•Optimized N fertilization and irrigation show a large potential for N2O mitigation.•Reduced tillage and crop residues management show a large potential for reducing net GHG emissions.•CH4 fluxes ...from paddies are controlled by management of water table and organic inputs.•Factors beyond the plot scale may outweigh mitigation measures.•Training to farmers on the application of practices will overcome barriers for implementation.
An integrated assessment of the potential of different management practices for mitigating specific components of the total GHG budget (N2O and CH4 emissions and C sequestration) of Mediterranean agrosystems was performed in this study. Their suitability regarding both yield and environmental (e.g. nitrate leaching and ammonia volatilization) sustainability, and regional barriers and opportunities for their implementation were also considered. Based on its results best strategies to abate GHG emissions in Mediterranean agro-systems were proposed. Adjusting N fertilization to crop needs in both irrigated and rain-fed systems could reduce N2O emissions up to 50% compared with a non-adjusted practice. Substitution of N synthetic fertilizers by solid manure can be also implemented in those systems, and may abate N2O emissions by about 20% under Mediterranean conditions, with additional indirect benefits associated to energy savings and positive effects in crop yields. The use of urease and nitrification inhibitors enhances N use efficiency of the cropping systems and may mitigate N2O emissions up to 80% and 50%, respectively. The type of irrigation may also have a great mitigation potential in the Mediterranean region. Drip-irrigated systems have on average 80% lower N2O emissions than sprinkler systems and drip-irrigation combined with optimized fertilization showed a reduction in direct N2O emissions up to 50%. Methane fluxes have a relatively small contribution to the total GHG budget of Mediterranean crops, which can mostly be controlled by careful management of the water table and organic inputs in paddies. Reduced soil tillage, improved management of crop residues and agro-industry by-products, and cover cropping in orchards, are the most suitable interventions to enhance organic C stocks in Mediterranean agricultural soils. The adoption of the proposed agricultural practices will require farmers training. The global analysis of life cycle emissions associated to irrigation type (drip, sprinkle and furrow) and N fertilization rate (100 and 300kgNha−1yr−1) revealed that these factors may outweigh the reduction in GHG emissions beyond the plot scale. The analysis of the impact of some structural changes on top-down mitigation of GHG emissions revealed that 3–15% of N2O emissions could be suppressed by avoiding food waste at the end-consumer level. A 40% reduction in meat and dairy consumption could reduce GHG emissions by 20–30%. Reintroducing the Mediterranean diet (i.e. ∼35% intake of animal protein) would therefore result in a significant decrease of GHG emissions from agricultural production systems under Mediterranean conditions.
Genetics and cardiac channelopathies Campuzano, Oscar; Beltrán-Álvarez, Pedro; Iglesias, Anna ...
Genetics in medicine,
20/May , Volume:
12, Issue:
5
Journal Article
Peer reviewed
Open access
Sudden cardiac death is a major contributor to mortality in industrialized nations; in fact, it is the cause of more deaths than acquired immune deficiency syndrome, lung and breast cancer, and ...stroke together. Frequently, the autopsy becomes the principal diagnostic tool because macroscopic and microscopic analyses reveal the underlying cause of death. However, a significant number of sudden cardiac deaths remain unexplained. These cases are referred to as “natural” or arrhythmogenic. In the young, in up to 50% of sudden cardiac death cases, sudden death is the first and only clinical manifestation of an inherited cardiac disease that had remained undetected by conventional clinical investigations. To improve diagnosis, genetic testing has recently been added to these clinical tools. During the last two decades, there has been considerable progress in the understanding about genetics of sudden cardiac death. With that new information, the probands and their family members can make an informed decision regarding their care and know whether and to what extent they are at risk of suffering from the disease. Thus, genetic technology and expertise have become essential for the diagnosis of some forms of inherited cardiac diseases and to provide a basis for subsequent prevention strategies. This review focuses on recent advances in the understanding of cardiopathies owing to genetic investigations.
Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by ...the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives.
Since 2011, the Global Influenza Hospital Surveillance Network (GIHSN) has used active surveillance to prospectively collect epidemiological and virological data on patients hospitalized with ...influenza virus infection. Here, we describe influenza virus strain circulation in the GIHSN participant countries during 2017-2018 season and examine factors associated with complicated hospitalization among patients admitted with laboratory-confirmed influenza illness.
The study enrolled patients who were hospitalized in a GIHSN hospital in the previous 48 h with acute respiratory symptoms and who had symptoms consistent with influenza within the 7 days before admission. Enrolled patients were tested by reverse transcription-polymerase chain reaction to confirm influenza virus infection. "Complicated hospitalization" was defined as a need for mechanical ventilation, admission to an intensive care unit, or in-hospital death. In each of four age strata (< 15, 15-< 50, 50-< 65, and ≥ 65 years), factors associated with complicated hospitalization in influenza-positive patients were identified by mixed effects logistic regression and those associated with length of hospital stay using a linear mixed-effects regression model.
The study included 12,803 hospitalized patients at 14 coordinating sites in 13 countries, of which 4306 (34%) tested positive for influenza. Influenza viruses B/Yamagata, A/H3N2, and A/H1N1pdm09 strains dominated and cocirculated, although the dominant strains varied between sites. Complicated hospitalization occurred in 10.6% of influenza-positive patients. Factors associated with complicated hospitalization in influenza-positive patients included chronic obstructive pulmonary disease (15-< 50 years and ≥ 65 years), diabetes (15-< 50 years), male sex (50-< 65 years), hospitalization during the last 12 months (50-< 65 years), and current smoking (≥65 years). Chronic obstructive pulmonary disease (50-< 65 years), other chronic conditions (15-< 50 years), influenza A (50-< 65 years), and hospitalization during the last 12 months (< 15 years) were associated with a longer hospital stay. The proportion of patients with complicated influenza did not differ between influenza A and B.
Complicated hospitalizations occurred in over 10% of patients hospitalized with influenza virus infection. Factors commonly associated with complicated or longer hospitalization differed by age group but commonly included chronic obstructive pulmonary disease, diabetes, and hospitalization during the last 12 months.
Aim
The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE).
Methods
A multi-ethnic, multi-national Latin American ...SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed.
Results
Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20–37) years and 47.8 (17.9–68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48–0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69–10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35–16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10–2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01–1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11–1.34; p < 0.0001) were predictive factors of serious infections.
Conclusions
Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.
Hypomyelinating leukodystrophies comprise a subclass of genetic disorders with deficient myelination of the CNS white matter. Here we report four unrelated families with a hypomyelinating ...leukodystrophy phenotype harbouring variants in TMEM163 (NM_030923.5). The initial clinical presentation resembled Pelizaeus-Merzbacher disease with congenital nystagmus, hypotonia, delayed global development and neuroimaging findings suggestive of significant and diffuse hypomyelination. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. TMEM163 is highly expressed in the CNS particularly in newly myelinating oligodendrocytes and was recently revealed to function as a zinc efflux transporter. All the variants identified lie in highly conserved residues in the cytoplasmic domain of the protein, and functional in vitro analysis of the mutant protein demonstrated significant impairment in the ability to efflux zinc out of the cell. Expression of the mutant proteins in an oligodendroglial cell line resulted in substantially reduced mRNA expression of key myelin genes, reduced branching and increased cell death. Our findings indicate that variants in TMEM163 cause a hypomyelinating leukodystrophy and uncover a novel role for zinc homeostasis in oligodendrocyte development and myelin formation.
Abstract Aims To determine the factors predictive of disease activity early in the course of SLE (baseline visit). Methods Patients from GLADEL, a multi-national, multi-ethnic, Latin American lupus ...cohort were included. Disease activity was evaluated at baseline with the SLEDAI score. Demographic characteristics (age at diagnosis, gender, ethnicity, marital status, educational level, medical coverage and socioeconomic status) were assessed. Disease duration was defined as the time between the fourth ACR criterion and baseline. Time to criteria accrual was defined as the interval between the first and fourth ACR criterion. Use of glucocorticoids was recorded as the highest dose received before the baseline visit. Antimalarials and immunosuppressive drugs were recorded as use or not use. Univariable and multivariable analysis were performed. Model selection was based on backward elimination. Results One thousand two hundred sixty-eight patients were included; 1136 (89.6%) of them were female. Mean age at diagnosis was 29.2 (SD: 12.3) years. Five hundred sixty-five (44.6%) were Mestizo, 539 (42.5%) were Caucasians and 164 (12.9%) were African-Latin-Americans. The mean SLEDAI at baseline was 10.9 (SD: 8.4). Longer time between first and fourth ACR criterion, medical coverage, a dose of prednisone between 15 and 60 mg/d, and the use of antimalarials were factors protective of disease activity, while Mestizo and African-Latin-American ethnicities were predictive factors. Conclusions Mestizo and African-Latin-American ethnicities were predictive whereas antimalarial use, medical coverage, and longer time to criteria accrual were protective of higher disease activity early in the disease course.
SBA-15 mesoporous materials were synthesized using the method reported by Zhao et al. Surfactant was removed from as-made materials by means of different techniques: thermal treatment under air ...atmosphere, solvent washing at different temperatures, and supercritical CO2 extraction in the presence and absence of cosolvents. The structure of resulting materials was characterized using conventional techniques: nitrogen and argon adsorption measurements, powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), infrared spectroscopy (FT-IR), and 29Si MAS NMR. The efficiency of surfactant removal using CO2 under supercritical conditions is similar to that obtained by means of solvent washing under reflux but shows some improvements in the presence of cosolvents. Mesoscopic properties of mild-temperature solvent extracted SBA-15 materials depend on the efficiency of the surfactant removal and the use of supercritical CO2 as solvent. Likewise, the size and volume of the complementary microporosity detected in the treated materials is closely related to the strategy of removal of hydrophilic poly(ethyleneoxide) chains of the triblock copolymer template occluded within the siliceous walls of the SBA-15 mesophase during the synthesis.
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