Diaphragm motor unit recruitment in rats

We hypothesized that considerable force reserve exists for the diaphragm muscle (DIAm) to generate transdiaphragmatic pressures (Pdi) necessary to sustain ventilation. In rats, we measured Pdi and DIAm EMG activity during different ventilatory (eupnea and hypoxia (10% O₂)–hypercapnia (5% CO₂)) and non-ventilatory (airway occlusion and sneezing induced by intranasal capsaicin) behaviors. Compared to maximum Pdi (Pdi_max generated by bilateral phrenic nerve stimulation), the Pdi generated during eupnea (21 ± 2%) and hypoxia–hypercapnia (28 ± 4%) were significantly less (p < 0.0001) than that generated during airway occlusion (63 ± 4%) and sneezing (94 ± 5%). The Pdi generated during spontaneous sighs was 62 ± 5% of Pdi_max. Relative DIAm EMG activity (root mean square [RMS] amplitude) paralleled the changes in Pdi during different ventilatory and non-ventilatory behaviors (r² = 0.78; p < 0.0001). These results support our hypothesis of a considerable force reserve for the DIAm to accomplish ventilatory behaviors. A model for DIAm motor unit recruitment predicted that ventilatory behaviors would require activation of only fatigue resistant units.     

Non-stationarity and power spectral shifts in EMG activity reflect motor unit recruitment in rat diaphragm muscle

We hypothesized that a shift in diaphragm muscle (DIAm) EMG power spectral density (PSD) to higher frequencies reflects recruitment of more fatigable fast-twitch motor units and motor unit recruitment is reflected by EMG non-stationarity. DIAm EMG was recorded in anesthetized rats during eupnea, hypoxia-hypercapnia (10% O₂–5% CO₂), airway occlusion, and sneezing (maximal DIAm force). Although power in all frequency bands increased progressively across motor behaviors, PSD centroid frequency increased only during sneezing (p < 0.05). The non-stationary period at the onset of EMG activity ranged from ∼80 ms during airway occlusion to ∼150 ms during eupnea. Within the initial non-stationary period of EMG activity 80–95% of motor units were recruited during different motor behaviors. Motor units augmented their discharge frequencies progressively beyond the non-stationary period; yet, EMG signal became stationary. In conclusion, non-stationarity of DIAm EMG reflects the period of motor unit recruitment, while a shift in the PSD towards higher frequencies reflects recruitment of more fatigable fast-twitch motor units.     

Striatum brain-derived neurotrophic factor levels are decreased in dystrophin-deficient mice

Brain dystrophin is enriched in the postsynaptic densities of pyramidal neurons specialized regions of the subsynaptic cytoskeletal network, which are critical for synaptic transmission and plasticity. Lack of dystrophin in brain structures have been involved with impaired cognitive functions. The brain-derived neurotrophic factor (BDNF) is a regulator of neuronal survival, fast synaptic transmission, and activity-dependent synaptic plasticity. The present study investigated BDNF protein levels by Elisa analysis in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx (n = 5) and normal C57BL10 mouse (n = 5). We observed that the mdx mouse display diminution in BDNF levels in striatum (t = 6.073; df = 6; p = 0.001), while a tendency of decrease in BDNF levels was observed in the prefrontal cortex region (t = 1.962; df = 6; p = 0.096). The cerebellum (t = 1.258; df = 7; p = 0.249), hippocampus (t = 0.631; df = 7; p = 0.548) and cortex (t = 0.572; df = 7; p = 0.586) showed no significant alterations as compared to wt mouse. In conclusion, we demonstrate that only striatum decreased BDNF levels compared with wild-type (wt) mouse, differently to the other areas of the brain. This dystrophin deficiency may be affecting BDNF levels in striatum and contributing, in part, in memory storage and restoring.     

Estradiol reduces anxiety- and depression-like behavior of aged female mice

Beneficial effects of the ovarian steroid, 17β-estradiol (E₂), for affective behavior have been reported in young individuals, but less is known about the effects of E₂ among older individuals, and the capacity of older individuals to respond to E₂ following its decline. In the present study, the effects of acute E₂ administration to aged mice for anxiety-like and depression-like behaviors were investigated. Intact female C57BL/6 mice (N = 18) that were approximately 24 months old were administered vehicle (sesame oil, n = 9) or E₂ (10 μg, n = 9) subcutaneously 1 h prior to behavioral testing. Mice were tested for anxiety-like behavior (open field, elevated plus maze, mirror chamber, light-dark transition task, Vogel conflict task) and depression-like behavior (forced swim task). To assess the role of general motor behavior and coordination in these aged mice, performance in an activity monitor and rotarod task, and total entries made in tasks (open field, elevated plus maze, light-dark transition task) were determined. Mice administered E₂, compared to vehicle, demonstrated anti-anxiety behavior in the open field, mirror chamber, and light-dark transition task, and anti-depressive-like behavior in the forced swim task. E₂ also tended to have anti-anxiety effects in the elevated plus maze and Vogel task compared to vehicle administration, but these effects did not reach statistical significance. E₂ did not alter motor behavior and/or coordination in the activity monitor, open field, or rotarod tasks. Thus, an acute E₂ regimen produced specific anti-anxiety and anti-depressant effects, independent of effects on motor behavior, when administered to aged female C57BL/6 mice.     

Trophic factor expression in phrenic motor neurons

The function of a motor neuron and the muscle fibers it innervates (i.e., a motor unit) determines neuromotor output. Unlike other skeletal muscles, respiratory muscles (e.g., the diaphragm, DIAm) must function from birth onwards in sustaining ventilation. DIAm motor units are capable of both ventilatory and non-ventilatory behaviors, including expulsive behaviors important for airway clearance. There is significant diversity in motor unit properties across different types of motor units in the DIAm. The mechanisms underlying the development and maintenance of motor unit diversity in respiratory muscles (including the DIAm) are not well understood. Recent studies suggest that trophic factor influences contribute to this diversity. Remarkably little is known about the expression of trophic factors and their receptors in phrenic motor neurons. This review will focus on the contribution of trophic factors to the establishment and maintenance of motor unit diversity in the DIAm, during development and in response to injury or disease.     

Family involvement is helpful and harmful to patients’ self-care and glycemic control

Objective

We assessed the relationships between supportive and obstructive family behaviors and patients’ diabetes self-care activities and HbA_1C, and potential interaction effects and differences by demographic characteristics.

Methods

In a cross-sectional study, 192 adults with type 2 diabetes completed the Diabetes Family Behavior Checklist-II, the Summary of Diabetes Self-Care Activities, and a glycemic control (HbA_1C) test.

Results

Participants reported similar rates of supportive and obstructive behaviors that were positively correlated (rho = 0.61, p < 0.001). In adjusted analyses, supportive family behaviors were associated with adherence to different self-care behaviors (β = 0.20 to 0.50, p < 0.05), whereas obstructive family behaviors were associated with less adherence to self-care behaviors (β = −0.28 to −0.39, p < 0.01) and worse HbA_1C (β = 0.18, p < 0.05). Supportive behaviors protected against the detrimental effect of obstructive behaviors on HbA_1C (interaction β = −0.22, p < 0.001). Non-Whites reported more supportive and obstructive behaviors than Whites, but race did not affect the relationships between family behaviors and self-care or HbA_1C.

Conclusion

Involving family members in patients’ diabetes management may impede patients’ self-care and compromise their glycemic control unless family members are taught to avoid obstructive behaviors.

Practice implications

Our findings endorse interventions that help family members develop actionable plans to support patients’ self-care and train them to communicate productively about diabetes management.     

Augmented peripheral chemoreflex in patients with heart failure and inspiratory muscle weakness

We hypothesized that heart failure patients with inspiratory muscle weakness (IMW) present greater peripheral chemoreflex responsiveness and augmented exercise ventilatory oscillation compared to patients with preserved inspiratory muscle strength. We studied 19 heart failure patients: 9 with IMW (maximal inspiratory pressure [PImax] < 70% of predicted) and 10 with preserved inspiratory muscle strength. Inspiratory muscle strength was measured via pressure transducer. Peripheral chemoreflex was evaluated by the single-breath CO₂ test. Exercise ventilatory oscillation was determined as the ratio between amplitude and mean of each oscillation during incremental exercise. Patients with IMW had greater peripheral chemoreflex response (0.11 ± 0.03 l min⁻¹ Torr⁻¹) than those with preserved inspiratory muscle strength (0.07 ± 0.03 l min⁻¹ Torr⁻¹, p = 0.02). Moreover, there was a significant and inverse correlation between PImax and peripheral chemoreflex response (r = −0.57, p = 0.01). Likewise, there was a significant and inverse correlation between PImax and ventilatory oscillations (r = −0.46, p = 0.04). Our findings indicate that IMW is linked to increased peripheral chemoreflex and augmented exercise ventilatory oscillation in patients with chronic heart failure.     

Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)_n repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)_n repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z = 1.91, p = 0.055). An excess of non-transmissions was detected for the 150 and 152 bp alleles (Z = −2.26, p = 0.023; Z = −2.20, p = 0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p = 0.011), and lower effort (p = 0.008), activation (p = 0.008) and attention (p = 0.01) cluster scores. We did not replicate association findings in the case–control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)_n repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.     

Do different delivery systems of hormone therapy have different effects on psychological symptoms in surgically menopausal women? A randomized controlled trial

Objective

To compare the influence of different delivery forms of estrogen therapy on menopausal and psychological symptoms in surgically menopausal women.

Study design

Surgically menopausal women were assigned to a 1-year-therapy with oral conjugated estrogen 0.625 mg/day (n = 35), intranasal 300 μg/day estradiol hemihidrate (n = 33), percutaneous gel 1.5 mg/day estradiol hemihidrate (n = 32) or no treatment (control group, n = 32). Serum E₂ and FSH levels, Kupperman's Scale used to assess climacteric symptoms, Hamilton Depression Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) scores were assessed before and after 1-year-therapy.

Results

After 1 year, the greatest increase in E₂ was in the oral group, followed by the transdermal gel, and then the intranasal group (oral vs transdermal gel: p = 0.022: oral vs intranasal: p = 0.0001; transdermal gel vs intranasal: p = 0.0001). All treatment groups improved significantly in total Kupperman index score and HARS (p < 0.05) with no difference between the groups. With regard to HDRS, all treatment groups improved significantly (p < 0.05) with the greatest improvement in the oral group, and no difference between transdermal gel and intranasal groups (oral vs transdermal gel: p = 0.015; oral vs intranasal: p = 0.001; transdermal gel vs intranasal: p = 0.735). Control group scored worse in all tests after study (p < 0.05). All scores correlated significantly with post-treatment serum E₂ and FSH levels (p < 0.001).

Conclusion

Oral, intranasal and percutaneous gel estradiol therapies significantly improve menopausal and psychological symptoms in surgically menopausal women with oral route better than transdermal gel and intranasal modalities against depressive mood.     

Genetic variants of FOXP3 influence graft survival in kidney transplant patients

FOXP3⁺ regulatory T cells (T_reg) play a role in controlling alloreactivity. It has been shown that short (GT)_n dinucleotide repeats (?(GT)₁₅; S) in the promoter region of the FOXP3 gene enhance the promoter activity when compared to long (GT)_n repeats (?(GT)₁₆; L). The present study retrospectively investigated the influence of this (GT)_n FOXP3 gene polymorphism on renal allograft survival. A total of 599 consecutive first-time kidney transplant patients (median follow-up time 7.7 years) were subdivided according to their FOXP3 genotype into the S-genotype group (SG) and the L-genotype group (LG). The SG was superior to the LG in both general graft survival censored for death (logrank test, p = 0.013) and graft survival following acute rejection (p = 0.021). Multivariate analysis defined the (GT)_n FOXP3 dinucleotide repeat polymorphism as an independent factor and confirmed an advantage for the SG in renal allograft survival (HR = 0.67, 95% CI 0.48–0.94, p = 0.02). This gene association study identified a beneficial effect of FOXP3 genetic variants on graft survival in kidney transplant patients.     

Effect of 4 weeks of Acu-TENS on functional capacity and β-endorphin level in subjects with chronic obstructive pulmonary disease: A randomized controlled trial

Our recent studies showed that one session of transcutaneous electrical nerve stimulation on acupoints (Acu-TENS) improved forced expiratory volume in 1 s (FEV₁) in patients with chronic obstructive pulmonary disease (COPD). This study investigated the effect of 4-week Acu-TENS on physical and psychosocial function in these patients. Twenty-eight patients were randomly allocated to receive 4-weeks of 45-min, 5-days/week, of either Acu-TENS (over Dingchuan), Placebo-TENS (same protocol without electrical output), or Sham-TENS (over the patellae). Variables measured before and after intervention included FEV₁, forced vital capacity (FVC), 6-min walk distance (6MWD), St. George's Respiratory Questionnaire score (SGRQ), β-endorphin and blood inflammatory marker levels. Only the Acu-TENS group attained significant improvement in FEV₁ (p = 0.046), physical activity (p = 0.007) and total SGRQ score (p = 0.028). The increase in β-endorphin (p = 0.012) correlated positively with the improvement in FEV₁ (r = 0.526, p = 0.008). To conclude, 4 weeks of Acu-TENS improved the functional capacity of patients with COPD, probably due to the bronchodilation induced by β-endorphin elevation.     

Neuronal calcium sensor-1 and cocaine addiction: A genetic association study in African-Americans and European Americans

Genes involved in drug reward pathways are plausible candidates for susceptibility to substance use disorders. Given the prominent role of dopamine in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role in the pathophysiology of cocaine addiction (CA). In this study, we investigated whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611, rs1342043) was attempted using a replication sample of African American (AA) ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry (cases n = 336, controls n = 656). Secondary sex specific analysis was also carried out for each SNP in both AA and EA individuals. Genotyping of the discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA in AAs; however, this marker could not be confirmed in either the AA or EA replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043 showed a significant association with CA (genotypic p = 0.0001, allelic p = 0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p = 0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to susceptibility of CA in individuals of African descent.     

Can interactive skills-based seminars with standardized patients enhance clinicians’ prevention skills? Measuring the impact of a CME program

Objective

Communication skills are crucial for high-risk behavior screening and counseling. Practicing physicians have limited opportunities to improve these skills. This paper assesses the impact of a continuing medical education (CME) program for Student Health Center clinicians that targeted communication skills, screening practices and patient satisfaction.

Methods

Program evaluation included pre- and post-objective structured clinical examinations (OSCE's), chart review, and provider and patient satisfaction surveys. Data were analyzed using paired t-tests and ranked sum tests.

Results

OSCE scores (n = 15) revealed significant improvements in communication skills overall (p = 0.004) and within specific domains (data gathering: p = 0.003; rapport building: p = 0.01; patient education: p = 0.02), but no change in case-specific knowledge (p = 0.1). Participants (n = 14) reported high satisfaction with program methods (mean = 4.6/5) and content (mean = 4.7/5), 70% planning to alter their clinical practice. Chart audits (pre = 96, post = 103) showed increased screening for smoking (RR 1.65, p = 0.03), depressed mood (RR 1.40, p = 0.04), anhedonia (RR 1.47, p = 0.01), sexual activity (RR 1.73, p = 0.002) and drinking (RR 1.77, p = 0.04). Sampling of satisfaction among participants’ patients (pre n = 689, post n = 383) detected no increase in already high baseline satisfaction.

Conclusion

This curriculum improved clinicians’ relevant skills and screening behavior.

Practice implications

Skills-oriented CME can improve clinicians’ communication skills and screening and counseling practices.     

Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.     

The effect of lung stretch during sleep on airway mechanics in overweight and obese asthma

Both obesity and sleep reduce lung volume and limit deep breaths, possibly contributing to asthma. We hypothesize that increasing lung volume dynamically during sleep would reduce airway resistance in asthma. Asthma (n = 10) and control (n = 10) subjects were studied during sleep at baseline and with increased lung volume via bi-level positive airway pressure (BPAP). Using forced oscillations, respiratory system resistance (R_rs) and reactance (X_rs) were measured during sleep and R_rs was partitioned to upper and lower airway resistance (R_up, R_low) using an epiglottic pressure catheter. R_rs and R_up increased with sleep (p < 0.01) and X_rs was decreased in REM (p = 0.02) as compared to wake. R_rs, R_up, and R_low, were larger (p < 0.01) and X_rs was decreased (p < 0.02) in asthma. On BPAP, R_rs and R_up were decreased (p < 0.001) and X_rs increased (p < 0.01), but R_low was unchanged. High R_up was observed in asthma, which reduced with BPAP. We conclude that the upper airway is a major component of R_rs and larger lung volume changes may be required to alter R_low.     

A chronic mouse model of Parkinson's disease has a reduced gait pattern certainty

The purpose of this investigation was to determine if a chronic Parkinson's disease mouse model will display less certainty in its gait pattern due to basal ganglia dysfunction. A chronic Parkinson's disease mouse model was induced by injecting male C57/BL mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) (MPTP) and probenecid (250 mg/kg) (P) over 5 weeks. This chronic model produces a severe and persistent loss of nigrostriatal neurons resulting in dopamine depletion and locomotor impairment. The control mice were treated with probenecid alone. Fifteen weeks after the last MPTP/P treatment, the mice were videotaped in the sagittal plane with a digital camera (60 Hz) as they ran on a motorized treadmill at a speed of 10 m/min. The indices of gait and gait variability were calculated. Stride length was significantly (p = 0.016) more variable in the chronic MPTP/P mice. Additionally, the chronic MPTP/P mice had a statistically less certain gait pattern when compared to the control mice (p = 0.02). These results suggest that variability in the gait pattern can be used to evaluate changes in neural function. Additionally, our results imply that disorder of the basal ganglia results in less certainty in modulating the descending motor command that controls the gait pattern.     

Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO2 enriched air in panic disorder, social phobia, and healthy controls

Inhalation of carbon dioxide (CO₂) enriched air triggers anxiety in panic disorder (PD) patients, which is often interpreted as a sign of biological vulnerability. However, most studies have not measured respiration in these tasks. We compared patients with PD (n = 20) and social phobia (SP, n = 19) to healthy controls (n = 18) during eight inhalations of 20% CO₂, preceded and followed by two inhalations of room air, while continuously measuring subjective anxiety and dyspnea as well as autonomic and respiratory variables. PD patients showed increased reactivity and delayed recovery during CO₂ inhalations for most measures. Unlike both other groups, the PD group's tidal volume responses did not habituate across CO₂ inhalations. However, PD patients did not differ from SP patients on most other measures, supporting a continuum model of CO₂ sensitivity across anxiety disorders. Both patient groups showed continued reactivity during the last air inhalations, which is unlikely to be due to a biological sensitivity.     

Risperidone alters food intake, core body temperature, and locomotor activity in mice

Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p = 0.050) and gained more weight (p = 0.0001) than PLA-treated mice after 3 weeks. During the initial 2 days of treatment, there was an acute effect of treatment on activity (p = 0.046), but not body temperature (p = 0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p = 0.0001), and tended to be higher during the dark phase (p = 0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p = 0.006); there were no differences in activity during the light phase (p = 0.47). UCP1 (p < 0.01) and UCP3 (p < 0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p < 0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.     

Communicating consequences of risky behaviors: Life expectancy versus risk of disease

Objective

We investigate (1) whether presenting consequences of health-related behaviors in terms of life expectancy, rather than risk of disease, improves recall and (2) if yes, through which underlying mechanisms; (3) whether these effects hold for both low- and high-numeracy people and (4) in two countries with different cultural environments and medical systems.

Methods

Experiment within a computerized survey on probabilistic samples in the United States (n = 513) and Germany (n = 534).

Results

When consequences of health-related behaviors were presented in terms of changes in life expectancy, recall was better than when they were presented in terms of risks of a disease both after 10 min, Cohen's h = .51, F(1,543) = 34.12, p = .001, and after 3 weeks, h = .62, F(1,543) = 48.98, p = .001. This was so for participants of both high and low numeracy, and in both countries. The improved recall seems to be due to better imaginability of changes in life expectancy.

Conclusions

Consequences of health-related behaviors are easier to imagine and are recalled better when expressed as changes in life expectancy rather than as changes in risk of diseases.

Practice implications

When communicating with patients about medical risks, we recommend using concepts that they can readily relate to their own everyday experiences.     

Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas

Triple negative breast cancers (TNBC) are characterized by aggressive tumor biology, lack of targeted treatments and poor prognosis. Anthracyclins were shown to induce immunogenic death in target cells, potentially leading to “endogenous” vaccination. We comparatively assessed expression of cancer testis antigens (CTA) and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype, BL morphology and conventional clinicopathological factors. The study included 83 patients undergoing surgery between January 2003 and December 2009. Tissue sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10, NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL immunophenotype and 48.2% had BL morphology. MAGE-A1 specific staining was most frequently detectable (69.2%), followed by multi-MAGE-A (58%), NY-ESO (27.1%) and MAGE-A10 (16%) specific staining. MAGE-A10 expression significantly correlated with tumor size (p = 0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A specific stainings significantly correlated with advanced clinical stage (p = 0.024, p = 0.041, p = 0.031, respectively). We found no significant association between CTA expression and disease free (DFS) or overall survival (OS). Most interestingly, a significant correlation was observed between expression of MAGE-A10 and NY-ESO and expression of TOPO2A (p = 0.005, p = 0.013). Expression of defined CTA and TOPO2A are significantly correlated in TNBC. Considering the limited therapeutic options for TNBC, these findings might suggest novel forms of combination therapies that should be further explored.