Mastoiditis--paleopathological evidence of a rarely reported disease

Since antibiotics have become available, mastoiditis has become a rare disease in modern Western societies. However, it is still common in developing countries. It can be hypothesized that in earlier historical and prehistoric times, mastoiditis must have posed a serious threat to people's lives, and that the prevalence of this disease is probably underrepresented in the paleopathological literature. The present study identifies pathological changes in the pneumatized cells of the mastoid process in human skeletal samples from two early medieval cemeteries from Germany (Dirmstein: n = 152 mastoids, Rhens: n = 71 mastoids), using macroscopic, endoscopic, low-power microscopic, scanning-electron and light microscopic techniques, and draws some epidemiological conclusions as to the frequency of the disease diagnosed in the archaeological samples. Osseous changes because of mastoiditis were diagnosed in 83.4% of the temporal bones. The frequency in the skeletal sample from Dirmstein was higher than in the sample from Rhens. In both populations, males were more often affected than females and older individuals more often than younger individuals. The high frequency of mastoiditis observed was most likely due to an accumulation of osseous changes during individual lifetimes and supports the hypothesis that mastoiditis was a serious health problem in pre-antibiotic times. It may be assumed that subclinical forms of mastoiditis and their osseous manifestations may even nowadays occur more often than was previously thought. It is suggested that the disease should be given more consideration in paleopathological investigations.     

Heterozygosity correlates with body size,nest site quality and productivity in a colonial waterbird,the whiskered tern (Chlidonias hybrida,Aves: Sternidae)

Positive effects of individual heterozygosity on naturally selected traits have been reported in wild populations of many animal taxa. The aim of this study was to test whether heterozygosity predicts the quality of acquired nest sites and productivity in a colonially breeding waterbird, the whiskered tern (Chlidonias hybrida). For this purpose, 40 adult terns from a small, recently established population in Central Poland were typed at eight microsatellite loci. We demonstrate that individual heterozygosity is positively related to hatching success. We hypothesize that this association could be mediated by direct effects of heterozygosity on the competitive abilities of individuals. We found that more heterozygous terns tended to breed in better protected central parts of the colony, suggesting that they had capabilities of outcompeting less heterozygous individuals and relegating them to the less attractive peripheries of the colony. It was also demonstrated that the link between heterozygosity and individual abilities to acquire more attractive nest site could be mediated by the larger size of heterozygous individuals. Although no correlations between heterozygosity and different components of condition were found, there was a positive association between female heterozygosity and both clutch size and egg size. We suggest that demonstrated heterozygosity‐fitness correlations could be primarily caused by inbreeding depression in the studied whiskered tern population.     

A stochastic compartment model representation of chronic disease dependence: Techniques for evaluating parameters of partially unobserved age inhomogeneous stochastic processes

Human disease states are commonly viewed in one of two ways. First, there is the clinical definition of disease as the presence or absence of a pathological condition. Second, there is the biologist's representation of disease as a point in a multivariate space of continuous physiological variables associated with suboptimal performance and survival. We present a model to represent dependency between multiple disease processes. The model is consistent with both concepts of disease and is designed to be estimated in the usual context of chronic disease information, i.e., a general lack of information about the time of disease incidence and progression. Consideration is made of the effects of individuals' differential susceptibility to disease and how these effects distinguish the disease incidence functions estimated at the individual level from those estimated for a population.     

Clonal expansions of mitochondrial genomes: implications for in vivo mutational spectra

It is often assumed mutant frequencies, as measured in a DNA sample, faithfully represent basic mutation rates associated with these mutations. This paradigm was extremely helpful for in vitro studies of the mechanisms of mutagenesis/repair and causes of mutations. However, in vivo, mutant fractions appear to vary dramatically and randomly from sample to sample. It's unlikely that basic mutational rates vary so much. Such variations are probably caused by clonal expansions of mutants within tissue. Whether a particular tissue sample includes an expansion or not, is a matter of chance, which explains the observed random fluctuations of mutant fractions. Well-known examples of clonal expansions involve pathological conditions such as cancer or mitochondrial disease. It is less appreciated that even in normal tissue, expansions of somatic mutants create local deviations from the "expected" mutant frequencies. The sizes of clonal expansions appear to span a wide range and thus, may affect samples of various sizes, from individual cells to individuals. In conclusion, human body appears to be a sort of a "gambling ground" for clonally expanding mutants. We speculate that expansion of early mutants rather than de novo mutation at old age may be the major source of at least some aging-specific mutants in our bodies.     

Skeletal Pathologies in a Population of Alouatta palliata: Behavioral, Ecological, and Evolutionary Implications

We examined the pathological conditions in a sample of 200 skulls of Alouatta palliata recovered from Barro Colorado Island (BCI), Panama, to investigate the prevalence of disease and injury in a free-ranging monkey population. Forty-five individuals (22.5%) have some type of nondental pathological condition, indicating that illness and injury are relatively common in this population. Ten individuals, all older adult males, exhibit clear signs of antemortem trauma in the form of healed fractures. We attribute the trauma primarily to fighting, and its frequency (16.4% of adult males) contradicts previous assertions that BCI howlers are nonaggressive. Nine of the 37 scorable immature individuals (24%) have signs of a larval infestation, supporting the suggestion that ectoparasites play an important role in BCI howler mortality. Other pathological conditions in the sample include shifted muscle attachments, periostitis, arthritis, neoplasm, periapical abscesses, and facial deformity, as well as various dental abnormalities.     

Reduced reproductive performance prior to death in the Black‐legged Kittiwake: senescence or terminal illness?

The breeding of Black-legged Kittiwakes Rissa tridactyla in their last breeding season has been compared with that of pairs which survived to the next breeding season. The time of laying was not affected but the clutch size, breeding success and productivity were significantly lower and a higher proportion of pairs totally failed to rear any young in pairs where one of the partners died before the next breeding season. When both partners died before the next breeding season, the breeding performance was reduced to a greater extent, suggesting an additive influence. The depressive effect on the last breeding attempt was confirmed by comparing the breeding success of individual females in their ultimate and penultimate breeding attempts. The effect was present in breeding birds of all ages, from first time breeders to the oldest individuals, and so could not be interpreted as an effect of senescence. Most of the adults which died apparently did so several months after breeding, during the winter half of the year when the kittiwake is oceanic. It is suggested that this depressive effect on breeding is the result of terminal illness which caused the birds to lose condition progressively over several weeks or months. It is possible that stress in the form of disease or parasite infections is primarily responsible for the death of many of the individuals. Attention is drawn to the possible confusion between the effect reported here and claims that senescence leads to lower reproductive output in old birds. It is suggested that more critical examinations are needed of claims that senescence directly affects the breeding success of birds.     

Frequency of micronuclei in peripheral blood lymphocytes from subjects occupationally exposed to low levels of ionizing radiation

The aim of this study was to evaluate the genotoxic effect of low dose of occupational radiation exposure in Nuclear Medicine Department employees, by using cytokinesis-blocked micronucleus assay in peripheral blood lymphocytes. The study included 46 exposed individuals together with 27 from the same area without occupational exposure to radiation which served as controls. The results obtained were evaluated with respect to age, gender, smoking habits, pathological condition and the occupational exposure to radiation of the individuals. The frequency of micronuclei increased significantly with the age of the subjects (P = 0.007). However there were no significant differences in micronucleus frequency with gender, smoking habits and occupational exposure. The frequency of micronuclei was significantly higher in individuals with presence of pathological condition (P < 0.0001) in comparison to healthy population irrespective of their exposure status.     

Differences in the Striaton Pattern in individuals with Unilateral Buccal Pathologies

A sample of individuals with different unilateral pathologies affecting the masticatory apparatus has been studied. Replicas of the same teeth (first or second molar) on both sides have been obtained and observed by SEM. The number, length and orientation of buccal striations have been determined for each individual. Differences in the microwear pattern have been observed between pathological sides. Each individual displays a particular striation pattern, especially referred to the striation number variables. It is concluded that individuals exhibiting pathologies likely to affect mastication should be excluded from studies relating striation patterns to diet.     

An event-based model of superspreading in epidemics

Many recent disease outbreaks (e.g. SARS, foot-and-mouth disease) exhibit superspreading, where relatively few individuals cause a large number of secondary cases. Epidemic models have previously treated this as a demographic phenomenon where each individual has an infectivity allocated at random from some distribution. Here, it is shown that superspreading can also be regarded as being caused by environmental variability, where superspreading events (SSEs) occur as a stochastic consequence of the complex network of interactions made by individuals. This interpretation based on SSEs is compared with data and its efficacy in evaluating epidemic control strategies is discussed.     

On the principle underlying the tabular method to compute coancestry

Summary The tabular method to compute coancestry between two individuals is based on the principle that coancestry may be computed as the average coancestry between one individual and the parents of the other, on the condition that the former individual is not a direct descendent of the latter. It follows that coancestry also may be computed as the average of the four coancestries between the parents of the two individuals, on the condition that each individual is not a direct descendent of the other. The requirement for these conditions is explained.This research was supported in part by the Illinois Agricultural Experiment Station, Hatch Projects 35-345 and 35-367     

Distribution of the disease pathogen Batrachochytrium dendrobatidis in non‐epidemic amphibian communities of western Canada

Chytridiomycosis is an emerging infectious disease of amphibians caused by the waterborne pathogen Batrachochytrium dendrobatidis (Bd) and is responsible for the recent decline of species worldwide. Elucidating patterns in disease prevalence has proved challenging, as small‐scale studies to date have provided conflicting results. We present data on the prevalence of Bd (the proportion of individuals with Bd) collected from amphibians sampled throughout British Columbia. We had two different datasets: our original dataset includes 1129 individuals sampled in 103 sites representing 14 species. A second dataset has 839 individuals sampled in 19 sites representing 10 species. We use a Bayesian state‐space occupancy modelling approach to estimate the probability that an individual is Bd+ as a function of individual and site characteristics. Cross‐validation techniques and the original dataset were used to find the best model: this model includes species, life stage, and geographic location. Our results suggest that Bd prevalence is not strongly related to seasonality, latitude or site type. Within a species, Bd prevalence depended on life stage; the watershed in which a site occurs may also usefully predict prevalence. Overall observed infection prevalence was ～16%. Our best model accurately assigns Bd status to an individual ～ 42% of the time. Taking advantage of the Bayesian framework, we ran an analysis with the second dataset using estimates from the original model as prior values. We present posterior density distributions for those sites and species with narrow credible intervals, and show that sites tend to be either highly likely or highly unlikely to have individuals with Bd, while individuals of some stages of some species have an intermediate likelihood of being Bd‐positive. The Bayesian model using informed priors had increased accuracy rates in assigning Bd status to both individuals and groups of individuals.     

The Upper Paleolithic triple burial of Dolní Vestonice: pathology and funerary behavior

This work focuses on paleopathological analysis of one of the skeletons from the Gravettian triple burial of Dolní Vestonice (Moravia) and addresses issues of Upper Paleolithic funerary behavior. The burial includes the well-preserved skeletons of three young individuals. The skeleton in the middle (DV 15) is pathological and very problematic to sex; the other two (DV 13 and DV 14) are males and lie in an unusual position. The young age, the possibility of a simultaneous interment, and the position of the three specimens have given rise to speculations about the symbolic significance of this spectacular and intriguing funerary pattern. The pathological condition of the skeleton in the middle further emphasizes its peculiarity. Main pathological changes of the DV 15 skeleton include: asymmetric shortening of the right femur and of left forearm bones, bowing of the right femur, right humerus, and left radius, elongation of fibulae, dysplasias of the vertebral column, and very marked enamel hypoplasias. Scrutiny of the medical literature suggests that the most likely etiology is chondrodysplasia calcificans punctata (CCP) complicated by trauma and early fractures of the upper limbs. CCP is a rare inherited disorder characterized by stippled ossification of the epiphyses. The cartilaginous stippling is a transient phenomenon that disappears during infancy, leaving permanent deformities on affected bones. Among the different forms of CCP, the X-linked dominant form is that resulting in asymmetric shortening and is lethal during early infancy in males. Thus, survival of DV 15 until young adult age would require the specimen to be a female. Clinical findings often associated with the disease (erythemas, ichthyosis, alopecia, cataracts, and joint contractures, among others) would emphasize the singular aspect of this individual, pointing to a condition that should be carefully taken into account when speculating on the significance of that peculiar burial.     

Internal standard-based analysis of microarray data2--analysis of functional associations between HVE-genes

In this work we apply the Internal Standard-based analytical approach that we described in an earlier communication and here we demonstrate experimental results on functional associations among the hypervariably-expressed genes (HVE-genes). Our working assumption was that those genetic components, which initiate the disease, involve HVE-genes for which the level of expression is undistinguishable among healthy individuals and individuals with pathology. We show that analysis of the functional associations of the HVE-genes is indeed suitable to revealing disease-specific differences. We show also that another possible exploit of HVE-genes for characterization of pathological alterations is by using multivariate classification methods. This in turn offers important clues on naturally occurring dynamic processes in the organism and is further used for dynamic discrimination of groups of compared samples. We conclude that our approach can uncover principally new collective differences that cannot be discerned by individual gene analysis.     

Pitfalls in determining size homoplasy of microsatellite loci

Size homoplasy of microsatellite loci can be detected by single‐strand conformation polymorphism analysis (SSCP) or sequence analysis. The present note demonstrates pitfalls of sequencing microsatellite loci. A complex chloroplast microsatellite locus was polymerase chain reaction (PCR) amplified from 33 Abies alba individuals, and the products cloned and sequenced. After 2–7 clones per individual had been sequenced and aligned, differences in repeat numbers occurred among clones of the same individual. It was concluded that the DNA polymerase slippage during PCR most probably caused this variation. A solution specific to the analysed complex locus was found by splitting it into two new loci.     

Resting-state multi-spectrum functional connectivity networks for identification of MCI patients

In this paper, a high-dimensional pattern classification framework, based on functional associations between brain regions during resting-state, is proposed to accurately identify MCI individuals from subjects who experience normal aging. The proposed technique employs multi-spectrum networks to characterize the complex yet subtle blood oxygenation level dependent (BOLD) signal changes caused by pathological attacks. The utilization of multi-spectrum networks in identifying MCI individuals is motivated by the inherent frequency-specific properties of BOLD spectrum. It is believed that frequency specific information extracted from different spectra may delineate the complex yet subtle variations of BOLD signals more effectively. In the proposed technique, regional mean time series of each region-of-interest (ROI) is band-pass filtered (0.025 ≤ ? ≤ 0.100 Hz) before it is decomposed into five frequency sub-bands. Five connectivity networks are constructed, one from each frequency sub-band. Clustering coefficient of each ROI in relation to the other ROIs are extracted as features for classification. Classification accuracy was evaluated via leave-one-out cross-validation to ensure generalization of performance. The classification accuracy obtained by this approach is 86.5%, which is an increase of at least 18.9% from the conventional full-spectrum methods. A cross-validation estimation of the generalization performance shows an area of 0.863 under the receiver operating characteristic (ROC) curve, indicating good diagnostic power. It was also found that, based on the selected features, portions of the prefrontal cortex, orbitofrontal cortex, temporal lobe, and parietal lobe regions provided the most discriminant information for classification, in line with results reported in previous studies. Analysis on individual frequency sub-bands demonstrated that different sub-bands contribute differently to classification, providing extra evidence regarding frequency-specific distribution of BOLD signals. Our MCI classification framework, which allows accurate early detection of functional brain abnormalities, makes an important positive contribution to the treatment management of potential AD patients.     

Identification of a transparent mutant tiger barb Puntius tetrazona and its use for in vivo observation of a Pleistophora sp. (Microsporidia) infection

A transparent mutant tiger barb Puntius tetrazona was identified and characterized by its transparent body, which allows clear visualization of internal organs. Hybridization of this mutant with the albino variant produces a transparent and albinoid double phenotype, and the transparency of this mutant is controlled by a recessive allele. Light microscopic and ultrastructural examinations show that in contrast to normal individuals, transparent mutants lack iridophores, and light penetrates unimpeded through the body. Pleistophora sp. infection was observed in vivo, allowing live observation of parasite dissemination and the consequent pathological alterations in the fish body as well as the simultaneous acquisition of data on the dynamics and spatial pattern of pathogenic invasion. It is superior to common fish models, as dynamic experimental data can be obtained from individual fish.     

Redox Regulation of Programmed Cell Death in Lymphocytes

A redox imbalance caused by an over-production of prooxidants or a decrease in antioxidants seems to play a role in the programmed cell death that occurs in various developmental programs. Such a physiological function for oxidative stress is particularly applicable to the immune system, wherein individual lymphocytes undergo continuous scrutiny to determine if they should be preserved or programmed to die. Following activation, lymphocytes produced increased levels of reactive oxygen species (ROS) which may serve as intracellular signaling molecules. The ultimate outcome of this increased ROS formation, i.e., lymphocyte proliferation versus programmed cell death, may be dictated by macrophage-derived costimulatory molecules that bolster or diminish lymphocyte antioxidant defenses. HIV-1-infected individuals display multiple symptoms of redox imbalance consistent with their being in oxidative stress, and lymphocytes from such individuals are more prone to undergo apoptosis in vitro. It is suggested that oxidative stress is a physiological mediator of programmed cell death in lymphoid cells, and that HIV disease represents an extreme case of what can happen when regulatory safeguards are compromised.     

The Young,the Weak and the Sick: Evidence of Natural Selection by Predation

It is assumed that predators mainly prey on substandard individuals, but even though some studies partially support this idea, evidence with large sample sizes, exhaustive analysis of prey and robust analysis is lacking. We gathered data from a culling program of yellow-legged gulls killed by two methods: by the use of raptors or by shooting at random. We compared both data sets to assess whether birds of prey killed randomly or by relying on specific individual features of the prey. We carried out a meticulous post-mortem examination of individuals, and analysing multiple prey characteristics simultaneously we show that raptors did not hunt randomly, but rather preferentially predate on juveniles, sick gulls, and individuals with poor muscle condition. Strikingly, gulls with an unusually good muscle condition were also predated more than expected, supporting the mass-dependent predation risk theory. This article provides a reliable example of how natural selection may operate in the wild and proves that predators mainly prey on substandard individuals.     

Rare temporal bone pathology of the Singa calvaria from Sudan

Evidence has recently accumulated that the Singa calvaria from Sudan probably dates from Oxygen Isotope Stage 6 (>130 ka). Morphological studies have indicated a mixture of archaic and more modern human traits, but such analyses are complicated by the possibility that the vault is pathologically deformed, although the exact etiology has not been established. Now computed tomography (CT) has revealed that the right temporal bone lacks the structures of the bony labyrinth. The most likely cause of this rare pathological condition appears to be labyrinthine ossification, in which newly deposited bone obliterates the inner ear spaces following an infectious disease or occlusion of the labyrinthine blood supply. A possible cause of vascular compromise could have been the presence of an expanding acoustic neuroma in the internal acoustic meatus, which is suggested by a significantly wider right meatus compared with the left side. Interestingly, labyrinthine ossification is also consistent with the controversial diagnosis that an anemia caused the characteristic diploic widening at the parietal bosses, because prime etiological factors of ossification are among the common complications of some of these blood diseases. CT examination of the vault and a review of the literature suggest that a blood disorder may well have caused the unusual parietal morphology. Given the nature of these pathological conditions, the Singa individual must have experienced a period of considerable disability. The morphological evidence from the normal bony labyrinth on the left side and from the CT evaluation of the vault is consistent with the interpretation of Singa as a late archaic hominid or an early representative of Homo sapiens drawn from a population which might be directly ancestral to modern humans. Am J Phys Anthropol 107:41–50, 1998. © 1998 Wiley-Liss, Inc.