Abstract basins of attraction

Abstract basins appear naturally in different areas of several complex variables. In this survey we want to describe three different topics in which they play an important role, leading to interesting open problems

Experimental determination of the frequency and field dependence of Specific Loss Power in Magnetic Fluid Hyperthermia

Magnetic nanoparticles are promising systems for biomedical applications and in particular for Magnetic Fluid Hyperthermia, a promising therapy that utilizes the heat released by such systems to damage tumor cells. We present an experimental study of the physical properties that influences the capability of heat release, i.e. the Specific Loss Power, SLP, of three biocompatible ferrofluid samples having a magnetic core of maghemite with different core diameter d= 10.2, 14.6 and 19.7 nm. The SLP was measured as a function of frequency f and intensity of the applied alternating magnetic field H, and it turned out to depend on the core diameter, as expected. The results allowed us to highlight experimentally that the physical mechanism responsible for the heating is size-dependent and to establish, at applied constant frequency, the phenomenological functional relationship SLP=cH^x, with 2<x<3 for all samples. The x-value depends on sample size and field frequency/ intensity, here chosen in the typical range of operating magnetic hyperthermia devices. For the smallest sample, the effective relaxation time Teff=19.5 ns obtained from SLP data is in agreement with the value estimated from magnetization data, thus confirming the validity of the Linear Response Theory model for this system at properly chosen field intensity and frequency

Investigating masking effects of age trends on the correlations among tree ring proxies

Age-related trends are present in tree-ring widths (TRW), but their presence in tree rings isotope is debated. It is unclear how cambial age influences the relationships between TRW and isotopes. Tree-ring isotopes of alpine larch and cembran-pine trees showed only trends in the juvenile period (>100 years), which might mask the inter-relations between tree-ring proxies during cambial age. This work tries to unmask the age-trend influences by examining the correlations in TRW-stable isotopes with and without age-trend correction. The non-detrended and linear-detrended values of TRW, of δD and δ18O showed significant correlations for ages up to 100 years, but not afterward. However, the correlation values, after spline or first-difference time-series detrending, were not age-related. Thus, detrending methods affect the correlations in the juvenile phase and may affect climate-related interpretations. The correlations between TRW and δ13C were not age-related, while those among the isotopes were significant throughout the ages. The correlation between δ13C and δD was the exception, as it became significant only after age > 100 years, suggesting a different use of reserves in the juvenile phase. In conclusion, the relationships among the tree-ring parameters are stable in all the different detrend scenarios after the juvenile phase, and they can be used together in multi-proxy paleoclimatic studies. The data of the juvenile phase can be used after spline-detrending or first-difference time-series calculation, depending on the purpose of the analysis to remove age-related trends. The work also provides clues on the possible causes of juvenile age trends

Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression:Do We Have a Translational Perspective?

Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the "neurotrophin hypothesis of depression" involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD

Cabergoline Withdrawal Before and After Menopause : Outcomes in Microprolactinomas

Natural course of prolactinomas after menopause is not fully elucidated. The aim of this study was to compare recurrence rate after cabergoline withdrawal in premenopausal vs. postmenopausal women with microprolactinoma. Sixty-two women with microprolactinoma treated with cabergoline for at least 1 year and followed for 2 years after drug withdrawal were retrospectively selected. Patients were divided into two groups: 48 patients stopped cabergoline before menopause ("PRE" group), while 14 after menopause ("POST" group). Recurrence was defined by prolactin levels above normal, confirmed on two occasions. Overall, 39/62 women relapsed. Patients who relapsed apparently had higher prolactin before withdrawal (median 216.2, range 21.2-464.3 mIU/L) compared with those in long-term remission (94.3, 29.7-402.8 mIU/L; p &lt; 0.05), and the risk of recurrence seemed lower in POST women (4/14, 29%) than in PRE ones (35/48, 73%, p &lt; 0.005, OR 0.149, 95% CI 0.040-0.558). However, none of the factors (prolactin before withdrawal, menopausal status, treatment duration, complete adenoma regression) showed a correlation with recurrence risk in multivariate analysis. The best strategy able to optimize CBG treatment and withdrawal's outcomes is still to be defined in microprolactinomas. Postmenopausal status cannot reliably predict long-term remission, and follow-up is needed also in women of this age

Efficacy of Nutritional Interventions as Stand-Alone or Synergistic Treatments with Exercise for the Management of Sarcopenia

Sarcopenia is an age-related and accelerated process characterized by a progressive loss of muscle mass and strength/function. It is a multifactorial process associated with several adverse outcomes including falls, frailty, functional decline, hospitalization, and mortality. Hence, sarcopenia represents a major public health problem and has become the focus of intense research. Unfortunately, no pharmacological treatments are yet available to prevent or treat this age-related condition. At present, the only strategies for the management of sarcopenia are mainly based on nutritional and physical exercise interventions. The purpose of this review is, thus, to provide an overview on the role of proteins and other key nutrients, alone or in combination with physical exercise, on muscle parameters

Exosome determinants of physiological aging and age-related neurodegenerative diseases

Aging is consistently reported as the most important independent risk factor for neurodegenerative diseases. As life expectancy has significantly increased during the last decades, neurodegenerative diseases became one of the most critical public health problem in our society. The most investigated neurodegenerative diseases during aging are Alzheimer disease (AD), Frontotemporal Dementia (FTD) and Parkinson disease (PD). The search for biomarkers has been focused so far on cerebrospinal fluid (CSF) and blood. Recently, exosomes emerged as novel biological source with increasing interest for age-related neurodegenerative disease biomarkers. Exosomes are tiny Extracellular vesicles (EVs; 30\u2013100 nm in size) released by all cell types which originate from the endosomal compartment. They constitute important vesicles for the release and transfer of multiple (signaling, toxic, and regulatory) molecules among cells. Initially considered with merely waste disposal function, instead exosomes have been recently recognized as fundamental mediators of intercellular communication. They can move from the site of release by diffusion and be retrieved in several body fluids, where they may dynamically reflect pathological changes of cells present in inaccessible sites such as the brain. Multiple evidence has implicated exosomes in age-associated neurodegenerative processes, which lead to cognitive impairment in later life. Critically, consolidated evidence indicates that pathological protein aggregates, including A\u3b2, tau, and \u3b1-synuclein are released from brain cells in association with exosomes. Importantly, exosomes act as vehicles between cells not only of proteins but also of nucleic acids [DNA, mRNA transcripts, miRNA, and non-coding RNAs (ncRNAs)] thus potentially influencing gene expression in target cells. In this framework, exosomes could contribute to elucidate the molecular mechanisms underneath neurodegenerative diseases and could represent a promising source of biomarkers. Despite the involvement of exosomes in age-associated neurodegeneration, the study of exosomes and their genetic cargo in physiological aging and in neurodegenerative diseases is still in its infancy. Here, we review, the current knowledge on protein and ncRNAs cargo of exosomes in normal aging and in age-related neurodegenerative diseases

&#946;-Glucuronidase triggers extracellular MMAE release from an integrin-targeted conjugate

A non-internalizing \u3b1v\u3b23 integrin ligand was conjugated to the anticancer drug MMAE through a \u3b2-glucuronidase-responsive linker. In the presence of \u3b2-glucuronidase, only the conjugate bearing a PEG4 spacer inhibited the proliferation of integrin-expressing cancer cells at low nanomolar concentrations, indicating important structural requirements for the efficacy of these therapeutics

25 hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly

Background: Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroiditis (AT). The aim of the study was to investigate the association of AT with low 25(OH) vitamin D levels in the elderly. Methods: One hundred sixty-eight elderly subjects (mean age: 81.6 ± 9.4 years) were enrolled. Serum levels of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured. Results: The prevalence of AT was significantly higher in subjects with vitamin D deficiency (25(OH) vitamin D < 20 ng/mL) when compared with subjects with normal 25(OH) vitamin D (25(OH) vitamin D ≥ 20 ng/mL) levels (28% vs. 8%, respectively, p = 0.002). Patients with AT and vitamin D deficiency had a comparable hormonal profile compared to patients with AT and vitamin D sufficiency in terms of TSH (p = 0.39), FT3 (p = 0.30), FT4 (p = 0.31), TG-Ab (0.44) and TPO-Ab (0.35). Interestingly, a significant correlation between 25(OH) vitamin D and TPO-Ab (r = −0.27, p = 0.03) and FT3 (r = 0.35, p = 0.006) has been found in subjects with AT while no correlation was found between 25(OH) vitamin D levels and TG-Ab (r = −0.15, p = 0.25), TSH (r = −0.014, p = 0.09) and FT4 (r = 0.13, p = 0.32). Conclusions: These findings suggest that vitamin D deficiency was significantly associated with AT in the elderly. Therefore, the screening for AT should be suggested in subjects with vitamin D deficiency

Variable response in alpine tree-ring stable isotopes following volcanic eruptions in the tropics and iceland

The importance of the stable isotopes in tree rings for the study of the climate variations caused by volcanic eruptions is still unclear. We studied &delta;18O, &delta;D, &delta;13C stable isotopes of larch and cembran pine cellulose around four major eruptions with annual resolution, along with a superposed epoch analysis of 34 eruptions with 5-year resolution. Initial analysis of the tropical Tambora (1815 CE) and Samalas (1257 CE) eruptions showed a post-eruption decrease in &delta;18O values attributed to post-volcanic cooling and increased summer precipitation in Southern Europe, as documented by observations and climate simulations. The post-volcanic cooling was captured by the &delta;D of speleothem fluid inclusion. The &delta;18O decrease was also observed in the analysis of 34 major tropical eruptions over the last 2000 years. In contrast, the eruptions of c. 750, 756, and 764 CE attributed to Icelandic volcanoes left no significant responses in the cellulose isotopes. Further analysis of all major Icelandic eruptions in the last 2000 years showed no consistent isotopic fingerprints, with the exception of lower post-volcanic &delta;13C values in larch. In summary, the &delta;18O values of cellulose can provide relevant information on climatic and hydroclimatic variations following major tropical volcanic eruptions, even when using the 5-year resolution wood samples of the Alpine Tree-Ring Isotope Record database