Person-centred care in the context of higher education - a discourse analysis based on interviews with programme directors.

BACKGROUND: As person centred care (PCC) is being implemented globally, higher educational institutions (HEI) have begun to play a crucial part in enabling this transition. In Sweden, however, the delivery of PCC is inconsistently implemented in medicine, nursing, occupational therapy, and physiotherapy study programmes. This inconsistency is partly the result of a lack of a national strategy across HEI. Program directors are responsible for the PCC content of their programs, so their views influence how PCC is taught. Using interviews with programme directors in higher education, we aim to deepen the understanding of the preconditions needed to implement PCC by exploring discourses and identifying subject positions of how PCC is taught and learned. METHODS: We performed a discourse analysis based on interviews with program directors in the above-mentioned national study programmes. A discourse can be seen as a struggle over identity. The subject position - i.e., discourses designate positions for persons to occupy as subjects - guided our analysis and identification of the subject positions of the teacher and the student in teaching and learning PCC. RESULTS: This study unfolded in two main antagonistic aspects with respect to teaching and learning PCC, resulting in four subject positions for the teacher and four corresponding subject positions for the students. First, the teacher and student were given a subject position as change agents towards a more egalitarian healthcare and were assigned a subject position to cope with a practical reality they could not change. Second, the teacher and student were assigned a subject position that embodied profession-specific identities, navigating and valuing these boundaries. Simultaneously, both teachers and students assumed a subject position that required interprofessional interaction and co-creation for teaching and learning PCC. CONCLUSION: This study demonstrates the discursive tension surrounding the implementation of PCC in HEI, and the findings can serve as a basis for creating future relevant and high-quality learning activities. The process of negotiating diverse and co-existing perspectives as well as building interprofessional trust when incorporating PCC into higher education is essential and requires further exploration.

Person-centred care on the move - an interview study with programme directors in Swedish higher education.

BACKGROUND: There is an increasing trend towards person-centred care (PCC) worldwide, suggesting that PCC should be mastered by future health care professionals. This study aims to explore programme directors' views on facilitators and barriers to implementing PCC in four of the largest national study programmes in Sweden training future health care professionals. METHODS: A qualitative design was applied and interviews were conducted with 19 programme directors of Swedish national study programmes in medicine, nursing, occupational therapy and physiotherapy. The interviews were analysed using qualitative content analysis. Themes were sorted according to the Consolidated Framework for Implementation Research (CFIR) in an abductive approach. COREQ guidelines were applied. RESULTS: The overarching theme, as interpreted from the programme directors' experiences, was 'Person-centred care is on the move at different paces.' The theme relates to the domains identified by the CFIR as outer setting, innovation, inner setting and process. PCC was understood as something familiar but yet new, and the higher education institutions were in a state of understanding and adapting PCC to their own contexts. The movement in the outer setting consists of numerous stakeholders advocating for increased patient influence, which has stirred a movement in the inner setting where the higher educational institutions are trying to accommodate these new demands. Different meanings and values are ascribed to PCC, and the concept is thus also 'on the move', being adapted to traditions at each educational setting. CONCLUSION: Implementation of PCC in Swedish higher education is ongoing but fragmented and driven by individuals with a specific interest. There is uncertainty and ambiguity around the meaning and value of PCC and how to implement it. More knowledge is needed about the core of PCC as a subject for teaching and learning and also didactic strategies suitable to support students in becoming person-centred practitioners.

X-Ray Absorption Spectrum of the N_{2}

The x-ray absorption spectrum of N_{2}^{+} in the K-edge region has been measured by irradiation of ions stored in a cryogenic radio frequency ion trap with synchrotron radiation. We interpret the experimental results with the help of restricted active space multiconfiguration theory. Spectroscopic constants of the 1σ_{u}^{-1} ^{2}Σ_{u}^{+} state, and the two 1σ_{u}^{-1}3σ_{g}^{-1}1π_{g} ^{2}Π_{u} states are determined from the measurements. The charge of the ground state together with spin coupling involving several open shells give rise to double excitations and configuration mixing, and a complete breakdown of the orbital picture for higher lying core-excited states.

Complications and number of follow-up visits after using septal stapler in septoplasty.

BACKGROUND: Septoplasties have traditionally been closed with transseptal sutures, silicone splints, or packing with nasal tamponade. In 2015, our clinic began to employ a septal stapler. The stapler adheres the mucosa to the septal cartilage with bioresorbable staples, replacing both sutures and silicone splints and limiting the use of nasal tamponade for bleeding cases. The complications of stapler versus other methods have not been reported on previously. Thus, the aim of this study was to investigate whether the use of stapler in septoplasties makes a difference in complication rates, operation time, or number of follow-up visits when compared to the traditional closure or filling methods. METHODOLOGY: Patient records from 101 septoplasties in which the stapler had been used, and a reference group of 356 septoplasties in which the stapler had not been used, were retrospectively reviewed and analysed. RESULTS: No significant difference was seen in the complication rate between the stapler and the control group. Overall follow-up visits were fewer in the stapler group when compared to the control group, however there was no significant difference in the number of unplanned follow-up visits between the groups. CONCLUSIONS: By using the stapler in septoplasty, the number of postoperative follow-up visits might be reduced. Neither complication rate, nor operation time differed when using the stapler as compared to the traditional methods of closure.

Similar survival outcome after endoscopic and open approaches for sinonasal mucosal melanoma.

BACKGROUND: To describe a cohort of sinonasal mucosal melanoma (SNMM) patients, and to assess if choice of surgical approach (open versus endoscopic) has impact on survival. METHODOLOGY: Adequate data on clinical presentation, treatment, and recurrence pattern were available for 58 consecutive patients treated for SNMM at the Helsinki University Hospital (HUH) between 1983 and 2016. RESULTS: The 5-year disease-specific survival (DSS) was 27% and overall survival 25% for the whole cohort. The 3-year DSS for patients treated with curative intent with endoscopic surgery was comparable to open surgery (56% and 51%, respectively). Patients with tumours arising from the paranasal sinuses and patients with Stage IV disease had significantly worse prognosis compared with other locations and Stage III patients. All patients who had disease persistence at three months after primary treatment succumbed to SNMM. Post-operative radiotherapy did not affect survival significantly, but a trend towards improved local control was observed. CONCLUSIONS: Local control after endoscopic surgery was comparable to open surgery. Small tumours without local or locoregional spread had improved prognosis, independent of surgical approach. Disease persistence after treatment with curative intent led to death invariably.

Smokeless tobacco (snus) is associated with an increased risk of type 2 diabetes: results from five pooled cohorts.

BACKGROUND: Smoking and nicotine exposure increase insulin resistance and the risk of type 2 diabetes. Swedish smokeless tobacco (snus) is high in nicotine, and its use is prevalent in Scandinavian countries, but few studies have investigated snus use in relation to diabetes risk. OBJECTIVE: To explore the association between snus use and risk of type 2 diabetes using pooled data from five cohorts. METHODS: Analyses were based on prospective studies conducted between 1990 and 2013 including 54 531 never-smoking men and 2441 incident cases of type 2 diabetes identified through screening, self-reporting and hospital and prescription registries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed and adjusted for age, body mass index, educational level, alcohol consumption and physical activity. RESULTS: Compared to never users, the HR of type 2 diabetes was 1.15 (95% CI: 1.00-1.32) in current users of snus. In individuals consuming 5-6 boxes per week, the HR was 1.42 (95% CI: 1.07-1.87); in those consuming ≥7 boxes per week, the HR was 1.68 (95% CI: 1.17-2.41). Each additional box of snus consumed per week yielded an HR of 1.08 (95% CI: 1.01-1.16). CONCLUSION: Our findings indicate that high consumption of snus is a risk factor for type 2 diabetes. The risk was similar to that in smokers, implying that smokers will not reduce their risk of type 2 diabetes by changing to snus use. The results also support the notion that nicotine increases the risk of type 2 diabetes.

Studies on the antibody response and side effects after intramuscular and intraperitoneal injection of Atlantic lumpfish (Cyclopterus lumpus L.) with different oil-based vaccines.

Atlantic lumpfish (Cyclopterus lumpus L.) is used as a biological delousing agent for sea lice (Lepeophtheirus salmonis K.) infestations in Norwegian aquaculture. Here, we present a study on the antibody response and vaccine side effects after intramuscular and intraperitoneal injection of lumpfish with two vaccines. Both vaccines contained bacterial antigens from atypical Aeromonas salmonicida A-layer types V and VI, Vibrio anguillarum serotype O1 and Moritella viscosa sp., but one vaccine contained a vegetable oil-based adjuvant, while the other contained a mineral oil-based adjuvant. Intramuscular injection of the mineral oil-based vaccine caused a high acute mortality of fish within 48 hr after immunization. Intraperitoneal injection of the mineral oil-based vaccine resulted in a lower severity of intra-abdominal side effects than the vegetable oil-based vaccine. Intramuscular injection of the mineral oil-based vaccine resulted in a significantly higher antibody response against A. salmonicida when compared to controls and the vegetable oil-based vaccine group. The antibody response was poor against V. anguillarum and M. viscosa for all groups. Our results indicate that intramuscular injection of oil-based vaccines might be feasible for providing immunological protection for Atlantic lumpfish against bacterial diseases, especially atypical A. salmonicida, but more work is required to identity optimal adjuvants.

Ability to perform a single heel-rise is significantly related to patient-reported outcome after Achilles tendon rupture.

This study evaluated the short-term recovery of function after an acute Achilles tendon rupture, measured by a single-legged heel-rise test, with main emphasis on the relation to the patient-reported outcomes and fear of physical activity and movement (kinesiophobia). Eighty-one patients treated surgically or non-surgically with early active rehabilitation after Achilles tendon rupture were included in the study. Patient's ability to perform a single-legged heel-rise, physical activity level, patient-reported symptoms, general health, and kinesiophobia was evaluated 12 weeks after the injury. The heel-rise test showed that 40 out of 81 (49%) patients were unable to perform a single heel-rise 12 weeks after the injury. We found that patients who were able to perform a heel-rise were significantly younger, more often of male gender, reported a lesser degree of symptoms, and also had a higher degree of physical activity at 12 weeks. There was also a significant negative correlation between kinesiophobia and all the patient-reported outcomes and the physical activity level. The heel-rise ability appears to be an important early achievement and reflects the general level of healing, which influences patient-reported outcome and physical activity. Future treatment protocols focusing on regaining strength early after the injury therefore seem to be of great importance. Kinesiophobia needs to be addressed early during the rehabilitation process.

Adolescents' experiences of Help Overcoming Pain Early-A school based person-centred intervention for adolescents with chronic pain.

To illuminate adolescents' experiences of Help Overcoming Pain Early (HOPE), a person-centred intervention delivered in a school setting by school nurses. Twenty-one adolescents with chronic pain recruited from secondary school, who had completed the HOPE intervention, were included in the interview study. The HOPE intervention was built on person-centred ethics and consisted of four meetings between school nurses and adolescents on the subject of stress and pain management. A qualitative method using content analysis with an inductive approach was employed. In the interviews, the adolescents describe how they reclaim their lives with the help of HOPE. They use different strategies and parts of the intervention to move on with their lives. A trustful relationship, as that with the school nurse, was essential to dare to change. The overarching theme summarizes in Becoming myself again and is built up by three sub-themes: Trust a pillar for growth, Making sense of my life with pain, and Putting myself into the world again. A person-centred intervention such as HOPE applied in a school context is promising for promoting confidence in adolescents with chronic pain. A trust-building process emerged, in terms of both the adolescents' trust in the healthcare staff they meet and their confidence in their own ability to handle and influence their situation, which in the long term can promote trust in themselves as a person.

Unmet challenges in septoplasty-nordic studies from a uniform healthcare and geographical area.

Purpose: Nasal septoplasty is one of the most common surgical procedures in otorhinolaryngology and optimising both patient selection and the surgery is a challenge. The Nordic countries have similar public healthcare systems and comparable populations in terms of size. Methods: This is a review of studies of outcome and predictors related to septoplasty from Denmark, Finland, Norway and Sweden, published during the last decade. The aim of this review was to identify areas in need of further research to meet the challenges of septoplasty in the Nordic countries with reference to international data. Results: Postoperative patient satisfaction at 6-12 months was reported in around 2/3 of the patients and well in line with international data. Patients with more severe symptoms had a higher chance of improvement. Lack of standardisation in patient selection, surgical methods and skills, and follow up procedures, still makes it difficult to explain the 25% failure rate in septoplasty surgery. Conclusion: This review of the Nordic studies from the last decade shows that septoplasty in general is effective in relieving nasal obstruction. There is a need for studies addressing the standardisation of diagnostic tools and algorithms and the systematic and continuous implementation of follow-up of the surgical results at both departmental and personal level. This includes an awareness of how surgical skills in septoplasty are obtained and maintained.

Characterization of a divergent chromosome region in the willow warbler Phylloscopus trochilus using avian genomic resources.

Genome scans have made it possible to find outlier markers thought to have been influenced by divergent selection in almost any wild population. However, the lack of genomic information in nonmodel species often makes it difficult to associate these markers with certain genes or chromosome regions. Furthermore, the extent of linkage disequilibrium (LD) in the genome will determine the density of markers required to identify the genes under selection. In this study, we investigated a chromosome region in the willow warbler Phylloscopus trochilus surrounding a single marker previously identified in a genome scan. We first located the marker in the assembled genome of another species, the zebra finch Taeniopygia guttata, and amplified surrounding sequences in Fennoscandian willow warblers. Within an investigated chromosome region of 7.3 Mb as mapped to the zebra finch genome, we observed elevated genetic differentiation between a southern and a northern population across a 2.5-Mb interval comprising numerous coding genes. Within the southern and northern populations, higher values of LD were mostly found between SNPs within the same locus, but extended across distantly situated loci when the analyses were restricted to sampling sites showing intermediate allele frequencies of southern and northern alleles. Our study shows that cross-species genome information is a useful resource to obtain candidate sequences adjacent to outlier markers in nonmodel species.

Large differences in levodopa dose requirement in Parkinson's disease: men use higher doses than women.

BACKGROUND AND PURPOSE: The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low-dose and high-dose patients with Parkinson's disease (PD) in a university hospital. METHODS: Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with at least 5 years of PD duration. RESULTS: In total, 33 534 levodopa users with > or = 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. CONCLUSIONS: We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients.

Inception of electronic damage of matter by photon-driven post-ionization mechanisms.

"Probe-before-destroy" methodology permitted diffraction and imaging measurements of intact specimens using ultrabright but highly destructive X-ray free-electron laser (XFEL) pulses. The methodology takes advantage of XFEL pulses ultrashort duration to outrun the destructive nature of the X-rays. Atomic movement, generally on the order of >50 fs, regulates the maximum pulse duration for intact specimen measurements. In this contribution, we report the electronic structure damage of a molecule with ultrashort X-ray pulses under preservation of the atoms' positions. A detailed investigation of the X-ray induced processes revealed that X-ray absorption events in the solvent produce a significant number of solvated electrons within attosecond and femtosecond timescales that are capable of coulombic interactions with the probed molecules. The presented findings show a strong influence on the experimental spectra coming from ionization of the probed atoms' surroundings leading to electronic structure modification much faster than direct absorption of photons. This work calls for consideration of this phenomenon in cases focused on samples embedded in, e.g., solutions or in matrices, which in fact concerns most of the experimental studies.

p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes.

Myocyte cell loss is a prominent and important pathogenic feature of cardiac ischemia. We have used cultured neonatal rat cardiac myocytes exposed to prolonged hypoxia as an experimental system to identify critical factors involved in cardiomyocyte death. Exposure of myocytes to hypoxia for 48 h resulted in intranucleosomal cleavage of genomic DNA characteristic of apoptosis and was accompanied by increased p53 transactivating activity and protein accumulation. Expression of p21/WAF-1/CIP-1, a well-characterized target of p53 transactivation, also increased in response to hypoxia. Hypoxia did not cause DNA laddering or cell loss in cardiac fibroblasts. To determine whether the increase in p53 expression in myocytes was sufficient to induce apoptosis, normoxic cultures were infected with a replication-defective adenovirus expressing wild-type human p53 (AdCMV.p53). Infected cells expressed high intracellular levels of p53 protein and exhibited the morphological changes and genomic DNA fragmentation characteristic of apoptosis. In contrast, no genomic DNA fragmentation was observed in myocytes infected with the control virus lacking an insert (AdCMV.null) or in cardiac fibroblasts infected with AdCMV.p53. These results suggest that the intracellular signaling pathways activated by p53 might play a critical role in the regulation of hypoxia-induced apoptosis of cardiomyocytes.

Treatment process for MSW combustion fly ash laboratory and pilot plant experiments.

Fly ash from combustion of municipal solid waste sometimes contains large amounts of soluble salts, such as NaCl, even though the content of soluble toxic metal compounds is relatively low. Removal of the salts by washing with water has been suggested as a method to increase the stability of this type of ash. In the work presented here, a simple washing process was studied and evaluated. The process includes three steps: leaching with water, filtration and displacement washing. Basic data were obtained in laboratory experiments and used in the construction of pilot plant equipment at a full size fluidized bed boiler, where a side-stream of the cyclone ash was treated. The process was designed to minimize the water consumption while obtaining an effective removal of salts and a stable ash residue. In order to achieve this, recirculation of leaching liquor was used and the displacement washing was adjusted to become close to ideal. The results showed that an ash/water slurry with a liquid to solid ratio as low as 3 could be handled without difficulty in the mixing, pumping and filtration units. Washing of the filter cake at a liquid to solid ratio of 0.5 removed the major part of the remaining dissolved salts in the pore liquid. About 90% of the chloride content was removed from the ash, whereas the contents of Na, K, Ca, Cd, Pb and a number of other minor elements were removed by 10-30%. Before treatment, the results of ash leaching tests were sometimes too high for chloride (2003/33/EC), but the treatment reduced the amount of soluble chlorides to far below the limit values. The leachability of most metals was reduced or unaffected by the ash treatment. For Na, K and Cl, it was less than 10% of the value for the untreated ash. However, the results showed that some ash components may be mobilized by the washing. Antimony is the most important due to its toxicity.

ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells.

Ischemia induces apoptosis as well as necrosis of cardiac myocytes. We recently reported the cloning of a cDNA that encodes an apoptotic inhibitor, ARC, that is expressed predominantly in cardiac and skeletal muscle. In the present study, we examined the ability of ARC to protect rat embryonic heart-derived H9c2 cells from apoptosis induced by hypoxia, a component of ischemia. We found that H9c2 cells express ARC and that exposure to hypoxia substantially reduces ARC expression while inducing apoptosis. Transfected H9c2 cells in which cytosolic ARC protein levels remain elevated during hypoxia were significantly more resistant to hypoxia-induced apoptosis than parental H9c2 cells or H9c2 cells transfected with a control vector. Loss of endogenous ARC in the cytosol of H9c2 cells was associated with translocation of ARC from the cytosol to intracellular membranes, release of cytochrome c from the mitochondria, activation of caspase-3, poly(ADP-ribose)polymerase (PARP) cleavage, and DNA fragmentation. All of these events were inhibited in H9c2 cells overexpressing ARC when compared with control cells. In contrast, caspase inhibitors prevented PARP cleavage but not cytochrome c release, suggesting that exogenously expressed ARC acts upstream of caspase activation in this model of apoptosis. These results demonstrate that ARC can protect heart myogenic H9c2 cells from hypoxia-induced apoptosis, and that ARC prevents cytochrome c release by acting upstream of caspase activation, perhaps at the mitochondrial level.

The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3'-kinase.

Recent studies have shown that chronic beta-adrenergic receptor (beta-AR) stimulation alters cardiac myocyte survival in a receptor subtype-specific manner. We examined the effect of selective beta(1)- and beta(2)-AR subtype stimulation on apoptosis induced by hypoxia or H(2)O(2) in rat neonatal cardiac myocytes. Although neither beta(1)- nor beta(2)-AR stimulation had any significant effect on the basal level of apoptosis, selective beta(2)-AR stimulation protected myocytes from apoptosis. beta(2)-AR stimulation markedly increased mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activation as well as phosphatidylinositol-3'-kinase (PI-3K) activity and Akt/protein kinase B phosphorylation. beta(1)-AR stimulation also markedly increased MAPK/ERK activation but only minimally activated PI-3K and Akt. Pretreatment with pertussis toxin blocked beta(2)-AR-mediated protection from apoptosis as well as the beta(2)-AR-stimulated changes in MAPK/ERK, PI-3K, and Akt/protein kinase B. The selective PI-3K inhibitor, LY 294002, also blocked beta(2)-AR-mediated protection, whereas inhibition of MAPK/ERK activation at an inhibitor concentration that blocked agonist-induced activation but not the basal level of activation had no effect on beta(2)-AR-mediated protection. These findings demonstrate that beta(2)-ARs activate a PI-3K-dependent, pertussis toxin-sensitive signaling pathway in cardiac myocytes that is required for protection from apoptosis-inducing stimuli often associated with ischemic stress.

HIV prevention among injecting drug users: three years of experience from a syringe exchange program in Sweden.

Exchange of syringes and needles has for the last 3 years been offered to injecting drug users as part of an HIV prevention project in a small university town in south Sweden. The program at the local hospital has been visited by 979 drug users, of which 182 have participated on a more regular basis. The typical participant is a 30-year-old male who has injected amphetamine or heroin for at least 10 years. The seroprevalence for HIV among drug users in south Sweden has been maintained at approximately 1% in contrast to up to 60% in subpopulations from other Scandinavian regions with a comparable drug problem. No project participant has become HIV infected during the study period and a reduction in risk behavior has been noted among local drug injectors. The HIV prevention project has attracted many individuals with no previous contact with drug rehabilitation programs; for a number of drug users, the syringe exchange has served as an introduction to such treatment efforts.

Cadmium exposure and end-stage renal disease.

Environmental exposure to cadmium may cause kidney damage and tubular proteinuria. We investigated the relationship between low-level cadmium exposure and end-stage renal disease (ESRD), indicated by renal replacement therapy (RRT), in a Swedish population environmentally or occupationally exposed to cadmium. Based on records of all persons in the population previously or presently employed in cadmium-battery production or residing in cadmium-polluted areas near the battery plants, we defined exposure as high (occupational), moderate (domicile < 2 km from a plant), low (domicile 2 to 10 km from a plant), or no exposure (domicile > 10 km from a plant). Comprehensive data were available for all individuals undergoing RRT since 1978. The annual incidence of RRT increased from 41 per million in the age group 20 to 29 years to 243 per million in the age group 70 to 79 years and was greater in a priori-defined populations with cadmium exposure. Adjusting for age and sex gave an increased Mantel-Haenszel rate ratio (MH-RR) of 1.8 (95% confidence interval [CI], 1.3 to 2.3) for RRT in the cadmium-exposed population compared with the unexposed group; the MH-RR was even higher for women (MH-RR, 2.3; 95% CI, 1.5 to 3.5). Directly age-standardized rate ratios for RRT and cadmium exposure increased from 1.4 (95% CI, 0.8 to 2.0) in the low-exposure group to 1.9 (95% CI, 1.3 to 2.5) and 2.3 (95% CI, 0.6 to 6.0) in the moderate- and high-exposure groups, respectively. We conclude that exposure to occupational or relatively low environmental levels of cadmium appears to be a determinant for the development of ESRD.

Age-related changes in the signaling and function of vascular smooth muscle cells.

Aging is an independent risk factor for the development of atherosclerosis, a vascular abnormality that plays a significant role in the development of many cardiovascular disorders. Animal experiments have demonstrated that aging predisposes the vasculature to advanced atherosclerotic disease and vessel injury and that this predisposition is a function of age-associated changes in the vessel wall itself. Because vascular smooth muscle cells play important roles in the pathogenesis of many vascular disorders, identifying age-associated differences in the way these cells respond to extracellular clues has been an area of active research. Currently, the most remarkable differences in intracellular signaling between vascular smooth muscle cells isolated from young and old animals are related to the control of cell migration through the CamKII pathways and the accelerated transition of older vascular smooth muscle cells from the contractile to the synthetic phenotype. These differences may be due to alternative signaling pathways revealed by the inability of older cells to respond to inhibitors, such as transforming growth factor (TGF)-beta1, or to altered interactions with the extracellular matrix resulting from age-associated shifts in integrin expression or changes in the matrix composition of blood vessels. The exact role that these alterations have in explaining age-associated differences in the response of the vessel wall to injury and its increased susceptibility to developing advanced atherosclerotic lesions remains to be determined but will be guided by studies on intracellular signaling mechanisms.