Opposite patterns of age-associated changes in neurons and glial cells of the thalamus of human brain

In an autopsy series of 19 individuals, age-ranged 24–94, a relatively age-spared region, the anterior–ventral thalamus, was analyzed by immunohistochemical techniques to visualize neurons (neurofilament protein), astrocytes (glial fibrillary acidic protein), microglial cells (CD68) and amyloid precursor protein. The pattern of immunoreactivity was determined by surface fractal dimension and lacunarity, the size by the field area (FA) and the spatial uniformity by the uniformity index. From the normalized FA values of immunoreactivity for the four markers studied, a global parameter was defined to give an overall characterization of the age-dependent changes in the glio-neuronal networks. A significant exponential decline of the GP was observed with increasing age. This finding suggests that early in life (age < 50 years) an adaptive response might be triggered, involving the glio-neuronal networks in plastic adaptive adjustments to cope with the environmental challenges and the continuous wearing off of the neuronal structures. The slow decay of the GP observed in a later phase (age > 70 years) could be due to the non-trophic reserve still available.     

Plastid inheritance in Oenothera: paternal input may influence transmission patterns

Summary Prior genetic analysis of Oenothera to assess the mechanism(s) controlling differential (biparental) plastid transmission patterns have indicated that the plastome plays an integral role. However, the influence of putative variation in paternal plastid input remains unclear. Pollen collected from Oenothera hookeri plants containing one of four different plastome types (I–IV) in a constant nuclear background (A₁A₁) was examined cytologically by DAPI/ epifluorescence microscopy. The number of plastid DNA aggregates per pollen generative cell was found to differ significantly. Plants containing plastome types I or II displayed an average of about ten plastid DNA aggregates per generative cell whereas plants containing types III or IV displayed, on average, 15 plastid DNA aggregates. The potential paternal plastid contribution to the egg cell at syngamy (III=IV>I=II) differs from the previously determined survival frequencies of the same four plastid types (I>III>II>IV) progeny.Scientific article no. A-5036, contribution no. 8084 of the Maryland Agricultural Experimental Station     

Fc fragments of human IgG may influence allergic reactions

The antiallergic effect of Fc fragments prepared from human polyclonal IgG was investigated in several experimental models. In an in vitro assay, isolated ileum of cynomolgus monkeys was sensitized with serum from atopic patients. In six of fifteen monkeys the subsequent addition of specific allergens reproducibly resulted in an ileum contraction measured in the Schultz-Dale apparatus. In all six positive monkeys pre-treatment of the isolated ileum with Fc (papain) before sensitization inhibited ileum contraction. Fc (plasmin) or Fc (pepsin) was less or not effective, aggregated IgG, monomeric IgG, sulfonated IgG, the Fc-free F(ab')2 moiety, or albumin had no significant or no reproducible inhibitory effect. In an in vivo assay passive cutaneous anaphylaxis was studied in 28 cynomolgus monkeys. Different dilutions in PBS of the particular specific allergens were subsequently administered to sensitized skin sites, simultaneously to i.v. injection of Evans blue. The degree of the local allergic (passive cutaneous anaphylactia) reaction was evaluated by measuring the diameter of the blue area at the dermal injection sites. About 50% of sera induced positive reaction in monkeys. Compared to the control (application of PBS), the degree of the positive reactions could be reduced by about 50% if Fc (papain) (optimal dose 25 mg/kg body weight) was injected i.v. either 2 h before or after local sensitization. No significant inhibitory effect could be found with the Fab moiety of IgG. Follow-up studies showed that the inhibitory effect of Fc lasted for about 10 days. The pharmacological basis of the observed antiallergic action of Fc is not yet understood.     

Cardiovascular mortality and morbidity in dialysis patients

Dialysis patients constitute a high-risk group for cardiovascular disease, which accounts for 40% of deaths in these patients. After stratification for age, race and gender, cardiovascular mortality is several orders of magnitude (10-20 times) higher in dialysis patients than in the general population. A clustering of risk factors renders dialysis patients especially susceptible to cardiovascular disease. Their morbidity and mortality can be favorably altered by interventional measures which systematically address and modify each individual risk factor. It is necessary to institute intervention during the course of progressive renal failure, well before the onset of end-stage renal disease and the initiation of dialysis.     

Present cardiovascular morbidity and mortality in Croatia

Individual clinical and/or epidemiological studies on the prevalence of cardiovascular diseases in Croatia are described. The studies based on regional approach and distribution are specially analyzed, with a note that there have been only few such studies from the highland parts of Croatia. An overview of several studies dealing with the influence of region, air pollution, and specific mortality due to cardiovascular diseases is also presented. An overview of available literature sources from international tertiary databases and National University Library is provided.     

How seasonal temperature variations may influence the structure of annual squid populations

Email: ericg{at}stams.strath.ac.uk Email: s.desclers{at}ic.ac.uk Previous laboratory studies have established that temperatureis highly influential in affecting both the growth and lifespan of Cephalopoda. A major unresolved question is how suchsensitivity to environmental factors may determine populationstructure. Extending a hypothesis first advanced by Forsythe(1993, in: Recent Advances in Fisheries Biology (T. Okutani,R. K. O'Dor, & T. Kubdera, eds.), Tokyo, Tokai UniversityPress), we formulate a simple individual-level model which incorporatesa two-stage growth response for squid hatchlings exposed tocontinuous seasonal fluctuations of temperature. We show thatin seasonally fluctuating temperatures such a growth ‘duality’can directly affect the size distribution of squid over theyear and we demonstrate how in seasonally warming waters thismechanism may lead to younger individuals surpassing the sizeof older individuals. By postulating that development statuscan be inferred directly from size, we go on to propose a circle-mapmodel of the whole squid life cycle. Numerical investigationsinto the iterative dynamics support the hypothesis that theprogeny from such a population can rapidly separate to a lownumber of tightly synchronized cohorts within a few generations.     

Steroids and the reversal of age-associated changes in myelination and remyelination

The myelin sheaths that surround all but the smallest diameter axons within the mammalian central nervous system (CNS) must maintain their structural integrity for many years. Like many tissues, however, this function is prone to the effects of ageing, and various structural anomalies become apparent in the aged CNS. Similarly, the regenerative process by which myelin sheaths, lost as a consequence of exposure to a demyelinating insult, are restored (remyelination) is also affected by age. As animals grow older, the efficiency of remyelination progressively declines. In this article, we review both phenomena and describe how both can be partially reversed by steroid hormones and their derivatives.     

Discovery and integration of univariate patterns from daily individual organ-failure scores for intensive care mortality prediction

OBJECTIVES: The current established mortality predictive models in the intensive care rely only on patient information gathered within the first 24 hours of admission. Recent research demonstrated the added prognostic value residing in the sequential organ-failure assessment (SOFA) score which quantifies on each day the cumulative patient organ derangement. The objective of this paper is to develop and study predictive models that also incorporate univariate patterns of the six individual organ systems underlining the SOFA score. A model for a given day d predicts the probability of in-hospital mortality. MATERIALS AND METHODS: We use the logistic framework to combine a summary statistic of the historic SOFA information for a patient together with selected dummy variables indicating the occurrence of univariate frequent temporal patterns of individual organ system functioning. We demonstrate the application of our method to a large real-life data set from an intensive care unit (ICU) in a teaching hospital. Model performance is tested in terms of the AUC and the Brier score. RESULTS: An algorithm for categorization, discovery, and selection of univariate patterns of individual organ scores and the induction of predictive models. The case-study resulted in six daily models corresponding to days 2-7. Their AUC ranged between 0.715 and 0.794 and the Brier scores between 0.161 and 0.216. Models using only admission data but recalibrated for days 2-7 generated AUC ranging between 0.643 and 0.761 and Brier scores ranged between 0.175 and 0.230. CONCLUSIONS: The results show that temporal organ-failure episodes improve predictions' quality in terms of both discrimination and calibration. In addition, they enhance the interpretability of models. Our approach should be applicable to many other medical domains where severity scores and sub-scores are collected.     

Structure,innervation, and age-associated changes of mouse forearm muscles

In spite of a decline in muscle strength with age, the cause of the overall decrease in motor performance in aged mammals, including rodents, is incompletely understood. To add clarity, the gross organization, innervation, histochemical fiber types, and age-associated changes are described for mouse forearm muscles used in a variety of motor functions. The anterior (flexor) and posterior (extensor) forearm compartments have the same arrangement of muscles and gross pattern of innervation as the rat. Two primary histochemical fiber types, fast/oxidative/glycolytic (FOG) and fast/glycolytic (FG), with characteristic hitsochemical staining patterns were observed in all forearm muscles. Additionally, there was a small population of slow/oxidative (SO) fibers confined to the deep region of a single muscle, the flexor carpi ulnaris (FCU). Between 18 and 26 months the FCU muscle displayed fibers with morphological features distinct from earlier ages. Fibers displayed a greater variation in size, a loss of their uniform polygonal shape, and a dramatic increase in clumps of subsarcolemmal mitochondria, lysosomes, and lipofuscin granules. Many of the fibers had a distinctly atrophic, angular shape consistent with recent denervation. Morphometric analyses of the FCU's source of innervation, the ulnar nerve and one of its ventral roots (C8), were consistent with the denervation-like changes in the muscle fibers. Although, there was no net loss of myelinated axons between 4 and 26 months of age, there was a significant increase in the density of degenerating cells in both the ulnar nerve and ventral root C8. © 1993 Wiley-Liss, Inc.     

Tonsil epithelial factors may influence oropharyngeal human immunodeficiency virus transmission

Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcRgammaIII, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission.     

Trematode-associated morbidity and mortality of tadpoles in Israel

Amphibians stand at the forefront of the global biodiversity crisis. The causes of their decline are diverse and include a rise in amphibian malformations due to various factors, especially trematode infection. However, linking amphibian mortality and morbidity with trematode infection has proven to be challenging due to the complex life cycle of the trematodes and the fact that trematodes are nonfastidious in their choice of definitive hosts. In Israel, the decline in local amphibian populations has been mostly attributed to the loss and degradation of wetlands and riparian habitats. Recently, however, there have been several reports of morbidity and mortality of tadpoles with signs of edema and malformations from various localities in Israel. We collected dead and morbid tadpoles and metamorphs of Hyla savignyi and Pelophylax bedriagae, and we showed that the morbidity and the deformations observed in the field are the result of infection by trematodes. We also isolated an echinostomatid trematode from the malformed and edematous tadpoles and from the freshwater snail Bulinus truncatus, all from the same site. We further succeeded in experimentally infecting H. savignyi tadpoles by echinostomatid cercariae that were shed from the snails, and we showed that infection had significantly increased the mortality rates of these tadpoles. The combination of high trematode prevalence and their pathogenic effects suggests that in nature, the effect of echinostome infection on amphibians may be substantial and could become an emerging disease in Israel.     

Prescribing patterns and morbidity in a tropical practice

A retrospective study of morbidity and prescribing habits in a tropical practice is presented. The common symptoms of pain, cough, and fever accounted for 60 per cent of all cases seen while analgesics accounted for 30 per cent of all drugs prescribed.     

Inhaled corticosteroids: impact on asthma morbidity and mortality

Inhaled corticosteroids are now recommended as first-line therapy for asthma. Although these drugs clearly improve the symptoms of the disease and the associated physiologic abnormalities, epidemiologic studies provide important information on their effectiveness in preventing asthma morbidity and mortality. We review the evidence regarding the role of inhaled corticosteroids in the prevention of asthma fatality and hospitalization. In the process, we discuss the methodologic complexities of the nonexperimental studies and the implications of the methodologic issues on the evaluation of the impact of these drugs. Eight of the cohort and ecologic studies conducted to date strongly suggest that inhaled corticosteroids, when taken regularly, decrease the number of hospitalizations for asthma by up to 80%. For asthma death, the results of 11 investigations appear less consistent, especially those of several cohort and case-control studies whose principal objective was to examine not the benefit of inhaled corticosteroids but the adverse effects of other drug classes. Much of the inconsistency in the results, however, can be explained by weaknesses in study design and analysis-in particular, the failure to consider exposure in terms of regular use of inhaled corticosteroids. When the most recent study involving the use of the Saskatchewan databases is considered, it is evident that regular treatment with conventional or low-dose inhaled cortico-steroids results in a significant reduction in fatalities due to asthma. In all, the evidence to date strongly indicates that regular use of inhaled corticosteroids, even at low doses, would prevent the major portion of asthma hospitalizations and deaths.     

Preventing cold-related morbidity and mortality in a changing climate

Winter weather patterns are anticipated to become more variable with increasing average global temperatures. Research shows that excess morbidity and mortality occurs during cold weather periods. We critically reviewed evidence relating temperature variability, health outcomes, and adaptation strategies to cold weather. Health outcomes included cardiovascular-, respiratory-, cerebrovascular-, and all-cause morbidity and mortality. Individual and contextual risk factors were assessed to highlight associations between individual- and neighborhood-level characteristics that contribute to a person's vulnerability to variability in cold weather events. Epidemiologic studies indicate that the populations most vulnerable to variations in cold winter weather are the elderly, rural and, generally, populations living in moderate winter climates. Fortunately, cold-related morbidity and mortality are preventable and strategies exist for protecting populations from these adverse health outcomes. We present a range of adaptation strategies that can be implemented at the individual, building, and neighborhood level to protect vulnerable populations from cold-related morbidity and mortality. The existing research justifies the need for increased outreach to individuals and communities for education on protective adaptations in cold weather. We propose that future climate change adaptation research couple building energy and thermal comfort models with epidemiological data to evaluate and quantify the impacts of adaptation strategies.