The influence of neighbourhoods and the social environment on sedentary behaviour in older adults in three prospective cohorts

Sedentary behaviour is an emerging risk factor for poor health. This study aimed to identify ecological determinants of sedentary behaviour, for which evidence is currently scarce. The analysed participants were community dwelling adults aged around 79, 83, and 64 years from, respectively, the Lothian Birth Cohort 1936 (n=271) and the 1930s (n=119) and 1950s (n=310) cohorts of the West of Scotland Twenty-07 study. The outcome measure, percentage of waking time spent sedentary (sedentary time), was measured using an activPAL activity monitor worn continuously for seven days. Potential determinants included objective and subjective neighbourhood measures such as natural space, crime, social cohesion and fear of crime. Other determinants included measures of social participation such as social support, social group membership and providing care. Results from multivariable regression analyses indicated that providing care was associated with reduced sedentary time in retired participants in all cohorts. Fear of crime and perceived absence of services were associated with increased sedentary time for retired 1950s cohort members. Higher crime rates were associated with increased sedentary time in all cohorts but this was not significant after adjustment for socio-demographic characteristics. Most other neighbourhood and social participation measures showed no association with sedentary time

A novel MSMB-related microprotein in the postovulatory egg coats of marsupials

<p>Abstract</p> <p>Background</p> <p>Early marsupial conceptuses differ markedly from those of eutherian mammals, especially during cleavage and early blastocyst stages of development. Additionally, in marsupials the zona pellucida is surrounded by two acellular layers, the mucoid coat and shell, which are formed from secretions from the reproductive tract.</p> <p>Results</p> <p>We report the identification of a novel postovulatory coat component in marsupials, which we call uterinesecreted microprotein (USM). USM belongs to a family of disulfide-rich microproteins of unconfirmed function that is found throughout deuterostomes and in some protostomes, and includes β-microseminoprotein (MSMB) and prostate-associated microseminoprotein (MSMP). We describe the evolution of this family in detail, including USM-related sequences in other vertebrates. The orthologue of <it>USM </it>in the tammar wallaby, <it>USM1</it>, is expressed by the endometrium with a dynamic temporal profile, possibly under the control of progesterone.</p> <p>Conclusions</p> <p>USM appears to have evolved in a mammalian ancestor specifically as a component of the postovulatory coats. By analogy with the known properties of MSMB, it may have roles in regulating sperm motility/survival or in the immune system. However, its C-terminal domain is greatly truncated compared with MSMB, suggesting a divergent function.</p

Expression and protein localisation of IGF2 in the marsupial placenta

<p>Abstract</p> <p>Background</p> <p>In eutherian mammals, genomic imprinting is critical for normal placentation and embryo survival. <it>Insulin-like growth factor 2 </it>(<it>IGF2</it>) is imprinted in the placenta of both eutherians and marsupials, but its function, or that of any imprinted gene, has not been investigated in any marsupial. This study examines the role of <it>IGF2 </it>in the yolk sac placenta of the tammar wallaby, <it>Macropus eugenii</it>.</p> <p>Results</p> <p><it>IGF2 </it>mRNA and protein were produced in the marsupial placenta. Both IGF2 receptors were present in the placenta, and presumably mediate IGF2 mitogenic actions. <it>IGF2 </it>mRNA levels were highest in the vascular region of the yolk sac placenta. IGF2 increased <it>vascular endothelial growth factor </it>expression in placental explant cultures, suggesting that IGF2 promotes vascularisation of the yolk sac.</p> <p>Conclusion</p> <p>This is the first demonstration of a physiological role for any imprinted gene in marsupial placentation. The conserved imprinting of <it>IGF2</it> in this marsupial and in all eutherian species so far investigated, but not in monotremes, suggests that imprinting of this gene may have originated in the placenta of the therian ancestor.</p

Differential roles of TGIF family genes in mammalian reproduction

<p>Abstract</p> <p>Background</p> <p>TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins including TGIF1, TGIF2 and TGIFLX/Y in human. Both TGIF1 and TGIF2 act as transcription factors repressing TGF-β signalling. Human <it>TGIFLX </it>and its orthologue, <it>Tex1 </it>in the mouse, are X-linked genes that are only expressed in the adult testis. <it>TGIF2 </it>arose from <it>TGIF1 </it>by duplication, whereas <it>TGIFLX </it>arose by retrotransposition to the X-chromosome. These genes have not been characterised in any non-eutherian mammals. We therefore studied the TGIF family in the tammar wallaby (a marsupial mammal) to investigate their roles in reproduction and how and when these genes may have evolved their functions and chromosomal locations.</p> <p>Results</p> <p>Both <it>TGIF1 </it>and <it>TGIF2 </it>were present in the tammar genome on autosomes but <it>TGIFLX </it>was absent. Tammar <it>TGIF1 </it>shared a similar expression pattern during embryogenesis, sexual differentiation and in adult tissues to that of <it>TGIF1 </it>in eutherian mammals, suggesting it has been functionally conserved. Tammar <it>TGIF2 </it>was ubiquitously expressed throughout early development as in the human and mouse, but in the adult, it was expressed only in the gonads and spleen, more like the expression pattern of human <it>TGIFLX </it>and mouse <it>Tex1</it>. Tammar <it>TGIF2 </it>mRNA was specifically detected in round and elongated spermatids. There was no mRNA detected in mature spermatozoa. TGIF2 protein was specifically located in the cytoplasm of spermatids, and in the residual body and the mid-piece of the mature sperm tail. These data suggest that tammar <it>TGIF2 </it>may participate in spermiogenesis, like <it>TGIFLX </it>does in eutherians. <it>TGIF2 </it>was detected for the first time in the ovary with mRNA produced in the granulosa and theca cells, suggesting it may also play a role in folliculogenesis.</p> <p>Conclusions</p> <p>The restricted and very similar expression of tammar <it>TGIF2 </it>to X-linked paralogues in eutherians suggests that the evolution of <it>TGIF1</it>, <it>TGIF2 </it>and <it>TGIFLX </it>in eutherians was accompanied by a change from ubiquitous to tissue-specific expression. The distribution and localization of TGIF2 in tammar adult gonads suggest that there has been an ultra-conserved function for the TGIF family in fertility and that <it>TGIF2 </it>already functioned in spermatogenesis and potentially folliculogenesis long before its retrotransposition to the X-chromosome of eutherian mammals. These results also provide further evidence that the eutherian X-chromosome has actively recruited sex and reproductive-related genes during mammalian evolution.</p

Increased insulin resistance in intensive care: longitudinal retrospective analysis of glycaemic control patients in a New Zealand ICU

Background: Critical care populations experience demographic shifts in response to trends in population and healthcare, with increasing severity and/or complexity of illness a common observation worldwide. Inflammation in critical illness impacts glucose–insulin metabolism, and hyperglycaemia is associated with mortality and morbidity. This study examines longitudinal trends in insulin sensitivity across almost a decade of glycaemic control in a single unit. Methods: A clinically validated model of glucose–insulin dynamics is used to assess hour–hour insulin sensitivity over the first 72 h of insulin therapy. Insulin sensitivity and its hour–hour percent variability are examined over 8 calendar years alongside severity scores and diagnostics. Results: Insulin sensitivity was found to decrease by 50–55% from 2011 to 2015, and remain low from 2015 to 2018, with no concomitant trends in age, severity scores or risk of death, or diagnostic category. Insulin sensitivity variability was found to remain largely unchanged year to year and was clinically equivalent (95% confidence interval) at the median and interquartile range. Insulin resistance was associated with greater incidence of high insulin doses in the effect saturation range (6–8 U/h), with the 75th percentile of hourly insulin doses rising from 4–4.5 U/h in 2011–2014 to 6 U/h in 2015–2018. Conclusions: Increasing insulin resistance was observed alongside no change in insulin sensitivity variability, implying greater insulin needs but equivalent (variability) challenge to glycaemic control. Increasing insulin resistance may imply greater inflammation and severity of illness not captured by existing severity scores. Insulin resistance reduces glucose tolerance, and can cause greater incidence of insulin saturation and resultant hyperglycaemia. Overall, these results have significant clinical implications for glycaemic control and nutrition management

Evolution of the CDKN1C-KCNQ1 imprinted domain

<p>Abstract</p> <p>Background</p> <p>Genomic imprinting occurs in both marsupial and eutherian mammals. The <it>CDKN1C </it>and <it>IGF2 </it>genes are both imprinted and syntenic in the mouse and human, but in marsupials only <it>IGF2 </it>is imprinted. This study examines the evolution of features that, in eutherians, regulate <it>CDKN1C </it>imprinting.</p> <p>Results</p> <p>Despite the absence of imprinting, CDKN1C protein was present in the tammar wallaby placenta. Genomic analysis of the tammar region confirmed that <it>CDKN1C </it>is syntenic with <it>IGF2</it>. However, there are fewer LTR and DNA elements in the region and in intron 9 of <it>KCNQ1</it>. In addition there are fewer LINEs in the tammar compared with human and mouse. While the CpG island in intron 10 of <it>KCNQ1 </it>and promoter elements could not be detected, the antisense transcript <it>KCNQ1OT1 </it>that regulates <it>CDKN1C </it>imprinting in human and mouse is still expressed.</p> <p>Conclusion</p> <p>CDKN1C has a conserved function, likely antagonistic to IGF2, in the mammalian placenta that preceded its acquisition of imprinting. CDKN1C resides in synteny with IGF2, demonstrating that imprinting of the two genes did not occur concurrently to balance maternal and paternal influences on the growth of the placenta. The expression of <it>KCNQ1OT1 </it>in the absence of CDKN1C imprinting suggests that antisense transcription at this locus preceded imprinting of this domain. These findings demonstrate the stepwise accumulation of control mechanisms within imprinted domains and show that <it>CDKN1C </it>imprinting cannot be due to its synteny with <it>IGF2 </it>or with its placental expression in mammals.</p

Cognitive ability does not predict objectively measured sedentary behaviour: evidence from three older cohorts

Higher cognitive ability is associated with being more physically active. Much less is known about the associations between cognitive ability and sedentary behavior. Ours is the first study to examine whether historic and contemporaneous cognitive ability predicts objectively measured sedentary behavior in older age. Participants were drawn from 3 cohorts (Lothian Birth Cohort, 1936 [LBC1936] [n = 271]; and 2 West of Scotland Twenty-07 cohorts: 1950s [n = 310] and 1930s [n = 119]). Regression models were used to assess the associations between a range of cognitive tests measured at different points in the life course, with sedentary behavior in older age recorded over 7 days. Prior simple reaction time (RT) was significantly related to later sedentary time in the youngest, Twenty-07 1950s cohort (p = .04). The relationship was nonsignificant after controlling for long-standing illness or employment status, or after correcting for multiple comparisons in the initial model. None of the cognitive measures were related to sedentary behavior in either of the 2 older cohorts (LBC1936, Twenty-07 1930s). There was no association between any of the cognitive tests and the number of sit-to-stand transitions in any of the 3 cohorts. The meta-analytic estimates for the measures of simple and choice RT that were identical in all cohorts (n = 700) were also not significant. In conclusion, we found no evidence that objectively measured sedentary time in older adults is associated with measures of cognitive ability at different time points in life, including cognitive change from childhood to older age

Measuring lung mechanics of expiratory tidal breathing with non-invasive breath occlusion

Background and objective: Lung mechanics measurements provide clinically useful information about disease progression and lung health. Currently, there are no commonly practiced methods to non-invasively measure both resistive and elastic lung mechanics during tidal breathing, preventing the important information provided by lung mechanics from being utilised. This study presents a novel method to easily assess lung mechanics of spontaneously breathing subjects using a dynamic elastance, single-compartment lung model. Methods: A spirometer with a built-in shutter was used to occlude expiration during tidal breathing, creating exponentially decaying flow when the shutter re-opened. The lung mechanics measured were respiratory system elastance and resistance, separated from the exponentially decaying flow, and interrupter resistance calculated at shutter closure. Progressively increasing resistance was added to the spirometer mouthpiece to simulate upper airway obstruction. The lung mechanics of 17 healthy subjects were successfully measured through spirometry. Results: N = 17 (8 female, 9 male) healthy subjects were recruited. Measured decay rates ranged from 5 to 42/s, subjects with large variation of decay rates showed higher muscular breathing effort. Lung elastance measurements ranged from 3.9 to 21.2 cmH -2 2 O/L, with no clear trend between change in elastance and added resistance. Resistance calculated from decay rate and elastance ranged from 0.15 to 1.95 cmH -2 2 Os/L. These very small resistance values are due to the airflow measured originating from low-resistance areas in the centre of airways. Occlusion resistance measurements were as expected for healthy subjects, and increased as expected as resistance was added. Conclusions: This test was able to identify reasonable dynamic lung elastance and occlusion resistance values, providing new insight into expiratory breathing effort. Clinically, this lung function test could impact current practice. It does not require high levels of cooperation from the subject, allowing a wider cohort of patients to be assessed more easily. Additionally, this test can be simply implemented in a small standalone device, or with standard lung function testing equipment