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Background: Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. Aim: Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. Methods: Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. Results: Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. Conclusions: The prevalence of sarcopenia in p

Background. Nutritional status (NS) impacts on quality of life and prognosis of patients with respiratory diseases including idiopathic pulmonary fibrosis (IPF). However, there is a lack of studies performing an extensive nutritional assessment of IPF patients. This study aims to investigate the NS and to identify nutritional phenotypes in a cohort of IPF patients at diagnosis. Methods. Patients underwent a thorough pulmonary and nutritional evaluation including questionnaires on NS and physical activity, anthropometry, body impedence, dynamometry, 4- meter gait speed and blood tests. Results. 90 IPF patients (78.9% males, mean age 72.7 years) were enrolled. The majority of patients were classified as Gender-Age-Physiology Index stage 2 (47, 52.2%) with an inactive lifestyle according to International Physical Activity Questionnaire score (39, 43.3%) and had mean forced vital capacity and diffusing capacity for carbon monoxide 86.5% and 54.2%, respectively. In regards to nutritional phenotypes, the majority of patients were normally nourished (67.8%, 95% Confidence Interval (CI):58.6-77.7), followed by non-sarcopenic obese (25.3%, 95%CI:16.1-35.2), sarcopenic (4.6%, 95%CI:0.0-14.5) and sarcopenic obese (2.3%, 95%CI:0.0-12.2). Among normally nourished, 49.2% showed early signs of nutritional and physical performance alterations, including body mass index≥ 30 in 4.3%, history of weight loss≥ 5% in 11.9%, reduction of gait speed and hand grip strength in 11.9% and 35.6%, respectively. Low vitamin D values were observed in 56.3% of cases. Conclusions. IPF patients at diagnosis are mainly normally nourished and obese, but early signs of nutritional and physical performance impairment can already be identified at this stage.

The original version of this article contained an error in two references (listed below) for Bonda et al. (1996). Bonda E, Ostry D, Evans A (1996a) Specific involvement of human parietal systems in the perception of biological motion and the amygdala. J Neurosci 76(11):3737-3744 Bonda E, Petrides M, Ostry D, Evans A (1996b) Specific involvement of human parietal systems and the amygdala in the perception of biological motion. J Neurosci 16:3737-3744 They should be deleted and substituted with just one paper whose the correct reference is: Bonda E, Petrides M, Ostry D, Evans A (1996) Specific involvement of human parietal systems and the amygdala in the perception of biological motion. J Neurosci 16(11):3737-3744.

IMPORTANCE Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS The Incremental Diagnostic Value ofAmyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairmentwere evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15%and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosiswas made, diagnostic confidencewas estimated, and drug treatmentwas provided. At the time of thisworkup, an amyloid PET/computed tomographic scanwas performed, and the resultwas communicated to physicians afterworkup completion. Physicianswere asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The studywas conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES Primary outcomeswere prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2%in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9%in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and

In the present study, shards from Roman wall paintings (from the end of the first century to the fourth century A.D.) decorating the domus below the Basilica of SS. John and Paul on the Caelian Hill (Rome), were analyzed in order to identify the pigments used. The analytical techniques employed for the characterization of the pigments were the scanning electron microscope coupled with an energy dispersive spectrometer (SEM-EDS) and infrared spectroscopy (ATR and micro ATR). While SEM-EDS allowed to perform a qualitative analysis of the material, by FT-IR chemical species have been identified. The pigments identified were those mentioned in the literature for the Imperial Roman fresco painting: different types of ochre (yellow and red), mixtures containing lead, green earths and precious pigments such as cinnabar and Egyptian blue. They were often used as mixtures and the use of the most valuable pigments (cinnabar and Egyptian blue) were found in the most ancient rooms

The superior temporal gyrus (STG) has been found to play a crucial role in the recognition of actions and facial expressions and may, therefore, be critical for the processing of humorous information. Here we investigated whether tDCS application to the STG would modulate the ability to recognize and appreciate the comic element in serious and comedic situations of misfortune. To this aim, the effects of different types of tDCS stimulation on the STG were analyzed during a task in which the participants were instructed to categorize various misfortunate situations as “comic” or “not comic”. Participants underwent three different tDCS conditions: Anodal-right/Cathodal-left; Cathodal-right/Anodal-left; Sham. Images depicting people involved in accidents were grouped into three categories based on the facial expression of the victim: angry or painful (Affective); bewildered and funny (Comic); and images that did not contain the victim’s face (No Face). An improvement in mean reaction times in response to both the Comic and No Face stimuli was observed following Anodal-left/Cathodal-right stimulation when compared to sham stimulation. This suggests that this stimulation type reduced the reaction times to socio-emotional complex scenes, regardless of facial expression. The Anodal-right/Cathodal-left stimulation reduced the mean reaction times for Comic stimuli only, suggesting that specifically the right STG may be involved in facial expression recognition and in the appreciation of the comic element in misfortunate situations. These results suggest a functional hemispheric asymmetry in STG response to social stimuli: the left STG might have a role in a general comprehension of social complex situations, while the right STG may be involved in the ability to recognize and integrate specific emotional aspects in a complex scene.

GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel.

Cosmogenic 21Ne and 10Be analyses across a subhorizontal fossil alluvial fan flanking the Cape Mountains near Laingsburg (Western Cape, South Africa) indicate a formation age for this fan of at least 2 Ma. Maximum erosion rates obtained from samples of quartzite ridges protruding through the fan alluvium deposits are very low (<~0.4 m/Ma) and analytically indistinguishable from those derived from pebbles from the fan surface (<~1.5 m/Ma). Our results are consistent with the low denudation rates obtained from other cosmogenic nuclide analyses and predicted by apatite fission-track and offshore sedimentation analyses for southern Africa during the Cenozoic. They integrate already existing substantial evidence to show that relative tectonic stability has prevailed across southern Africa throughout this period, and that the present-day large-scale topography is largely inherited from the Cretaceous and has been only minimally resculptured by denudation during the Cenozoic.

Cosmogenic 21Ne and 10Be analyses across a subhorizontal fossil alluvial fan flanking the Cape Mountains near Laingsburg (Western Cape, South Africa) indicate a formation age for this fan of at least 2 Ma. Maximum erosion rates obtained from samples of quartzite ridges protruding through the fan alluvium deposits are very low (<~0.4 m/Ma) and analytically indistinguishable from those derived from pebbles from the fan surface (<~1.5 m/Ma). Our results are consistent with the low denudation rates obtained from other cosmogenic nuclide analyses and predicted by apatite fission-track and offshore sedimentation analyses for southern Africa during the Cenozoic. They integrate already existing substantial evidence to show that relative tectonic stability has prevailed across southern Africa throughout this period, and that the present-day large-scale topography is largely inherited from the Cretaceous and has been only minimally resculptured by denudation during the Cenozoic.

Ovarian cancer is the most lethal gynecologic malignancy. Recently, NACT (Neo Adjuvant Chemotherapy) has been tested as alternative approach for the management of ovarian cancer patients. A biological predictor helpful in selecting patients for NACT would be desirable. This study was aimed at identifying actionable mechanisms of resistance to NACT. Expression of a panel of microRNAs was screened in a discovery set of 85 patients. Analysis of the potential targets was conducted in the same RNAs by calculating significant correlations between microRNAs and genes. Quantitative fluorescent immunohistochemistry was employed in a validation set of 109 patients. MiR-193a-5p was significantly overexpressed in the NACT setting. Analysis of its potential targets demonstrated that this microRNA is also significantly correlated with HGF and MET genes. Analysis of protein expression in samples taken before and after NACT demonstrated that both HGF and c-Met are increased after NACT. Patients who relapse shortly after NACT exhibited the highest relative basal expression of both HGF and c-Met, while the opposite phenomenon was observed in the best responders. Mir-193a-5p, HGF and c-Met expression may help select eligible patients for this modality of treatment. Moreover, inhibitors of this pathway may improve the efficacy of NACT.

Studies of meteorites are based mostly on samples that fell to Earth in the recent past (i.e., a few million years at most). The Morokweng LL-chondrite meteorite is a particularly interesting specimen as its fall is much older (ca. 145 Ma) than most other meteorites and because it is the only macro-meteorite clast (width intersected in drill core: 25 cm) found in a melt sheet of a large impact structure. When applied to the Morokweng meteorite, 40Ar/39Ar thermochronology provides an opportunity to study (1) effects associated with pre-impact and post-impact processes and (2) collision events within a potentially distinct and as yet unsampled asteroid population.A single multi-grain aliquot yielded an inverse isochron age of 625 ± 163 Ma. This suggests a major in-space collisional event at this time. We have modeled the diffusion of 40Ar* within the meteorite and plagioclase during and after the 145 Ma impact on Earth to tentatively explain why pre-terrestrial impact 40Ar* has been preserved within the plagioclase grains. The 145 Ma terrestrial impact age is recorded in the low-retentivity sites of the meteorite plagioclase grains that yielded a composite inverse isochron age at 141 ± 15 Ma and thus, confirms that age information about major (terrestrial or extraterrestrial) impacts can be recorded in the K-rich mineral phases of a meteorite and measured by the 40Ar/39Ar technique. More studies on fossil meteorites need to be carried out to understand if the rough 0.6 Ga age proposed here corresponds to major LL-chondrite asteroid population destructions or, rather, to an isolated collision event.

The diagnostic algorithm of thyroid diseases, the most frequent dysendocrine condition, can be today integrated by the newly developed molecular methodologies. From the early diagnostic approaches, centered on the assessment of thyroid function, either by in vivo radioisotopic techniques, or by in vitro radioimmunological measurement of hormone plasma concentrations, it is nowadays possible to precisely define the molecular events triggered by the iodothyronine signal at the level of target tissues. In this brief review will be discussed the recent progresses on cloning and characterization of several genes involved in the regulation of thyroid differentiation, ability to trap iodine, synthesis and secretion of iodothyronines, regulation of thyroid function by TSH, transduction of the hormonal signal to subcellular structures involved in the translation of the hormone message in specific biological, effects such as those on metabolic homeostasis, cell proliferation and differentiation. It will be also discussed the most recent advancements on the genetics of thyroid diseases which have allowed to characterize the molecular basis of several thyropathies such as congenital hypothyroidism, thyroid hormone resistance syndrome, hyperthyroidism or hypothyroidism caused by TSH-receptor alterations, molecular abnormalities of oncogenes or tumor suppressor genes which are associated with benign or malignant thyroid cell transformation. The most recent developments of the diagnostic procedures of thyroid diseases, also in their pre-clinical stage, will be also reviewed together with a brief highlight on the most recent treatment options, centered on prophylactic therapeutic intervention or on the development of gene therapy strategies which will be possibly applied in a near future.

Factor XII (FXII) is a liver-specific zymogen involved in the regulation of hemostasis, particularly in the activation of fibrinolysis. Transcription of the FXII gene is stimulated by estrogens through specific interaction of the estrogen receptor alpha (ER alpha) with an estrogen response element present on FXII promoter. Interestingly, the magnitude of ER alpha induction in liver HepG2 cells is much lower than in NIH3T3 fibroblasts, suggesting that cell-specific factors may modulate ER alpha-dependent trans-activation. Comparative footprinting analysis of FXII promoter (from nucleotides -181 to +49) in liver vs. non-liver cell environments allowed identification of four deoxyribonuclease I-protected sites only in the presence of HepG2 nuclear extracts. Computerized homology search identified sites III and IV as consensus binding sequences for the liver-enriched transcription factor hepatocyte nuclear factor-4 (HNF-4), formerly an orphan receptor belonging to the superfamily of steroid/thyroid hormone nuclear receptors. In transient transfection assays in NIH3T3 cells, HNF-4 significantly inhibited (70%) estrogen induction of FXII promoter while not affecting basal promoter activity. Conversely, HNF-4 did not inhibit estrogen inducibility of FXII promoter in HepG2 cells due to the high endogenous levels of HNF-4 protein. In gel shift assays, HNF-4, either present in HepG2 nuclear extracts or generated by in vitro transcription/translation, specifically bound FXII promoter. This interaction is strictly required in eliciting the antagonistic effect because in NIH3T3 cells, selective mutations of sites III and IV abrogated HNF-4 inhibitory properties. In the liver-specific environment, the same mutant construct exhibited higher estrogen-dependent inducibility compared with native promoter. Rescue of estrogen responsiveness was also achieved using a dominant negative HNF-4, which counteracted endogenous HNF-4 activity. In conclusion, our findings address a direct role

Alterations of the tumor suppressor gene p53 are uncommon in differentiated thyroid neoplasia but are detected at high frequency in anaplastic thyroid carcinoma suggesting that impaired p53 function may contribute to the undifferentiated and highly aggressive phenotype of these tumors. Effects of wild type p53 (wt-p53) re-expression were investigated in a human anaplastic thyroid carcinoma cell line (ARO) expressing a mutated p53. ARO cells were stably transfected with the temperature-sensitive p53 Val135 gene (ts-p53) which exhibits wild type-like activity at 32 degrees C. Exogenous wt-p53 function in ARO-tsp53 clones was assessed by evaluating its transcriptional activity on a CAT reporter vector containing p53 binding sites. At 32 degrees C, a significant reduction in the proliferation rate (approximately or equal to 50%) was observed, with accumulation of cells in the G0/G1 phase of the cell cycle. This effect was accompanied by induction of the expression of the growth inhibitor p21/Waf1 gene. At 32 degrees C, ARO-tsp53 clones also showed a marked impairment of their tumorigenic potential. Furthermore, transfected clones re-acquired the ability to respond to thyrotropin (TSH) stimulation showing an increased expression of thyroid-specific genes (thyroglobulin, thyroperoxidase and TSH receptor). In conclusion, re-expression of wt-p53 activity in ARO cells, inhibits cell proliferation and restores responsiveness to physiological stimuli.

A clinical and pathological study was undertaken to define the prevalence, clinical presentation and outcome of thyroid carcinoma in children and adolescents. Clinical records from 48 patients under 20 years of age at diagnosis, out of 372 patients with thyroid cancer examined between 1980 and 1994, were retrospectively reviewed. Female/male ratio was 3.8/1. None had a previous positive history of head and neck irradiation. Patients underwent near-total (44 patients) or partial (4 patients) thyroidectomy followed by 131I ablation of residual thyroid tissue. The mean follow up period was 58.4 months, ranging between 2 and 190 months. Clinically a thyroid mass was present in 41 patients, 28 of whom also showed neck lymph node involvement. Node metastases were present in 50% of the patients and lung metastases in 4.2%. Histological type was papillary in 41, follicular in 6, and medullary in 1 case. Surgical complications were observed in 19 patients (40%). In 3 patients papillary thyroid cancer was associated with chronic lymphocytic thyroiditis. All patients were treated with 1-thyroxine suppressive therapy. Recurrences of cancer after surgical and radio-iodine treatment was observed only in one patient 8 months after surgery. CONCLUSION: Our experience demonstrates that thyroid carcinoma in childhood cannot be considered a rare occurrence, since it represents about 13% of all thyroid cancers, and is frequently associated with lymph node but rarely with distant metastases. Nevertheless, the prognosis of thyroid carcinoma in childhood is fairly good.

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Estrogen therapy has been reported to cause multiple alterations in hemostasis and to increase blood levels of several procoagulants, including Hageman factor [factor XII (FXII)]. Liver FXII gene expression has been investigated in ovariectomized rats, treated or not with 17 beta-estradiol. A 6-fold stimulation of FXII gene transcription was observed in treated compared to untreated animals, indicating that 17 beta-estradiol is able to induce FXII gene expression in vivo. We have recently shown that human FXII promoter contains an imperfect palindrome, 5'-GGGCAnnnTGACC-3', at position -43/-31 resembling the consensus estrogen-responsive element (ERE). Portions of different length of the FXII promoter were fused to the chloramphenicol acetyltransferase (CAT) coding sequence and transiently cotransfected with human estrogen receptor (ER) into NIH3T3 and HepG2 cells in the presence or absence of 17 beta-estradiol. A 230-base pair fragment of FXII promoter, spanning nucleotides - 181/49, conferred a strong estrogen responsiveness to the CAT reporter gene, suggesting that a functional ERE resides in this region. Cognate receptors, such as those for thyroid hormone or retinoic acid, did not stimulate CAT activity. Gel mobility assays demonstrated a specific interaction between ER and the 230-bp FXII promoter fragment containing the putative ERE palindrome. Similar results were obtained when an oligonucleotide spanning the consensus ERE was used; the complex between ER and FXII promoter sequences was supershifted after the addition of an anti-ER monoclonal antibody. Insertion of FXII-ERE into the heterologous thymidine kinase promoter conferred a strong estrogen responsiveness that was abolished by mutations of the 5'-half of the palindrome. These results represent the first demonstration at the molecular level of the regulation of a blood coagulation factor gene by 17 beta-estradiol as well as the first identification of a functional ERE within this class of genes.

Fine needle aspiration (FNA) cytology represents a reliable diagnostic procedure for preoperative identification of thyroid carcinoma. For improving its diagnostic accuracy, a technique that allows the analysis of cancer-related gene abnormalities on thyroid FNA smears has been developed. Cells were collected by scraping from thyroid smears, DNA-extracted and ras proto-oncogene sequences amplified by the polymerase chain reaction (PCR). Preliminary destaining of cytologic smears was essential for efficient PCR amplification. Twelve thyroid FNA cytologic smears, characterized by the indeterminate pattern of follicular neoplasia, were analysed for the presence of ras mutations known to confer an oncogenic potential. The same nucleotide substitution at codon 12 of the H-ras proto-oncogene was detected in two different thyroid nodules among six cases that, at final histology, were identified as follicular carcinomas. No ras mutations were observed in the remaining six cases that were diagnosed as follicular adenoma at histologic examination. Molecular analysis of FNA smears may provide additional information on the nature of the lesion underlying thyroid neoplasia, thus improving diagnostic accuracy of conventional FNA cytology.

A microscale method, based on two-colour dye immunolabelling and flow sorting cytofluorometry, was used to characterize lymphocyte subsets in thyroid tissue specimens obtained by fine-needle aspiration (FNA) in 21 patients with autonomously functioning thyroid nodule (AFTN) and five patients with cold thyroid nodule (CTN). Inversion of the ratio between CD4+ and CD8+ lymphocytes, due to a relative increase of CD8+ cells, was found among intrathyroidal lymphocytes in AFTN patients. The abnormal lymphocyte subset distribution was not observed in the peripheral blood of the same group of patients. In patients with CTN the lymphocyte subset distribution was normal, both in the thyroid and in the peripheral blood. In AFTN patients, a significant correlation was observed between the decrease of intrathyroidal CD4+/CD8+ ratio and the increase of plasma thyroid hormone levels. Whether the immunological abnormalities found in AFTN could play a pathogenetic role in the clinical presentation and outcome of the disease remains to be established. The FNA-applied micromethod used in this study could be extended as a routine investigation to characterize the immunogenic substrate of thyroid disorders.

We describe the role of fine needle aspiration in the preoperative diagnosis of thyroid nodules