Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production

Single-gene mutations that extend lifespan provide valuable tools for the exploration of the molecular basis for age-related changes in cell and tissue function and for the pathophysiology of age-dependent diseases. We show here that mice homozygous for loss-of-function mutations at the Pit1 (Snell dwarf) locus show a >40% increase in mean and maximal longevity on the relatively long-lived (C3H/HeJ × DW/J)F1 background. Mutant dwJ/dw animals show delays in age-dependent collagen cross-linking and in six age-sensitive indices of immune system status. These findings thus demonstrate that a single gene can control maximum lifespan and the timing of both cellular and extracellular senescence in a mammal. Pituitary transplantation into dwarf mice does not reverse the lifespan effect, suggesting that the effect is not due to lowered prolactin levels. In contrast, homozygosity for the Ghrhrlit mutation, which like the Pit1dw mutation lowers plasma growth hormone levels, does lead to a significant increase in longevity. Male Snell dwarf mice, unlike calorically restricted mice, become obese and exhibit proportionately high leptin levels in old age, showing that their exceptional longevity is not simply due to alterations in adiposity per se. Further studies of the Pit1dw mutant, and the closely related, long-lived Prop-1df (Ames dwarf) mutant, should provide new insights into the hormonal regulation of senescence, longevity, and late life disease.

Examining retirement housing preferences among international retiree migrants

Housing demand models based on individual consumer’s utility function reflect preferences about the structure and lot, neighborhood, and location as related to socioeconomic characteristics of the occupants. As a growing proportion of aging residents in many countries are undertaking late life moves, their preferences will have an influence on destination housing markets. We examine the characteristics, attitudes and preferences about retirement housing among immigrant retirees currently living in traditional housing in a retirement destination in Alicante, Spain. Using results from a survey of German and British retirees living in the region, we find through logistic regression that preference for retirement housing is associated with aging and gaining access to in-home support services.

Validation of a mobility item bank for older patients in primary care

Background: To develop and validate an item bank to measure mobility in older people in primary care and to analyse differential item functioning (DIF) and differential bundle functioning (DBF) by sex. Methods: A pool of 48 mobility items was administered by interview to 593 older people attending primary health care practices. The pool contained four domains based on the International Classification of Functioning: changing and maintaining body position, carrying, lifting and pushing, walking and going up and down stairs. Results: The Late Life Mobility item bank consisted of 35 items, and measured with a reliability of 0.90 or more across the full spectrum of mobility, except at the higher end of better functioning. No evidence was found of non-uniform DIF but uniform DIF was observed, mainly for items in the changing and maintaining body position and carrying, lifting and pushing domains. The walking domain did not display DBF, but the other three domains did, principally the carrying, lifting and pushing items. Conclusions: During the design and validation of an item bank to measure mobility in older people, we found that strength (carrying, lifting and pushing) items formed a secondary dimension that produced DBF. More research is needed to determine how best to include strength items in a mobility measure, or whether it would be more appropriate to design separate measures for each construct.

The role of morphine-6-glucuronide (M6G) in pain control

Morphine-6beta-D-glucuronide (M6G) is an analgesically active metabolite of morphine, accounting for approximate to10% of the morphine dose when administered by systemic routes to humans. Although M6G is more hydrophilic than morphine, it crosses the blood-brain barrier, albeit relatively slowly. For this reason, it is generally thought that, after chronic dosing, M6G contributes significantly to the analgesic effects of systemically administered morphine. Owing to its polar nature, M6G is cleared from the systemic circulation primarily via renal elimination. As M6G accumulates in patients with renal impairment, there is an increased risk of M6G-induced respiratory depression in renal failure patients who are being dosed chronically with systemic morphine. Consistent with its analgesic and respiratory depressant properties, M6G binds to the p-opioid receptor in a naloxone-reversible manner. Although the affinity of M6G for the mu-opioid receptor is similar to or slightly less than that of morphine, preclinical studies in rodents show that M6G is one to two orders of magnitude more potent than morphine when administered by central routes. This major discrepancy between the markedly higher intrinsic antinociceptive potency of M6G relative to morphine, despite their similar p-opioid receptor binding affinities, is difficult to reconcile. It has been proposed that M6G mediates its pain-relieving effects through a novel 'M6G opioid receptor', while others have argued that M6G may have higher efficacy than morphine for transduction of intracellular events. When administered by parenteral routes to rodents, M6G's antinociceptive potency is no more than twofold higher than morphine. In humans, the analgesic efficacy and respiratory depressant potency of M6G relative to morphine have been assessed in a number of short-term studies involving the intrathecal or intravenous routes of administration. For example, in hip replacement patients, intrathecal M6G provided excellent postoperative analgesia but the occurrence of late respiratory depression in 10% of these patients raised serious concern about safety. In postoperative patients, intravenous M6G administered by means of patient-controlled analgesia (PCA), or bolus plus PCA, produced no analgesia in one study and limited analgesia in another. Similarly, there was a lack of significant analgesia in healthy volunteers who received intravenous M6G for the alleviation of experimental pain (carbon dioxide applied to the nasal mucosa). In contrast, satisfactory analgesia was produced by bolus doses of intravenous M6G administered to patients with cancer pain, and to healthy volunteers with experimentally-induced ischaemic, electrical or thermal (ice water) pain. Studies to date in healthy volunteers suggest that intravenous M6G may be a less potent respiratory depressant and have a lower propensity for producing nausea and vomiting than morphine. However, it is unclear whether equi-analgesic doses of M6G and morphine were compared. Clearly, more extensive short-term trials, together with studies involving chronic M6G administration, are necessary before the potential clinical utility of M6G as an analgesic drug in its own right can be determined.

ESTRESSE, DEPRESSÃO, SATISFAÇÃO SEXUAL, VIVÊNCIAS EMOCIONAIS E QUALIDADE DE VIDA EM PACIENTES DE AMBULATÓRIOS DE REPRODUÇÃO HUMANA

Este estudo teve como objetivos avaliar a Qualidade de Vida (QV), sintomas depressivos, estresse, satisfação sexual e vivências emocionais em pacientes que apresentam infertilidade. Participaram deste estudo 500 pessoas (mulheres e homens), com idade igual ou maior a 18 anos, pacientes de um ambulatório de reprodução humana localizado no Grande ABC Paulista. O estudo utilizou instrumentos de avaliação autoaplicáveis: WHOQOL-Bref, BDI-II, ISQ, ICQ, ISS e questionário sócio-demográfico. A caracterização da amostra estudada demostrou alto nível escolar (62,4pc), boa condição econômica (80,2pc, idade superior a 30 anos (82,8pc) e a maioria apresenta infertilidade primária (73,2pc). Quanto à QV, níveis de depressão e estresse os homens apresentam melhores resultados quando comparados às mulheres. No que ser refere aos níveis de satisfação sexual 56,6% dos participantes descrevem ter satisfação sexual, mas 45,4% afirmam ter insatisfação sexual e não houve diferença entre os gêneros. As análises dos dados mostraram que é maior o número de mulheres do que o de homens que procuram atendimento para infertilidade (64,8pc). Pôde-se comprovar que além das dificuldades provenientes da infertilidade, o tratamento, também, impacta sobre a vida dessas pessoas. Foram diversos participantes que descreveram significativas mudanças (42,8pc), dos quais apontaram em maioria absoluta (92,6pc) uma piora no estado de humor devido ao tratamento. Como também é alto o índice de pessoas que descrevem sintomas de depressão (38,8pc) e estresse (31,4pc) acima da média da população geral. Ao considerar as especificidades da qualidade de vida averiguou-se um maior impacto no domínio psicológico dos pacientes (15,20 pontos) comparado ao físico (15,68 pontos). Estes resultados ressaltam a importância do atendimento psicológico para as pessoas em programas de reprodução humana.

Okay Cool No Smoking Love Pony

This poetry collection moves from the narrator’s childhood in the marshes of Canada to her coming of age in a new, southern swamp in South Florida. Many of the poems use free verse as well as fairly recent poetic forms like the Golden Shovel and the Pecha Kucha. Others rely on wordplay and nonce forms. Influenced by Hector Veil Temperly, Matthew Zapruder, Dorothea Lasky, Laura Kasischke and Anne Carson, the poems often employ simple language in stream of consciousness, and oscillate between lyric and narrative. These poems are feverish creations inspired by the oracular tradition and induced by the psychic crush of modern life: depression of the body and mind, cultural paranoia, and the decline of nature. The reader is privy not only to the personal biography of the narrator, but also to the inner workings of the narrator’s mind as it encounters and interprets the world.

Rede Social Pessoal, Qualidade de Vida e Depressão em Idosos

Em Portugal e no Mundo Ocidental a população está a envelhecer, colocando esta nova realidade enormes desafios à sociedade. A sua crescente relevância deve-se sobretudo às consideráveis repercussões a nível pessoal, familiar, sociopolítico e económico e que afetam pessoas de todas as idades e a sociedade como um todo, colocando desafios específicos relativamente às relações interpessoais, à qualidade de vida e à saúde mental na pessoa idosa. Deste modo, o presente trabalho tem como objetivo analisar a associação entre a qualidade de vida, a depressão e as características das redes sociais pessoais dos idosos. Participaram no estudo 317 indivíduos, sendo 202 do sexo feminino e 115 do sexo masculino, com idade igual ou superior a 65 anos, com uma média de 77 anos (DP=7,57). Na recolha de dados recorremos a três instrumentos: Geriatric Depression Scale (GDS Short Form 15), (Yesavage et al., 1983; Almeida & Almeida, 1999); Instrumento de Avaliação de Qualidade de Vida da OMS (WHOQOL), (OMS, 1998; Canavarro et al., 2006); Instrumento de Avaliação das Redes Sociais Pessoais (IARSP – Idosos), (Guadalupe, 2010; Guadalupe & Vicente, 2012). Dos resultados destacamos que as características funcionais da rede social pessoal se diferenciaram de forma estatisticamente significativa entre as subamostras de idosos segundo os níveis de qualidade de vida percebida. Saliente-se que, além da relação significativa entre a depressão e qualidade de vida, em que os idosos com um nível mais baixo de qualidade de vida percebida apresentam maiores níveis de depressão (p<0,001), as características funcionais das redes sociais apresentam uma associação clara com a qualidade de vida (p<0,005) e a maioria com a depressão (p<0,014), o que não acontece com as estruturais e com as relacionais-contextuais. Outros resultados indicam que indivíduos com diferentes níveis de qualidade de vida percebida possuem uma estrutura idêntica da rede social pessoal. Ao nível da análise da associação entre as variáveis funcionais da Rede Social Pessoal, Qualidade de Vida e Depressão, o modelo analítico transmite-nos indicadores de investigação e intervenção precisos, o que demonstra a necessidade da continuidade e aprofundamento do presente estudo num âmbito amostral mais alargado e heterogéneo. / In Portugal and in the eastern world, the aging of population creates huge challenges to societies. It's growing relevance is owed to considerable repercussions on the personal, familiar, socio-politic and economic level that affect people of all ages and society as a whole, creating specific challenges regarding interpersonal relationships, quality of life and mental health of the elderly. The current work has the objective of analyzing the association between quality of life, depression and the characteristics of personal social networks of the elderly. 317 individuals have participated in this study, 202 female and 115 male, with age equal or above 65 years old, with an average of 77 years old (DP=7,57). We used three assessment instruments to collect data: Geriatric Depression Scale (GDS Short Form 15), (Yesavage et al., 1983; Almeida & Almeida, 1999); WHO’s Quality of Life Evaluation instrument (WHOQOL) (WHO, 1998; Canavarro et al., 2006); Personal Social Network Analysis Tool (IARSP-Elderly),(Guadalupe, 2010; Guadalupe & Vicente, 2012). The results show that the functional personal network characteristics are significantly different according to their level of quality of life. It should also be noted that not only there is a significant association between depression and quality of life, in which elderly people with a lower quality of life level show higher levels of depression (p<0,001), there is also a clear association between the functional social network characteristics and quality of life (p<0,005), and the majority with depression (p<0,014), which doesn’t happen with structural and relational-contextual social network characteristics. Other results indicate that different levels of quality of life acquire an identical social network structure. On the matter of association between the functional variables of social networks, quality of fife and depression, the analytic model shows precise indicators of research and intervention, which instills us a need to continue and enlarge this study with an wider and more heterogeneous sample.

Le succès reproducteur au début de la vie, la longévité et le succès reproducteur tardif chez la femelle de la chèvre de montagne

La théorie biodémographique liée à l’âge prédit un compromis entre l’allocation reproductrice au début de la vie et la reproduction tardive, la survie, ou ces deux composantes de la valeur adaptative à la fois. Actuellement, la notion de compromis a été démontrée par plusieurs études en milieu naturel. Par contre, l’effet des conditions environnementales et de la qualité des individus a rarement été étudié. Grâce aux données longitudinales récoltées dans la population de chèvres de montagne (Oreamnos americanus) de Caw Ridge, Alberta, nous avons pu examiner l’influence de l’âge à la première reproduction (APR) et du succès reproducteur au début de la vie (SRD) sur la longévité et sur le succès reproducteur tardif, en tenant compte des conditions environnementales natales et de la qualité des individus. Contrairement à nos prédictions, nous n’avons pas détecté la présence d’un compromis entre l’allocation reproductrice au début de la vie et la performance tardive dans cette population. Au contraire, l’APR et le SRD avaient des effets directs et faiblement positifs sur le succès reproducteur tardif. La densité de population à la naissance d’une femelle a fortement réduit le succès reproducteur tardif de manière directe. Elle l’affectait également de manière indirecte par son effet sur l’APR et le SRD. La densité était le seul facteur déterminant de la longévité, par un effet direct et fortement négatif. Tel que démontré dans des études précédentes sur la même population, les femelles de bonne qualité avaient un SRD élevé par rapport aux femelles de mauvaise qualité. Ces résultats fournissent une vision intégrée des compromis au début et à la fin de la vie, en soulignant l’importance de tenir compte des conditions environnementales, qui pourraient engendrer des implications à long terme sur la dynamique des populations.

Impacto de la resiliencia en pacientes con Artritis Reumatoide

Introducción: La artritis reumatoide (AR) es una enfermedad autoinmune-inflamatoria, que compromete las articulaciones diartrodiales. Tiene una importante repercusión sistémica que incluye la depresión; por lo tanto, tiene un severo impacto sobre la calidad de vida. Es posible que mecanismos de defensa, tales como la resiliencia, puedan amortiguar dicho impacto. Metodología: estudio de corte transversal, multicéntrico (análisis inicial dentro del grupo AR, con muestra no probabilística de 66 pacientes, posterior selección aleatoria simple de 16 pacientes de la muestra inicial y selección de 16 individuos sanos pareados). Posteriormente, se comparó la resiliencia entre sujetos con AR y sujetos sanos, mediante las escalas RS y CD-RISC25. Adicionalmente, se aplicaron las escalas EEAE, EADZ, SF-36 y PANAS. Los datos fueron evaluados mediante el coeficiente de correlación de Spearman, las pruebas U Mann-Whitney, Kruskall-Wallis, T de Student y análisis de varianza. Resultados: se encontraron diferencias significativas en las estrategias de afrontamiento no espirituales en grupos de resiliencia baja, media y alta; diferencias en las medianas de resiliencia en los grupos de depresión por EAZD en los pacientes. No se encontraron resultados significativos en las variables clínicas de la AR ni en la comparación con sujetos sanos. Conclusiones: el uso de estrategias de afrontamiento no espirituales y la ausencia de depresión, se asoció a mayores niveles de resiliencia en los pacientes con AR, por lo cual, los componentes emocionales y cognitivos se asocian a la resiliencia.

Ideación suicida y desesperanza en pacientes con cáncer

El objetivo de la presente investigación fue identificar la relación entre ideación suicida y desesperanza en 160 pacientes con cáncer. La ideación suicida se midió a través de dos ítems de una entrevista semiestructurada, la escala de ideación suicida (ISS), el ítem 9 del inventario de depresión de Beck (BDI-IA). La desesperanza se midió con la escala de desesperanza de Beck (BHS). Los resultados obtenidos indicaron una relación significativa (p=.000) entre ideación suicida y desesperanza; una prevalencia de ideación suicida en los pacientes con cáncer entre 4.4% y 13.8% y de riesgo de suicidio entre 5.6% y 30.6%; y algún grado de desesperanza en 31.9 % de los participantes. De acuerdo con lo anterior, se confirma que existe relación entre la desesperanza y la ideación suicida en pacientes oncológicos adultos. Adicionalmente, que estas variables están presentes en los pacientes y que ameritan atención en la intervención interdisciplinaria.

The impact of perceived stage of cancer on carers’ anxiety and depression during the patients’ final year of life

Objective: This paper explores the effects of perceived stage of cancer (PSOC) on carers' anxiety and depression during the patients' final year. Methods: A consecutive sample of patients and carers (N=98) were surveyed at regular intervals regarding PSOC, and anxiety and depression using the Hospital Anxiety and Depression Scale. Means were compared by gender using the Mann-Whitney U-test. The chi-square was used to analyse categorical data. Agreement between carers' and patients' PSOC was estimated using kappa statistics. Correlations between carers' PSOC and their anxiety and depression were calculated using the Spearman's rank correlation. Results: Over time, an increasing proportion of carers reported that the cancer was advanced, culminating at 43% near death. Agreement regarding PSOC was fair (kappa=0.29-0.34) until near death (kappa=0.21). Carers' anxiety increased over the year; depression increased in the final 6 months. Females were more anxious (p=0.049, 6 months; p=0.009, 3 months) than males, and more depressed until 1 month to death. The proportion of carers reporting moderate-severe anxiety almost doubled over the year to 27%, with more females in this category at 6 months (p=0.05). Carers with moderate-severe depression increased from 6 to 15% over the year. Increased PSOC was weakly correlated with increased anxiety and depression. Conclusions: Carers' anxiety exceeded depression in severity during advanced cancer. Females generally experienced greater anxiety and depression. Carers were more realistic than patients regarding the ultimate outcome, which was reflected in their declining mental health, particularly near the end.

Low birth weight in MZ twins discordant for birth weight is associated with shorter telomere length and lower IQ, but not anxiety/depression in later life

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Depression and Cognition in Type 2 Diabetes from a Life Course Perspective

Background: Type 2 diabetes is linked to several complications which add to both physical and mental distress. Depression is a common co-morbidity of diabetes which can occur both as a cause and a consequence of type 2 diabetes. Depression has been shown to correlate with glucose regulation and treating depression might prove beneficial for glucose regulation as well as for mental well being. Another complication which might affect diabetes management is cognitive decline. Several risk factors and complications of diabetes might modify the risk for developing cognitive impairment, which is increased 1.5 times among subjects with type 2 diabetes. Type 2 diabetes, depression and impaired cognitive performance have all been linked to low birth weight. This thesis aimed to explore the effects and interactions of birth weight, depression and cognitive ability in relation to type 2 diabetes from a life course perspective. Subjects and methods: Studies I, II and V were part of the Helsinki Birth Cohort Study. 2003 subjects participated in an extensive clinical examination at an average age of 61 years. A standard glucose tolerance test (OGTT) was performed and depressive symptoms were assessed using the Beck Depression Inventory (BDI). In addition data was obtained from child welfare clinics and national registers. A subset of the cohort (n=1247) also performed a test on cognitive performance (CogState ®) at the average age of 64. Studies III and IV were randomised clinical trials where mildly depressed diabetic subjects were treated with paroxetine or placebo and the effect on metabolic parameters and quality of life was assessed. The first trial included 14 women and lasted 10 weeks, while the second trial included 43 subjects, both men and women, and lasted 6 months. Results: Type 2 diabetes was positively associated with the occurrence of depressive symptoms. Among diabetic subjects 23.6% had depressive symptoms, compared to 16.7% of subjects with normal glucose tolerance (OR = 1.77, p<0.001). Formal mediation analysis revealed that cardiovascular disease (CVD) is likely to act as a mediator in the association. Furthermore, low birth weight was found to modify the association between type 2 diabetes, CVD and depression. The association between BDI score and having type 2 diabetes or CVD was twice as strong in the subgroup with low birth weight (≤ 2500g) compared with the group with birth weight > 2500g (p for interaction 0.058). In the six months long randomised clinical trial (study IV) paroxetine had a transient beneficial effect on glycosylated haemoglobin A1c (GHbA1c) and quality of life when compared to placebo after three months of treatment. In study V we found that subjects with known diabetes had a consistently poorer level of cognitive performance than subjects with normal glucose tolerance in most of the tested cognitive domains. This effect was further amplified among those born with a small birth weight (p for interaction 0.002). Conclusions: Type 2 diabetes is associated with a higher occurrence of depressive symptoms compared to subjects with normal glucose tolerance. This association is especially strong among subjects with CVD and those born with a low birth weight. Treating depressed diabetic subjects with paroxetine has no long term effect on glucose regulation. Physicians should be aware of depression as an important co-morbidity of type 2 diabetes. Both depression and the cognitive decline often seen among diabetic subjects are increased if the subject is born with a low birth weight. Physicians should recognise low birth weight as an additional risk factor and modifier of diabetic complications.

Island life in the Cretaceous - faunal composition, biogeography, evolution, and extinction of land-living vertebrates on the Late Cretaceous European archipelago

The Late Cretaceous was a time of tremendous global change, as the final stages of the Age of Dinosaurs were shaped by climate and sea level fluctuations and witness to marked paleogeographic and faunal changes, before the end-Cretaceous bolide impact. The terrestrial fossil record of Late Cretaceous Europe is becoming increasingly better understood, based largely on intensive fieldwork over the past two decades, promising new insights into latest Cretaceous faunal evolution. We review the terrestrial Late Cretaceous record from Europe and discuss its importance for understanding the paleogeography, ecology, evolution, and extinction of land-dwelling vertebrates. We review the major Late Cretaceous faunas from Austria, Hungary, France, Spain, Portugal, and Romania, as well as more fragmentary records from elsewhere in Europe. We discuss the paleogeographic background and history of assembly of these faunas, and argue that they are comprised of an endemic 'core' supplemented with various immigration waves. These faunas lived on an island archipelago, and we describe how this insular setting led to ecological peculiarities such as low diversity, a preponderance of primitive taxa, and marked changes in morphology (particularly body size dwarfing). We conclude by discussing the importance of the European record in understanding the end-Cretaceous extinction and show that there is no clear evidence that dinosaurs or other groups were undergoing long-term declines in Europe prior to the bolide impact.