Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution.

Immune priming and pathogen resistance in ant queens.

Growing empirical evidence indicates that invertebrates become more resistant to a pathogen following initial exposure to a nonlethal dose; yet the generality, mechanisms, and adaptive value of such immune priming are still under debate. Because life-history theory predicts that immune priming and large investment in immunity should be more frequent in long-lived species, we here tested for immune priming and pathogen resistance in ant queens, which have extraordinarily long life span. We exposed virgin and mated queens of Lasius niger and Formica selysi to a low dose of the entomopathogenic fungus Beauveria bassiana, before challenging them with a high dose of the same pathogen. We found evidence for immune priming in naturally mated queens of L. niger. In contrast, we found no sign of priming in virgin queens of L. niger, nor in virgin or experimentally mated queens of F. selysi, which indicates that immune priming in ant queens varies according to mating status and mating conditions or species. In both ant species, mated queens showed higher pathogen resistance than virgin queens, which suggests that mating triggers an up-regulation of the immune system. Overall, mated ant queens combine high reproductive output, very long life span, and elevated investment in immune defense. Hence, ant queens are able to invest heavily in both reproduction and maintenance, which can be explained by the fact that mature queens will be protected and nourished by their worker offspring.

Speciation of naturally-accumulated uranium in an organic-rich soil of an alpine region (Switzerland)

Very high concentrations of uranium (up to 4000 ppm) were found in a natural soil in the Dischma valley, an alpine region in the Grisons canton in Switzerland. The goal of this study was to examine the redox state and the nature of uranium binding in the soil matrix in order to understand the accumulation mechanism. Pore water profiles collected from Dischma soil revealed the establishment of anoxic conditions with increasing soil depth. A combination of chemical extraction methods and spectroscopy was applied to characterize the redox state and binding environment of uranium in the soil. Bicarbonate extraction under anoxic conditions released most of the uranium indicating that uranium occurs predominantly in the hexavalent form. Surprisingly, the uranium redox state did not vary greatly as a function of depth. X-ray absorption near edge spectroscopy (XANES), confirmed that uranium was present as a mixture of U(VI) and U(IV) with U(VI) dominating. Sequential extractions of soil samples showed that the dissolution of solid organic matter resulted in the simultaneous release of the majority of the soil uranium content (>95%). Extended X-ray absorption fine structure (EXAFS) spectroscopy also revealed that soil-associated uranium in the soil matrix was mainly octahedrally coordinated, with an average of 1.7 axial (at about 1.76 Å) and 4.6 to 5.3 equatorial oxygen atoms (at about 2.36 Å) indicating the dominance of a uranyl-like (UO22+) structure presumably mixed with some U(IV). An additional EXAFS signal (at about 3.2 Å) identified in some spectra suggested that uranium was also bound (via an oxygen atom) to a light element such as carbon, phosphorus or silicon. Gamma spectrometric measurements of soil profiles failed to identify uranium long-life daughter products in the soil which is an indication that uranium originates elsewhere and was transported to its current location by water. Finally, it was found that the release of uranium from the soil was significantly promoted at very low pH values (pH 2) and increased with increasing pH values (between pH 5 and 9).

What is the Omega-Loop Gastric Bypass and Why is it Criticized?

The omega-loop gastric bypass (OLGBP), also called "mini-gastric bypass" or "single-anastomosis" gastric bypass is a form of gastric bypass where a long, narrow gastric pouch is created and anastomosed to the jejunum about 200- 250 cm from the angle of Treitz in an omega loop fashion, thereby avoiding a jejuno-jejunostomy.Proponents of the OLGBP claim that it is a safer and simpler operation than the traditional Roux-en-Y gastric bypass (RYGBP), easier to teach, that gives the same results in terms of weight loss than the RYGBP. One randomized study comparing the two techniques showed similar results after five years.The OLGBP is criticized because it creates an anastomosis between the gastric pouch and the jejunum where a large amount of biliopancreatic juices travel, thereby creating a situation where reflux of the latter into the stomach and distal esophagus is likely to develop. Such a situation has clearly been associated, in several animal studies, with an increased incidence of gastric cancer, especially at or close to the gastro-jejunostomy, and with an increased risk of lower esophageal cancer. In clinical practice, omega-loop gastrojejunostomies such as those used for reconstruction after gastric resection for benign disease or distal gastric cancer have been associated with the so called classical anastomotic cancer, linked to biliary reflux into the stomach, despite the fact that epidemiological studies about this do not show uniform results. Although no evidence at the present time links OLGBP to an increased risk of gastric cancer in the human, this possibility raises a concern among many bariatric surgeons, especially in the view that bariatric surgery is performed in relatively young patients with a long life expectancy, hence prone to develop cancer if indeed the risk is increased. Another arguments used against the OLGBP is that the jejuno-jejunostomy in the traditional RYGBP is easy to perform and associated with virtually no complication.Supporters of the OLGBP claim that the liquid that refluxes into the stomach after their procedure is not pure bile and pancreatic juice, but a combination of those with jejunal secretions, and that the latter is not as harmful. We would urge the proponents of the OLGBP to undertake the necessary animal studies to show that their assumption is indeed true before the procedure is performed widely, possibly leading to the development of hundreds of late gastric or esophageal carcinoma in the bariatric population. In the meantime, we strongly believe that RYGBP should remain the gold standard in gastric bypass surgery for morbid obesity.

Increased axonal regrowth of lesioned rat sciatic nerve by veratrylguanidine methane sulfonate.

Neurotrophic factors appear as essential factors for normal development and repair of the nervous tissue. Veratrylguanidine methane sulfonate, has been shown to induce important neurite outgrowth of cultured dorsal root ganglia isolated from newborn rats. Its action was similar to that of NGF and was found to be additive to that of NGF. In order to see if this compound was able to stimulate axonal growth in adult animals, we examined the effect of this substance on the regeneration of the lesioned sciatic nerve. Using histochemical, immunohistochemical and ultrastructural studies, it is shown that a single intraperitoneal injection of veratrylguanidine methane sulfonate significantly increases the axonal growth during repair of the adult rat sciatic nerve. The efficiency of this substance is explained by its good targeting and long life time in the sciatic nerve.

Long-term health-related quality of life and walking capacity of lung recipients with and without bronchiolitis obliterans syndrome.

BACKGROUND: Outcome after lung transplantation (LTx) is affected by the onset of bronchiolitis obliterans syndrome (BOS) and lung function decline. Reduced health-related quality of life (HRQL) and physical mobility have been shown in patients developing BOS, but the impact on the capacity to walk is unknown. We aimed to compare the long-term HRQL and 6-minute walk test (6MWT) between lung recipients affected or not by BOS Grade > or =2. METHODS: Fifty-eight patients were prospectively followed for 5.6 +/- 2.9 years after LTx. Assessments included the St George's Respiratory Questionnaire (SGRQ) and the 6MWT, which were performed yearly. Moreover, clinical complications were recorded to estimate the proportion of the follow-up time lived without clinical intercurrences after transplant. Analyses were performed using adjusted linear regression and repeated-measures analysis of variance. RESULTS: BOS was a significant predictor of lower SGRQ scores (p < 0.01) and reduced time free of clinical complications (p = 0.001), but not of 6MWT distance (p = 0.12). At 7 years post-transplant, results were: 69.0 +/- 21.8% vs 86.9 +/- 5.6%, p < 0.05 (SGRQ); 58.5 +/- 21.6% vs 88.7 +/- 11.4%, p < 0.01 (proportion of time lived without clinical complications); and 82.2 +/- 10.9% vs 91.9 +/- 14.2%, p = 0.27 (percent of predicted 6MWT), respectively, for patients with BOS and without BOS. CONCLUSIONS: Despite significantly less time lived without clinical complications and progressive decline of self-reported health status, the capacity to walk of patients affected by BOS remained relatively stable over time. These findings may indicate that the development of moderate to severe BOS does not prevent lung recipients from walking independently and pursuing an autonomous life.

Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

Cognition, mood and fatigue in patients in the early stage of multiple sclerosis.

QUESTION UNDER STUDY: Cognitive impairment occurs during multiple sclerosis (MS) and contributes to the burden of the disease, but its effect in the initial phase of MS still needs to be better understood. METHODS: We prospectively studied 127 early MS patients presenting with a clinically isolated syndrome (CIS) or definite MS, a mean disease duration of 2.6 years, and with minor disability (mean Expanded Disability Status Scale score 1.8). Patients were tested for long-term memory, executive functions, attention, fatigue, mood disorders, functional handicap and quality of life (QoL). Twenty-one CIS patients were excluded from study as the diagnosis of MS could not be confirmed. RESULTS: Over the 106 MS patients analysed, 31 (29.3%) were cognitively impaired (23.6% for memory, 10.4% for attention and 5.7% for executive functions). Cognitive deficits were already present in CIS patients in whom the diagnosis was not yet confirmed (20%). Impaired cognition was associated with anxiety (p = 0.05), depression(p = 0.004), fatigue (p = 0.03), handicap (p <0.001) and a lower QoL (p <0.001). After adjustment for QoL, handicap, depression, anxiety and fatigue were no longer associated with the presence of cognitive deficits. CONCLUSIONS: In this well-defined early MS group one third of the patients already exhibited cognitive deficits, which were usually apparent in an effortful learning situation and were generally mild. Mood disorders, fatigue, handicap and decreased QoL were all associated with the occurrence of cognitive deficits. QoL itself appeared to take all the other factors into account. Our results confirm the existence of an interplay between cognitive, affective and functional changes and fatigue in early MS.

Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer

A very long half-life of paroxetine (195 h instead of the usual value of around 16 h) was measured after an overdose with 2 g paroxetine and 1 g clorazepate in a patient who was an extensive cytochrome P4502D6 metabolizer. The patient recovered well without any clinically significant complications. A consequence of the close monitoring of paroxetine levels in this patient was that it was decided not to reintroduce any other antidepressant despite her suicide attempt, until normal levels of paroxetine had been reached, which took over 1 month.

Devenir à long terme des patients intubés pour état de mal asthmatique [Late outcome after life-threatening asthma]

Pour connaître le devenir à long terme des patients intubés pour état de mal asthmatique, nous avons recontacté en 1990 les 34 patients qui avaient présenté, entre 1978 et 1988, quarante épisodes de détresse respiratoire aiguë. Deux patients sont vivants mais ont été perdus de vue, 3 sont morts dont un seul d'état de mal asthmatique 6 mois après l'épisode initial. Des 29 patients restants (7 hommes et 22 femmes, âge moyen de 48,5 ans) représentant un suivi moyen de 9,6 ans, quinze n'ont jamais été réhospitalisés; des 14 autres, seuls 5 ont requis une intubation et une ventilation mécanique lors d'un épiode ultérieur. La majorité des hospitalisations ultérieures (81%) sont survenues dans les 6 ans suivant l'épiode initial

Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL). Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL) was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36), which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%). Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6) compared to those without (55.8;p=0.005), but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.