Perioperative Naltrexone Management: A Scoping Review by the Perioperative Pain and Addiction Interdisciplinary Network.

Substance use disorders, including alcohol use disorder, are a public health concern that affect more than 150 million people globally. The opioid antagonist naltrexone is being increasingly prescribed to treat opioid use disorder, alcohol use disorder, and chronic pain. Perioperative management of patients on naltrexone is inconsistent and remains a controversial topic, with mismanagement posing a significant risk to the long-term health of these patients. This scoping review was conducted to identify human studies in which the perioperative management of naltrexone was described. This review includes a systematic literature search involving Medline, Medline In-Process, Embase, PsycINFO, and Web of Science. Seventeen articles that describe perioperative naltrexone management strategies were included, including thirteen guidelines, one case report, and three randomized trials. Despite its use in patients with alcohol use disorder and chronic pain, no clinical studies, case reports, or guidelines addressed naltrexone use in these clinical populations. All of the guideline documents recommended the preoperative cessation of naltrexone, irrespective of dose, indication, or route of administration. None of these guideline documents were designed on the basis of a systematic literature search or a Delphi protocol. As described by the primary studies, perioperative pain relief varied depending on naltrexone dose and route of administration, time since last naltrexone administration, and underlying substance use disorder. None of the studies commented on the maintenance of recovery for the patient's substance use disorder in the context of perioperative naltrexone management. The current understanding of the risks and benefits of continuing or stopping naltrexone perioperatively is limited by a lack of high-quality evidence. In patients with risk factors for return to use of opioids or alcohol, the discontinuation of naltrexone should have a strong rationale. Future studies and guidelines should seek to address both acute pain management and maintaining recovery when discussing perioperative naltrexone management strategies.

Global trends and decision-making in the management of arachnoid cysts.

OBJECTIVE: In pediatric patients, middle cranial fossa (MCF) arachnoid cysts are often discovered incidentally on imaging in asymptomatic patients during workup for other indications. This study aims to describe current management gestalt and threshold for surgical intervention by surveying an international cohort of neurosurgeons. METHODS: A web-based survey was circulated via email list of attendants of the 2019 Canadian Pediatric Neurosurgery Study Group (CPNSG) and International Society of Pediatric Neurosurgery (ISPN) mailing list. The survey consisted of 8 clinical scenarios involving patients with MCF arachnoid cysts. Demographic variables of respondents and their decisions regarding management for each scenario were analyzed using R computing software. RESULTS: A total of 107 respondents were included. Cysts in asymptomatic patients (92%), younger age at diagnosis (81%), and presence of a mild learning delay were predominantly managed non-surgically (80.7 ± 9.4%). Patients with cyst enlargement, headaches, new seizures, or hemorrhage were divided between non-surgical (55.8 ± 3.3%) and surgical (44.2 ± 2.9%) management. Patients with contralateral hemiparesis were treated predominantly surgically (67%). For both Galassi I and II, papilledema was favored as the primary indication for surgical intervention in 54% of patients. Those inclined to surgery (n = 17) were more likely to practice and train outside North America compared to those not pro-surgical (adjusted P = 0.092). CONCLUSION: Incidental MCF arachnoid cysts in asymptomatic patients and younger age of diagnosis are predominantly managed non-surgically. Mild learning delay was not considered an indication to intervene. In contrast, radiological progression, hemorrhagic evolution, or non-focal neurological deficits lead to uncertainty in management, while focal neurological deficits and papilledema with MCF cysts were favored to be intervened surgically. Among the provider level factors, only location of training and practice trended towards a pro-surgery approach.

Effects of forest management practices on carbon dynamics of China's boreal forests under changing climates.

Climate change and forest management practices influence forest productivity and carbon budgets, and understanding their interactions is necessary to develop accurate predictions of carbon dynamics as many countries in the world strive towards carbon neutrality. Here, we developed a model-coupling framework to simulate the carbon dynamics of boreal forests in China. The expected dynamics of forest recovery and change following intense timber harvesting in the recent past and projected carbon dynamics into the future under different climate change scenarios and forest management practices (e.g., restoration, afforestation, tending, and fuel management). We predict that under current management strategies, climate change would lead to increased fire frequency and intensity, eventually shifting these forests from carbon sinks towards being carbon sources. This study suggests that future boreal forest management should be altered to reduce the probability of fire occurrence and carbon losses caused by catastrophic fires through planting deciduous species, mechanical removal, and prescribed fire.

Artificial intelligence deep learning for 3D IC reliability prediction.

Three-dimensional integrated circuit (3D IC) technologies have been receiving much attention recently due to the near-ending of Moore's law of minimization in 2D IC. However, the reliability of 3D IC, which is greatly influenced by voids and failure in interconnects during the fabrication processes, typically requires slow testing and relies on human's judgement. Thus, the growing demand for 3D IC has generated considerable attention on the importance of reliability analysis and failure prediction. This research conducts 3D X-ray tomographic images combining with AI deep learning based on a convolutional neural network (CNN) for non-destructive analysis of solder interconnects. By training the AI machine using a reliable database of collected images, the AI can quickly detect and predict the interconnect operational faults of solder joints with an accuracy of up to 89.9% based on non-destructive 3D X-ray tomographic images. The important features which determine the "Good" or "Failure" condition for a reflowed microbump, such as area loss percentage at the middle cross-section, are also revealed.

Repurposing loperamide to overcome gefitinib resistance by triggering apoptosis independent of autophagy induction in KRAS mutant NSCLC cells.

BACKGROUND: Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for first-line treatment of non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. However, NSCLC patients bearing mutant KRAS are inherently unresponsive to gefitinib. Defective autophagy was proposed to mediate resistance to EGFR-TKIs. In this study, the reversal of primary resistance to gefitinib in NSCLC by putative autophagy inducers was investigated. MATERIALS AND METHODS: A few putative autophagy inducers were investigated in NSCLC cells harboring KRAS or EGFR mutations. Quantitative real-time PCR and Western blot analysis were used to evaluate expression of autophagy-related genes and proteins. Sulforhodamine B assay was used to evaluate cytotoxicity of drug combinations. Flow cytometric asssays were used to study apoptotic and cell cycle effects. RESULTS: The antidiarrheal agent loperamide was identified as an autophagy inducer. Loperamide promoted the formation of autophagosomes and it potentiated the cytotoxic effect of gefitinib specifically in NSCLC cells bearing mutant KRAS and wild-type EGFR. Gefitinib-loperamide combination enhanced apoptosis and G1 cell cycle arrest, both of which could not be reversed by pharmacological autophagy inhibitor (3-methyladenine). Moreover, synergistic anticancer effect of gefitinib-loperamide combination was observed in both autophagy-proficient (Atg5-wild type) and -deficient (Atg5-knockout) mouse embryonic fibroblasts. Loperamide overcome gefitinib resistance in NSCLC harboring mutant KRAS and wild-type EGFR through increased apoptosis but independent of autophagy induction. CONCLUSION: Loperamide could be repurposed to overcome primary resistance to gefitinib in KRAS-mutation bearing NSCLC as it also helps relieve the common side effect of diarrhea caused by EGFR-TKIs.

Repurposing of niclosamide as a STAT3 inhibitor to enhance the anticancer effect of chemotherapeutic drugs in treating colorectal cancer.

AIMS: Colorectal cancer (CRC) is the third most common cancer worldwide. Mutation of various cell signaling molecules or aberrant activation of signaling pathways leads to poor response to chemotherapy in CRC. Signal transducer and activator of transcription protein 3 (STAT3) is an important signaling molecule, which plays crucial roles in regulating cell survival and growth. In this study, the potentitation of chemotherapy by putative STAT3 inhibitors for treating CRC was investigated. MAIN METHODS: A few putative STAT3 inhibitors were investigated. Niclosamide, originally indicated for the treatment of tapeworm infection, was chosen for further investigation in five CRC cell lines (HCT116, HT29, HCC2998, LoVo and SW480). Western blot analysis was used to evaluate the expression of STAT3/phospho-STAT3 and its downstream targets. Sulforhodamine B assay was used to evaluate the cytotoxicity of drug combinations. Flow cytometric assays were used to investigate the apoptotic and cell cycle effect. KEY FINDINGS: Niclosamide was found to inhibit expression and activation of STAT3 in a concentration- and time-dependent manner, thereby downregulating STAT3 downstream targets including survivin and cyclin-D1 to induce apoptosis and cell cycle arrest. When combined with niclosamide or specific STAT3 inhibitor (C188-9), the cytotoxicity and DNA damage response from SN38 (the active metabolite from irinotecan) were significantly enhanced. The sequential exposure of SN38 followed by niclosamide was found to be the most potent treatment sequence for the drug combination. SIGNIFICANCE: Niclosamide represents a promising candidate for repurposing to potentiate the anticancer activity of chemotherapeutic drugs.

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development.

Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6-22 years old, mean age: 13.6 +/-3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues.