Order of amino acid recruitment into the genetic code resolved by Last Universal Common Ancestor's protein domains.

The current "consensus" order in which amino acids were added to the genetic code is based on potentially biased criteria such as absence of sulfur-containing amino acids from the Urey-Miller experiment which lacked sulfur. Even if inferred perfectly, abiotic abundance might not reflect abundance in the organisms in which the genetic code evolved. Here, we instead exploit the fact that proteins that emerged prior to the genetic code's completion are likely enriched in early amino acids and depleted in late amino acids. We identify the most ancient protein-coding sequences born prior to the archaeal-bacterial split. Amino acid usage in protein sequences whose ancestors date back to a single homolog in the Last Universal Common Ancestor (LUCA) largely matches the consensus order. However, our findings indicate that metal-binding (cysteine and histidine) and sulfur-containing (cysteine and methionine) amino acids were added to the genetic code much earlier than previously thought. Surprisingly, even more ancient protein sequences - those that had already diversified into multiple distinct copies in LUCA - show a different pattern to single copy LUCA sequences: significantly less depleted in the late amino acids tryptophan and tyrosine, and enriched rather than depleted in phenylalanine. This is compatible with at least some of these sequences predating the current genetic code. Their distinct enrichment patterns thus provide hints about earlier, alternative genetic codes.

Tumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer.

BACKGROUND: Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA11a linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response. METHODS: Methods involved RNA-SEQ on NSCLC cells with depleted hMENA isoforms. A retrospective observational study assessed tissues from surgically treated N0 patients with NSCLC, using immunohistochemistry for tumoral and stromal hMENA isoforms, fibronectin, and TLS presence. ICB-treated patient tumors were analyzed using Nanostring nCounter and GeoMx spatial transcriptomics. Multiparametric flow cytometry characterized B cells and tissue-resident memory T cells (TRM). Survival and ICB response were estimated in the cohort and validated using bioinformatics pipelines in different datasets. FINDINGS: Findings indicate that hMENA11a in NSCLC cells upregulates the TLS regulator LTßR, decreases fibronectin, and favors CXCL13 production by TRM. Conversely, hMENAΔv6 in CAFs inhibits LTßR-related NF-kB pathway, reduces CXCL13 secretion, and promotes fibronectin production. These patterns are validated in N0 NSCLC tumors, where hMENA11ahigh expression, CAF hMENAΔv6low, and stromal fibronectinlow are associated with intratumoral TLS, linked to memory B cells and predictive of longer survival. The hMENA isoform pattern, fibronectin, and LTßR expression broadly predict ICB response in tumors where TLS indicates an anti-tumor immune response. INTERPRETATION: This study uncovers hMENA alternative splicing as an unexplored contributor to TLS-related Tumor Immune Microenvironment (TIME) and a promising biomarker for clinical outcomes and likely ICB responsiveness in N0 patients with NSCLC. FUNDING: This work is supported by AIRC (IG 19822), ACC (RCR-2019-23669120), CAL.HUB.RIA Ministero Salute PNRR-POS T4, "Ricerca Corrente" granted by the Italian Ministry of Health.

Shared graft-versus-leukemia minor histocompatibility antigens in DISCOVeRY-BMT.

T-cell responses to minor histocompatibility antigens (mHAs) mediate graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation. Therapies that boost T-cell responses improve allogeneic hematopoietic cell transplant (alloHCT) efficacy but are limited by concurrent increases in the incidence and severity of GVHD. mHAs with expression restricted to hematopoietic tissue (GVL mHAs) are attractive targets for driving GVL without causing GVHD. Prior work to identify mHAs has focused on a small set of mHAs or population-level single-nucleotide polymorphism-association studies. We report the discovery of a large set of novel GVL mHAs based on predicted immunogenicity, tissue expression, and degree of sharing among donor-recipient pairs (DRPs) in the DISCOVeRY-BMT data set of 3231 alloHCT DRPs. The total number of predicted mHAs varied by HLA allele, and the total number and number of each class of mHA significantly differed by recipient genomic ancestry group. From the pool of predicted mHAs, we identified the smallest sets of GVL mHAs needed to cover 100% of DRPs with a given HLA allele. We used mass spectrometry to search for high-population frequency mHAs for 3 common HLA alleles. We validated 24 predicted novel GVL mHAs that are found cumulatively within 98.8%, 60.7%, and 78.9% of DRPs within DISCOVeRY-BMT that express HLA-A∗02:01, HLA-B∗35:01, and HLA-C∗07:02, respectively. We confirmed the immunogenicity of an example novel mHA via T-cell coculture with peptide-pulsed dendritic cells. This work demonstrates that the identification of shared mHAs is a feasible and promising technique for expanding mHA-targeting immunotherapeutics.

Adherence to the healthy lifestyle guideline in relation to the metabolic syndrome: Analyses from the 2013 and 2018 Indonesian national health surveys.

In this study, we aimed to investigate differences in lifestyle factors and prevalence of metabolic syndrome (MetS) in the Indonesian population between 2013 and 2018. In addition, we investigated whether adherence to the 2015-released national healthy lifestyle guideline ('GERMAS') is associated with MetS in different sex, age, urban/rural, and BMI categories. We performed cross-sectional analyses in individuals aged >15 of the 2013 (n = 34,274) and 2018 (n = 33,786) Indonesian National Health Surveys. A stratified, multi-stage, systematic random sampling design and the probability proportional to size method were used to select households in the 34 provinces across the country. MetS was defined according to the Joint Interim Statement Criteria, and adherence to 'GERMAS' guideline was defined as fulfilling the national healthy lifestyle recommendations of ≥150 min/week physical activity (PA), ≥5 portions/day fruit and vegetable (FV), no smoking (NS), and no alcohol consumption (NA). We examined the associations of each lifestyle factor with MetS using logistic regression categorised by sex, age groups, urban/rural, and BMI, and adjusted for sociodemographic factors. We observed that men who adhered to the guideline had lower odds ratio of MetS [OR(95%CI) associated with PA: 0.85(0.75-0.97); NA: 0.75(0.56-1.00)] than non-adherent men. Middle-aged adults who adhered to the guideline had lower OR of MetS [PA: 0.85(0.72-1.01); FV: 0.78(0.62-0.99); NA: 0.66(0.46-0.93)] than non-adherent adults <45 years. The adherent urban population had lower OR of MetS [FV: 0.85(0.67-1.07); NA: 0.74(0.52-1.07)] than the non-adherent urban population. Those with overweight or obesity who adhered to the guideline had relatively lower odds of MetS than those who did not. In conclusion, in this nationally representative study, adherence to the 'GERMAS' guideline may confer cardiometabolic health benefits to several groups of the Indonesian population, particularly men, middle-aged, those with overweight and obesity, and potentially urban population.

Cardiovascular disease prediction model for Indonesian adult population with prediabetes and diabetes mellitus: The Bogor Cohort study of Noncommunicable Diseases Risk Factors.

BACKGROUND AND AIMS: This study aims to develop a predictive model of cardiovascular events in dysglycemia among the Indonesian adult population. METHODS: This is a retrospective cohort study conducted on subjects over 25 years in the "The Bogor Cohort Study of Noncommunicable Diseases Risk Factors" from 2011 to 2018. Data associated with age, gender, blood pressure, body mass index, waist circumference, blood glucose, cholesterol, smoking habits, family history of cardiovascular disease, and physical activity were obtained. Cardiovascular events in six years were observed; this included coronary heart disease, stroke, or all-cause cardiovascular mortality. Cox proportional hazards regression models were used to determine independent predictors of cardiovascular events. RESULTS: A total of 1085 subjects with prediabetes and diabetes mellitus were included in this study, with 73.5% female. The cumulative incidence of cardiovascular events in six years was 9.7%. Predictors of cardiovascular events were age ≥45 years (HR = 2.737; 95% CI 1.565-4.787) and hypertension (HR = 2.580; 95% CI 1.619-4.112). CONCLUSIONS: Age ≥45 years and hypertension were predictors of cardiovascular events in six years among the adult Indonesian population with prediabetes and diabetes, necessitating targeted intervention among these subjects.

Impact of Sodium Butyrate Treatment in LPS-Stimulated Peripheral Blood Mononuclear Cells of Poorly Controlled Type 2 DM.

Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation, which is marked by the dysregulation of innate and adaptive immune responses. Therefore, reducing inflammation, possibly through an immunoregulatory agent, may play a role in T2DM treatment. Butyrate is the most potent short-chain fatty acid (SCFA), and it exerts anti-inflammatory properties by inhibiting histone deacetylase activity. As an immunoregulatory agent, sodium butyrate can inhibit nuclear factor kB (NF-kB) activation and reduce the production of pro-inflammatory cytokines in immune cells. The aim of the study was to measure the level of plasma butyrate in poorly controlled T2DM and normoglycemic participants and to compare the response of peripheral blood mononuclear cells (PBMCs) to sodium butyrate treatment between the groups by measuring production of the following cytokines: tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-13, and IL-10. The in vitro study examined the PBMCs of 15 participants with poorly controlled T2DM and 15 normoglycemic participants. PBMCs were cultured with the following stimulations for two days at a temperature of 37°C and 5% CO2: 100 ng/mL lipopolysaccharide (LPS), 1 mM sodium butyrate, or a combination of 100 ng/mL LPS and 1 mM sodium butyrate. Plasma butyrate was measured using gas chromatography-mass spectrometry, and cytokines from culture supernatant were analyzed using magnetic beads multiplex assay. Plasma butyrate levels in participants with poorly controlled T2DM did not significantly differ from those in normoglycemic participants (p = 0.105). Compared to treatment with an LPS-stimulated PBMC culture, treatment with 1 mM sodium butyrate reduced the levels of TNF-α (p < 0.039) and IFN-γ (p < 0.038) in normoglycemic participants. The same general trend was seen in PBMC from participants with poorly controlled T2DM, but higher variability appeared to preclude statistical significance. These data suggest that butyrate may modulate inflammatory cytokine production in human PBMCs, but more research is needed to determine if butyrate is anti-inflammatory in poorly controlled T2DM.

ADA Diabetes Risk Test Adaptation in Indonesian Adult Populations: Can It Replace Random Blood Glucose Screening Test?

AIMS: The use of non-invasive and easily available assessment tools such as the ADA diabetes risk test is recommended for diabetes screening among general population. This study aims to assess the validity of the ADA diabetes risk test in screening for screening hyperglycemia in Indonesian population. METHODS: This cross-sectional study conducted at primary health care in Cibeber sub district at Cilegon city, Banten province, Indonesia. Subjects were aged ≥45 years old without a prior diagnosis of diabetes were recruited consecutively. The risk of hyperglycemia was measured using the ADA Diabetes Risk Test. Random capillary blood glucose (RcBG) with a cut-off value >140 mg/dL used as a comparison. RESULTS: From a total of 134 subjects, 23.13% of subjects (n = 31) had hyperglycemia. The ADA Diabetes Risk Test gave an area under the ROC curve (AUC) of 0.71 (95% CI: 0.60-0.81) with an optimal cut-off of value ≥5. The sensitivity of the ADA diabetes risk test in diagnosing hyperglycemia was 68% with a false-negative rate (FNR) of 32.26%. Meanwhile, at a cut-off value ≥4, the sensitivity of the ADA Diabetes Risk Test was 93% with an FNR of 9.7%. CONCLUSION: ADA diabetes risk test provides a valuable result as a diabetes screening tool in the Indonesian population, thus promotes intervention strategies for population known to be at risk.

Improved T-cell Receptor Diversity Estimates Associate with Survival and Response to Anti-PD-1 Therapy.

T-cell receptor (TCR) repertoire profiling has emerged as a powerful tool for biological discovery and biomarker development in cancer immunology and immunotherapy. A key statistic derived from repertoire profiling data is diversity, which summarizes the frequency distribution of TCRs within a mixed population. Despite the growing use of TCR diversity metrics in clinical trial correlative studies in oncology, their accuracy has not been validated using published ground-truth datasets. Here, we reported the performance characteristics of methods for TCR repertoire profiling from RNA-sequencing data, showed undersampling as a prominent source of bias in diversity estimates, and derived a model via statistical learning that attenuates bias to produce corrected diversity estimates. This modeled diversity improved discrimination in The Cancer Genome Atlas data and associated with survival and treatment response in patients with melanoma treated with anti-PD-1 therapy, where the commonly used diversity normalizations did not. These findings have the potential to increase our understanding of the tumor immune microenvironment and improve the accuracy of predictions of patient responses to immunotherapy.

Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma.

BACKGROUNDSurgery remains the frontline therapy for patients with localized clear cell renal cell carcinoma (ccRCC); however, 20%-40% recur. Angiogenesis inhibitors have improved survival in metastatic patients and may result in responses in the neoadjuvant setting. The impact of these agents on the tumor genetic heterogeneity or the immune milieu is largely unknown. This phase II study was designed to evaluate safety, response, and effect on tumor tissue of neoadjuvant pazopanib.METHODSccRCC patients with localized disease received pazopanib (800 mg daily; median 8 weeks), followed by nephrectomy. Five tumors were examined for mutations by whole exome sequencing from samples collected before therapy and at nephrectomy. These samples underwent RNA sequencing; 17 samples were available for posttreatment assessment.RESULTSTwenty-one patients were enrolled. The overall response rate was 8 of 21 (38%). No patients with progressive disease. At 1-year, response-free survival and overall survival was 83% and 89%, respectively. The most frequent grade 3 toxicity was hypertension (33%, 7 of 21). Sequencing revealed strong concordance between pre- and posttreatment samples within individual tumors, suggesting tumors harbor stable core profiles. However, a reduction in private mutations followed treatment, suggesting a selective process favoring enrichment of driver mutations.CONCLUSIONNeoadjuvant pazopanib is safe and active in ccRCC. Future genomic analyses may enable the segregation of driver and passenger mutations. Furthermore, tumor infiltrating immune cells persist during therapy, suggesting that pazopanib can be combined with immune checkpoint inhibitors without dampening the immune response.FUNDINGSupport was provided by Novartis and GlaxoSmithKline as part of an investigator-initiated study.

Neuronal-like response of N2a living cells to nanoporous patterns of thin supported anodic alumina.

We report about the response of N2a cells, a mouse neuroblastoma cell line, cultured on inert substrates with controlled porous nanostructure. The substrate surfaces were obtained by anodization and post-fabrication etching of thin aluminum films previously deposited onto glass. The morphology of the adherent cells was assessed by scanning electron microscopy. After fluorescent labelling, confocal microscopy was used to assess both the cell density, by cell nuclei counting, and their growth, by characterizing the neurite extensions in both number and length. By comparing with flat and smooth aluminum oxide, we can conclude that the nanoporous morphology of the anodized aluminum is favorable for cell development, which is probably correlated with the high density of regions with high local curvature. The intermediate pore size in the given range seems unfavorable for the number of cells, while the cell shape and the number of extensions point to a dominating differentiation of the N2a cells in correspondence with a characteristic pore size of 60 nm. These results are promising in view of the application of anodic alumina as a platform for the development of neuronal bioassays based on cell interconnectivity.

Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties.

Parasitic worms have a remarkable ability to modulate host immune responses through several mechanisms including excreted/secreted proteins (ESP), yet the exact nature of these proteins and their targets often remains elusive. Here, we performed mass spectrometry analyses of ESP (TsESP) from larval and adult stages of the pig whipworm Trichuris suis (Ts) and identified ~350 proteins. Transcriptomic analyses revealed large subsets of differentially expressed genes in the various life cycle stages of the parasite. Exposure of bone marrow-derived macrophages and dendritic cells to TsESP markedly diminished secretion of the pro-inflammatory cytokines TNFα and IL-12p70. Conversely, TsESP exposure strongly induced release of the anti-inflammatory cytokine IL-10, and also induced high levels of nitric oxide (NO) and upregulated arginase activity in macrophages. Interestingly, TsESP failed to directly induce CD4+ CD25+ FoxP3+ regulatory T cells (Treg cells), while OVA-pulsed TsESP-treated dendritic cells suppressed antigen-specific OT-II CD4+ T cell proliferation. Fractionation of TsESP identified a subset of proteins that promoted anti-inflammatory functions, an activity that was recapitulated using recombinant T. suis triosephosphate isomerase (TPI) and nucleoside diphosphate kinase (NDK). Our study helps illuminate the intricate balance that is characteristic of parasite-host interactions at the immunological interface, and further establishes the principle that specific parasite-derived proteins can modulate immune cell functions.

Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma.

Human endogenous retroviruses (hERVs) are remnants of exogenous retroviruses that have integrated into the genome throughout evolution. We developed a computational workflow, hervQuant, which identified more than 3,000 transcriptionally active hERVs within The Cancer Genome Atlas (TCGA) pan-cancer RNA-Seq database. hERV expression was associated with clinical prognosis in several tumor types, most significantly clear cell renal cell carcinoma (ccRCC). We explored two mechanisms by which hERV expression may influence the tumor immune microenvironment in ccRCC: (i) RIG-I-like signaling and (ii) retroviral antigen activation of adaptive immunity. We demonstrated the ability of hERV signatures associated with these immune mechanisms to predict patient survival in ccRCC, independent of clinical staging and molecular subtyping. We identified potential tumor-specific hERV epitopes with evidence of translational activity through the use of a ccRCC ribosome profiling (Ribo-Seq) dataset, validated their ability to bind HLA in vitro, and identified the presence of MHC tetramer-positive T cells against predicted epitopes. hERV sequences identified through this screening approach were significantly more highly expressed in ccRCC tumors responsive to treatment with programmed death receptor 1 (PD-1) inhibition. hervQuant provides insights into the role of hERVs within the tumor immune microenvironment, as well as evidence that hERV expression could serve as a biomarker for patient prognosis and response to immunotherapy.

Computational modeling and confirmation of leukemia-associated minor histocompatibility antigens.

T-cell responses to minor histocompatibility antigens (mHAs) mediate both antitumor immunity (graft-versus-leukemia [GVL]) and graft-versus-host disease (GVHD) in allogeneic stem cell transplant. Identifying mHAs with high allele frequency, tight binding affinity to common HLA molecules, and narrow tissue restriction could enhance immunotherapy against leukemia. Genotyping and HLA allele data from 101 HLA-matched donor-recipient pairs (DRPs) were computationally analyzed to predict both class I and class II mHAs likely to induce either GVL or GVHD. Roughly twice as many mHAs were predicted in HLA-matched unrelated donor (MUD) stem cell transplantation (SCT) compared with HLA-matched related transplants, an expected result given greater genetic disparity in MUD SCT. Computational analysis predicted 14 of 18 previously identified mHAs, with 2 minor antigen mismatches not being contained in the patient cohort, 1 missed mHA resulting from a noncanonical translation of the peptide antigen, and 1 case of poor binding prediction. A predicted peptide epitope derived from GRK4, a protein expressed in acute myeloid leukemia and testis, was confirmed by targeted differential ion mobility spectrometry-tandem mass spectrometry. T cells specific to UNC-GRK4-V were identified by tetramer analysis both in DRPs where a minor antigen mismatch was predicted and in DRPs where the donor contained the allele encoding UNC-GRK4-V, suggesting that this antigen could be both an mHA and a cancer-testis antigen. Computational analysis of genomic and transcriptomic data can reliably predict leukemia-associated mHA and can be used to guide targeted mHA discovery.

The Immune Landscape of Cancer.

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-ß dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.

Parathyroid Adenoma in a Young Female Presenting Multiple Fractures and Postoperative Hungry Bone Syndrome.

A young 18-year-old female patient with general bone pain and history of multiple fractures brought her to our medical attention. Laboratory work showed hypercalcemia and high parathyroid hormone levels in the blood. Radiograph imaging revealed severe scoliosis with multiple vertebrae fractures with decreased bone mineral density. Sestamibi showed parathyroid adenoma. This case emphasizes the importance of maintaining a primary hyperparathyroidism as a differential diagnosis when a young patient presents with a multiple pathologic fractures history.

Molecular and Clinical Characterization of a Claudin-Low Subtype of Gastric Cancer.

PURPOSE: Claudin-low molecular subtypes have been identified in breast and bladder cancers and are characterized by low expression of claudins, enrichment for epithelial-to-mesenchymal transition (EMT), and tumor-initiating cell (TIC) features. We evaluated whether the claudin-low subtype also exists in gastric cancer. MATERIALS AND METHODS: Four hundred fifteen tumors from The Cancer Genome Atlas (TCGA) gastric cancer mRNA data set were clustered on the claudin, EMT, and TIC gene sets to identify claudin-low tumors. We derived a 24-gene predictor that classifies gastric cancer into claudin-low and non-claudin-low subtypes. This predictor was validated with the Asian Cancer Research Group (ACRG) data set. We characterized molecular and clinical features of claudin-low tumors. RESULTS: We identified 46 tumors that had consensus enrichment for claudin-low features in TCGA data set. Claudin-low tumors were most commonly diffuse histologic type (82%) and originally classified as TCGA genomically stable (GS) subtype (78%). Compared with GS subtype, claudin-low subtype had significant activation in Rho family of GTPases signaling, which appears to play a key role in its EMT and TIC properties. In the ACRG data set, 28 of 300 samples were classified as claudin-low tumors by the 24-gene predictor and were phenotypically similar to the initially derived claudin-low tumors. Clinically, claudin-low subtype had the worst overall survival. Of note, the hazard ratios that compared claudin-low versus GS subtype were 2.10 (95% CI, 1.07 to 4.11) in TCGA and 2.32 (95% CI, 1.18 to 4.55) in the ACRG cohorts, with adjustment for age and pathologic stage. CONCLUSION: We identified a gastric claudin-low subtype that carries a poor prognosis likely related to therapeutic resistance as a result of its EMT and TIC phenotypes.

La coronarioectasia difiere en los factores de riesgo clásicos de enfermedad coronaria / Compared to usual coronary artery disease risk factors are different in those with coronary ectasia

Introducción: La coronarioectasia (CE), es una infrecuente forma de enfermedad coronaria, en que dilataciones coronarias coexisten con placas ateroes-cleróticas. Puede presentarse como cuadros agudos o crónicos, aún sin estenosis significativa. Distintas series lo han asociado a perfiles variados de factores de riesgo cardiovascular. Métodos: Se efectuó un estudio analítico de cohorte retrospectivo, evaluando las coronariografías realizadas en nuestro centro entre Junio de 2009 a Julio de 2015. Se definió CE como dilatación >1,5 veces comparado con el diámetro de la arteria de referencia. Se estudiaron factores de riesgo cardiovascular clásicos y se compararon con un grupo control elegido de forma aleatoria. Resultados: De 9648 coronariografías, 64 presentaban CE. La mayor parte eran hombres, de menor edad, con menos hipertensión arterial, diabetes e hiperlipidemia, comparados con los controles. En la mayoría de los casos la CE afectaba a 3 vasos (83,3%) y en solo 5 casos (28%) coexistía con estenosis. El análisis multivariado señaló como factores de riesgo significativos a la edad < 55 años (OR: 2,63, IC: 1,4 -4,9, p<0,05), Obesidad (OR: 3,2; IC:1,7-5,8, p<0,05) e Hiperlipidemia (OR: 0,09; IC: 0,016-0,54). Considerando los pacientes que se presentaron como SCA se observó que los pacientes con CE fueron más jóvenes (45,9 años; DE: 5,9 v/s 48,8 años; DE: 5,3; p=0,02), y con menos hiperlipidemia (OR:0,2; IC:0,06-0,7, p=0,01). Respecto a la obesidad, esta fue más preva-lente en pacientes con CE (OR: 2,49; IC: 0,956-6,4. p=ns). Conclusión: La CE es una entidad poco frecuente, que puede producir SCA aun en ausencia de estenosis significativa. Son pacientes más jóvenes y con menos antecedente de dislipidemia, por lo que en su patogenia aparentemente participan factores diferentes a los de la enfermedad ateroesclerótica obstructiva.

Background: Coronary ectasia (CE) is an uncommon condition where coronary artery dilatation coexists with atherosclerotic plaques. It may present as either acute or chronic syndromes even in the absence of coronary artery stenosis. Differences in risk factors associated to CE compared to those associated to usual CAD have been described. Methods: We retrospectively analyzed coronary arteriograms performed between June 2009 and July 2015. CE was defined as the presence of dilatation >1.5 times the diameter of the unaffected vessel. Cardiovascular risk factors were compared in CE vs a random sample of non-CE patients. Results: Out of 9648 coronary arteriograms 64 showed CE (9.5%). Compared to controls, CE patients were males, younger and hat lower prevalence or hypertension, diabetes and hyperlipidemia. CE was present in all 3 main vessels in 83.3% of CE patients and co-existed with significant stenosis in only 28%. Multivariate analysis showed that significant differences in risk factors were age <55 years (OR: 2.63; CI: 1.4 to 4.9, p <0.05), obesity (OR: 3 2; CI: 1.7 to 5.8, p <0.05) and hyperlipidemia (OR: 0.09; CI: 0.016 to 0.54). In patients presenting with an acute coronary syndrome, those with CE were younger (45,9 years; SD: 5,9 v/s 48,8 years; SD: 5,3; p=0,02), y and a lower prevalence or hyperlipidemia (OR:0,2; IC:0,06-0,7, p=0,01). Conclusion: CE is an infrequent condition in CAD. It may me associated to either acute or chronic syndromes. They are younger, have a lower prevalence of dyslipidemia suggesting that risk factors other than traditionally recognized in obstructive CAD influence de development of CE.

Managing Hypertriglyceridemia in Daily Practice.

Hypertriglyceridemia is a form of dyslipidemia, which usually occurs in combination with hypercholesterolemia, high-LDL or low-HDL cholesterol level. Most studies suggest that hypertriglyceridemia is associated with many metabolic disorders such as metabolic syndrome, diabetes, obesity, and also cardio-cerebrovascular diseases. Treatment of hypertriglyceridemia is often not comprehensively addressed by many physicians, who usually only include prescribing drugs without encouraging patients to perform physical activity, to take a true healthy diet for dyslipidemia and to stop smoking. This review article discusses evaluation, diagnosis and a comprehensive, yet simple management of hypertriglyceridemia, which can be easily applied in daily clinical practice.

Prevalence of internal parasites in beef cows in the United States: Results of the National Animal Health Monitoring System's (NAHMS) beef study, 2007-2008.

During the United States Department of Agriculture (USDA) National Animal Health Monitoring System's (NAHMS) 2007-2008 beef study, 567 producers from 24 US States were offered the opportunity to collect fecal samples from weaned beef calves and have them evaluated for the presence of parasite eggs (Phase 1). Participating producers were provided with instructions and materials for sample collection. Up to 20 fresh fecal samples were collected from each of the 99 participating operations. Fresh fecal samples were submitted to one of 3 randomly assigned laboratories for evaluation. Upon arrival at the laboratories, all samples were processed for the enumeration of strongyle, Nematodirus, and Trichuris eggs using the modified Wisconsin technique. The presence or absence of coccidian oocysts and tapeworm eggs was also noted. In submissions where the strongyle eggs per gram exceeded 30, aliquots from 2 to 6 animals were pooled for DNA extraction. Extracted DNA was subjected to genus level polymerase chain reaction (PCR) identification for the presence of Ostertagia, Cooperia, Haemonchus, Oesophagostomum, and Trichostrongylus. In this study, 85.6% of the samples had strongyle type, Nematodirus, and Trichuris eggs. Among the samples evaluated, 91% had Cooperia, 79% Ostertagia, 53% Haemonchus, 38% Oesophagostomum, 18% Nematodirus, 7% Trichuris, and 3% Trichostrongylus. The prevalence of coccidia and tapeworm eggs was 59.9% and 13.7%, respectively.

Pendant l'étude de 2007­2008 chez les bovins effectuée par le Système national de surveillance des maladies animales (NAHMS) du Département de l'agriculture des États-Unis (USDA), 567 producteurs provenant de 24 états américains se sont vus offrir l'opportunité de prélever des échantillons de fèces de veaux sevrés et de les faire analyser pour la présence d'oeufs de parasite (Phase 1). On a fourni aux producteurs participants les instructions et le matériel pour le prélèvement d'échantillon. Jusqu'à 20 échantillons de fèces fraiches furent prélevés de chacune des 99 opérations participantes. Les échantillons de fèces fraiches furent soumis de manière aléatoire pour évaluation à l'un des trois laboratoires participants. Suite à l'arrivée au laboratoire, tous les échantillons étaient traités pour énumération des strongles, de Nematodirus, et d'oeufs de Trichuris en utilisant la technique de Wisconsin modifiée. La présence ou l'absence d'ookystes de coccidie et d'oeufs de vers plats furent également notées. Dans les échantillons soumis et dont le nombre d'oeufs de strongles par gramme dépassait 30, des aliquots de 2 à 6 animaux étaient regroupés pour extraction de l'ADN. L'ADN extrait était soumis à une réaction d'amplification en chaine par la polymérase (PCR) pour une identification au genre de la présence d'Ostertagia, de Cooperia, d'Haemonchus, d'Oesophagostomum, et de Trichostrongylus. Dans la présente étude, 85,6 % des échantillons avaient des strongles, du Nematodirus, et des oeufs de Trichuris. Parmi les échantillons évalués, 91 % avaient du Cooperia, 79 % de l'Ostertagia, 53 % de l'Haemoncus, 38 % de l'Oesophagostomum, 18 % du Nematodirus, 7 % du Trichuris, et 3 % du Trichostrongylus. Les prévalences de coccidies et d'oeufs de vers plats étaient respectivement de 59,9 % et 13,7 %.(Traduit par Docteur Serge Messier).