Hyalinizing trabecular tumour of the thyroid: fine-needle aspiration cytological diagnosis and correlation with histology.

Hyalinizing trabecular tumour (HTT) is a rare thyroid neoplasm of follicular cell origin characterised by a trabecular growth pattern and prominent intratrabecular and intertrabecular hyalinisation. These peculiar histological features allow the prompt recognition of this neoplasm in surgical specimens. However, cytological diagnosis of HTT remains elusive and misleading because of overlapping characteristics with other thyroid tumours, particularly papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC) and the newly described non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Nevertheless, the proper recognition of this neoplasm on preoperative cytological preparations is important to avoid unnecessary overtreatment of this indolent lesion. A thorough review of the literature has revealed that the correct diagnosis of HTT in cytological smears is achieved in only 8% of cases. In a further 6% of cases, diagnostic doubt has been indicated. Sixty percent of published cases of HTT have been misdiagnosed as suggestive, suspicious or positive for PTC. These findings underline the difficulties of a cytological-based diagnosis of such entity. In this article we review the cytomorphological features of HTT and their correlation to histological features to provide the reader with the tools to improve diagnostic performance in the identification of HTT on preoperative cytology

A Heuristic Approach to Analysis of the Genetic Susceptibility Profile in Patients Affected by Airway Allergies

Allergic respiratory diseases such as asthma might be considered multifactorial diseases, having a complex pathogenesis that involves environmental factors and the activation of a large set of immune response pathways and mechanisms. In addition, variations in genetic background seem to play a central role. The method developed for the analysis of the complexities, as association rule mining, nowadays may be applied to different research areas including genetic and biological complexities such as atopic airway diseases to identify complex genetic or biological markers and enlighten new diagnostic and therapeutic targets. A total of 308 allergic patients and 205 controls were typed for 13 single nucleotide polymorphisms (SNPs) of cytokine and receptors genes involved in type 1 and type 2 inflammatory response (IL-4 rs2243250 C/T, IL-4R rs1801275A/G, IL-6 rs1800795 G/C, IL-10 rs1800872 A/C and rs1800896 A/G, IL-10RB rs2834167A/G, IL-13 rs1800925 C/T, IL-18 rs187238G/C, IFNγ rs 24030561A/T and IFNγR2 rs2834213G/A), the rs2228137C/T of CD23 receptor gene and rs577912C/T and rs564481C/T of Klotho genes, using KASPar SNP genotyping method. Clinical and laboratory data of patients were analyzed by formal statistic tools and by a data-mining technique—market basket analysis—selecting a minimum threshold of 90% of rule confidence. Formal statistical analyses show that IL-6 rs1800795GG, IL-10RB rs2834167G positive genotypes, IL-13 rs1800925CC, CD23 rs2228137TT Klotho rs564481TT, might be risk factors for allergy. Applying the association rule methodology, we identify 10 genotype combination patterns associated with susceptibility to allergies. Together these data necessitate being confirmed in further studies, indicating that the heuristic approach might be a straightforward and useful tool to find predictive and diagnostic molecular patterns that might be also considered potential therapeutic targets in allergy

SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy

We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high Creactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60-40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment. Copyright

Electromagnetic response functions of few-nucleon systems

Inclusive electromagnetic reactions in few-nucleon systems are studied basing on accurate three- and four-body calculations. The longitudinal 4He(e,e') response function obtained at q\le 600 MeV/c completely agrees with experiment. The exact 4He spectral function obtained in a semirealistic potential model is presented, and the accuracy of the quasielastic response calculated with its help is assessed, as well as the accuracy of some simpler approximations for the response. The photodisintegration cross section of 3He obtained with the realistic AV14 NN force plus UrbanaVIII NNN force agrees with experiment. It is shown that this cross section is very sensitive to underlying nuclear dynamics in the E_\gamma\simeq 70-100 MeV region. In particular, the NNN nuclear force clearly manifests itself in this region.Comment: 10 pages, Latex, style file is included, 7 ps figures, to appear in Proc. of the 2nd Int. Conf. on Perspectives in Hadronic Physics, ITCP, Triest, May 1999, World Sci., Singapor

Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B

Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia. Method comparison showed that capillary electrophoresis of long-range PCR amplification products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, − 2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, − 27.66 to 40.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92 to 1.04]; intercept: 10.62 [95% CI, − 7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, − 41.93 to 39.15]). Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. We also identified 9 French patients (9/53; 17%) and 2 of their relatives who carried an FGF14 (GAA)≥250 expansion. This novel strategy reliably detected and sized FGF14 GAA expansions, and compared favorably to long-read sequencing

HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

Urban biodiversity : State of the science and future directions

Since the 1990s, recognition of urban biodiversity research has increased steadily. Knowledge of how ecological communities respond to urban pressures can assist in addressing global questions related to biodiversity. To assess the state of this research field in meeting this aim, we conducted a systematic review of the urban biodiversity literature published since 1990. We obtained data from 1209 studies that sampled ecological communities representing 12 taxonomic groups. While advances have been made in the field over the last 30 years, we found that urban biodiversity research has primarily been conducted in single cities within the Palearctic and Nearctic realms, within forest remnants and residential locations, and predominantly surveys plants and birds, with significant gaps in research within the Global South and little integration of multi-species and multi-trophic interactions. Sample sizes remain limited in spatial and temporal scope, but citizen science and remote sensing resources have broadened these efforts. Analytical approaches still rely on taxonomic diversity to describe urban plant and animal communities, with increasing numbers of integrated phylogenetic and trait-based analyses. Despite the implementation of nature-based solutions across the world's cities, only 5% of studies link biodiversity to ecosystem function and services, pointing to substantial gaps in our understanding of such solutions. We advocate for future research that encompasses a greater diversity of taxonomic groups and urban systems, focusing on biodiversity hotspots. Implementing such research would enable researchers to move forward in an equitable and multidisciplinary way to tackle the complex issues facing global urban biodiversity.Peer reviewe

Estrategias de tratamiento no farmacológico en un caso de Alzheimer de inicio temprano

El tratamiento de los pacientes con cuadros de Enfermedad de Alzheimer (EA) con inicio temprano se nos presenta como un desafío institucional. La EA de inicio temprano como entidad clínica a ser abordada por las terapias no farmacológicas requiere un capítulo aparte, ya que la presentación sintomática y la evolución del cuadro difieren de las típicas presentaciones de EA de inicio tardío. En este trabajo, se presenta un caso EA de inicio temprano con el objetivo de analizar el tratamiento interdisciplinario no farmacológico en este tipo de presentación.Facultad de Ciencias Médica

2010-2014 Seismic activity images the activated fault system in the Pollino area, at the Appennines-Calabrian arc boundary region

The main goal of this study is to increase the understanding of the physical mechanisms behind the ongoing seismic activity in the Pollino area and its influence on the seismic hazard of the Apennines-Calabrian arc boundary region. The study area, near the Pollino massif, is located at the northernmost edge of the Calabrian Arc, which is the last oceanic subduction segment along the Africa-Eurasian plate. The subduction results from the sinking of the Ionian oceanic plate beneath the Calabrian Arc-Southern Tyrrhenian Sea and is part of the fragmented tectonic boundary between two macro-plates: Africa and Eurasia. The subduction geometry is well-documented by several seismological studies (i.e. Chiarabba et al., 2005), and the lithospheric structure of the area is quietly well known (i.e. Totaro et al., 2014 and Piana Agostinetti and Amato, 2009) Despite the slow N-S convergence between these major plates, the Southern Tyrrhenian Sea is a large basin characterized by E-W extensional tectonic. Since Late Miocene, the Calabrian Arc slab experienced rapid rollback, moving E to SE at a rate of 5-6 cm/yr, which is by far higher than the ~1-2 cm/yr rate of convergence between Africa and Europa (Faccenna et al., 2004). However, during late Pleistocene, rollback and subduction have slowed and is likely proceeding at less than 1 cm/yr (D’Agostino and Selvaggi., 2004). Geodetic measurements show that the Pollino Range is subject to NE-SW anti-apenninic extension. In the region the strain rate field shows a continuous belt of extensional deformation that follows the ridge of the Southern Apennines and extends in the Pollino region. The extension rate appears to decrease from the Southern Apennines to the Calabria- Lucania border region (D’Agostino et al., 2013). This finding indeed reveals that the Pollino region is deforming and accumulating tectonic strain which results in a complex system of normal active faults striking sub-parallel to the Apennines. Two principal normal faults are present in the Italian Database of the Individual Seismogenic Sources DISS version 3.1.1 (DISS Working Group, 2010) in the Pollino area: the Pollino (P) fault and the “Rimendiello-Mormanno” (RM) fault system. The RM fault is an active seismogenic structure it strikes about NNW-SSE and dips toward NE; it has hosted in its northernmost part a M 5.0 earthquake on 9th September 1998. The P fault has similar strike but dips toward SW: it shows no recent seismicity and is hence one of the most prominent seismic gaps in the Italian historical seismic catalogue (Rovida et al., 2011). Paleoseismic studies have shown that the P fault was active in the last ten thousand years and is capable to produce events with magnitude above 6.0. The DISS database reports as debated source also the Piana Perretti fault (Brozzetti et al., 2009). A detailed structural map of the area interested by the seismic sequence shows three fault systems (Brozzetti et al., 2013) consisting of several aligned fault segments that have been active during the Late Pleistocene and are reasonably presently active. The first fault system strikes NW-SE and dips toward SW (including the Piana Perretti fault at the NE edge of the Mercure Basin), the second one has similar strike and NE dip, while the third one strikes about E-W. Earthquakes reported in the historical catalogues for this area are not very strong. Few earthquakes with magnitude probably less than 6 affected the area, including the Mw=5.6 “Mercure” event in 1998 (Brozzetti et al., 2009). The Parametric Catalogue of Italian earthquakes (CPTI11, Rovida et al., 2011), shows very well the lack of strong earthquakes in the region: there is a clear evidence of large earthquakes in the Campania-Basilicata area (M~7.0) and several strong earthquakes in the Sila region and in the whole Calabrian territory. According to the seismic classification of the national territory, the area affected by the 2010-2014 seismic activity have a relatively higher probability to be shaken by a strong acceleration (Gruppo di Lavoro MPS, 2004). Most of the seismic events occurred in areas where the peak ground acceleration having 10% chance of being exceeded in next 50 years is between the values of 0.225 g and 0.275 g.PublishedBologna2T. Tettonica attiva3T. Pericolosità sismica e contributo alla definizione del rischio5T. Sorveglianza sismica e operatività post-terremoto1IT. Reti di monitoraggio e Osservazioniope