Rural Caregivers and Social Isolation: Some Properties and Dimensions

There are an estimated 400,000 people with multiple sclerosis (MS) in the United States. Many rely on an informal caregiver for assistance. Caregivers are more likely than non-caregivers to report feelings of social isolation. Rural MS caregivers are especially prone to these feelings of isolation. We conducted in-depth interviews with rural caregivers of veterans with MS and used a grounded theory approach to data collection and analysis to illustrate some properties and dimensions of social isolation in a rural MS caregiving sample. These properties include: isolation and the rural environment; isolation from family; isolation from friends; and isolation from the person for whom they provide care

Temperature- and chemical-induced neurotoxicity in zebrafish

Throughout their lives, humans encounter a plethora of substances capable of inducing neurotoxic effects, including drugs, heavy metals and pesticides. Neurotoxicity manifests when exposure to these chemicals disrupts the normal functioning of the nervous system, and some neurotoxic agents have been linked to neurodegenerative pathologies such as Parkinson's and Alzheimer's disease. The growing concern surrounding the neurotoxic impacts of both naturally occurring and man-made toxic substances necessitates the identification of animal models for rapid testing across a wide spectrum of substances and concentrations, and the utilization of tools capable of detecting nervous system alterations spanning from the molecular level up to the behavioural one. Zebrafish (Danio rerio) is gaining prominence in the field of neuroscience due to its versatility. The possibility of analysing all developmental stages (embryo, larva and adult), applying the most common "omics" approaches (transcriptomics, proteomics, lipidomics, etc.) and conducting a wide range of behavioural tests makes zebrafish an excellent model for neurotoxicity studies. This review delves into the main experimental approaches adopted and the main markers analysed in neurotoxicity studies in zebrafish, showing that neurotoxic phenomena can be triggered not only by exposure to chemical substances but also by fluctuations in temperature. The findings presented here serve as a valuable resource for the study of neurotoxicity in zebrafish and define new scenarios in ecotoxicology suggesting that alterations in temperature can synergistically compound the neurotoxic effects of chemical substances, intensifying their detrimental impact on fish populations

Food hoarding of an avian predator: sex- and age-related differences under fluctuating food conditions

Hoarding behaviour (storing food for a later use) has evolved to reduce starvation risk when resources are scarce. Different age and sex classes often show differences in foraging due to experience, skills or life history strategy, but such differences in hoarding under spatio-temporally varying environmental conditions have rarely been studied in the wild. We studied hoarding behaviour of Eurasian pygmy owls (Glaucidium passerinum) during 2003-2016 in western Finland, where the abundance of their main prey (voles) fluctuates in three-year population cycles. In 14years, 1056 food stores were found during the hoarding season (Oct-Dec) and 330 pygmy owls were trapped at these stores. The number of stores per individual did not vary in relation to age, sex or vole abundance. Adults (+1-year old) had their stores farther apart than yearlings. Both the number of stores per year and the biomass of stored prey items increased with vole abundance. Females and yearlings had larger and heavier stores than males and adults, respectively. The same individuals stored more food as yearlings than as adults. These sex- and age-differences in hoarding indicate that it is not constrained by experience or skills. It rather seems that less-experienced yearlings rely more on stored food than adults. Females may need more food due to their larger size and need to accumulate energy reserves before reproduction. A detailed knowledge of age- and sex-related differences in hoarding behaviour under fluctuating abundances of main foods is fundamental to better understand a population response to climate change and forest management.Significance statementThe hoarding behaviour of animals has evolved to cope with the problem of food limitation. On the basis of 14-year data from pygmy owls, we show that the number of stores per year and the biomass of prey items per store increased with vole abundance in the environment. Adults had stores farther apart than yearlings, and females and yearlings stored more prey items and biomass compared to males and adults, respectively. These results indicate that hoarding behaviour responds to the available main prey abundance and varies with traits such as age and sex. Because different age and sex classes might respond differently to variation in food abundance, due to habitat alterations or climate change, a detailed knowledge of hoarding behaviour can be of particular importance to understand changes in body condition, reproductive success and survival of pygmy owls under changing climate and management of boreal forest

Age and sex differences in numerical responses, dietary shifts, and total responses of a generalist predator to population dynamics of main prey

Fluctuations in the abundance of main prey species might shape animal communities, by inducing numerical responses and dietary shifts in predators. Whether numerical responses and dietary shifts differ among individuals of different age and sex has so far gained little attention. These differences could affect how much predators consume main and alternative prey, thus causing variation in predation pressure on main and alternative prey species. We studied the effect of fluctuating main prey abundance (voles) in autumn on the age and sex composition of a food-hoarding population of Eurasian pygmy owls Glaucidium passerinum (327 individuals), and on the species composition of their food stores in western Finland during 2003-2017 (629 food stores). Numbers of yearlings (< 1-year old) of both sexes and adult (+ 1-year old) females increased with increasing vole abundance. During low vole abundance, adult owls stored more small birds and less small mammals than yearlings. Females stored more small mammals than males and showed a tendency to store less birds. The amount of consumed birds (the most important alternative prey), and in particular of crested, willow, great, and blue tits, increased with low vole densities. Our results show that numerical, functional, and total responses of pygmy owls, and probably also other vertebrate predators, to the availability of the main prey in winter are shaped by the age and sex composition of the predator population, which both show large spatio-temporal variation in boreal forests

Haplotypic structure of the X chromosome in the COGA population sample and the quality of its reconstruction by extant software packages

BACKGROUND: The haplotypes of the X chromosome are accessible to direct count in males, whereas the diplotypes of the females may be inferred knowing the haplotype of their sons or fathers. Here, we investigated: 1) the possible large-scale haplotypic structure of the X chromosome in a Caucasian population sample, given the single-nucleotide polymorphism (SNP) maps and genotypes provided by Illumina and Affimetrix for Genetic Analysis Workshop 14, and, 2) the performances of widely used programs in reconstructing haplotypes from population genotypic data, given their known distribution in a sample of unrelated individuals. RESULTS: All possible unrelated mother-son pairs of Caucasian ancestry (N = 104) were selected from the 143 families of the Collaborative Study on the Genetics of Alcoholism pedigree files, and the diplotypes of the mothers were inferred from the X chromosomes of their sons. The marker set included 313 SNPs at an average density of 0.47 Mb. Linkage disequilibrium between pairs of markers was computed by the parameter D', whereas for measuring multilocus disequilibrium, we developed here an index called D*, and applied it to all possible sliding windows of 5 markers each. Results showed a complex pattern of haplotypic structure, with regions of low linkage disequilibrium separated by regions of high values of D*. The following programs were evaluated for their accuracy in inferring population haplotype frequencies: 1) ARLEQUIN 2.001; 2) PHASE 2.1.1; 3) SNPHAP 1.1; 4) HAPLOBLOCK 1.2; 5) HAPLOTYPER 1.0. Performances were evaluated by Pearson correlation (r) coefficient between the true and the inferred distribution of haplotype frequencies. CONCLUSION: The SNP haplotypic structure of the X chromosome is complex, with regions of high haplotype conservation interspersed among regions of higher haplotype diversity. All the tested programs were accurate (r = 1) in reconstructing the distribution of haplotype frequencies in case of high D* values. However, only the program PHASE realized a high correlation coefficient (r > 0.7) in conditions of low linkage disequilibrium

The emerging role of cancer nanotechnology in the panorama of sarcoma

In the field of nanomedicine a multitude of nanovectors have been developed for cancer application. In this regard, a less exploited target is represented by connective tissue. Sarcoma lesions encompass a wide range of rare entities of mesenchymal origin affecting connective tissues. The extraordinary diversity and rarity of these mesenchymal tumors is reflected in their classification, grading and management which are still challenging. Although they include more than 70 histologic subtypes, the first line-treatment for advanced and metastatic sarcoma has remained unchanged in the last fifty years, excluding specific histotypes in which targeted therapy has emerged. The role of chemotherapy has not been completely elucidated and the outcomes are still very limited. At the beginning of the century, nano-sized particles clinically approved for other solid lesions were tested in these neoplasms but the results were anecdotal and the clinical benefit was not substantial. Recently, a new nanosystem formulation NBTXR3 for the treatment of sarcoma has landed in a phase 2-3 trial. The preliminary results are encouraging and could open new avenues for research in nanotechnology. This review provides an update on the recent advancements in the field of nanomedicine for sarcoma. In this regard, preclinical evidence especially focusing on the development of smart materials and drug delivery systems will be summarized. Moreover, the sarcoma patient management exploiting nanotechnology products will be summed up. Finally, an overlook on future perspectives will be provided

Inferring relationships between pairs of individuals from locus heterozygosities

BACKGROUND: The traditional exact method for inferring relationships between individuals from genetic data is not easily applicable in all situations that may be encountered in several fields of applied genetics. This study describes an approach that gives affordable results and is easily applicable; it is based on the probabilities that two individuals share 0, 1 or both alleles at a locus identical by state. RESULTS: We show that these probabilities (z(i)) depend on locus heterozygosity (H), and are scarcely affected by variation of the distribution of allele frequencies. This allows us to obtain empirical curves relating z(i)'s to H for a series of common relationships, so that the likelihood ratio of a pair of relationships between any two individuals, given their genotypes at a locus, is a function of a single parameter, H. Application to large samples of mother-child and full-sib pairs shows that the statistical power of this method to infer the correct relationship is not much lower than the exact method. Analysis of a large database of STR data proves that locus heterozygosity does not vary significantly among Caucasian populations, apart from special cases, so that the likelihood ratio of the more common relationships between pairs of individuals may be obtained by looking at tabulated z(i )values. CONCLUSIONS: A simple method is provided, which may be used by any scientist with the help of a calculator or a spreadsheet to compute the likelihood ratios of common alternative relationships between pairs of individuals

Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis

Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an up- regulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition in- dexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) “Dino Amadori”, Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4–13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9–10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9–6.7 months) in underweight patients (BMI 18.49 kg/m2) and 10.1 months (95% CI: 3.7–28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation