Publications by authors named "Diego Rodriguez"

167 Publications

Growth performance and carcass quality are not different between pigs fed diets containing cold-fermented low-oil distillers dried grains with solubles (DDGS) and pigs fed conventional DDGS, but pelleting improves gain to feed ratio regardless of source of DDGS.

J Anim Sci 2021 May 27. Epub 2021 May 27.

Department of Animal Sciences, University of Illinois, Urbana 61801, USA.

The objective was to test the hypothesis that growth performance and carcass characteristics of pig fed diets containing cold-fermented, low oil distillers dried grains with solubles (DDGS) is not different from that of pigs fed diets containing conventional DDGS regardless of the physical form of the diets. A total of 160 barrows and gilts were used. There were 4 diets, 10 pens per diet, and 4 pigs per pen. Pigs were weaned at 21 d of age and fed a common phase 1 diet that did not contain DDGS during the initial 7 d post-weaning. Pigs were then allotted to the 4 diets that were arranged in a 2 × 2 factorial design with 2 sources of DDGS (cold-fermented and conventional DDGS) and 2 diet forms (meal and pellets). Pigs were fed phase 2 diets from d 7 to 21 and phase 3 diets from d 21 to 43 post-weaning. All diets were based on corn and soybean meal, but phase 2 diets also contained 15% DDGS and phase 3 diets contained 30% DDGS. From d 43, pigs were fed grower diets for 38 d, early finisher diets for 38 d, and late finisher diets for 18 d and these diets also contained 30% DDGS. Feed was provided on an ad libitum basis and daily feed allotments were recorded. Pigs were weighed at the beginning of each phase and at the conclusion of the experiment. On the last day of the experiment, the pig in each pen with a body weight that was closest to the pen average was slaughtered and carcass measurements were determined. Combined results for the 2 nursery phases indicated that feeding meal diets instead of pelleted diets increased (P < 0.001) average daily feed intake and decreased (P < 0.05) gain to feed ratio. However, no differences between the 2 sources of DDGS were observed for the overall growth performance of weanling pigs. For the entire growing-finishing period, the source of DDGS did not affect growth performance, but pigs fed meal diets had reduced (P < 0.001) gain to feed ratio compared with pigs fed the pelleted diets. There were no differences between the 2 sources of DDGS for carcass characteristics. Back fat was greater (P < 0.05) for pigs fed pelleted diets than for pigs fed meal diets. In conclusion, no differences in growth performance or carcass characteristics between pigs fed cold-fermented DDGS and pigs fed conventional DDGS were observed. However, pigs fed pelleted diets had greater gain to feed ratio and greater back fat than pigs fed meal diets.
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http://dx.doi.org/10.1093/jas/skab129DOI Listing
May 2021

Interatrial septal tachycardias following atrial fibrillation ablation or cardiac surgery: Electrophysiological features and ablation outcomes.

Heart Rhythm 2021 May 11. Epub 2021 May 11.

Electrophysiology Section, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Interatrial septal tachycardias (IAS-ATs) following atrial fibrillation (AF) ablation or cardiac surgery are rare, and their management is challenging.

Objective: The purpose of this study was to investigate the electrophysiological features and outcomes associated with catheter ablation of IAS-AT.

Methods: We screened 338 patients undergoing catheter ablation of ATs following AF ablation or cardiac surgery. Diagnosis of IAS-AT was based on activation mapping and analysis of response to atrial overdrive pacing.

Results: Twenty-nine patients (9%) had IAS-AT (cycle length [CL] 311 ± 104 ms); 16 (55%) had prior AF ablation procedures (median 3; range 1-5), 3 (10%) had prior surgical maze, and 12 (41%) had prior cardiac surgery (including atrial septal defect surgical repair in 5 and left atrial myxoma resection in 1). IAS substrate abnormalities were documented in all patients. Activation mapping always demonstrated a diffuse early IAS breakout with centrifugal biatrial activation, and atrial overdrive pacing showed a good postpacing interval (equal or within 25 ms of the AT CL) only at 1 or 2 anatomically opposite IAS sites in all cases. Ablation was acutely successful in 27 patients (93%) (from only the right IAS in 2, only the left IAS in 9, both IAS sides with sequential ablation in 13, and both IAS sides with bipolar ablation in 3). After median follow-up of 15 (6-52) months, 17 patients (59%) remained free from recurrent arrhythmias.

Conclusion: IAS-ATs are rare and typically occur in patients with evidence of IAS substrate abnormalities and prior cardiac surgery. Catheter ablation can be challenging and may require sequential unipolar ablation or bipolar ablation.
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http://dx.doi.org/10.1016/j.hrthm.2021.04.036DOI Listing
May 2021

HIF-Prolyl Hydroxylase Domain Proteins (PHDs) in Cancer-Potential Targets for Anti-Tumor Therapy?

Cancers (Basel) 2021 Feb 27;13(5). Epub 2021 Feb 27.

Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, 01307 Dresden, Germany.

Solid tumors are typically associated with unbridled proliferation of malignant cells, accompanied by an immature and dysfunctional tumor-associated vascular network. Consequent impairment in transport of nutrients and oxygen eventually leads to a hypoxic environment wherein cells must adapt to survive and overcome these stresses. Hypoxia inducible factors (HIFs) are central transcription factors in the hypoxia response and drive the expression of a vast number of survival genes in cancer cells and in cells in the tumor microenvironment. HIFs are tightly controlled by a class of oxygen sensors, the HIF-prolyl hydroxylase domain proteins (PHDs), which hydroxylate HIFs, thereby marking them for proteasomal degradation. Remarkable and intense research during the past decade has revealed that, contrary to expectations, PHDs are often overexpressed in many tumor types, and that inhibition of PHDs can lead to decreased tumor growth, impaired metastasis, and diminished tumor-associated immune-tolerance. Therefore, PHDs represent an attractive therapeutic target in cancer research. Multiple PHD inhibitors have been developed that were either recently accepted in China as erythropoiesis stimulating agents (ESA) or are currently in phase III trials. We review here the function of HIFs and PHDs in cancer and related therapeutic opportunities.
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http://dx.doi.org/10.3390/cancers13050988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956578PMC
February 2021

Malnutrition According to GLIM Criteria Is Associated with Mortality and Hospitalizations in Rehabilitation Patients with Stable Chronic Obstructive Pulmonary Disease.

Nutrients 2021 Jan 26;13(2). Epub 2021 Jan 26.

Physical Medicine and Rehabilitation Department, Parc Salut Mar (Hospital del Mar Hospital de l'Esperança), Passeig Maritim de la Barceloneta 25-29, 08003 Barcelona, Spain.

Malnutrition has a negative impact on patients with chronic pulmonary obstructive disease (COPD). The purpose of this study was to assess the prevalence of malnutrition, defined by the Global Leadership Initiative for Malnutrition (GLIM), in stable COPD patients referred to pulmonary rehabilitation, and to explore potential associations of malnutrition according to GLIM, and its components, with increased risk of mortality and hospitalizations in 2 years. In a post-hoc analysis of a prospective cohort of 200 rehabilitation patients with stable COPD, main outcome variables were hospital admissions, length of stay, and mortality during a 2-year follow-up. Covariates were malnutrition according to GLIM and its phenotypic criteria: unintentional weight loss, low body mass index (BMI), and low fat-free mass (FFM). Univariate and multivariate analysis were performed using logistic and proportional hazard Cox regression. Malnutrition according to GLIM showed 45% prevalence and was associated with increased mortality risk. Low age-related BMI and FFM were independently associated with mortality, which persisted after adjustment for age and lung function. Malnutrition and low BMI were also associated with increased risk of hospitalization. Malnutrition according to GLIM criteria was highly prevalent in rehabilitation patients with COPD and was associated with nearly 3 times greater mortality and hospitalization risk.
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http://dx.doi.org/10.3390/nu13020369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911981PMC
January 2021

Comparison of cost-effectiveness of implantable cardioverter defibrillator therapy in patients for primary prevention in Latin America: an analysis using the Improve SCA study.

J Med Econ 2021 Jan-Dec;24(1):173-180

Reimbursement, Andean Region, Medtronic plc, Bogotá DC, Colombia.

Objective: The mortality benefit of implantable cardioverter defibrillators (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) has been well-established, but ICD therapy remains globally underutilized. The results of the Improve SCA study showed a 49% relative risk reduction in all-cause mortality among ICD patients with 1.5 primary prevention (1.5PP) characteristics (patients with one or more risk factors,  < 0.0001). We evaluated the cost-effectiveness of ICD compared to no ICD therapy among patients with 1.5PP characteristics in three Latin American countries and analyzed the factors involved in cost-effectiveness.

Methods: We used a published Markov model that compares costs and outcomes of ICD to no ICD therapy from local payers' perspective and included country-specific and disease-specific inputs from the Improve SCA study and current literature. We used WHO-recommended willingness-to-pay (WTP) thresholds to assess cost-effectiveness and compared model outcomes between countries.

Results: Incremental costs per QALY (quality-adjusted life year) saved by ICD compared to no ICD therapy are Colombian Pesos COP$46,729,026 in Colombia, Mexican Pesos MXN$246,016 in Mexico, and Uruguayan Pesos UYU$1,213,614 in Uruguay in the base case scenario; all three figures are between 1-3-times GDP per capita for each country. One-way and probabilistic sensitivity analyses confirm the base case scenario results. Non-cardiac accumulated deaths are lower in Mexico, resulting in a comparatively increased cost-effective ICD therapy.

Limitations: The Improve SCA study was not randomized, so clinical results could be biased; however, measures were taken to reduce this bias. Costs and benefits were modelled beyond the timeline of direct observation in the Improve SCA study.

Conclusions: ICD therapy is cost-effective in Mexico and Uruguay and potentially cost-effective in Colombia for a 1.5PP population. Variability in ICER estimates by country can be explained by differences in non-cardiac deaths and cost inputs.
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http://dx.doi.org/10.1080/13696998.2021.1877451DOI Listing
January 2021

The complete mitochondrial and plastid genomes of the invasive marine red alga (Caulacanthaceae, Rhodophyta) from Moss Landing, California, USA.

Mitochondrial DNA B Resour 2020 May 13;5(3):2067-2069. Epub 2020 May 13.

Division of Mathematics, Science, and Engineering, Hartnell College, Salinas, CA, USA.

is an invasive red alga that forms extensive mats in sheltered marine habitats around the world. To determine its genomic structure and genetic relationship to native and other non-native populations of , high-throughput sequencing analysis was performed on an introduced specimen from Bennett Slough, Moss Landing, California, USA. Assembly of 23,146,595 filtered 150 bp paired-end Illumina sequencing reads yielded its complete mitogenome (GenBank accession MT193839) and plastid genome (GenBank accession MT193838). The mitogenome is 25,995 bp in length and contains 50 genes. The plastid genome is 173,516 bp and contains 234 genes. Comparison of the organellar chromosomes to other Gigartinales revealed a high-level of gene synteny. BLAST analysis of marker sequences (L, 1, ) of from Moss Landing identified four identical DNA sequences: one from a specimen from a native population of from South Korea and three from specimens representing invasive populations from France, Spain, and the USA. These genetic results confirm the presence of in central California, USA, and represent the first complete mitogenome and plastid genome from the Caulacanthaceae.
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http://dx.doi.org/10.1080/23802359.2020.1763870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782071PMC
May 2020

Extrusion of soybean hulls does not increase digestibility of amino acids or concentrations of digestible and metabolizable energy when fed to growing pigs.

Transl Anim Sci 2020 Jul 10;4(3):txaa169. Epub 2020 Sep 10.

Department of Animal Sciences, University of Illinois, Urbana, IL.

Two experiments were conducted to determine effects of extrusion on energy and nutrient digestibility in soybean hulls. One source of soybean hulls was ground and divided into two batches. One batch was used without further processing, whereas the other batch was extruded. In Exp. 1, four diets were formulated to determine crude protein (CP) and amino acid (AA) digestibility in soybean hulls. A soybean meal-based diet in which soybean meal provided all the CP and AA was formulated. Two diets were formulated to contain 30% nonextruded or extruded soybean hulls and 18% soybean meal. An N-free diet that was used to determine the endogenous losses of CP and AA was also used. Eight growing barrows (initial body weight = 37.0 ± 3.9 kg) had a T-cannula installed in the distal ileum and were allotted to a replicated 4 × 4 Latin square design. Each experimental period lasted 7 d with the initial 5 d being the adaptation period and ileal digesta were collected for 8 h on day 6 and 7. Results indicated that extrusion of soybean hulls did not change the standardized ileal digestibility (SID) of CP and most AA with the exception that the SID of Ile and Leu tended ( < 0.10) to be greater in extruded than nonextruded soybean hulls. In Exp. 2, three diets were formulated to determine energy digestibility in soybean hulls. One corn-soybean meal based basal diet, and two diets that contained corn, soybean meal, and 32% extruded or nonextruded soybean hulls were formulated. Twenty-four growing barrows (initial body weight = 59.9 ± 3.4 kg) were allotted to a randomized complete block design. Pigs were housed individually in metabolism crates and feces and urine were collected separately for 4 d after 5 d of adaptation. The apparent total tract digestibility (ATTD) of gross energy (GE) and the digestible energy (DE) and metabolizable energy (ME) were reduced ( < 0.05) in diets containing nonextruded or extruded soybean hulls compared with the basal diet. However, the ATTD of GE and values for DE and ME in soybean hulls were not improved by extrusion. Likewise, extrusion did not change the concentration of total dietary fiber in soybean hulls. In conclusion, there were no effects of extrusion of soybean hulls on SID of AA, energy digestibility, or ME concentration in soybean hulls.
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http://dx.doi.org/10.1093/tas/txaa169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759737PMC
July 2020

Yorkie-Warts Complexes are an Ensemble of Interconverting Conformers Formed by Multivalent Interactions.

J Mol Biol 2021 02 28;433(4):166776. Epub 2020 Dec 28.

Department of Biochemistry & Biophysics, Oregon State University, Corvallis, OR 97331, USA. Electronic address:

Multiple copies of WW domains and PPXY motif sequences are often reciprocally presented by regulatory proteins that interact at crucial regulatory steps in the cell life cycle. While biophysical studies of single WW domain-single PPXY motif complexes abound in the literature, the molecular mechanisms of multivalent WW domain-PPXY assemblies are still poorly understood. By way of investigating such assemblies, we characterized the multivalent association of the entire cognate binding domains, two WW sequences and five PPXY motifs respectively, of the Yorkie transcription coactivator and the Warts tumor suppressor. Isothermal titration calorimetry, sedimentation velocity, size-exclusion chromatography coupled to multi-angle light scattering and native-state mass spectrometry of Yorkie WW domains interactions with the full-length Warts PPXY domain, and numerous PPXY motif variants of Warts show that the two proteins assemble via binding of tandem WW domains to adjacent PPXY pairs to produce an ensemble of interconverting complexes of variable stoichiometries, binding energetics and WW domain occupancy. Apparently, the Yorkie tandem WW domains first target the two adjacent PPXY motifs at the C-terminus of the Warts polypeptide and additional WW domains bind unoccupied motifs. Similar ensembles of interconverting conformers may be common in multivalent WW domain-PPXY interactions to promote the adaptability and versatility of WW domain-PPXY mediated cellular processes.
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http://dx.doi.org/10.1016/j.jmb.2020.166776DOI Listing
February 2021

Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.

Int J Mol Sci 2020 Oct 30;21(21). Epub 2020 Oct 30.

Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, 01307 Dresden, Germany.

Erythropoiesis is a complex process driving the production of red blood cells. During homeostasis, adult erythropoiesis takes place in the bone marrow and is tightly controlled by erythropoietin (EPO), a central hormone mainly produced in renal EPO-producing cells. The expression of EPO is strictly regulated by local changes in oxygen partial pressure (pO) as under-deprived oxygen (hypoxia); the transcription factor hypoxia-inducible factor-2 induces EPO. However, erythropoiesis regulation extends beyond the well-established hypoxia-inducible factor (HIF)-EPO axis and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism. The importance of a number of these factors is evident as their altered expression has been associated with various anemia-related disorders, including chronic kidney disease. Eventually, our emerging understanding of HPPs and their regulatory feedback will be instrumental in developing specific therapies for anemic patients and beyond.
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http://dx.doi.org/10.3390/ijms21218131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662373PMC
October 2020

Deficient muscle regeneration potential in sarcopenic COPD patients: Role of satellite cells.

J Cell Physiol 2021 Apr 28;236(4):3083-3098. Epub 2020 Sep 28.

Pulmonology Department, Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.

Sarcopenia is a major comorbidity in chronic obstructive pulmonary (COPD). Whether deficient muscle repair mechanisms and regeneration exist in the vastus lateralis (VL) of sarcopenic COPD remains debatable. In the VL of control subjects and severe COPD patients with/without sarcopenia, satellite cells (SCs) were identified (immunofluorescence, specific antibodies, anti-Pax-7, and anti-Myf-5): activated (Pax-7+/Myf-5+), quiescent/regenerative potential (Pax-7+/Myf-5-), and total SCs, nuclear activation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling [TUNEL]), and muscle fiber type (morphometry and slow- and fast-twitch, and hybrid fibers), muscle damage (hematoxylin-eosin staining), muscle regeneration markers (Pax-7, Myf-5, myogenin, and MyoD), and myostatin levels were identified. Compared to controls, in VL of sarcopenic COPD patients, myostatin content, activated SCs, hybrid fiber proportions, TUNEL-positive cells, internal nuclei, and muscle damage significantly increased, while quadriceps muscle strength, numbers of Pax-7+/Myf-5- and slow- and fast-twitch, and hybrid myofiber areas decreased. In the VL of sarcopenic and nonsarcopenic patients, TUNEL-positive cells were greater, whereas muscle regeneration marker expression was lower than in controls. In VL of severe COPD patients regardless of the sarcopenia level, the muscle regeneration process is triggered as identified by SC activation and increased internal nuclei. Nonetheless, a lower regenerative potential along with significant alterations in muscle phenotype and damage, and increased myostatin were prominently seen in sarcopenic COPD.
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http://dx.doi.org/10.1002/jcp.30073DOI Listing
April 2021

Tunable from Blue to Red Emissive Composites and Solids of Silver Diphosphane Systems with Higher Quantum Yields than the Diphosphane Ligands.

Inorg Chem 2020 Oct 27;59(19):14447-14456. Epub 2020 Sep 27.

Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH). Universidad de Zaragoza-CSIC. E-50009 Zaragoza, Spain.

PMMA composites and solids of complexes of formulas [AgX(P-P)] [ = 1 and 2; X = Cl, NO, ClO, CFCOO, and OTf; P-P = dppb, xantphos, (PR)CBH (R = Ph and Pr)] display the whole palette of colors from blue to red upon selection of the anionic ligand (X) and the diphosphane (P-P). The diphosphane seems to play the most important role in tuning the emission energy and thermally activated delayed fluorescence (TADF) behavior. The PMMA composites of the complexes exhibit higher quantum yields than that of the diphosphane ligands and those with dppb are between 28 and 53%. Remarkably, instead of blue-green emissions which dominate the luminescence of silver diphosphane complexes in rigid phases, those with carborane diphosphanes are yellow-orange or orange-red emitters. Theoretical studies have been carried out for complexes with P-P = dppb, X = Cl; P-P = dppic, X = NO; P-P = dppcc, X = Cl, NO, and OTf and the mononuclear complexes [AgX(xantphos)] (X = Cl, Br). Optimization of the first excited triplet state was only possible for [AgX(xantphos)] (X = Cl and Br). A mixed MLCT and MC nature could be attributed to the S → T transition in these three-coordinated complexes.
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http://dx.doi.org/10.1021/acs.inorgchem.0c02238DOI Listing
October 2020

Intraoperative Fluoroscopy Reduces Complication and Reoperation Rate in Facial Fractures.

Facial Plast Surg Aesthet Med 2020 Sep 8. Epub 2020 Sep 8.

Division of Maxillofacial Surgery, Hospital del Trabajador, Santiago, Chile.

The purpose of this study is to evaluate surgical outcomes of facial fractures after the introduction of intraoperative radiology. An historic cohort of patients without intraoperative fluoroscopy (IOF) was compared with a prospective cohort of patients with IOF. Main outcomes were postoperative complications and reoperation rate. There were 51 in the non-IOF group and 49 in the IOF group. In the group with IOF 10 patients required intraoperative revisions (20.46%). Overall postoperative complication rate was higher in the non-IOF group (25.49% vs. 6.12%) due to the significantly higher bone-related complication rate (15.69% vs. 2.04%). Reoperation rate was also higher in the non-IOF group (11.76% vs. 0%). This study demonstrates that IOF reduces bone-related complication and reoperation rate by allowing correction of surgical errors immediately during surgery.
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http://dx.doi.org/10.1089/fpsam.2020.0274DOI Listing
September 2020

Digestibility of amino acids, but not fiber, fat, or energy, is greater in cold-fermented, low-oil distillers dried grains with solubles (DDGS) compared with conventional DDGS fed to growing pigs.

J Anim Sci 2020 Oct;98(10)

Department of Animal Sciences, University of Illinois, Urbana, IL.

Two experiments were conducted to test the hypothesis that the digestibility of gross energy (GE) and nutrients, and concentrations of digestible energy (DE) and metabolizable energy (ME) in two sources of distillers dried grains with solubles (DDGS) are not different despite different concentrations of fat in the two sources. Cold-fermented DDGS (6.82% fat) and a conventional DDGS (9.54% fat) were used. In experiment 1, 12 growing barrows (initial body weight = 55.2 ± 3.6 kg) that had a T-cannula installed in the distal ileum were allotted to one of three diets and two periods. Two diets contained either cold-fermented or conventional DDGS as the sole source of crude protein (CP) and amino acids (AA). The third diet was an N-free diet that was used to determine the basal endogenous losses of AA from the pigs. Each experimental period lasted 7 d and ileal digesta were collected on days 6 and 7 of each period. Results demonstrated that values for the standardized ileal digestibility (SID) of CP and most AA were greater (P < 0.05) or tended to be greater (P < 0.10) in cold-fermented than in conventional DDGS. In experiment 2, 24 barrows (initial body weight = 17.3 ± 1.3 kg) were randomly allotted to three diets with 8 replicate pigs per diet. A corn-based basal diet and two diets containing corn and either cold-fermented DDGS or conventional DDGS were formulated. Pigs were housed individually in metabolism crates and feces and urine were collected separately for 5 d after 7 d of adaptation. The apparent total tract digestibility (ATTD) of neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid-hydrolyzed ether extract (AEE) was greater (P < 0.01) in conventional DDGS than in cold-fermented DDGS, but there was no difference in ATTD of GE between the two sources of DDGS. However, conventional DDGS contained more (P < 0.001) DE and ME than cold-fermented DDGS because of greater GE. In conclusion, the SID of AA was greater in cold-fermented DDGS than in the conventional DDGS that was evaluated in this experiment, but the ATTD of NDF, ADF, and AEE, and ME were greater in conventional DDGS than in cold-fermented DDGS.
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http://dx.doi.org/10.1093/jas/skaa297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568432PMC
October 2020

4-Styrylquinolines from cyclocondensation reactions between (2-aminophenyl)chalcones and 1,3-diketones: crystal structures and regiochemistry.

Acta Crystallogr C Struct Chem 2020 Sep 13;76(Pt 9):883-890. Epub 2020 Aug 13.

School of Chemistry, University of St Andrews, Fife KY16 9ST, Scotland.

Structures are reported for two matched sets of substituted 4-styrylquinolines which were prepared by the formation of the heterocyclic ring in cyclocondensation reactions between 1-(2-aminophenyl)-3-arylprop-2-en-1-ones with 1,3-dicarbonyl compounds. (E)-3-Acetyl-4-[2-(4-methoxyphenyl)ethenyl]-2-methylquinoline, CHNO, (I), (E)-3-acetyl-4-[2-(4-bromophenyl)ethenyl]-2-methylquinoline, CHBrNO, (II), and (E)-3-acetyl-2-methyl-4-{2-[4-(trifluoromethyl)phenyl]ethenyl}quinoline, CHFNO, (III), are isomorphous and in each structure the molecules are linked by a single C-H...O hydrogen bond to form C(6) chains. In (I), but not in (II) or (III), this is augmented by a C-H...π(arene) hydrogen bond to form a chain of rings; hence, (I)-(III) are not strictly isostructural. By contrast with (I)-(III), no two of ethyl (E)-4-[2-(4-methoxyphenyl)ethenyl]-2-methylquinoline-3-carboxylate, CHNO, (IV), ethyl (E)-4-[2-(4-bromophenyl)ethenyl]-2-methylquinoline-3-carboxylate, CHBrNO, (V), and ethyl (E)-2-methyl-4-{2-[4-(trifluoromethyl)phenyl]ethenyl}quinoline-3-carboxylate, CHFNO, (VI), are isomorphous. The molecules of (IV) are linked by a single C-H...O hydrogen bond to form C(13) chains, but cyclic centrosymmetric dimers are formed in both (V) and (VI). The dimer in (V) contains a C-H...π(pyridyl) hydrogen bond, while that in (VI) contains two independent C-H...O hydrogen bonds. Comparisons are made with some related structures, and both the regiochemistry and the mechanism of the heterocyclic ring formation are discussed.
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http://dx.doi.org/10.1107/S2053229620010803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474186PMC
September 2020

Necroptosis restricts influenza A virus as a stand-alone cell death mechanism.

J Exp Med 2020 11;217(11)

Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA.

Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV-or indeed any virus-in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, "stand-alone" cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense.
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http://dx.doi.org/10.1084/jem.20191259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596817PMC
November 2020

Digestibility of amino acids and concentrations of metabolizable energy and net energy are greater in high-shear dry soybean expellers than in soybean meal when fed to growing pigs.

J Anim Sci 2020 Jul;98(7)

Department of Animal Sciences, University of Illinois, Urbana, IL.

Soybean expellers may be produced by dry extrusion and mechanical oil pressing of soybeans, but there is limited information about the nutritional value of expellers produced via this procedure. Therefore, 2 experiments were conducted to test the hypothesis that standardized ileal digestibility (SID) of CP and amino acids (AA), apparent total tract digestibility (ATTD) of energy and total dietary fiber (TDF), and concentrations of DE, ME, and NE are greater in soybean expellers than in soybean meal (SBM) when fed to growing pigs. Pigs were the offspring of Line 359 boars mated to Camborough females (Pig Improvement Company, Hendersonville, TN). In experiment 1, nine growing barrows (initial BW: 55.98 kg ± 13.75 kg) with T-cannulas installed in the distal ileum were allotted to 1 of 3 diets using a triplicated 3 × 3 Latin square design with 3 periods. Two diets were formulated to contain 35% soybean expellers or 33% SBM as the sole source of AA. A N-free diet was used to determine basal endogenous losses of AA. Ileal digesta were collected on days 6 and 7 of each 7-d period. Results indicated that the SID of most indispensable and dispensable AA were greater (P < 0.05) or tended (P < 0.10) to be greater in soybean expellers than in SBM. In experiment 2, a corn-based diet and 2 diets based on corn and each of the 2 soybean products were formulated. Twenty-four growing barrows (initial BW: 44.88 kg ± 2.17 kg) were allotted to 1 of the 3 diets with 8 pigs per diet. Urine and fecal samples were collected for 4 d after 5 d of adaptation. Results indicated that the ATTD of energy and TDF was not different between soybean expellers and SBM, but the ATTD of TDF in the 2 soybean products was greater (P < 0.05) than in corn. Concentrations of DE and ME in soybean expellers were greater (P < 0.05) compared with corn or SBM. Soybean expellers had greater (P < 0.05) calculated NE compared with SBM, but there was no difference in NE between corn and soybean expellers. In conclusion, values for SID of most AA and DE, ME, and NE in soybean expellers were greater than in SBM.
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http://dx.doi.org/10.1093/jas/skaa215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392529PMC
July 2020

Transhepatic right vein access for radiofrequency ablation of atrioventricular nodal reentry tachycardia in a patient with infrarenal vena cava agenesis.

J Interv Card Electrophysiol 2021 Jan 12;60(1):159-160. Epub 2020 Jul 12.

Electrophysiologist of International Arrhythmia Center, Cardioinfantil Foundation, Bogotá, Colombia.

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http://dx.doi.org/10.1007/s10840-020-00820-zDOI Listing
January 2021

[Triage criteria for cardiopulmonary resuscitation and advanced life support during the COVID-19 epidemic].

Med Clin (Barc) 2020 09 8;155(5):215-219. Epub 2020 May 8.

Comité de Ética Asistencial, Hospital Universitario de La Princesa, Madrid, España; Unidad de Cuidados Paliativos, Hospital Universitario de La Princesa, Madrid, España.

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http://dx.doi.org/10.1016/j.medcli.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205666PMC
September 2020

Telerehabilitation Programme as a Maintenance Strategy for COPD Patients: A 12-Month Randomized Clinical Trial.

Arch Bronconeumol (Engl Ed) 2021 Mar 19;57(3):195-204. Epub 2020 May 19.

Clinical Epidemiology Unit, Hospital Universitario de Cruces, Biocruces Bizkaia, Health Research Institute, Bilbao, Spain.

Background: There is uncertainty regarding efficacy of telehealth-based approaches in COPD patients for sustaining benefits achieved with intensive pulmonary rehabilitation (PR).

Research Question: To determine whether a maintenance pulmonary telerehabilitation (TelePR) programme, after intensive initial PR, is superior to usual care in sustaining over time benefits achieved by intensive PR.

Study Design And Methods: A multicentre open-label pragmatic parallel-group randomized clinical trial was conducted. Two groups were created at completion of an 8-week intensive outpatient hospital PR programme. Intervention group (IG) patients were given appropriate training equipment and instructed to perform three weekly training sessions and send performance data through an app to a web-based platform. Patients in the control group (CG) were advised to exercise regularly (usual care).

Results: Ninety-four patients (46 IG, 48 CG) were randomized. The analysis of covariance showed non-significant improvements in 6-min walk distance [19.9m (95% CI -4.1/+43.8)] and Chronic Respiratory Disease Questionnaire - Emotion score [0.4 points (0-0.8)] in the IG. Secondary linear mixed models showed improvements in the IG in Short Form-36 mental component summary [9.7, (4.0-15.4)] and Chronic Respiratory Disease Questionnaire - Emotion [0.5, (0.2-0.9)] scores, but there was no association between compliance and outcomes. Acute exacerbations were associated with a marginally significant decrease in 6-minute walk distance of 15.8m (-32.3/0.8) in linear models.

Conclusions: The TelePR maintenance strategy was both feasible and safe but failed to show superiority over usual care, despite improvements in some HRQoL domains. Acute exacerbations may have an important negative influence on long-term physical function. CLINICALTRIALS.

Gov Identifier: NCT03247933.
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http://dx.doi.org/10.1016/j.arbres.2020.03.034DOI Listing
March 2021

Caspase-8-Dependent Inflammatory Responses Are Controlled by Its Adaptor, FADD, and Necroptosis.

Immunity 2020 06 18;52(6):994-1006.e8. Epub 2020 May 18.

Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address:

Cell death pathways regulate various homeostatic processes. Autoimmune lymphoproliferative syndrome (ALPS) in humans and lymphoproliferative (LPR) disease in mice result from abrogated CD95-induced apoptosis. Because caspase-8 mediates CD95 signaling, we applied genetic approaches to dissect the roles of caspase-8 in cell death and inflammation. Here, we describe oligomerization-deficient Caspase-8 and non-cleavable Caspase-8 mutant mice with defective caspase-8-mediated apoptosis. Although neither mouse developed LPR disease, removal of the necroptosis effector Mlkl from Caspase-8 mice revealed an inflammatory role of caspase-8. Ablation of one allele of Fasl, Fadd, or Ripk1 prevented the pathology of Casp8Mlkl animals. Removing both Fadd alleles from these mice resulted in early lethality prior to post-natal day 15 (P15), which was prevented by co-ablation of either Ripk1 or Caspase-1. Our results suggest an in vivo role of the inflammatory RIPK1-caspase-8-FADD (FADDosome) complex and reveal a FADD-independent inflammatory role of caspase-8 that involves activation of an inflammasome.
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http://dx.doi.org/10.1016/j.immuni.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306001PMC
June 2020

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

Ann Hepatol 2020 Jul - Aug;19(4):396-403. Epub 2020 Apr 23.

Gastroenterology Department, Hospital Dr. Sotero del Río, Santiago, Chile.

Introduction & Objectives: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes.

Methods: A cross sectional, multicenter survey of hospitalized cirrhotic patients.

Results: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22).

Conclusions: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.
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http://dx.doi.org/10.1016/j.aohep.2020.03.007DOI Listing
June 2021

Inferior approach instead of standard "pull-down" technique for transseptal puncture in difficult anatomy.

J Interv Card Electrophysiol 2020 Sep 12;58(3):363-364. Epub 2020 May 12.

Electrophysiologist of International Arrhythmia Center, Cardioinfantil Foundation, Bogota, Colombia.

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http://dx.doi.org/10.1007/s10840-020-00750-wDOI Listing
September 2020

Two Linear Regimes in Optical Conductivity of a Type-I Weyl Semimetal: The Case of Elemental Tellurium.

Phys Rev Lett 2020 Apr;124(13):136402

1. Physikalisches Institut, Universität Stuttgart, 70569 Stuttgart, Germany.

Employing high-pressure infrared spectroscopy we unveil the Weyl semimetal phase of elemental Te and its topological properties. The linear frequency dependence of the optical conductivity provides clear evidence for metallization of trigonal tellurium (Te-I) and the linear band dispersion above 3.0 GPa. This semimetallic Weyl phase can be tuned by increasing pressure further: a kink separates two linear regimes in the optical conductivity (at 3.7 GPa), a signature proposed for Type-II Weyl semimetals with tilted cones; this however reveals a different origin in trigonal tellurium. Our density-functional calculations do not reveal any significant tilting and suggest that Te-I remains in the Type-I Weyl phase, but with two valence bands in the vicinity of the Fermi level. Their interplay gives rise to the peculiar optical conductivity behavior with more than one linear regime. Pressure above 4.3 GPa stabilizes the more complex Te-II and Te-III polymorphs, which are robust metals.
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http://dx.doi.org/10.1103/PhysRevLett.124.136402DOI Listing
April 2020

Linking cadmium and mercury accumulation to nutritional intake in common dolphins (Delphinus delphis) from Patagonia, Argentina.

Environ Pollut 2020 Aug 1;263(Pt A):114480. Epub 2020 Apr 1.

Instituto de Investigaciones Marinas y Costeras, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, CONICET, Funes 3350, Mar del Plata, B7602AYL, Argentina; Laboratorio de Ecotoxicología, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Mar del Plata, Argentina.

Bioaccumulation of Hg and Cd from food is a complex ecological process that has been oversimplified in the past. Common dolphins (Delphinus delphis) provide a powerful model to biomonitor metal concentrations in marine environments worldwide. We combined proportions-based nutritional geometry with metal analysis, stomach content analysis and the proximate composition of prey, to yield novel insights into the accumulation of Hg and Cd. Our analysis showed an age-related accumulation trend for Cd and Hg in kidney and liver, with highest concentrations found at 18 years of age. When viewed through the lens of nutritional ecology, Argentine anchovy (58.1 Mass %) and South American long-finned squid (22.7 Mass %), provided most of the dietary intake of protein (P) and lipids (L) (P:L ratio = 2.6:1.0) and also represented the main source for Cd and Hg levels accumulated in their bodies. This study presents unprecedented evidence on metal accumulation in relation to age and nutritional intake in a marine predator.
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http://dx.doi.org/10.1016/j.envpol.2020.114480DOI Listing
August 2020

Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis.

Cell 2020 03;180(6):1115-1129.e13

Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address:

Influenza A virus (IAV) is a lytic RNA virus that triggers receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated pathways of apoptosis and mixed lineage kinase domain-like pseudokinase (MLKL)-dependent necroptosis in infected cells. ZBP1 initiates RIPK3-driven cell death by sensing IAV RNA and activating RIPK3. Here, we show that replicating IAV generates Z-RNAs, which activate ZBP1 in the nucleus of infected cells. ZBP1 then initiates RIPK3-mediated MLKL activation in the nucleus, resulting in nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis. Cell death induced by nuclear MLKL was a potent activator of neutrophils, a cell type known to drive inflammatory pathology in virulent IAV disease. Consequently, MLKL-deficient mice manifest reduced nuclear disruption of lung epithelia, decreased neutrophil recruitment into infected lungs, and increased survival following a lethal dose of IAV. These results implicate Z-RNA as a new pathogen-associated molecular pattern and describe a ZBP1-initiated nucleus-to-plasma membrane "inside-out" death pathway with potentially pathogenic consequences in severe cases of influenza.
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http://dx.doi.org/10.1016/j.cell.2020.02.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153753PMC
March 2020

Rapidly progressive interstitial lung disease without cutaneous involvement associated to anti-MDA5 antibodies.

Med Clin (Barc) 2021 04 3;156(8):413-414. Epub 2020 Mar 3.

Unidad de Cuidados Intensivos, Hospital de La Princesa, IIS-Princesa, Madrid, España.

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http://dx.doi.org/10.1016/j.medcli.2020.01.012DOI Listing
April 2021

Intrinsic disorder and amino acid specificity modulate binding of the WW2 domain in kidney and brain protein (KIBRA) to synaptopodin.

J Biol Chem 2019 11 9;294(46):17383-17394. Epub 2019 Oct 9.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331

The second WW domain (WW2) of the kidney and brain scaffolding protein, KIBRA, has an isoleucine (Ile-81) rather than a second conserved tryptophan and is primarily unstructured. However, it adopts the canonical triple-stranded antiparallel β-sheet structure of WW domains when bound to a two-PPY motif peptide of the synaptic protein Dendrin. Here, using a series of biophysical experiments, we demonstrate that the WW2 domain remains largely disordered when bound to a 69-residue two-PPY motif polypeptide of the synaptic and podocyte protein synaptopodin (SYNPO). Isothermal titration calorimetry and CD experiments revealed that the interactions of the disordered WW2 domain with SYNPO are significantly weaker than SYNPO's interactions with the well-folded WW1 domain and that an I81W substitution in the WW2 domain neither enhances binding affinity nor induces substantial WW2 domain folding. In the tandem polypeptide, the two WW domains synergized, enhancing the overall binding affinity with the I81W variant tandem polypeptide 2-fold compared with the WT polypeptide. Solution NMR results showed that SYNPO binding induces small but definite chemical shift perturbations in the WW2 domain, confirming the disordered state of the WW2 domain in this complex. These analyses also disclosed that SYNPO binds the tandem WW domain polypeptide in an antiparallel manner, that is, the WW1 domain binds the second PPY motif of SYNPO. We propose a binding model consisting of a bipartite interaction mode in which the largely disordered WW2 forms a "fuzzy" complex with SYNPO. This binding mode may be important for specific cellular functions.
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http://dx.doi.org/10.1074/jbc.RA119.009589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873182PMC
November 2019

Hematopoiesis in aged female mice devoid of thyroid hormone receptors.

J Endocrinol 2020 01;244(1):83-94

Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.

Hypothyroidism is often associated with anemia and immunological disorders. Similar defects are found in patients and in mice with a mutated dominant-negative thyroid hormone receptor α (TRα) and in knockout mice devoid of this receptor, suggesting that this isoform is responsible for the effects of the thyroid hormones in hematopoiesis. However, the hematological phenotype of mice lacking also TRβ has not yet been examined. We show here that TRα1/TRβ-knockout female mice, lacking all known thyroid hormone receptors with capacity to bind thyroid hormones, do not have overt anemia and in contrast with hypothyroid mice do not present reduced Gata1 or Hif1 gene expression. Similar to that found in hypothyroidism or TRα deficiency during the juvenile period, the B-cell population is reduced in the spleen and bone marrow of ageing TRα1/TRβ-knockout mice, suggesting that TRβ does not play a major role in B-cell development. However, splenic hypotrophy is more marked in hypothyroid mice than in TRα1/TRβ-knockout mice and the splenic population of T-lymphocytes is not significantly impaired in these mice in contrast with the reduction found in hypothyroidism. Our results show that the overall hematopoietic phenotype of the TRα1/TRβ-knockout mice is milder than that found in the absence of hormone. Although other mechanism/s cannot be ruled out, our results suggest that the unoccupied TRs could have a negative effect on hematopoiesis, likely secondary to repression of hematopoietic gene expression.
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http://dx.doi.org/10.1530/JOE-19-0339DOI Listing
January 2020