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1.
Farm Hosp ; 48(4): T159-T163, 2024.
Article in English, Spanish | MEDLINE | ID: mdl-38772807

ABSTRACT

OBJECTIVES: The main aim was to compare the effects of two parenteral lipid emulsions on retinopathy of prematurity (ROP) incidence, severity, and need for treatment. Secondary aim was to compare the effect on weight gain in the first 6 weeks of life. METHODS: Single-center, observational, retrospective study analyzing preterm infants with a gestational age < 31 weeks and a birth weight < 1,251 g, born between April 2015 and December 2018. The infants' medical records were reviewed to collect clinical data. Parenteral nutrition details were obtained from the hospital pharmacy database. RESULTS: In total, 180 patients were included: 90 received ClinOleic® and 90 received SMOFlipid®. No significant differences were observed for the incidence of ROP (40% in ClinOleic® group and 41% in SMOFlipid® group, p=0.88) or ROP requiring treatment (4% and 10% respectively, p=0.152). Weekly weight gain was similar in the two groups. CONCLUSIONS: This study showed no difference between the two groups regarding ROP, ROP requiring treatment or weekly weight gain in the first 6 weeks of life.


Subject(s)
Fat Emulsions, Intravenous , Infant, Premature , Parenteral Nutrition , Retinopathy of Prematurity , Weight Gain , Humans , Retinopathy of Prematurity/prevention & control , Retrospective Studies , Infant, Newborn , Male , Female , Fat Emulsions, Intravenous/therapeutic use , Soybean Oil/therapeutic use , Soybean Oil/administration & dosage , Phospholipids/therapeutic use , Phospholipids/administration & dosage , Gestational Age , Incidence , Treatment Outcome , Olive Oil , Fish Oils , Plant Oils , Triglycerides
2.
Infection ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691231

ABSTRACT

OBJECTIVES: Mastitis is mainly caused by Gram-positive bacteria and usually involves treatment with beta-lactam antibiotics and clindamycin. Oxazolidinones show good results in the treatment of skin and soft tissue infections (SSTIs) due to its pharmacokinetic characteristics. We aimed to describe clinical characteristics and outcomes of patients who received oxazolidinones for the treatment of SSTIs of the mammary tissue. METHODS: Retrospective single-centre study of patients with a diagnosis of breast infection who received treatment with oxazolidinones as initial or salvage therapy between September 2016 and November 2022. Patients were identified through the pharmacy database. The primary outcome was clinical cure. RESULTS: Twenty-nine patients received oxazolidinones: 27 received linezolid and 2 tedizolid. Median age was 41 years (IQR 31.0-56.5) and 28 patients were female. Ten patients (35%) had a history of breast cancer, while three (10%) had an immunosuppressive condition. Microbiological isolation was obtained in 24 individuals (83%). Predominant isolations were methicillin-resistant Staphylococcus aureus (8, 28%) and methicillin-susceptible S. aureus (7, 24%). Twenty-four patients (83%) received oxazolidinones as a salvage therapy, with a median duration of 14 days (IQR 10-17). Clinical cure was achieved in 24 patients (83%), while 4 relapsed after a median of 15 days (IQR 4-34). One was lost to follow-up. Three patients (10%) were taking selective serotonin reuptake inhibitors, and one of them concurrently received linezolid for 4 days with no adverse events recorded. Cytopenia during treatment was observed in 2/12 individuals. Oxazolidinones allowed hospital discharge in 11/13 hospitalized patients. CONCLUSIONS: Oxazolidinones could be considered as an alternative for treating breast infections.

3.
Farm Hosp ; 48(4): 159-163, 2024.
Article in English, Spanish | MEDLINE | ID: mdl-38556369

ABSTRACT

OBJECTIVES: The main aim was to compare the effects of 2 parenteral lipid emulsions on retinopathy of prematurity (ROP) incidence, severity, and need for treatment. Secondary aim was to compare the effect on weight gain in the first 6 weeks of life. METHODS: Single-center, observational, retrospective study analyzing preterm infants with a gestational age (GA) <31 weeks and a birth weight <1251 g born between April 2015 and December 2018. The infants' medical records were reviewed to collect clinical data. Parenteral nutrition (PN) details were obtained from the hospital pharmacy database. RESULTS: In total, 180 patients were included: 90 received ClinOleic® and 90 received SMOFlipid®. No significant differences were observed for the incidence of ROP (40% in ClinOleic® group and 41% in SMOFlipid® group, p=.88) or ROP requiring treatment (4% and 10%, respectively, p=.152). Weekly weight gain was similar in the 2 groups. CONCLUSIONS: This study showed no difference between the 2 groups regarding ROP, ROP requiring treatment, or weekly weight gain in the first 6 weeks of life.


Subject(s)
Fat Emulsions, Intravenous , Infant, Premature , Parenteral Nutrition , Retinopathy of Prematurity , Weight Gain , Humans , Retinopathy of Prematurity/prevention & control , Retrospective Studies , Infant, Newborn , Fat Emulsions, Intravenous/therapeutic use , Fat Emulsions, Intravenous/administration & dosage , Male , Female , Soybean Oil/therapeutic use , Soybean Oil/administration & dosage , Gestational Age , Phospholipids/therapeutic use , Phospholipids/administration & dosage , Incidence , Treatment Outcome , Olive Oil , Fish Oils , Plant Oils , Triglycerides
4.
Paediatr Drugs ; 26(3): 331-346, 2024 May.
Article in English | MEDLINE | ID: mdl-38507036

ABSTRACT

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing. OBJECTIVE: The aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance. METHODS: This observational and ambispective single-centre study was conducted in paediatric patients with IBD treated with infliximab between July 2016 and July 2022 in the Paediatric Gastroenterology Service of the Hospital Universitari Vall d'Hebron (HUVH) (Spain). Demographic, clinical, and analytical variables were collected. Twenty SNPs potentially associated with variations in the response to infliximab plasma concentrations were analysed. infliximab serum concentrations and antibodies to infliximab (ATI) were determined by ELISA. PopPK modelling was performed using nonlinear mixed-effects analysis (NONMEM). RESULTS: Thirty patients (21 males) were included. The median age (range) at the start of infliximab treatment was 13 years (16 months to 16 years). A total of 190 samples were obtained for model development (49 [25.8%] during the induction phase). The pharmacokinetics (PK) of infliximab were described using a two-compartment model. Weight, erythrocyte sedimentation rate (ESR), faecal calprotectin (FC), and the SNP rs1048610 (ADAM17) showed statistical significance for clearance (CL), and albumin for inter-compartmental clearance (Q). Estimates of CL1 (genotype 1-AA), CL2 (genotype 2-AG), CL3 (genotype 3-GG), Q, Vc, and Vp (central and peripheral distribution volumes) were 0.0066 L/h/46.4 kg, 0.0055 L/h/46.4 kg, 0.0081 L/h/46.4 kg, 0.0029 L/h/46.4 kg, 0.6750 L/46.4 kg, and 1.19 L/46.4 kg, respectively. The interindividual variability (IIV) estimates for clearance, Vc, and Vp were 19.33, 16.42, and 36.02%, respectively. CONCLUSIONS: A popPK model utilising weight, albumin, FC, ESR, and the SNP rs1048610 accurately predicted infliximab trough concentrations in children with IBD.


Subject(s)
Biomarkers , Drug Monitoring , Inflammatory Bowel Diseases , Infliximab , Polymorphism, Single Nucleotide , Humans , Infliximab/pharmacokinetics , Infliximab/therapeutic use , Child , Male , Adolescent , Female , Child, Preschool , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Biomarkers/blood , Drug Monitoring/methods , Infant , Gastrointestinal Agents/pharmacokinetics , Gastrointestinal Agents/therapeutic use , Models, Biological , Spain
6.
Eur J Pharm Biopharm ; 184: 103-115, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36669672

ABSTRACT

Teduglutide (Revestive®) is a glucagon-like peptide-2 analogue used for the treatment of short bowel syndrome, a rare life-threatening condition in which the amount of functional gut is too short to enable proper absorption of nutrients and fluids. During handling prior to administration to the patient in hospital, it is possible that peptide-based medicines may be exposed to environmental stress conditions that could affect their quality. It is therefore essential to carry out stress testing studies to evaluate how such medicines respond to these stresses. For this reason, in this paper we present a strategy for a comprehensive analytical characterization of a peptide and a stress testing study in which it was subjected to various stress conditions: heating at 40 °C and 60 °C, light exposure and shaking. Several complementary analytical techniques were used throughout this study: Far UV circular dichroism, intrinsic protein fluorescence spectroscopy, dynamic light scattering, size-exclusion chromatography and intact and peptide mapping reverse-phase chromatography coupled to mass spectrometry. To the best of our knowledge, this is the first study to offer an in-depth description of the chemical structure of teduglutide peptide and its physicochemical characteristics after stress stimuli were applied to the reconstituted medicine Revestive®.


Subject(s)
Peptides , Short Bowel Syndrome , Humans , Short Bowel Syndrome/drug therapy , Glucagon-Like Peptide 2/therapeutic use , Mass Spectrometry , Gastrointestinal Agents
7.
Anal Methods ; 14(43): 4359-4369, 2022 11 10.
Article in English | MEDLINE | ID: mdl-36263764

ABSTRACT

Teduglutide (Revestive®, 10 mg mL-1) is a recombinant human glucagon-like peptide 2 analogue, used in the treatment of short bowel syndrome, a serious and highly disabling condition which results from either too small a length of intestine or loss of critical intestinal function. The determination of therapeutic compounds of protein-nature is always challenging due to their complex structure. In this work, we present a fast, straightforward reversed phase (RP)UHPLC-UV-(HESI/ORBITRAP)MS method for the identification and quantification of the intact teduglutide peptide. The method has been developed and validated in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines; therefore, linearity, limits of detection and quantification, accuracy (precision and trueness), robustness, system suitability and specificity using the signal from the UV and MS, have been evaluated. The validation performance parameters obtained from the UV and MS signals were compared throughout the work, to select the most suitable. To study the specificity of the method and the impact of medicine mishandling under hospital conditions, force degradation studies were performed, i.e. thermal (40 °C and 60 °C), shaking (mechanical) and light (accelerated exposition) effects. Identification by the exact mass of teduglutide was achieved and it was confirmed that the peptide does not undergo any post-translational modifications (PTMs). To the best of our knowledge, the present work reports the first method developed for the simultaneous identification, structural characterization, and quantification of the therapeutic teduglutide peptide. Finally, the proposed method is able to indicate stability when quantifying the intact teduglutide since detects and characterises the exact mass of the degradation/modification products.


Subject(s)
Short Bowel Syndrome , Humans , Chromatography, High Pressure Liquid/methods , Short Bowel Syndrome/drug therapy , Glucagon-Like Peptide 2/therapeutic use , Peptides/therapeutic use
8.
J Pharm Biomed Anal ; 221: 115064, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36152491

ABSTRACT

Teduglutide, the active ingredient of the medicine Revestive® (5 mg), is a recombinant therapeutic peptide that mimics the effects of the endogenous glucagon-like peptide 2 (GLP-2). It stimulates intestinal growth, adaptation and function in patients with Short Bowel Syndrome who are dependent on parenteral nutrition. The Summary of Product Characteristics recommends immediate use of the reconstituted solutions and the discarding of any subsequent surplus. This study aims to carry out a long-term stability study that reproduces hospital conditions of use which provide sound evidence regarding the use of teduglutide surplus beyond the Summary Product Characteristics recommendations. We conducted a stability study of teduglutide solutions prepared from a 5 mg vial of Revestive®. Some of the solutions were stored in their original vial after reconstitution, while others were repackaged in plastic syringes to evaluate their physicochemical stability over time. For this purpose, we applied a set of previously validated analytical methodologies to evaluate the main critical quality attributes of teduglutide, i.e., primary (including post-tralational modifications), secondary and tertiary structures, aggregates, particulate, concentration and pH. The results indicate that the solutions maintain high physicochemical stability over time, regardless of the storage temperature (4ºC or -20ºC) or the storage container (vials or syringes). This research provides new data on the stability of Revestive® that will be of great value to hospital pharmacists. This comprehensive assessment of the physicochemical long-term stability of TGT has demonstrated that under the storage conditions and over the period studied here, the medicine maintains its quality, efficacy and safety profiles.


Subject(s)
Glucagon-Like Peptide 2 , Short Bowel Syndrome , Gastrointestinal Agents , Glucagon-Like Peptide 2/therapeutic use , Humans , Peptides/pharmacology , Plastics , Short Bowel Syndrome/drug therapy
9.
Eur J Obstet Gynecol Reprod Biol ; 275: 106-109, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35779331

ABSTRACT

OBJECTIVE: The physical compatibility of atosiban and selected drugs during simulated Y-site administration was evaluated. We also searched for any compatibility predictions regarding its physicochemical properties. STUDY DESIGN: Test admixtures were prepared by mixing 5 mL of each study drug solution with 5 mL of atosiban solution in a 1:1 ratio to simulate Y-site infusion. Assessments were made immediately after mixing (baseline), and at 0.5, 1, and 3 h. Visual incompatibility was defined as a presence of haze or any visible particulate matter, gas formation, or colour change. Turbidity and pH variation of the admixtures were also assessed using instrumental methods. RESULTS: None of the admixtures used with atosiban exhibited visual changes and no incompatibility regarding instrumental methods were observed, because no admixture had an increase of 0.5 nephelometric turbidity units, and no pH change was above one unit when compared to baseline. However, the pH of ampicillin and omeprazole admixtures fell outside of the atosiban stability range. CONCLUSIONS: Our study showed no physical incompatibility between atosiban and the test drugs in terms of visual changes or nephelometric and pH measurements. However, we recommend against atosiban and ampicillin or omeprazole coadministration until complementary compatibility studies are performed.


Subject(s)
Ampicillin , Omeprazole , Acetates , Drug Incompatibility , Humans , Infusions, Intravenous , Vasotocin/analogs & derivatives
10.
J Matern Fetal Neonatal Med ; 35(25): 8027-8031, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34157934

ABSTRACT

OBJECTIVE: To study the association between gestational age (GA) and weight at birth and the development of retinopathy of prematurity (ROP), and in particular the link between postnatal weight gain during the first 6 weeks and need for ROP treatment. MATERIAL AND METHODS: Retrospective observational study of premature infants who underwent ophthalmoscopy at Hospital Universitari Vall d'Hebron in Barcelona, Spain, between June 2017 and December 2018. We collected data on obstetric and birth characteristics, comorbidities, GA and weight at birth, and weekly weight for the first 6 weeks. RESULTS: Ninety patients with a mean ± SD GA of 26.87 ± 1.90 weeks and a mean birth weight of 884.29 ± 227.40 g were studied. The mean weight at 6 weeks was 1656.89 ± 478.51 g, which corresponds to a gain of 776.17 ± 298.12 g. Thirty-seven patients (41.1%) were diagnosed with ROP and nine (10%) needed treatment. Significant predictors of the need for treatment in patients with ROP were GA (p = .018) and weight at 6 weeks (p = .021). Birth weight was not significant (p = .361). CONCLUSIONS: GA and weight gain during the first 6 weeks of life are significantly associated with the need for treatment in infants with ROP. Sex and birth weight were not significant predictors. Postnatal weight gain at 6 weeks is predictive of the need for ROP treatment.


Subject(s)
Retinopathy of Prematurity , Infant, Newborn , Infant , Humans , Retinopathy of Prematurity/epidemiology , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/diagnosis , Birth Weight , Risk Factors , Gestational Age , Weight Gain , Retrospective Studies
11.
An Pediatr (Engl Ed) ; 95(3): 139-146, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34507648

ABSTRACT

INTRODUCTION: Aggressive parenteral nutrition with delivery of high amino acid and energy doses is used to improve growth and neurodevelopmental outcomes in very low birth weight (VLBW) preterm infants. Recent findings, however, suggest that this approach may cause electrolyte imbalances. The aim of our study was to compare the prevalence of hypercalcaemia, hypophosphataemia, and hypokalaemia in 2 groups of preterm infants that received parenteral nutrition with different amounts of amino acids and to analyse perinatal and nutritional variables associated with the development of electrolyte imbalances. METHODS: We conducted a retrospective observational study comparing 2 groups of preterm infants born before 33 weeks' gestation with birth weights of less than 1500 g managed with parenteral nutrition. One of the groups received less than 3 g/kg/day of amino acids and the other received 3 g/kg//day of amino acids or more. We analysed the prevalence of electrolyte imbalances and possible associations with aggressive parenteral nutrition, adjusting for potential confounders. RESULTS: We studied 114 infants: 60 given less than 3 g/kg/day of amino acids (low-intake group) and 54 given at least 3 g/kg/day (high-intake group). The prevalence of electrolyte imbalances was similar in both groups. The prevalence of hypercalcaemia was 1.67% in the low-intake group and 1.85% in the high-intake group (P > .99), the prevalence of severe hypophosphataemia 11.7% vs 9.3%, and the prevalence of hypokalaemia 15.0% vs 11.1% (P > .99). A calcium to phosphorus ratio greater than 1.05 had a protective effect against hypophosphataemia (P = .007). CONCLUSIONS: We did not find an association between hypercalcaemia, hypophosphataemia, and hypokalaemia and the amino acid dose delivered by PN in the high-intake group of preterm infants.


Subject(s)
Infant, Premature , Parenteral Nutrition/adverse effects , Electrolytes/blood , Electrolytes/urine , Female , Humans , Hypercalcemia/blood , Hypercalcemia/epidemiology , Hypophosphatemia/epidemiology , Incidence , Infant , Infant, Newborn , Infant, Very Low Birth Weight , Pregnancy , Refeeding Syndrome , Retrospective Studies
12.
An. pediatr. (2003. Ed. impr.) ; 95(3): 139-146, Sept. 2021. tab, ilus
Article in English, Spanish | IBECS | ID: ibc-207764

ABSTRACT

Introducción: La nutrición parenteral agresiva con aportes energéticos y proteicos altos se utiliza para mejorar el crecimiento y el neurodesarrollo en recién nacidos prematuros de muy bajo peso. No obstante, hallazgos recientes sugieren que su uso puede ocasionar alteraciones electrolíticas. El objetivo del estudio era comparar la prevalencia de hipercalcemia, hipofosfatemia e hipopotasemia en dos grupos de recién nacidos prematuros que recibieron nutrición parenteral con distintos aportes de aminoácidos y analizar variables perinatales y nutricionales asociadas a la ocurrencia de alteraciones electrolíticas. Métodos: Estudio retrospectivo observacional, con comparación de dos grupos de recién nacidos prematuros con peso < 1.500 g y edad gestacional < 33 semanas, que recibían nutrición parenteral. Uno de los grupos recibió < 3 g/kg/d de aminoácidos, mientras que el otro recibió ≥ 3 g/kg/d. Se analizó la prevalencia de distintas alteraciones electrolíticas y su asociación con la nutrición parenteral agresiva, con ajustes para posibles factores de confusión. Resultados: El análisis incluyó 114 recién nacidos: 60 que recibieron < 3 g/kg/d de aminoácidos (bajo aporte) y 54 que recibieron ≥ 3 g/kg/d (alto aporte). La prevalencia de alteraciones electrolíticas fue similar en ambos grupos. La prevalencia de hipercalcemia fue de 1,67% en el grupo de bajo aporte y 1,85% en el grupo de alto aporte (p > 0,99). Los respectivos valores para las otras alteraciones fueron 11,7 vs. 9,3% en el caso de la hipofosfatemia grave y 15,0 vs. 11,1% en el caso de la hipopotasemia (p > 0,99). Se observó que una relación calcio:fósforo superior a 1,05 mostraba un efecto protector frente a la hipofosfatemia (p = 0,007). Conclusiones: No se observó asociación entre la hipercalcemia, hipofosfatemia o la hipopotasemia y el aporte de aminoácidos mediante nutrición parenteral en la población de recién nacidos prematuros con altos aportes de aminoácidos. (AU)


Introduction: Aggressive parenteral nutrition with delivery of high amino acid and energy doses is used to improve growth and neurodevelopmental outcomes in very low birth weight (VLBW) preterm infants. Recent findings, however, suggest that this approach may cause electrolyte imbalances. The aim of our study was to compare the prevalence of hypercalcaemia, hypophosphataemia, and hypokalaemia in 2 groups of preterm infants that received parenteral nutrition with different amounts of amino acids and to analyse perinatal and nutritional variables associated with the development of electrolyte imbalances. Methods: We conducted a retrospective observational study comparing 2 groups of preterm infants born before 33 weeks’ gestation with birth weights of less than 1,500 g managed with parenteral nutrition. One of the groups received less than 3 g/kg/day of amino acids and the other received 3 g/kg/day of amino acids or more. We analysed the prevalence of electrolyte imbalances and possible associations with aggressive parenteral nutrition, adjusting for potential confounders. Results: We studied 114 infants: 60 given less than 3 g/kg/day of amino acids (low-intake group) and 54 given at least 3 g/kg/day (high-intake group). The prevalence of electrolyte imbalances was similar in both groups. The prevalence of hypercalcaemia was 1.67% in the low-intake group and 1.85% in the high-intake group (p > .99), the prevalence of severe hypophosphataemia 11.7 vs. 9.3%, and the prevalence of hypokalaemia 15.0 vs. 11.1% (p > .99). A calcium to phosphorus ratio greater than 1.05 had a protective effect against hypophosphataemia (p = .007). Conclusions: We did not find any association between hypercalcemia, hypophosphatemia, and hypokalemia and amino acid intake by PN in the population of premature infants with quite high amino acid intake values. (AU)


Subject(s)
Humans , Infant, Newborn , Parenteral Nutrition , Infant, Premature , Hypercalcemia , Hypophosphatemia , Hypokalemia , Retrospective Studies , Infant, Very Low Birth Weight
13.
Mol Ther Methods Clin Dev ; 20: 1-17, 2021 Mar 12.
Article in English | MEDLINE | ID: mdl-33335943

ABSTRACT

Fabry disease is a rare X-linked disorder affecting α-galactosidase A, a rate-limiting enzyme in lysosomal catabolism of glycosphingolipids. Current treatments present important limitations, such as low half-life and limited distribution, which gene therapy can overcome. The aim of this work was to test a novel adeno-associated viral vector, serotype 9 (AAV9), ubiquitously expressing human α-galactosidase A to treat Fabry disease (scAAV9-PGK-GLA). The vector was preliminary tested in newborns of a Fabry disease mouse model. 5 months after treatment, α-galactosidase A activity was detectable in the analyzed tissues, including the central nervous system. Moreover, we tested the vector in adult animals of both sexes at two doses and disease stages (presymptomatic and symptomatic) by single intravenous injection. We found that the exogenous α-galactosidase A was active in peripheral tissues as well as the central nervous system and prevented glycosphingolipid accumulation in treated animals up to 5 months following injection. Antibodies against α-galactosidase A were produced in 9 out of 32 treated animals, although enzyme activity in tissues was not significantly affected. These results demonstrate that scAAV9-PGK-GLA can drive widespread and sustained expression of α-galactosidase A, cross the blood brain barrier after systemic delivery, and reduce pathological signs of the Fabry disease mouse model.

14.
Cell Rep ; 31(5): 107616, 2020 05 05.
Article in English | MEDLINE | ID: mdl-32375043

ABSTRACT

A G4C2 hexanucleotide repeat expansion in an intron of C9orf72 is the most common cause of frontal temporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). A remarkably similar intronic TG3C2 repeat expansion is associated with spinocerebellar ataxia 36 (SCA36). Both expansions are widely expressed, form RNA foci, and can undergo repeat-associated non-ATG (RAN) translation to form similar dipeptide repeat proteins (DPRs). Yet, these diseases result in the degeneration of distinct subsets of neurons. We show that the expression of these repeat expansions in mice is sufficient to recapitulate the unique features of each disease, including this selective neuronal vulnerability. Furthermore, only the G4C2 repeat induces the formation of aberrant stress granules and pTDP-43 inclusions. Overall, our results demonstrate that the pathomechanisms responsible for each disease are intrinsic to the individual repeat sequence, highlighting the importance of sequence-specific RNA-mediated toxicity in each disorder.


Subject(s)
C9orf72 Protein/genetics , Nuclear Proteins/genetics , RNA/metabolism , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , Animals , DNA Repeat Expansion/genetics , Frontotemporal Dementia/genetics , Frontotemporal Dementia/metabolism , Humans , Inclusion Bodies/metabolism , Mice , Neurons/metabolism
15.
Insects ; 11(1)2020 Jan 18.
Article in English | MEDLINE | ID: mdl-31963626

ABSTRACT

The ecological functioning of dryland ecosystems is closely related to the spatial pattern of the vegetation, which is typically structured in patches. Ground arthropods mediate key soil functions and ecological processes, yet little is known about the influence of dryland vegetation pattern on their abundance and diversity. Here, we investigate how patch size and cover, and distance between patches relate to the abundance and diversity of meso-and microarthropods in semi-arid steppes. We found that species richness and abundance of ground arthropods exponentially increase with vegetation cover, patch size, and patch closeness. The communities under vegetation patches mainly respond to patch size, while the communities in the bare-soil interpatches are mostly controlled by the average distance between patches, independently of the concurrent changes in vegetation cover. Large patches seem to play a critical role as reserve and source of ground arthropod diversity. Our results suggest that decreasing vegetation cover and/or changes in vegetation pattern towards small and over-dispersed vegetation patches can fast lead to a significant loss of ground arthropods diversity in drylands.

16.
Sci Total Environ ; 704: 135397, 2020 Feb 20.
Article in English | MEDLINE | ID: mdl-31810678

ABSTRACT

The Brazilian savanna (Cerrado) has been extensively converted to croplands, pastures and forestry plantations, and the deforestation frontier continues expanding. Land conversion may cause critical changes in soil functioning, yet very little is still known about the impact of Cerrado conversion on nutrient cycling and soil fertility. Here, we addressed this knowledge gap by investigating the effects of the woodland cerrado (cerradão) conversion into pastures and Eucalyptus plantations on nitrogen availability and mineralization potential, considering a wide range of spatial and temporal variability due to soil depth, site conditions, and seasonal variation. For three sites in São Paulo state and each of the target land cover types, we assessed the total N and inorganic N (NH4-N and NO3-N) pools, potentially mineralizable nitrogen (PMN) and soil urease activity in the first 2 m of the soil profile. Cerrado conversion to either pastures or Eucalyptus plantations significantly reduced NH4-N, while NO3-N showed similar values in Cerrado and Eucalyptus and lower values in pastures. We found a consistent pattern of lower N mineralization in the uppermost soil layers associated to Cerrado conversion, with decreases in PMN rate and urease activity. The soil below 30 cm depth showed no relevant changes. Considering the first 30 cm of the soil profile, the reduction in the stocks of inorganic N (NH4-N + NO3-N) ranged from ~14% for the conversion to Eucalyptus to ∽20% for the conversion to pasture. The impact of land conversion on N cycling surpassed the influence of the spatial (between-site) and seasonal variation. Overall, the results indicate a decline in available N and overall soil fertility due to Cerrado conversion, which could further increase N limitation in the Cerrado region, increase fertilization needs for future exploitation, and compromise the recovery of Cerrado in case of land abandonment or restoration.


Subject(s)
Agriculture , Conservation of Natural Resources , Ecosystem , Environmental Monitoring , Eucalyptus , Nitrogen/analysis , Brazil , Forestry , Forests , Grassland , Soil
17.
New Phytol ; 225(4): 1500-1515, 2020 02.
Article in English | MEDLINE | ID: mdl-31605639

ABSTRACT

Recent observations suggest that repeated fires could drive Mediterranean forests to shrublands, hosting flammable vegetation that regrows quickly after fire. This feedback supposedly favours shrubland persistence and may be strengthened in the future by predicted increased aridity. An assessment was made of how fires and aridity in combination modulated the dynamics of Mediterranean ecosystems and whether the feedback could be strong enough to maintain shrubland as an alternative stable state to forest. A model was developed for vegetation dynamics, including stochastic fires and different plant fire-responses. Parameters were calibrated using observational data from a period up to 100 yr ago, from 77 sites with and without fires in Southeast Spain and Southern France. The forest state was resilient to the separate impact of fires and increased aridity. However, water stress could convert forests into open shrublands by hampering post-fire recovery, with a possible tipping point at intermediate aridity. Projected increases in aridity may reduce the resilience of Mediterranean forests against fires and drive post-fire ecosystem dynamics toward open shrubland. The main effect of increased aridity is the limitation of post-fire recovery. Including plant fire-responses is thus fundamental when modelling the fate of Mediterranean-type vegetation under climate-change scenarios.


Subject(s)
Forests , Plants/classification , Rain , Wildfires , Climate Change , Mediterranean Region , Models, Biological
18.
PLoS One ; 14(8): e0221667, 2019.
Article in English | MEDLINE | ID: mdl-31442283

ABSTRACT

Competition is a major factor structuring plant communities and controlling their productivity. The functional similarity between the interacting species and the context resource availability are assumed to be most critical factors that modulate the strength, sign, and outcome of plant competition, yet their roles and interactions are subjected to debate. In a glasshouse experiment, we constructed monocultures and bi-specific cultures of three common perennial grasses of Mediterranean drylands, the short grass Brachypodium retusum and the tussock grasses Stipa tenacissima and Lygeum spartum, and investigated how the functional similarity between these species modulate their interactions and culture productivity under contrasting levels of water availability. Regardless the degree of functional similarity between the interacting species, B. retusum consistently exhibited a greater competitive ability than the other two species, followed by L. spartum, and with S. tenacissima behaving as the weakest competitor. Bi-specific cultures of B. retusum and either L. spartum or S. tenacissima produced higher biomass than the average biomass of the respective monocultures (i.e. overyielding), whereas the combination of the most similar species, L. spartum-S. tenacissima, which exhibited the highest competition symmetry (i.e., the more similar mutual impact), did not show any significant overyielding. Higher water availability increased productivity and promoted transgressive overyielding for the most dissimilar species, B. retusum and L. spartum, which however exhibited intermediate competition asymmetry. This study calls attention to the thin line between differences in functional traits and competition asymmetry that could eventually lead to either competitive exclusion or resource partitioning and coexistence.


Subject(s)
Grassland , Poaceae/growth & development , Poaceae/physiology , Biomass , Mediterranean Region , Plant Development , Plant Leaves/anatomy & histology , Poaceae/anatomy & histology , Species Specificity , Water
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