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The mode of action of phloretin and its analogs on the permeability of natural membranes for neutral and charged molecules, such as urea, glucose and chloride has been characterized 25 years ago. In contrast to signal molecules with primary effects on transport systems of natural membranes, phloretin also affects model membranes, i.e., artificial membranes, which do not contain proteins. Since the dipole potential reducing effect of phloretin on mono- and bilayers has been found, it became clear that its primary effect must be a biophysical one: phloretin adsorbs to lipid layers and changes biophysical parameters of these layers. The aim of this work was the characterization of the interaction between the surface-active molecule phloretin and artificial lipid layers. We were able to describe structural and functional parameters of the model systems mono- and bilayer as functions of one or few variables. One of these parameters, the dipole potential, measured as a function of the aqueous phloretin concentration, allowed a critical examination of the Langmuir adsorption model that has been postulated for the interaction between phloretin and lipid layers. Surface pressure versus area per lipid molecule isotherms and surface (dipole) potential change versus area per lipid molecule isotherms, measured at lipid monolayers, allowed a structural description of the phloretin-lipid interaction: phloretin integrates into monolayers dependent on the surface pressure and the phase state of the lipid. Calorimetric measurements confirmed the integration of phloretin into membranes because of the strong decrease of the phase transition temperature, but they also showed that the cooperativity of phase transition is hardly affected, even at very high amounts of phloretin in the membrane. Obviously the interaction between phloretin and lipids is restricted to the head groups, an integration into the hydrocarbon layer is unlikely. 2H NMR measurements with spherical unilamellar vesicles of headgroup-deuterated lipid showed changed quadrupolar splittings indicating the interaction between phloretin and headgroups of the lipids.
Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81% — local recurrence, 19% (n = 65) — distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.
Background
Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome.
Methods
This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included.
Results
A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different “low volume” hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different “high volume” hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications.
Conclusion
Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals.
Adding amino acids to a sucrose diet is not sufficient to support longevity of adult bumble bees
(2020)
Dietary macro-nutrients (i.e., carbohydrates, protein, and fat) are important for bee larval development and, thus, colony health and fitness. To which extent different diets (varying in macro-nutrient composition) affect adult bees and whether they can thrive on nectar as the sole amino acid source has, however, been little investigated. We investigated how diets varying in protein concentration and overall nutrient composition affected consumption, longevity, and breeding behavior of the buff-tailed bumble bee, Bombus terrestris (Hymenoptera: Apidae). Queenless micro-colonies were fed either natural nutrient sources (pollen), nearly pure protein (i.e., the milk protein casein), or sucrose solutions with low and with high essential amino acid content in concentrations as can be found in nectar. We observed micro-colonies for 110 days. We found that longevity was highest for pure pollen and lowest for pure sucrose solution and sucrose solution supplemented with amino acids in concentrations as found in the nectar of several plant species. Adding higher concentrations of amino acids to sucrose solution did only slightly increase longevity compared to sucrose alone. Consequently, sucrose solution with the applied concentrations and proportions of amino acids or other protein sources (e.g., casein) alone did not meet the nutritional needs of healthy adult bumble bees. In fact, longevity was highest and reproduction only successful in micro-colonies fed pollen. These results indicate that, in addition to carbohydrates and protein, adult bumble bees, like larvae, need further nutrients (e.g., lipids and micro-nutrients) for their well-being. An appropriate nutritional composition seemed to be best provided by floral pollen, suggesting that pollen is an essential dietary component not only for larvae but also for adult bees.
Background: According to the classical model of Macevicz and Oster, annual eusocial insects should show a clear dichotomous "bang-bang" strategy of resource allocation; colony fitness is maximised when a period of pure colony growth (exclusive production of workers) is followed by a single reproductive period characterised by the exclusive production of sexuals. However, in several species graded investment strategies with a simultaneous production of workers and sexuals have been observed. Such deviations from the "bang-bang" strategy are usually interpreted as an adaptive (bet-hedging) response to environmental fluctuations such as variation in season length or food availability. To generate predictions about the optimal investment pattern of insect colonies in fluctuating environments, we slightly modified Macevicz and Oster's classical model of annual colony dynamics and used a dynamic programming approach nested into a recurrence procedure for the solution of the stochastic optimal control problem. Results: 1) The optimal switching time between pure colony growth and the exclusive production of sexuals decreases with increasing environmental variance. 2) Yet, for reasonable levels of environmental fluctuations no deviation from the typical bang-bang strategy is predicted. 3) Model calculations for the halictid bee Lasioglossum malachurum reveal that bet-hedging is not likely to be the reason for the graded allocation into sexuals versus workers observed in this species. 4) When environmental variance reaches a critical level our model predicts an abrupt change from dichotomous behaviour to graded allocation strategies, but the transition between colony growth and production of sexuals is not necessarily monotonic. Both, the critical level of environmental variance as well as the characteristic pattern of resource allocation strongly depend on the type of function used to describe environmental fluctuations. Conclusion: Up to now bet-hedging as an evolutionary response to variation in season length has been the main argument to explain field observations of graded resource allocation in annual eusocial insect species. However, our model shows that the effect of moderate fluctuations of environmental conditions does not select for deviation from the classical bang-bang strategy and that the evolution of graded allocation strategies can be triggered only by extreme fluctuations. Detailed quantitative observations on resource allocation in eusocial insects are needed to analyse the relevance of alternative explanations, e.g. logistic colony growth or reproductive conflict between queen and workers, for the evolution of graded allocation strategies.
Hyperolius viridiflavus nitidulus inhabits parts of the seasonally very hot and dry West African savanna. During the long lasting dry season, the small frog is sitting unhidden on mostly dry plants and has to deal with high solar radiation load (SRL), evaporative water loss (EWL) and small energy reserves. It seems to be very badly equipped to survive such harsh climatic conditions (unfavorable surface to volume ratio, very limited capacity to störe energy and water). Therefore, it must have developed extraordinary efficient mechanisms to solve the mentioned Problems. Some of these mechanisms are to be looked for within the skin of the animal (e.g. protection against fast desiccation, deleterious effects of UV radiation and over-heating). The morphology of the wet season skin is, in most aspects, that of a "normal" anuran skin. It differs in the Organization of the processes of the melanophores and in the arrangement of the chromatophores in the Stratum spongiosum, forming no "Dermal Chromatophore Unit". During the adaptation to dry season conditions the number of iridophores in dorsal and ventral skin is increased 4-6 times compared to wet season skin. This increase is accompanied by a very conspicuous change of the wet season color pattern. Now, at air temperatures below 35° C the color becomes brownish white or grey and changes to a brilliant white at air temperatures near and over 40° C. Thus, in dry season State the frog retains its ability for rapid color change. In wet season State the platelets of the iridophores are irregularly distributed. In dry season State many platelets become arranged almost parallel to the surface. These purine crystals probably act as quarter-wave-length interference reflectors, reducing SRL by reflecting a considerable amount of the radiated energy input. EWL is as low as that of much larger xeric reptilians. The impermeability of the skin seems to be the result of several mechanisms (ground substance, iridophores, lipids, mucus) supplementing each other. The light red skin at the pelvic region and inner sides of the limbs is specialized for rapid uptake of water allowing the frog to replenish the unavoidable EWL by using single drops of dew or rain, available for only very short periods.
Reed frogs of the superspecies Hyperolius viridiflavus occur throughout the seasonally very dry and hot African savannas. Despite their small size (300-700 mg), estivating reed frogs do not avoid stressful conditions above ground by burrowing into the soil, but endure the inhospitable climate relatively unprotected, clinging to mostly dry grass sterns. They must have emcient mechanisms to enable them to survive e.g. very high temperatures, low relative hurnidities, and high solar radiation loads. Mechanisms must also have developed to prevent poisoning by the nitrogenous wastes that inevitably result from protein and nucleotide turnover. In contrast to fossorial amphibians, estivating reed frogs do not become torpid. Reduction in metabolism is therefore rather Iimited so that nitrogenous wastes accumulate faster in these frogs than in fossorial amphibians. This severely aggravates the osmotic problems caused by dehydration. During dry periods total plasma osmolarity greatly increases, mainly due to urea accumulation. Of the total urea accumulated over 42 days of experimental water deprivation, 30% was produced during the first 7 days. In the next 7 days rise in plasma urea content was negligible. This strong initial increase of urea is seen as a byproduct of elevated amino acid catabolism following the onset of dry conditions. Tbe rise in total plasma osmolarity due to urea accumulation, however, is not totally disadvantageous, but enables fast rehydration when water is available for very short periods only. Voiding of urine and feces eeases once evaporative water loss exceeds 10% of body weight. Tberefore, during continuous water deprivation, nitrogenous end products are not excreted. After 42 days of water deprivation, bladder fluid was substantially depleted, and urea coneentration in the remaining urine (up to 447 mM) was never greater than in plasma fluid. Feces voided at the end of the dry period after water uptake contained only small amounts of nitrogenous end products. DSF (dry season frogs) seemed not to be uricotelic. Instead, up to 35% of the total nitrogenous wastes produced over 42 days of water deprivation were deposited in an osmotically inert and nontoxic form in iridophore crystals. The increase in skin purine content averaged 150 µg/mg dry weight. If urea had been the only nitrogenous waste product during an estivation period of 42 days, lethal limits of total osmolarity (about 700 mOsm) would have been reached 10-14 days earlier. Thus iridophores are not only involved in colour change and in reducing heat load by radiation remission, but are also important in osmoregulation during dry periods. The seIective advantages of deposition of guanine rather than uric acid are discussed.