Commentary on: Berger-Karin C, Hendricks U, Geyer-Lippmann J. Comparison of natural and artificial aging of ballpoint inks

We would like to comment this study recently published in JFS. It is a short technical note proposing an artificial aging technique for the dating of ballpoint pen inks. This is a very difficult and controversial topic, and we are worried about the nature of this paper. The authors propose several ideas to differentiate fast aging and slow aging inks, but their experimental data is not validly represented and/or discussed. The data is insufficient to draw any conclusions about any potential of the method for ink dating purposes. This lack of information on the subject must be filled before proposing such methods for practical caseworks. These are preliminary and unconvincing results from development research performed in a laboratory on controlled samples without due warnings about potential shortcomings. They cannot be used or even compared to results obtained in real situations on uncontrolled specimens of limited size, unknown composition and undefined storage conditions. This can leave an undeserved feeling that these methods are ready for implementation when the task of ensuring their scientific validity is still far away.

A study of the aging of fingerprints by GC/MS analysis.

Determining the time since deposition of fingermarks may prove necessary in order to assess their relevance to criminal investigations. The crucial factor is the initial composition of fingermarks because it represents the starting point of any ageing model. This study mainly aimed to characterize the initial composition of fingerprints, which show a high variability between donors (inter-variability), but also to investigate the variations among fingerprints from the same donor (intra-variability). Solutions to reduce this initial variability using squalene and cholesterol as target compounds are proposed and should be further investigated. The influence of substrates was also evaluated and the initial composition was observed to be larger on porous surface than non-porous surfaces. Preliminary aging of fingerprints over 30 days was finally studied on a porous and a non-porous substrate to evaluate the potential for dating of fingermarks. Squalene was observed to decrease in a faster rate on a non-porous substrate.

Birth records from Swiss married couples analyzed over of the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened

RésuméIntroduction : Le travail de thèse est un article publié dans le journal « Fertility & Sterility » s'intitulant « Birth records from Swiss married couples analyzed over the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened ».Méthodes : Les données concernant l'âge auquel les femmes mariées donnaient naissance ont été obtenues de l'Office fédéral de la statistique. Nous avons examiné la période allant de 1969 à 2006. Cet intervalle de temps choisi nous a permis de prendre en considération un total de 2'716'370 naissances. L'âge moyen des parturientes à la naissance de leur 1er, 2ème et 3ème enfant a été calculé pour chaque année à l'aide du logiciel Excel. Grâce à ces données on a pu obtenir les intervalles inter-gestationnels théoriques entre le 1er et 2ème enfant, ainsi qu'entre le 2ème et 3ème enfant.Résultats : Nous pouvons constater que l'intervalle inter-gestationnel théorique entre la première et la deuxième grossesse était de 23.2 mois en 1969 et passait à 13.0 mois en 2006. L'intervalle compris entre la deuxième et la troisième grossesse passait de 22.4 mois en 1969 à 7.9 mois en 2006. Notre analyse suggère donc que c'est le facteur social qui exerce un effet plus important que le facteur biologique sur les intervalles inter-gestationnels, car ces intervalles diminuaient malgré l'augmentation de l'âge des mères à la naissance.

Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways.

Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies.

Development of a novel headspace sorptive extraction method to study the aging of volatile compounds in spent handgun cartridges

Estimating the time since the last discharge of firearms and/or spent cartridges may be a useful piece of information in forensic firearm-related cases. The current approach consists of studying the diffusion of selected volatile organic compounds (such as naphthalene) released during the shooting using solid phase micro-extraction (SPME). However, this technique works poorly on handgun car-tridges because the extracted quantities quickly fall below the limit of detection. In order to find more effective solutions and further investigate the aging of organic gunshot residue after the discharge of handgun cartridges, an extensive study was carried out in this work using a novel approach based on high capacity headspace sorptive extraction (HSSE). By adopting this technique, for the first time 51 gunshot residue (GSR) volatile organic compounds could be simultaneously detected from fired handgun cartridge cases. Application to aged specimens showed that many of those compounds presented significant and complementary aging profiles. Compound-to-compound ratios were also tested and proved to be beneficial both in reducing the variability of the aging curves and in enlarging the time window useful in a forensic casework perspective. The obtained results were thus particularly promising for the development of a new complete forensic dating methodology.

Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013.

Retinoblastoma has the unique capacity to accelerate its own intra-ocular propagation by adopting semi-solid or even liquid growth properties through seeding. Until recently, the presence of any degree of seeding was mostly incompatible with successful conservative management, due to the multiresistant nature of the seeds. Surprisingly, this well-recognized retinoblastoma behavior has not undergone any detailed description of seeding patterns and anatomic sites. In this paper, we describe the phenotypic variability of seeds across the four possible intraocular seeding compartments and classify them into three fundamental types: namely dust, spheres, and clouds. We also provide an overview of the different therapeutic strategies developed for seeding, with special attention to intravitreal chemotherapy as the treatment of choice for vitreous and retro-hyaloid seeding. Finally, we propose criteria to enable assessment of the response to treatment by reporting seed regression patterns, as well as a clinical grading system for the retinal toxicity observed following intravitreal melphalan.

Birth records from Swiss married couples analyzed over the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened.

Although the general trend for delaying childbearing is generally viewed as causing infertility, its consequences on the interpregnancy interval have been unknown. A study of birth records for Swiss married women from 1969 to 2006 revealed that the woman's age at first birth has increased from 25.0 to 30.1 years, whereas calculated theoretical interpregnancy intervals after the first and second child decreased from 23.2 to 13 and from 22.4 to 7.9 months, respectively.

Epidemiology and prevention of cardiovascular disease in the Seychelles Islands (Indian Ocean)

This article presents selected findings and lessons from a cardiovascular research and prevention program initiated in 1989 in the Republic of Seychelles, a country in demographic and epidemiological transition. Rapid and sustained aging of the population (e.g., two-fold increase of people aged 30-39 from 1979 to 1995) implies, over the next few decades, further dramatic increase of the burden of chronic diseases, particularly cardiovascular disease (CVD). Epidemiological surveillance shows high age-specific rates of CVD (particularly stroke), high prevalence of peripheral atherosclerosis (plaques in carotid and femoral arteries), high prevalence of classical modifiable risk factors in the adult population (particularly hypertension), and substantial proportions of children with overweight. Stagnant life expectancy in men and an increase in women have been observed over the last two decades; this occurred despite largely improved health services and reduced infant mortality rates, and may reflect the large CVD burden found in middle-aged men (less so in middle-aged women). A national program of prevention of CVD has been initiated since 1991, which includes a mix of interventions to reduce risk factors in the general population and in high-risk individuals. Substantial research to back the prevention program indeed shows, at the moment, epidemiological patterns in Seychelles similar to those observed in Western countries (e.g., an association between peripheral atherosclerosis [as a proxy of CVD] and low density lipoprotein-cholesterol, smoking, diabetes, and [inversely] walking). This clearly supports the view that promotion of healthy lifestyles and control of conventional risk factors should be the main targets for CVD prevention and control.

Proteomics of blood and derived products: what's next?

Proteomics has changed the way proteins are analyzed in living systems. This approach has been applied to blood products and protein profiling has evolved in parallel with the development of techniques. The identification of proteins belonging to red blood cell, platelets or plasma was achieved at the end of the last century. Then, the questions on the applications emerged. Hence, several studies have focused on problems related to blood banking and products, such as the aging of blood products, identification of biomarkers, related diseases and the protein-protein interactions. More recently, a mass spectrometry-based proteomics approach to quality control has been applied in order to offer solutions and improve the quality of blood products. The current challenge we face is developing a closer relationship between transfusion medicine and proteomics. In this article, these issues will be approached by focusing first on the proteome identification of blood products and then on the applications and future developments within the field of proteomics and blood products.

Recurrence of keratoconus characteristics: a clinical and histologic follow-up analysis of donor grafts.

PURPOSE: To report on clinical corneal topography, histopathologic analysis, and fine structure findings in failed grafts after penetrating keratoplasty (PK) for keratoconus (KC). DESIGN: Retrospective, consecutive, interventional case series with histologic and clinical correlation. PARTICIPANTS: Twelve corneal buttons were obtained from consecutive patients undergoing repeated PK 10 to 28 years after the initial PK for KC. The indication for regrafting was endothelial deficiency in seven cases, irreversible immune graft rejection in two cases, and corneal ectasia in three cases. METHODS: Removed corneal buttons were examined by light and transmission electron microscopy. A potential correlation between the clinical and videokeratoscopic findings and the microscopic structural observations was analyzed. RESULTS: Preoperative simulated keratometry measured by TMS-1 (Tomey, New York, NY) or EyeSys CAS (EyeSys Technology, Houston, TX) ranged from 49.8 to 66.1 diopters. A pattern compatible with KC characteristics was observed in all cases. Fine structure analysis revealed Bowman's layer disruption or folds and stromal deposits in all corneal buttons. However, central corneal thinning was not present in any of the removed buttons. CONCLUSIONS: Structure changes compatible with the diagnosis of KC were observed in all donor buttons many years after PK on KC recipients. Recurrence of the KC characteristics may result from graft repopulation by recipients' keratocytes, aging of the grafted tissue, or both.

Epidemiologie der Osteoporose. [The epidemiology of osteoporosis].

Osteoporosis is characterized by low bone mass, micro architectural impairment of bone tissue, and a subsequent in crease in fracture risk. Fractures or the vertebrae and distal forearm, as well as the proximal femur, or hip fracture, are included. Hip fracture is associated with high mortality, morbidity and medical expenses. There is a dramatic increase in the incidence of hip fracture with age. Hip fracture incidence is 350 times higher in women aged 85 years and over comparatively to women between 35 and 44 years of age. In recent studies in Switzerland, it was observed that the annual age adjusted incidence rate of hip fracture was comparable with similar rates for white population in industrialized countries, although in men the rates were relatively high. Among the major risk factors for osteoporosis are age, female gender, white and Asian race, and menopause. Postmenopausal estrogen replacement therapy reduces bone resorption. Family history of osteoporosis, frail constitution, as well as excessive alcohol intake, cigarette smoking, chronic insufficient nutritional calcium intake and physical inactivity are other risk factors. A cardinal element is the peak bone mass reached in the third or fourth decade of life. Independently of osteoporosis, falls are a key agent in fractures; several medical conditions and drugs increase the risk of falling. There is an enormous social and financial cost of osteoporosis; the annual cost of medical treatment only for hip fracture is close to Fr. 200 million in Switzerland. The burden of osteoporosis is likely to increase in the future because of the demographic aging of the population unless large scale preventive interventions are undertaken.

Jambes lourdes, insuffisance veineuse des membres inférieurs et hormonothérapie substitutive [Heavy legs, venous insufficiency of the legs and hormone substitution therapy]

The effects of estrogens and gestagens on veins and circulation have been studied since prescription of these hormones as oral contraception and description of related thromboembolic events. The identification of different receptors and the description of these receptors in venous walls have helped to understand some hormonal effects. However, the actual knowledge remains insufficient to explain the complexity of the actions of hormones on venous function. The distribution, the density and the receptor types vary with age, gender, hormonal status and vascular bed. Gestagens mainly reduce the tone of venous walls, whereas estrogens have various effects. Between 25% and 50% of European adults and even 80% or more in some risk groups complain about heavy legs, with or without chronic venous insufficiency. The number of women to whom hormonal substitution is or could be prescribed increases along with aging of populations and the better understanding of potential benefits. The need for a better understanding of vascular effects of sexual hormones is growing, since the incidence of chronic venous insufficiency of the legs increases with age. The life prognosis will not be affected by a deterioration of a chronic venous insufficiency. In contrast, the quality of life, morbidity and the cost of treatment will be expected to change. In addition, thromboembolic events have to be considered, as has been shown in recent studies. These findings outline the need for further studies on the relation between hormones and venous function and for some caution when prescribing hormonal substitution.

Initial Results on the Composition of Fingerprints and its Evolution as a Function of Time by GC/MS Analysis

Determining the time since deposition of fingermarks may prove necessary to assess their relevance to criminal investigations. The crucial factor is the initial composition of fingermarks, because it represents the starting point of any aging model. This study mainly aimed to characterize the initial composition of fingerprints, which show a high variability between donors (inter-variability), but also to investigate the variations among fingerprints from the same donor (intra-variability). Solutions to reduce this initial variability using squalene and cholesterol as target compounds are proposed and should be further investigated. The influence of substrates was also evaluated, and the initial composition was observed to be larger on porous surface than nonporous surfaces. Preliminary aging of fingerprints over 30 days was finally studied on a porous and a nonporous substrate to evaluate the potential for dating of fingermarks. Squalene was observed to decrease in a faster rate on a nonporous substrate.

PROTEOMICS OF OXIDATIVE LESIONS OCCURRING DURING TRANSFUSION-PURPOSED STORAGE OF ERYTHROCYTE CONCENTRATES

Erythrocyte concentrates (ECs) are the major labile blood product being transfused worldwide, aiming at curing anemia of diverse origins. In Switzerland, ECs are stored at 4 °C up to 42 days in saline-adenine-glucose-mannitol (SAGM). Such storage induces cellular lesions, altering red blood cells (RBCs) metabolism, protein content and rheological properties. A hot debate exists regarding the impact of the storage lesions, thus the age of ECs on transfusion-related clinical adverse outcomes. Several studies tend to show that poorer outcomes occur in patients receiving older blood products. However, no clear association was demonstrated up to date. While metabolism and early rheological changes are reversible through transfusion of the blood units, oxidized proteins cannot be repaired, and it is likely such irreversible damages would affect the quality of the blood product and the efficiency of the transfusion. In vivo, RBCs are constantly exposed to oxygen fluxes, and are thus well equipped to deal with oxidative challenges. Moreover, functional 20S proteasome complexes allow for recognition and proteolysis of fairly oxidized protein, and some proteins can be eliminated from RBCs by the release of microvesicles. The present PhD thesis is involved in a global research project which goal is to characterize the effect of processing and storage on the quality of ECs. Assessing protein oxidative damages during RBC storage is of major importance to understand the mechanisms of aging of stored RBCs. To this purpose, redox proteomic-based investigations were conducted here. In a first part, cysteine oxidation and protein carbonylation were addressed via 2D-DIGE and derivatization-driven immunodetection approaches, respectively. Then, the oxidized sub- proteomes were characterized through LC-MS/MS identification of proteins in spots of interest (cysteine oxidation) or affinity-purified carbonylated proteins. Gene ontology annotation allowed classifying targets of oxidation according to their molecular functions. In a third part, the P20S activity was evaluated throughout the storage period of ECs, and its susceptibility to highly oxidized environment was investigated. The potential defensive role of microvesiculation was also addressed through the quantification of eliminated carbonylated proteins. We highlighted distinct protein groups differentially affected by cysteine oxidation, either reversibly or irreversibly. In addition, soluble extracts showed a decrease in carbonylation at the beginning of the storage and membrane extracts revealed increasing carbonylation after 4 weeks of storage. Engaged molecular functions revealed that antioxidant (AO) are rather reversibly oxidized at their cysteine residue(s), but are irreversibly oxidized through carbonylation. In the meantime, the 20S proteasome activity is decreased by around 40 % at the end of the storage period. Incubation of fresh RBCs extracts with exogenous oxidized proteins showed a dose-dependent and protein-dependent inhibitory effect. Finally, we proved that the release of microvesicles allows the elimination of increasing quantities of carbonylated proteins. Taken together, these results revealed an oxidative pathway model of RBCs storage, on which further investigation towards improved storage conditions will be based. -- Les concentrés érythrocytaires (CE) sont le produit sanguin le plus délivré au monde, permettant de traiter différentes formes d'anémies. En Suisse, les CE sont stocké à 4 °C pendant 42 jours dans une solution saline d'adénine, glucose et mannitol (SAGM). Une telle conservation induit des lésions de stockage qui altèrent le métabolisme, les protéines et les propriétés rhéologique du globule rouge (GR). Un débat important concerne l'impact du temps de stockage des CE sur les risques de réaction transfusionnelles, certaines études tentant de démontrer que des transfusions de sang vieux réduiraient l'espérance de vie des patients. Cependant, aucune association concrète n'a été prouvée à ce jour. Alors que les modifications du métabolisme et changement précoces des propriétés rhéologiques sont réversibles suite à la transfusion du CE, les protéines oxydées ne peuvent être réparées, et il est probable que de telles lésions affectent la qualité et l'efficacité des produits sanguins. In vivo, les GR sont constamment exposés à l'oxygène, et sont donc bien équipés pour résister aux lésions oxydatives. De plus, les complexes fonctionnels de proteasome 20S reconnaissent et dégradent les protéines modérément oxydées, et certaines protéines peuvent être éliminées par les microparticules. Cette thèse de doctorat est imbriquée dans un projet de recherche global ayant pour objectif la caractérisation des effets de la préparation et du stockage sur la qualité des GR. Evaluer les dommages oxydatifs du GR pendant le stockage est primordial pour comprendre les mécanismes de vieillissement des produits sanguin. Dans ce but, des recherches orientées redoxomique ont été conduites. Dans une première partie, l'oxydation des cystéines et la carbonylation des protéines sont évaluées par électrophorèse bidimensionnelle différentielle et par immunodétection de protéines dérivatisées. Ensuite, les protéines d'intérêt ainsi que les protéines carbonylées, purifiées par affinité, sont identifiées par spectrométrie de masse en tandem. Les protéines cibles de l'oxydation sont classées selon leur fonction moléculaire. Dans une troisième partie, l'activité protéolytique du protéasome 20S est suivie durant la période de stockage. L'impact du stress oxydant sur cette activité a été évalué en utilisant des protéines exogènes oxydées in vitro. Le potentiel rôle défensif de la microvesiculation a également été étudié par la quantification des protéines carbonylées éliminées. Dans ce travail, nous avons observé que différents groupes de protéines sont affectés par l'oxydation réversible ou irréversible de leurs cystéines. De plus, une diminution de la carbonylation en début de stockage dans les extraits solubles et une augmentation de la carbonylation après 4 semaines dans les extraits membranaires ont été montrées. Les fonctions moléculaires engagées par les protéines altérées montrent que les défenses antioxydantes sont oxydées de façon réversible sur leurs résidus cystéines, mais sont également irréversiblement carbonylées. Pendant ce temps, l'activité protéolytique du protéasome 20S décroit de 40 % en fin de stockage. L'incubation d'extraits de GR en début de stockage avec des protéines oxydées exogènes montre un effet inhibiteur « dose-dépendant » et « protéine-dépendant ». Enfin, les microvésicules s'avèrent éliminer des quantités croissantes de protéines carbonylées. La synthèse de ces résultats permet de modéliser une voie oxydative du stockage des GRs, à partir de laquelle de futures recherches seront menées avec pour but l'amélioration des conditions de stockage.

Understanding and meeting the needs of the older population: a global challenge.

BACKGROUND: In the past century, there has been a significant rise in life expectancy in almost all regions of the world, contributing to an increasingly older population. The aging of the population, in conjunction with urbanization and industrialization, has resulted in an important epidemiological transition marked by a widespread increase in the prevalence of chronic diseases and their sequelae. Current trends suggest that the transition will have a greater impact on developing countries compared to developed countries. An adequate response to the transition requires a strong emphasis on primary prevention and adequate resource allocation.