Safety and timing of early therapeutic anticoagulation therapy after craniotomy.

Background: To date, there are few guidelines and studies to guide the timing of initiation of therapeutic anticoagulation (AC) after craniotomy. The goal of this study was to assess the timing, safety, and outcomes of patients following the administration of therapeutic AC after craniotomy. Methods: A retrospective case-control study was performed evaluating all craniotomy patients from August 2017 to July 2021. Cases were selected if they received therapeutic AC within ten days of craniotomy. Nineteen out of 1013 craniotomy patients met the inclusion criteria. Indications for therapeutic AC were diverse, including deep venous thrombosis, pulmonary embolism, dural venous sinus thrombosis, mechanical heart valve, and left ventricular thrombus. Results: The mean and median time to therapeutic AC were 5.35 and 5 days, respectively. Three patients developed intracerebral hemorrhage (ICH) that was stable on repeat imaging and did not require any surgical intervention or result in new neurologic deficits. There was no significant association between therapeutic AC and postoperative ICH (P = 0.067). Conclusion: This study demonstrated that the initiation of therapeutic AC in postoperative craniotomy patients from postoperative days 2 to 10 did not result in any major complications. A prospective study is warranted to clarify the indications and safety of therapeutic AC after craniotomy.

Persistent brainstem abscess requiring repeat microsurgical drainage: case report.

In this paper, we present a patient who was treated for a pontine abscess at our institution. This patient underwent sub-occipital craniotomy for microscopic abscess drainage after which cultures grew Streptococcus intermedius. She was treated with antibiotics but failed to show clinical improvement and was taken back to the operating room for repeat abscess drainage. Clinical improvement was seen after the second operation. This case report describes open surgical technique as a safe and effective way of treating brainstem abscess.

A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR.

BACKGROUND: Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. METHODS: Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study. Measured were: opioid-induced constipation [bowel function index score (BFI)]; analgesic efficacy (NRS 0-10); daily laxative rescue medication use; rescue medication use, and the number of complete spontaneous bowel movements (CSBMs) per week. A subanalysis was conducted in cancer patients. RESULTS: Greater reductions in mean BFI scores were reported for the OXN PR group compared with OxyPR from Week 1 onwards; at Week 5 the mean change from baseline was -32.5 versus -14.2. Average 24-h pain scores were low and remained stable in the range 3-4 in both treatment groups. Analgesic rescue medication use was similar between the groups. Patients receiving OXN PR used significantly lower mean daily doses of laxative rescue medication than those receiving OxyPR (P = 0.006). The number of CSBM in the OXN PR group approximately doubled compared with a 25% decrease in the OxyPR group. Comparable results to the total study population were reported in the cancer patient subgroup. CONCLUSIONS: OXN PR in daily doses of up to 160/80 mg significantly improves bowel function compared with equivalent doses of OxyPR while still providing comparable analgesic efficacy. SIGNIFICANCE: Effective analgesia can be achieved using oxycodone/naloxone PR up to 160/80 mg daily without compromising bowel function. A similar outcome was reported in cancer and non-cancer patients.

Long-term efficacy and safety of oxycodone-naloxone prolonged-release formulation (up to 180/90 mg daily) - results of the open-label extension phase of a phase III multicenter, multiple-dose, randomized, controlled study.

BACKGROUND: The inclusion of naloxone with oxycodone in a fixed combination prolonged-release formulation (OXN PR) improves bowel function compared with oxycodone (Oxy) alone without compromising analgesic efficacy. In a recent 5-week, randomized, double-blind comparative trial of OXN PR and OxyPR, it could be shown that the beneficial properties of OXN PR extend to doses up to 160/80 mg. METHODS: Bowel function, pain, quality of life (QoL) and safety of OXN PR up to 180/90 mg daily were evaluated in a 24-week open-label extension phase of the 5-week randomized comparative study in patients with non-malignant or malignant pain requiring opioids and suffering from opioid-induced constipation. RESULTS: During treatment with a mean (SD) daily dose OXN PR of 130.7 (26.56) mg (median, maximum: 120 and 180 mg), the Bowel Function Index (BFI) decreased from 45.3 (26.37) to 26.7 (21.37) with the largest decrease seen in the first week. The average pain over the last 24 h remained stable (median Pain Intensity Scale score 4.0) and QoL was maintained throughout the study. Adverse events were consistent with the known effects of OXN PR and no new safety concerns emerged. Equivalent efficacy and safety benefits were observed in cancer patients. CONCLUSIONS: The OXN PR in doses up to 180/90 mg provides effective analgesia with maintenance of bowel function during long-term treatment. The beneficial effects of such dose levels of OXN PR contribute to stable patient-reported QoL and health status despite serious underlying pain conditions, such as cancer. SIGNIFICANCE: In patients with pain requiring continuous opioid therapy at doses above 80 mg of oxycodone, stable and effective long-term analgesia can be achieved using OXN PR up to 180/90 mg daily without compromising bowel function and may be preferential to supplemental oxycodone.

The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin ligase for the miRNA pathway protein Ago2.

The let-7 miRNA and its target gene Lin-28 interact in a regulatory circuit controlling pluripotency. We investigated an additional let-7 target, mLin41 (mouse homologue of lin-41), as a potential contributor to this circuit. We demonstrate the presence of mLin41 protein in several stem cell niches, including the embryonic ectoderm, epidermis and male germ line. mLin41 colocalized to cytoplasmic foci with P-body markers and the miRNA pathway proteins Ago2, Mov10 and Tnrc6b. In co-precipitation assays, mLin41 interacted with Dicer and the Argonaute proteins Ago1, Ago2 and Ago4. Moreover, we show that mLin41 acts as an E3 ubiquitin ligase in an auto-ubiquitylation assay and that mLin41 mediates ubiquitylation of Ago2 in vitro and in vivo. Overexpression and depletion of mLin41 led to inverse changes in the level of Ago2 protein, implicating mLin41 in the regulation of Ago2 turnover. mLin41 interfered with silencing of target mRNAs for let-7 and miR-124, at least in part by antagonizing Ago2. Furthermore, mLin41 cooperated with the pluripotency factor Lin-28 in suppressing let-7 activity, revealing a dual control mechanism regulating let-7 in stem cells.

Downstream elements from the pea albumin 1 gene confer sulfur responsiveness on a reporter gene.

The levels of mRNAs for some of the sulfur-rich proteins in seeds are regulated by the level of sulfur supplied to the plants. In peas, there is a mechanism that lowers the level of mRNA for legumin and pea albumin 1 (PA1) when plants are grown under sulfur-deficient conditions. This mechanism acts after transcription initiation. In this study, a gene encoding PA1 was expressed in leaves of transgenic tobacco. Expression of the gene was controlled by the level of sulfur supplied to the plants, mimicking the behaviour of the intact gene in peas. A gene encoding a different high-sulfur protein, ovalbumin, was unresponsive to sulfur status and was used as a reporter gene to test defined regions of the PA1 gene for sulfur responsiveness. These constructs, together with a set of PA1 gene deletions, were tested in transgenic tobacco and yielded the following observations: the PA1 gene was sensitive to sulfur status in the leaf as well as the seed; intron processing of the PA1 transcript was not required for sensitivity to sulfur stress; both the coding region and the 3' flanking regions of the PA1 gene contained sequences which conferred sensitivity to sulfur stress; the sulfur-responsive sequence in the 3' region was contained within a 134-nucleotide segment downstream of the end of the coding sequence. We conclude that there are at least two downstream elements which confer sensitivity to sulfur supply.

Guidelines for specification of animals and husbandry methods when reporting the results of animal experiments. Working Committee for the Biological Characterization of Laboratory Animals/GV-SOLAS.

Any report on the results of animal studies must include sufficient information on the animals used and their conditions of husbandry to enable the reader to understand how the investigation was performed. Only then can he properly interpret the findings. These guide-lines provide a catalogue of the minimum information which should be included in such reports.