Textbook outcome in patients with biliary duct injury during cholecystectomy.

BACKGROUND: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management. METHODS: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications. RESULTS: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001). CONCLUSION: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI.

Machine Learning-Based Analysis in the Management of Iatrogenic Bile Duct Injury During Cholecystectomy: a Nationwide Multicenter Study.

BACKGROUND: Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. METHODS: This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. RESULTS: We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes. DISCUSSION: Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients.

Aphid feeding induces the relaxation of epigenetic control and the associated regulation of the defense response in Arabidopsis.

Environmentally induced changes in the epigenome help individuals to quickly adapt to fluctuations in the conditions of their habitats. We explored those changes in Arabidopsis thaliana plants subjected to multiple biotic and abiotic stresses, and identified transposable element (TE) activation in plants infested with the green peach aphid, Myzus persicae. We performed a genome-wide analysis mRNA expression, small RNA accumulation and DNA methylation Our results demonstrate that aphid feeding induces loss of methylation of hundreds of loci, mainly TEs. This loss of methylation has the potential to regulate gene expression and we found evidence that it is involved in the control of plant immunity genes. Accordingly, mutant plants deficient in DNA and H3K9 methylation (kyp) showed increased resistance to M. persicae infestation. Collectively, our results show that changes in DNA methylation play a significant role in the regulation of the plant transcriptional response and induction of defense response against aphid feeding.

The G123 rice mutant, carrying a mutation in SE13, presents alterations in the expression patterns of photosynthetic and major flowering regulatory genes.

Day length is a determinant of flowering time in rice. Phytochromes participate in flowering regulation by measuring the number of daylight hours to which the plant is exposed. Here we describe G123, a rice mutant generated by irradiation, which displays insensitivity to the photoperiod and early flowering under both long day and short day conditions. To detect the mutation responsible for the early flowering phenotype exhibited by G123, we generated an F2 population, derived from crossing with the wild-type, and used a pipeline to detect genomic structural variation, initially developed for human genomes. We detected a deletion in the G123 genome that affects the PHOTOPERIOD SENSITIVITY13 (SE13) gene, which encodes a phytochromobilin synthase, an enzyme implicated in phytochrome chromophore biosynthesis. The transcriptomic analysis, performed by RNA-seq, in the G123 plants indicated an alteration in photosynthesis and other processes related to response to light. The expression patterns of the main flowering regulatory genes, such as Ghd7, Ghd8 and PRR37, were altered in the plants grown under both long day and short day conditions. These findings indicate that phytochromes are also involved in the regulation of these genes under short day conditions, and extend the role of phytochromes in flowering regulation in rice.

Genome-wide association study of agronomic traits in rice cultivated in temperate regions.

BACKGROUND: Rice plants are sensitive to the agro-climate conditions, being photoperiod one of main factor contributing to their adaptation to the region where they are grown. Dissecting the genetic bases underlying diversity in rice populations adapted to specific environmental conditions is a fundamental resource for breeding. In this study we have analysed a collection of japonica varieties adapted to temperate regions to perform association studies with traits of high agronomical interest such as heading date, plant height, number of panicles, panicle length and number of grains per panicle. RESULTS: We have performed a genome wide association study using a panel of 1713 SNPs that, based on previous linkage disequilibrium estimations, provides a full coverage of the whole genome. We have found a total of 43 SNPs associated with variations in the different traits. The identified SNPs were distributed across the genome except in chromosome 12, where no associated SNPs were found. The inspection of the vicinity of these markers also revealed a set of genes associated with physiological functions strongly linked to agronomic traits. Of special relevance are two genes involved in gibberellin homeostasis that are associated with plant height and panicle length. We also detected novel associated sites with heading date, panicle length and number of grain per panicle. CONCLUSION: We have identified loci associated with important agronomic traits among cultivars adapted to temperate conditions. Some of these markers co-localized with already known genes or QTLs, but the association also provided novel molecular markers that can be of help to elucidate the complicated genetic mechanism controlling important agronomic traits, as flowering regulation in the non-dependent photoperiod pathway. The detected associated markers may provide important tools for the genetic improvement of rice cultivars in temperate regions.

Genetic Diversity and Population Structure of Rice Varieties Cultivated in Temperate Regions.

BACKGROUND: After its domestication, rice cultivation expanded from tropical regions towards northern latitudes with temperate climate in a progressive process to overcome limiting photoperiod and temperature conditions. This process has originated a wide range of diversity that can be regarded as a valuable resource for crop improvement. In general, current rice breeding programs have to deal with a lack of both germplasm accessions specifically adapted to local agro-environmental conditions and adapted donors carrying desired agronomical traits. Comprehensive maps of genome variability and population structure would facilitate genome-wide association studies of complex traits, functional gene investigations and the selection of appropriate donors for breeding purposes. RESULTS: A collection of 217 rice varieties mainly cultivated in temperate regions was generated. The collection encompasses modern elite and old cultivars, as well as traditional landraces covering a wide genetic diversity available for rice breeders. Whole Genome Sequencing was performed on 14 cultivars representative of the collection and the genomic profiles of all cultivars were constructed using a panel of 2697 SNPs with wide coverage throughout the rice genome, obtained from the sequencing data. The population structure and genetic relationship analyses showed a strong substructure in the temperate rice population, predominantly based on grain type and the origin of the cultivars. Dendrogram also agrees population structure results. CONCLUSIONS: Based on SNP markers, we have elucidated the genetic relationship and the degree of genetic diversity among a collection of 217 temperate rice varieties possessing an enormous variety of agromorphological and physiological characters. Taken together, the data indicated the occurrence of relatively high gene flow and elevated rates of admixture between cultivars grown in remote regions, probably favoured by local breeding activities. The results of this study significantly expand the current genetic resources available for temperate varieties of rice, providing a valuable tool for future association mapping studies.

Physiological Basis and Transcriptional Profiling of Three Salt-Tolerant Mutant Lines of Rice.

Salinity is a complex trait that affects growth and productivity in many crops, including rice. Mutation induction, a useful tool to generate salt tolerant plants, enables the analysis of plants with similar genetic background, facilitating the understanding of the salt tolerance mechanisms. In this work, we generated three salt tolerant mutant lines by irradiation of a salt-sensitive cultivar plants and screened M2 plants at seedling stage in the presence of high salinity. These three lines, SaT20, SaS62, and SaT58, showed different responses to salinity, but exhibited similar phenotype to wild type plants, except SaT20 that displayed shorter height when grown in the absence of salt. Under salt conditions, all three mutants and the parental line showed similar reduction in yield, although relevant differences in other physiological parameters, such as Na+ accumulation in healthy leaves of SaT20, were registered. Microarray analyses of gene expression profiles in roots revealed the occurrence of common and specific responses in the mutants. The three mutants showed up-regulation of responsive genes, the activation of oxido-reduction process and the inhibition of ion transport. The participation of jasmonate in the plant response to salt was evident by down-regulation of a gene coding for a jasmonate O-methyltransferase. Genes dealing with lipid transport and metabolism were, in general, up-regulated except in SaS62, that also exhibited down-regulation of genes involved in ion transport and Ca2+ signal transduction. The two most tolerant varieties, SaS62 and SaT20, displayed lower levels of transcripts involved in K+ uptake. The physiological study and the description of the expression analysis evidenced that the three lines showed different responses to salt: SaT20 showed a high Na+ content in leaves, SaS62 presented an inhibition of lipid metabolism and ion transport and SaT58 differs in both features in the response to salinity. The analysis of these salt tolerant mutants illustrates the complexity of this trait evidencing the breadth of the plant responses to salinity including simultaneous cooperation of alternative or complementary mechanisms.

Quality of Life in an Adult Population of More than 60 Years of Age without Cognitive Impairment.

OBJECTIVES: To analyse the quality of life (QoL) of persons over 60 years of age in Bizkaia (Basque Country, Spain), not institutionalised and without cognitive impairment, and the relation and possible influence of the perception of the state of health with the cognitive level and the activities that they carry out. SUBJECTS AND METHODS: Evaluation of a sample of 317 persons that belong to a longitudinal study. In 269 cases, there was a reliable informant. The general cognitive state was evaluated by means of the Mini-Mental State Examination (MMSE) and the Global Deterioration Scale (GDS). Two GDS, one of the family member (GDSf) and another of the evaluator (GDSe), were used and memory was evaluated by the Text Memory subtest of the Barcelona Test. The QoL was assessed with the SF-36 Health Survey and the mental, physical and social activities that they carry out were recorded. RESULTS: In the SF-36, the participants showed values that exceed the reference values of the Spanish population in all dimensions of the SF-36, except in that of bodily pain. There were low correlations between the dimensions of the SF-36 and the mental, physical and social activities. A low correlation was observed between the memory tests and the SF-36. In 59.3% of the cases, there were no differences between the GDSf and the GDSe. CONCLUSIONS: The participants of this study present a better perception of their state of health than the Spanish population, but this perception is not observed to be influenced by the type or by the quantity of activities that they carry out or by their cognitive state. The informants present a vision very close to the cognitive state of their family members.

Normative data for a Spanish version of the Rey auditory-verbal learning test in older people.

The Rey Auditory-Verbal Learning Test is an easy to administer test that assesses many memory domains and is, therefore, widely used in the area of clinical neuropsychology. The purpose of this study was to provide normative data for an elderly population living in Spain. The sample of this study was comprised of 156 volunteers over 60 years of age, which were grouped into six different age groups. These groups comprised of 10 participants between the ages of 61 and 65 in the first group, 23 participants (66-70) in the second, 28 participants (71-75) in the third, 35 participants (76-80) in the fourth, 32 participants (81-85)in the fifth and 28 participants (86-95) in the sixth group. Demographic data were collected and means, deviations, and ranges of all the measures were evaluated. Normative data were calculated from the percentiles, and then converted into age-corrected scaled scores with a mean of 10 and a standard deviation of 3.

Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE {varepsilon}4 carriers: a case-control study.

OBJECTIVES: Examine the role of single nucleotide polymorphisms (SNPs) in the oestrogen receptor (ER) genes: rs9340799, rs2234693, rs2228480 (in the ESR1 gene) and rs4986938 (in the ESR2 gene) as a risk factor for amnesic mild cognitive impairment (MCIa) and Alzheimer's disease (AD) and its possible association with the apolipoprotein E (APOE) gene. DESIGN: We have investigated the independent and combined association of different alleles of the oestrogen receptor genes and APOE*ε4 allele with cognitive impairment using a case-control design. SETTING: Participants were prospectively recruited from the neurology departments of several Basque Country hospitals. PARTICIPANTS: This study comprised 816 Caucasian participants who were aged 50 years and older: 204 MCIa, 350 sporadic patients with AD and 262 healthy controls. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical criteria and neuropsychological tests were used to establish the diagnostic groups (MCIa, AD and healthy controls). A dichotomous variable was used for each allele and genotype and the association with MCIa and AD was established using Logistic Regression Models. RESULTS: Neither alleles nor genotypes of SNPs rs9340799, rs2234693, rs2228480 and rs4986938 of oestrogen receptor genes (ESR1 and ESR2) are independently associated with the risk of MCIa or AD. However, the genetic profile created with the combination of the less represented alleles of these SNPs (expressed as XPAA) was associated with an increased risk for MCIa (OR=3.30, 95% CI 1.28 to 8.54, p=0.014) and AD (OR=5.16, 95% CI 2.19 to 12.14, p<0.001) in women APOE*ε4 allele carriers. CONCLUSIONS: The less represented alleles of SNPs studied are associated with MCIa and AD in APOE*E4 carriers. In particular, the genetic profile created with the less represented alleles of ESR1 and ESR2 SNPs are associated with an increased risk for MCIa and AD in women APOEε4 allele carriers.

Normative data for a Spanish version of the rey auditory-verbal learning test in older people

The Rey Auditory-Verbal Learning Test is an easy to administer test that assesses many memory domains and is, therefore, widely used in the area of clinical neuropsychology. The purpose of this study was to provide normative data for an elderly population living in Spain. The sample of this study was comprised of 156 volunteers over 60 years of age, which were grouped into six different age groups. These groups comprised of 10 participants between the ages of 61and 65 in the first group, 23 participants (66-70) in the second, 28 participants (71-75) in the third, 35 participants (76-80) in the fourth, 32 participants (81-85) in the fifth and 28 participants (86-95) in the sixth group. Demographic data were collected and means, deviations, and ranges of all the measures were evaluated. Normative data were calculated from the percentiles, and then converted into age-corrected scaled scores with a mean of 10 and a standard deviation of 3 (AU)

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Depresión y apatía en los accidentes cerebrovasculares agudos / Poststroke depression and apathy

A pesar de que la mayoría de los pacientes que han sufrido un ictus van a presentar algún tipo de alteración psicopatológica, no se le suele prestar una adecuada atención. La depresión post-ictus (DPI) es el síndrome psiquiátrico más frecuente, afecta a alrededor del 35 % de los pacientes, y su presencia acarrea a éstos un peor pronóstico funcional y vital. La fisiopatología de la DPI es aún desconocida, aunque se sospecha que el sistema serotoninérgico está implicado, y el uso de fármacos que estimulan dicho sistema parece ser útil en su tratamiento. La apatía post-ictus, también muy presente entre los pacientes con ictus y con una prevalencia del 25%, es mucho menos conocida(AU)

Despite the big prevalence of psychopatological disorders in stroke patients, these have received a very little attention. Poststroke depression (PSD) is the most frequent psychiatric complication of stroke, and its prevalence has been estimated to be around 35%. Stroke patients with PSD suffer higher mortality rates and show a worse functional outcomes and quality of life. PSD pathophysiology is still debated, but the serotoninergic hypothesis is the best choice, and the antidepressant therapy appear to be effective. Post-stroke apathy prevalence is around 25% but little is known about this(AU)

Interrelationship between myocardial perfusion imaging, coronary calcium score, and endothelial function in asymptomatic diabetics and controls.

BACKGROUND: Coronary artery disease is a leading cause of death among diabetics, and silent ischemia is a major concern in patients with diabetes mellitus (DM). METHODS: To detect the prevalence of ischemia in diabetics by myocardial perfusion imaging (MPI), and compare it to a control group without DM but with coronary risk factors, as well as to explore the relationship between silent ischemia, endothelial dysfunction, and coronary calcium, 59 patients (Group I) and 42 controls (Group II) were included. All underwent clinical and laboratory evaluations, gated MPI, brachial artery vasodilation measured by ultrasonography, and coronary calcium score (CCS). RESULTS: Twenty diabetics showed perfusion defects, vs seven controls (P = .04). There was no significant difference between both groups regarding the brachial artery vasodilator responsiveness: 4.49% ± 4.26% (diabetics) vs 4.70% ± 4.98% (controls). Mean CCS was 74 in diabetics vs five in controls (P = .01). The only risk factor significantly associated with an abnormal MPI was the presence of diabetes (P = .03). In the whole population of patients and in diabetics, the abnormal endothelium-dependent vasodilation, the CCS >100, and the cholesterol/HDL ratio >4, showed an OR >1. CCS exhibited the higher OR among the whole population: OR 2.15 [95% CI 0.42-10.99]; while for diabetics it was the cholesterol/HDL ratio: OR 3.95 [95% CI 0.71-21.84]. CONCLUSIONS: Reversible perfusion defects and coronary calcium are more frequent in diabetics. CCS, abnormal endothelium-dependent vasodilation, and cholesterol/HDL ratio higher than 4, showed an association with perfusion abnormalities in asymptomatic diabetics.

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers.

BACKGROUND: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE).A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. RESULTS: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectively). In AD patients this effect was greater in women.In MCI patients such as synergistic effect was only found between AG and APOE epsilon4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01). CONCLUSION: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon4 allele that proves greater in women with AD.

Left ventricular dysfunction secondary to ischemia in women with angina and normal coronary angiograms.

BACKGROUND: Microvascular disease is proposed as a cause of segmental myocardial blood flow abnormalities and heterogeneous myocardial perfusion in cardiac syndrome X. OBJECTIVE: To assess if myocardial ischemia can be evidenced through both perfusion abnormalities and poststress left ventricular ejection fraction (LVEF) reduction by gated single photon emission tomography (SPECT) myocardial scintigraphy in women with syndrome X in a similar way to those with epicardial coronary lesions. METHODS: Three groups of postmenopausal women were studied: group I, 20 women with angina, perfusion defects, and normal coronary angiography; group II, 20 women with epicardial coronary lesions (> or =50% of coronary lumen reduction); group III, 15 volunteers without signs or symptoms of ischemia (control group). Each underwent technetium-99m ((99m)TC) methoxyisobutylisonitrile gated SPECT myocardial scintigraphy (protocol: exercise-stress-rest), brachial artery endothelial function measured by ultrasonography, and lipidogram. RESULTS: Groups I and III patients had a higher body mass index (BMI). There were more smokers in groups I and II. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides were higher in group II patients. The brachial artery vasodilator responsiveness after 5 minutes of ischemia was similarly lower in patients of groups I and II compared with those of group III (3% vs. 6.5%, respectively; p = 0.03 group III vs. group I and group II). Mean DeltaLVEF (LVEF poststress minus LVEF at rest) was -3.86%, -2.90%, and 4.18% in groups I, II, and III, respectively (p = NS between I and II, p = 0.005 between II and III, and p = 0.003 between I and III). In 43% of group I patients and in 10 of 18 group III patients with perfusion defects, there was a poststress LVEF reduction >5%. CONCLUSIONS: Stress-induced ischemia is associated with poststress LVEF reduction as a probable manifestation of myocardial stunning in postmenopausal women with typical angina and normal coronary angiography.

Ischemia in women with angina and normal coronary angiograms.

BACKGROUND: Coronary artery disease is frequent in postmenopausal women. Myocardial ischemia has been induced with stress testing, and a relationship between endothelial dysfunction and perfusion defects has been reported. OBJECTIVE: To evaluate whether myocardial ischemia can be evidenced both by perfusion and function abnormalities using gated single-photon emission computed-tomography myocardial scintigraphy with technetium-labeled compounds in women with typical angina, normal coronary angiography, and endothelial dysfunction. METHODS AND RESULTS: Fifty-nine postmenopausal patients were studied. Each underwent technetium-99m methoxy-isobutyl-isonitrile myocardial scintigraphy (protocol: exercise stress-rest), brachial artery endothelial function measured by ultrasonography, lipidogram, and 24-h ambulatory ECG recording (Holter). Twenty-one patients (group I) showed perfusion defects in myocardial scintigraphy, whereas the other 38 patients (group II) did not. Group I patients exhibited endothelial dysfunction more frequently (57 vs. 29%) than those of group II. Among group I patients, 12 showed a reversible perfusion defect that, in 75% of the cases, was associated with poststress left ventricular ejection fraction reduction greater than 5% and a regional hypokinesis. Nine patients had fixed defects, which in 56% of the cases were associated with poststress left ventricular ejection fraction reduction greater than 5%. Left ventricular ejection fraction poststress minus left ventricular ejection fraction at rest was -5.2% in group I patients versus -1.8% in group II (P<0.001). Three patients in group I showed evidence of ischemia by Holter compared with four in group II. CONCLUSION: Stress-induced ischemia is associated with poststress left ventricular ejection fraction reduction in postmenopausal women with typical angina, normal coronary angiography, and a trend toward abnormal endothelial-mediated vasodilation.

Mental stress-induced myocardial ischemia in women with angina and normal coronary angiograms.

BACKGROUND: Coronary artery disease is frequent in postmenopausal women. Silent myocardial ischemia has been induced with mental stress testing. METHODS AND RESULTS: To evaluate whether mental stress can induce ischemia in women with typical angina and normal coronary angiography, postmenopausal patients (n = 16) were studied. Each underwent technetium 99m methoxyisobutylisonitrile myocardial scintigraphy (exercise stress/rest/mental stress protocol), brachial artery endothelial function measurement by ultrasonography, and 24-hour ambulatory electrocardiographic recording (Holter). During mental stress testing, 6 patients (group I) had reversible perfusion defects on myocardial scintigraphy whereas the other 10 patients (group II) did not. Group I patients exhibited endothelial dysfunction more frequently than those in group II (83% vs 20%). Myocardial scintigraphy showed anteroapical/septal ischemia in 5 patients and inferoapical ischemia in one other patient, with both types of stress. Among group II patients, none showed a reversible perfusion defect during physical or mental stress. No group I patients had evidence of ischemia by Holter monitoring, whereas 2 of 10 group II patients did. CONCLUSION: In postmenopausal women with typical angina and normal coronary arteries, mental stress may provoke myocardial ischemia, which can be concordant with ischemia induced by exercise stress, and is associated with endothelial dysfunction.