Liver abscess is a serious condition that is uncommon in otherwise normal children. Predisposing factors include immunosuppression, surgery and travel to certain areas. We present a patient with ...liver abscess 4 months after appendectomy. In addition, we reviewed 7 cases of liver abscess that occurred in a 22-year period.
High-power short-duration (HPSD) radiofrequency ablation of atrial fibrillation (AF) increases first-pass pulmonary vein isolation (PVI) and freedom from atrial arrhythmias while decreasing ...procedural time. However, the optimal power setting in terms of safety and efficacy has not been determined.
This study compared the procedural characteristics and clinical outcomes of 50-W vs 40-W during HPSD ablation of paroxysmal AF.
Patients from the REAL-AF prospective multicenter registry (Real-World Experience of Catheter Ablation for Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation) undergoing HPSD ablation of paroxysmal AF, either using 50-W or 40-W, were included. The primary efficacy outcome was freedom from all-atrial arrhythmias. The primary safety outcome was the occurrence of any procedural complication at 12 months. Secondary outcomes included procedural characteristics, AF-related symptoms, and the occurrence of transient ischemic attack or stroke at 12 months.
A total of 383 patients were included. Freedom from all-atrial arrhythmias at 12 months was 80.7% in the 50-W group and 77.3% in the 40-W group (Log-rank P = 0.387). The primary safety outcome occurred in 3.7% of patients in the 50-W group vs 2.8% in the 40-W group (P = 0.646). The 50-W group had a higher rate of first-pass PVI (82.3% vs 76.2%; P = 0.040) as well as shorter procedural (67 minutes IQR: 54-87.5 minutes vs 93 minutes IQR: 80.5-111 minutes; P < 0.001) and radiofrequency ablation times (15 minutes IQR: 11.4-20 minutes vs 27 minutes IQR: 21.5-34.6 minutes; P < 0.001) than the 40-W group.
There was no significant difference in freedom from all-atrial arrhythmias or procedural safety outcomes between 50-W and 40-W during HPSD ablation of paroxysmal AF. The use of 50-W was associated with a higher rate of first-pass PVI as well as shorter procedural times.
Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. ...Here we follow the migratory pathways of B cells emerging from germinal centers (B
) and find that many B
cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B
cells may exit the lymph node to enter distant tissues, while some B
cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of B
cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B
cells and transport of antigen back to GC may support affinity maturation to antigenic drift.
The prevalence of dementia in Parkinson disease (PD) increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests ...clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established.
To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients.
We analyzed the coding regions of the amyloid-beta precursor protein (
), Presenilin 1 and 2 (
), and Granulin (
) genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES) data by single variant and gene base (SKAT-O and burden tests) analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and
carrier status.
Known AD pathogenic mutations in the
(p.A79V) and
(p.V148I) genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the
and
genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the
, and
genes exhibit lower cognitive tests scores than non-carrier PD patients (
= 2.0 × 10
), independent of age at PD diagnosis, age at evaluation,
status or recruitment site.
Pathogenic mutations in the Alzheimer disease-causing genes (
and
are found in sporadic PD patients. PD patients with cognitive decline carry rare variants in dementia-causing genes. Variants in genes causing Mendelian neurodegenerative diseases exhibit pleiotropic effects.
Autosomal-dominant Alzheimer's disease (ADAD) is caused by pathogenic mutations in APP, PSEN1, and PSEN2, which usually lead to an early age at onset (< 65). Circular RNAs are a family of non-coding ...RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD.
We obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts for PSEN1, PSEN2 and APP genes. Only circPSEN1 passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performed in-silico functional analyses using the Circular RNA interactome website and DIANA mirPath software.
Our results show significant differences in gene counts of circPSEN1 in ADAD individuals, when compared to sporadic AD and controls (ADAD = 21, AD = 253, Controls = 23-ADADvsCO: log
FC = 0.794, p = 1.63 × 10
, ADADvsAD: log
FC = 0.602, p = 8.22 × 10
). The high gene counts are contributed by two circPSEN1 species (hsa_circ_0008521 and hsa_circ_0003848). No significant differences were observed in linear PSEN1 gene expression between cases and controls, indicating that this finding is specific to the circular forms. In addition, the high circPSEN1 levels do not seem to be specific to PSEN1 mutation carriers; the counts are also elevated in APP and PSEN2 mutation carriers. In-silico functional analyses suggest that circPSEN1 is involved in several pathways such as axon guidance (p = 3.39 × 10
), hippo signaling pathway (p = 7.38 × 10
), lysine degradation (p = 2.48 × 10
) or Wnt signaling pathway (p = 5.58 × 10
) among other KEGG pathways. Additionally, circPSEN1 counts were able to discriminate ADAD from sporadic AD and controls with an AUC above 0.70.
Our findings show the differential expression of circPSEN1 is increased in ADAD. Given the biological function previously ascribed to circular RNAs and the results of our in-silico analyses, we hypothesize that this finding might be related to neuroinflammatory events that lead or that are caused by the accumulation of amyloid-beta.
This special issue on the genetics of Alzheimer's disease was edited by Drs. Laura Ibanez and Justin Miller in 2021. It contains 10 original articles and reviews that help readers understand specific ...genetic contributions to Alzheimer's disease and how genetics will play a role in future Alzheimer's disease research.
There is a need for affordable, scalable, and specific blood-based biomarkers for Alzheimer’s disease that can be applied to a population level. We have developed and validated disease-specific ...cell-free transcriptomic blood-based biomarkers composed by a scalable number of transcripts that capture AD pathobiology even in the presymptomatic stages of the disease. Accuracies are in the range of the current CSF and plasma biomarkers, and specificities are high against other neurodegenerative diseases.
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•Plasma cfRNA reflects transcriptional changes related to AD pathology•Plasma cfRNA predictive models accurately predict presymptomatic AD•Plasma cfRNA is informative of brain amyloid positivity•Plasma cfRNA models have limited power to predict non-AD neurodegenerative diseases
Clinical finding; Disease; Biochemistry; Molecular biology
En 2018, casos de abuso y explotación sexual sacudieron a las ONG de Desarrollo (ONGD). Estos hechos demostraron que las organizaciones no son ajenas a las dinámicas opresivas hacia la población ...femenina que se registran en otros ámbitos de la sociedad. Las ONGD han implementado una serie de medidas con la finalidad de atajar estos casos. A estas reflexiones y prácticas, se realiza en esta investigación una aportación adicional desde el ámbito de la comunicación. Para ello, analizamos la representación efectuada sobre las mujeres del Sur con el propósito de conocer si aún presentan al colectivo de manera victimista y paternalista. Asimismo, se estudia posibles cambios en la representación que se hayan podido desencadenar posteriormente a los sucesos acaecidos en 2018. Concretamente, se han analizado los boletines para socios/as de Oxfam Intermón durante los periodos 2015-2016 y 2018-2019. El principal resultado de la investigación evidencia que la característica predominante de la imagen que la ONGD construye en torno a las mujeres del Sur es la ambivalencia. La representación aún conserva elementos de corte asistencialista porque ellas son tenidas en cuenta por la ONGD en cuanto a su condición de víctimas y, en consecuencia, de beneficiarias de las intervenciones. No obstante, estos roles son combinados con otros recursos que permiten mostrarlas como agentes clave en los ámbitos doméstico, productivo y público. Así, son retratadas como actoras relevantes para las economías familiares en actividades como la agricultura o la ganadería y como importantes agentes comunitarios. Sin embargo, estas últimas funciones no están exentas de contrariedad, pues, en definitiva, se las interpreta como una ampliación y traslación de sus roles reproductivos a los espacios productivo y comunitario.
Common and rare variants in the LRRK2 locus are associated with Parkinson's disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed ...comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel). We identified eleven independent SNPs in the LRRK2 locus associated with the levels of 25 proteins as well as PD risk. Of these, only eleven proteins have been previously associated with PD risk (e.g., GRN or GPNMB). Proteome-wide association study (PWAS) analyses suggested that the levels of ten of those proteins were genetically correlated with PD risk, and seven were validated in the PPMI cohort. Mendelian randomization analyses identified GPNMB, LCT, and CD68 causal for PD and nominate one more (ITGB2). These 25 proteins were enriched for microglia-specific proteins and trafficking pathways (both lysosome and intracellular). This study not only demonstrates that protein phenome-wide association studies (PheWAS) and trans-protein quantitative trail loci (pQTL) analyses are powerful for identifying novel protein interactions in an unbiased manner, but also that LRRK2 is linked with the regulation of PD-associated proteins that are enriched in microglial cells and specific lysosomal pathways.
The pathogenesis of IPD remains unknown, especially among middle-aged individuals without risk factors (WRF).
The aim of the present study was to investigate the role of single nucleotide ...polymorphisms (SNP) within key genes involved in innate immune response on IPD susceptibility.
Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls.
The allele distribution of the NFKBIA rs1050851 and NFKBIE rs2282151 variants were associated with IPD susceptibility (χ2 = 4.23, p = 0.04 and χ2 = 5.13, p = 0.02, respectively). Additionally, the genotype distribution of NFKBIZ rs645781 (χ2 = 8.25, p = 0.02) and IL1R1 rs3917254 (χ2 = 6.70, p = 0.04) were also associated with IPD risk. When only IPD-WRF patients were considered; the allele distribution of IL1R1 rs2160227 (χ2 = 5.62, p = 0.03), rs13020778 (χ2 = 5.73, p = 0.02), rs3917267 (χ2 = 3.72, p = 0.05) and IL4 rs2227284 (χ2 = 3.76, p = 0.05) and the genotype distribution of IL10 rs3024509 (χ2 = 7.70, p = 0.02), IL1R1 rs3917254 (χ2 = 13.40, p = 0.001), NFKBIZ rs645781 (χ2 = 13.86, p = 0.001) and rs677011 (χ2 = 9.06, p = 0.01) variants were associated with IPD risk.
We found several associations between variants in the IL1R1, IL4, IL10, NFKBIE, NFKBIA, and NFKBIZ genes and risk of IPD. If validated, these biomarkers may help to identify people with higher risk of IPD.
•We investigate the role of single nucleotide polymorphisms (SNP) within key genes involved in innate immune response on Invasive Pneumococcal Disease (IPD).•Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls.•We found associations between variants in the IL1R1, IL4, IL10, NFKBIE, NFKBIA, and NFKBIZ genes and risk of IPD.•If validated, these biomarkers may help to identify people with higher risk of IPD.
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