Changes over time in self-efficacy to cope with cancer and well-being in women with breast cancer: a cross-cultural study.

OBJECTIVE: This study aimed to examine whether self-efficacy to cope with cancer changes over time in patients with breast cancer and whether these potential changes are similar across patients. It also aimed to examine whether these trajectories are related to patient psychological well-being and overall quality of life. METHODS: Participants (N = 404) from four countries (i.e. Finland, Israel, Italy, and Portugal) were enrolled in the study few weeks after breast surgery or biopsy. Self-efficacy to cope with cancer was assessed at baseline, six and 12 months later. Well-being indices were assessed at baseline, 12 and 18 months later. RESULTS: Using Latent Class Growth Analysis, two groups of patients were identified. The majority of patients reported high levels of self-efficacy to cope, which increased over time. For almost 15% of the patients, however, self-efficacy declined over time. Diminishing levels of self-efficacy to cope predicted worse levels of well-being. The pattern of self-efficacy changes and their relationships to well-being was consistent across countries. CONCLUSION: Monitoring self-efficacy to cope with cancer is probably important in order to detect alarming changes in its levels, as a declining self-efficacy to cope may serve as a signal of the need for intervention to prevent adaptation difficulties.

The Interplay Between Trait Resilience and Coping Self-efficacy in Patients with Breast Cancer: An International Study.

The role of self-efficacy to cope with breast cancer as a mediator and/or moderator in the relationship of trait resilience to quality of life and psychological symptoms was examined in this study. Data from the BOUNCE Project ( https://www.bounce-project.eu/ ) were used. Women diagnosed with and in treatment for breast cancer (N = 484), from four countries, participated in the study. Trait resilience and coping self-efficacy were assessed at baseline (soon after the beginning of systemic treatment), and outcomes (quality of life, psychological symptoms) 3 months later. Hierarchical regression, mediation, moderation, and conditional (moderated) mediation and moderation analyses were performed to examine the study hypotheses. Coping self-efficacy mediated the impact of trait resilience. In addition, higher levels of resilience in combination with higher levels of coping self-efficacy were associated with better outcomes. Country of origin had no impact on these results. Overall, it seems that coping self-efficacy is a key factor that should be taken into account for research and intervention efforts in cancer.

The mutual determination of self-efficacy to cope with cancer and cancer-related coping over time: a prospective study in women with breast cancer.

OBJECTIVE: The aim of this study was to examine the longitudinal impact of self-efficacy to cope with cancer on the cancer-related coping reactions of breast cancer patients and vice versa. DESIGN AND MAIN OUTCOMES MEASURES: Data from the BOUNCE Project (https://www.bounce-project.eu/) were used to address the hypotheses. Participants (N = 403) were enrolled in the study a few weeks after surgery or biopsy. Coping self-efficacy was assessed at baseline and six months later (M6). Cancer-related coping was assessed three (M3) and nine months (M9) after baseline. The analyses were performed using structural equation modeling with Mplus 8.6. RESULTS: Baseline coping self-efficacy predicted all M3 coping reactions, while M6 coping self-efficacy also predicted changes in all but one M9 coping reaction. Moreover, one of the M3 coping reactions, that is, hopelessness/helplessness, predicted the changes in M6 coping self-efficacy. The relation between coping self-efficacy and one coping reaction (i.e. cognitive avoidance) was rather weak. Stability paths from M3 to M9 coping reactions were moderate to high. CONCLUSION: The relationship between self-efficacy to cope with cancer and cancer-related coping is complex. New theoretical models are needed to more accurately describe the diverse aspects of this association.

Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast: Expression of γH2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases.

BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies are urgently needed. Immune check point inhibitors have shown activity in programmed death-ligand 1 (PD-L1) - positive metastatic triple negative breast carcinoma (TNBC), which raises the possibility that immunotherapy may also be effective in MpBC as most of the MpBCs are triple negative. The aim of the present study was to assess genomic instability and immunogenicity in tumor specimens of patients with MpBC. METHODS: A total of 76 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for tumor cell PD-L1, immune cell PD-L1 and p53 on tissue microarrays (TMAs), analyzed stromal and intratumoral tumor infiltrating lymphocytes (TILs) from hematoxylin and eosin-stained (H&E) slides and scored gamma-H2AX (γH2AX) and phosphorylated-RPA2 (pRPA2) from whole tissue sections. We correlated marker expression with clinicopathologic features and clinical outcome. RESULTS: All tumors expressed γH2AX and pRPA2 with median expressions of 43% and 44%. P53- (68%), tumor cell PD-L1- (59%) and immune cell PD-L1-positivity (62%) were common in MpBCs. Median stromal TIL and intratumoral TIL counts were 5% and 0. The spindle and squamous cell carcinomas expressed the highest levels of PD-L1 and TILs, and carcinoma with mesenchymal differentiation the lowest. CONCLUSIONS: MpBC appears to be an immunogenic cancer with high genomic instability and frequent PD-L1-positivity, implying that check point inhibitors might be effective in MpBC. Expression levels of PD-L1 and TILs varied across different histologic subtypes, suggesting that immunotherapy might be less effective in carcinoma with mesenchymal differentiation.

Young children's voices in an unlocked Sweden during the COVID-19 pandemic.

AIMS: During the COVID-19 pandemic, Sweden was one of the few countries that rejected lockdowns in favour of recommendations for restrictions, including careful hand hygiene and social distancing. Preschools and primary schools remained open. Several studies have shown negative impacts of the pandemic on children, particularly high levels of anxiety. The study aim was to explore how Swedish school-aged children aged 6-14 years, experienced the COVID-19 pandemic and their perceived anxiety. METHODS: In total, 774 children aged 6-14 years and their guardians answered an online questionnaire containing 24 questions, along with two instruments measuring anxiety: the Children's Anxiety Questionnaire and the Numerical Rating Scale. A convergent parallel mixed-methods design was used for analysing the quantitative and qualitative data. Each data source was first analysed separately, followed by a merged interpretative analysis. RESULTS: The results showed generally low levels of anxiety, with no significant sex differences. Children who refrained from normal social activities or group activities (n=377) had significantly higher levels of anxiety. Most of the children were able to appreciate the bright side of life, despite the social distancing and refraining from activities, which prevented them from meeting and hugging their loved ones. CONCLUSIONS: These Swedish children generally experienced low levels of anxiety, except those who refrained from social activities. Life was nonetheless mostly experienced as normal, largely because schools remained open. Keeping life as normal as possible could be one important factor in preventing higher anxiety and depression levels in children during a pandemic.

To be or not to be vaccinated against COVID-19 - The adolescents' perspective - A mixed-methods study in Sweden.

Vaccination of the population seems to be an important strategy in halting the COVID-19 pandemic in both local and global society. The aim of this study was to explore Swedish adolescents' willingness to be vaccinated against COVID-19 and its association with sociodemographic and other possible factors. A survey was distributed in Sweden between 7 July and 8 November 2020. The main qualitative question concerned adolescents' thoughts on vaccination against COVID-19 and evaluated whether the adolescents would like to be vaccinated when a COVID-19 vaccine is made available. In total, 702 adolescents aged between 15 and 19 responded to the questionnaire. A convergent parallel mixed-methods design was used. The results showed that nearly one in three adolescents had not decided if they wanted to get a COVID-19 vaccine, i.e. 30.5%: n = 214. Of the participants 54.3% (n = 381) were willing to be vaccinated. Girls had higher levels of anxiety about the vaccine compared to boys. In addition, high levels of anxiety impacted on the participants' willingness to be vaccinated. One reason for being undecided about the vaccine was that participants felt they did not know enough about it. Practising social distancing increased willingness to be vaccinated, as reflected in the qualitative results which showed participants wanted to be vaccinated to protect others. The results impart important knowledge to healthcare professionals and contribute to their communication with adolescents about vaccine hesitancy.

Validating a generic cancer consumer quality index in eight European countries, patient reported experiences and the influence of cultural differences.

BACKGROUND: Taking patient centeredness into account is important in healthcare. The European Cancer Consumer Quality Index (ECCQI) is a validated tool for international benchmarking of patient experiences and satisfaction. This study aimed to further validate the ECCQI in larger and more uniform groups of high volume tumours such as breast and prostate cancer. A second objective was the verification of the influence of cultural factors of the country to determine its possible use in international benchmarking. METHODS: Data from two survey studies in eight European countries were combined. Socio-demographic correlations were analysed with Kruskall-Wallis and Mann-Whitney tests. Cronbach's alpha was calculated to validate internal consistency. Influences of masculinity (MAS), power distance (PD) and uncertainty avoidance (UA) were determined by linear regression analysis in a general model and subgroup models. RESULTS: A total of 1322 surveys were included in the analysis (1093 breast- and 348 prostate cancer patients). Cronbach's alpha was good (α ≥ 0.7) or acceptable (0.5 ≤ α ≤ 0.7) in 8 out of 9 questionnaire categories, except in the category 'Safety' (α = 0.305). Overall ECCQI scores ranged from 22.1 to 25.1 between countries on a 1-35 scale (categories had a 1-4 scale). In certain subcategories such as 'Organisation' (range 2.2 vs 3.0) and 'Supervision & Support' (range 3.0 vs 3.8) a large difference was observed between countries. Differences in 'Overall opinion' were however small: mean scores of 3.7 vs 3.9, whereas median scores were all the maximum of 4.0. Power distance was positively associated with higher patient satisfaction scores whereas Uncertainty avoidance was negatively associated with these scores. Masculinity was only associated with patient satisfaction scores in lower educated patients. We found the highest impact of culture on overall scores in Hungary and Portugal and the lowest in Romania. CONCLUSIONS: The ECCQI shows high internal consistency in all categories except 'Safety'. Especially in separate categories and overall ECCQI scores the questionnaire showed discriminative value. This study showed a positive correlation of power distance and a negative correlation for uncertainty avoidance in some countries. When using the ECCQI for international benchmarking these two dimensions of culture should be taken into account.

Axillary nodal metastatic burden in patients with breast cancer with clinically positive axillary nodes.

BACKGROUND: The aim of this study was to determine preoperative factors and tumour characteristics related to a high nodal tumour burden in patients with clinically node-positive breast cancer. These findings were used to construct a predictive tool to evaluate the patient-specific risk of having more than two axillary lymph node metastases. METHODS: Altogether, 507 consecutive patients with breast cancer and axillary lymph node metastasis diagnosed by preoperative ultrasound-guided needle biopsy were reviewed. These patients underwent breast surgery and axillary lymph node dissection at Helsinki University Hospital between 2010 and 2014. Patients were grouped into those with one or two, and those with more than two lymph node metastases. RESULTS: There were 153 patients (30·2 per cent) with one or two lymph node metastases and 354 (69·8 per cent) with more than two metastases. Five-year disease-free survival was poorer for the latter group (P = 0·032). Five-year overall survival estimates for patients with one or two and those with more than two lymph node metastases were 87·0 and 81·4 per cent respectively (P = 0·215). In multivariable analysis, factors significantly associated with more than two lymph node metastases were: age, tumour size, lymphovascular invasion in the primary tumour, extracapsular extension of metastasis in lymph nodes, and morphology of lymph nodes. These factors were included in a multivariable predictive model, which had an area under the curve of 0·828 (95 per cent c.i. 0·787 to 0·869). CONCLUSION: The present study provides a patient-specific prediction model for evaluating nodal tumour burden in patients with clinically node-positive breast cancer.

Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. SUMMARY: Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of platelet-expressed FVIII than are required for therapeutic efficacy in hemophilia A are not associated with a thrombotic predilection.

Studies of human polyomaviruses, with HPyV7, BKPyV, and JCPyV present in urine of allogeneic hematopoietic stem cell transplanted patients with or without hemorrhagic cystitis.

BACKGROUND: BK polyomavirus (BKPyV) can cause hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients and polyomavirus-associated nephritis in renal transplant patients, while JC polyomavirus (JCPyV) can generate progressive multifocal leukoencephalopathy in immunocompromised individuals. Since 2007, additional human polyomaviruses (HPyVs) have been identified. In this study, we examined the urines of allo-HSCT patients for possible presence of polyomaviruses BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, and HPyV10 (MWPyV). METHODS: A total of 185 urinary samples obtained 2002-2007 from 105 allo-HSCT patients, 32/105 with HC, were tested for the above-listed HPyVs by a bead-based multiplex assay. Of these, 142 urine samples had previously been tested for BKPyV and JCPyV by nested polymerase chain reaction (PCR). RESULTS: Aside from BKPyV and JCPyV, which dominated, HPyV7 was detected in 5 BKPyV-positive urinary samples from 1 patient. The multiplex assay was more sensitive and specific than the nested PCR. BKPyV and/or JCPyV were found in all but 1 of the previously BKPyV- or JCPyV-positive samples, although 6 previously BKPyV-positive cases were now JCPyV-positive or the reverse. Furthermore, 18/79 previously negative samples were found to be BKPyV and/or JCPyV positive, and a total of 21 double infections were found. Lastly, in 1/29 HC patients, only JCPyV was detected. CONCLUSION: HPyV7 was found for the first time in urine of an allo-HSCT patient, and BKPyV and JCPyV were more commonly found in urine samples using the bead-based assay compared to testing by nested PCR. Finally, only JCPyV was detected in the urine of 1 HC patient.

Identification of scapular kinematics using surface mapping: a validation study.

The immediate goal of this study was to develop and validate a noninvasive, computational surface mapping approach for measuring scapular kinematics by using available motion capture technology in an innovative manner. The long-term goal is to facilitate clinical determination of the role of the scapula in children with brachial plexus birth palsy (BPBP). The population for this study consisted of fourteen healthy adults with prominent scapulae. Subject-specific scapular templates were created using the coordinates of five scapular landmarks obtained from palpation with subjects seated and arms relaxed in a neutral position. The scapular landmarks were re-palpated and their locations recorded in the six arm positions of the modified Mallet classification. The six Mallet positions were repeated with approximately 300 markers covering the scapula. The markers formed a surface map covering the tissue over the scapula. The scapular template created in the neutral position was iteratively fit to the surface map of each trial, providing an estimate of the orientation of the scapula. These estimates of scapular orientation were compared to the known scapular orientation determined from the scapular landmarks palpated in each Mallet position. The magnitude of the largest mean difference about an anatomical axis between the two measures of scapular orientation was 3.8° with an RMS error of 5.9°. This technique is practical for populations with visibly prominent scapulae (e.g., BPBP patients), for which it is a viable alternative to existing clinical methods with comparable accuracy.

Different impact of intermediate and unfavourable cytogenetics at the time of diagnosis on outcome of de novo AML after allo-SCT: a long-term retrospective analysis from a single institution.

Karyotype of myeloblasts at the time of AML diagnosis has been shown to be prognostic significant for pre-remission outcome and outcome after allo-SCT, but the latter requires further studies. We conducted a retrospective analysis of the impact of intermediate and unfavourable cytogenetics at the time of primary diagnosis on outcome after allo-SCT in de novo AML. The study included 169 patients who underwent allo-SCT at Karolinska University Hospital between 1980 and 2010. Intermediate and unfavourable cytogenetics were found in 129 (76%) and 40 patients (24%), respectively. Myeloablative and reduced-intensity conditioning were given to 120 (71%) and 49 (29%) patients, respectively. Allo-SCT was performed in CR1 in 122 patients (72%). TRM was 16% in both cytogenetics groups. Relapse occurred in 29% patients with intermediate and in 45% patients with unfavourable cytogenetics (P=0.01). The probabilities of 5-year OS for patients with intermediate and unfavourable cytogenetics were 60 and 43%, respectively (P=0.02). Multivariate analysis revealed intermediate cytogenetics, chronic GVHD, and recipient CMV-negative serostatus as variables associated with favourable OS. Our study showed that outcome after allo-SCT in de novo AML differs depending on cytogenetic risk-group; however its position in post-remission therapy of eligible AML patients is not threatened.

Effect of a contusion injury on muscular force, power, work, and fatigue.

The purpose of the investigation was to compare alterations in muscular force, power, work, and fatigue following a contusion injury. We hypothesized that power and work would be more greatly reduced than isometric force due to several mechanisms that would alter the force-velocity relationship and impair activation/relaxation kinetics specific to dynamic muscle contractions. Contusion injury was administered to the gastrocnemius muscle of adult rats using the drop-mass technique. Isometric force, power during shortening (10, 25, and 40 mm/s), work produced during cyclic contractions (2 and 4 Hz), and fatigue during 60 work loops, were normalized to dry muscle mass and analyzed in control animals (n=11), as well as 1 h (n=11) and 48 h (n=9) following contusion injury. Passive work increased (30-38%) 48 h after injury compared with control (P<0.01). Isometric force, power, and work were significantly reduced by similar magnitudes 1 h (28-33%) and 48 h (28-38%) after injury compared with control (P<0.01). Fatigue index 1 h post-injury was significantly less than control (75% vs 85%; P=0.02). The observed increases in muscle hysteresis were apparently not large enough to cause greater reductions in power and work than isometric force. We conclude that isometric measures provide adequate quantification of muscular dysfunction following a contusion injury in these animals and may offer sufficient information to determine recovery status in clinical settings as well.

Breast cancer in very young women.

AIMS: The purpose was to analyse the characteristics, treatment, recurrences and survival of very young women with breast cancer. METHODS: 212 female breast cancer patients ≤35 years old were treated during 1997-2007. The median follow-up time was 78 months. RESULTS: 117 patients had lymph node metastases and 14 distant metastases at diagnosis. 81 (38%) tumours were hormone receptor negative and 130 (65%) grade 3. HER2 positivity was seen in 47 (34%) and triple negativity in 35 (26%) of the 137 tumours with known HER2 status. 140 women were treated with mastectomy and 68 with breast conserving surgery. 163 patients received postoperative radiotherapy, 175 adjuvant chemotherapy, 95 endocrine therapy and 18 trastuzumab. 63 patients experienced a recurrence, of which 20 had only a locoregional recurrence. 10 (15%) of the women with breast conserving surgery experienced ipsilateral breast tumour recurrence while ipsilateral thoracic wall recurrence was seen in 8 patients (6%) after mastectomy. Seven of these eight patients did not receive postmastectomy radiotherapy. DFI was shorter in patients with hormone receptor positive tumours. At the end of follow-up 44 women had died. The 5-year OS was 80%. CONCLUSIONS: The 5-year OS for young women has become better but is still lower than for all breast cancer patients. DFI was shorter in patients with hormone receptor positive disease. Locoregional recurrences were seen more often after breast conserving surgery.

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers.

The aim of the present study was to determine whether systemic sensitisation and chronic aeroallergen challenge in macaques replicate the classical and emerging immunology and molecular pathology of human asthma. Macaques were immunised and periodically challenged over 2 yrs with house dust mite allergen. At key time-points, serum, bronchoalveolar lavage (BAL) and bronchial biopsies were assayed for genes, proteins and lymphocyte subpopulations relevant to clinical asthma. Immunisation and periodic airway challenge induced changes in immunoglobulin E, airway physiology and eosinophilia consistent with chronic, dual-phase asthma. Sensitisation increased interleukin (IL)-1ß and -6 concentrations in serum, and IL-13 expression in BAL cells. Airway challenge increased: early expression of IL-5, -6, -13 and -19, and eotaxin; and variable late-phase expression of IL-4, -5 and -13, and thymus- and activation-regulated chemokine in BAL cells. CD4+ lymphocytes comprised 30% of the CD3+ cells in BAL, increasing to 50% in the late phase. Natural killer T-cells represented <3% of the CD3+ cells. Corticosteroid treatment reduced serum histamine levels, percentage of CD4+ cells and monocyte-derived chemokine expression, while increasing CD3+ and CD8+ cells in BAL. Sensitisation and periodic aeroallergen challenge of cynomolgus macaques results in physiological, cellular, molecular and protein phenotypes, and therapeutic responses observed in human asthma, providing a model system useful in target and biomarker discovery, and translational asthma research.

Maximal force is unaffected by emphysema-induced atrophy in extensor digitorium longus.

Patients with chronic obstructive pulmonary disease (COPD) demonstrate a limited exercise capacity. It is unknown whether muscle fiber atrophy and subsequent decrease in force production contributes to this functional limitation. Therefore, the purpose of this investigation was to determine whether emphysema-induced muscle fiber atrophy leads to a reduction in locomotory muscle force production. Maximal muscle force production and fiber cross-sectional area were measured in the almost exclusively fast-twitch extensor digitorium longus muscles at 4 and 8 months following saline (control, n=8/time period) or elastase (emphysema, n=15/time period) instillation in the lungs of hamsters. Excised lung volume increased 145 and 161% with emphysema at 4 and 8 months, respectively (both P<0.01). Muscle mass, maximal force, and fiber cross-section were unaltered at 4 months. However, absolute mass (-15%) and fiber cross-sectional area (-18%) were reduced at 8 months (both P<0.01). Surprisingly, maximal force was preserved in emphysema animals. These data demonstrate that maximal muscle force may be preserved in the face of emphysema-induced fiber atrophy.

BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts.

The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twenty-seven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both P<0.001), and with an HLA-mismatched donor (P<0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0-21.7; P=0.001), MC (OR 6.0; 95% CI 2.1-17.3; P<0.001) and URD (OR 3.4; 95% CI 1.1-10.6; P=0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8-19.3; P=0.004) and MC (OR 5.9; 95% CI 1.3-11.3; P=0.009) increased the risk for HC only with a URD, but not with an RD graft.

Differential effects of emphysema on skeletal muscle fibre atrophy in hamsters.

Patients afflicted with emphysema demonstrate altered peripheral skeletal muscle fibre composition and atrophy. It is unknown whether these alterations are general to all skeletal muscles independent of function, phenotype or oxidative capacity. Therefore, the purpose of this investigation was to determine whether emphysema induces alterations in muscle fibre composition or atrophy in respiratory and locomotory muscles with diverse fibre types and metabolic profiles. Fibre composition and cross-sectional area were measured in selected hindlimb muscles and diaphragm of hamsters following saline (control, n=7) or elastase (emphysema, n=15) instillation. Excised lung volume increased 145% with emphysema. Fibre composition was largely unaltered, with the exception of a 13% reduction in IIB fibres in the tibialis anterior muscle of emphysema animals. Type I fibre size was also mainly unaltered, except for a diminished cross-sectional area in plantaris muscle. However, fibre cross-sectional area of fast-twitch types IIA, IIX and/or IIB fibres was reduced in the caudal biceps femoris, vastus lateralis, tibialis anterior, gastrocnemius and plantaris muscles of emphysema animals. In contrast, there was a trend for emphysema to increase the cross-sectional area of type IIA fibres in the diaphragm. These data demonstrate that emphysema-induced atrophy primarily affects locomotory muscles, independent of phenotype or oxidative capacity.

A group-IV ferromagnetic semiconductor: MnxGe1-x.

We report on the epitaxial growth of a group-IV ferromagnetic semiconductor, Mn(x)Ge(1-x), in which the Curie temperature is found to increase linearly with manganese (Mn) concentration from 25 to 116 kelvin. The p-type semiconducting character and hole-mediated exchange permit control of ferromagnetic order through application of a +/-0.5-volt gate voltage, a value compatible with present microelectronic technology. Total-energy calculations within density-functional theory show that the magnetically ordered phase arises from a long-range ferromagnetic interaction that dominates a short-range antiferromagnetic interaction. Calculated spin interactions and percolation theory predict transition temperatures larger than measured, consistent with the observed suppression of magnetically active Mn atoms and hole concentration.