Evolutionary Trends in the Mitochondrial Genome of Archaeplastida: How Does the GC Bias Affect the Transition from Water to Land?

[EN] Among the most intriguing mysteries in the evolutionary biology of photosynthetic organisms are the genesis and consequences of the dramatic increase in the mitochondrial and nuclear genome sizes, together with the concomitant evolution of the three genetic compartments, particularly during the transition from water to land. To clarify the evolutionary trends in the mitochondrial genome of Archaeplastida, we analyzed the sequences from 37 complete genomes. Therefore, we utilized mitochondrial, plastidial and nuclear ribosomal DNA molecular markers on 100 species of Streptophyta for each subunit. Hierarchical models of sequence evolution were fitted to test the heterogeneity in the base composition. The best resulting phylogenies were used for reconstructing the ancestral Guanine-Cytosine (GC) content and equilibrium GC frequency (GC*) using non-homogeneous and non-stationary models fitted with a maximum likelihood approach. The mitochondrial genome length was strongly related to repetitive sequences across Archaeplastida evolution; however, the length seemed not to be linked to the other studied variables, as different lineages showed diverse evolutionary patterns. In contrast, Streptophyta exhibited a powerful positive relationship between the GC content, non-coding DNA, and repetitive sequences, while the evolution of Chlorophyta reflected a strong positive linear relationship between the genome length and the number of genes.This research was funded by the European Commission (Environment - LIFE Programme) project for the Comunidad Valenciana (Spain), LIFE05 NAT/E/000060.Pedrola-Monfort, J.; Lázaro-Gimeno, D.; Boluda, CG.; Pedrola, L.; Garmendia, A.; Soler, C.; Soriano, JM. (2020). Evolutionary Trends in the Mitochondrial Genome of Archaeplastida: How Does the GC Bias Affect the Transition from Water to Land?. Plants. 9(3):1-15. https://doi.org/10.3390/plants9030358S1159

Evolutionary Trends in the Mitochondrial Genome of Archaeplastida: How Does the GC Bias Affect the Transition from Water to Land?

Among the most intriguing mysteries in the evolutionary biology of photosynthetic organisms are the genesis and consequences of the dramatic increase in the mitochondrial and nuclear genome sizes, together with the concomitant evolution of the three genetic compartments, particularly during the transition from water to land. To clarify the evolutionary trends in the mitochondrial genome of Archaeplastida, we analyzed the sequences from 37 complete genomes. Therefore, we utilized mitochondrial, plastidial and nuclear ribosomal DNA molecular markers on 100 species of Streptophyta for each subunit. Hierarchical models of sequence evolution were fitted to test the heterogeneity in the base composition. The best resulting phylogenies were used for reconstructing the ancestral Guanine-Cytosine (GC) content and equilibrium GC frequency (GC*) using non-homogeneous and non-stationary models fitted with a maximum likelihood approach. The mitochondrial genome length was strongly related to repetitive sequences across Archaeplastida evolution; however, the length seemed not to be linked to the other studied variables, as different lineages showed diverse evolutionary patterns. In contrast, Streptophyta exhibited a powerful positive relationship between the GC content, non-coding DNA, and repetitive sequences, while the evolution of Chlorophyta reflected a strong positive linear relationship between the genome length and the number of genes

Etiología y manejo de la neuropatía diabética dolorosa

Aetiology: Painful diabetic neuropathy affects approximately 25% of diabetic patients, those treated with insulin and/or glucose lowering drugs, and is characterised by presenting as a distal symmetric neuropathy associated with chronic pain. Pathophysiology The cause is generally vascular, which produces a lesion of the primary sensory nerves due to neuronal hypoxia and lack of nutrients. Symptoms: The onset is usually bilateral in the toes and feet. In cases where it is asymmetric, it progresses to be bilateral. It can gradually progress to the calves and the knees, in which case the patient may experience symptoms of pain and/or paresthesia both in the hands and feet ("glove-stocking" pattern). They describe the pain using diverse terms: burning, electric, deep, etc. Allodynia and hyperalgesia are less common. The pain intensity is usually gets worse at night. Other symptoms: vascular claudication, dysautonomic signs (skin colour, abnormal temperature, sweating), depression and anxiety, sleep disorders. Physical findings: Sensory loss and the loss or decrease in Achilles tendon reflex is characteristic in "glove-stocking", although some patients who only have small nerve fibres involvement may have normal reflexes and vibratory sensitivity. Diagnosis: It is clinical. There is no need for electro-physiological studies when the history and physical findings are consistent with the diagnosis of painful diabetic neuropathy. Natural history: The natural history of painful diabetic neuropathy varies and its clinical course unpredictable. In some patients, the pain may improve after months or years, while in others it persists and gets worse. Treatment: Due the great number of causal and contributing factors in the pathogenesis of diabetic neuropathy, there is no single satisfactory treatment. The maintenance of a glycosylated haemoglobin between 6.5 and 7.5% can slow down and even prevent the progression of neuropathy. The current treatment recommendations for painful diabetic neuropathy can be seen in table 5 and figure 1.Etiología: La neuropatía diabética dolorosa afecta aproximadamente al 25% de los pacientes diabéticos, aquellos tratados con insulina y/o hipoglucemiantes orales, y se caracteriza por presentarse como una neuropatía distal simétrica asociada a dolor crónico. Fisiopatología: Generalmente es de causa vascular, que provoca lesión de los nervios sensitivos primarios por hipoxia neuronal y déficit de nutrientes. Síntomas: El inicio suele ser bilateral en dedos y pies. En los casos de origen asimétrico, la progresión es hacia la bilateralidad. Puede progresar gradualmente a pantorrillas y rodillas, en cuyo caso los pacientes pueden notar síntomas álgicos y/o parestesias de forma conjunta en manos y pies (patrón de «guante-calcetín»). El dolor lo describen con diversos términos: urente, eléctrico, profundo. La alodinia y la hiperalgesia son menos comunes. La intensidad del dolor suele empeorar por la noche. Otros síntomas: claudicación vascular, signos disautonómicos (color de la piel y temperatura anormal, sudoración), depresión y ansiedad, trastornos del sueño. Hallazgos físicos: Es característico el déficit sensitivo en «guante-calcetín» y la pérdida o disminución del reflejo aquíleo, aunque algunos pacientes que solo tienen afectación de fibras nerviosas pequeñas pueden tener preservados los reflejos y la sensibilidad vibratoria. Diagnóstico: Es clínico. No hay necesidad de realizar estudios electrofisiológicos cuando la historia y los hallazgos físicos son consistentes con el diagnóstico de neuropatía diabética dolorosa. Historia natural: La historia natural de la neuropatía diabética dolorosa es variable y su curso clínico, impredecible. En algunos pacientes, el dolor puede mejorar después de meses o años, mientras que en otros persiste y empeora. Tratamiento: Debido a la gran variedad de factores causales y contribuyentes en la patogenia de la neuropatía diabética, no existe un tratamiento único satisfactorio. El mantenimiento de una hemoglobina glicosilada entre 6,5 y 7,5% puede enlentecer e incluso prevenir la progresión de la neuropatía. En la actualidad las recomendaciones de tratamiento de la neuropatía diabética dolorosa se pueden observar en la tabla 5 y figura 1

Lack of GDAP1 Induces Neuronal Calcium and Mitochondrial Defects in a Knockout Mouse Model of Charcot-Marie-Tooth Neuropathy

27 páginas, 9 figuras.Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic reticulum (ER) Ca2+, likely in association with an abnormal distribution of the mitochondrial network. To investigate the functional consequences of lack of GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals presented abnormal motor behavior starting at the age of 3 months. Electrophysiological and biochemical studies confirmed the axonal nature of the neuropathy whereas histopathological studies over time showed progressive loss of motor neurons (MNs) in the anterior horn of the spinal cord and defects in neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root ganglia neurons from affected animals demonstrated large and defective mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal α-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced cytosolic calcium and SOCE response. The development and characterization of the GDAP1 neuropathy mice model thus revealed that some of the pathophysiological changes present in axonal recessive form of the GDAP1-related CMT might be the consequence of changes in the mitochondrial network biology and mitochondria-endoplasmic reticulum interaction leading to abnormalities in calcium homeostasis.This work has been funded by grants from the Spanish Ministry of Economy and Competitiveness, grants no. SAF2009-07063 and SAF2012-32425 (to FP), the Collaborative Joint Project awarded by IRDiRC and funded by ISCIII grant IR11/TREAT-CMT, Instituto de Salud Carlos III (to both FP and JMC), the Generalitat Valenciana Prometeo Programme 2009/059 and 2014/029 (to FP) and the Swiss National Science Foundation, grant no. 31003A_135735/1 (to RC). This work has also been funded by the CIBERER, an initiative from the Instituto de Salud Carlos III. MB-M is the recipient of a FPI fellowship, from the Spanish Ministry of Economy and Competitiveness. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Intraoperative transfusion practices in Europe

BACKGROUND: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. METHODS: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. RESULTS: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl(-1) and increased to 9.8 (1.8) g dl(-1) after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). CONCLUSION: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl(-1)), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold. CLINICAL TRIAL REGISTRATION: NCT 01604083

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj −0·3%, 95% CI −2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; −0·4%, −3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. Funding: European Society of Anaesthesiology

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications.Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged >= 18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARR(adj)). This study is registered with ClinicalTrials. gov, number NCT01865513.Findings Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7.6%] of 21 694); ORadj 1.86, 95% CI 1.53-2.26; ARR(adj) -4.4%, 95% CI -5.5 to -3.2). Only 2.3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1.31, 95% CI 1.15-1.49; ARR(adj) -2.6%, 95% CI -3.9 to -1.4) and the administration of reversal agents (1.23, 1.07-1.41; -1.9%, -3.2 to -0.7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1.03, 95% CI 0.85-1 center dot 25; ARR(adj) -0.3%, 95% CI -2.4 to 1.5) nor extubation at a train-of-four ratio of 0.9 or more (1.03, 0.82-1.31; -0.4%, -3.5 to 2.2) was associated with better pulmonary outcomes.Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications

Management practices for postdural puncture headache in obstetrics : a prospective, international, cohort study

Background: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP. Methods: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months. Results: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19-1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score <= 3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group. Conclusions: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP