[The impact of novel drugs on the survival of patients with multiple myeloma in two chilean centers]. / Mieloma múltiple en Chile. Uso de drogas noveles en dos centros nacionales.

BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. AIM: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. RESULTS: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

Subclinical Ultrasound Characteristics of Infantile Hemangiomas That May Potentially Affect Involution.

OBJECTIVES: Infantile hemangiomas (IHs) are the most common benign tumors in children. Color Doppler ultrasound is a noninvasive imaging modality that can show subclinical anatomic parameters in a wide range of dermatologic conditions. The purpose of this study was to describe the ultrasound characteristics of IHs and look for subclinical features with the potential to influence the involution and therapeutic response. METHODS: A review of the ultrasound database of children with clinical and ultrasound IH diagnoses was conducted. The clinically reported duration and the ultrasound assessment of the proliferative phase were compared. Descriptive and statistical analyses of qualitative and quantitative parameters of the series were performed. Significance was set at P < .05. RESULTS: A total of 204 IHs were included. Twenty percent had arteriovenous shunts; 15% had afferent branches from main regional arteries; and almost 30% showed involvement of deep structures. Sixty-one percent of IHs were in the head and neck. Deep hemangiomas showed significantly thicker lesional vessels. A prolonged proliferative stage was significantly associated with a higher presence of arteriovenous shunts and a higher peak systolic velocity of the arterial vessels (≥15 cm/s) within the lesions. CONCLUSIONS: Color Doppler ultrasound can support the detection of subclinical anatomic features that may potentially influence the involution and response to treatment of IHs. Some of these characteristics may serve as potential markers to predict and manage IHs in prolonged proliferative stages.

Seventy-MHz Ultrasound Detection of Early Signs Linked to the Severity, Patterns of Keratin Fragmentation, and Mechanisms of Generation of Collections and Tunnels in Hidradenitis Suppurativa.

OBJECTIVES: To test the capability of 70-MHz ultrasound for detecting initial ultrasound signs of hidradenitis suppurativa (HS) linked to severity. METHODS: A cross-sectional study of the ultrasound images of patients with HS was conducted and compared with a healthy control group. Detection and identification of early subclinical ultrasound signs in the lesional and perilesional areas of the HS cases in comparison with the control group were performed. Statistical analyses included mean, dispersion measures, the Kruskal-Wallis test, and bivariate and multivariate ordered logistic regression studies. Significance was assessed at P < .05. RESULTS: A total of 139 patients with HS met the criteria and showed abnormalities of the hair follicles such as a curved shape, ballooning, and protrusion into pseudocysts, collections, or tunnels (donor of keratin sign). Significant increases in the sizes of the hair follicles and hair shafts were found in HS cases. The following ultrasound signs were significantly linked to severity: a connecting band between the base of adjacent hair follicles (bridge sign), a fragment of the hair shaft extruding through a dilated hair follicle (sword sign), and retained cylindrical fragments of keratin in the dermis. Two patterns of fragmentation of the keratin were detected: multifragment and cylindrical. CONCLUSIONS: Ultrasound can detect early HS signs that are significantly linked to severity and 2 types of fragmentation of the keratin, which could support the generation and perpetuation of the fluid collections and tunnels. These ultrasound signs can help prompt diagnosis and management, the development and testing of medications, and the measure of treatment outcomes in HS.

Identification of a nuclear localization signal and importin beta members mediating NUAK1 nuclear import inhibited by oxidative stress.

NUAK1 is a serine/threonine kinase member of the AMPK-α family. NUAK1 regulates several processes in tumorigenesis; however, its regulation and molecular targets are still poorly understood. Bioinformatics analysis predicted that the majority of NUAK1 localizes in the nucleus. However, there are no studies about the regulation of NUAK1 subcellular distribution. Here, we analyzed NUAK1 localization in several human cell lines, mouse embryo fibroblasts, and normal mouse tissues. We found that NUAK1 is located in the nucleus and also in the cytoplasm. Through bioinformatics analysis and studies comparing subcellular localization of wild type and NUAK1 mutants, we identified a conserved bipartite nuclear localization signal at the N-terminal domain of NUAK1. Based on mass spectrometry analysis, we found that NUAK1 interacts with importin-ß members including importin-ß1 (KPNB1), importin-7 (IPO7), and importin-9 (IPO9). We confirmed that importin-ß members are responsible for NUAK1 nuclear import through the inhibition of importin-ß by Importazole and the knockdown of either IPO7 or IPO9. In addition, we found that oxidative stress induces NUAK1 cytoplasmic accumulation, indicating that oxidative stress affects NUAK1 nuclear transport. Thus, our study is the first evidence of an active nuclear transport mechanism regulating NUAK1 subcellular localization. These data will lead to investigations of the molecular targets of NUAK1 according to its subcellular distribution, which could be new biomarkers or targets for cancer therapies.

ß-catenin aggregation in models of ALS motor neurons: GSK3ß inhibition effect and neuronal differentiation.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron death. A 20% of familial ALS cases are associated with mutations in the gene coding for superoxide dismutase 1 (SOD1). The accumulation of abnormal aggregates of different proteins is a common feature in motor neurons of patients and transgenic ALS mice models, which are thought to contribute to disease pathogenesis. Developmental morphogens, such as the Wnt family, regulate numerous features of neuronal physiology in the adult brain and have been implicated in neurodegeneration. ß-catenin is a central mediator of both, Wnt signaling activity and cell-cell interactions. We previously reported that the expression of mutant SOD1 in the NSC34 motor neuron cell line decreases basal Wnt pathway activity, which correlates with cytosolic ß-catenin accumulation and impaired neuronal differentiation. In this work, we aimed a deeper characterization of ß-catenin distribution in models of ALS motor neurons. We observed extensive accumulation of ß-catenin supramolecular structures in motor neuron somas of pre-symptomatic mutant SOD1 mice. In cell-cell appositional zones of NSC34 cells expressing mutant SOD1, ß-catenin displays a reduced co-distribution with E-cadherin accompanied by an increased association with the gap junction protein Connexin-43; these findings correlate with impaired intercellular adhesion and exacerbated cell coupling. Remarkably, pharmacological inhibition of the glycogen synthase kinase-3ß (GSK3ß) in both NSC34 cell lines reverted both, ß-catenin aggregation and the adverse effects of mutant SOD1 expression on neuronal differentiation. Our findings suggest that early defects in ß-catenin distribution could be an underlying factor affecting the onset of neurodegeneration in familial ALS.

Ultrasound Characteristics of the Hair Follicles and Tracts, Sebaceous Glands, Montgomery Glands, Apocrine Glands, and Arrector Pili Muscles.

OBJECTIVES: To explore the capability of very high-frequency ultrasound (US; 50-71 MHz) to detect the normal morphologic characteristics of the hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles. METHODS: A retrospective study, approved by the Institutional Review Board, evaluated the normal US morphologic characteristics of the hair and adnexal structures in a database of very high-frequency US images extracted from the perilesional or contralateral healthy skin of 1117 consecutive patients who underwent US examinations for localized lesions of the skin and 10 healthy individuals from December 2017 to June 2018. These images were matched with their counterparts from the database of normal histologic images according to the corporal region. The Cohen concordance test and regional mean diameters of the hair follicles and adnexal structures were analyzed. RESULTS: The normal hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles were observed on US images and matched their histological counterparts in all the corporal regions. There was significant US concordance (κ = 0.82; P = .0001) among observers. Regional mean diameters (millimeters) of the hair follicles, sebaceous glands, and apocrine glands are provided. CONCLUSIONS: The hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles are detectable with very high-frequency US, including some regional and anatomic variants. Knowledge of their normal US appearances is a requisite for detecting subclinical changes, understanding the physiopathologic characteristics, and supporting the early diagnosis and management of common dermatologic diseases.

A Remote Collaborative Care Program for Patients with Depression Living in Rural Areas: Open-Label Trial.

BACKGROUND: In the treatment of depression, primary care teams have an essential role, but they are most effective when inserted into a collaborative care model for disease management. In rural areas, the shortage of specialized mental health resources may hamper management of depressed patients. OBJECTIVE: The aim was to test the feasibility, acceptability, and effectiveness of a remote collaborative care program for patients with depression living in rural areas. METHODS: In a nonrandomized, open-label (blinded outcome assessor), two-arm clinical trial, physicians from 15 rural community hospitals recruited 250 patients aged 18 to 70 years with a major depressive episode (DSM-IV criteria). Patients were assigned to the remote collaborative care program (n=111) or to usual care (n=139). The remote collaborative care program used Web-based shared clinical records between rural primary care teams and a specialized/centralized mental health team, telephone monitoring of patients, and remote supervision by psychiatrists through the Web-based shared clinical records and/or telephone. Depressive symptoms, health-related quality of life, service use, and patient satisfaction were measured 3 and 6 months after baseline assessment. RESULTS: Six-month follow-up assessments were completed by 84.4% (221/250) of patients. The remote collaborative care program achieved higher user satisfaction (odds ratio [OR] 1.94, 95% CI 1.25-3.00) and better treatment adherence rates (OR 1.81, 95% CI 1.02-3.19) at 6 months compared to usual care. There were no statically significant differences in depressive symptoms between the remote collaborative care program and usual care. Significant differences between groups in favor of remote collaborative care program were observed at 3 months for mental health-related quality of life (beta 3.11, 95% CI 0.19-6.02). CONCLUSIONS: Higher rates of treatment adherence in the remote collaborative care program suggest that technology-assisted interventions may help rural primary care teams in the management of depressive patients. Future cost-effectiveness studies are needed. TRIAL REGISTRATION: Clinicaltrials.gov NCT02200367; https://clinicaltrials.gov/ct2/show/NCT02200367 (Archived by WebCite at http://www.webcitation.org/6xtZ7OijZ).

Developmental SALL2 transcription factor: a new player in cancer.

SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family of transcription factors involved in development and conserved through evolution. Since its identification in 1996, findings indicate that SALL2 plays a role in neurogenesis, neuronal differentiation and eye development. Consistently, SALL2 deficiency associates with neural tube defects and coloboma, a congenital eye disease. Relevant to cancer, clinical studies indicate that SALL2 is deregulated in various cancers and is a specific biomarker for Synovial Sarcoma. However, the significance of SALL2 deregulation in this disease is controversial. Here, we present and discuss all available information about SALL2 since its discovery, including isoforms, regulation, targets and functions. We specifically discuss the role of SALL2 in the regulation of cell proliferation and survival within the context of the identified target genes, its interaction with viral oncogenes, and its association with the TP53 tumor suppressor and MYC oncogene. Special attention is given to p53-independent SALL2 regulation of pro-apoptotic genes BAX and PMAIP1, and the implication of these findings on the apoptotic response of cancer cells to therapy. Understanding SALL2 function and the molecular mechanisms governing its expression and activity is critical to comprehend why and how SALL2 could contribute to disease. This knowledge will open new perspectives for the development of molecular targeted approaches in disease.

Rapamycin requires AMPK activity and p27 expression for promoting autophagy-dependent Tsc2-null cell survival.

Tuberous sclerosis complex (TSC) disease results from inactivation of the TSC1 or TSC2 gene, and is characterized by benign tumors in several organs. Because TSC tumorigenesis correlates with hyperactivation of mTORC1, current therapies focus on mTORC1 inhibition with rapamycin or its analogs. Rapamycin-induced tumor shrinkage has been reported, but tumor recurrence occurs on withdrawal from rapamycin. Autophagy has been associated with development of TSC tumors and with tumor cell survival during rapamycin treatment. mTORC1 and AMPK directly inhibit and activate autophagy, respectively. AMPK is hyperactivated in TSC cells and tumors, and drives cytoplasmic sequestration of the cell-cycle inhibitor p27KIP (p27). Whether AMPK and p27 are involved in rapamycin-induced autophagy and survival of TSC cells remain unexplored. Here, we show that inhibition of AMPK by compound C or by shRNA-mediated depletion of LKB1 reduces activation of autophagy by rapamycin in Tsc2-null cells. Similarly, shRNA-mediated depletion of p27 inhibited rapamycin-induced autophagy. In support of p27 lying downstream of AMPK on the activation of autophagy in Tsc2-null cells, a p27 mutant that preferentially localizes in the cytosol recovered the effect of rapamycin on autophagy in both p27- and LKB1-depleted cells, but a nuclear p27 mutant was inactive. Finally, we show that p27-dependent activation of autophagy is involved in Tsc2-null cell survival under rapamycin treatment. These results indicate that an AMPK/p27 axis is promoting a survival mechanism that could explain in part the relapse of TSC tumors treated with rapamycin, exposing new avenues for designing more efficient treatments for TSC patients.

Sonographic Comparison of Morphologic Characteristics Between Pilonidal Cysts and Hidradenitis Suppurativa.

OBJECTIVES: To compare the sonographic characteristics of pilonidal cysts and hidradenitis suppurativa. METHODS: A retrospective study of sonographic examinations was performed on 2 groups: 1 with pilonidal cysts and the other with hidradenitis suppurativa. The sonographic characteristics of the pilonidal cyst and hidradenitis suppurativa groups were analyzed, compared, and correlated, including an analysis of the histologic findings. For the pilonidal cyst group, the distribution, morphologic characteristics, location, shape, diameter, axis, vascularity, and scarring were also described. Statistical analyses included Spearman, Wilcoxon, Kruskall-Wallis, χ2 , and Fisher tests. RESULTS: The sonographic examinations of 84 patients were reviewed: 43 with pilonidal cysts and 41 with hidradenitis suppurativa. The comparison of the morphologic characteristics of the key lesions between the pilonidal cyst and hidradenitis suppurativa groups showed no statistically significant differences (P < .05). Both groups had similar dermal and hypodermal saclike and bandlike structures that communicated with the widened base of the hair follicles. Retained fragments of hair tracts within the lesions were sonographically detected in both pilonidal cysts (100%) and hidradenitis suppurativa (83%) and also found on histologic specimens; however, the density of hair tracts per structure was higher in pilonidal cysts. Sonographic signs of scarring were absent in 63% of pilonidal cysts. Only 2% of pilonidal cysts showed communicating bandlike structures. CONCLUSIONS: Key lesions of pilonidal cysts and hidradenitis suppurativa have similar sonographic morphologic characteristics, which suggests that a pilonidal cyst may be a variant or localized form of hidradenitis suppurativa. The retained fragments of hair tracts frequently detected in both entities may be caused by ectopic production of hair and not by embedding. Common therapeutic strategies and research can be designed for both entities.

[Comorbidity in people with depression seeking help at primary health care centers in Santiago, Chile]. / Comorbilidad en personas con depresión que consultan en centros de la atención primaria de salud en Santiago, Chile.

BACKGROUND: International evidence has shown the complex interaction between depression and chronic physical diseases. Depression in scenarios involving multiple comorbidities has not received enough attention in Chile. AIM: To characterize the depressed people who consult at Primary Health Care Centers (PHCCs), taking into account the presence of chronic physical or psychiatric comorbidity. MATERIALS AND METHODS: A secondary analysis of databases used in a clinical trial. Two hundred fifty six adults seeking professional help were recruited in four PHCCs located in the Metropolitan Region. These people had a major depressive episode, identified with a structured psychiatric interview (MINI), and gave their informed consent to participate. Socio-demographic information was collected, depressive symptomatology was measured with the patient health questionnaire 9 (PHQ-9), psychiatric morbidity was assessed using the Mini International Neuropsychiatric Interview (MINI), and chronic physical diseases were self-reported by the patients. Descriptive analyses of all the variables were conducted. RESULTS: Seventy percent of patients had a history of depression, with a median of two prior depressive episodes. Depressive symptoms were mostly considered as moderate to severe and severe and 31% of the patients had high suicide risk. Seventy eight percent displayed a physical or psychiatric comorbidity. Of these patients, 29% only had a chronic physical comorbidity, while 46% suffered from an additional psychiatric disorder. CONCLUSIONS: Depressed individuals who seek help at PHCCs constitute an especially complex population that must be treated taking into account multiple comorbidities.

Ascertainment bias from imputation methods evaluation in wheat.

BACKGROUND: Whole-genome genotyping techniques like Genotyping-by-sequencing (GBS) are being used for genetic studies such as Genome-Wide Association (GWAS) and Genomewide Selection (GS), where different strategies for imputation have been developed. Nevertheless, imputation error may lead to poor performance (i.e. smaller power or higher false positive rate) when complete data is not required as it is for GWAS, and each marker is taken at a time. The aim of this study was to compare the performance of GWAS analysis for Quantitative Trait Loci (QTL) of major and minor effect using different imputation methods when no reference panel is available in a wheat GBS panel. RESULTS: In this study, we compared the power and false positive rate of dissecting quantitative traits for imputed and not-imputed marker score matrices in: (1) a complete molecular marker barley panel array, and (2) a GBS wheat panel with missing data. We found that there is an ascertainment bias in imputation method comparisons. Simulating over a complete matrix and creating missing data at random proved that imputation methods have a poorer performance. Furthermore, we found that when QTL were simulated with imputed data, the imputation methods performed better than the not-imputed ones. On the other hand, when QTL were simulated with not-imputed data, the not-imputed method and one of the imputation methods performed better for dissecting quantitative traits. Moreover, larger differences between imputation methods were detected for QTL of major effect than QTL of minor effect. We also compared the different marker score matrices for GWAS analysis in a real wheat phenotype dataset, and we found minimal differences indicating that imputation did not improve the GWAS performance when a reference panel was not available. CONCLUSIONS: Poorer performance was found in GWAS analysis when an imputed marker score matrix was used, no reference panel is available, in a wheat GBS panel.

Rheb signaling and tumorigenesis: mTORC1 and new horizons.

Rheb is a conserved small GTPase that belongs to the Ras superfamily, and is mainly involved in activation of cell growth through stimulation of mTORC1 activity. Because deregulation of the Rheb/mTORC1 signaling is associated with proliferative disorders and cancer, inhibition of mTORC1 has been therapeutically approached. Although this therapy has proven antitumor activity, its efficacy is not as expected. Here, we will review the main work on the identification of the role of Rheb in cell growth, and on the relevance of Rheb in proliferative disorders, including cancer. We will also review the Rheb functions that could explain tumor resistance to therapies with mTORC1 inhibitors, and will mainly focus our discussion on mTORC1-independent Rheb functions that could also be implicated in cancer cell survival and tumorigenesis. The current progress on the understanding of the noncanonical Rheb functions prompts future studies to establish their relevance in cancer and in the context of current cancer therapies.

Rheb promotes cancer cell survival through p27Kip1-dependent activation of autophagy.

We previously found that the small GTPase Rheb regulates the cell-cycle inhibitor p27KIP1 (p27) in colon cancer cells by a mTORC1-independent mechanism. However, the biological function of the Rheb/p27 axis in cancer cells remains unknown. Here, we show that siRNA-mediated depletion of Rheb decreases survival of human colon cancer cells under serum deprivation. As autophagy can support cell survival, we analyzed the effect of Rheb on this process by detecting the modification of the autophagy marker protein LC3 by western blot and imunofluorescence. We found that Rheb promotes autophagy in several human cancer cell lines under serum deprivation. Accordingly, blocking autophagy inhibited the pro-survival effect of Rheb in colon cancer cells. We then analyzed whether p27 was involved in the biological effect of Rheb. Depletion of p27 inhibited colon cancer cell survival, and Rheb induction of autophagy. These results suggest that p27 has an essential role in the effect of Rheb in response to serum deprivation. In addition, we demonstrated that the role of p27 in autophagy stands on the N-terminal portion of the protein, where the CDK-inhibitory domain is located. Our results indicate that a Rheb/p27 axis accounts for the activation of autophagy that supports cancer cell survival. Our work therefore highlights a biological function of Rheb and prompts the need for future studies to address whether the mTORC1-independent Rheb/p27 axis could contribute to tumorigenesis and/or resistance to mTOR inhibitors.

Color Doppler ultrasound assessment of morphology and types of fistulous tracts in hidradenitis suppurativa (HS).

BACKGROUND: Fistulous tracts in hidradenitis suppurativa (HS) are key signs of severity and their clinical evaluation alone may be limited for assessing their presence and morphology. There is also a need to determine the factors that allow reversibility of the anatomic changes in HS. OBJECTIVE: We sought to categorize fistulous tracts in HS. METHODS: A retrospective study of color Doppler ultrasound images of cases with positive clinical and sonographic criteria of HS with fistulous tracts was performed. The sonographic staging of HS, location, and anatomic characteristics of the tracts were registered and graded. Statistical analysis for correlating variables was performed using bivariate and multivariate studies. RESULTS: In all, 52 patients presenting 96 fistulous tracts met the criteria. Morphology was defined and a sonographic classification into 3 types of fistulae was developed. Type 3 concentrated 71% of the cases presenting communicating tracts, and type 2, 29%. Types 2 and 3 represented 63% of patients with multiple fistulous tracts. Fistulous tracts types 2 and 3 were significantly correlated with age 35 years or older and groin location. LIMITATIONS: Ultrasound cannot detect lesions less than 0.1 mm. CONCLUSION: Fistulous tracts in HS can be categorized using ultrasound, which may support earlier and more precise management.

Pedometers to enhance physical activity in COPD: a randomised controlled trial.

Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality. Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD. COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme. Assessments were performed by investigators blinded to treatment allocation. Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George's respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups. 102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%. Both groups had comparable characteristics at baseline. The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day(-1) versus 138.3±1950 steps·day(-1) (p<0.001); SGRQ -8.8±12.2 versus -3.8±10.9 (p=0.01); CAT score -3.5±5.5 versus -0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus -0.7±24.4 m (p=0.02) than patients receiving activity encouragement only. A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.

Multi-environment multi-QTL association mapping identifies disease resistance QTL in barley germplasm from Latin America.

KEY MESSAGE: Multi-environment multi-QTL mixed models were used in a GWAS context to identify QTL for disease resistance. The use of mega-environments aided the interpretation of environment-specific and general QTL. Diseases represent a major constraint for barley (Hordeum vulgare L.) production in Latin America. Spot blotch (caused by Cochliobolus sativus), stripe rust (caused by Puccinia striiformis f.sp. hordei) and leaf rust (caused by Puccinia hordei) are three of the most important diseases that affect the crop in the region. Since fungicide application is not an economically or environmentally sound solution, the development of durably resistant varieties is a priority for breeding programs. Therefore, new resistance sources are needed. The objective of this work was to detect genomic regions associated with field level plant resistance to spot blotch, stripe rust, and leaf rust in Latin American germplasm. Disease severities measured in multi-environment trials across the Americas and 1,096 SNPs in a population of 360 genotypes were used to identify genomic regions associated with disease resistance. Optimized experimental design and spatial modeling were used in each trial to estimate genotypic means. Genome-Wide Association Mapping (GWAS) in each environment was used to detect Quantitative Trait Loci (QTL). All significant environment-specific QTL were subsequently included in a multi-environment-multi-QTL (MEMQ) model. Geographical origin and inflorescence type were the main determinants of population structure. Spot blotch severity was low to intermediate while leaf and stripe rust severity was high in all environments. Mega-environments were defined by locations for spot blotch and leaf rust. Significant marker-trait associations for spot blotch (9 QTL), leaf (6 QTL) and stripe rust (7 QTL) and both global and environment-specific QTL were detected that will be useful for future breeding efforts.

[Benign focal liver lesions detected by computed tomography: Review of 1,184 examinations]. / Lesiones focales hepáticas benignas: un hallazgo frecuente a la tomografía computada.

BACKGROUND: Multidetector computed tomography (MDCT) of the abdomen, with use of contrast medium, is able to detect and differentiate most focal liver lesions. AIM: To determine the prevalence and features of benign focal liver lesions (BFLL) detected by abdominal MDCT. PATIENTS AND METHODS: We reviewed the reports of contrast abdominal MDCT performed to outpatients between August 2011 and July 2012. Clinical data of examined patients and imaging findings in terms of description of the hepatic parenchyma and the presence of BFLL, were recorded. RESULTS: Data from 1,184 studies were analyzed. Of these, 461 studies (38.4%) reported BFLL. The most prevalent lesions were simple cysts in 290 studies (24%) and hemangiomas in 61 studies (5.1%), granuloma-calcification in 39 (3.2%), focal nodular hyperplasia in 19 (1.6%) and one adenoma. If patients with known causes of liver disease were excluded, the prevalence of BFLL did not change substantially (lesions were found in 396 (37.5%) patients). Compared with livers with signs of damage, normal livers had more cystic lesions (27 and 16.2% respectively, p = 0.014) and hemangiomas (5.3 and 1.1% respectively, p = 0.043). CONCLUSIONS: BFLL are very common findings in MDCT studies. Most of these lesions are simple cysts and hemangiomas.

[Follow-up of patients with good exercise capacity in stress test with myocardial single-photon emission computed tomography (SPECT)]. / Seguimiento clínico en pacientes con buena capacidad metabólica en la prueba de esfuerzo con SPECT miocárdico.

BACKGROUND: The evaluation of coronary artery disease (CAD) can be performed with stress test and myocardial SPECT tomography. AIM: To assess the predictive value of myocardial SPECT using stress test for cardiovascular events in patients with good exercise capacity. MATERIAL AND METHODS: We included 102 males aged 56 ± 10 years and 19 females aged 52 ± 10 years, all able to achieve 10 METs and ≥ 85% of the theoretical maximum heart rate and at least 8 min in their stress test with gated 99mTc-sestamibi SPECT. Eighty two percent of patients were followed clinically for 33 ± 17 months. RESULTS: Sixty seven percent of patients were studied for CAD screening and the rest for known disease assessment. Treadmill stress test was negative in 75.4%; 37% of patients with moderate to severe Duke Score presented ischemia. Normal myocardial perfusion SPECT was observed in 70.2%. Reversible defects appeared in 24.8% of cases, which were of moderate or severe degree (> 10% left ventricular extension) in 56.6%. Only seven cases had coronary events after the SPECT. Two major (myocardial infarction and emergency coronary revascularization) and 5 minor events (elective revascularization) ere observed in the follow-up. In a multivariate analysis, SPECT ischemia was the only statistically significant parameter that increased the probability of having a major or minor event. CONCLUSIONS: Nearly a quarter of our patients with good exercise capacity demonstrated reversible defects in their myocardial perfusion SPECT. In the intermediate-term follow-up, a low rate of cardiac events was observed, being the isotopic ischemia the only significant predictive parameter.