Xanthogranuloma in the External Auditory Canal in Childhood, an Unexpected Lesion.

Pedunculated lesions in the external auditory canal present a broad differential diagnosis. It is crucial to rule out malignant neoplasms and consider the possibility of xanthogranulomas, which are very rare in this location. Management is determined by associated complications, and otolaryngologists must consider this for appropriate treatment.

Coherent spore dispersion via drop-leaf interaction.

The dispersion of plant pathogens, such as rust spores, is responsible for more than 20% of global crop yield loss annually. However, the release mechanism of pathogens from flexible plant surfaces into the canopy is not well understood. In this study, we investigated the interplay between leaf elasticity and rainfall, revealing how a flexible leaf structure can generate a lateral flow stream, with embedded coherent structures that enhance transport. We first modeled the linear coupling between drop momentum, leaf vibration, and the stream flux from leaf surfaces. With Lagrangian diagnostics, we further mapped out the nested coherent structures around the fluttering profile, providing a dynamical description for local spore delivery. We hope the mechanistic details extracted here can facilitate the construction of physically informed analytical models for local crop disease management.

Mild hypophosphatasia may be twice as prevalent as previously estimated: an effective clinical algorithm to detect undiagnosed cases.

OBJECTIVES: Since the prevalence of hypophosphatasia (HPP), a rare genetic disease, seems to be underestimated in clinical practice, in this study, a new diagnostic algorithm to identify missed cases of HPP was developed and implemented. METHODS: Analytical determinations recorded in the Clinical Analysis Unit of the Hospital Universitario Clínico San Cecilio in the period June 2018 - December 2020 were reviewed. A new clinical algorithm to detect HPP-misdiagnosed cases was used including the following steps: confirmation of persistent hypophosphatasemia, exclusion of secondary causes of hypophosphatasemia, determination of serum pyridoxal-5'-phosphate (PLP) and genetic study of ALPL gene. RESULTS: Twenty-four subjects were selected to participate in the study and genetic testing was carried out in 20 of them following clinical algorithm criteria. Eighty percent of patients was misdiagnosed with HPP following the current standard clinical practice. Extrapolating these results to the current Spanish population means that there could be up to 27,177 cases of undiagnosed HPP in Spain. In addition, we found a substantial proportion of HPP patients affected by other comorbidities, such as autoimmune diseases (∼40 %). CONCLUSIONS: This new algorithm was effective in detecting previously undiagnosed cases of HPP, which appears to be twice as prevalent as previously estimated for the European population. In the near future, our algorithm could be globally applied routinely in clinical practice to minimize the underdiagnosis of HPP. Additionally, some relevant findings, such as the high prevalence of autoimmune diseases in HPP-affected patients, should be investigated to better characterize this disorder.

Cardioprotective function of sclerostin by reducing calcium deposition, proliferation, and apoptosis in human vascular smooth muscle cells.

BACKGROUND: Sclerostin is an inhibitor of the Wnt/b-catenin pathway, which regulates bone formation, and can be expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD) and increased serum and tissue expression of sclerostin. However, whether the role of sclerostin is detrimental or protective in the development of CVD is unknown. Therefore, our aims are to determine the level of sclerostin in T2D patients with/without CVD and in controls, both at serum and vascular tissue, and to analyze the role of sclerostin in VSMCs under calcified environments. METHODS: Cross-sectional study including 121 controls and 139 T2D patients with/without CVD (48/91). Sclerostin levels in serum were determined by ELISA, and sclerostin expression was analyzed by RT-qPCR and immunohistochemistry in calcified and non-calcified artery of lower limb from T2D patients (n = 7) and controls (n = 3). In vitro experiments were performed in VSMCs (mock and sclerostin overexpression) under calcifying conditions analyzing the sclerostin function by determination of calcium and phosphate concentrations, and quantification of calcium deposits by Alizarin Red. Proliferation and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The regulation of the expression of genes involved in bone metabolism was determined by RT-qPCR. RESULTS: A significant increase in serum sclerostin levels in T2D patients with CVD compared to T2D patients without CVD and controls (p < 0.001) was observed. Moreover, higher circulating sclerostin levels were independently associated with CVD in T2D patients. Increased sclerostin expression was observed in calcified arteries of T2D patients compared to non-calcified arteries of controls (p = 0.003). In vitro experiments using VSMCs under calcified conditions, revealed that sclerostin overexpression reduced intracellular calcium (p = 0.001), calcium deposits (p < 0.001), cell proliferation (p < 0.001) and promoted cell survival (p = 0.015). Furthermore, sclerostin overexpression exhibited up-regulation of ALPL (p = 0.009), RUNX2 (p = 0.001) and COX2 (p = 0.003) and down-regulation of inflammatory genes, such as, IL1ß (p = 0.005), IL6 (p = 0.001) and IL8 (p = 0.003). CONCLUSIONS: Sclerostin could play a protective role in the development of atherosclerosis in T2D patients by reducing calcium deposits, decreasing proliferation and inflammation, and promoting cell survival in VSMCs under calcifying conditions. Therefore, considering the bone-vascular axis, treatment with anti-sclerostin for bone disease should be used with caution.

Exploring the role of osteoglycin in type 2 diabetes: implications for insulin resistance and vascular pathophysiology.

Osteoglycin, a fundamental proteoglycan within the vascular extracellular matrix, is expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with cardiovascular disease (CVD) but the role of osteoglycin in the development of CVD is controversial to date. Therefore, our aims are to determine and compare the level of osteoglycin in T2D patients with/without CVD versus control subjects both at serum and vascular tissue and to analyze in vitro role of osteoglycin in VSMCs under calcified conditions. For this, serum osteoglycin levels were determined by enzyme-linked immunosorbent assay (ELISA) in 117 controls and 129 patients with T2D (46 with CVD and 83 without CVD), revealing a significant increase in patients with T2D compared with controls. Osteoglycin level was not an estimator of CVD but correlated with markers of insulin resistance (triglycerides and triglycerides/high-density lipoprotein cholesterol index) in patients with T2D. At the vascular level, osteoglycin expression was assessed by RT-qPCR and immunohistochemistry, and no significant differences were observed between calcified arteries from patients with T2D and noncalcified arteries from controls. In vitro experiments using VSMCs (mock and overexpressing osteoglycin) under calcifying conditions were performed to analyze the osteoglycin function. The overexpression of osteoglycin in VMSCs under calcifying conditions revealed an increase of cell proliferation without effect on apoptosis and an upregulation of the expression of autotaxin (ATX) involved in inflammatory processes. In conclusion, osteoglycin could play a role in glycemic homeostasis, being a potential biomarker of insulin resistance in patients with T2D. Furthermore, osteoglycin could indirectly participate in the development of atherosclerosis through its regulatory effect on ATX and by proliferating VSMCs.NEW & NOTEWORTHY This study uncovers an increase of serum osteoglycin levels in patients with type 2 diabetes, which does not appear to be associated with the development of atherosclerosis, but rather with insulin resistance in this population. Overexpression of osteoglycin increased proliferation and upregulated the expression of autotaxin in vascular smooth muscle cells within calcified environments. Osteoglycin could be a biomarker of insulin resistance for type 2 diabetes and could be indirectly involved in the development of atherosclerosis.

Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM.

Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case-control study. Metabolomic analysis was conducted on 55 pediatric patients with xenobiotic liver toxicity and 88 healthy controls. The results revealed clear differences between the two groups. Several metabolites, including hydroxydecanoylcarnitine, octanoylcarnitine, lysophosphatidylcholine, glycocholic acid, and taurocholic acid, were identified as potential biomarkers (area under the curve: 0.817; 95% confidence interval: 0.696-0.913). Pathway analysis indicated involvement of primary bile acid biosynthesis and the metabolism of taurine and hypotaurine (p < 0.05). The findings from untargeted metabolomic analysis demonstrated an increase in bile acids in children with hepatotoxicity. The accumulation of cytotoxic bile acids should be further investigated to elucidate the role of these metabolites in drug-induced liver injury.

Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks.

Non-alcoholic fatty liver disease (NAFLD) seems to have some molecular links with atherosclerosis (ATH); however, the molecular pathways which connect both pathologies remain unexplored to date. The identification of common factors is of great interest to explore some therapeutic strategies to improve the outcomes for those affected patients. Differentially expressed genes (DEGs) for NAFLD and ATH were extracted from the GSE89632 and GSE100927 datasets, and common up- and downregulated DEGs were identified. Subsequently, a protein-protein interaction (PPI) network based on the common DEGs was performed. Functional modules were identified, and the hub genes were extracted. Then, a Gene Ontology (GO) and pathway analysis of common DEGs was performed. DEGs analysis in NAFLD and ATH showed 21 genes that were regulated similarly in both pathologies. The common DEGs with high centrality scores were ADAMTS1 and CEBPA which appeared to be down- and up-regulated in both disorders, respectively. For the analysis of functional modules, two modules were identified. The first one was oriented to post-translational protein modification, where ADAMTS1 and ADAMTS4 were identified, and the second one mainly related to the immune response, where CSF3 was identified. These factors could be key proteins with an important role in the NAFLD/ATH axis.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) in Chile: lessons learned from challenging cases.

BACKGROUND: Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Associated Disease (MOGAD) is an emerging disorder recognized as a clinical entity distinct from Multiple Sclerosis and Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorders (NMOSD-AQP4+), and its phenotypic spectrum continues to expand. Most information about its clinical course has emerged from retrospective studies, and treatment response both in acute and chronic-relapsing disease is still limited. We aimed to describe the clinical and paraclinical characteristics of monophasic and relapsing, paediatric and adult patients with MOGAD under regular clinical care in Chile, highlighting some challenging cases that are far from being considered benign. METHODS: Observational, retrospective, and prospective longitudinal multicentre study including patients with positive serum MOG-IgG assessed by cell-based assay. RESULTS: We include 35 patients, 71% women, median age at onset 30 years (range 1-68), 23% had paediatric onset, with a median disease-duration 24 months (range 12-348). In the whole cohort, the most frequent symptoms at onset were isolated optic neuritis (ON) (34%) and myelitis (22%). Encephalitis with seizures or encephalomyelitis was the most common presentation in paediatric-onset patients 75% (n = 6), compared to 11% (n = 3) of the adult-onset patients (p < 0.001). A relapsing course was observed in 34%, these patients were younger (25 vs. 34 years, p = 0.004) and with a longer disease duration (64 vs. 6 months, p = 0.004) compared to monophasic patients. Two patients developed encephalitis with seizures/status epilepticus, with concomitant positive CSF anti-NMDAR-IgG. Chronic immunotherapy was ever prescribed in 77%, the most frequent was rituximab (35%). Relapses under chronic immunotherapy occurred in 5/27 patients (18.5%), two of them under rituximab, one paediatric patient who started combined therapy with monthly IVIG and one adult patient that switched to satralizumab plus mycophenolate. The median EDSS at the last follow-up was 1.5 (range 0-6.0). CONCLUSION: In Chile, patients with MOGAD exhibit a wide spectrum of clinical presentations at disease onset and during relapses. Close monitoring is needed, particularly in younger patients with short follow-up periods.

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene.

Introduction: Hypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease. Methods: Patients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry. Results: Two previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction. Conclusions: The two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level.

National Burden and Trends for 29 Groups of Cancer in Mexico from 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

The global burden of cancer is on the rise, with varying national patterns. To gain a better understanding and control of cancer, it is essential to provide national estimates. Therefore, we present a comparative description of cancer incidence and mortality rates in Mexico from 1990 to 2019, by age and sex for 29 different cancer groups. Based on public data from the Global Burden of Disease Study 2019, we evaluated the national burden of cancer by analyzing counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and trends using the annual percentage change from 1990 to 2019. In 2019, cancer resulted in 222,060 incident cases and 105,591 deaths. In 2019, the highest incidence of cancer was observed in non-melanoma skin cancer, prostate cancer, and breast cancer. Additionally, 53% of deaths were attributed to six cancer groups (lung, colorectal, stomach, prostate, breast, and pancreatic). From 1990 to 2019, there was an increasing trend in incidence and mortality rates, which varied by 10-436% among cancer groups. Furthermore, there were cancer-specific sex differences in crude and age-standardized rates. The results show an increase in the national cancer burden with sex-specific patterns of change. These findings can guide national efforts to reduce health loss due to cancer.

Exploring the Role of Sclerostin as a Biomarker of Cardiovascular Disease and Mortality: A Scoping Review.

Sclerostin is most recognized for its role in controlling bone formation; however, it is also expressed in the heart, aorta, coronary, and peripheral arteries. Human studies have associated high circulating sclerostin levels with the presence of different cardiovascular diseases (CVD), surrogate CVD markers, and a high risk of cardiovascular events in some populations. However, this is still a matter of scientific debate, as the results have been very heterogeneous among studies. In the present review, the association between serum sclerostin levels and CVD and/or cardiovascular mortality was analyzed. For this purpose, a scoping review was performed in which articles measuring serum sclerostin levels and cardiovascular risk in patients were selected. Eleven articles answered the research question; of these articles, 8/11 evaluated the association between sclerostin and CVD, of which 4/8 found a positive association, 2/8 found a negative association, and 2/8 found no association between variables. Five (5/11) of the articles included in the study evaluated cardiovascular mortality, of which 3/5 found a positive association, 1/5 found a negative association, and 1/5 found no association between variables. In conclusion, we did not find sufficient results to be able to demonstrate an association between elevated sclerostin levels and the development of CVD and/or cardiovascular mortality in the general population due to heterogeneity in the results. However, there seems to be a tendency to consider increased sclerostin levels as a risk factor for both the development of cardiovascular events and cardiovascular mortality in specific populations. Further studies in this field will help to solve some of the inconsistencies found during this scoping review and allow for the future use of sclerostin measurement as a strategy in the prevention and diagnosis of CVD and/or cardiovascular mortality.

The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus.

Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents "mandatory damage" in the development of microvascular complications and only "introductory damage" in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

Undercarboxylated Osteocalcin: A Promising Target for Early Diagnosis of Cardiovascular and Glycemic Disorders in Patients with Metabolic Syndrome: A Pilot Study.

Lifestyle changes are causing an exponential increase in the prevalence of obesity and metabolic syndrome (MetS) worldwide. The most frequent complications of these are the development of diabetes (T2D) and cardiovascular disease (CVD). Accurate tools are needed to classify the cardiovascular risk (CVR) in the MetS population. In recent years, numerous biomarkers of bone metabolism have been associated with CVR. The aim of this study was to determine the levels of undercarboxylated osteocalcin (ucOC) in a cohort of patients with MetS and to analyse its association with MetS parameters and CVR as well as with T2D prevalence. A longitudinal study was conducted in which a MetS population was followed for one year. Weight change, adherence to the Mediterranean diet (MedDiet), ucOC levels, MetS parameters and CVR were analysed and CVR was calculated using different scores. Our results showed a decrease of CVR associated with a better adherence to the MetDiet resulting in higher HDL-C and ucOC levels though the improvement of MetS risk factors. This bone protein appeared as a potential biomarker to classify CVR in the MetS population, especially for MetS patients without prevalent T2D. Furthermore, ucOC serum levels could be good predictors of T2D prevalence.

Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia.

Hypophosphatasia (HPP) a rare disease caused by mutations in the ALPL gene encoding for the tissue-nonspecific alkaline phosphatase protein (TNSALP), has been identified as a potentially under-diagnosed condition worldwide which may have higher prevalence than currently established. This is largely due to the overlapping of its symptomatology with that of other more frequent pathologies. Although HPP is usually associated with deficient bone mineralization, the high genetic variability of ALPL results in high clinical heterogeneity, which makes it difficult to establish a specific HPP symptomatology. In the present study, three variants of ALPL gene with uncertain significance and no previously described (p.Del Glu23_Lys24, p.Pro292Leu and p.His379Asn) were identified in heterozygosis in patients diagnosed with HPP. These variants were characterized at phenotypic, functional and structural levels. All genetic variants showed significantly lower in vitro ALP activity than the wild-type (WT) genotype (p-value <0.001). Structurally, p.His379Asn variant resulted in the loss of two Zn2+ binding sites in the protein dimer which may greatly affect ALP activity. In summary, we identified three novel ALPL gene mutations associated with adult HPP. The correct identification and characterization of new variants and the subsequent study of their phenotype will allow the establishment of genotype-phenotype relationships that facilitate the management of the disease as well as making it possible to individualize treatment for each specific patient. This would allow the therapeutic approach to HPP to be personalized according to the unique genetic characteristics and clinical manifestations of each patient.

Safety and humoral response rate of inactivated and mRNA vaccines against SARS-CoV-2 in patients with Multiple Sclerosis.

BACKGROUND: Safety and effectiveness outcomes in Multiple Sclerosis (MS) patients receiving different disease-modifying therapies (DMT) and different types of vaccines against SARS-CoV-2 are limited. Growing evidence coming mainly from Israel, Europe and North America using mRNA and adenoviral vector vaccines has been published. OBJECTIVES: To assess the safety and humoral response of inactivated virus and mRNA vaccines against SARS-CoV-2 in patients with MS. METHODS: Ongoing, multicentric, prospective, observational study performed between February and September 2021. Humoral response (antibodies against spike-1 protein) was determined at least 4 weeks after the complete schedule of anti-SARS-CoV-2 vaccines. Categorical outcome (positive/negative) and total antibody titres were recorded. Adverse events supposedly attributable to vaccination (AESAV) were collected. RESULTS: 178 patients, 68% women, mean age 39.7 ± 11.2 years, 123 received inactivated (Coronavac-Sinovac), 51 mRNA (Pfizer-BioNtech), and 4 adenoviral vector vaccines (CanSino n = 2, Jonhson&Johnson-Jannsen n = 1, Oxford-AstraZeneca n = 1). Six patients had a history of COVID-19 before vaccination. Overall humoral response was observed in 66.9% (62.6% inactivated vs. 78.4% mRNA, p = 0.04). Positive anti-S1-antibodies were observed in 100% of patients with no DMT (n = 3), 100% with interferon/glatiramer-acetate (n = 11), 100% with teriflunomide/dimethyl-fumarate (n = 16), 100% with natalizumab (n = 10), 100% with alemtuzumab (n = 8), 90% with cladribine (n = 10), and 88% with fingolimod (n = 17), while 43% of patients receiving antiCD20 (n = 99) were positive (38% inactivated vaccine vs. 59% mRNA vaccine, p = 0.05). In the multivariate analysis including antiCD20 patients, the predictors for a positive humoral response were receiving the mRNA vaccine (OR 8.11 (1.79-36.8), p = 0.007) and a lower number of total infusions (OR 0.44 (0.27-0.74) p = 0.002. The most frequent AESAV was local pain (14%), with 4 (2.2%) patients experiencing mild-moderate relapses within 8 weeks of first vaccination compared to 11 relapses (6.2%) within the 8 weeks before vaccination (Chi-squared 3.41, p = 0.06). DISCUSSION: A higher humoral response rate was observed using the mRNA compared to the inactivated vaccine, while patients using antiCD20 had a significantly lower response rate, and patients using antiCD20 and fingolimod had lower antibody titres. In this MS patient cohort, inactivated and mRNA vaccines against SARS-CoV-2 appear to be safe, with no increase in relapse rate. This information may help guidelines including booster shots and types of vaccines in selected populations.

Identification of Potential Targets Linked to the Cardiovascular/Alzheimer's Axis through Bioinformatics Approaches.

The identification of common targets in Alzheimer's disease (AD) and cardiovascular disease (CVD) in recent years makes the study of the CVD/AD axis a research topic of great interest. Besides aging, other links between CVD and AD have been described, suggesting the existence of common molecular mechanisms. Our study aimed to identify common targets in the CVD/AD axis. For this purpose, genomic data from calcified and healthy femoral artery samples were used to identify differentially expressed genes (DEGs), which were used to generate a protein-protein interaction network, where a module related to AD was identified. This module was enriched with the functionally closest proteins and analyzed using different centrality algorithms to determine the main targets in the CVD/AD axis. Validation was performed by proteomic and data mining analyses. The proteins identified with an important role in both pathologies were apolipoprotein E and haptoglobin as DEGs, with a fold change about +2 and -2, in calcified femoral artery vs healthy artery, respectively, and clusterin and alpha-2-macroglobulin as close interactors that matched in our proteomic analysis. However, further studies are needed to elucidate the specific role of these proteins, and to evaluate its function as biomarkers or therapeutic targets.

Selection and characterization of Spanish Trifolium-nodulating rhizobia for pasture inoculation.

Identification of elite nitrogen-fixing rhizobia strains is a continuous and never ending effort, since new legume species can be cultivated in different agro systems or are introduced into new areas. This current study reports on the taxonomic affiliation and symbiotic proficiency of nine strains of Trifolium-nodulating rhizobia isolated from different pasture areas in Spain, as well as three Rhizobium leguminosarum bv. trifolii reference strains, on eleven Trifolium species. Based on 16S rRNA gene sequences the strains belonged to the R. leguminosarum species complex. Additional phylogenetic analyses of the housekeeping genes recA, atpD and rpoB showed the strains were closely related to the species R. leguminosarum, R. laguerreae, R. indicum, R. ruizarguesonis or R. acidisoli. In addition, three strains had no clear affiliation and could represent putative new species, although two of the reference strains were positioned close to R. ruizarguesonis. nodC gene phylogeny allowed the discrimination between strains isolated from annual or perennial Trifolium species and placed all of them in the symbiovar trifolii. Neither geographic origin nor host-plant species could be correlated with the taxonomic affiliation of the strains and a high degree of phenotypic diversity was found among this set of strains. The strong interaction of plant species with the rhizobial strains found for biological nitrogen fixation (BNF) was noteworthy, and allowed the identification of rhizobial strains with a maximum proficiency for certain trefoil species. Several strains showed high BNF potential with a wide range of clover species, which made them valuable strains for inoculant manufacturers and they would be particularly useful for inoculation of seed mixtures in natural or cultivated pastures.

Lower trabecular bone score in type 2 diabetes mellitus: A role for fat mass and insulin resistance beyond hyperglycaemia.

AIMS: To examine the clinical and biochemical determinants of trabecular bone score (TBS) in type 2 diabetes mellitus (T2DM) patients. METHODS: Cross-sectional observational study in 137 T2DM patients (49-85 years). Whole-body fat percentage was estimated using the relative fat mass (RFM) equation. Bone mineral density (BMD) and TBS were assessed using dual-energy X-ray absorptiometry and TBS iNsight Software respectively. RESULTS: T2DM patients showed significantly lower TBS values (P < 0.001) despite significantly higher lumbar spine BMD (LS-BMD) (P = 0.025) compared to controls. TBS values ​​were negatively correlated with body mass index (BMI) (P < 0.001), waist circumference (P < 0.001), and HOMA-2IR index (P = 0.004) and positively correlated with sex hormone-binding globulin (SHBG) (P = 0.01) and LS-BMD (P = 0.003). RFM was negatively associated with TBS in both males (P < 0.001) and females (P = 0.005). The multivariate analysis showed that RFM, HOMA2-IR (negative), SHBG, and LS-BMD (positive) were the variables independently associated with TBS. ROC analysis revealed RFM as the variable with the highest predictive value for risk of degraded bone microarchitecture. CONCLUSIONS: The adiposity estimated by RFM may negatively affect TBS and this relationship may be influenced by insulin resistance and SHBG. RFM could act as a key estimator of degraded bone microarchitecture risk in the T2DM population.

[Analysis of 4,164 type 1 diabetes antibody profiles in a Chilean health centre]. / Marcadores inmunológicos de diabetes tipo 1: análisis de 4.164 perfiles en un centro de salud de Chile.

BACKGROUND: Previous studies have assessed the role of Type 1 diabetes (DM1) antibodies as predictors of the natural history of disease. AIM: To determine the frequency and combinations of positivity for DM1 antibodies in patients with DM1 and the relationship between antibody positivity and the age of the patient. To explore the relationship between history of insulin therapy or diabetic ketoacidosis (DKA) at the onset of the disease with antibody positivity in a subsample. MATERIAL AND METHODS: Data was gathered from every sample processed for DM1 antibodies in our laboratory between January 2015 and September 2019. Medical records from 84 patients who tested positive for at least one antibody were revised to study the relationship between insulin therapy or DKA at the onset of the disease with antibody positivity. RESULTS: Forty percent of DM1 antibody tests were positive. Among positive tests, 1, 2, 3 or 4 DM1 antibodies were detected in 48%, 33%, 17% and 3% of cases, respectively. The likelihood of testing positive was inversely related with age for ICA, GAD, IA-2, ZnT8 and directlyproportionalforIAA (p= -0,012; -0,013; -0,014; -0,009; 0,005 respectively). An association between DKA at the onset of the disease and IA-2 positivity was observed (Odds ratio (OR) 5.38 95% confidence intervals (CI) 1.79 - 16.16, P < 0.01). No association was found between IAA positivity and history of insulin therapy (OR 2.25 95%CI 0.63 - 7.90, P = 0.2403). The results obtained from this study represent a novel local profile of DM1 antibody data, highlighting a relationship between antibody positivity and age.