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2019
Salpietro, V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S et al..  2019.  AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders, 2019. Nature Communications. 10(1) Abstract

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.

Chelban, V, Wilson MP, Warman Chardon J, Vandrovcova J, Zanetti MN, Zamba-Papanicolaou E, Efthymiou S, Pope S, Conte MR, Abis G et al..  2019.  PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation, 2019. Annals of Neurology. 86(2) Abstract

Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240.

Xiao, M, Zang H, Ge T, Chen A, Zhu Z, Zhou P, Atere CT, Wu, J., Y. S, Kuzyakov Y.  2019.  Effect of nitrogen fertilizer on rice photosynthate allocation and Carbon input in paddy soil. European Journal of Soil Science . 70(4):786–795.
2017
Zhu, Z, Ge T, Xiao M, Yuan H, Wang, T., Liu S, Atere CT, Wu J.  2017.  Belowground carbon allocation and dynamics under rice cultivation depends on soil organic matter content. Plant and Soil. 410:247–258.
Shacklett, BL, Derdeyn CA, Folayan MO, Landovitz RJ, Anthony C, Behrens A-J, Hope TJ, Landais E, Leal L, Marrazzo JM, Morris L, Mugo N, Ngure K, Noseda V, Ranasinghe S, Tully DC, Voronin Y, Warren M, Wibmer CK, Xie IY, Scarlatti G, Thyagarajan B.  2017.  HIVR4P 2016, partnering for prevention: conference summary and highlights. . AIDS Research and Human Retroviruses Journal . :.doi:10.1089/AID.2017.0125.
2008
Perel, PA, Olldashi F, Muzha I, Filipi N, Lede R, Copertari P, Traverso C, Copertari A, Vergara EA, Montenegro C et al..  2008.  Predicting outcome after traumatic brain injury: Practical prognostic models based on large cohort of international patients, 2008. BMJ. 336(7641) Abstract

Objective: To develop and validate practical prognostic models for death at 14 days and for death or severe disability six months after traumatic brain injury. Design: Multivariable logistic regression to select variables that were independently associated with two patient outcomes. Two models designed: "basic" model (demographic and clinical variables only) and "CT" model (basic model plus results of computed tomography). The models were subsequently developed for high and low-middle income countries separately. Setting: Medical Research Council (MRC) CRASH Trial. Subjects: 10 008 patients with traumatic brain injury. Models externally validated in a cohort of 8509. Results: The basic model included four predictors: age, Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. The CT model also included the presence of petechial haemorrhages, obliteration of the third ventricle or basal cisterns, subarachnoid bleeding, midline shift, and non-evacuated haematoma. In the derivation sample the models showed excellent discrimination (C statistic above 0.80). The models showed good calibration graphically. The Hosmer-Lemeshow test also indicated good calibration, except for the CT model in low-middle income countries. External validation for unfavourable outcome at six months in high income countries showed that basic and CT models had good discrimination (C statistic 0.77 for both models) but poorer calibration. Conclusion: Simple prognostic models can be used to obtain valid predictions of relevant outcomes in patients with traumatic brain injury.

2004
Olldashi, F, Muzha I, Filipi N, Lede R, Copertari P, Traverso C, Copertari A, Vergara EA, Montenegro C, De Huidobro RR et al..  2004.  Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): Randomised placebo-controlled trial, 2004. The Lancet. 364(9442) Abstract

Background Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial—a multicentre international collaboration—aimed to confirm or refute such an effect by recruiting 20 000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. Methods 10 008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. Findings Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21·1%] vs 893 [17·9%] deaths; relative risk 1·18 [95% CI 1·09-1·27]; p=0·0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0·22) or time since injury (p=0·05). Interpretation Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.

1988
Aladesanmi, AJ, Adewunmi CO, Kelley CJ, Leary JD, Bischoff TA, Xiaolin Z, Snyder JK.  1988.  Lenticellarine, A Molluscicidal Alkaloid from Dysoxylum lenticellare, Phytochemistry. 27:3789-3792.