TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice.

In higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A. Ribosome profiling of mouse brain revealed that dysfunction of TRMT10A causes ribosome slowdown at the Gln(CAG) codon and increases translation of Atf4 due to higher frequency of leaky scanning of its upstream open reading frames. Broadly speaking, translation of a subset of mRNAs, especially those for neuronal structures, is perturbed in the mutant brain. Despite not showing discernable defects in the pancreas, liver, or kidney, Trmt10a null mice showed lower body weight and smaller hippocampal postsynaptic densities, which is associated with defective synaptic plasticity and memory. Taken together, our study provides mechanistic insight into the roles of TRMT10A in the brain, and exemplifies the importance of universal tRNA modification during translation of specific codons.

Surgical safety criteria for burr hole surgery with urokinase in patients with acute subdural hematoma: Retrospective comparison between burr hole surgery and craniotomy.

BACKGROUND: Acute subdural hematoma (ASDH) is a common disease and craniotomy is the first choice for removing hematoma. However, patients for whom craniotomy or general anesthesia is contraindicated are increasing due to population aging. In our department, we perform burr hole surgery under local anesthesia with urokinase administration for such patients. We compared the patient background and outcomes between burr hole surgery and craniotomy to investigate the surgical safety criteria for burr hole surgery. METHODS: We reviewed 24 patients who underwent burr hole surgery and 33 patients who underwent craniotomy between January 2010 and April 2020 retrospectively. RESULTS: The median age of the burr hole surgery group was older (P = 0.01) and they had multiple pre-existing conditions. Compared with the craniotomy group, neurological deficits and CT findings were minor in the burr hole surgery group, whereas the maximum hematoma thickness was not significantly different. The hematoma was excreted after a total of 54,000 IU of urokinase was administered for a median of 3 days. The Glasgow Coma Scale score improved in all patients in the burr hole surgery group and there were no deaths. Age, especially over 65 y.o., (OR 1.16, 95% CI 1.04-1.30) and the absence of basal cistern disappearance (OR 0.04, 95% CI 0.004-0.39) were significant factors. CONCLUSION: Burr hole surgery was performed safely in all patients based on the age, especially older than 65 y.o., and the absence of basal cistern disappearance. ASDH in the elderly is increasing and less invasive burr hole surgery with urokinase is suitable for the super-aging society.

Frontal Sinus Repair Using Polymethyl Methacrylate After Bifrontal Craniotomy.

BACKGROUND: In many cases in which bifrontal craniotomy is performed, the frontal sinus is opened, and postoperative complications occur. Various methods to close the frontal sinus have been reported. However, all these methods require skill to perform and take time. The aim of this study was to report results obtained with closure of the frontal sinus using polymethyl methacrylate, which is a simpler method. METHODS: From December 2008 to June 2018, 122 patients with a ruptured anterior communicating aneurysm were transported to the authors' facility, and 52 patients consecutively underwent bifrontal craniotomy with opening of the frontal sinuses, which were then filled with polymethyl methacrylate. RESULTS: Mean follow-up period was 21.8 months; the longest follow-up was 116 months. No cerebrospinal fluid leakage or other complications were observed. CONCLUSIONS: The method of filling the frontal sinus with polymethyl methacrylate reported in this study was safe and had no complications. This method should be considered as a method of frontal sinus closure.