Interaction Control and Bright Solitons in Coherently Coupled Bose-Einstein Condensates.

We demonstrate fast control of the interatomic interactions in a Bose-Einstein condensate by coherently coupling two atomic states with intra- and interstate scattering lengths of opposite signs. We measure the elastic and inelastic scattering properties of the system and find good agreement with a theoretical model describing the interactions between dressed states. In the attractive regime, we observe the formation of bright solitons formed by dressed-state atoms. Finally, we study the response of the system to an interaction quench from repulsive to attractive values, and observe how the resulting modulational instability develops into a bright soliton train.

Selective CD8 cell reduction by SARS-CoV-2 is associated with a worse prognosis and systemic inflammation in COVID-19 patients.

The lymphopenia exhibited in patients with COVID-19 has been associated with a worse prognosis in the development of the disease. To understand the factors associated with a worse evolution of COVID-19, we analyzed comorbidities, indicators of inflammation such as CRP and the ratio of neutrophils/lymphocytes, as well as the count of blood cells with T-lymphocyte subtypes in 172 hospitalized patients with COVID-19 pneumonia. Patients were grouped according to their needs for mechanical ventilation (ICU care) or not. Within the comorbidities studied, obesity was the only associated with greater severity and ICU admission. Both the percentage and the absolute number of neutrophils were higher in patients needing ICU care than non-ICU patients, whereas absolute lymphocyte count, and especially the percentage of lymphocytes, presented a deep decline in critical patients. There was no difference between the two groups of patients for CD4 T-lymphocytes, neither in percentage of lymphocyte nor in absolute number, however for CD8 T-cells the differences were significant for both parameters which were in decline in ICU patients. There was a firm correlation between the highest values of inflammation indicators with the decrease in percentage of CD8 T-lymphocytes. This effect was not seen with CD4 cells. Obesity together with lymphopenia, especially whether preferentially affects to CD8 T- lymphocytes, are factors that can predict a poor prognosis in patients with COVID-19.

Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

ECT beyond unipolar major depression: systematic review and meta-analysis of electroconvulsive therapy in bipolar depression.

OBJECTIVE: In this systematic review and meta-analysis, the response, remission, and speed of response in adults with major depressive disorder (MDD) and bipolar disorder in depressive episode (BDD) receiving an acute course of electroconvulsive therapy (ECT) were quantitatively analyzed. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, 1660 citations were identified through five electronic databases. Nineteen articles met final inclusion criteria for meta-analysis. RESULTS: The pooled response and remission rates with ECT in MDD were 74.2% (n = 1246/1680) and 52.3% (n = 850/1626), respectively. In BDD, they were 77.1% (n = 437/567) and 52.3% (n = 275/377), respectively. Although response rates to ECT were statistically higher in BDD (OR = 0.73, 95% CI: 0.56-0.95, P = 0.02), remission rates were similar (OR = 0.91, 95% CI: 0.65-1.26, P = 0.56). Individuals with BDD vs. MDD required fewer number of ECT sessions to achieve response (SMD = -0.23, 95% CI: -0.44 to -0.023, P = 0.03). There were no significant moderator effects identified. CONCLUSION: Response rates and speed of response are higher in individuals with BDD; however, remission rates are equivalent. These findings support increased utilization of ECT in individuals with treatment-refractory BDD.

Preventing the recurrence of depression with a Mediterranean diet supplemented with extra-virgin olive oil. The PREDI-DEP trial: study protocol.

BACKGROUND: The role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil-enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition. METHODS: Multicenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform ( https://predidep.es/participantes/ ) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year. DISCUSSION: To the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients. TRIAL REGISTRATION: The study has been prospectively registered in the U.S. National Library of Medicine ( https://clinicaltrials.gov ) with NCT number: NCT03081065.

[Treatment of Hodgkin lymphoma. Analysis of 915 patients]. / Evaluación del tratamiento de linfoma de Hodgkin con esquema ABVD en Chile.

BACKGROUND: Hodgkin lymphoma has a high rate of curability, even in advanced stages. AIM: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. MATERIAL AND METHODS: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. RESULTS: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. CONCLUSIONS: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.

[Autoimmune hemolytic anemia. Review of 43 cases]. / Anemia hemolítica autoinmune en Chile: un análisis retrospectivo de 43 pacientes.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is an uncommon disease. In its presentation, it can be severe and even lethal. There is only one clinical report concerning this pathology in Chile. OBJECTIVE: To describe the clinical characteristics and evolution of adult AIHA inpatients. MATERIALS AND METHODS: Retrospective review of clinical records of adult AIHA inpatients between January 2010 and June 2018 was done. Demographic, clinical, laboratory and therapeutic information was analyzed. A descriptive, analytical and survival analysis was performed. RESULTS: Forty-three adult patients diagnosed with AHIA were hospitalized in a period of 8 years. Median age was 63 years (range 22-86 years), mostly women (72%). Warm antibodies were detected in 36 cases (84%) and cold antibodies in seven. Seventy two percent of the patients had an underlying cause, and 58% were secondary to lymphoproliferative neoplasms. All patients except two, received steroids as initial treatment, with response in 37 (90%) of them. Three refractory patients received rituximab, with response in all of them, and relapse in one. Median follow-up was 38 months (range 2-98 months). Five year overall survival was 72%. CONCLUSION: AHIA in adults inpatients is a heterogeneous disease, mainly due to warm antibodies, and to secondary etiology.

Bright Soliton to Quantum Droplet Transition in a Mixture of Bose-Einstein Condensates.

Attractive Bose-Einstein condensates can host two types of macroscopic self-bound states: bright solitons and quantum droplets. Here, we investigate the connection between them with a Bose-Bose mixture confined in an optical waveguide. We show theoretically that, depending on atom number and interaction strength, solitons and droplets can be smoothly connected or remain distinct states coexisting only in a bistable region. We measure their spin composition, extract their density for a broad range of parameters, and map out the boundary of the region separating solitons from droplets.

[Myasthenia gravis and its association with lymphoproliferative disorders: a case series]. / Miastenia gravis y su asociación con trastornos linfoproliferativos: casos clínicos.

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. It is characterized by variable weakness and excessive fatigability of skeletal muscles. In the last few years, numerous reports have been published showing the association between autoimmune diseases, such as systemic erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The association between MG and lymphoid neoplasia seems to be less frequent. To analyze this association we reviewed the MG patients in the Department of Neurology, Hospital Salvador of Santiago, Chile. During a three-year period we identified four patients who developed different lymphoproliferative disorders: two with B-cell lymphoma, one with chronic lymphocytic leukaemia and one plasmacytoma with an associated amyloidosis. The MG was generalized but mild, all cases classified as type IIa according to the definition proposed by the MG Foundation of America. The neoplasia appeared two to 36 years after the onset of MG. These cases provide additional evidence of the association between MG and lymphoproliferative disorders.

[Impact of the Chilean Explicit Guaranties Health System (GES) on breast cancer treatment]. / Resultados del tratamiento del cáncer de mama, Programa Nacional de Cáncer del Adulto.

Background Breast cancer is the most common malignant tumor in women in the world. In 2005, it was incorporated to the Explicit Guaranties Health System (GES) in Chile. Aim To describe the demographic and clinical characteristics of breast cancer patients and to determine the effect of incorporating these women to GES. Material and Methods Medical records of 5,119 women with breast cancer aged 59 ± 14 years, attended at six public hospitals between 2000 and 2010 were reviewed. Median follow up was 87 months (range 1-182). Mortality was assessed using death certificates obtained at the National Identification Registry. Results Sixty six percent of women were in stage I-II, 29% in stage III and 5% in stage IV. Surgery was performed in 4023/5119 cases (79%), adyuvant radiotherapy in 3627/4517 cases (80%), chemotherapy in 3,204/3,424 cases (94%) and hormone therapy in 1,695/2,375 cases (71%). Between 2000 and 2010, there was a significant increase in the proportion of cases in stage I, from 8% to 25%, (p < 0.01). Overall survival (OS) increased 1% per year, since the beginning of GES system (p = 0.024). Five year OS was 75.1%. The figures for Stage I, II, III and IV were 93, 84, 62 and 27% respectively (p < 0.01). Patients without lymph node involvement and who were not triple negative, had a significantly better OS. Conclusions There was a significant increase in stage I cases, and a 1% per year OS improvement after GES system started, compared with the previous period.

Positive influence of a dental anaesthesia simulation model on the perception of learning by Mexican dental students.

INTRODUCTION: This study evaluated the influence of three-repetition training with a dental anaesthesia simulation model (DASM) on the perception of learning by dental students. MATERIALS AND METHODS: Dental students who had never used a dental anaesthesia technique were randomly divided into two groups that were taught the anterior superior alveolar nerve infiltrative anaesthesia technique. Group 1 (G1; N = 10) followed a three-stage learning method: (i) theoretical lecture, (ii) clinical demonstration and (iii) DASM training, including three repetitions of the anaesthesia technique. Group 2 (G2; N = 10) followed only the 1st and 2nd stages. The students in both groups then performed the anaesthesia technique. The perception of the students was evaluated by four learning concepts. Each was evaluated with a 5-point Likert scale questionnaire. The average score of each item of the questionnaire for G1 was compared with that of G2. Statistically significant differences were identified with the Mann-Whitney test. The average working time of each group was timed and compared by Student's t-test to identify possible statistically significant differences. RESULTS: Students in G1 showed higher average scores of perception in controlling the handling of the dental syringe and confidence in performing the injection (P < 0.05) and showed an average working time shorter than that of the students in G2 (P < 0.05). CONCLUSION: The DASM positively influenced the perception learning of the dental students; it increased their confidence and syringe handling ability, as well as skills to perform the injection of anaesthesia more quickly.

Serological profile and clinical features of nucleolar antinuclear pattern in patients with systemic lupus erythematosus from southwestern Spain.

Nucleolar staining of antinuclear antibodies (ANAs) is not exclusive to patients suffering systemic sclerosis (SSc) since it can occur in other autoimmune diseases, such as systemic lupus erythematosus (SLE). The nucleolar ANA pattern presents a low incidence in patients with SLE, with less than 9% reported in some studies. The significance of nucleolar staining and antinucleolar antibodies (ANoA) in SLE is still unknown, as is its association with clinical manifestations. To address these issues, a case-control study was carried out. Twenty-eight cases of SLE with nucleolar staining were enrolled, as well as 73 controls with no nucleolar staining and different ANA patterns (homogeneous, speckled, and combined homogeneous and speckled). The homogeneous nucleolar pattern was the most frequent (27 out of 28), and in 75% was combined with other ANA patterns. The anti-double stranded DNA antibodies showed no differences between the two groups of patients, nor the auto-antibodies detected by line immunoassay (LIA). However, we have found an increased frequency of anti-PM-Scl antibodies with respect to the controls (p = 0.02), in addition to the association between Raynaud's phenomenon (RP) and anti-PM-Scl antibodies (OR = 20.72, 95% CI 1.33-323.19, p = 0.03). Moreover, the cases of SLE showed a 7.78-fold increase in the risk of developing cancer (95%, CI 1.85-32.75, p = 0.005) with respect to the control group. Taken together these findings suggest that nucleolar staining represents a comorbidity factor in patients with SLE, although its significance must still be determined.

Immunotherapy reduces CD40L expression and modifies cytokine production in the CD4 cells of pollen allergy patients.

BACKGROUND: Allergen-specific immunotherapy (SIT) is the only intervention for IgE-mediated respiratory disorders. OBJECTIVE: The aim of the study was to investigate the immunological modifications induced by SIT in patients allergic to olive and/or grass pollen by attempting to establish an association between these modifications and clinical improvements. METHODS: We studied 29 patients who were allergic to olive and/or grass pollen. Patients were randomized to 2 groups: an active treatment group, comprising 19 allergic patients who received SIT, and a control group, formed by 10 allergic patients who received pharmacological treatment for their allergic symptoms but not immunotherapy. We used flow cytometry to analyze intracellular expression of the cytokines IL-4, IFN-gamma, IL-10, and TGF-beta1 in CD4+ T cells, as well as expression of Foxp3, the costimulatory CTLA-4 molecule, and the non-costimulatory CD40L molecule. To assess clinical changes, patients recorded their medication consumption, symptoms, and the limitation of daily activities using diary cards and quality of life questionnaires. RESULTS: Six months after initiation of SIT, we recorded a reduction in cell surface CD40L expression in the CD4+ T-cell population and a shift in the cytokine production profile (decrease in IL-4-producing CD4+ T cells and increase in IFN-gamma, IL-10, and TGF-beta1). These changes persisted after 12 months. Simultaneously, a clinical improvement was observed. CONCLUSIONS: SIT-induced clinical improvement is the result of immunological modifications such as a reduction in CD40L expression on CD4 cells and alteration in the cytokine production profile.

Short communication: Effects of increasing protein and energy in the milk replacer with or without direct-fed microbial supplementation on growth and performance of preweaned Holstein calves.

Forty-four Holstein calves were fed a direct-fed microbial (DFM) and 1 of 2 milk replacers to evaluate calf performance and growth. Treatments were (1) a control milk replacer [22:20; 22% crude protein (CP) and 20% fat], (2) an accelerated milk replacer (27:10; 27% CP and 10% fat), (3) the control milk replacer with added DFM (22:20+D), and (4) the accelerated milk replacer with added DFM (27:10+D). Dry matter intake, rectal temperatures, respiration scores and rates, and fecal scores were collected daily. Body weight, hip and withers height, heart girth, blood, and rumen fluid samples were collected weekly. Effects of treatment, sex, week, and their interactions were analyzed. Calves fed an accelerated milk replacer, regardless of DFM supplementation, consumed more CP and metabolizable energy in the milk replacer. No treatment differences were found for starter intake or intake of neutral detergent fiber or acid detergent fiber in the starter. Calves fed the accelerated milk replacer had greater preweaning and weaning body weight compared with calves fed the control milk replacer. Average daily gain was greater during the preweaning period for calves fed the accelerated milk replacer, but the same pattern did not hold true during the postweaning period. Feed efficiency did not differ among treatments. Hip height tended to be and withers height and heart girth were greater at weaning for calves fed the accelerated milk replacer compared with calves fed the control milk replacer. Fecal scores were greatest in calves fed DFM. Overall acetate, propionate, butyrate, and n-valerate concentrations were lower in calves fed the accelerated milk replacer, but DFM did not have an effect. Rumen pH was not different. Blood metabolites were unaffected by DFM supplementation, but calves fed the accelerated milk replacer had increased partial pressure of CO2, bicarbonate, and total bicarbonate in the blood. Direct-fed microbial supplementation did not appear to benefit the calf in this trial.

Direct and deferred sediment-transport events and seafloor disturbance induced by trawling in submarine canyons.

Bottom trawling on marine environments can drastically modify seafloor geomorphology and sedimentary dynamics not only on the fishing grounds but also in adjacent downslope regions, particularly in submarine canyons environments, which are hotspots of benthic biomass and productivity in the deep sea. When this type of fishery occurs along submarine canyon flanks, it can induce sediment gravity flows that descend along tributary gullies towards the main canyon axis. However, these flows had only been clearly identified in the Palamós Canyon, where they could be recorded synchronously with the passage of the trawling fleet. In this study we also recorded trawl-induced sediment gravity flows in the Blanes Canyon, both synchronously and asynchronously with the passage of trawlers. Increases in particulate matter fluxes in other trawled submarine canyons occurring in absence of natural triggering mechanisms, were not directly associated with bottom trawling because of the lack of direct synchronicity of these events with this human activity. Here we show, however, that the practice of bottom trawling along canyon flanks can not only resuspend and directly trigger sediment gravity flows, but they can also pile up disturbed sediment on steep areas, which can become unstable and collapse afterwards, asynchronically with the passage of trawlers. Our study provides evidence that sediment gravity flows in submarine canyons affected by bottom trawling, where the causal mechanisms are presently unidentified, may potentially be linked to instabilities in sediment originating from recurrent bottom trawling, which can precondition these events.

Long-Term Treatment with Alcaligenes faecalis A12C Improves Host Resistance to Pathogens in Septic Rats: Possible Contribution of Curdlan-Like Immune Trainer.

Curdlan, a ß-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1ß, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.

Differential expression of CD30 on CD3 T lymphocytes in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune systemic disease caused as a result of an imbalance of Th1-/Th2-type cytokines. The soluble form of CD30 (CD30s) released from peripheral blood cells has been described as a marker of active disease in Th2-type immune response as in SLE. However, the expression of CD30 on CD3 T lymphocytes from patients with SLE has not been studied yet. Therefore, we have addressed our study to attempt this issue, studying CD30 expression by flow cytometry on CD3 T lymphocytes and CD4/CD8 subsets in samples from SLE patients mainly with lupus nephritis. In parallel, we have determined the production of the cytokines IL-4 (Th2), IFNγ (Th1), IL-10 and TGFß by intracellular staining. Differences between positive CD30 T cells in healthy controls and patients with SLE were found, with a higher percentage of CD30-expressing T cells in patients with SLE (P = 0.001). In contrast to healthy controls, CD30 was mainly expressed on CD8 T cells from patients with SLE. The intracellular cytokine staining showed that TGFß is the main cytokine expressed in CD3 T cells from patients with SLE. In addition to this, we have found a positive correlation between CD30-expressing T cells and IL-4, IFNγ, and immunosuppressive cytokines (IL-10 and TGFß) (P < 0.05). These results suggest that CD30 could play a role in the pathogenesis of SLE and its expression on CD3 T lymphocytes is not restricted only to Th2-type response.

Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle.

BACKGROUND: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake. METHODS: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing. RESULTS: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF physiology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 µg/L). Analysing the correlation between various iron parameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes. CONCLUSIONS: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT03671122.

Complex traits analysis of chicken growth using targeted genetical genomics.

Dissecting the genetic control of complex trait variation remains very challenging, despite many advances in technology. The aim of this study was to use a major growth quantitative trait locus (QTL) in chickens mapped to chromosome 4 as a model for a targeted approach to dissect the QTL. We applied a variant of the genetical genomics approach to investigate genome-wide gene expression differences between two contrasting genotypes of a marked QTL. This targeted approach allows the direct quantification of the link between the genotypes and the genetic responses, thus narrowing the QTL-phenotype gap using fewer samples (i.e. microarrays) compared with the genome-wide genetical genomics studies. Four differentially expressed genes were localized under the region of the QTL. One of these genes is a potential positional candidate gene (AADAT) that affects lysine and tryptophan metabolism and has alternative splicing variants between the two genotypes. In addition, the lysine and glycolysis metabolism pathways were significantly enriched for differentially expressed genes across the genome. The targeted approach provided a complementary route to fine mapping of QTL by characterizing the local and the global downstream effects of the QTL and thus generating further hypotheses about the action of that QTL.