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Aging is a complex process of damage accumulation causing a functional decline. Several hallmarks of aging have been identified, of which, genomic instability plays a critical role in aging and age-related diseases and closely interacts with other hallmarks of aging. The genome is constantly challenged by exogenous DNA damaging sources, such as ionizing radiation, ultraviolet, and chemicals. But also, endogenous DNA damage caused by alkylation and hydrolysis can lead to chromosomal aberrations, mutations, and epimutations, eventually causing genomic instability and cellular dysfunction. The stressor-induced alterations include chromosomal (chromosome aneuploidy, chromosomal rearrangements, and fragile sites), genomic (increased genetic variability and mutated nucleic acid sequences), replicative (replication stress), and transcriptional impairments. In response to these damages, a wide range of sophisticated repair mechanisms have evolved to repair different types of damage to preserve genomic integrity, such as proper chromosome segregation, efficient DNA damage repair, and faithful DNA replication, to maintain normal function and promote organismal survival. Mammalian DNA damage response systems mainly comprise nonhomologous end joining, homologous recombination, nucleotide excision repair, base excision repair, mismatch repair, direct reversal repair, and translesion DNA synthesis. To ensure genomic stability there is crosstalk and redundancy between the different DNA repair pathways.

BACKGROUND: Non-communicable diseases are a leading cause of health loss worldwide, in part due to unhealthy lifestyles. Metabolic-based diseases are rising with an unhealthy body-mass index (BMI) in rural areas as the main risk factor in adults, which may be amplified by wider determinants of health. Changes in rural environments reflect the need of better understanding the factors affecting the self-ability for making balanced decisions. We assessed whether unhealthy lifestyles and environment in rural neighbourhoods are reflected into metabolic risks and health capability.METHODS: We conducted a community-based cross-sectional study in 15 Portuguese rural neighbourhoods to describe individuals' health functioning condition and to characterize the community environment. We followed a qualitatively driven mixed-method design to gather information about evidence-based data, lifestyles and neighbourhood satisfaction (incorporated in eVida technology), within a random sample of 270 individuals, and in-depth interviews to 107 individuals, to uncover whether environment influence the ability for improving or pursuing heath and well-being.RESULTS: Men showed to have a 75% higher probability of being overweight than women (p-value = 0.0954); and the reporting of health loss risks was higher in women (RR: 1.48; p-value = 0.122), individuals with larger waist circumference (RR: 2.21; IC: 1.19; 4.27), overweight and obesity (RR: 1.38; p-value = 0.293) and aged over 75 years (RR: 1.78; p-value = 0.235; when compared with participants under 40 years old). Metabolic risks were more associated to BMI and physical activity than diet (or sleeping habits). Overall, metabolic risk linked to BMI was higher in small villages than in municipalities. Seven dimensions, economic development, built (and natural) environment, social network, health care, demography, active lifestyles, and mobility, reflected the self-perceptions in place affecting the individual ability to

BACKGROUND: Non-communicable diseases are a leading cause of health loss worldwide, in part due to unhealthy lifestyles. Metabolic-based diseases are rising with an unhealthy body-mass index (BMI) in rural areas as the main risk factor in adults, which may be amplified by wider determinants of health. Changes in rural environments reflect the need of better understanding the factors affecting the self-ability for making balanced decisions. We assessed whether unhealthy lifestyles and environment in rural neighbourhoods are reflected into metabolic risks and health capability.METHODS: We conducted a community-based cross-sectional study in 15 Portuguese rural neighbourhoods to describe individuals' health functioning condition and to characterize the community environment. We followed a qualitatively driven mixed-method design to gather information about evidence-based data, lifestyles and neighbourhood satisfaction (incorporated in eVida technology), within a random sample of 270 individuals, and in-depth interviews to 107 individuals, to uncover whether environment influence the ability for improving or pursuing heath and well-being.RESULTS: Men showed to have a 75% higher probability of being overweight than women (p-value = 0.0954); and the reporting of health loss risks was higher in women (RR: 1.48; p-value = 0.122), individuals with larger waist circumference (RR: 2.21; IC: 1.19; 4.27), overweight and obesity (RR: 1.38; p-value = 0.293) and aged over 75 years (RR: 1.78; p-value = 0.235; when compared with participants under 40 years old). Metabolic risks were more associated to BMI and physical activity than diet (or sleeping habits). Overall, metabolic risk linked to BMI was higher in small villages than in municipalities. Seven dimensions, economic development, built (and natural) environment, social network, health care, demography, active lifestyles, and mobility, reflected the self-perceptions in place affecting the individual ability to

BACKGROUND: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained. METHODS: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases. RESULTS: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation. CONCLUSION: Within the studied EU countries, polypharmacy management was not widely addressed. These results, Jennifer McIntosh and Albert Alonso contributed equally to this work.

BACKGROUND: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained. METHODS: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases. RESULTS: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation. CONCLUSION: Within the studied EU countries, polypharmacy management was not widely addressed. These results, Jennifer McIntosh and Albert Alonso contributed equally to this work.

BACKGROUND: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained. METHODS: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases. RESULTS: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation. CONCLUSION: Within the studied EU countries, polypharmacy management was not widely addressed. These results, Jennifer McIntosh and Albert Alonso contributed equally to this work.

BACKGROUND: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained. METHODS: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases. RESULTS: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation. CONCLUSION: Within the studied EU countries, polypharmacy management was not widely addressed. These results, Jennifer McIntosh and Albert Alonso contributed equally to this work.

BACKGROUND: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained. METHODS: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases. RESULTS: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation. CONCLUSION: Within the studied EU countries, polypharmacy management was not widely addressed. These results, Jennifer McIntosh and Albert Alonso contributed equally to this work.

Udgivelsesdato: 2008-Jun, Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We describe that NPY promotes SVZ neurogenesis. NPY (1 microM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ, as shown by functional autoradiography. Moreover, short exposure to NPY increased immunoreactivity for the phosphorylated form of extracellular signal-regulated kinase 1/2 in the nucleus, compatible with a trigger for proliferation, whereas 6 hours of treatment amplified the phosphorylated form of c-Jun-NH(2)-terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell-based brain therapy. Disclosure of potential conflicts of interest is found at the end of this article.

Udgivelsesdato: 2008-Jun, Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We describe that NPY promotes SVZ neurogenesis. NPY (1 microM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ, as shown by functional autoradiography. Moreover, short exposure to NPY increased immunoreactivity for the phosphorylated form of extracellular signal-regulated kinase 1/2 in the nucleus, compatible with a trigger for proliferation, whereas 6 hours of treatment amplified the phosphorylated form of c-Jun-NH(2)-terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell-based brain therapy. Disclosure of potential conflicts of interest is found at the end of this article.