Síndrome de quilomicronemia: aspectos genéticos y revisión de la literatura / Chylomicronemia syndrome: genetic aspects and literature review

Chylomicronemia syndrome is a metabolic condition characterized by severe hypertriglyceridemia and fasting chylomicronemia, secondary to an alteration in the ability to metabolize triglycerides. It can respond to different etiologies, the most frequent being multifactorial. Familial chylomicronemia syndrome, on the other hand, represents an infrequent cause of chylomicronemia syndrome, showing an autosomal recessive inheritance pattern. It's caused by pathogenic variants in genes related to chylomicron's metabolism, mainly LPL1 gene. One of the main associated risks is the occurrence of acute pancreatitis, which can also have a recurrent course. The primary therapy goal in patients with this condition is prevention of pancreatitis and related comorbidities. The treatment basis consists in reduce chylomicron formation by restriction of dietary fat, in association with physical activity and pharmacologic therapy. It is important to distinguish the etiology of chylomicronemia syndrome since it has repercussions in terms of response to treatment, complications, and recurrence risk. (AU)

Tuning Coherent-Phonon Heat Transport in LaCoO3/SrTiO3 Superlattices.

Accessing the regime of coherent phonon propagation in nanostructures opens enormous possibilities to control the thermal conductivity in energy harvesting devices, phononic circuits, etc. In this paper we show that coherent phonons contribute substantially to the thermal conductivity of LaCoO3/SrTiO3 oxide superlattices, up to room temperature. We show that their contribution can be tuned through small variations of the superlattice periodicity, without changing the total superlattice thickness. Using this strategy, we tuned the thermal conductivity by 20% at room temperature. We also discuss the role of interface mixing and epitaxial relaxation as an extrinsic, material dependent key parameter for understanding the thermal conductivity of oxide superlattices.

A medicalized hotel as a public health resource for the containment of Covid-19: more than a place for quarantining.

BACKGROUND: To describe the implementation of a medicalized hotel in the community of Madrid as a public health resource for the containment of coronavirus disease (COVID-19) and to describe the characteristics of population benefitted. METHODS: A descriptive study of the implementation of the Via Castellana Medicalised Hotel (VCMH) was conducted. The average monthly household income, educational level and occupational social class of the subjects admitted were obtained through a survey conducted during their stay. RESULTS: There was no guidance for launching; however the hotel was coordinated by a tertiary referral hospital and attended the preventive medicine regulations and the decrees of legal regimes and authorization of health services in Madrid. Between 19 March and the 9 May 2020, 399 patients were admitted; 59% (235) were migrant; the main reason for referral (58%) was a lack of house conditions for quarantining, including overcrowding, which when compared with the migrant status a positive correlation was found. Some other reasons for referral were homelessness and eviction. Most of the survey participants had low monthly household income, educational level and social class. CONCLUSIONS: This medicalized hotel provided medical care and offered housing to a subgroup of vulnerable population who could not afford a safe quarantine.

Diseño de un protocolo de telegenética como asistencia al proceso de diagnóstico y registro de los recién nacidos con anomalías congénitas en las regiones de Los Lagos y de Arica y Parinacota / Design of a telegenetic protocol to assist in the diagnosis and registration process of newborns with congenital anomalies in the Los Lagos and Arica and Parinacota regions

The majority of clinical geneticists in Chile work in the Metropolitan Region (78%). To expand the area of Telemedicine and support the management of the Ministry of Health, we present this Telegenetics development project that includes innovation of assistance and educational nature directed to regions. The implementation of the National Registry of Congenital Anomalies in Chile (RENACH) in the public and private systems, in December 2015, and the obligation to record and describe the anomalies in all newborns, constitutes a favorable scenario that would benefit from the support of clinical geneticists. This proposal brings together a team of 18 specialists and 6 fellows, professionals from different Universities and / or Hospitals of Health Services, in a collaborative project in the area of clinical genetics, which, supported by the HCUCH + CIMT Telemedicine project, will contribute to two regions of Chile better tools for the diagnosis and comprehensive management of newborn patients with congenital anomalies. It can serve as a pilot for a new way to support the registration of malformations throughout Chile and teach clinical genetics concepts. The expected benefits are to improve the quality of care and health management in patients with little-known diseases. (AU)

Antiproliferative effects of Bortezomib in endothelial cells transformed by viral G protein-coupled receptor associated to Kaposi's sarcoma.

The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes. Bortezomib decreases ERK1/2 phosphorylation whereas induces the accumulation of MKP-3 - a specific ERK1/2 MAP kinase phosphatase - in time and concentration dependent manner (1.5-32h; 0.25-1nM). The transcription factor FOXO1 is activated by dephosphorylation and regulates p21 expression. Here, we demonstrated that Bortezomib increases FOXO1 protein and decreases its phosphorylation in a concentration dependent manner (0.25-1nM). Bortezomib (0.5nM, 24h) also increase nuclear FOXO1 protein, in line with FOXO1 dephosphorylation induced by the drug. Consistent with FOXO1 dephosphorylation/activation, p21 mRNA expression is increased by Bortezomib in a MKP-3-dependent way. Bortezomib (0.5nM, 24h) also decreases VEGF, an ERK1/2 -dependent effect. It is concluded that in vGPCR cells, Bortezomib decreases ERK1/2 and FOXO1 phosphorylation through MKP-3 accumulation, leading ERK1/2 deactivation and FOXO1 activation respectively and, consequently, to cell proliferation inhibition, p21 induction and VEGF repression. Taken together, all these events contribute to the anti-tumoral effect of Bortezomib.

Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice.

BACKGROUND AND PURPOSE: Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL-6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL-6 in mediating fasting/re-feeding changes in the expression of hepatic lipogenic enzymes. EXPERIMENTAL APPROACH: Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated in vivo. The involvement of STAT3 in mediating these IL-6 responses was investigated by using siRNA in human HepG2 cells. KEY RESULTS: During feeding, the up-regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL-6(-/-) mice. During fasting, expression of lipogenic genes decreased gradually over time in both strains, although the initial drop was more marked in IL-6(-/-) mice. Protein levels of hepatic lipogenic enzymes were lower in IL-6(-/-) than in WT mice at the end of the fasting period. In WT, circulating IL-6 levels paralleled gene expression of hepatic lipogenic enzymes. IL-6 administration in vivo and in vitro showed that IL-6-mediated signalling was associated with the up-regulation of hepatic lipogenic enzyme genes. Moreover, silencing STAT3 in HepG2 cells attenuated IL-6 mediated up-regulation of lipogenic gene transcription levels. CONCLUSIONS AND IMPLICATIONS: IL-6 sustains levels of hepatic lipogenic enzymes during fasting through activation of STAT3. Our findings indicate that clinical use of STAT3-associated signalling cytokines, particularly against steatosis, should be undertaken with caution.

Electronic Degeneracy and Intrinsic Magnetic Properties of EpitaxialNb: SrTiO3 Thin Films Controlled by Defects.

We report thermoelectric power experiments in e-doped thin films of SrTiO3 (STO) which demonstrate that the electronic band degeneracy can be lifted through defect management during growth. We show that even small amounts of cationic vacancies, combined with epitaxial stress, produce a homogeneous tetragonal distortion of the films, resulting in a Kondo-like resistance upturn at low temperature, large anisotropic magnetoresistance, and nonlinear Hall effect. Ab initio calculations confirm a different occupation of each band depending on the degree of tetragonal distortion. The phenomenology reported in this Letter for tetragonally distorted e-doped STO thin films, is similar to that observed in LaAlO3/STO interfaces and magnetic STO quantum wells.

Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD.

The pathogenic mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) are not fully understood. In this study, we aimed to assess the relationship between endoplasmic reticulum (ER) stress and autophagy in human and mouse hepatocytes during NAFLD. ER stress and autophagy markers were analyzed in livers from patients with biopsy-proven non-alcoholic steatosis (NAS) or non-alcoholic steatohepatitis (NASH) compared with livers from subjects with histologically normal liver, in livers from mice fed with chow diet (CHD) compared with mice fed with high fat diet (HFD) or methionine-choline-deficient (MCD) diet and in primary and Huh7 human hepatocytes loaded with palmitic acid (PA). In NASH patients, significant increases in hepatic messenger RNA levels of markers of ER stress (activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP)) and autophagy (BCN1) were found compared with NAS patients. Likewise, protein levels of GRP78, CHOP and p62/SQSTM1 (p62) autophagic substrate were significantly elevated in NASH compared with NAS patients. In livers from mice fed with HFD or MCD, ER stress-mediated signaling was parallel to the blockade of the autophagic flux assessed by increases in p62, microtubule-associated protein 2 light chain 3 (LC3-II)/LC3-I ratio and accumulation of autophagosomes compared with CHD fed mice. In Huh7 hepatic cells, treatment with PA for 8 h triggered activation of both unfolding protein response and the autophagic flux. Conversely, prolonged treatment with PA (24 h) induced ER stress and cell death together with a blockade of the autophagic flux. Under these conditions, cotreatment with rapamycin or CHOP silencing ameliorated these effects and decreased apoptosis. Our results demonstrated that the autophagic flux is impaired in the liver from both NAFLD patients and murine models of NAFLD, as well as in lipid-overloaded human hepatocytes, and it could be due to elevated ER stress leading to apoptosis. Consequently, therapies aimed to restore the autophagic flux might attenuate or prevent the progression of NAFLD.

Pivotal role of protein tyrosine phosphatase 1B (PTP1B) in the macrophage response to pro-inflammatory and anti-inflammatory challenge.

Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been suggested as an attractive target to improve insulin sensitivity in different cell types. In the present work, we have investigated the effect of PTP1B deficiency on the response of human and murine macrophages. Using in vitro and in vivo approaches in mice and silencing PTP1B in human macrophages with specific siRNAs, we have demonstrated that PTP1B deficiency increases the effects of pro-inflammatory stimuli in both human and rodent macrophages at the time that decreases the response to alternative stimulation. Moreover, the absence of PTP1B induces a loss of viability in resting macrophages and mainly after activation through the classic pathway. Analysis of early gene expression in macrophages treated with pro-inflammatory stimuli confirmed this exacerbated inflammatory response in PTP1B-deficient macrophages. Microarray analysis in samples from wild-type and PTP1B-deficient macrophages obtained after 24 h of pro-inflammatory stimulation showed an activation of the p53 pathway, including the excision base repair pathway and the insulin signaling pathway in the absence of PTP1B. In animal models of lipopolysaccharide (LPS) and D-galactosamine challenge as a way to reveal in vivo inflammatory responses, animals lacking PTP1B exhibited a higher rate of death. Moreover, these animals showed an enhanced response to irradiation, in agreement with the data obtained in the microarray analysis. In summary, these results indicate that, although inhibition of PTP1B has potential benefits for the treatment of diabetes, it accentuates pro-inflammatory responses compromising at least macrophage viability.

Magnetic field induced transition in vanadium spinels.

We study vanadium spinels AV2O4 (A = Cd,Mg) in pulsed magnetic fields up to 65 T. A jump in magnetization at µ0H≈40 T is observed in the single-crystal MgV2O4, indicating a field induced quantum phase transition between two distinct magnetic orders. In the multiferroic CdV2O4, the field induced transition is accompanied by a suppression of the electric polarization. By modeling the magnetic properties in the presence of strong spin-orbit coupling characteristic of vanadium spinels, we show that both features of the field induced transition can be successfully explained by including the effects of the local trigonal crystal field.

Vitamin D analogue TX 527 down-regulates the NF-κB pathway and controls the proliferation of endothelial cells transformed by Kaposi sarcoma herpesvirus.

BACKGROUND AND PURPOSE: The Kaposi sarcoma (KS)-associated herpesvirus GPCR (vGPCR) is a key molecule in the pathogenesis of KS, where it increases NF-κB gene expression and activates the NF-κB pathway. We investigated whether the less calcemic vitamin D analogue TX 527 inhibited the proliferation of endothelial cells transformed by vGPCR by modulation of the NF-κB pathway. EXPERIMENTAL APPROACH: Endothelial cells transformed by vGPCR (SVEC-vGPCR) were treated with TX 527. Proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and cell cycle by flow cytometry. mRNA and protein levels were measured by real-time quantitative reverse transcriptase-PCR (qRT-PCR) and immunoblot analysis respectively. KEY RESULTS: TX 527, similar to bortezomib (0.5 nM), a proteasome inhibitor that inhibits the activation of NF-κB, reduced proliferation and induced G0/G1 cell cycle arrest in SVEC-vGPCR. TX 527 like 1α,25(OH)2 D3 , biological active form of vitamin D, decreased the activity of NF-κB comparable with the effect of bortezomib. Time-response studies showed that TX 527 significantly decreased NF-κB and increased IκBα mRNA and protein levels. The increase of IκBα was accompanied by a reduction in p65/NF-κB translocation to the nucleus. These responses were abolished when vitamin D receptor (VDR) expression was suppressed by stable transfection of shRNA against VDR. In parallel with NF-κB inhibition, there was a down-regulation of inflammatory genes such as IL-6, CCL2/MCP and CCL20/MIP3α. CONCLUSIONS AND IMPLICATIONS: These results suggest that the anti-proliferative effects of the vitamin D analogue TX 527 in SVEC-vGPCR occur by modulation of the NF-κB pathway and are VDR dependent.

Ab initio study of the influence of nanoscale doping inhomogeneities in the phase separated state of La1-xCaxMnO3.

The chemical influence in the phase separation phenomenon that occurs in perovskite manganites is discussed by means of ab initio calculations. Supercells have been used to simulate a phase separated state, that occurs at Ca concentrations close to the localized itinerant crossover. We have first considered a model with two types of magnetic ordering coexisting within the same compound. This is not stable. However, a non-isotropic distribution of chemical dopants is found to be the ground state. This leads to regions in the system with different effective concentrations, that would always accompany the magnetic phase separation at the same nanometric scale, with hole-rich regions being more ferromagnetic in character and hole-poor regions being in the antiferromagnetic region of the phase diagram, as long as the system is close to a phase crossover.

Dirac point degenerate with massive bands at a topological quantum critical point.

The quasilinear bands in the topologically trivial skutterudite insulator CoSb(3) are studied under adiabatic, symmetry-conserving displacement of the Sb sublattice. In this cubic, time-reversal and inversion symmetric system, a transition from trivial insulator to topological point Fermi surface system occurs through a critical point in which massless (Dirac) bands appear, and moreover are degenerate with massive bands. Spin-orbit coupling, while small due to the type of band character, coupled with tetragonal strain opens the gap required to give the topological insulator. The mineral skutterudite (CoSb(3)) is very near the critical point in its natural state.

Estudios genéticos sobre espina Bífida en Chile: por dónde comenzar?: [revisión] / Genetic studies of spina bifida in Chile: where do we start?: [review]

Neural tube defects (NTDs) are a group of congenital anomalies that affect the central nervious system. Spina Bifida (SB) is the most frecuent NTD in live births andi t is usually associated to disease, disability; and mortality. NTDs are considered as a multifactorial disease. Women who use folic acid periconceptionally are at a 50-70% reduced risk for NTD-affected pregnancies. More than 80 candidates genes to SB are been studied, someones related to folic acid metabolic pathway. MTHFR gene is the gene more studied in NTDs. Its allele 677T is asóciate to higher risk to NTD. It is important to study polymorphisms in MTHFR gene in Chile because Chilean population has dfferent ethnic origen from others previous studied populations.

Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions.

Systemic lupus erythematosus may present with renal manifestations that frequently are difficult to categorize and lupus nephritis is an important predictor of poor outcome. The type and spectrum of renal injury may remain undiagnosed until full-blown nephritic and/or nephrotic syndrome appear with increased risk of end-stage renal disease. These abnormalities occur within the first few years after the diagnosis of lupus is made on clinical grounds and with the support of laboratory tests in high risk patients. An early renal biopsy is helpful in patients with an abnormal urinalysis and/or reduced glomerular filtration rate and the results form the basis for therapeutic decisions. The biopsy also provides vital prognostic information based on histological categorization of different types of lupus nephritis, the degree of activity, chronicity and the immunopathogenesis. In the current armamentarium, the use of cyclophosphamide and azathioprine and recently mycophenolate mofetil, reduce morbidity and maintenance therapies reduce the risk of end-stage renal disease. Clinical trials underway promise new, effective and safe immunosuppressive regimens for the treatment of proliferative lupus nephritis.

Fermiology and magnetism in weak itinerant ferromagnet CoS2: an ab initio study.

Electronic structure calculations have been performed on the compound CoS(2), an itinerant ferromagnet whose magnetic properties can be understood in terms of spin fluctuation theory. We have identified nesting features in the Fermi surface of the compound, active for long wavelength spin fluctuations. The electronic structure of the material is close to a half-metal. We show the importance of introducing spin-orbit coupling (SOC) in the calculations, which partially destroys the half-metallicity of the material. By means of transport properties calculations, we have quantified the influence of SOC in the conductivity at room temperature. Analyzing the effect of SOC helps in understanding the negative magnetoresistance of the material, whose conductivity varies within a few per cent with the introduction of small perturbations in the states around the Fermi level.

Tight-binding modeling and low-energy behavior of the semi-Dirac point.

We develop a tight-binding model description of semi-Dirac electronic spectra, with highly anisotropic dispersion around point Fermi surfaces, recently discovered in electronic structure calculations of VO2-TiO2 nanoheterostructures. We contrast their spectral properties with the well-known Dirac points on the honeycomb lattice relevant to graphene layers and the spectra of bands touching each other in zero-gap semiconductors. We also consider the lowest order dispersion around one of the semi-Dirac points and calculate the resulting electronic energy levels in an external magnetic field. In spite of apparently similar electronic structures, Dirac and semi-Dirac systems support diverse low-energy physics.

Enhanced dimerization of TiOCl under pressure: spin-Peierls to Peierls transition.

We report x-ray diffraction and magnetization measurements under pressure combined with ab initio calculations to show that high-pressure TiOCl corresponds to an enhanced Ti3+-Ti3+ dimerized phase existing already at room temperature. Our results demonstrate the formation of a metal-metal bond between Ti3+ ions along the b axis of TiOCl, accompanied by a strong reduction of the electronic gap. The evolution of the dimerization with pressure suggests a crossover from the spin-Peierls to a conventional Peierls situation at high pressures.

Homopolar bond formation in ZnV2O4 close to a metal-insulator transition.

Electronic structure calculations for spinel vanadate ZnV2O4 show that partial electronic delocalization in this system leads to a structural instability, with the formation of V-V dimers along the [011] and [101] directions, and readily accounts for the intriguing magnetic structure of this material. The formation of V-V bonds is a consequence of the proximity to the itinerant-electron boundary and is not related to orbital ordering. We discuss how this mechanism naturally couples charge and lattice degrees of freedom in magnetic insulators close to such a crossover.

Conocimiento sobre el ácido fólico en la prevención de defectos de cierre del tubo neural: una encuesta a mujeres que viven en Santiago de Chile / Awareness of post partum women on the effects of folie acid in the prevention of congenital anomalies

Background: Wheat flour in Chile is fortified with folie acid and pregnant women are also supplemented with the vitamin, but the population level of knowledge or awareness about this vitamin and its use by pregnant women is unknown. Aim: To assess the level of knowledge that postpartum women from Santiago de Chile have about folie acid. Material and methods: A questionnaire about folie acid and its efects on the prevention of neural tube defects was developed adapting questionnaires designed abroad. It was applied by medical students to puerperal women, hospitalized in public hospitals. Results: The questionnaire was applied to 342 women aged 26 ± 7 years. Sixty one percent were housewives and 55 percent completed high school education. Forty seven percent of these women had heard about folie acid, 9.6 percent knew that it was able to prevent congenital defects and only one received an adequate supplementation during pregnancy. Women aged 25 to 34 years and those with an adequate medical care during pregnancy had a significantly better knowledge about folie acid and its role in the prevention of congenital anormalies. The more commom means to receive information about folie acid were midwifes (34 percent), mass media (28 percent) and doctors (20 percent). Two hundred eleven women (62 percent) agreed to take folie acid in a future gestation and 58 percent preferred to do so using fortified foods. Conclusions: Post partum women from Santiago have a poor knowledge about the relevance of folie acid supplementation.