Play and the evolution of fairness: a game theory model

Bekoff [J. Consci. Stud. 8 (2001) 81] argued that mammalian social play is a useful behavioral phenotype on which to concentrate in order to learn more about the evolution of fairness. Here, we build a game theoretical model designed to formalize some of the ideas laid out by Bekoff, and to examine whether ‘fair’ strategies can in fact be evolutionarily stable. The models we present examine fairness at two different developmental stages during an individual's ontogeny, and hence we create four strategies—fair at time 1/fair at time 2, not fair at time 1/not fair at time 2, fair at time 1/not fair at time 2, not fair at time 1/fair at time 2. Our results suggest that when considering species where fairness can be expressed during two different developmental stages, acting fairly should be more common than never acting fairly. In addition, when no one strategy was evolutionarily stable, we found that all four strategies we model can coexist at evolutionary equilibrium. Even in the absence of an overwhelming database from which to test our model, the general predictions we make have significant implications for the evolution of fairness.     

Brood parasitism increases provisioning rate, and reduces offspring recruitment and adult return rates, in a cowbird host

Interspecific brood parasitism in birds presents a special problem for the host because the parasitic offspring exploit their foster parents, causing them to invest more energy in their current reproductive effort. Nestling brown-headed cowbirds (Molothrus ater) are a burden to relatively small hosts and may reduce fledgling quality and adult survival. We documented food-provisioning rates of one small host, the prothonotary warbler (Protonotaria citrea), at broods that were similar in age (containing nestlings 8–9 days old), but that varied in composition (number of warbler and cowbird nestlings) and mass, and measured the effect of brood parasitism on offspring recruitment and adult returns in the host. The rate of food provisioning increased with brood mass, and males and females contributed equally to feeding nestlings. Controlling for brood mass, the provisioning rate was higher for nests with cowbirds than those without. Recruitment of warbler fledglings from unparasitized nests was 1.6 and 3.7 times higher than that of fledglings from nests containing one or two cowbirds, respectively. Returns of double-brooded adult male and female warblers decreased with an increase in the number of cowbirds raised, but the decrease was more pronounced in males. Reduced returns of warbler adults and recruitment of warbler fledglings with increased cowbird parasitism was likely a result of reduced survival. Cowbird parasitism increased the warblers’ investment in current reproductive effort, while exerting additional costs to current reproduction and residual reproductive value. Our study provides the strongest evidence to date for negative effects of cowbird parasitism on recruitment of host fledglings and survival of host adults.     

Food makes you a target: disentangling genetic, physiological, and behavioral effects determining susceptibility to infection

Genetics, physiology, and behavior are all expected to influence the susceptibility of hosts to parasites. Furthermore, interactions between genetic and other factors are suggested to contribute to the maintenance of genetic polymorphism in resistance when the relative susceptibility of host genotypes is context dependent. We used a maternal sibship design and long- and short-term food deprivation treatments to test the role of family-level genetic variation, body condition, physiological state, and foraging behavior on the susceptibility of Lymnaea stagnalis snails to infection by a trematode parasite that uses chemical cues to locate its hosts. In experimental exposures, we found that snails in the long-term food deprivation treatment contracted fewer parasites than snails that were continuously well-fed, possibly because well-fed snails grew larger and attracted more transmission stages. When we kept the long-term feeding rates the same, but manipulated the physiological state and foraging behavior of the snails with short-term food deprivation treatment, we found that snails that were fed before the exposure contracted more parasites than snails that were fed during the exposure. This suggests that direct physiological effects of food processing, but not foraging behavior, predisposed snails to infection. Feeding treatments also affected the family-level variation in snail susceptibility, suggesting that the relative susceptibility of host genotypes was context dependent.     

The prognosis of acute and persistent low-back pain: a meta-analysis

Background:

Although low-back pain is a highly prevalent condition, its clinical course remains uncertain. Our main objective was to systematically review the literature on the clinical course of pain and disability in patients with acute and persistent low-back pain. Our secondary objective was to investigate whether pain and disability have similar courses.

Methods:

We performed a meta-analysis of inception cohort studies. We identified eligible studies by searching MEDLINE, Embase and CINAHL. We included prospective studies that enrolled an episode-inception cohort of patients with acute or persistent low-back pain and that measured pain, disability or recovery. Two independent reviewers extracted data and assessed methodologic quality. We used mixed models to determine pooled estimates of pain and disability over time.

Results:

Data from 33 discrete cohorts (11 166 participants) were included in the review. The variance-weighted mean pain score (out of a maximum score of 100) was 52 (95% CI 48–57) at baseline, 23 (95% CI 21–25) at 6 weeks, 12 (95% CI 9–15) at 26 weeks and 6 (95% CI 3–10) at 52 weeks after the onset of pain for cohorts with acute pain. Among cohorts with persistent pain, the variance-weighted mean pain score (out of 100) was 51 (95% CI 44–59) at baseline, 33 (95% CI 29–38) at 6 weeks, 26 (95% CI 20–33) at 26 weeks and 23 (95% CI 16–30) at 52 weeks after the onset of pain. The course of disability outcomes was similar to the time course of pain outcomes in the acute pain cohorts, but the pain outcomes were slightly worse than disability outcomes in the persistent pain cohorts.

Interpretation:

Patients who presented with acute or persistent low-back pain improved markedly in the first six weeks. After that time improvement slowed. Low to moderate levels of pain and disability were still present at one year, especially in the cohorts with persistent pain.Low-back pain is a highly prevalent condition associated with work absenteeism, disability and large health care costs; however, there is still disagreement about prognosis. For example, the European guidelines for the management of low-back pain states that 90% of patients with acute low-back pain recover in six weeks.¹ In contrast, some well-conducted cohort studies show a less optimistic picture, providing short-term estimates of recovery ranging from 39% to 76%.^2,3 This wide range of estimates of prognosis is likely explained by differences in cohorts and definitions used to define the onset or conclusion of an episode of low-back pain. Because very different definitions of recovery are often used, it is difficult to obtain pooled estimates of recovery rates. Instead, it might be more useful to describe the clinical course of low-back pain in terms of expected changes in pain or disability over time.A recent systematic review⁴ summarized the prognostic factors for persistent disabling low-back pain but did not describe the clinical course. The only meta-analysis to investigate the clinical course of acute low-back pain was published in 2003.⁵ This review concluded that both pain and disability improve rapidly within weeks (mean reduction of 58% of initial scores in the first month) and recurrences are common. A limitation of this review was that, although it retrieved 15 studies, only 5 were cohort studies; the remaining 10 were randomized controlled trials. Randomized trials often have narrow inclusion criteria and low rates of participation, which make them less suitable for inferring prognosis. The best design to describe the prognosis of a condition is a cohort study enrolling a representative sample of incident cases (i.e., by including patients at a similar early point in their condition).^6,7 Such studies are known as inception cohort studies. To the best of our knowledge, no review has yet investigated the clinical course of pain and disability among people with persistent low-back pain (subacute and chronic). Thus, the prognosis for people with persistent low-back pain is still uncertain.The aim of our study was to systematically review the clinical course of pain and disability in patients with acute and persistent low-back pain. We included only inception cohort studies. Our second aim was to investigate whether pain and disability have similar courses.     

Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults

There is preliminary clinical evidence to support the contention that the anti-inflammatory and analgesic properties of bromelain help to reduce symptoms of osteo- and rheumatoid arthritis. However, there have been no controlled studies of its effects on joint health in healthy subjects who lack such diagnosis. The current study investigated the effects of bromelain on mild acute knee pain of less than 3 months duration in otherwise healthy adults. The study was an open, dose-ranging postal study in volunteers who had been recruited through newspaper and magazine articles. Two validated questionnaires (WOMAC knee health Index and the Psychological Well-Being Index) were completed at baseline and after one month's intervention with bromelain, randomly allocated to volunteers as either 200 mg or 400 mg per day. Seventy seven subjects completed the study. In both treatment groups, all WOMAC symptom dimension scores were significantly reduced compared with baseline, with reductions in the final battery (total symptom score) of 41 and 59% (P = 0.0001 and <0.0001) in the low and high dose groups respectively. In addition, improvements in total symptom score (P = 0.036) and the stiffness (P = 0.026) and physical function (P = 0.021) dimensions were significantly greater in the high-dose (400 mg per day) compared with the low-dose group. Compared to baseline, overall psychological well-being was significantly improved in both groups after treatment (P = 0.015 and P = 0.0003 in the low and high dose groups respectively), and again, a significant dose-response relationship was observed. We conclude that bromelain may be effective in ameliorating physical symptoms and improving general well-being in otherwise healthy adults suffering from mild knee pain in a dose-dependant manner. Double blind, placebo-controlled studies are now warranted to confirm these results.     

Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment.

Chemokines are thought to contribute to the cellular infiltrate characteristic of renal transplant rejection. We show that Met-RANTES, a chemokine receptor antagonist, suppresses recruitment of inflammatory cells into renal allografts. In a renal transplant model (Fisher RT1(lvl) rat kidney into Lewis RT1(l) rat) where no additional immune suppressant was used, Met-RANTES-treated animals showed a significant reduction in vascular injury score (16.10 +/- 5.20 vs. 62.67 +/- 18.64) and tubular damage score (15.70 +/- 5.22 vs. 33.00 +/- 6.44) relative to untreated animals. In a more severe rejection model (Brown-Norway RT1(n) rat kidney into Lewis RT1(1) rat), Met-RANTES significantly augmented low-dose cyclosporin A treatment to reduce all aspects of renal injury including interstitial inflammation (score 71.00 +/- 6.10 vs. 157.30 +/- 21.30). The majority of infiltrating cells in these models (60-70%) consisted of monocytes. Potential mechanisms of action of Met-RANTES were tested using monocyte attachment assays on microvascular endothelium under physiological flow conditions. Preexposure of microvascular endothelium to RANTES resulted in RANTES immobilization and RANTES-induced firm adhesion of monocytes only after prestimulation of the endothelium with IL-1beta. Met-RANTES completely inhibited this RANTES-mediated arrest. Thus, Met-RANTES may counter acute rejection by blocking leukocyte firm adhesion to inflamed endothelium.     

Conspecific-only experience during development reduces the strength of heterospecific song discrimination in Zebra Finches (Taeniopygia guttata): a test of the optimal acceptance threshold hypothesis

Conspecifics during development provide the most reliable sensory cues for species recognition in parental bird species. The Zebra Finch (Taeniopygia guttata) is a sexually dimorphic model species used for investigations of the behavioural cues and neurobiological substrates of species recognition. Regarding acoustic conspecific cues, theory predicts that exposure to both con- and heterospecific vocalisations and other environmental sounds results in more accurate auditory species discrimination, because diverse vocal cues during development shift optimal conspecific acceptance thresholds to be more restrictive to yield fewer acceptance errors. We tested the behavioural preferences of female and male Zebra Finches raised in an outdoor environment (Control) and female and male Zebra Finches reared in an indoor colony with exposure to Zebra Finches only (Restricted), to playbacks of songs of Zebra Finches, Zebra Finches cross-fostered by Bengalese Finches (Lonchura striata var. domestica), and Bengalese Finches. Several behavioural measures revealed minimal sexual dimorphism in discrimination but showed that Control subjects preferred conspecifics’ songs over either the songs of cross-fostered Zebra Finches or Bengalese Finches. Restricted Zebra Finches in contrast did not discriminate behaviourally between the three song types. These results support the concept of a shift in the species acceptance threshold in the restricted treatment resulting in more acceptance errors. We discuss future work to test the role of exposure to diverse vocal cues of both con- and heterospecifics in the ontogeny of song perception in this important laboratory model species for social recognition research.     

Oral valdecoxib and injected parecoxib for acute postoperative pain: a quantitative systematic review

BACKGROUND: Clinical trials suggest that cyclo-oxygenase-2 specific inhibitors (coxibs) are an effective treatment for acute postoperative pain. The aims of this systematic review were to examine the evidence for oral valdecoxib and injected parecoxib, and quantify efficacy and adverse effects. METHODS: Information from randomized, double-blind studies in acute postoperative pain was sought. The area under the pain relief versus time curve over four to six hours was dichotomized using validated equations to derive the proportion of patients with treatment and placebo with at least 50% pain relief over four to six hours and calculate the number-needed-to-treat (NNT). Information on duration of analgesia and adverse events was also collected. RESULTS: The NNT for one patient to experience at least 50% relief over six hours following a single oral dose of valdecoxib 20 mg and 40 mg was 1.7 (1.4 to 2.0) and 1.6 (1.4 to 1.8) respectively. The NNT for one patient to have at least 50% relief over four to six hours with parecoxib 20 mg IV and 40 mg IV was 3.0 (2.3 to 4.1) and 2.3 (2.0 to 2.6) respectively. Mean time to remedication (weighted by trial size) was >24 hours with valdecoxib 40 mg, 8.7 hours with parecoxib 40 mg IV and 1.7 to 1.8 hours with placebo. There were no statistical differences between treatment and placebo for any adverse effect. CONCLUSION: Both oral valdecoxib and injected parecoxib are effective treatments for acute postoperative pain.     

Liposomal lidocaine to improve procedural success rates and reduce procedural pain among children: a randomized controlled trial

BackgroundHistorically, children have been undertreated for their pain, and they continue to undergo painful cutaneous procedures without analgesics. A new topical anesthetic, liposomal lidocaine 4% cream (Maxilene, RGR Pharma, Windsor, Ont.), has become available. It has pharmacologic properties that are superior to other topical anesthetics, including an onset of action of only 30 minutes. We sought to determine the success rate of cannulation, analgesic effectiveness, procedure duration and rate of adverse skin reactions when liposomal lidocaine is used before intravenous cannulation of children.MethodsIn this double-blind randomized controlled trial, children aged 1 month to 17 years received liposomal lidocaine or placebo before cannulation. Success on first cannulation attempt was recorded, and, among children 5 years and older, pain was evaluated before and after the attempt by the child, parents and research assistant using a validated measure (Faces Pain Scale-Revised). For children younger than 5 years, pain was evaluated by the parents and research assistant only. The total duration of the procedure and adverse skin reactions were also recorded.ResultsBaseline characteristics did not differ (p > 0.05) between children who received liposomal lidocaine (n = 69) and those who received placebo (n = 73). Cannulation on the first attempt was achieved in 74% of children who received liposomal lidocaine compared with 55% of those who received placebo (p = 0.03). Among children 5 years of age and older (n = 67), lower mean pain scores during cannulation were reported by those receiving liposomal lidocaine (p = 0.01). Similarly, lower mean pain scores during cannulation were reported by the parents and research assistant for all children who received liposomal lidocaine than for all those who received placebo (p < 0.001). The mean total procedure duration was shorter with liposomal lidocaine (6.7 v. 8.5 minutes; p = 0.04). The incidence of transient dermal changes was 23% in both groups (p = 1.0).ConclusionsUse of liposomal lidocaine was associated with a higher intravenous cannulation success rate, less pain, shorter total procedure time and minor dermal changes among children undergoing cannulation. Its routine use for painful cutaneous procedures should be considered whenever feasible.Painful medical procedures are routinely performed on children for diagnostic and therapeutic reasons. The provision of analgesia for these procedures, however, remains uncommon.¹ Untreated pain has both short-term and long-term consequences. In the short term, there is pain during the actual procedure. This contributes to a lack of cooperation by the child, unsuccessful procedure attempts, repeated attempts, additional pain and a prolonged total procedure time. In the long term, repeated painful procedures can lead to conditioned anxiety responses and increased pain perception.^2,3 Inadequate analgesia during an initial procedure may diminish analgesic effectiveness at subsequent procedures.⁴ Moreover, there is a relation between painful procedures in childhood and blood-injection-injury phobia,⁵ a condition that affects up to 10% of adults and may cause people to avoid medical care.⁶ In light of the cumulative evidence of the negative consequences of untreated pain in childhood, interventions are needed to diminish pain among children undergoing medical procedures and to facilitate successful completion of procedures.Intravenous cannulation is a common, painful medical procedure. Although local anesthetics reduce the pain of cannulation,^7,8,9,10,11 most preparations are not feasible for routine use. The “gold standard” for skin anesthesia, lidocaine–prilocaine 5% cream, requires a 60-minute application time. In addition, it causes vasoconstriction,¹² which potentially obscures landmarks and makes cannulation more difficult.¹³ Another commercially available preparation, amethocaine 4% gel, requires a 30-minute application time. However, it frequently causes vasodilatation and may induce hypersensitivity with repeated use.¹⁴ An alternative option, subcutaneous injection of lidocaine, requires only a few minutes to administer, but it is associated with an extra and painful puncture and is therefore not routinely used.¹⁵Liposomal lidocaine 4% cream¹⁶ (Maxilene, RGR Pharma, Windsor, Ont.) was launched in Canada in 2003. The liposome-encapsulated formulation protects the anesthetic from being metabolized too quickly.¹⁷ Liposomal lidocaine has the advantages of “needle-free” administration, a short onset of action and minimal vasoactive properties that minimize any potential interference with cannulation success. It is not associated with methemoglobinemia, a systemic side effect of lidocaine–prilocaine.¹⁸Among children, liposomal lidocaine is as effective as lidocaine–prilocaine for decreasing pain from venipuncture¹⁹ and intravenous cannulation,^20,21 and as effective as buffered lidocaine injection for decreasing intravenous cannulation pain.¹⁵ Previous studies have not compared liposomal lidocaine with placebo. We conducted such a comparison to determine whether liposomal lidocaine improves cannulation success rates. We also sought to determine whether it reduces pain and procedure duration and is associated with a low frequency of dermal reactions.     

Immediate and short-term pain relief by acute sciatic nerve press: a randomized controlled trial

Background

Despite much research, an immediately available, instantly effective and harmless pain relief technique has not been discovered. This study describes a new manipulation: a "2-minute sciatic nerve press", for rapid short-term relief of pain brought on by various dental and renal diseases.

Methods

This randomized, single-blind, placebo-controlled trial ran in three hospitals in Anhui Province, China, with an enrollment of 66 out of 111 solicited patients aged 16 to 74 years. Patients were recruited sequentially, by specific participating physicians at their clinic visits to three independent hospitals. The diseases in enrolled dental patients included dental caries, periodontal diseases and dental trauma. Renal diseases in recruits included kidney infections, stones and some other conditions. Patients were randomly assigned to receive the "2-minute sciatic nerve press" or the "placebo press". For the "2-minute sciatic nerve press", pressure was applied simultaneously to the sciatic nerves at the back of the thighs, using the fists while patients lay prone. For the "placebo press", pressure was applied simultaneously to a parallel spot on the front of the thighs, using the fists while patients lay supine. Each fist applied a pressure of 11 to 20 kg for 2 minutes, after which, patients arose to rate pain.

Results

The "2-minute sciatic nerve press" produced greater pain relief than the "placebo press". Within the first 10 minutes after sciatic pressure, immediate pain relief ratings averaged 66.4% (p < 0.001) for the dental patients, versus pain relief of 20% for the placebo press, and, 52.2% (p < 0.01) for the renal patients, versus relief of 14% for the placebo press, in median. The method worked excellently for dental caries and periodontal diseases, but poorly for dental trauma. Forty percent of renal patients with renal colic did not report any pain relief after the treatment.

Conclusion

Two minutes of pressure on both sciatic nerves can produce immediate significant conduction analgesia, providing a convenient, safe and powerful way to overcome clinical pain brought on by dental diseases and renal diseases for short term purposes.

Trial registration

ACTR 12606000439549     

Preterm birth and stillbirth rates during the COVID-19 pandemic: a population-based cohort study

BACKGROUND:Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada.METHODS:We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22–28, 29–32 and 33–36 weeks’ gestation, and stillbirths at term and preterm gestation. We used Laney control P′ charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years.RESULTS:We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%–8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%–0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses.INTERPRETATION:In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.

Preterm birth (birth before 37 weeks’ gestation) is a leading cause of mortality and morbidities in the neonatal period,¹ childhood and adulthood.² Stillbirth has devastating consequences for families.³ The causes of both preterm birth and stillbirth are multifactorial. During the pandemic, reports described reductions in preterm birth rates in Denmark,⁴ the Netherlands,⁵ Ireland⁶ and the United States.⁷ At the same time, increases in stillbirth rates were reported from the United Kingdom,⁸ Italy,⁹ Nepal¹⁰ and India,¹¹ with or without changes in rates of preterm births. Meta-analyses have emerged with differing conclusions.^12,13 Some speculated reasons for reductions in preterm births included reductions in physical activity during pregnancy, reduced stress related to work–life balance, less exposure to infection, fewer medical interventions, reduced travel and pollution,¹⁴ and improved hygiene and rest. Proposed reasons for increases in preterm birth rates include higher stress due to worry about the pandemic, employment or financial challenges, home schooling and reduced maternity services.¹⁵ Less stringent fetal surveillance from reduced attendance at medical appointments for fear of infection, cancellation of face-to-face appointments and reduced staffing for maternity services are possible reasons for increased rates of stillbirths. Thus, it is important to evaluate preterm births and stillbirths simultaneously to understand the true impact.¹⁶Some previous reports compared preterm birth and stillbirth rates during the pandemic to similar time periods in the past few years. However, within a jurisdiction, these rates are known to fluctuate between epochs¹⁷ and, thus, it is preferable to evaluate rates over longer periods to establish whether observed variations are usual (common cause variation) or unusual (special cause variation). Our objective was to evaluate whether the COVID-19 pandemic affected preterm birth or stillbirth rates in Ontario by comparing rates for the early COVID-19 pandemic time period with rates from the previous 17.5 years to identify patterns of variation.     

The legacy of climate change effects: previous drought increases short-term litter decomposition rates in a temperate mixed grass- and shrubland

Aims

Fungi play a central role in litter decomposition, a key process controlling the terrestrial carbon cycle and nutrient availability for plants and microorganisms. Climate change and elevated CO₂ affect soil fungi, but the relative importance of the global change variables for litter decomposition is still uncertain. The main objective was therefore to assess the short-term litter decomposition and associated fungal community in a global change manipulated temperate heath ecosystem.

Methods

The heath had been exposed to 6 years of warming, elevated atmospheric CO₂ and an extended pre-summer drought. Litterbags with litter from heather (Calluna vulgaris) and wavy-hair grass (Deschampsia flexuosa) were incubated in the litter layer for 6 months, where after we analyzed the litter-associated fungal community, litter loss, CO₂ respiration, and total content of carbon, nitrogen and phosphorus.

Results

Elevated temperature tended to increase litter decomposition rates, whereas elevated CO₂ had no effect on the process. The pre-summer drought treatment had a positive impact on litter decomposition, CO₂ respiration and fungal abundance in the litterbags, although we observed no major changes in fungal community composition.

Conclusions

The drought treatment during pre-summer had a legacy effect on litter decomposition as decomposition rates were positively affected later in the year. The community structure of litter-decomposing fungi was not affected by the drought treatment. Hence, the legacy effect was not mediated by a change in the fungal community structure.

     

Warm-up rates during arousal from torpor in heterothermic mammals: physiological correlates and a comparison with heterothermic insects

Summary This study examines the relationship between warm-up rate, body mass, metabolic rate, thermal conductance and normothermic body temperature in heterothermic mammals during arousal from torpor. Predictions based on the assumption that the energetic cost of arousal has been minimised are tested using data for 35 species. The observation that across-species warm-up rate correlates negatively with body mass is confirmed using a comparative technique which removes confounding effects due to the non-independence of species data due to shared common ancestry. Mean warm-up rate during arousal correlates negatively with basal metabolic rate and positively with the temperature difference through which the animal warms, having controlled for other factors. These results suggest that selection has operated to minimise the overall energetic, cost of warm-up. In contrast, peak warm-up rate during arousal correlates positively with peak metabolic rate during arousal, and negatively with thermal conductance, when body mass has been taken into account. These results suggest that peak warm-up rate is more sensitive to the fundamental processes of heat generation and loss. Although heterothermic marsupials have lower normothermic body temperatures and basal metabolic rates, marsupials and heterothermic eutherian mammals do not differ systematically in warm-up rate. Pre-flight warm-up rates in one group of endothermic insects, the bees, are significantly higher than predictions based on rates of arousal of a mammal of the same body mass.Abbreviations BMR basal metabolic rate - ICM independent comparisons method - MWR mean warm-up rate - PMR peak metabolic rate - PWR peak·warm-up rate - Tb_activity body temperature during activity - Tb_torpor body temperature during torpor - T _arousal increase in body temperature during arousal     

Dementia increases the risks of acute organ dysfunction, severe sepsis and mortality in hospitalized older patients: a national population-based study

Background

Dementia increases the risk of death in older patients hospitalized for acute illnesses. However, the effect of dementia on the risks of developing acute organ dysfunction and severe sepsis as well as on the risk of hospital mortality in hospitalized older patients remains unknown, especially when treatments for these life-threatening situations are considered.

Methods

In this population-based cohort study, we analyzed 41,672 older (≥65 years) patients, including 3,487 (8.4%) with dementia, from the first-time admission claim data between 2005 and 2007 for a nationally representative sample of one million beneficiaries enrolled in the Taiwan National Health Insurance Research Database. Outcomes included acute organ dysfunction, severe sepsis, and hospital mortality. The effect of dementia on outcomes was assessed using multivariable logistic regression.

Results

Dementia was associated with a 32% higher risk of acute organ dysfunction (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.19–1.46), a 50% higher risk of severe sepsis (aOR 1.50, 95% CI 1.32–1.69) and a 28% higher risk of hospital mortality (aOR 1.28, 95% CI 1.10–1.48) after controlling age, sex, surgical condition, comorbidity, principal diagnosis, infection status, hospital level, and length of hospital stay. However, the significant adverse effect of dementia on hospital mortality disappeared when life-support treatments, including vasopressor use, hemodialysis, mechanical ventilation, and intensive care, were also controlled.

Conclusions

In hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe sepsis and hospital mortality. However, after intervention using life-support treatments, dementia only exhibited a minor role on short-term mortality.     

Production and metabolic clearance rates of 1,25-dihydroxyvitamin D3 during maturation in rats: studies using a rapid, primed-infusion technique

I have adapted the primed-infusion technique for the rapid estimation of the metabolic clearance rate (MCR) and production rate (PR) of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in chronically catheterized conscious rats. Following a bolus injection, [3H]-1,25(OH)2D3 was infused iv at a constant rate for 7 h. Steady-state [3H]-1,25(OH)2D3 levels in plasma were achieved within 3 h. HPLC-purification of plasma [3H]-1,25(OH)2D3 was necessary. This rapid, primed-infusion technique thus eliminates the need for protracted infusions to achieve steady-state plasma [3H]-1,25(OH)2D3 levels. The MCR averaged 0.201 +/- 0.003 ml.min-1.kg-1 in fed male rats weighing 200-300 g. This MCR is approximately 50% lower than that seen in other species. Overnight fasting was without effect on the MCR. The MCR increased in direct proportion to body weight in maturing rats (6-16 weeks old) weighing 150-450 g. Thus, the MCR can be normalized per kg across this age range. However, 1,25(OH)2D3 production and plasma levels both decreased by 65-67% as the rats matured. The failure of a 3-fold decrease in plasma 1,25(OH)2D3 levels to affect the MCR suggests that 1,25(OH)2D3 stimulates its own catabolism only at markedly elevated concentrations.     

Liver mtDNA content increases during development: a comparison of methods and the importance of age- and tissue-specific controls for the diagnosis of mtDNA depletion

BACKGROUND: The quantitative loss of mitochondrial DNA (mtDNA) known as mtDNA depletion, often gives rise to liver disease. The diagnosis of mtDNA depletion syndrome is frequently imprecise, both for technical reasons and because of the lack of established age-adjusted normal ranges. We aimed to refine quantitative methods for diagnosing the hepatic type of mtDNA depletion syndrome, firstly by establishing an age-matched reference range for mitochondrial to nuclear DNA ratio (henceforth "mtDNA content") and secondly by investigating mtDNA in fibroblasts. METHODS: By comparing realtime PCR with an established method for quantifying mtDNA content we established a reference range for young children using biopsy and post-mortem material from patients <15 years. In addition, we investigated the arrangement of mtDNA in nucleoids from fibroblasts using fluorescence microscopy. RESULTS: Both methods showed that the mtDNA content of liver increases rapidly over the perinatal period. In a patient whose liver mtDNA content fell, but remained within the reference range, early investigation and age-matched controls were essential, as we found a progressive increase in muscle mtDNA copy number, respiratory chain activity and muscle power with age. In three further patients, fluorescence microscopy of the fibroblasts proved diagnostic. In one case a movement disorder was an important pointer. CONCLUSIONS: These cases highlight the (i) need for comparing mtDNA copy number data generated from patients to DNA isolated from an age-matched normal range from the tissue of interest and (ii) the utility of mtDNA staining with PicoGreen as a method to detect aberrant nucleoid morphology in mtDNA depletion patient fibroblast lines when affected tissues are not available for measuring mtDNA copy number.