Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior.

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.

Using psychometric ability to improve education in ultrasound-guided regional anaesthesia: a multicentre randomised controlled trial.

The learning curve for novices developing regional anaesthesia skills, such as real-time ultrasound-guided needle manipulation, may be affected by innate visuospatial ability, as this influences spatial cognition and motor co-ordination. We conducted a multinational randomised controlled trial to test if novices with low visuospatial ability would perform better at an ultrasound-guided needling task with deliberate practice training than with discovery learning. Visuospatial ability was evaluated using the mental rotations test-A. We recruited 140 medical students and randomly allocated them into low-ability control (discovery learning), low-ability intervention (received deliberate practice), high-ability control, and high-ability intervention groups. Primary outcome was the time taken to complete the needling task, and there was no significant difference between groups: median (IQR [range]) low-ability control 125 s (69-237 [43-600 s]); low-ability intervention 163 s (116-276 [44-600 s]); high-ability control 130 s (80-210 [41-384 s]); and high-ability intervention 177 s (113-285 [43-547 s]), p = 0.06. No difference was found using the global rating scale: mean (95%CI) low-ability control 53% (95%CI 46-60%); low-ability intervention 61% (95%CI 53-68%); high-ability control 63% (95%CI 56-70%); and high-ability intervention 66% (95%CI 60-72%), p = 0.05. For overall procedure pass/fail, the low-ability control group pass rate of 42% (14/33) was significantly less than the other three groups: low-ability intervention 69% (25/36); high-ability control 68% (25/37); and high-ability intervention 85% (29/34) p = 0.003. Further research is required to determine the role of visuospatial ability screening in training for ultrasound-guided needle skills.

Does the volume of supplemental intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized-double blind clinical trial.

AIM: To investigate the efficacy of 0.2 mL vs. 0.6 mL of 2% lidocaine when given as a supplementary intraligamentary injection after a failed inferior alveolar nerve block (IANB). METHODOLOGY: Ninety-seven adult patients with symptomatic irreversible pulpits received an IANB and root canal treatment was initiated. Pain during treatment was recorded using a visual analogue scale (Heft-Parker VAS). Patients with unsuccessful anaesthesia (n = 78) randomly received intraligamentary injection of either 0.2 mL or 0.6 mL of 2% lidocaine with 1 : 80 000 epinephrine. Root canal treatment was reinitiated. Success after primary injection or supplementary injection was defined as no or mild pain (HP VAS score ≤54 mm) during access preparation and root canal instrumentation. Heart rate was monitored using a finger pulse oximeter. The anaesthetic success rates were analysed with Pearson chi-square test at 5% significance levels. The heart rate changes were analysed using t-tests. RESULTS: The intraligamentary injections with 0.2 mL solution gave an anaesthetic success rate of 64%, whilst the 0.6 mL was successful in 84% of cases with failed primary IANB. (χ2  = 4.3, P = 0.03). There was no significant effect of the volume of intraligamentary injection on the change in heart rate. CONCLUSIONS: Increasing the volume of intraligamentary injection improved the success rates after a failed primary anaesthetic injection.

Comparison of the anaesthetic efficacy of epinephrine concentrations (1 : 80 000 and 1 : 200 000) in 2% lidocaine for inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a randomized, double-blind clinical trial.

AIM: The aim of this randomized controlled, double-blind trial was to comparatively evaluate the anaesthetic efficacy and injection pain of 1.8 mL of 2% lidocaine with different concentrations of epinephrine (1 : 80 000 and 1 : 200 000) in patients with symptomatic irreversible pulpitis. METHODOLOGY: Sixty-two adult volunteers, actively experiencing pain, were randomly allocated into 2 groups and received 1.8 mL of 2% lidocaine with either 1 : 80 000 or 1 : 200 000 epinephrine concentration. Endodontic access preparation was initiated 15 min after the initial IANB. Pain during treatment was recorded using the Heft-Parker visual analogue scale (HP VAS). The primary outcome measure, and the definition of 'success', was the ability to undertake pulp access and canal instrumentation with no or mild pain (HP VAS score <55 mm). Secondary outcome measure was the pain experienced during LA solution deposition. Statistical analysis was performed using Mann-Whitney U-test and chi-square test. RESULTS: The anaesthetic success rates of 2% lidocaine solutions containing 1 : 80 000 and 1 : 200 000 epinephrine concentrations were 20% and 28%, respectively. The difference was not statistically significant. There was also no significant difference in the pain experienced during deposition of the solutions. CONCLUSIONS: Two percent lidocaine solution used for IANB achieved similar success rates when used with 1 : 80 000 or 1 : 200 000 epinephrine concentration.

Progressive multifocal leucoencephalopathy in HIV/AIDS: observational study from a tertiary care centre in northern India.

BACKGROUND & OBJECTIVES: Progressive multifocal leucoencephalopathy (PML) is seen mostly in advanced human immunodeficiency virus (HIV) infection. Little is known about the epidemiology and disease course of these patients from India. This study was aimed to determine the frequency of PML in patients with HIV/AIDS, and the clinical features and survival of these patients. METHODS: The charts of HIV/AIDS patients with PML seen over a period of five years (2006-2011) at the Antiretroviral treatment (ART) centre at a tertiary care centre in New Delhi, India, were retrospectively reviewed. RESULTS: Of 1465 patients with HIV/AIDS, 18 (1.2%) were diagnosed with PML; four were laboratory confirmed and 14 had consistent clinical and radiological features. PML was the initial presentation of HIV infection in 10 (56%) patients, and 16 (89%) patients had CD4 count less than 200/µl. Insidious onset focal limb weakness (78%) and visual disturbance (28%) were common symptoms. Magnetic resonance imaging (MRI) of the brain revealed characteristic white matter lesions in all the patients. The estimated median survival was 7.6 months (95% CI, 0-20 months). INTERPRETATION & CONCLUSIONS: Our results show that the patients present late to access treatment with advanced immunosuppression at presentation. PML is associated with high morbidity and mortality despite institution of highly active antiretroviral therapy (HAART). There is a need to address the lacuna in diagnostic and management services for these patients in India.

Ultrasonographic evaluation of gallbladder volume in diabetics.

AIMS AND OBJECTIVE: Ultrasonographic determination of gallbladder volume in diabetics [both type I and type 2], it's comparison with a control group, and correlation of gallbladder volume in diabetics with parameters such as age, sex, body mass index, parity, hyperlipidaemia, and autonomic neuropathy. MATERIALS AND METHOD: Ninety one cases of diabetes mellitus and 40 healthy controls were recruited for the study. A detailed history and physical examination were recorded. Laboratory investigations done were--fasting and postprandial blood sugar, glycosylated haemoglobin, microalbuminuria, and serum lipid profile. Autonomic neuropathy was determined by using simple non-invasive bedside tests. Fasting gallbladder volume was measured by ultrasonography (calculated by ellipsoid formula). RESULTS: The mean fasting gallbladder volume was 18.20 +/- 2.54 ml in type I diabetics and 25.87 +/- 13.90 ml in type 2 diabetics, with a minimum value of 9.30 ml and maximum value of 88 ml. When type 2 diabetics were subgrouped according to the presence of autonomic neuropathy, higher gallbladder volumes were seen in patients with autonomic neuropathy. CONCLUSIONS: Cholecystomegaly, to a significant degree, was found in type 2 diabetics in the present study. It was significantly correlated with age, body mass index, and the severity of autonomic neuropathy. In male type 2 diabetics, gallbladder volume was significantly correlated with LDL cholesterol levels. In female type 2 diabetics, gallbladder volume was significantly correlated with waist-hip ratio. Gallbladder volume also had significant correlation with proliferative diabetic retinopathy, but not with glycaemic control, microalbuminuria, hypertension, or the duration of diabetes.

Breakage of insulin syringe needle in subcutaneous tissue.

We report the case of a young girl with diabetes mellitus whose insulin syringe needle broke and became embedded in subcutaneous tissue.

Self reported attitude and behavior of young diabetics about discussing their disease.

A performa-guided survey was conducted among 47 young patients of diabetes mellitus (onset of diabetes <30 years). Questions included were regarding the type of treatment, health status information about diabetes, and the assumptions and experiences of the patients on certain psychosocial behavior. A total of 59.6% subjects said that they could disclose everything about their disease to their friends and acquaintances. Twenty-seven percent felt that they could divulge only partial information and 12.8% did not want to discuss their disease with their friends and acquaintances. Subjects who said that they could disclose about their disease felt that they could do so because they were putting a lot of effort into achieving better control of their blood glucose. One of the fears expressed about not discussing their disease was that in doing so people would treat them differently or perceive them as sick. However only 38% experienced such a change in the behaviour of their acquaintances. Seventy-three percent of them had received unsolicited advice from others about food and dietary restrictions. Forty-three percent of the subjects had received instructions from acquaintances to stop all treatment and shift to household remedies. Hypoglycemia could be a motivating factor to help patients to discuss their illness with the acquaintances.