Mcam stabilizes luminal progenitor breast cancer phenotypes via Ck2 control and Src/Akt/Stat3 attenuation.

Breast cancers are categorized into subtypes with distinctive therapeutic vulnerabilities and prognoses based on their expression of clinically targetable receptors and gene expression patterns mimicking different cell types of the normal gland. Here, we tested the role of Mcam in breast cancer cell state control and tumorigenicity in a luminal progenitor-like murine tumor cell line (Py230) that exhibits lineage and tumor subtype plasticity. Mcam knockdown Py230 cells show augmented Stat3 and Pi3K/Akt activation associated with a lineage state switch away from a hormone-sensing/luminal progenitor state toward alveolar and basal cell related phenotypes that were refractory to growth inhibition by the anti-estrogen therapeutic, tamoxifen. Inhibition of Stat3, or the upstream activator Ck2, reversed these cell state changes. Mcam binds Ck2 and acts as a regulator of Ck2 substrate utilization across multiple mammary tumor cell lines. In Py230 cells this activity manifests as increased mesenchymal morphology, migration, and Src/Fak/Mapk/Paxillin adhesion complex signaling in vitro, in contrast to Mcam's reported roles in promoting mesenchymal phenotypes. In vivo, Mcam knockdown reduced tumor growth and take rate and inhibited cell state transition to Sox10+/neural crest like cells previously been associated with tumor aggressiveness. This contrasts with human luminal breast cancers where MCAM copy number loss is highly coupled to Cyclin D amplification, increased proliferation, and the more aggressive Luminal B subtype. Together these data indicate a critical role for Mcam and its regulation of Ck2 in control of breast cancer cell state plasticity with implications for progression, evasion of targeted therapies and combination therapy design.

Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control.

The regulation of translation provides a rapid and direct mechanism to modulate the cellular proteome. In eukaryotes, an established model for the recruitment of ribosomes to mRNA depends upon a set of conserved translation initiation factors. Nevertheless, how cells orchestrate and define the selection of individual mRNAs for translation, as opposed to other potential cytosolic fates, is poorly understood. We have previously found significant variation in the interaction between individual mRNAs and an array of translation initiation factors. Indeed, mRNAs can be separated into different classes based upon these interactions to provide a framework for understanding different modes of translation initiation. Here, we extend this approach to include new mRNA interaction profiles for additional proteins involved in shaping the cytoplasmic fate of mRNAs. This work defines a set of seven mRNA clusters, based on their interaction profiles with 12 factors involved in translation and/or RNA binding. The mRNA clusters share both physical and functional characteristics to provide a rationale for the interaction profiles. Moreover, a comparison with mRNA interaction profiles from a host of RNA binding proteins suggests that there are defined patterns in the interactions of functionally related mRNAs. Therefore, this work defines global cytoplasmic mRNA binding modules that likely coordinate the synthesis of functionally related proteins.

Interaction of the La-related protein Slf1 with colliding ribosomes maintains translation of oxidative-stress responsive mRNAs.

In response to oxidative stress cells reprogram gene expression to enhance levels of antioxidant enzymes and promote survival. In Saccharomyces cerevisiae the polysome-interacting La-related proteins (LARPs) Slf1 and Sro9 aid adaptation of protein synthesis during stress by undetermined means. To gain insight in their mechanisms of action in stress responses, we determined LARP mRNA binding positions in stressed and unstressed cells. Both proteins bind within coding regions of stress-regulated antioxidant enzyme and other highly translated mRNAs in both optimal and stressed conditions. LARP interaction sites are framed and enriched with ribosome footprints suggesting ribosome-LARP-mRNA complexes are identified. Although stress-induced translation of antioxidant enzyme mRNAs is attenuated in slf1Δ, these mRNAs remain on polysomes. Focusing further on Slf1, we find it binds to both monosomes and disomes following RNase treatment. slf1Δ reduces disome enrichment during stress and alters programmed ribosome frameshifting rates. We propose that Slf1 is a ribosome-associated translational modulator that stabilises stalled/collided ribosomes, prevents ribosome frameshifting and so promotes translation of a set of highly-translated mRNAs that together facilitate cell survival and adaptation to stress.

A Cell Membrane Fusion Assay for the Fish Pathogen Spring Viremia of Carp Virus (SVCV).

Fusion of the infected cell membranes is a characteristic effect of a wide number of viral infections. Spring viremia of carp virus (SVCV), a rhabdovirus causing disease in farmed carp, can induce membrane fusion of the infected cells by shifting the pH of the culture medium to slightly acidic. Membrane fusion leads to the formation of clusters of cell nuclei enclosed in a cell membrane, the so-called syncytia, that can be easily visualized by cell staining and light microscope inspection. In the present work, we report a protocol to induce syncytia formation in EPC cells infected with SVCV, where membrane fusion is triggered by a low-pH incubation step. Appearance of syncytia can be observed at 18 hours post infection. The syncytia formation assay described here may serve as an experimental platform to quantitate SVCV, to determine virus infectivity, and a useful tool to study virus entry into the cell as well as to test candidate antiviral compounds that could block the entry of SVCV into cells by inhibiting membrane fusion.

Application of multidisciplinary team conference for neuromodulation candidates facilitates patient selection and optimization.

Introduction: Psychological evaluation is required by insurance companies in the United States prior to proceeding with a spinal cord stimulation or a dorsal root ganglion stimulation trial. Since January 2017, we implemented a Multidisciplinary Team Conference for Neuromodulation in our center to facilitate the collaboration between pain physicians and psychologists and to optimize screening of neuromodulation candidates. This study aims to report the impact of this team conference on improvement of neuromodulation outcome in our center. Methods: Appropriateness of neuromodulation were discussed in the team conference after initial visit with the pain specialist and psychological evaluation. For this study, we prospectively and retrospectively collected data on neuromodulation candidates who went through the team conference and those who did not as controls. Results: We discussed 461 patients in the team conference sessions from January 2017 to July 2023. Out of these, a spinal cord stimulator or a dorsal root ganglion stimulator trial was performed in 164 patients with 80.5% (132 cases) trial success rate leading to 140 implants. Out of these implants, 26 (18.6%) explanted and 21 (15%) required revision in 41 (29.3%) patients. We performed neuraxial neuromodulation trial for 70 patients without going through the team conference from January 2016 to July 2023 with a trial success rate of 45.7% (32 cases). In this group, 7 (21.9%) and 6 (18.8%) patients underwent explant and revision. The differences between the groups were statistically significant for trial success rate (odds ratio of 4.9 with p-value of <0.01) but not for explant (odds ratio of 0.8 with p-value of 0.627) or revision (odds ratio of 0.8 with p-value of 0.595). Conclusion: Implementing Multidisciplinary Team Conference increased trial success rate in our center. Team conference provides therapeutic benefit for patients, and also provides the opportunity for an educational discussion for trainees.

Significantly increased risk of chronic obstructive pulmonary disease amongst adults with predominantly mild congenital heart disease.

Adults with congenital heart disease (CHD) face increased risk of various comorbid diseases. Previous work on lung dysfunction in this population has mainly focused on restrictive lung disease, in patients with severe CHD phenotypes. We examined the association of mild CHD with chronic obstructive pulmonary disease (COPD) in the UK Biobank (UKB). Electronic health records (EHR) were used to identify 3385 CHD cases and 479,765 healthy controls in UKB, before performing a case-control analysis over a 20-year study period for a total of > 9.5 M person-years of follow-up. Our analysis showed that UKB participants with CHD are at substantially greater risk of developing COPD than healthy controls (8.7% vs 3.1% prevalence, unadjusted OR 2.98, 95% CI 2.63, 3.36, P = 1.40e-53). Slightly increased rates of smoking were observed amongst CHD cases, however the association with COPD was shown to be robust to adjustment for smoking and other factors known to modulate COPD risk within a multivariable-adjusted Cox regression framework (fully adjusted HR 2.21, 95% CI 1.97, 2.48, P = 5.5e-41). Care for adults with CHD should aim to mitigate their increased risk of COPD, possibly via increased smoking cessation support.

Joint analysis of functionally related genes yields further candidates associated with Tetralogy of Fallot.

Although several genes involved in the development of Tetralogy of Fallot have been identified, no genetic diagnosis is available for the majority of patients. Low statistical power may have prevented the identification of further causative genes in gene-by-gene survey analyses. Thus, bigger samples and/or novel analytic approaches may be necessary. We studied if a joint analysis of groups of functionally related genes might be a useful alternative approach. Our reanalysis of whole-exome sequencing data identified 12 groups of genes that exceedingly contribute to the burden of Tetralogy of Fallot. Further analysis of those groups showed that genes with high-impact variants tend to interact with each other. Thus, our results strongly suggest that additional candidate genes may be found by studying the protein interaction network of known causative genes. Moreover, our results show that the joint analysis of functionally related genes can be a useful complementary approach to classical single-gene analyses.

Effectiveness of a multidisciplinary rehabilitation program in real-world patients with chronic back pain: A pilot cohort data analysis.

BACKGROUND: Randomized clinical trials (RCT) suggest a multidisciplinary approach to pain rehabilitation is superior to other active treatments in improving pain intensity, function, disability, and pain interference for patients with chronic pain, with small effect size (ds= 0.20-0.36) but its effectiveness remains unknown in real-world practice. OBJECTIVE: The current study examined the effectiveness of a multidisciplinary program to a cognitive and behavioral therapy (pain-CBT) in real-world patients with chronic back pain. METHODS: Twenty-eight patients (M𝑎𝑔𝑒= 57.6, 82.1% Female) completed a multidisciplinary program that included pain psychology and physical therapy. Eighteen patients (M𝑎𝑔𝑒= 58.9, 77.8% Female) completed a CBT-alone program. Using a learning healthcare system, the Pain Catastrophizing Scale, 0-10 Numerical Pain Rating Scale, and Patient-Reported Outcomes Measurement Information System® measures were administered before and after the programs. RESULTS: We found significant improvement in mobility and pain behavior only after a multidisciplinary program (p's < 0.031; d= 0.69 and 0.55). We also found significant improvement in pain interference, fatigue, depression, anxiety, social role satisfaction, and pain catastrophizing after pain-CBT or multidisciplinary programs (p's < 0.037; ds = 0.29-0.73). Pain ratings were not significantly changed by either program (p's > 0.207). CONCLUSIONS: The effect of a multidisciplinary rehabilitation program observed in RCT would be generalizable to real-world practice.

Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.

Improvement in the quality of life of patients with persistent or long-standing persistent atrial fibrillation after hybrid ablation.

BACKGROUND: Hybrid ablation (i.e., a combination of a thoracoscopic surgical ablation followed by a catheter ablation) is a treatment option for patients with non-paroxysmal atrial fibrillation (AF). Despite its promising efficacy, it is a surgical procedure with a relatively high risk of complications that could affect the quality of life (QoL) of patients, even when sinus rhythm is restored. OBJECTIVE: To describe changes in the QoL of patients with non-paroxysmal AF before and after a hybrid ablation. METHODS: Patients after hybrid ablation for persistent or long-standing persistent AF were prospectively studied. Follow-up visits were scheduled at 1, 3, 6, 9, and 12 months. The maintenance of SR was assessed using 1-week Holter recordings at 6 and 12 months and 24-h Holter recordings at 3 and 9 months, or via an implantable loop recorder. QoL was assessed using the Atrial Fibrillation Effect on Quality-of-life (AFEQT) and the EuroQoL-5Dimensions (EQ-5D) questionnaires before and 12 months after ablation. RESULTS: Seventy-five patients (49 men, age 62.9 ± 8.45 years, 48 (64%) with long-standing persistent AF) were enrolled. Fifty-two (69.3%, SR group) were AF-free during the 12-month follow-up, 16 (21.3%, PAROX group) had only paroxysms of AF after ablation, and 7 (9.3%, PERM group) were on rate control due to permanent AF reoccurrence. The AFEQT score increased significantly in the SR group from 59.9 ± 19.4 to 91.4 ± 10.8 (p < 0.001), and in the PAROX group from 58.8 ± 19.0 to 81.5 ± 14.1 (p = 0.002) but remained unchanged in the PERM group (44.6 ± 7.5 vs. 47.4 ± 5.5, p = 0.24). The EQ-5D score significantly decreased in the descriptive part (from 7.90 ± 2.61 to 6.64 ± 1.90, p = 0.0001) and increased on the visual analog scale (from 63.56 ± 19.11 to 79.30 ± 16.9, p < 0.0001) in the SR group. In the PAROX group, no significant change was present on either the descriptive part (p = 0.3) or in the visual analog scale (p = 0.48). Similarly, no significant changes were present on either the descriptive part (p = 0.93) or the visual analog scale (p = 0.4) in the PERM group. CONCLUSION: The QoL of patients with non-paroxysmal AF and patients with AF paroxysms, after successful hybrid ablation, improved significantly in patients with SR. No significant improvement was present in patients on rate control after an unsuccessful ablation.

Five-year outcomes in cardiac surgery patients with atrial fibrillation undergoing concomitant surgical ablation versus no ablation. The long-term follow-up of the PRAGUE-12 Study.

BACKGROUND: The long-term effect of concomitant surgical ablation (SA) on clinical outcomes in an unselected population of patients has not been sufficiently reported in randomized studies. OBJECTIVE: The aim of this study was to assess clinical outcomes of the SA after 5 years of follow-up. METHODS: The PRAGUE-12 study was a prospective, randomized clinical trial assessing cardiac surgery with ablation for AF vs cardiac surgery alone. Patients with AF who were also indicated for cardiac surgery (coronary artery disease [CAD], valve surgery) were randomized to SA or control (no ablation) group. All patients were followed for 5 years. The primary endpoint was a composite of cardiovascular death, stroke, hospitalization for heart failure, or severe bleeding. Secondary endpoint was a recurrence of AF. RESULTS: A total of 207 patients were analyzed (SA group = 108 patients, control group = 99 patients). Both groups were similar relative to important clinical characteristics except for CAD, which was more common in the control group. Cumulative incidence curves showed a higher incidence of the primary endpoint in the control group (P = .024, Gray's test). However, after adjusting for all covariables, the difference between groups was not significant (subhazard ratio [SHR] 0.69 [0.47-1.02], P = .068). The incidence of stroke and AF recurrences were significantly reduced in the SA group, and remained significant even after adjustment for all covariables, including CAD (stroke: SHR 0.32 [0.12-0.84], P = .02, AF recurrences: SHR 0.44 [0.31-0.62], P < .001). CONCLUSIONS: Concomitant SA of AF is associated with a greater likelihood of maintaining sinus rhythm and a decreased risk of stroke.

Sleep-related problems and suicide behavior and ideation among Black and White trauma-exposed psychiatric inpatients.

OBJECTIVE: Sleep-related problems (SRPs) are associated with increased risk for suicide-related behavior and death. Given that Black adults report greater SRPs as compared to White adults, the purpose of the current study was to examine sleep problems, suicide-related psychiatric admission, and suicide ideation, in Black and White trauma-exposed adults. METHOD: Suicide-related behavior (i.e., intent, plan, and/or behavior) as reason for hospital admission was obtained via medical records review for 172 Black and White adults who were admitted to an acute-care psychiatric facility; all participants completed validated measures of sleep quality and suicide ideation. RESULTS: Adjusted logistic regression analyses revealed that sleep-related daytime dysfunction (AOR = 4.32, p < .05) and poor sleep quality (AOR = 3.64, p < .05) were associated with significantly increased odds that Black participants were admitted for suicide-related psychiatric care. Poorer sleep quality (AOR = 2.10, p < .05) was also associated with increased odds of suicide-related admission among White participants. However, shorter sleep duration was marginally associated with suicide ideation in Black participants only. CONCLUSIONS: SRPs may be related to suicide-related behavior and ideation differently for vulnerable Black and White adults. More research is needed to understand potential race group differences and mechanisms by which SRPs increase risk for suicide crisis across racial groups.

Perceived Discrimination and Suicide Ideation: Moderating Roles of Anxiety Symptoms and Ethnic Identity among Asian American, African American, and Hispanic Emerging Adults.

Suicide is a leading cause of death for vulnerable ethnic minority emerging adults in the United States (Web-based injury statistics query and reporting system [WISQARS], 2015). Perceived discrimination (Journal of Youth and Adolescence, 40, 2011, 1465) and anxiety symptoms (Asian American Journal of Psychology, 1, 2010, 18) are two predictors that are theoretically and conceptually related, but have yet to be examined in a simultaneous model for suicide ideation. Existing theory and research suggest that these variables activate similar pathways (American Behavioral Scientist, 51, 2007, 551). This study sought to address this gap in the literature by examining the simultaneous relationship between perceived discrimination and anxiety symptoms as predictors of suicide ideation. The moderating effect of anxiety symptoms on the relationship between perceived discrimination and suicide ideation was examined in a multiethnic sample of emerging adults. Results indicated that anxiety symptoms moderated the perceived discrimination-suicide ideation relationship for Hispanic emerging adults, but not for their Asian American and African American counterparts. Furthermore, ethnic identity has been shown to mitigate suicide risk in the face of other stressors (Cultural Diversity and Ethnic Minority Psychology, 14, 2008, 75). Ethnic identity emerged as a protective factor for Hispanic emerging adults by further interacting with perceived discrimination and anxiety symptoms to negatively predict suicide ideation. The implications of these findings are discussed.

Deciphering Protein Glycosylation by Computational Integration of On-chip Profiling, Glycan-array Data, and Mass Spectrometry.

The difficulty in uncovering detailed information about protein glycosylation stems from the complexity of glycans and the large amount of material needed for the experiments. Here we report a method that gives information on the isomeric variants of glycans in a format compatible with analyzing low-abundance proteins. On-chip glycan modification and probing (on-chip gmap) uses sequential and parallel rounds of exoglycosidase cleavage and lectin profiling of microspots of proteins, together with algorithms that incorporate glycan-array analyses and information from mass spectrometry, when available, to computationally interpret the data. In tests on control proteins with simple or complex glycosylation, on-chip gmap accurately characterized the relative proportions of core types and terminal features of glycans. Subterminal features (monosaccharides and linkages under a terminal monosaccharide) were accurately probed using a rationally designed sequence of lectin and exoglycosidase incubations. The integration of mass information further improved accuracy in each case. An alternative use of on-chip gmap was to complement the mass spectrometry analysis of detached glycans by specifying the isomers that comprise the glycans identified by mass spectrometry. On-chip gmap provides the potential for detailed studies of glycosylation in a format compatible with clinical specimens or other low-abundance sources.

Rise and shine: A treatment experiment testing a morning routine to decrease subjective sleep inertia in insomnia and bipolar disorder.

Sleep inertia involves decreased performance or disorientation upon waking that lasts several hours and impairs functioning. Though sleep inertia is common in insomnia and may interfere with treatment, Cognitive Behavioral Therapy for Insomnia (CBTI) does not routinely include a component to address sleep inertia. The present study evaluates such a component, the RISE-UP routine, in CBTI for insomnia comorbid with bipolar disorder. We hypothesized that the RISE-UP routine would increase physical activity in the morning and reduce the duration and severity of self-reported sleep inertia. Sleep and sleep inertia were monitored in the week prior to and following the intervention with daily sleep diaries, actigraphy, and ecological momentary assessment (EMA). Participants were randomized to a bipolar-specific modification of CBT-I (CBTI-BP) with RISE-UP (N = 20) or a psychoeducation (PE) comparison condition (N = 20). The treatment experiment (RISE-UP vs PE) was completed in the first treatment session. RISE-UP reduced the duration and severity of self-reported sleep inertia, as measured by diary reports and by EMA ratings, and was rated as acceptable and credible. Compliance was high, and increases in morning activity levels were verified via actigraphy. Addressing morning sleep inertia via behavioral modifications upon waking may be a useful addition to CBTI.

Does purpose in life or ethnic identity moderate the association for racial discrimination and suicide ideation in racial/ethnic minority emerging adults?

OBJECTIVE: To examine purpose in life (PIL) and ethnic identity (EI) as buffers to suicide ideation for Asian American, Hispanic, and Black emerging adults who perceive racial discrimination. METHOD: Two-hundred eighty-nine undergraduate students enrolled at a large university in the southwestern region of the United States (40.8% Asian American, 32.5% Hispanic, 26.6% Black; 61.2% women; mean age = 20.47, SD = 1.83) reported on experiences of racial discrimination, PIL, EI, and suicidal thoughts. Covariates were intrinsic religiosity, gender, and age. RESULTS: Regression analysis showed that EI was not a significant moderator for the association between perceived racial discrimination (PRD) and suicidal ideation (ß = -.08, p = .13; 95% confidence interval (CI) [-.19, .03]). However, PIL was a significant moderator (ß = -.11, p = .025; CI [-.20, -.01]). A hierarchical regression showed that PIL as a moderator explained additional variance (ΔR2 = 0.11, p < .001) in suicide ideation above and beyond EI. CONCLUSIONS: These findings provide some insight into how life purpose might ameliorate the impact of social stressors above and beyond a positive cultural identity for young racial/ethnic minority adults. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Molecular insights into genome-wide association studies of chronic kidney disease-defining traits.

Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.

Evaluación del proceso de soporte nutricional en un hospital comarcal / Evaluation of nutritional support in a regional hospital

Introducción: La desnutrición relacionada con la enfermedad (DRE) es una enfermedad con alta prevalencia en el medio hospitalario español (uno de cada 4 pacientes). La alianza «Más Nutridos» ha desarrollado un plan de acción para combatir esta entidad. El Sistema Extremeño de Salud ha incluido el cribado nutricional como único paso para luchar contra la DRE. Se realiza una evaluación de los resultados obtenidos por esta estrategia. Pacientes y métodos: Estudio de concordancia en condiciones de práctica clínica habitual estudiando los siguientes indicadores: tasa de cribado nutricional, tasa de diagnósticos nutricionales codificados, tasa de pacientes con valoración del estado nutricional (VEN), tasa de pacientes con cálculo de requerimientos en función de la situación clínica y el estado nutricional, tasa de pacientes con cumplimiento de requerimientos calóricos y proteicos estimados, tasa de pacientes con peso al ingreso, tasa de pacientes con talla al ingreso, tasa de pacientes con peso al alta, tasa de pacientes derivados a la Unidad de Nutrición Clínica y Dietética (UNCYD). Se comparan con los datos obtenidos por el programa de lucha contra la desnutrición en Holanda, que se utilizaron como estándares. Resultados: La tasa de cribado nutricional ascendió al 20,5% (IC95: 18,00-21,00%). La tasa de codificación y de valoración del estado nutricional al ingreso fue del 13%. El peso se determinó en el 16,5% de los pacientes al ingreso y en el 20% al alta (mismo resultado para talla). En el 30% se realizó un cálculo de requerimientos, que no fue prácticamente monitorizado (4 de 30 pacientes). Solo el 15% de los pacientes fueron derivados a la UNCYD. Todos los indicadores obtuvieron valores significativamente inferiores a los estándares (p<0,05), con valores de Kappa que en todo caso fueron inferiores a 0,2. El análisis ofreció resultados peores tras suprimir los pacientes atendidos por la UNCYD. Conclusiones: Una estrategia integral de detección y tratamiento de desnutrición propuesta por el Sistema Extremeño de Salud basada solamente en un cribado nutricional es ineficiente a todos los efectos en un hospital de las características del HVP

Introduction: Disease-related malnutrition (DRM) is highly prevalent in Spanish hospitals (occurring in 1 out of every 4 patients). The 'Más Nutridos' Alliance has developed an action plan to detect and treat DRM. In Extremadura (Spain), the public health system has included nutritional screening as the only mechanism to fight malnutrition. The results of this strategy are evaluated here. Patients and methods: An agreement study was conducted in standard clinical practice. Variables collected included the following rates: nutritional screening at entry, coded nutritional diagnoses, nutritional status assessment, nutritional requirements, successful nutritional therapy, weight and height at entry and discharge, referral to a nutritional support unit (NSU). Standards to comparison based on the results of the Netherland Program to Fight Malnutrition. Results: Nutritional screening rate at entry was 20.5% (95% CI: 18.00-21.00). Coding and nutritional status assessment rate at entry was 13%. Weight and height were both measured in 16.5% of patients at entry and 20% at discharge. Nutritional requirements were estimated in 30% and were poorly monitored (13.3%). Only 15% of patients were referred to a NSU. Significantly lower values were found for all indicators as compared to standards, with kappa values lower than 0.2 in all cases. Data analysis showed poorer results when patients referred to the NSU were excluded. Conclusions: A strategy to fight malnutrition based on nutritional screening alone is highly inefficient in hospitals such as HVP

Archetypal transcriptional blocks underpin yeast gene regulation in response to changes in growth conditions.

The transcriptional responses of yeast cells to diverse stresses typically include gene activation and repression. Specific stress defense, citric acid cycle and oxidative phosphorylation genes are activated, whereas protein synthesis genes are coordinately repressed. This view was achieved from comparative transcriptomic experiments delineating sets of genes whose expression greatly changed with specific stresses. Less attention has been paid to the biological significance of 1) consistent, albeit modest, changes in RNA levels across multiple conditions, and 2) the global gene expression correlations observed when comparing numerous genome-wide studies. To address this, we performed a meta-analysis of 1379 microarray-based experiments in yeast, and identified 1388 blocks of RNAs whose expression changes correlate across multiple and diverse conditions. Many of these blocks represent sets of functionally-related RNAs that act in a coordinated fashion under normal and stress conditions, and map to global cell defense and growth responses. Subsequently, we used the blocks to analyze novel RNA-seq experiments, demonstrating their utility and confirming the conclusions drawn from the meta-analysis. Our results provide a new framework for understanding the biological significance of changes in gene expression: 'archetypal' transcriptional blocks that are regulated in a concerted fashion in response to external stimuli.