Interleukin 1 gene polymorphism and susceptibility to disease

The Interleukin 1 (IL-1) family plays a central role in the generation and regulation of inflammatory responses, in both innate and adaptive immunity. Although the IL-1 molecules are traditionally considered to be classical proinflammatory cytokines, their functions are not restricted to inflammation, and they have also been shown to play a key role in a wide range of additional physiological and pathological functions, including learning modulation, sleep, pregnancy, depression, appetite, hematopoiesis, metabolism, and many others. Since their effect as cytokines and regulators of inflammation is so pleiotropic, any shift of the biological balance between agonistic and antagonistic signals has the potential to cause disease. Here, we consider the genetic influence of interleukin-1 gene polymorphism in the context of susceptibility to human diseases. We review known single nucleotide polymorphisms (SNP) of IL-1 genes linked to human diseases, and suggest how exploring biological effects of IL-1 gene cluster polymorphism may lead to new directions in understanding and diagnostic of disease and effective treatment.     

Immunoglobulin free light chains in saliva: a potential marker for disease activity in multiple sclerosis

A new procedure was developed and applied to study immunoglobulin free light chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis (MS). The procedure was based on a Western blot analysis for detection and semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices accounting for the total FLC levels and for the monomer/dimer ratios of κ and λ FLC were calculated, and the cut‐off values of the FLC indices were determined to distinguish healthy state from MS disease. The obtained FLC index values were statistically different in the saliva of three groups: active MS patients, MS patients in remission and healthy subjects groups. Our FLC monomer–dimer analysis allowed differentiation between healthy state and active MS with specificity of 100% and a sensitivity of 88·5%. The developed technique may serve as a new non‐invasive complementary tool to evaluate the disease state by differentiating active MS from remission with sensitivity of 89% and specificity of 80%.     

Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti‐SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi‐allelic inactivating events were found by NGS‐based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild‐type sequence. We then validated the anti‐SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non‐meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non‐meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker.     

From the Cover: Parasitism alters three power laws of scaling in a metazoan community: Taylor’s law,density-mass allometry,and variance-mass allometry

How do the lifestyles (free-living unparasitized, free-living parasitized, and parasitic) of animal species affect major ecological power-law relationships? We investigated this question in metazoan communities in lakes of Otago, New Zealand. In 13,752 samples comprising 1,037,058 organisms, we found that species of different lifestyles differed in taxonomic distribution and body mass and were well described by three power laws: a spatial Taylor’s law (the spatial variance in population density was a power-law function of the spatial mean population density); density-mass allometry (the spatial mean population density was a power-law function of mean body mass); and variance-mass allometry (the spatial variance in population density was a power-law function of mean body mass). To our knowledge, this constitutes the first empirical confirmation of variance-mass allometry for any animal community. We found that the parameter values of all three relationships differed for species with different lifestyles in the same communities. Taylor''s law and density-mass allometry accurately predicted the form and parameter values of variance-mass allometry. We conclude that species of different lifestyles in these metazoan communities obeyed the same major ecological power-law relationships but did so with parameters specific to each lifestyle, probably reflecting differences among lifestyles in population dynamics and spatial distribution.Variation in population density has long been a central topic in ecology (e.g., ref. 1). Taylor’s law (TL) (2, 3) is a pattern of variation that has been widely verified for population density in basic and applied ecology and for other quantities in other fields. In its ecological interpretations, TL asserts that, in multiple sets of populations, the sample variance in population density within each set is proportional to a power (usually positive) of the sample mean population density within that set. We specify TL in greater detail below.Morand and Guégan (4) showed that TL described well the variations of abundance per host in 828 populations of parasitic nematodes from 66 terrestrial mammalian species. Morand and Krasnov (5) reviewed examples of TL in parasitology and epidemiology and interpreted the exponent of the TL power law in terms of the aggregation of parasites and epidemiological dynamics. These studies used the number of individual parasites per individual host as the measure of population density. Following a suggestion of Taylor (2), these studies interpreted the exponent of the power-law relationship of variance of population density to mean of population density as an index of parasite aggregation among hosts. A purely random distribution of parasites per host leads to a Poisson distribution, which gives a TL exponent equal to 1 as the mean population density varies. A TL exponent greater than 1 reflects greater heterogeneity in numbers of individuals per host than expected from a purely random distribution. More importantly, the TL exponent may also be used to assess the strength of parasite population regulation via processes such as interspecific competition or vaccination, and may distinguish between epidemic and endemic infections (5–7).Here we ask how three lifestyles (free-living unparasitized, free-living parasitized, and parasitic) of animal species affect major ecological power-law relationships, including TL, using new data on all metazoans from the littoral zone of four lakes in coastal and central Otago, South Island, New Zealand. Unlike previous studies of TL in parasitology, we measured the population density of parasites as the number of individuals per square meter of habitat, not per individual host. Additionally, unlike previous studies, in addition to quantifying the population density of parasitic species (separately for each life stage), we quantified the population density of the free-living parasitized species and of the free-living unparasitized species in the same habitat. Contrasting TL and other power-law relationships among organisms with different lifestyles can reveal differences in the degree to which spatial heterogeneity in their abundance is regulated.Using these data, we tested the validity of TL for metazoans of each lifestyle in the same habitat. Intuitively, it seemed plausible, and we investigated the hypothesis, that the interactions of free-living parasitized species and parasites added variability to the population dynamics of species of both lifestyles compared with free-living unparasitized species. This qualitative argument led us to expect larger values of the exponent of TL for free-living parasitized species and parasites compared with the exponent of TL for free-living unparasitized species.In addition to testing TL and the effects of lifestyle on the parameters of TL, we examined the allometric relationship between mean population density and mean body mass (density-mass allometry, or DMA). Marquet et al. (8) and Cohen et al. (9) independently showed theoretically that TL and DMA combine to predict the form and parameters of an allometric relationship between the variance of population density and mean body mass (variance-mass allometry, or VMA). (The details of these predictions are in SI Appendix.) We tested and verified all three relations empirically for each lifestyle in the same habitat. The parameter values of all three relationships depended on lifestyle.Although DMA has been very widely confirmed for a great variety of organisms (e.g., refs. 10–18), including parasitic nematodes (19) and other parasites (20), VMA has previously been confirmed empirically only for congeneric trees (Quercus spp.) in a temperate forest (9). These new data permitted us to verify the predicted VMA empirically, to our knowledge for the first time for any animals and for the first time for all metazoans in a local community. Empirical confirmation of VMA for all metazoans in a local community makes it possible to use average body mass to predict the variability of population densities of different species, in addition to predicting the mean population density from DMA. This variability bears on risks of extinction, population outbreaks, and epidemics. The ability to predict this variability from a factor as easily measured as average body mass could be valuable for economically important species.     

Risk factors associated with lymphedema after lymph node dissection in melanoma patients

Background

Secondary lymphedema is a frequent complication after lymphadenectomy in melanoma patients, although few studies in melanoma adequately characterize risk factors for lymphedema, and of these, sample size is limited. This study aims to identify risk factors associated with the lymphedema after axillary lymph node dissection (ALND) and inguinal lymph node dissection (ILND) in a more robust cohort of melanoma patients.

Methods

We identified 269 ALND or ILND melanoma patients treated between 2008 and 2014. Demographic, clinical, and postoperative data were collected by review of the electronic medical record. Univariate and multivariate analysis were used to determine independent predictors of lymphedema.

Results

Fifty-six (20.8%) of the patients developed lymphedema after lymph node dissection with a median staging group of 3. ILND (odds ratio [OR] = 4.506, P < .001, 95% confidence interval [CI]: 2.289 to 8.869) and peripheral vascular disease (PVD; OR = 3.849, P = .020, 95% CI: 1.237 to 11.975) were significant predictors of lymphedema in multivariate analysis. Obese body mass index approached significance (OR = 1.802, P = .069, 95% CI: .955 to 3.399).

Conclusions

PVD and ILND were the 2 factors associated with the highest risk of lymphedema in melanoma surgery with PVD increasing risk 2-fold in ILND patients and 3-fold in ALND patients. These findings may improve surgeon-patient communication of care goals and surgical risk assessment.