prevent damage to UHMWPE fibers during composite fabrication, long shelf-life, and low viscosity to improve flow during molding. Dynamic mechanical analysis (DMA) is used to study rheological and thermomechanical properties. Composite mechanical properties, obtained using several standardized tests, are reported. Improvement in composite stiffness, through the addition of carbon fiber skin layers, is investigated. Radiation shielding performance is evaluated using computer-based simulations. The composites demonstrate clear advantages over benchmark materials in terms of combined structural and radiation shielding performance.

Development of Hydrogen-Rich Benzoxazine Resins with Low Polymerization Temperature for Space Radiation Shielding.

A systematic study has been carried out to develop a material with significant protection properties from galactic cosmic radiation and solar energetic particles. The research focused on the development of hydrogen-rich benzoxazines, which are particularly effective for shielding against such radiation. Newly developed benzoxazine resin can be polymerized at 120 °C, which meets the low-temperature processing requirements for use with ultrahigh molecular weight polyethylene (UHMWPE) fiber, a hydrogen-rich composite reinforcement. This highly reactive benzoxazine resin also exhibits low viscosity and good shelf-life. The structure of the benzoxazine monomer is confirmed by proton nuclear magnetic resonance and Fourier transform infrared spectroscopy. Polymerization behavior and thermal properties are evaluated by differential scanning calorimetry and thermogravimetric analysis. Dynamic mechanical analysis is used to study chemorheological properties of the benzoxazine monomer, rheological properties of the cross-linked polybenzoxazine, and rheological properties of UHMWPE-reinforced polybenzoxazine composites. The theoretical radiation shielding capability of the composite is also evaluated using computer-based simulations.

A Review and Proposed Approach to the Neutrophilic Dermatoses of Childhood.

Neutrophilic dermatoses (NDs) are inflammatory skin conditions that are not associated with infection. The classification and clinical approach to these conditions in children is poorly described. This review classifies these conditions into five nosological subtypes: Sweet's syndrome, pyoderma gangrenosum, aseptic pustules, neutrophilic urticarial dermatoses, and Marshall's syndrome. In addition, we review the various secondary diseases that need to be excluded in the clinical management of the NDs of childhood, with a focus on the autoinflammatory conditions that the reader may not be familiar with. We propose a practical clinical approach to these disorders.

TBX2 represses CST6 resulting in uncontrolled legumain activity to sustain breast cancer proliferation: a novel cancer-selective target pathway with therapeutic opportunities.

TBX2 is an oncogenic transcription factor known to drive breast cancer proliferation. We have identified the cysteine protease inhibitor Cystatin 6 (CST6) as a consistently repressed TBX2 target gene, co-repressed through a mechanism involving Early Growth Response 1 (EGR1). Exogenous expression of CST6 in TBX2-expressing breast cancer cells resulted in significant apoptosis whilst non-tumorigenic breast cells remained unaffected. CST6 is an important tumor suppressor in multiple tissues, acting as a dual protease inhibitor of both papain-like cathepsins and asparaginyl endopeptidases (AEPs) such as Legumain (LGMN). Mutation of the CST6 LGMN-inhibitory domain completely abrogated its ability to induce apoptosis in TBX2-expressing breast cancer cells, whilst mutation of the cathepsin-inhibitory domain or treatment with a pan-cathepsin inhibitor had no effect, suggesting that LGMN is the key oncogenic driver enzyme. LGMN activity assays confirmed the observed growth inhibitory effects were consistent with CST6 inhibition of LGMN. Knockdown of LGMN and the only other known AEP enzyme (GPI8) by siRNA confirmed that LGMN was the enzyme responsible for maintaining breast cancer proliferation. CST6 did not require secretion or glycosylation to elicit its cell killing effects, suggesting an intracellular mode of action. Finally, we show that TBX2 and CST6 displayed reciprocal expression in a cohort of primary breast cancers with increased TBX2 expression associating with increased metastases. We have also noted that tumors with altered TBX2/CST6 expression show poor overall survival. This novel TBX2-CST6-LGMN signaling pathway, therefore, represents an exciting opportunity for the development of novel therapies to target TBX2 driven breast cancers.

Microvascular decompression for superior oblique myokymia: case report.

BACKGROUND: Superior oblique myokymia (SOM) is a rare disorder in which the patient suffers episodic uniocular torsional eye movement associated with diplopia and oscillopsia . Although the pathophysiology has been narrowed down to erratic discharge of the trochlear nerve, yet the exact etiology remains unclear; a handful of cases have been described in association with an identifiable space occupying lesions or dural AV fistulae. Neurovascular compression theory has been postulated in the early 1980s and to our knowledge, very few reports exist in the literature accrediting this hypothesis in the pathogenesis of superior oblique myokymia. CASE REPORT: We report a case of successful resolution of severe medication refractory SOM following microvascular decompression of the trochlear nerve. The clinical response has been sustained for a follow-up period of 18 months to date. CONCLUSION: Microvascular decompression may be considered as a definitive and least destructive surgical option for the treatment of medication refractory superior oblique myokymia.

Evaluating noise reduction techniques while considering anatomical noise in dual-energy contrast-enhanced mammography.

PURPOSE: The authors describe modifications to previously developed cascaded systems analysis to include the anatomical noise in evaluation of dual-energy noise reduction techniques. Previous models have ignored the anatomical noise in theoretical analysis of noise reduction techniques. The inclusion of anatomical noise leads to more accurate estimation of potential noise reduction improvements and optimization. METHODS: The model is applied to dual-energy contrast-enhanced mammography. The effect of linear noise reduction filters on the anatomical noise is taken into account using cascaded systems analysis. The noise model is included in the ideal observer detectability for performance evaluation of the noise reduction techniques. RESULTS: Dual-energy image noise with and without including the effect of anatomical noise in noise reduction technique analysis is reported. The theoretical model is compared with clinical images from a previous dual-energy contrast enhanced mammography clinical study and good agreement is observed. The results suggest that the inclusion of anatomical noise in the evaluation and comparison of noise reduction techniques is highly warranted for more accurate analysis. CONCLUSIONS: This work establishes a useful extension to dual-energy cascaded systems analysis for maximizing image quality using noise reduction techniques. The extension includes the effect of linear image filtering, such as that used for noise reduction, on anatomical noise. The results suggest that the inclusion of anatomical noise in the evaluation of noise reduction techniques can lead to more accurate optimization, noise, and performance estimations.

Health behaviors among cancer survivors receiving screening mammography.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of cancer-related behavioral risk factors among female cancer survivors, relative to women without a previous diagnosis of cancer. METHODS: In a large cohort of 19,948 women presenting for screening mammography, questionnaires on health behaviors were administered. RESULTS: A total of 18,510 had detailed history on health behaviors and previous cancer history. Overall 2713 (14.7%) reported a previous cancer history. We found statistically significant results indicating that cancer survivors were less likely than those with no cancer history to: report their overall health as "excellent" (13.6% vs. 21.5%), to engage in moderate or strenuous exercise (56.5% vs. 63.3%), and to use complementary and alternative medicine (57.4% vs. 60.2%). Conversely, cancer survivors were more likely to be current smokers (6.3% vs. 5.5%), rate their overall health as "poor" (15.8% vs. 9.1%), and to report more weight gain over time. Among cancer survivors, differences also emerged by the type of primary cancer. For example, cervical cancer survivors (n = 370) were most likely to report being current smokers (15.7%) and regular alcohol users (71.7%) compared with other survivors. Ovarian (n = 185) and uterine (n = 262) cancer survivors most frequently reported being obese (41% and 34.4%, respectively). Cervical cancer survivors reported the largest weight gain (4.9 lbs at 5 y and 13.4 lbs at 10 y). CONCLUSIONS: These results suggest opportunities for tailored behavioral health risk factor interventions for specific populations of cancer survivors.

Age and androgen-deprivation therapy on exercise outcomes in men with prostate cancer.

PURPOSE: The purpose of this study is to examine the effects of age (≤ 65 years or >65 years) and androgen-deprivation therapy (ADT, presence or absence) as factors that may predict changes in body composition and fitness following a 24-week exercise program in prostate cancer patients. METHODS: One hundred twenty-one men were randomly allocated to either: (1) aerobic exercise (AE), (2) resistance exercise (RE), or (3) usual care (UC). Body composition was assessed by DXA. Aerobic fitness was assessed through a maximal treadmill test. Muscular strength was assessed by leg extension and bench press using the eight-repetition maximum test. Responses were compared between younger (≤ 65 years) and older (> 65 years) patients with or without ADT. RESULTS: There did not appear to be an interaction between age and ADT on body composition or fitness, nor were there any significant changes in body composition for participants ≤ 65 years. In participants aged >65 years, lean mass decreased in AE (p = 0.013) and UC (p = 0.006), but was preserved in RE. In participants receiving ADT, there was a decrease in lean mass in AE (p = 0.003) and UC (p < 0.001) but not in RE. The non-ADT group did not show any changes in body composition but did show improvements in muscular fitness following resistance training (p < 0.001). CONCLUSION: Changes in body composition and physical fitness following a 24-week exercise program in men with prostate cancer are not influenced by age and/or ADT. Resistance training appears to attenuate the age-related decrease in lean mass and increase in body fat in older patients with prostate cancer and those receiving ADT.

Fibrodysplasia ossificans progressiva (FOP) in South Africa: dental implications in 5 cases.

Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disorder in which progressive ossification of subcutaneous tissues leads to immobility and profound physical handicap. Dental management of affected persons may be constrained by impaired mobility of the temporomandibular joints. Equally, the traumatic aspects of dental intervention can exacerbate the ossification process. In the later stages of the disorder, thoracic immobility impairs pulmonary ventilation and compromises dental anesthesia. We have undertaken dental appraisal and treatment of 5 South Africans with FOP, with ages ranging from 2 to 52 years. The age relationship of the manifestations of FOP was apparent in these persons, as were the dental problems that emerged. These dental observations illustrate the importance of accurate diagnosis and the awareness of potential complications that may be encountered in dental management. Our observations are presented and discussed in this article.

Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer.

PURPOSE: Radiotherapy for prostate cancer (PCa) may cause unfavorable changes in fatigue, quality of life (QOL), and physical fitness. We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue, QOL, physical fitness, body composition, prostate-specific antigen, testosterone, hemoglobin, and lipid levels in men with PCa receiving radiotherapy. PATIENTS AND METHODS: Between 2003 and 2006, we conducted a randomized controlled trial in Ottawa, Canada, where 121 PCa patients initiating radiotherapy with or without androgen deprivation therapy were randomly assigned to usual care (n = 41), resistance (n = 40), or aerobic exercise (n = 40) for 24 weeks. Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale. RESULTS: The follow-up assessment rate for our primary end point of fatigue was 92.6%. Median adherence to prescribed exercise was 85.5%. Mixed-model repeated measures analyses indicated both resistance (P =.010) and aerobic exercise (P = .004) mitigated fatigue over the short term. Resistance exercise also produced longer-term improvements (P = .002). Compared with usual care, resistance training improved QOL (P = .015), aerobic fitness (P = .041), upper- (P < .001) and lower-body (P < .001) strength, and triglycerides (P = .036), while preventing an increase in body fat (P = .049). Aerobic training also improved fitness (P = .052). One serious adverse event occurred in the group that performed aerobic exercise. CONCLUSION: In the short term, both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy. Resistance exercise generated longer-term improvements and additional benefits for QOL, strength, triglycerides, and body fat.

Three independent factors predicted adherence in a randomized controlled trial of resistance exercise training among prostate cancer survivors.

OBJECTIVE: To examine predictors of adherence in a randomized controlled trial of resistance exercise training (RET) in prostate cancer survivors receiving androgen deprivation therapy. STUDY DESIGN AND SETTING: A randomized controlled trial conducted at fitness centers in Ottawa and Edmonton, Canada. Prostate cancer survivors (n=155) completed measures of social cognitive variables, quality of life (QOL), behavior, and fitness before being randomized to either an exercise (n=82) or control (n=73) group. The exercise group was asked to perform supervised RET three times per week for 12 weeks. RESULTS: The exercise group attended 28.2 of the 36 (78.3%) RET sessions. Univariate analyses revealed eight different significant (Ps <.05) predictors of exercise adherence including exercise stage of change, intention, age, QOL, fatigue, subjective norm, leg-press test, and perceived behavioral control. A multivariate analysis indicated that there were three independent predictors of adherence that explained 20.4% of the variance: exercise stage of change (beta=0.26; P=.013), age (beta=-0.22; P=.037), and intention (beta=0.19; P=.073). CONCLUSION: Exercise adherence in the trial was very good but not optimal. Adherence was predicted by variables from many different categories including social cognitive, QOL, behavioral, fitness, and demographic. These findings may have important implications for maximizing adherence during clinical trials of exercise in prostate cancer survivors.

Reconstruction of in vivo time-evolving neuroendocrine dose-response properties unveils admixed deterministic and stochastic elements.

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising (i) a deterministic basic feedback and feedforward ensemble structure; (ii) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose-response properties; and (iii) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human (i) illustrates probabilistic estimation of endogenous effector dose-response properties; and (ii) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to (i) reconstruct deterministic properties of interglandular signaling in the intact mammal and (ii) quantify apparent signal-response variability over short time scales in vivo. The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Resistance exercise in men receiving androgen deprivation therapy for prostate cancer.

PURPOSE: Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat. METHODS: In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition. RESULTS: Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P =.002) and higher quality of life (P =.001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P =.009) and lower body (P <.001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds. CONCLUSION: Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.