Immunity acquired by a minority active fraction of the population could explain COVID-19 spread in Greater Buenos Aires (June-November 2020).

The coronavirus disease 2019 (COVID-19) pandemic had an uneven development in different countries. In Argentina, the pandemic began in March 2020 and, during the first 3 months, the vast majority of cases were concentrated in a densely populated region that includes the city of Buenos Aires (country capital) and the Greater Buenos Aires (GBA) area that surrounds it. This work focuses on the spread of COVID-19 between June and November 2020 in GBA. Within this period of time there was no vaccine, basically only the early wild strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was present, and the official restriction and distancing measures in this region remained more or less constant. Under these particular conditions, the incidences show a sharp rise from June 2020 and begin to decrease towards the end of August until the end of November 2020. In this work we study, through mathematical modelling and available epidemiological information, the spread of COVID-19 in this region and period of time. We show that a coherent explanation of the evolution of incidences can be obtained assuming that only a minority fraction of the population got involved in the spread process, so that the incidences decreased as this group of people was becoming immune. The observed evolution of the incidences could then be a consequence at the population level of lasting immunity conferred by SARS-CoV-2.

Anomalous out-of-equilibrium dynamics in the spin-ice material Dy2Ti2O7 under moderate magnetic fields.

We study experimentally and numerically the dynamics of the spin ice material Dy2Ti2O7 in the low temperature (T) and moderate magnetic field ( B ) regime (T ∈ [0.1, 1.7] K, B ∈ [0, 0.3] T). Our objective is to understand the main physics shaping the out-of-equilibrium magnetisation vs temperature curves in two different regimes. Very far from equilibrium, turning on the magnetic field after having cooled the system in zero field (ZFC) can increase the concentration of magnetic monopoles (localised thermal excitations present in these systems); this accelerates the dynamics. Similarly to electrolytes, this occurs through dissociation of bound monopole pairs. However, for spin ices the polarisation of the vacuum out of which the monopole pairs are created is a key factor shaping the magnetisation curves, with no analog. We observe a threshold field near 0.2 T for this fast dynamics to take place, linked to the maximum magnetic force between the attracting pairs. Surprisingly, within a regime of low temperatures and moderate fields, an extended Ohm's law can be used to describe the ZFC magnetisation curve obtained with the dipolar spin-ice model. However, in real samples the acceleration of the dynamics appears even sharper than in simulations, possibly due to the presence of avalanches. On the other hand, the effect of the field nearer equilibrium can be just the opposite to that at very low temperatures. Single crystals, as noted before for powders, abandon equilibrium at a blocking temperature T B which increases with field. Curiously, this behaviour is present in numerical simulations even within the nearest-neighbours interactions model. Simulations and experiments show that the increasing trend in T B is stronger for B ‖[100]. This suggests that the field plays a part in the dynamical arrest through monopole suppression, which is quite manifest for this field orientation.

Uniaxial pressure control of competing orders in a high-temperature superconductor.

Cuprates exhibit antiferromagnetic, charge density wave (CDW), and high-temperature superconducting ground states that can be tuned by means of doping and external magnetic fields. However, disorder generated by these tuning methods complicates the interpretation of such experiments. Here, we report a high-resolution inelastic x-ray scattering study of the high-temperature superconductor YBa2Cu3O6.67 under uniaxial stress, and we show that a three-dimensional long-range-ordered CDW state can be induced through pressure along the a axis, in the absence of magnetic fields. A pronounced softening of an optical phonon mode is associated with the CDW transition. The amplitude of the CDW is suppressed below the superconducting transition temperature, indicating competition with superconductivity. The results provide insights into the normal-state properties of cuprates and illustrate the potential of uniaxial-pressure control of competing orders in quantum materials.

Glycogen Synthase Kinase-3ß Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.

Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3ß inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3ß inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and ß-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3ß inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3ß enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.

The 3D Kasteleyn transition in dipolar spin ice: a numerical study with the conserved monopoles algorithm.

We study the three-dimensional Kasteleyn transition in both nearest neighbours and dipolar spin ice models using an algorithm that conserves the number of excitations. We first limit the interactions range to nearest neighbours to test the method in the presence of a field applied along [Formula: see text], and then focus on the dipolar spin ice model. The effect of dipolar interactions, which is known to be greatly self screened at zero field, is particularly strong near full polarization. It shifts the Kasteleyn transition to lower temperatures, which decreases ≈0.4 K for the parameters corresponding to the best known spin ice materials, [Formula: see text] and [Formula: see text]. This shift implies effective dipolar fields as big as 0.05 T opposing the applied field, and thus favouring the creation of 'strings' of reversed spins. We compare the reduction in the transition temperature with results in previous experiments, and study the phenomenon quantitatively using a simple molecular field approach. Finally, we relate the presence of the effective residual field to the appearance of string-ordered phases at low fields and temperatures, and we check numerically that for fields applied along [Formula: see text] there are only three different stable phases at zero temperature.

Hydroxytyrosol modulates the levels of microRNA-9 and its target sirtuin-1 thereby counteracting oxidative stress-induced chondrocyte death.

OBJECTIVE: Nutraceutical compounds, such as hydroxytyrosol (HT), have been found to exert protective effects in osteoarthritis (OA) by affecting a variety of key molecular and cellular processes in chondrocytes. However, to our knowledge, no relationship has been reported between nutraceuticals and microRNA (miR) network in OA models. Here, we identified a miR that is implicated in HT-mediated chondroprotection following oxidative stress condition by targeting sirtuin-1 (SIRT-1). METHODS: Human primary and C-28/I2 chondrocytes were pre-treated with 100 µM HT 30 min before 100 µM H2O2 addition. In silico analyses were exploited to select putative candidate miRs able to target SIRT-1 mRNA. Luciferase-based gene reporter assay was employed to demonstrate the direct link between miR-9 and its putative mRNA target. Transient transfection approach was performed to examine the effects of miR-9 levels on caspase activity, cell viability and expression of OA-related genes. RESULTS: MiR-9 was identified and confirmed as a post-transcriptional regulator of SIRT-1. MiR-9 and SIRT-1 levels showed opposite changes in chondrocytes following H2O2 and HT treatment. Moreover mir-9 silencing inhibited cell death induced by H2O2 partly through down-regulation of SIRT-1, whereas miR-9 overexpression markedly reduced the protective effect of HT. The manipulation of miR-9 levels also resulted in the modulation of OA-related gene expression, including MMP-13, VEGF and RUNX-2. CONCLUSIONS: These results show that miR-9 is a critical mediator of the deleterious and OA-related effects of oxidative stress in chondrocytes and that modulation of miR expression may be a crucial mechanism underlying the protective action of HT.

Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis.

OBJECTIVE: Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by joint structure changes and inflammation, both mediated by the IκB kinase (IKK) signalosome complex. The ability of N-acetyl phenylalanine derivative (NAPA) to increase cartilage matrix components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity, has been observed in vitro. The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM). DESIGN: 26 mice were divided into three groups: (1) DMM surgery without treatment; (2) DMM surgery treated after 2 weeks with one intra-articular injection of NAPA (2.5 mM) and (3) no DMM surgery. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and microhardness of subchondral bone (SB) tests. RESULTS: The injection of NAPA significantly improved cartilage thickness (CT) and reduced Chambers and Mankin modified scores and fibrillation index (FI), with weaker MMP13, ADAMTS5, MMP10 and IKKα staining. The microhardness measurements did not shown statistically significant differences between the different groups. CONCLUSIONS: NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo.

Field-Tuned Order by Disorder in Frustrated Ising Magnets with Antiferromagnetic Interactions.

We demonstrate the appearance of thermal order by disorder in Ising pyrochlores with staggered antiferromagnetic order frustrated by an applied magnetic field. We use a mean-field cluster variational method, a low-temperature expansion, and Monte Carlo simulations to characterize the order-by-disorder transition. By direct evaluation of the density of states, we quantitatively show how a symmetry-broken state is selected by thermal excitations. We discuss the relevance of our results to experiments in 2D and 3D samples and evaluate how anomalous finite-size effects could be exploited to detect this phenomenon experimentally in two-dimensional artificial systems, or in antiferromagnetic all-in-all-out pyrochlores like Nd_{2}Hf_{2}O_{7} or Nd_{2}Zr_{2}O_{7}, for the first time.

Intermediate magnetization state and competing orders in Dy2Ti2O7 and Ho2Ti2O7.

Among the frustrated magnetic materials, spin-ice stands out as a particularly interesting system. Residual entropy, freezing and glassiness, Kasteleyn transitions and fractionalization of excitations in three dimensions all stem from a simple classical Hamiltonian. But is the usual spin-ice Hamiltonian a correct description of the experimental systems? Here we address this issue by measuring magnetic susceptibility in the two most studied spin-ice compounds, Dy2Ti2O7 and Ho2Ti2O7, using a vector magnet. Using these results, and guided by a theoretical analysis of possible distortions to the pyrochlore lattice, we construct an effective Hamiltonian and explore it using Monte Carlo simulations. We show how this Hamiltonian reproduces the experimental results, including the formation of a phase of intermediate polarization, and gives important information about the possible ground state of real spin-ice systems. Our work suggests an unusual situation in which distortions might contribute to the preservation rather than relief of the effects of frustration.

PKCε is a regulator of hypertrophic differentiation of chondrocytes in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a common and highly debilitating degenerative disease whose complex pathogenesis and the multiplicity of the molecular processes involved, hinder its complete understanding. Protein Kinase C (PKC) novel isozyme PKCε recently proved to be an interesting molecule for further investigations as it can represent an intriguing, new actor in the acquisition of a OA phenotype by the chondrocyte. DESIGN: PKCε was modulated in primary chondrocytes from human OA patient knee cartilage samples by means of short hairpin RNA (ShRNA) and the expression of cartilage specific markers observed at mRNA and protein level. The involvement of Histone deacetylases (HDACs) signaling pathway was also investigated through the use of specific inhibitors MS-275 and Inhibitor VIII. RESULTS: PKCε loss induces up-regulation of Runt-domain transcription factor (RUNX2), Metalloproteinase 13 (MMP13) and Collagen X (COL10) as well as an enhanced calcium deposition in OA chondrocyte cultures. In parallel, PKCε knock-down also leads to SOX9 and Collagen II (COL2) down-modulation and to a lower deposition of glycosaminoglycans (GAGs) in the extracellular matrix (ECM). This novel regulatory role of PKCε over cartilage hypertrophic phenotype is exerted via an HDAC-mediated pathway, as HDAC2 and HDAC4 expression is modulated by PKCε. HDAC2 and HDAC4, in turn, are at least in part responsible for the modulation of the master transcription factors RUNX2 and SOX9, key regulators of chondrocyte phenotype. CONCLUSIONS: PKCε prevents the phenotypic progression of the OA chondrocyte, acting on cartilage specific markers through the modulation of the transcription factors SOX9 and RUNX2. The loss of PKCε enhances, in fact, the OA hypertrophic phenotype, with clear implications in the pathophysiology of the disease.

Cell death in human articular chondrocyte: a morpho-functional study in micromass model.

Chondrocyte death and loss of extracellular matrix are the central features in articular cartilage degeneration during osteoarthritis pathogenesis. Cartilage diseases and, in particular, osteoarthritis are widely correlated to apoptosis but, chondrocytes undergoing apoptosis "in vivo" more often display peculiar features that correspond to a distinct process of programmed cell death termed "chondroptosis". Programmed cell death of primary human chondrocyte has been here investigated in micromasses, a tridimensional culture model, that represents a convenient means for studying chondrocyte biology. Cell death has been induced by different physical or chemical apoptotic agents, such as UVB radiation, hyperthermia and staurosporine delivered at both 1 and 3 weeks maturation. Conventional electron microscopy was used to analyse morphological changes. Occurrence of DNA fragmentation and caspase involvement were also investigated. At Transmission Electron Microscopy, control cells appear rounding or slightly elongated with plurilobated nucleus and diffusely dispersed chromatin. Typically UVB radiation and staurosporine induce chromatin apoptotic features, while hyperthermia triggers the "chondroptotic" phenotype. A weak TUNEL positivity appears in control, correlated to the well known cell death patterns occurring along cartilage differentiation. UVB radiation produces a strong positivity, mostly localized at the micromass periphery. After hyperthermia a higher number of fluorescent nuclei appears, in particular at 3 weeks. Staurosporine evidences a diffuse, but reduced, positivity. Therefore, DNA fragmentation is a common pattern in dying chondrocytes, both in apoptotic and "chondroptotic" cells. Moreover, all triggers induce caspase pathway activation, even if to a different extent, suggesting a fundamental role of apoptotic features, in chondrocyte cell death.

Charge ordering in a pure spin model: dipolar spin ice.

We study the dipolar spin-ice model at fixed density of single excitations, ρ, using a Monte Carlo algorithm where processes of creation and annihilation of such excitations are banned. In the limit of ρ going to zero, this model coincides with the usual dipolar spin-ice model at low temperatures, with the additional advantage that a negligible number of monopoles allows for equilibration even at the lowest temperatures. Thus, the transition to the ordered fundamental state found by Melko, den Hertog, and Gingras in 2001 is reached using simple local spin flip dynamics. As the density is increased, the monopolar nature of the excitations becomes apparent: the system shows a rich ρ vs T phase diagram with "charge" ordering transitions analogous to that observed for Coulomb charges in lattices. A further layer of complexity is revealed by the existence of order both within the charges and their associated vacuum, which can only be described in terms of spins--the true microscopic degrees of freedom of the system.

Fast sweep-rate plastic Faraday force magnetometer with simultaneous sample temperature measurement.

We present a design for a magnetometer capable of operating at temperatures down to 50 mK and magnetic fields up to 15 T with integrated sample temperature measurement. Our design is based on the concept of a Faraday force magnetometer with a load-sensing variable capacitor. A plastic body allows for fast sweep rates and sample temperature measurement, and the possibility of regulating the initial capacitance simplifies the initial bridge balancing. Under moderate gradient fields of ~1 T/m our prototype performed with a resolution better than 1 × 10(-5) emu. The magnetometer can be operated either in a dc mode, or in an oscillatory mode which allows the determination of the magnetic susceptibility. We present measurements on Dy(2)Ti(2)O(7) and Sr(3)Ru(2)O(7) as an example of its performance.

Role of polyamines in hypertrophy and terminal differentiation of osteoarthritic chondrocytes.

Polyamines are naturally occurring, positively charged polycations which are able to control several cellular processes in different cell types, by interacting with negatively charged compounds and structures within the living cell. Functional genomics in rodents targeting key biosynthetic or catabolic enzymes have revealed a series of phenotypic changes, many of them related to human diseases. Several pieces of evidence from the literature point at a role of polyamines in promoting chondrocyte differentiation, a process which is physiological in growth plate maturation or fracture healing, but has pathological consequences in articular chondrocytes, programmed to keep a maturational arrested state. Inappropriate differentiation of articular chondrocytes results in osteoarthritis. Thus, we have studied the effects of exogenously added spermine or spermidine in chondrocyte maturation recapitulated in 3D cultures, to tease out the effects on gene and protein expression of key chondrogenesis regulatory transcription factors, markers and effectors, as well as their posttranscriptional regulation. The results indicate that both polyamines are able to increase the rate and the extent of chondrogenesis, with enhanced collagen 2 deposition and remodeling with downstream generation of collagen 2 bioactive peptides. These were able to promote nuclear localization of RUNX-2, the pivotal transcription factor in chondrocyte hypertrophy and osteoblast generation. Indeed, samples stimulated with polyamines showed an enhanced mineralization, along with increased caspase activity, indicating increased chondrocyte terminal differentiation. In conclusion these results indicate that the polyamine pathway can represent a potential target to control and correct chondrocyte inappropriate maturation in osteoarthritis.

Unconventional magnetization processes and thermal runaway in spin-ice Dy2Ti2O7.

We investigate the nonequilibrium behavior of the spin-ice Dy2Ti2O7 by studying its magnetization as a function of the field sweep rate. Below the enigmatic ''freezing'' temperature T(equil)≈600 mK, we find that even the slowest sweeps fail to yield the equilibrium magnetization curve and instead give an initially much flatter curve. For higher sweep rates, the magnetization develops sharp steps accompanied by similarly sharp peaks in the temperature of the sample. We ascribe the former behavior to the energy barriers encountered in the magnetization process, which proceeds via flipping of spins on filaments traced out by the field-driven motion of the gapped, long-range interacting magnetic monopole excitations. The peaks in temperature result from the released Zeeman energy not being carried away efficiently; the resulting heating triggers a chain reaction.

Quantum oscillations in the anomalous phase in Sr3Ru2O7.

We report measurements of quantum oscillations detected in the putative nematic phase of Sr3Ru2O7. Improvements in sample purity enabled the resolution of small amplitude de Haas-van Alphen (dHvA) oscillations between two first order metamagnetic transitions delimiting the phase. Two distinct frequencies were observed, whose amplitudes follow the normal Lifshitz-Kosevich profile. Variations of the dHvA frequencies are explained in terms of a chemical potential shift produced by reaching a peak in the density of states, and an anomalous field dependence of the oscillatory amplitude provides information on domains.

[Carotid body tumor. An often misdiagnosed disease]. / Chemodectoma carotideo. Una entità spesso misconosciuta.

Chemodectomas are uncommon neoplasms, born by glomic cell of extra-adrenegic system. Usually, these neoplasms are benign and non functioning, but when they are more than 4 cm can induce a neuro-vascular compressive syndrome. In this study the Authors propose the guidelines for diagnostic, clinical and therapeutic management, of these tumors according to their experience.

[Differentiated thyroid cancers]. / I carcinomi tiroidei differenziati.

The Authors, after a review of the topic of thyroid cancer, focus on the epidemiology, aetiology and diagnosis of well-differentiated thyroid cancers. They then describe their own case series and their many years' experience in treating the patients affected by this pathology, which is generally regarded as having low malignancy. Nowadays the Authors consider the treatment of choice the total thyroidectomy with central compartment lymphectomy, eventually associated with metabolic radiotherapy.

[Hyperparathyroidism from mediastinal parathyroid adenoma. Case report]. / Iperparatiroidismo da adenoma paratiroideo a localizzazione mediastinica. Caso clinico.

The authors, after reviewing parathyroid gland diseases, their location, and the modern strategies that can be used for their pre-operative detection, describe a case of primary hyperparathyroidism which recently came to their attention. The use of a combination of instrumental techniques (US, scintigraphy and SPEcT) enabled them to establish, prior to surgery, the mediastinal ectopic site of the parathyroid adenoma. Mini-invasive surgery proved to be the optimal technique to performing a targeted surgical excision that reduced the operative time and the hospitalisation.