Search

Over the past decades, the global prevalence of Type 2 diabetes mellitus (T2D) and impaired glucose tolerance (IGT) has been increasing at an epidemic rate, yet the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms and sleep disturbances. Concurrently, exposures to light at night have been closely linked to circadian and sleep disturbances. However, there is no direct experiment on primates to demonstrate the precise extent of how serious light pollution impairs glucose metabolism, whether people will eventually become accustomed to this environment, and whether the pollution has synergistic impairing effects with aging and weight on glucose metabolism. To quantitatively address these questions, 137 cynomolgus were exposed to three distinct nocturnal light intensities for consecutive 10 months. Monthly glucose metabolism assessments were conducted. Data pertaining to the mortality rate of preexisting diabetes, incidence of light‐induced diabetes and IGT, and alterations in insulin secretion were collected and analyzed. The results show that nocturnal light (1) caused premature deaths in individuals with preexisting diabetes; (2) intensity‐dependently induced diabetes and IGT in previous healthy monkeys; (3) intensity‐dependently reduced melatonin secretion; (4) had a synergistic impairing effect on glucose metabolism with aging and weight; and (5) although monkeys would eventually adapt to the environment, the disrupted glucose metabolism would not fully recover in most individuals. In conclusion, nocturnal light is associated with the global high prevalence of T2D and IGT. The harmful effects of light pollution on glucose metabolism are synergistic with age and weight. [ABSTRACT FROM AUTHOR]

In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which is induced by the novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) is the most common comorbidity. This triangular relationship can be attributed to the dysfunction of the insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible to SARS-CoV-2 infection due to the widespread expression of angiotensin converting enzyme 2 (ACE2) in their pancreatic beta cells, which serves as the cellular port for the SARS-CoV-2 to infect and enter the cell. This infection can exacerbate chronic pain and insulin resistance for various reasons. Peripherally, once infected, the virus can cause damage to peripheral nerves and pancreatic β-cells, further exacerbating pain and glucose metabolism conditions. Additionally, in the central nervous system, dysfunctional IRSS is closely linked to chronic pain. Over the past few years of the COVID-19 pandemic, an increasing body of evidence suggests that insulin and other medications currently used in clinical practice for hyperglycemia control may not be safe for treating these patients. Therefore, we need a proper approach for the treatment of chronic pain in long COVID patients, especially patients with T2D. This review presents evidence that transcutaneous auricular vagal nerve stimulation (taVNS) may provide a viable treatment option for chronic pain and metabolic dysfunction by improving the function of IRSS in both the central nervous system and peripheral tissues. [ABSTRACT FROM AUTHOR]

Background: As lymphovascular space invasion (LVSI) was closely related to lymph node metastasis and prognosis, the preoperative assessment of LVSI in early‐stage cervical cancer is crucial for patients. Purpose: To develop and validate nomogram based on multimodal MR radiomics to assess LVSI status in cervical cancer patients. Study Type: Retrospective. Population: The study included 168 cervical cancer patients, of whom 129 cases (age 51.36 ± 9.99 years) from institution 1 were included as the training cohort and 39 cases (age 52.59 ± 10.23 years) from institution 2 were included as the external test cohort. Field Strength/Sequence: There were 1.5 T and 3.0 T MRI scans (T1‐weighted imaging [T1WI], fat‐saturated T2‐weighted imaging [FS‐T2WI], and contrast‐enhanced [CE]). Assessment: Six machine learning models were built and selected to construct the radiomics signature. The nomogram model was constructed by combining the radiomics signature with the clinical signature, which was then validated for discrimination, calibration, and clinical usefulness. Statistical Tests: The clinical characteristics were compared using t‐tests, Mann–Whitney U tests, or chi‐square tests. The Spearman and LASSO methods were used to select radiomics features. The receiver operating characteristic (ROC) analysis was performed, and the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated. Results: The logistic regression (LR) model performed best in each sequence. The AUC of CE‐T1‐T2WI‐combined was the highest in the LR model, with an AUC of 0.775 (95% CI: 0.570–0.979) in external test cohort. The nomogram showed high predictive performance in the training (AUC: 0.883 [95% CI: 0.823–0.943]) and test cohort (AUC: 0.830 [95% CI: 0.657–1.000]) for predicting LVSI. Decision curve analysis demonstrated that the nomogram was clinically useful. Data Conclusion: Our findings suggest that the proposed nomogram model based on multimodal MRI of CE T1WI‐T2WI‐combined could be used to assess LVSI status in early cervical cancer. Evidence Level: 4. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

Additional sex combs‐like 1 (ASXL1) mutations, a hotspot in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have been frequently reported for their potential prognostic value, but the results are controversial. Therefore, a meta‐analysis was performed. Databases, including PubMed, Embase, and Cochrane Library, were searched for relevant studies published up to January 13, 2022. STATA v16.0 software was used to calculate the combined hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and AML transformation. Subgroup analysis was used to explore the effects of the grouping factors on heterogeneity.Ten studies on ASXL1 mutations and the prognosis of MDS were selected. Our results indicate that ASXL1 mutations have an adverse prognostic impact on OS (HR = 1.68,95%CI:1.45–1.94, p <.0001) and AML transformation (HR = 2.20,95% CI:1.68–2.87, p <.0001). The results for different age groups were not significantly different (HR = 1.87,95% CI: 1.31–2.67; HR = 1.62,95% CI:1.35–2.07). Ten studies covering 5816 patients with AML were included. The pooled HR for OS was 1.37 (95% CI:1.20–1.56, p <.0001). ASXL1 mutations were especially associated with a poorer OS in the subgroup aged ≥60 years (HR = 2.86, 95% CI:1.34–6.08, p =.006); when considering cytogenetically normal AML (CN‐AML), the HR was 1.78(95% CI:1.27–2.49, p =.001). This meta‐analysis indicates an independent, adverse prognostic impact of ASXL1 mutations in patients with MDS and AML, which also applies to patients with CN‐AML. Age was a risk factor for patients with AML and ASXL1 mutations but not for patients with MDS. [ABSTRACT FROM AUTHOR]

Pain and depression are frequently comorbid disorders, but the mechanism underlying this association is unknown. Here, we report that brain indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, [...]

Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1[beta] through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain., Introduction Pain resulting from injury to the nervous system (neuropathic pain) has several salient clinical features, including hyperalgesia and allodynia beyond the dermatome distribution. Both peripheral and central mechanisms, including [...]