Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease A PRISMA-compliant systematic review and meta-analysis

Background/aims: Several neuropathological, biochemical, and pharmacological data suggested a possible role of histamine in the etiopathogenesis of Parkinson disease (PD). The single nucleotide polymorphism (SNP) rs11558538 in the histamine Nmethyltransferase (HNMT) gene has been associated with the risk of developing PD by several studies but not by some others. We carried out a systematic review that included all the studies published on PD risk related to the rs11558538 SNP, and we conducted a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods: We used several databases to perform the systematic review, the software Meta-DiSc 1.1.1 to perform the metaanalysis of the eligible studies, and the Q-statistic to test heterogeneity between studies. Results: The meta-analysis included 4 eligible case–control association studies for the HNMT rs11558538 SNP and the risk for PD (2108 patients, 2158 controls). The frequency of the minor allele positivity showed a statistically significant association with a decreased risk for PD, both in the total series and in Caucasians. Although homozygosity for the minor allele did not reach statistical significance, the test for trend indicates the occurrence of a gene–dose effect. Global diagnostic odds ratios (95% confidence intervals) for rs11558538T were 0.61 (0.46–0.81) for the total group, and 0.63 (0.45–0.88) for Caucasian patients. Conclusion: The present meta-analysis confirms published evidence suggesting that the HNMT rs11558538 minor allele is related to a reduced risk of developing PD.Trabajo financiado por: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria. Ayudas PI12/00241, PI12/00324, PI15/00303 y RETICS RD12/0013/0002 Junta de Extremadura y Fondos FEDER. Ayuda GR15026peerReviewe

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

The development of clinica lpractice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance withr regard to adverse drug reactions.The poten-tial of pharmacogenomicbiomarkers has been extensively investigated in recent years.However,several barriers to implementing the use of pharmacogenomics testing exist.We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of majorgene/drug pairs.Of 11 potential barriers,the highest importance was attributed to lack of institutional support for pharmacogenomic stesting,and to the issues related to the lack of guidelines.Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen.In this perspective article,we compare the relative importance of 29 gene/drugpairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutic sstudy,and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testingThe work in the author’s laboratory is financed by Grants PS09/00943, PS09/00469, RETICS RIRAAF RD07/0064/0016, and CIBERehd from Instituto de Salud CarlosIII,Madrid, Spain, and by Grants GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Unio

Clinical characteristics of COVID-19 in older adults. A retrospective study in long-term nursing homes in Catalonia

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Residències d'avis; Taxes de mortalitatCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hogares de ancianos; Tasas de mortalidadCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Nursing homes; Death ratesThe natural history of COVID-19 and predictors of mortality in older adults need to be investigated to inform clinical operations and healthcare policy planning. A retrospective study took place in 80 long-term nursing homes in Catalonia, Spain collecting data from March 1st to May 31st, 2020. Demographic and clinical data from 2,092 RT-PCR confirmed cases of SARS-CoV-2 infection were registered, including structural characteristics of the facilities. Descriptive statistics to describe the demographic, clinical, and molecular characteristics of our sample were prepared, both overall and by their symptomatology was performed and an analysis of statistically significant bivariate differences and constructions of a logistic regression model were carried out to assess the relationship between variables. The incidence of the infection was 28%. 71% of the residents showed symptoms. Five major symptoms included: fever, dyspnea, dry cough, asthenia and diarrhea. Fever and dyspnea were by far the most frequent (50% and 28%, respectively). The presentation was predominantly acute and symptomatology persisted from days to weeks (mean 9.1 days, SD = 10,9). 16% of residents had confirmed pneumonia and 22% required hospitalization. The accumulated mortality rate was 21.75% (86% concentrated during the first 28 days at onset). A multivariate logistic regression analysis showed a positive predictive value for mortality for some variables such as age, pneumonia, fever, dyspnea, stupor refusal to oral intake and dementia (p<0.01 for all variables). Results suggest that density in the nursing homes did not account for differences in the incidence of the infection within the facilities. This study provides insights into the natural history of the disease in older adults with high dependency living in long-term nursing homes during the first pandemic wave of March-May 2020 in the region of Catalonia, and suggests that some comorbidities and symptoms have a strong predictive value for mortality.The authors(s) received to specific funding for this work

Heme oxygenase 1 and 2 common genetic variants and risk for essential tremor

Varios informes sugirieren que una función hemo oxigenasa 1 y 2 de los genes HMOX HMOX1 y 2 modifican el riesgo de desarrollar la enfermedad de Parkinson (EP). Porque el temblor esencial (ET) y PD comparten fenotipo y, probablemente, unos factores etiológicos semejantes, analizamos si tales genes están relacionados con el riesgo de desarrollar ET. Se analizó la distribución de las frecuencias genotípicas y alélicas de los HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 y rs1051308 HMOX2 polimorfismos de nucleótido único, así como la presencia de variaciones de número de copias de estos genes en 202 sujetos con ET familiar y 747 controles sanos. Las frecuencias alélicas de rs2071746T y R1051308G ET fueron significativamente menores en los pacientes que en los controles. Ninguno de los polimorfismos estudiados influyeron en el comienzo de la enfermedad. El presente estudio sugiere una débil asociación entre HMOX1 rs2071746 y rs1051308 HMOX2 polimorfismo y el riesgo de desarrollar ET en la población española.Several reports suggested a role of heme oxygenase genes 1 and 2 (HMOX1 and HMOX2) in modifying the risk to develop Parkinson disease (PD). Because essential tremor (ET) and PD share phenotypical and, probably, etiologic factors of the similarities, we analyzed whether such genes are related with the risk to develop ET. We analyzed the distribution of allelic and genotype frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 single nucleotide polymorphisms, as well as the presence of copy number variations of these genes in 202 subjects with familial ET and 747 healthy controls. Allelic frequencies of rs2071746T and rs1051308G were significantly lower in ET patients than in controls. None of the studied polymorphisms influenced the disease onset. The present study suggests a weak association between HMOX1 rs2071746 and HMOX2 rs1051308 polymorphisms and the risk to develop ET in the Spanish population.T• Instituto de Salud Carlos III, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 • Junta de Extremadura: Ayuda GR10068 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011–2013) • Parcialmente financiado Fondos FEDER – Fondo Europeo de Desarrollo RegionalpeerReviewe

Heme oxygenase-1 and 2 common genetic variants and risk for restless legs syndrome

Varios neurotransmisores, neuropatológicos, neuroimagen, y los datos experimentales, sugieren que la deficiencia de hierro juega un papel importante en la fisiopatología del síndrome de piernas inquietas (RLS). HMOX (Hemeoxygenases) es un importante mecanismo de defensa contra el estrés oxidativo, principalmente a través de la degradación del hemo a biliverdin, libre de hierro, y monóxido de carbono. Hemos analizado si los genes HMOX1 y HMOX2 están relacionados con el riesgo de desarrollar el síndrome de piernas inquietas. Se analizó la distribución de genotipos y las frecuencias alélicas de los HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 y rs1051308 HMOX2 SNPs, así como la presencia de variaciones de número de copia (CNVs) de estos genes en 205 sujetos RLS y 445 controles sanos. Las frecuencias de rs2071746 genotipo TT y R2071746T variante alélica fueron significativamente inferiores en los pacientes de SPI que en controles, aunque los otros 3 SNPs estudiados RLS no difirió entre pacientes y controles. Ninguno de los polimorfismos estudiados influyeron en el inicio de la enfermedad, la gravedad de la RLS, historia familiar de SPI, la ferritina sérica, o respuesta a agonistas dopaminérgicos, clonazepam o GABAergic drogas. El presente estudio sugiere una débil asociación entre el polimorfismo rs2071746 HMOX1 y el riesgo de desarrollar el SPI en la población española.Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Hemeoxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls. The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs. The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.• Instituto de Salud Carlos III, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 • Junta de Extremadura: Ayuda GR10068 GR10068 y PRIS10016 (Fundesalud,Mérida, Spain) • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011–2013) • Parcialmente financiado Fondos FEDER – Fondo Europeo de Desarrollo RegionalpeerReviewe

Association between vitamin D receptor rs731236 (Taq1) polymorphism and risk for restless legs syndrome in the Spanish caucasian population

Varios trabajos recientes sugieren un posible papel de la deficiencia de vitamina D en la etiología o el síndrome de las piernas inquietas (RLS). Hemos analizado la posible relación de 2 polimorfismos de un solo nucleótido (SNP) en el receptor de la vitamina D3 (GEN VDR) con el riesgo de SPI. Hemos estudiado la variante alélica genotipo y frecuencias de VDR rs2228570 y rs731236 VDR SNPs en 205 RLS pacientes y 445 controles sanos mediante un ensayo TaqMan. Las frecuencias de los rs731236AAgenotype y la variante alélica rs731236un SPI fue significativamente inferior en los pacientes que en los controles (P<0,005 y 0,01, respectivamente). El síndrome de las piernas inquietas pacientes portadoras de la variante alélica rs731236G había una edad temprana en el inicio, y los portadores del genotipo GG731236rs tuvieron mayor severidad de RLS, aunque estos datos desaparecieron después de los análisis multivariados. Ninguno de los SNPs estudiados estaba relacionada con la positividad de la historia familiar de SPI. Estos resultados sugieren una modesta, pero significativa asociación entre rs731236 VDR SNP y el riesgo de síndrome de piernas inquietas.Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS. We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay. The frequencies of the rs731236AAgenotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P<0.005 and<0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS. These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.• Instituto de Salud Carlos III, Madrid, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324, y RETICS RD12/0013/0002 • Junta de Extremadura: GR15026 y PRIS10016 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011-2013) • Parciamente financiado con Fondos FEDERpeerReviewe

Association between vitamin D receptor rs731236 (Taq1) polymorphism and risk for restless legs syndrome in the Spanish caucasian population

Varios trabajos recientes sugieren un posible papel de la deficiencia de vitamina D en la etiología o el síndrome de las piernas inquietas (RLS). Hemos analizado la posible relación de 2 polimorfismos de un solo nucleótido (SNP) en el receptor de la vitamina D3 (GEN VDR) con el riesgo de SPI. Hemos estudiado la variante alélica genotipo y frecuencias de VDR rs2228570 y rs731236 VDR SNPs en 205 RLS pacientes y 445 controles sanos mediante un ensayo TaqMan. Las frecuencias de los rs731236AAgenotype y la variante alélica rs731236un SPI fue significativamente inferior en los pacientes que en los controles (P<0,005 y 0,01, respectivamente). El síndrome de las piernas inquietas pacientes portadoras de la variante alélica rs731236G había una edad temprana en el inicio, y los portadores del genotipo GG731236rs tuvieron mayor severidad de RLS, aunque estos datos desaparecieron después de los análisis multivariados. Ninguno de los SNPs estudiados estaba relacionada con la positividad de la historia familiar de SPI. Estos resultados sugieren una modesta, pero significativa asociación entre rs731236 VDR SNP y el riesgo de síndrome de piernas inquietas.Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS. We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay. The frequencies of the rs731236AAgenotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P<0.005 and<0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS. These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.• Instituto de Salud Carlos III, Madrid, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324, y RETICS RD12/0013/0002 • Junta de Extremadura: GR15026 y PRIS10016 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011-2013) • Parciamente financiado con Fondos FEDERpeerReviewe

Predictive Value of Cardiac Magnetic Resonance Feature Tracking after Acute Myocardial Infarction: A Comparison with Dobutamine Stress Echocardiography

Ecocardiografía de seguimiento de manchas; Deformación del miocardio; Seguimiento de características de resonancia magnética cardíacaSpeckle-tracking echocardiography; Myocardial deformation; Cardiac magnetic resonance feature-trackingEcocardiografia de seguiment de taques; Deformació del miocardi; Seguiment de característiques de ressonància magnètica cardíacaIn acute ST-segment elevation myocardial infarction (STEMI) late gadolinium enhancement (LGE) may underestimate segmental functional recovery. We evaluated the predictive value of cardiac magnetic resonance (CMR) feature-tracking (FT) for functional recovery and whether it incremented the value of LGE compared to low-dose dobutamine stress echocardiography (LDDSE) and speckle-tracking echocardiography (STE). Eighty patients underwent LDDSE and CMR within 5–7 days after STEMI and segmental functional recovery was defined as improvement in wall-motion at 6-months CMR. Optimal conventional and FT parameters were analyzed and then also applied to an external validation cohort of 222 STEMI patients. Circumferential strain (CS) was the strongest CMR-FT predictor and addition to LGE increased the overall accuracy to 74% and was especially relevant in segments with 50–74% LGE (AUC 0.60 vs. 0.75, p = 0.001). LDDSE increased the overall accuracy to 71%, and in the 50–74% LGE subgroup improved the AUC from 0.60 to 0.69 (p = 0.039). LGE + CS showed similar value as LGE + LDDSE. In the validation cohort, CS was also the strongest CMR-FT predictor of recovery and addition of CS to LGE improved overall accuracy to 73% although this difference was not significant (AUC 0.69, p = 0.44). Conclusion: CS is the strongest CMR-FT predictor of segmental functional recovery after STEMI. Its incremental value to LGE is comparable to that of LDDSE whilst avoiding an inotropic stress agent. CS is especially relevant in segments with 50–74% LGE where accuracy is lower and further testing is frequently required to clarify the potential for recovery.This research was supported by the Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional (FEDER) (grant numbers PI17/01836 and CIBERCV16/11/00486). JG and DM acknowledge financial support from the “Agencia Valenciana de la Innovación, Generalitat Valenciana” (grant) and from the “Conselleria d’Educació, Investigació, Cultura i Esport, Generalitat Valenciana” (grant number AEST/2019/037)

Hacking ético para profundizar en la implementación de sistemas informáticos seguros

Memoria ID-052 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

VER USAL: Plataforma web para el diseño y ejecución de Escape Rooms Virtuales educacionales destinados al aprendizaje de conocimientos aplicando técnicas de gamificación

Memoria ID2022-025. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023