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Elevations in intracellular glucose concentrations are essential for epithelial cell differentiation by mechanisms that are not fully understood. Glucose has recently been found to directly bind several proteins to alter their functions to enhance differentiation. Among the newly identified glucose-binding proteins is NSUN2, an RNA-binding protein that we identified as indispensable for epidermal differentiation. Glucose was found to bind conserved sequences within NSUN2, enhancing its binding to S-adenosyl-L-methionine and boosting its enzymatic activity. Additionally, glucose enhanced NSUN2's proximity to proteins involved in mRNA translation, with NSUN2 modulating global messenger RNA (mRNA) translation, particularly that of key pro-differentiation mRNAs containing m5C modifications, such as GRHL3. Glucose thus engages diverse molecular mechanisms beyond its energetic roles to facilitate cellular differentiation processes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Two cases of severe bone pains from metastatic cancer, without clinical or radiological evidence of fractures on admission, are presented. Pain control and mobilization were achieved initially with local anaesthetic-opioid epidural infusion. Subsequent loss of analgesia prompted a re-examination, which revealed pathological fractures of the femur. Internal fixation of the fractures resulted in good control such that strong opioids were no longer required.

Sixty-one women undergoing major gynaecological surgery received slow release morphine (MST) 60 mg, with placebo, hyoscine 0.6 mg or diazepam 10 mg, by mouth 2 h before surgery. Plasma morphine concentrations reached a steady level usually within 3 h after administration of MST, and did not increase after surgery unless supplementary opioid was given. Hyoscine delayed morphine absorption. Before operation no fewer than 50% of patients were sedated after MST alone, but this increased to 85% after MST and diazepam. Similarly, only the combination MST and diazepam produced anxiolysis. Postoperative mood was unhappier after MST and hyoscine. Emesis occurred in 40-57% of patients, and was not reduced by hyoscine. Therefore premedication with MST alone did not produce reliable sedation or anxiolysis. A combination of hyoscine and MST premedication cannot be recommended, as it did not produce sedation, anxiolysis or antiemesis and hyoscine may have delayed morphine absorption.

Cryoanalgesia, the local application of extreme cold to nerves to produce analgesia, has been used to treat patients with intractable perineal pain. The cryoprobe was inserted percutaneously through the sacral hiatus into the sacral canal to produce anaesthesia of the lower sacral nerve roots. Forty patients received a total of 70 treatments: 31 patients (78%) were helped by the procedure and the median duration of improvement was 30 days. The treatment was more successful in relieving symptoms in patients suffering from pelvic cancer and coccydynia. The best results were obtained in those patients who received numerous freeze applications or prolonged freezing.

Our results show that about 40% of patients who have cordotomies for non-malignant pain gain a prolonged and worthwhile period of relief, allowing a return to work and normal living. The available evidence, though scanty, suggests that the decline in the analgesic efficacy of cordotomy tends to 'plateau' with the passage of time, though the exact pattern of this change remains undefined. We conclude that, while the complication rate of cordotomy is undoubtedly high, and its effectiveness far from ideal, it may nevertheless have a place in the treatment of carefully selected patients with intractable pain due to non-malignant causes.

A case is reported of bilateral chronic subdural haematomas in a 29-year-old woman 1 month after childbirth under attempted epidural analgesia. The possible link between leakage of cerebrospinal fluid through a hole in the lumbar theca and the later development of an intracranial chronic subdural haematoma is discussed, with a review of eleven previous reported cases.