Management of post-acute COVID-19 patients in geriatric rehabilitation: EuGMS guidance.

PURPOSE: To describe a guidance on the management of post-acute COVID 19 patients in geriatric rehabilitation. METHODS: The guidance is based on guidelines for post-acute COVID-19 geriatric rehabilitation developed in the Netherlands, updated with recent insights from literature, related guidance from other countries and disciplines, and combined with experiences from experts in countries participating in the Geriatric Rehabilitation Special Interest Group of the European Geriatric Medicine Society. RESULTS: This guidance for post-acute COVID-19 rehabilitation is divided into a section addressing general recommendations for geriatric rehabilitation and a section addressing specific processes and procedures. The Sect. "General recommendations for geriatric rehabilitation" addresses: (1) general requirements for post-acute COVID-19 rehabilitation and (2) critical aspects for quality assurance during COVID-19 pandemic. The Sect. "Specific processes and procedures", addresses the following topics: (1) patient selection; (2) admission; (3) treatment; (4) discharge; and (5) follow-up and monitoring. CONCLUSION: Providing tailored geriatric rehabilitation treatment to post-acute COVID-19 patients is a challenge for which the guidance is designed to provide support. There is a strong need for additional evidence on COVID-19 geriatric rehabilitation including developing an understanding of risk profiles of older patients living with frailty to develop individualised treatment regimes. The present guidance will be regularly updated based on additional evidence from practice and research.

Regulation of membrane phospholipids during the adult life of worker honey bee.

Two female castes that are genetically identical are found in honey bees: workers and queens. Adult female honey bees differ in their morphology and behaviors, but the most intriguing difference between the castes is the difference in their longevity. Queens live for years while workers live generally for weeks. The mechanisms that mediate this extraordinary difference in lifespan remain mostly unknown. Both castes share similar developmental stages and are fed liquid food (i.e. a jelly) during development. However, after emergence, workers begin to feed on pollen while queens are fed the same larval food for their entire life. Pollen has a high content of polyunsaturated fatty acids (PUFA) while royal jelly has negligible amounts. The difference in food during adult life leads to drastic changes in membrane phospholipids of female honey bees, and those changes have been proposed as mechanisms that could explain the difference in lifespan. To provide further details on those mechanisms, we characterized the membrane phospholipids of adult workers at seven different ages covering all life-history stages. Our results suggest that the majority of changes in worker membranes occur in the first four days of adult life. Shortly after emergence, workers increase their level of total phospholipids by producing phospholipids that contained saturated (SFA) and monounsaturated fatty acids (MUFA). From the second day, workers start replacing fatty acid chains from those pre-synthesized molecules with PUFA acquired from pollen. After four days, worker membranes are set and appear to be maintained for the rest of adult life, suggesting that damaged PUFA are replaced effectively. Plasmalogen phospholipids increase continuously throughout worker adult life, suggesting that plasmalogen might help to reduce lipid peroxidation in worker membranes. We postulate that the diet-induced increase in PUFA in worker membranes makes them far more prone to lipid-based oxidative damage compared to queens.

The adult lifespan of the female honey bee (Apis mellifera): Metabolic rate, AGE pigment and the effect of dietary fatty acids.

Female honey bees can be queens or workers and although genetically identical, workers have an adult lifespan of weeks while queens can live for years. The mechanisms underlying this extraordinary difference remain unknown. This study examines three potential explanations of the queen-worker lifespan difference. Metabolic rates were similar in age-matched queens and workers and thus are not an explanation. The accumulation of fluorescent AGE pigment has been successfully used as a good measure of cellular senescence in many species. Unlike other animals, AGE pigment level reduced during adult life of queens and workers. This unusual finding suggests female honey bees can either modify, or remove from their body, AGE pigment. Another queen-worker difference is that, as adults, workers eat pollen but queens do not. Pollen is a source of polyunsaturated fatty acids. Its consumption explains the queen-worker difference in membrane fat composition of female adult honey bees which has previously been suggested as a cause of the lifespan difference. We were able to produce "queen-worker" membrane differences in workers by manipulation of diet that did not change worker lifespan and we can, thus, also rule out pollen consumption by workers as an explanation of the dramatic queen-worker lifespan difference.

Handover Structure and Quality in the Acute Medical Assessment Unit: A Prospective Observational Study.

OBJECTIVES: Inadequate patient handovers are associated with the occurrence of medical errors. The objective of the present study was to explore the structure and quality of handovers in the acute medical assessment unit. METHODS: A prospective observational study was conducted in an academic hospital in the Netherlands. Handover structure was observed by ordering handover information according to the elements of the Situation, Background, Assessment, Recommendation, and Read back (SBAR-R) handover tool. Handover quality was measured by means of a questionnaire, i.e., the rating tool for handover quality, and by assessing situation awareness of the degree to which professionals after a handover agreed on the complexity of the patient's care needs. RESULTS: A total of 71 handovers were observed. In most handovers, different elements of the SBAR-R were used frequently (median, 7.5 elements; range, 2.0-15.0). On the quality of handovers, 109 respondents (44.1%) completed the questionnaire. On a 0-to-100 scale, median scores on information transfer were 67.9 (interquartile range [IQR],17.9), 75.0 (IQR, 25.0) on shared understanding, and 75.0 (IQR, 16.7) on working atmosphere. Agreement in situation awareness was 70.0%. CONCLUSIONS: Handovers in the acute medical assessment unit were poorly structured; however, the perceived quality of handovers was substantial. Implementing the SBAR-R may be an effective strategy to improve handover practice and situation awareness, although further study to its applicability in acute medical assessment units is necessary.

Effectiveness of deep cleaning followed by hydrogen peroxide decontamination during high Clostridium difficile infection incidence.

BACKGROUND: Clostridium difficile infection (CDI) remains an infection control challenge, especially when environmental spore contamination and suboptimal cleaning may increase transmission risk. AIM: To substantiate the long-term effectiveness throughout a stroke rehabilitation unit (SRU) of deep cleaning and hydrogen peroxide decontamination (HPD), following a high incidence of CDI. METHODS: Extensive environmental sampling (342 sites on each occasion) for C. difficile using sponge wipes was performed: before and after deep cleaning with detergent/chlorine agent; immediately following HPD; and on two further occasions, 19 days and 20 weeks following HPD. C. difficile isolates underwent polymerase chain reaction ribotyping and multi-locus variable repeat analysis (MLVA). FINDINGS: C. difficile was recovered from 10.8%, 6.1%, 0.9%, 0% and 3.5% of sites at baseline, following deep cleaning, immediately after HPD, and 19 days and 20 weeks after HPD, respectively. C. difficile ribotypes recovered after deep cleaning matched those from CDI cases in the SRU during the previous 10 months. Similarly, 10/12 of the positive sites identified at 20 weeks post-HPD harboured the same C. difficile ribotype (002) and MLVA pattern as the isolate from the first post-HPD CDI case. CDI incidence [number of cases on SRU per 10 months (January-October 2011)] declined from 20 before to seven after the intervention. CONCLUSION: HPD, after deep cleaning with a detergent/chlorine agent, was highly effective for removing environmental C. difficile contamination. Long-term follow-up demonstrated that a CDI symptomatic patient can rapidly recontaminate the immediate environment. Determining a role for HPD should include long-term cost-effectiveness evaluations.

Exploring perinatal shift-to-shift handover communication and process: an observational study.

RATIONALE, AIMS AND OBJECTIVES: Loss of situation awareness (SA) by health professionals during handover is a major threat to patient safety in perinatal care. SA refers to knowing what is going on around. Adequate handover communication and process may support situation assessment, a precursor of SA. This study describes current practices and opinions of perinatal handover to identify potential improvements. METHODS: Structured direct observations of shift-to-shift patient handovers (n = 70) in an academic perinatal setting were used to measure handover communication (presence and order of levels of SA: current situation, background, assessment and recommendation) and process (duration, interruptions/distractions, eye contact, active inquiry and reading information back). Afterwards, receivers' opinions of handover communication (n = 51) were measured by means of a questionnaire. RESULTS: All levels of SA were present in 7% of handovers, the current situation in 86%, the background in 99%, an assessment in 24% and a recommendation in 46%. In 77% of handovers the background was mentioned first, followed by the current situation. Forty-four per cent of handovers took 2 minutes or more per patient. In 52% distractions occurred, in 43% there was no active inquiry, in 32% no eye contact and in 97% information was not read back. The overall mean of the receivers' opinions of handover communication was 4.1 (standard deviation ± 0.7; scale 1-5, where 5 is excellent). CONCLUSIONS: Perinatal handovers are currently at risk for inadequate situation assessment because of variability and limitations in handover communication and process. However, receivers' opinions of handover communication were very positive, indicating a lack of awareness of patient safety threats during handover. Therefore, the staff's awareness of current limitations should be raised, for example through video reflection or simulation training.

Thermal acclimation and regulation of metabolism in a reptile (Crocodylus porosus): the importance of transcriptional mechanisms and membrane composition.

Energy metabolism is fundamental for animal fitness because it fuels locomotion, growth, and reproduction. Mitochondrial capacities often acclimate to compensate for negative thermodynamic effects. Our aim was to determine the importance of transcriptional regulation and membrane fatty acid composition in modulating oxidative capacities at body temperatures selected in a cold and a warm environment by a reptile (Crocodylus porosus). In the cool environment (mean selected T(b) = 21 degrees C), mRNA concentrations of the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivator PPARgamma coactivator 1 alpha (PGC-1alpha), as well as of the cytochrome c oxidase (COX) subunits COX1 and COX5, were significantly higher in the liver but not in skeletal muscle compared with animals in the warm environment (mean selected T(b) = 29 degrees C). F(O)F(1)-ATPase subunit alpha mRNA concentrations were significantly higher in both muscle and the liver in the cool animals. A positive relationship between PGC-1alpha and PPARgamma mRNA concentrations, with an indicator of mitochondrial density (16S rRNA) in muscle and COX and F(O)F(1)-ATPase subunit alpha mRNA concentrations in liver, suggest that these proteins regulate quantity increases of mitochondria during acclimation. The percent saturated fatty acids in liver membranes of cool animals was significantly lower, and the n3 fatty acid content was significantly higher, compared with in warm animals. The n3 fatty acid content was positively related to COX enzyme activity in the liver, and there was a negative relationship between n7 fatty acid content and COX activity in muscle. Hence, metabolic acclimation is mediated by both transcriptional regulation and membrane fatty acid composition. The importance of PGC-1alpha and PPARgamma in a reptile indicate that the mechanisms that regulate metabolism are conserved among vertebrates.

Metabolic depression during aestivation does not involve remodelling of membrane fatty acids in two Australian frogs.

Changes in membrane lipid composition (membrane remodelling) have been associated with metabolic depression in some aestivating snails but has not been studied in aestivating frogs. This study examined the membrane phospholipid composition of two Australian aestivating frog species Cyclorana alboguttata and Cyclorana australis. The results showed no major membrane remodelling of tissue in either frog species, or in mitochondria of C. alboguttata due to aestivation. Mitochondrial membrane remodelling was not investigated in C. australis. Where investigated in C. alboguttata, total protein and phospholipid content, and citrate synthase (CS) and cytochrome c oxidase (CCO) activities in tissues and mitochondria mostly did not change with aestivation in liver. In skeletal muscle, however, CS and CCO activities, mitochondrial and tissue phospholipids, and mitochondrial protein decreased with aestivation. These decreases in muscle indicate that skeletal muscle mitochondrial content may decrease during aestivation. Na(+)K(+)ATPase activity of both frog species showed no effect of aestivation. In C. alboguttata different fat diets had a major effect on both tissue and mitochondrial phospholipid composition indicating an ability to remodel membrane composition that is not utilised in aestivation. Therefore, changes in lipid composition associated with some aestivating snails do not occur during aestivation in these Australian frogs.

Membranes and the setting of energy demand.

In his classic 1961 book, The Fire of Life, Max Kleiber presented a critique of the theories advanced to explain the BMR-body size relationship. One of the theories he dismissed was that the chemical composition of animals varies with body size. Since this time, however, much has been learned about the make-up of BMR in different animals as well as the chemical composition of different-sized animals. Specifically, in recent years it has become obvious that mammal species and bird species do vary in chemical composition in a systematic manner associated with the body size of the species. Small mammal and bird species have cellular membranes that are predominantly polyunsaturated, and as mammal and bird species increase in size, their cellular membranes become progressively less polyunsaturated. Since Kleiber's time, it has also become obvious that a substantial amount of the energy turnover of BMR is associated with the activity of membrane processes, specifically the maintenance of trans-membrane gradients, such as the Na+ gradient across the plasmalemmal membrane and the H+ gradient across the mitochondrial inner membrane. The variation in both membrane composition and membrane processes associated with body size variation in metabolic rate has been combined in the 'membrane pacemaker' theory of metabolism. This theory proposes that: (1) membrane-associated activities are significant and dominant components of BMR; (2) when BMR varies among species, all the activities that constitute BMR vary in unison; (3) species with high mass-specific BMR have highly polyunsaturated membranes while those with low BMR have less polyunsaturation of their membranes; (4) highly polyunsaturated membranes have distinctive physical properties that cause the proteins in the membranes to have a high molecular activity, and this results in higher rates of metabolism of cells, tissues and, consequently, the whole animal. Evidence supporting this theory is both correlative and experimental. Manipulation of membrane composition changes the molecular activity of membrane proteins. These differences in membrane composition may also represent a link between metabolism and aging. They probably explain the lifespan-body size relationship in mammals and birds and also the mammal-bird difference in lifespan.

Dietary fats and membrane function: implications for metabolism and disease.

Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment--in this case dietary fats), membrane lipid composition appears as a predominantly regulated parameter. Membranes remain relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty acid levels over a wide range of dietary variation for these fatty acids. Membrane composition was found to be more responsive to n-6 and n-3 polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3 PUFA and to the n-3/n-6 ratio. These differential responses are probably due to the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by higher animals. Diet-induced modifications in membrane lipid composition are associated with changes in the rates of membrane-linked cellular processes that are major contributors to energy metabolism. For example, in the intrinsic activity of fundamental processes such as the Na+/K+ pump and proton pump-leak cycle. Equally, dietary lipid profile impacts substantially on diseases of the metabolic syndrome with evidence accruing for changes in metabolic rate and neuropeptide regulation (thus influencing both sides of the energy balance equation), in second messenger generation and in gene expression influencing a range of glucose and lipid handling pathways. Finally, there is a growing literature relating changes in dietary fatty acid profile to many aspects of mental health. The understanding of dietary lipid profile and its influence on membrane function in relation to metabolic dysregulation has exciting potential for the prevention and treatment of a range of prevalent disease states.

Membrane lipids and sodium pumps of cattle and crocodiles: an experimental test of the membrane pacemaker theory of metabolism.

The influence of membrane lipid composition on the molecular activity of a major membrane protein (the sodium pump) was examined as a test of the membrane pacemaker theory of metabolism. Microsomal membranes from the kidneys of cattle (Bos taurus) and crocodiles (Crocodylus porosus) were found to possess similar sodium pump concentrations, but cattle membranes showed a four- to fivefold higher enzyme (Na(+)-K(+)-ATPase) activity when measured at 37 degrees C. The molecular activity of the sodium pumps (ATP/min) from both species was fully recoverable when delipidated pumps were reconstituted with membrane from the original source (same species). The results of experiments involving species membrane crossovers showed cattle sodium pump molecular activity to progressively decrease from 3,245 to 1,953 (P < 0.005) to 1,031 (P < 0.003) ATP/min when subjected to two cycles of delipidation and reconstitution with crocodile membrane as a lipid source. In contrast, the molecular activity of crocodile sodium pumps progressively increased from 729 to 908 (P < 0.01) to 1,476 (P = 0.01) ATP/min when subjected to two cycles of delipidation and reconstitution with cattle membrane as a lipid source. The lipid composition of the two membrane preparations showed similar levels of saturated ( approximately 31-34%) and monounsaturated ( approximately 23-25%) fatty acids. Cattle membrane had fourfold more n-3 polyunsaturated fatty acids (11.2 vs. 2.9%) but had a reduced n-6 polyunsaturate content (29 vs. 43%). The results support the membrane pacemaker theory of metabolism and suggest membrane lipids and their polyunsaturates play a significant role in determining the molecular activity of the sodium pump.

Basal metabolic rate: history, composition, regulation, and usefulness.

The concept of basal metabolic rate (BMR) was developed to compare the metabolic rate of animals and initially was important in a clinical context as a means of determining thyroid status of humans. It was also important in defining the allometric relationship between body mass and metabolic rate of mammals. The BMR of mammals varies with body mass, with the same allometric exponent as field metabolic rate and with many physiological and biochemical rates. The membrane pacemaker theory proposes that the fatty acid composition of membrane bilayers is an important determinant of a species BMR. In both mammals and birds, membrane polyunsaturation decreases and monounsaturation increases with increasing body mass and a decrease in mass-specific BMR. The secretion and production of thyroid hormones in mammals are related to body mass, with the allometric exponent similar to BMR; yet there is no body size-related variation in either total or free concentrations of thyroid hormones in plasma of mammals. It is suggested that in different-sized mammals, the secretion/production of thyroid hormones is a result of BMR differences rather than their cause. BMR is a useful concept in some situations but not in others.

Acyl composition of muscle membranes varies with body size in birds.

The acyl composition of phospholipids from pectoral muscle of eight species of birds, ranging in size from the 13 g zebra finch to the 34 kg emu, were measured and combined with recent published results for a 3 g hummingbird. This represents an approximately 11000-fold range in body mass. Muscle phospholipids, and thus muscle membrane bilayers, from birds had a relatively constant unsaturated acyl chain content of 62% but exhibited a significant allometric decline in unsaturation index (number of double bonds per 100 acyl chains) with increasing body mass. There was a significant allometric increase in the percentage of mono-unsaturates and a significant allometric decline in the percentage of n-3 polyunsaturates with increasing body mass, whilst there were no significant allometric trends in either percentage of n-6 or percentage of total polyunsaturates in bird muscle. The relative content of the highly polyunsaturated docosahexaenoic acid (22:6 n-3) showed the greatest scaling with body mass, having an allometric exponent of -0.28. The contribution of this n-3 polyunsaturate to the unsaturation index varied with body size, ranging from less than a 6% contribution in the emu to approximately 70% in the hummingbird. Such allometric variation in the acyl composition of bird muscle phospholipids is similar to that observed in mammals, although birds have fewer n-3 polyunsaturates and more n-6 polyunsaturates than do mammalian phospholipids. This allometric variation in phospholipid acyl composition is discussed with respect to both the metabolic intensity and lifespan of different sized bird species.

Proton leak in hepatocytes and liver mitochondria from archosaurs (crocodiles) and allometric relationships for ectotherms.

It has previously been shown that mitochondrial proton conductance decreases with increasing body mass in mammals and is lower in a 250-g lizard than the laboratory rat. To examine whether mitochondrial proton conductance is extremely low in very large reptiles, hepatocytes and mitochondria were prepared from saltwater crocodiles ( Crocodylus porosus) and freshwater crocodiles ( Crocodylus johnstoni). Respiration rates of hepatocytes and liver mitochondria were measured at 37 degrees C and compared with values obtained for rat or previously measured for other species. Respiration rates of hepatocytes from either species of crocodile were similar to those reported for lizards and approximately one fifth of the rates measured using cells from mammals (rat and sheep). Ten-to-thirty percent of crocodile hepatocyte respiration was used to drive mitochondrial proton leak, similar to the proportion in other species. Respiration rates of crocodile liver mitochondria were similar to those of mammalian species. Proton leak rate in isolated liver mitochondria was measured as a function of membrane potential. Contrary to our prediction, the mitochondrial proton conductance of liver mitochondria from crocodiles was greater than that of liver mitochondria from lizards and was similar to that of rats. The acyl composition of liver mitochondrial phospholipids from the crocodiles was more similar to that in mitochondria from rats than in mitochondria from lizards. The relatively high mitochondrial proton conductance was associated with a relatively small liver, which seems to be characteristic of crocodilians. Comparison of data from a number of diverse ectothermic species suggested that hepatocyte respiration rate may decrease with body mass, with an allometric exponent of about -0.2, similar to the exponent in mammalian hepatocytes. However, unlike mammals, liver mitochondrial proton conductance in ectotherms showed no allometric relationship with body size.

Molecular activity of Na(+)/K(+)-ATPase from different sources is related to the packing of membrane lipids.

The activity of the ubiquitous Na(+)/K(+)-ATPase represents a substantial portion of the resting metabolic activity of cells, and the molecular activity of this enzyme from tissues of different vertebrates can vary several-fold. Microsomes were prepared from the kidney and brain of the rat (Rattus norvegicus) and the cane toad (Bufo marinus), and Na(+)/K(+)-ATPase molecular activity was determined. The membrane lipids surrounding this enzyme were isolated and phospholipids prepared. 'Surface pressure/area' isotherms were measured in monolayers for both membrane lipids and phospholipids using classic Langmuir trough techniques. Microsomal lipid composition was also measured. Whilst significant correlations were observed between membrane composition and Na(+)/K(+)-ATPase molecular activity, the strongest correlations were found between the molecular activity and parameters describing the packing of the surrounding membrane lipids and phospholipids. The influence of membrane lipid composition, especially membrane acyl composition, on the activity of a membrane protein mediated by physical properties of the lipids may represent a fundamental principle applicable to other membrane proteins.

Diet composition and insulin action in animal models.

Critical insights into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by strictly controlled dietary interventions not possible in human studies. Overall, the literature has moved from a focus on macronutrient proportions to understanding the unique effects of individual subtypes of fats, carbohydrates and proteins. Substantial evidence has now accumulated for a major role of dietary fat subtypes in insulin action. Intake of saturated fats is strongly linked to development of obesity and insulin resistance, while that of polyunsaturated fats (PUFAs) is not. This is consistent with observations that saturated fats are poorly oxidized for energy and thus readily stored, are poorly mobilized by lipolytic stimuli, impair membrane function, and increase the expression of genes associated with adipocyte profileration (making their own home). PUFAs have contrasting effects in each instance. It is therefore not surprising that increased PUFA intake in animal models is associated with improved insulin action and reduced adiposity. Less information is available for carbohydrate subtypes. Early work clearly demonstrated that diets high in simple sugars (in particular fructose) led to insulin resistance. However, again attention has rightly shifted to the very interesting issue of subtypes of complex carbohydrates. While no differences in insulin action have yet been shown, differences in substrate flux suggest there could be long-term beneficial effects on the fat balance of diets enhanced in slowly digested/resistant starches. A new area of major interest is in protein subtypes. Recent results have shown that rats fed high-fat diets where the protein component was from casein or soy were insulin-resistant, but when the protein source was from cod they were not. These are exciting times in our growing understanding of dietary factors and insulin action. While it has been clear for some time that 'oils ain't oils', the same is now proving true for carbohydrates and proteins.

Mechanisms underlying the cost of living in animals.

The cost of living can be measured as an animal's metabolic rate. Basal metabolic rate (BMR) is factorially related to other metabolic rates. Analysis of BMR variation suggests that metabolism is a series of linked processes varying in unison. Membrane processes, such as maintenance of ion gradients, are important costs and components of BMR. Membrane bilayers in metabolically active systems are more polyunsaturated and less monounsaturated than metabolically less-active systems. Such polyunsaturated membranes have been proposed to result in an increased molecular activity of membrane proteins, and in this manner the amount of membrane and its composition can act as a pacemaker for metabolism. The potential importance of membrane acyl composition in metabolic depression, hormonal control of metabolism, the evolution of endothermy, as well as its implications for lifespan and human health, are briefly discussed.

What role for membranes in determining the higher sodium pump molecular activity of mammals compared to ectotherms?

The major body organs of mammals have sodium pumps that turn over energy (ATP) three to four times faster than those of ectotherms, at the same temperature. To examine if membranes play a role in these differences in molecular activity, membrane cross-over experiments were performed using two representative species, Rattus norvegicus and Bufo marinus. Microsomal membrane of kidney and brain displayed characteristic molecular activity differences (three- to four-fold) between the species. These molecular activity differences could be removed by delipidation. Pre-existing molecular activities and differences could be restored when reconstituted with original membrane. Using the same reconstitution method, species membrane cross-over experiments resulted in toad sodium pumps in rat membrane significantly increasing (approximately 30-40%) and rat sodium pumps in toad membrane significantly decreasing (approximately 40%) activities in both kidney and brain. Analysis of membrane composition showed reduced cholesterol content and differences in the fatty acids of phospholipids with higher overall unsaturation in the mammal. The scope for membranes to determine protein performance and its broader implications for metabolism are discussed.

Membranes as possible pacemakers of metabolism.

Basal metabolic rate (BMR) varies dramatically among vertebrate species, both (i) being several fold higher in the endothermic mammals and birds compared to the ectothermic reptiles, amphibians and fish, and (ii) being much greater, on a body mass basis, in small vertebrates compared to large vertebrates. These differences in whole animal BMR are also manifest at the cellular level with substantial contributions to basal metabolic activity from the maintenance of various trans-membrane gradients. The percentage contribution of various processes to basal metabolism is remarkably consistent between different vertebrates and when BMR varies, the components of metabolic activity vary in relative unison. Membrane composition also varies between vertebrates and the degree of polyunsaturation of membrane phospholipids is correlated with cellular metabolic activity. In general, the tissue phospholipids and thus membrane bilayers of endotherms are more polyunsaturated than those from similar-sized ectotherms. In mammals membrane polyunsaturation is allometrically related to body mass. We suggest that membranes can act as pacemakers for overall metabolic activity. We propose that such membrane polyunsaturation increases the molecular activity of many membrane-bound proteins and consequently some specific membrane leak-pump cycles and cellular metabolic activity. We hypothesize a possible mechanistic basis for this effect that is based on a greater transfer of energy during intermolecular collisions of membrane proteins with the unsaturated two carbon units (C=C) of polyunsaturates compared to the single carbon units of saturated acyl chains, as well as the more even distribution of such units throughout the depth of the bilayer when membranes contain polyunsaturated acyl chains compared to monounsaturated ones. The proposed pacemaker role of differences in membrane bilayer composition is briefly discussed with respect to the brain (and sensory cells), evolution of mammalian endothermic metabolism, and its clinical implications for humans.