Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with many systemic comorbidities, including sensory dysfunctions. A growing body of literature explored patients’ unusually ...intense reactions to innocuous sensory stimuli but very little is known about ASD patients’ response to noxious stimuli such as pain. Patients with ASD are thought to have low sensitivity to pain, but currently, there is no clear consensus on pain responsivity/sensitivity/expression in patients with ASD. Pain is likely a significant source of suffering for patients with ASD, but limited literature suggest that it may be underdiagnosed and undertreated, due to patients’ potentially abnormal reaction to pain/pain expression, and their limited social communication skills. In this article, we first discuss the abnormalities in pain sensitivity and expression, two key obstacles in pain management for patients with autism. Next, we explore currently available tools in pain diagnosis for patients with autism. The third, we discuss pain management in autism patient with an emphasis on the perioperative setting where literature is most abundant. Last, we call for further research and offer suggestions for implementing better pain assessment and management protocols based on our understanding of this unique population.
Purpose
Head and neck squamous cell carcinoma (HNSCC) incidence is increasing, and evidence suggests survival disparities between non-Hispanic (nH) black and white males. However, temporal changes in ...HNSCCs and factors contributing to survival differences have not been examined at the national level.
Methods
National Cancer Database (NCDB) cases were used to evaluate temporal trends in HNSCC anatomical sites and site groupings (i.e., oral cavity, oropharyngeal, non-oropharyngeal), and to estimate incidence ratios (IRs) comparing nH black and white males in demographic and clinical characteristics.
Results
Between 1998 and 2012, 18,443 (11 %) nH black males and 145,611 (89 %) nH white males were diagnosed with HNSCCs. Cases rose from 9094 diagnosed in 1998 to 13,838 in 2012, driven by increases in oropharyngeal tumors, particularly tumors of the tonsil and tongue. Annual percent changes in nH black males and nH white males were 1.93 and 3.17, respectively. Additionally, nH black males had higher incidence of the more aggressive non-oropharyngeal tumors (
p
< .0001) and distant-stage tumors (76 vs. 64 %,
p
< .0001). However, nH white males had higher incidence of high-risk HPV types (IRs range from 1.68, 95 % CI 1.50–1.88 in oropharyngeal tumors to 3.03, 95 % CI 1.11–8.25 in non-oropharyngeal tumors).
Conclusions
Incidence of oropharyngeal tumors has risen in both nH black and white males. However, nH white males have higher incidence of HPV, and nH black males have higher incidence of more aggressive and advanced HNSCCs. Racial differences in clinical characteristics associated with poorer survival exist, and future studies should determine factors associated with these differences.
The reduced antidepressant and antihyperalgesic effects of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine during maintenance treatment has been reported, but little is known about ...the molecular mechanism of this phenomenon. In three comorbid pain and depression animal models (genetic predisposition, chronic social stress, arthritis), we showed that the fluoxetine's antidepressant and antihyperalgesic effects were reduced during the maintenance treatment. Fluoxetine exposure induced upregulation of the 5-hydroxytryptamine 1A (5-HT1A) auto-receptor and indoleamine 2,3 dioxygenase 1 (IDO1, a rate-limiting enzyme of tryptophan metabolism) in the brainstem dorsal raphe nucleus (DRN), which shifted the tryptophan metabolism away from the 5-HT biosynthesis. Mechanistically, IDO1 upregulation was downstream to fluoxetine-induced 5-HT1A receptor expression because 1) antagonism of the 5-HT1A receptor with WAY100635 or 5-HT1A receptor knockout blocked the IDO1 upregulation, and 2) inhibition of IDO1 activity did not block the 5-HT1A receptor upregulation following fluoxetine exposure. Importantly, inhibition of either the 5-HT1A receptor or IDO1 activity sustained the fluoxetine's antidepressant and antihyperalgesic effects, indicating that 5-HT1A-mediated IDO1 upregulation in the brainstem DRN contributed to the reduced antidepressant and antihyperalgesic effects of fluoxetine. These results suggest a new strategy to improving the therapeutic efficacy of SSRI during maintenance treatment.
Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate ...neuronal excitability and are involved in the development and maintenance of chronic pain. However, the effect of HCN channel activity in the Gasserian ganglion on trigeminal neuropathic pain has not been examined. We evaluated nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine into the Gasserian ganglion in rats with trigeminal nerve injury. Both blockers dose-dependently ameliorated evoked and spontaneous nociceptive behavior in rats with trigeminal neuropathic pain. Moreover, the clinically available HCN channel blocker ivabradine showed a prolonged antinociceptive effect. In the Gasserian ganglion, HCN1 and HCN2 are major HCN isoforms. After trigeminal nerve injury, the counts of HCN1 as well as HCN2 immuno-positive punctae were increased in the ipsilateral Gasserian ganglions. These results indicate that the increased HCN channel activity in the Gasserian ganglion directly contributes to neuropathic pain resulting from trigeminal nerve injury.
Trigeminal nerve damage-induced orofacial pain is severe and more resistant to standard pharmacological treatment than other types of neuropathic pain. Our study suggests that targeting HCN channel activities in the Gasserian ganglion may provide an alternative treatment of trigeminal neuropathy including trigeminal neuralgia.
Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 85% of all lung cancers are non-small cell histology non-small cell lung cancer (NSCLC). Modern treatment strategies ...for NSCLC target driver oncogenes and immune checkpoints. However, less than 15% of patients survive beyond 5 years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells, which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide. We demonstrate that constitutive IFN-stimulated gene expression, including an IFN-related DNA damage resistance signature, predicts for sensitivity to SAR. Importantly, tumor cell-intrinsic expression of PD-L1 is IFN-inducible and abrogated by SAR. Taken together, these findings suggest potential dual roles for JAK2 inhibitors, both as a novel monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune checkpoint inhibition.
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Recently, we developed a systems engineering model of the human cardiorespiratory system Kurian et al. ACS Omega 2023, 8 (23), 20524–20535. DOI: 10.1021/acsomega.3c00854 based on existing models of ...physiological processes and adapted it for chronic obstructive pulmonary disease (COPD)an inflammatory lung disease with multiple manifestations and one of the leading causes of death in the world. This control engineering-based model is extended here to allow for variable metabolic rates established at different levels of physical activity. This required several changes to the original model: the model of the controller was enhanced to include the feedforward loop that is responsible for cardiorespiratory control under varying metabolic rates (activity level, characterized as metabolic equivalent of the taskR m and normalized to one at rest). In addition, a few refinements were made to the cardiorespiratory mechanics, primarily to introduce physiological processes that were not modeled earlier but became important at high metabolic rates. The extended model is verified by analyzing the impact of exercise (R m > 1) on the cardiorespiratory system of healthy individuals. We further formally justify our previously proposed adaptation of the model for COPD patients through sensitivity analysis and refine the parameter tuning through the use of a parallel tempering stochastic global optimization method. The extended model successfully replicates experimentally observed abnormalities in COPDthe drop in arterial oxygen tension and dynamic hyperinflation under high metabolic rateswithout being explicitly trained on any related data. It also supports the prospects of remote patient monitoring in COPD.
At our residency program, incoming interns are traditionally taught fundamental open surgical skills like suturing and knot tying in a group setting by viewing 12 instructional videos consecutively ...followed by individual baseline skill testing. We sought to evaluate if introduction to open surgical skills via self-paced viewing of video tutorials, as opposed to traditional group viewing, results in improved surgical skill acquisition in Obstetrics and Gynecology (OBGYN) interns as measured by higher proficiency score with decreased workload stress and anxiety.
A randomized control trial was conducted in which OBGYN PGY-1 residents in 2015 and 2016 (N = 35) were introduced to basic open surgical skills, such as knot tying and suturing, by viewing 12 video tutorials produced at UTSW (https://youtu.be/4w3hyL9muVU) for a surgical skills curriculum. Residents were randomized to 2 groups: group viewing vs self-paced viewing. Performance scores were calculated based on time and accuracy while workload and anxiety were measured by preand post-testing surveys using the National Aeronautics and Space Administration-Task Load Index and Spielberger State-Trait Anxiety Inventory 6 item questionnaires.
There was no significant difference in proficiency score between the group vs self-paced viewing in 8 out of 12 tasks using the Wilcoxon signed rank test (p > 0.10). There was no statistically significant differences in workload stress based on the National Aeronautics and Space Administration-Task Load Index questionnaire (p = 0.399) or self-reported anxiety based on the Spielberger State-Trait Anxiety Inventory 6 item questionnaire (p = 0.607).
Contrary to recent educational data suggesting self-paced learning may improve outcomes, viewing instructional videos in a group setting continues to be a time efficient method to introduce basic open surgical skills to incoming OBGYN interns.
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