Organic Reserves Research Articles

The Unmet Need in Chronic Lymphocytic Leukemia: Impact of Comorbidity Burden on Treatment Patterns and Outcomes in Elderly Patients

Introduction: Chronic lymphocytic leukemia (CLL) is a disease of the elderly. Elderly patients often have increased comorbidity burden and loss of organ reserve that may impact their ability to tolerate cancer therapy. We described realworld characteristics of typical CLL patients and identified factors predictive of receiving treatment. Methods: A retrospective cohort analysis of 8343 first primary CLL patients was performed using the linked Surveillance, Epidemiology, and End Results-Medicare database. Patients were diagnosed from 1/1/1998 to 12/31/2007, >66 years, and continuously enrolled in Medicare Parts A and B in the year prior to diagnosis. Comorbidity was examined using the National Cancer Institute comorbidity index and the Cumulative Illness Rating Scale. Cox and Logistic regression modeling assessed patient characteristics predictive of receiving treatment within the first year after diagnosis. Results: Median follow-up time from diagnosis was 782 days. During the study time period, there were 3366 (40%) treated patients and 4977 (60%) untreated. Even among those diagnosed with advanced stage (n = 4213), 57% were not treated. Treated patients were younger at diagnosis compared to untreated (76 vs. 79; p 80 years, females, and with early stage disease; and significantly decreased with increasing comorbidity burden. Conclusions: Age, gender, comorbidity and stage were predictive of receiving treatment. Among patients with advanced stage, 57% were not being treated possibly due to older age and/or higher comorbidity burden.

Biochemical composition of the hemolymph, hepatopancreas, ovary, and muscle during ovarian maturation in the penaeid shrimps Fenneropenaeus merguiensis and F. penicillatus (Crustacea: Decapoda)

The present study quantifies the concentrations of proteins, carbohydrates, and lipids in the hemolymph, ovary, hepatopancreas, and muscle of Fenneropenaeus merguiensis and F. penicillatus during ovarian maturation. Proteins were the major constituent in the hemolymph and ovaries of the 2 species, while lipids were the major constituent in the hepatopancreas. The protein, carbohydrate, and lipid contents in the ovaries of both species increased as ovaries matured. The increase in the protein, carbohydrate, and lipid contents in the ovaries during maturation indicates that the ovaries utilize these constituents to mature. Concentrations of lipids in the hepatopancreas decreased with ovarian maturation in both species. It appears that the lipid demands of ovarian maturation are met by the hepatopancreas reserves, as lipid decrease in the hepatopancreas coincided with an increase in fully mature ovaries. The increase of protein, lipid, and carbohydrate contents in the hemolymph with ovarian maturation in both species shows that the hemolymph serves as a vehicle for the mobilization of organic reserves. Proteins, carbohydrates, and lipids in the muscles of the 2 species did not seem to be related to ovarian maturation. In the present study, both the gonadosomatic index and the hepatopancreatic index also increased with ovarian maturation in F. merguiensis and F. penicillatus.

Specific features of soil organic matter in forest landscapes of Karelia

The organic matter reserves and the soil humus state are assessed in three types of landscapes of the middle taiga (Karelia). Peat soils are the main organic matter reservoir. Hence, the greater their area, the higher the organic matter reserves in a particular landscape. The organic matter stocks in the group of semihydromorphic and hydromorphic soils clearly correlate with the degree of their waterlogging. The distribution of organic matter reserves within these soils depends on the ratio between the areas of boggy forests and open mires. The forest supporting quality of the soil is related to the organic matter composition and parent rock (the properties of the soil mineral horizons) rather than to the organic matter stocks. The data obtained may be used for assessing the forest supporting qualities of the soils and the basis for estimating the carbon budget in the landscapes.

Response-Adapted Therapy for Diffuse Large B-Cell Non-Hodgkin's Lymphoma (DLBCL)Based On Early [18F] FDG-PET Scanning: An Eastern Cooperative Oncology Group Study (E3404)

AbstractAbstract 687 Background:A persistently positive PET scan after just a few cycles of therapy is predictive of a poor clinical outcome in diffuse large B-cell lymphoma (DLBCL). Prior data suggested that about one third of patients remain PET positive after 2–4 cycles, with ≤ 20% 2 year progression-free survival (PFS) for such patients. A response-adapted strategy was studied in E3404 to test the hypothesis that an early treatment change to four cycles of R-ICE might reduce the treatment failure rate of patients whose PET scan remained positive after an initial 3 cycles of R-CHOP. Study Design:Previously untreated patients with DLBCL stage III, IV, or bulky II, with measurable disease, HIV negative, and with adequate organ reserve, were eligible. PET/CT scan was performed before treatment and again after 3 cycles of R-CHOP. A fourth cycle of R-CHOP was given while the scan was centrally reviewed and scored as either positive or negative for FDG-avid tumor by a single reviewer using criteria based on modifications of the Harmonization Criteria. Persistently PET-positive patients received 4 cycles of R-ICE, while PET-negative patients received 2 more cycles of R-CHOP, for a total of 6 cycles. PET/CT was performed again at the end of treatment. A ≥45% 2 year PFS for mid-treatment PET- positive patients was viewed as a promising result, with 88% power if 33 such patients were accrued. Total accrual of 99 patients was therefore planned. Results:Of 100 patients accrued, 78 were eligible; all but 1 ineligibility was based on central pathology review. Fifty-eight were male; median age was 62 years (20–74); 13% IPI 0–1, 31% IPI 2, 37% IPI 3, and 19% IPI 4–5. Seventy-four of 78 (95%) patients completed the first 3 cycles of R-CHOP. Of 72 patients continuing treatment, 67 (93%) completed protocol treatment: 83% of mid-treatment PET-positive and 93% of PET-negative patients. Of 74 patients undergoing mid-treatment PET scan, 12 (16%) were scored as positive, and 62 (84%) as negative. At the end of treatment, 13% were scored as positive, and 87% as negative. Two-year PFS, from the time of study entry, was 72% among all eligible patients. Two year PFS from the time of mid-treatment PET scan was 45% (90% CI, 21–67%) for patients scored as mid-treatment PET-positive, and 77% (90% CI 67–85%) for patients scored as mid-treatment PET-negative. The 80% confidence interval (corresponding to a test with a one-sided type I error of 10%) did not include the null hypothesis of 25%, implying that the results met the pre-specified threshold. Among all 78 eligible patients, 10 have died (13%); 5-year overall survival was 87% (90% CI 78–92%) Three-year overall survival was 67% (90% CI 40–84%) for mid-treatment PET-positive patients, and 93% (90% CI 85–97%) for mid-treatment PET-negative patients. Conclusions:The 2-year PFS for mid-treatment PET-positive patients met the threshold to be considered promising, but the confidence interval was wider than expected due to the small patient number. In addition, the inter-observer variability in the interpretation of mid-treatment PET scans as a binary variable in this study (studied and reported separately in Horning SJ et al. Blood 2010) implies that treatment modification based on early PET scanning should remain confined to clinical trials. [Display omitted] [Display omitted] Disclosures:Swinnen:Celgene: Consultancy; Genentech: Research Funding. Quon:Genentech: Research Funding. Advani:Pharmacyclics: Research Funding. Kahl:Roche/Genentech: Consultancy; Celgene: Consultancy; Cell Therapeutics: Consultancy; Janssen: Consultancy; GSK: Consultancy; Gilead: Consultancy. Horning:Genentech: Employment; Roche: stock, stock Other.

Transitory Carbohydrate Reserves in Vegetative Organs of Coconut Under Different Growth Conditions and Its Relation with Reproductive and Vegetative Growth of The Palm

The study evaluated the non structural carbohydrate reserves in vegetative organs and vegetative and reproductive growth rates of a 25 year old Tall x Tall coconut (Cocos nucifera L) during the peak season of coconut yield (May/June) under S2 and S4 Land Suitability Classes (LSC) in three Agro Ecological Regions (WL3, IL1a and DL3). Trunk (inner and outer), root (new roots and mature roots) and leaf samples (petiole, leaf blade and leaf ekel from 9th, 14th and 22nd fronds) were collected, total soluble sugars (TSS) and starch concentrations were analyzed and TSS and starch reserves at palm level were estimated. Growth rate of trunk and leaves (vegetative) and developing nuts of all bunches of a palm (reproductive) were measured. The highest (3.86 kg month-1) and the lowest (0.81 kg month-1) reproductive growth rates and the highest (3.8 kg month-1) and the lowest (2.1 kg month-1) vegetative growth rates were found in the palms grown under S2 and S4 LSC in the DL3, respectively. There was a constant vegetative growth rate of 3.3 kg month-1 for the palms in WL3 and IL1a irrespective of the AER or LSC. The most dominant nonstructural reserve substance in the vegetative organs of coconut was soluble sugars (TSS) and the starch concentration was approximately half the TSS concentration in all vegetative parts irrespective of the AER or the LSC. TSS and starch showed a marked pattern of distribution, with highest concentration in trunk (114-134 mg g-1 TSS and 60-83 mg g-1 starch), intermediate in leaves (69-117 mg g-1 TSS and 33-69 mg g-1 starch) and lowest in roots (22-79 mg g-1 TSS and 17-33 mg g-1 starch). The highest TSS and starch reserves in leaf compartments (kg per palm) were found in the S2-grown palms of the DL3 which had the highest reproductive and vegetative growth rates during May-June season. DOI: http://dx.doi.org/10.4038/cocos.v19i2.4753

Anestesia nel grande anziano: generale vs ALR

The number of patients aged more than 80 years, so-called great elders, that undergo surgery is growing in relation to increased life expectancy. Due to the reduction of functional reserves of organs and systems, the choice of anesthesia, between general and locoregional, must be carefully considered and tailored to the patient. This report presents the case record of our Institute for the years 2009–2011.

Vascular Rejuvenation Through the Stromal Cell-Derived Factor 1α/CXC Chemokine Receptor Type 4/Janus Kinase 2 Signalling Pathway

See related article, pp 1225–1231 Aging progressively narrows the functional reserve of several organs and tissues, in association with variable degrees of morphological changes. Current views strongly indicate that resident stem and progenitor cells contribute to tissue homeostasis throughout life in virtually all organs and tissues, even those traditionally considered as postmitotic. In the aging human heart, the progressive loss of cardiomyocytes is balanced by an increased myocyte turnover through cardiac stem cells.1 However, this balance is compromised, and net cardiomyocyte loss is accelerated when cardiovascular risk factors are present, either nonmodifiable, such as male sex,1 or modifiable, such as diabetes mellitus.2 Similarly, an endothelial damage is normally repaired by resident endothelial cells and endothelial progenitors (EPCs), but this mechanism is impaired by cardiovascular risk factors and age, per se.3 Several authors have documented that bone marrow-derived EPCs from aged animals or humans are quantitatively reduced and dysfunctional,4,5 thus predisposing to atherosclerosis. This has important pathophysiological and therapeutic implications, because autologous EPCs are being used in cell therapy trials that often involve aging individuals. Aging is a major determinant of bone marrow function, which can explain the reduced EPC levels in the elderly. On the other …

The potential role of podocysts in perpetuation of the common jellyfish Aurelia aurita s.l. (Cnidaria: Scyphozoa) in anthropogenically perturbed coastal waters

Common moon jellyfish, Aurelia spp. bloom seasonally in eutrophic or polluted coastal waters around the world. We hypothesized that podocysts, a part of asexual reproduction of the benthic polyps, were important in perpetuating populations of Aurelia aurita s.l. in anthropogenically perturbed waters. We examined the effects of temperature, salinity, dissolved oxygen concentrations, and food on the encystment and excystment of A. aurita podocysts. Podocysts were formed only by unfed or poorly-fed polyps (≤4.8 μg C polyp−1 day−1), indicating that starvation was the primary cause of encystment, while increased temperatures accelerated podocyst production rate. Encystment was never induced by changed salinity (15–32) or dissolved oxygen concentration (1–5 mg O2 l−1). Excystment occurred only when podocysts were returned to 19°C from 28°C and to oxic waters from hypoxic (0.2–1.0 mg O2 l−1). The podocysts were capable of surviving for up to 3.2 year. Histology revealed that newly-formed podocysts contained rich organic reserves (e.g., carbohydrate, protein, and lipid) that were gradually consumed while encysted. Podocysts may contribute minimally to increasing A. aurita polyp abundance, but they can insure maintenance of the population in adverse environmental conditions and in predator attacks. Podocysts may also enable the population to extend to areas where polyp survival is marginal.

Abstract PR5: A phase II study of sorafenib in patients with stage IV non-small cell lung cancer (NSCLC) with a K-Ras mutation

Abstract Background: In a pilot study (1) we found sorafenib to display clinical activity against patients with K-Ras positive NSCLC, sufficient for formal phase II testing. Methods: Patients with K-Ras mutated NSCLC that progressed after at least 1 platinum containing regimen with adequate organ reserve, ECOG 0–2, who provided written informed consent according to local IRB regulations were eligible. A tumor biopsy confirming the presence of a K-Ras mutation was mandatory. Treatment consisted of sorafenib 400 mg BID until disease progression or unacceptable toxicity. Dose reductions and delays were specified per protocol in the face of CTC toxicities grade 3 and 4. Primary endpoint: Rate of No Progression (NPR) at 6 weeks. Secondary endpoints: duration of response, progression free survival (PFS), overall survival and treatment related toxicities. A 2-stage design was implemented (Simon's optimal design; p0=40%, p1=60%, alpha=0.05, beta=0.20) for a total number of 48 pts. Results: 59 patients were entered between May 1st 2010 and February 18 2011. Median age was 58 (range 46–79) years, 17 Male/42 Female, ECOG PS 0/1/2 23/32/4. 57 patients started treatment. At 6 weeks 5 PR, 25 SD, 27 PD were observed; NPR 52.6%. Fifteen patients stopped treatment before 6 weeks, of which 10 patients stopped due to (clinical) progression. Median duration of treatment was 9 (range 0–62) weeks, 2 patients are still on treatment. Median duration of response was 32 (range 5–58) weeks. Median PFS was 2.3 months, median OS was 4.9 months, 14 patients still alive. Dose modifications were realized in 21 patients, of whom 4 discontinued treatment. Most reported adverse events were fatigue (6.4%), hand-foot reaction (5.7%), dyspnea (5.6%), anorexia (3.7%) diarrhea (3.6%) and cough (3.6%). Sorafenib related grade 3-4 toxicity was reported in 10 patients. Five patients with grade 3 skin toxicity, 4 patients with grade 3 gastrointestinal toxicity and 1 patient with both grade 3 metabolic abnormalities and a grade 3 pneumonitis. Conclusion: Treatment with sorafenib has relevant clinical activity in patients with K-Ras mutational status. Further randomized study with this agent is warranted. This abstract is also presented as Poster B18.

How can we Improve Drug Safety When Treating Frail Elderly Patients?

Studies on drug safety are often done on patients with a single medical condition receiving few or no other drugs. In clinical practice, however, such patients are rare. A more typical patient is old, has several medical conditions and uses many drugs. These patients should be our focus when studying and reducing drug-related problems (DRPs). A DRP is defined as “an event or circumstance involving drug treat ment that actually or potentially interferes with a patient’s experiencing an optimum outcome of medical care” [1]. According to this definition, DRPs include adverse drug reactions (ADRs), but also overdosage, subtherapeutic dosage, noncompliance and drug-drug interactions. DRPs are a well-known cause of morbidity and mortality in the elderly, but are often preventable [2-5]. The potential for DRPs and ADRs increases with age [6]. Older people are vulnerable to DRPs for several reasons, including physiological alterations that affect pharmacody namics and pharmacokinetics, resulting in enhanced and prolonged drug effects; increased prevalence of chronic diseases; and concomitant use of other medications. Physiological Alterations with Age Older people have lower physiologic reserves in most organs compared to younger adults, and with aging, they possess negatively affect ing homeostatic mechanisms. Together with the alterations in pharmacodynamics and pharmacokinetics, this increases the risk of ADRs.

Seasonally and Spatially Coordinated Strategy of Detritus Conservation and Use in the World’s Largest Mangrove Ecosystem

A study in the inter-tidal regions of Indian Sundarban mangrove forest has revealed that intensified detritus input into marine estuaries during pre-monsoon (summer) coupled with lowest volume and intensity of water influx into the sea through the Ganges during this time create a localized and relatively static pool of nutrients in the estuarine water. This detritus reserve immediately acts as the source of nutrients for the huge population of detrivores that invade these estuaries during the monsoon when water flow through the rivers is huge and is coupled with severe rolling of water in the confluence zones. Rolling of water facilitates the uplifting and pushing of organic reserves of these inundated estuaries more towards the sea for the availability to animals migrating from sea towards the river mouth. C/N ratio has been very high in the soil with high soil organic C content indicating soil N limitation. Huge detritus supply has been ensured by a moderate decomposition of a huge litter-fall, with a maximum of 9721 g m−2 year−1 and high below ground fine + coarse root production that can range up to 3265 g m−2 year−1 measured up to a depth of 15 cm only. Peak litter fall coupled with high root mortality have been encountered during pre-monsoon when soil water’s salinity is highest and dissolved oxygen concentration is at its lowest. As a part of nutrient conservation strategy, lion share of the total organic trash instead of being acted upon by decomposers goes into a very efficient mechanism of ‘formation’ of relatively static (lacks much mobilization) detritus food reserve particularly during pre monsoon, for its subsequent ‘best possible utilization’ by the detrivores that invade the ecosystem and reproduce in large numbers during monsoon.

Late nitrogen fertilization affects nitrogen remobilization in wheat

AbstractA pot experiment with wheat plants was carried out to study how late application of nitrogen (N) fertilizer affects the use of pre‐anthesis N reserves during the grain‐filling period. Increasing doses of N fertilizer were applied (0, 40, and 52 mg N plant–1), either in two amendments (growth stages GS20 and GS30, according to Zadoks scale) or in three amendments (GS20, GS30, and GS37). The experiment was arranged in a complete randomized three‐block design with 129 plants per treatment. The plants were watered daily, harvested every 2 d between anthesis and maturity, and were separated into roots, leaf sheaths, leaf blades, and ears for further N determination. Grain N concentration improved due to a late N application in GS37 by 14% (higher N dose) and by 7% (further splitting the same N‐fertilizer dose, respectively). The higher the N‐fertilizer dose applied, the greater was the amount of pre‐anthesis reserves in vegetative organs, these reserves became later available for remobilization. Although splitting the same N dose in three amendments did not increase the N reserves, these reserves were more efficiently remobilized allowing an improvement in grain N concentration. The fertilizer management did not change the temporary pattern of N accumulation in the ear, but did induce a change in the amount of N remobilized and in the contribution of each organ (root, leaf sheath, leaf blade) to this remobilization. Late N amendment allowed a greater N availability of leaf blades and ear N reserves (from 20% up to 26% and from 19% up to 22%, respectively) for remobilization towards the grain, decreasing the root contribution from 28% down to 15%, while the contribution of leaf sheaths was maintained around 35% irrespective of the N applied.

Age-Related Changes in Pharmacokinetics

Ageing is characterized by a progressive decline in the functional reserve of multiple organs and systems, which can influence drug disposition. In addition, comorbidity and polypharmacy are highly prevalent in the elderly. As ageing is associated with some reduction in first-pass metabolism, bioavailability of a few drugs can be increased. With ageing body fat increases and total body water as well as lean body mass decrease. Consequently, hydrophilic drugs have a smaller apparent volume of distribution (V) and lipophilic drugs have an increased V with a prolonged half-life. Drugs with a high hepatic extraction ratio display some age-related decrease in systemic clearance (CL), but for most drugs with a low hepatic extraction ratio, CL is not reduced with advancing age. In general, activities of cytochrome P450 enzymes are preserved in normal ageing and the genetic influence is much more striking than age effects. Drug transporters play an important role in pharmacokinetic processes, but their function and pharmacology have not yet been fully examined for agerelated effects. One third of elderly persons show no decrease in renal function (GFR > 70 mL/min/1.73 m2). In about two thirds of elderly subjects, the age-related decline of renal function was associated with coexisting cardiovascular diseases and other risk factors. In the elderly a large interindividual variability in drug disposition is particularly prominent. In conclusion, the complexity of interactions between comorbidity, polypharmacy, and age-related changes in pharmacokinetics (and pharmacodynamics) justify the old and well-known dosing aphorism " start low, go slow" for aged individuals.

Changes of carbon and nitrogen metabolites in white spruce (Picea glauca [Moench] Voss) of contrasted growth phenotypes

The present study documents the changes occurring at the biochemical level in white spruce trees (Picea glauca [Moench] Voss) with contrasted growth phenotypes during the summer period. Full-siblings of tall versus small spruces were grown under controlled conditions at constant day/night temperatures (24/15°C) and exposed to a decreasing photoperiod (15.7–12.2 h) simulating natural photoperiod reduction during the summer in eastern Canada. Growth parameters (stem height and tree biomass) were determined and non structural carbohydrates, soluble proteins and amino acids were quantified in current-year needles and stem, oldest stem and roots from mid-July until the end of September 2006. Sucrose was the main soluble sugar found in all organs, but its concentrations did not significantly change during the summer. In contrast, starch concentrations rapidly declined by the end of the experiment, especially in needles and stems. Both sucrose and starch did not generally differ between growth phenotypes. Total soluble protein significantly accumulated by mid-August (14.4 h of photoperiod) in small trees. Arginine and glutamine were the most abundant amino acids found in spruce organs, and their concentrations strongly increased at 14.4 h of photoperiod, especially in small trees. Our results highlight marked differences in nitrogen metabolism in late summer between contrasted growth phenotypes, especially for arginine, an amino acid typically associated with growth arrest and nitrogen reserve in perennial species. They also reveal that old stems and roots are important storage organs of organic reserves.

Maintaining Tissue Perfusion in High-Risk Surgical Patients

Surgical patients with limited organic reserve are considered high-risk patients and have an increased perioperative mortality. For this reason, they need a more rigorous perioperative protocol of hemodynamic control to prevent tissue hypoperfusion. In this study, we systematically reviewed the randomized controlled clinical trials that used a hemodynamic protocol to maintain adequate tissue perfusion in the high-risk surgical patient. We searched MEDLINE, Embase, LILACS, and Cochrane databases to identify randomized controlled clinical studies of surgical patients studied using a perioperative hemodynamic protocol of tissue perfusion aiming to reduce mortality and morbidity; the latter characterized at least one dysfunctional organ in the postoperative period. Pooled odds ratio (POR) and 95% confidence interval (CI) were calculated for categorical outcomes. Thirty-two clinical trials were selected, comprising 5056 high-risk surgical patients. Global meta-analysis showed a significant reduction in mortality rate (POR: 0.67; 95% CI: 0.55-0.82; P < 0.001) and in postoperative organ dysfunction incidence (POR: 0.62; 95% CI: 0.55-0.70; P < 0.00,001) when a hemodynamic protocol was used to maintain tissue perfusion. When the mortality rate was >20% in the control group, the use of a hemodynamic protocol to maintain tissue optimization resulted in a further reduction in mortality (POR: 0.32; 95% CI: 0.21-0.47; P < 0.00,001). Monitoring cardiac output with a pulmonary artery catheter and increasing oxygen transport and/or decreasing consumption also significantly reduced mortality (POR: 0.67; 95% CI: 0.54-0.84; P < 0.001 and POR: 0.71; 95% CI: 0.57-0.88; P < 0.05, respectively). Therapy directed at increasing mixed or central venous oxygen saturation did not significantly reduce mortality (POR: 0.68; 95% CI: 0.22-2.10; P > 0.05). The only study using lactate as a marker of tissue perfusion failed to demonstrate a statistically significant reduction in mortality (OR: 0.33; 95% CI: 0.07-1.65; P > 0.05). In high-risk surgical patients, the use of a hemodynamic protocol to maintain tissue perfusion decreased mortality and postoperative organ failure. Monitoring cardiac output calculating oxygen transport and consumption helped to guide therapy. Additional randomized controlled clinical studies are necessary to analyze the value of monitoring mixed or central venous oxygen saturation and lactate in high-risk surgical patients.

Organic matter in present-day ecosystems of the Arctic Ocean

Global climate changes in the Arctic region that resulted in thawing and significant displacement of ice, which cleared approximately 30% of the Arctic Ocean surface, naturally affected the state of its eco� systems. In this connection, the assessment of organic mat� ter reserves and intensity of productive/destructive processes in different ecosystems of the Arctic basin has become a topical task. Bearing this in mind, we conducted complex biohydrochemical studies of aqueous and ice ecosystems of the Arctic basin during Cruise 28 of the R/V Akademik Fedorov (August–Sep� tember 2008) in the framework of the program “Inter� national Polar Year 2007–2008.” These works included study of several parameters for these ecosys� tems: (1) the spatial distribution of dissolved and sus� pended organic carbon (Corg), mineral and organic N and P forms, and the main biochemical components in organic matter (proteins, lipids, carbohydrates); (2) concentrations of carotenoids and chlorophyll forms a, b, and c; (3) intensity of hydrolytical and redox reactions of organic matter decomposition up to its complete mineralization with the formation of sim� ple oxides. The targeted water sampling was conducted by the Rosette equipment with 5 l plastic Niskin bathometers and a CTD sonde with account for vertical changes in the temperature and salinity. In total, 420 water sam� ples were collected. The sampling methods, treatment of samples prior to their analysis, and procedures of corresponding measurements are described in detail in [1, 2]. The analysis of the obtained data reveals that dis� similar to shelf ecosystems of the Arctic seas, where processes of primary organic matter production were

Esophageal cancer: definitive chemoradiotherapy for elderly patients

To investigate the efficacy and toxicity of definitive chemoradiotherapy (CRT) for elderly patients with locally advanced esophageal cancer. Twenty-two patients aged over 75 that performed definitive CRT were retrospectively reviewed. The regimen included concurrent CRT consisting of two cycles of chemotherapy (CTx) of platinum and 5-fluorouracil, and radiation therapy (RT) of 50-50.4 Gy (actual range: 45.4-71.4 Gy), and additional CTx where possible. Both CTx and RT were reduced in dose and field where necessary. The disease-free survival rate and the overall survival rate at 3 years were 33.3% ± 11.4% and 25.9% ± 10.8%. Grade 4 leukocytopenia and thrombocytopenia occurred in three (14%) and four (18%) patients. Treatment-related death was suspected in up to four (18%) patients at the most. Univariate analyses for disease-free survival showed that neither total radiation dose nor number of total cycles of CTx was significant. The pattern of relapse was predominantly more frequent in the intra-RT field than outside the RT field. For elderly patients, adverse events are frequent, and decreased organ reserve may cause treatment-related death. Reduction in CTx dose or RT field, appropriate only for two cycles of CTx, and careful monitoring may help to minimize toxicity. Physicians should not be too afraid of adverse events or be negative about CRT for elderly patients, as long as comorbidities and complications are managed carefully.

Applied Healthspan engineering.

According to the Homeric Hymn to Aphrodite, when Eos asked Zeus for Tithonus to be granted immortality, she forgot to ask for eternal youth. Applied Healthspan Engineering (AHE) seeks to address this problem. All organisms have a minimal level of functional reserve required to sustain life that eventually declines to a point incompatible with survival at death. AHE seeks to maintain or restore optimal functional reserve of critical tissues and organs. Tissue reserve correlates with well being. Diet, physical exercise, and currently available small-molecule-based therapeutics may attenuate the rate of decline of specific organs or organ systems, but are unlikely to restore lost reserve. Inherent evolutionary-derived limitations in tissue homeostasis and cell maintenance necessitate the development of therapies to enhance regenerative processes and possibly replace whole organs or tissues. AHE supports the study of cell, tissue, and organ homeostatic mechanisms to derive new regenerative and tissue replacement therapies to extend the period of human health.

Treatment of small‐cell lung cancer in elderly patients

Small-cell lung cancer (SCLC) represents 15% to 20% of all lung carcinomas. Approximately 30% to 40% of these cases are diagnosed in patients older than 70 years of age. Staging of SCLC classifies patients as having either limited or extensive-stage disease. The standard treatment for limited-stage disease is platinum-based chemotherapy, combined with external-beam thoracic radiotherapy, whereas platinum-based regimens alone represent the standard of care for extensive-stage disease. In the elderly population, treatment of SCLC is more challenging given the decline in physiological organ reserve and the presence of comorbidities. The majority of data are drawn from retrospective studies, which are likely to suffer from selection bias. However, limited prospective data are available to guide treatment decisions in that special population. Nonetheless, these data demonstrate that standard approaches are feasible in carefully selected elderly patients. The purpose of this article is to review the currently available evidence on treatment of SCLC in patients older than 65-70 years of age.

Can we intervene in human ageing?

Ageing is a progressive failure of defence and repair processes that produces physiological frailty (the loss of organ reserve with age), loss of homeostasis and eventual death. Over the past ten years exceptional progress has been made in understanding both why the ageing process happens and the mechanisms that are responsible for it. The study of natural mutants that accelerate some, but not all, of the features of the human ageing process has now progressed to a degree that drug trials are either taking place or can be envisaged. Simultaneously, a series of mutations have been identified in different species that confer extended healthy life, indicating that the ageing process is much more malleable than might have been expected and that single interventions have the potential to delay the onset of multiple age-associated conditions. Data generated using these organisms have led to the formulation of a powerful new hypothesis, the 'green theory' of ageing. This proposes that a finite capacity to carry out broad-spectrum detoxification and recycling is the primary mechanistic limit on organismal lifespan. This is turn suggests important new experimental approaches and potential interventions designed to increase healthy lifespan.