Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function

NK cells play a crucial role in host protection during tumorigenesis. Throughout tumor development, however, NK cells become progressively dysfunctional through a combination of dynamic tissue-specific and systemic factors. While a number of immunosuppressive mechanisms present within the tumor microenvironment have been characterized, few studies have contextualized the spatiotemporal dynamics of these mechanisms during disease progression and across anatomical sites. Understanding how NK cell immunosuppression evolves in these contexts will be necessary to optimize NK cell therapy for solid and metastatic cancers. Here, we outline the spatiotemporal determinants of antitumor NK cell regulation, including heterogeneous tumor architecture, temporal disease states, diverse cellular communities, as well as the complex changes in NK cell states produced by the sum of these higher-order elements. Understanding of the signals encountered by NK cells across time and space may reveal new therapeutic targets to harness the full potential of NK cell therapy for cancer.

Opioid Prescription Is Associated With Increased Survival in Older Adult Patients With Pancreatic Cancer in the United States: A Propensity Score Analysis

PURPOSE: Few studies have assessed the interaction between pain treatment and mortality in pancreatic cancer. The aim of this study was to investigate the association between receipt of opioid prescriptions and survival in adults with pancreatic cancer. METHODS: The SEER-Medicare linked database was used to identify patients diagnosed with late-stage pancreatic cancer between 2007 and 2015. Kaplan-Meier models were used to assess the association between opioid prescriptions in the year after cancer diagnosis and survival. Cox proportional hazard models were used to determine the association between opioid receipt and survival, adjusting for propensity score and other relevant confounders including cancer-directed therapies and palliative care referral. RESULTS: A total of 5,770 older adults with pancreatic cancer were identified; 1,678 (29.1%) were prescribed opioids for at least 60 days. Median survival was increased in those with opioid prescriptions (6.0 months) compared with those without (4.0 months, P < .0001). After adjustment for confounders, opioid prescriptions were still associated with improved survival (hazard ratio 0.80; 95% CI, 0.75 to 0.86). On multivariable analysis, opioid prescriptions were associated with older age, female sex, residing in nonmetro areas, and treatment with celiac plexus neurolysis, chemotherapy, and radiation. CONCLUSION: Receipt of opioid prescriptions is associated with longer survival in patients with pancreatic cancer. This may be due to the impact of cancer-related pain, although further studies are needed to better understand the interaction between pain management, cancer-directed therapies, and systemic factors, such as palliative care, availability of opioids, and clinical practice culture.

Improving Communication in Children With ASD

Raising a child with ASD is generally considered a challenging experience for families due to the pervasive difficulties in communication, social skills, and other adaptive behaviors encountered in these children. The family system restructures and adapts to accommodate the needs of the child with ASD. In this chapter, the author highlights the importance of communication skills for the development of children with ASD and summarizes the evidence-based individual interventions for improving them. Although there is robust evidence for the family's beneficial contribution to developing adaptive communication skills in children with ASD, there is still room for uplifting the existing programs in terms of accessibility, efficacy, and culture-based elements. In the final part of the chapter, the author provides recommendations for designing future family interventions addressed to communication skills in children with ASD and argues that culture-specific and systemic factors (such as support policies for children with disabilities) enhance program success.

Time-related OCT-A changes in preclinical retinopathy and their association with systemic factors

Background. Optical coherence tomography angiography (OCT-A) is a promising tool for the detection of microvascular impairment at the preclinical stage of diabetic retinopathy (DR). Evaluation of dynamic OCT-A changes and their association with systemic factors can help to reveal early biomarkers of DR progression.Aim: to evaluate time-related OCT-A changes and their association with systemic factors in type 1 diabetes mellitus (DM1) patients with no apparent DRMaterials and methods. 38 DM1 patients with no apparent DR and 39 healthy volunteers were included in the study. All participants underwent 7-fi eld fundus photography, OCT and OCT-A. We analyzed OCT-A parameters (foveal avascular zone (FAZ) area (mm2), acircularity index (AI), vessel density (VD), skeletonized density (SD)) as well as the results of blood and urea tests.Results. After one year of observation, AI was significantly higher (р = 0.005) and VD0–300 was signifi cantly lower in superfi cial vascular plexus (SVP, p < 0.0001) and deep capillary plexus (DCP, р = 0.032) in DM1 patients. We have also registered a positive correlation between AI and triglycerides (TG) level (r = 0.627, p = 0.007) as well as a negative correlation between ketones and VD (SVP VD0–300: r = –0.695, p = 0.030; intermediate capillary plexus (ICP, VD0–300: r = –0.551, p = 0.041; DCP, VD0–300: r = –0.704, p = 0.003; SVP, VD300–600: r = –0.853, p = 0.001).Conclusions. After one year of observation, we have registered an increase in AI level and a decline in VD in SVP and DCP which can be the earliest signs of DR progression. A signifi cant correlation between these parameters and systemic factors indicates their role as potential DR biomarkers.

Music in Secondary Education: Predictors of Music Subject Choices and Associations with Academic Achievement

This paper investigates the relationship between music qualification choice and academic performance in secondary education in England at Key Stage 4 (KS4; usually at age 15 and 16). We analysed data from 2257 pupils at 18 educational settings in a city in the southeast of England. Two regression analyses with clustered errors modelled KS4 music qualification choice and GCSE academic achievement in English, Mathematics, and other English Baccalaureate subjects, while controlling for a range of demographic, academic, and socio-economic variables. Choice of music as a subject at KS4 was positively associated with the total volume of KS4 qualifications entered for examination and was also predicted by coming from an affluent neighbourhood. Furthermore, this choice of music at KS4 was associated with greater academic performance on English Baccalaureate subjects above and beyond other significant predictors (gender, language, prior academic achievement, total volume of KS4 qualifications, and neighbourhood socio-economic status; local Cohen’s f-squared = .09). These results point to a small but significant additive effect of studying music at KS4 in relation to performance on core GCSE subjects. We also found that schools with KS4 music qualification choice greater than the national average were higher in overall academic attainment, in the proportion of pupils attending extra-curricular instrumental lessons, and in our composite measure of school’s engagement with a local music education hub. The results are interpreted in light of sociological theories of education in an attempt to better understand the underlying systemic factors affecting youth music engagement.

Inequities in Palliative and Dementia Care and Health in Long-Term Supportive Services Settings

Most older adults with serious illness, including Alzheimer’s Disease and Related Dementias (ADRD) reside in community-based settings. These individuals and their care partners rely on Long Term Supportive Services (LTSS) including nursing home, home health, hospice, and adult day centers to provide support. LTSS are often under-resourced and reimbursed however, with significant regulatory restrictions on the care they can provide. These issues combined with other systemic factors in our healthcare system and society, including racism and poverty, lead to substantial inequities. Even preceding the use of LTSS, ADRD is diagnosed later in non-white individuals and access to high-quality services, including palliative care is severely limited. Moreover, few palliative care interventions address ADRD and even fewer have been specifically tailored to address the needs of our multi-cultural, racially and ethnically diverse society. This symposium will therefore utilize data from several nationwide data sets collected as part of routine care for clinical, billing, and/or regulatory purposes to assess inequities that exist across LTSS sites related to ADRD and palliative care. The individual abstracts show a clear pattern of inequities that stem from endemic systems failures towards people of color in the United States that must be addressed through a multipronged approach. This research shows that policies must be changed to require adequate collection of social determinants of health, to target policies that allow sub-standard or limited access to care, and research and clinical reform to produce a more culturally sensitive approach to care for those with ADRD and other serious illnesses.

Muscle Bioenergetics and Cognitive Executive Function: The SOMMA Study Baseline

Better executive function has been associated with faster walking speed, but the basis for this association is unclear. Systemic factors appear to contribute mitochondrial function across multiple tissues including muscle and brain. We hypothesized that muscle-based measures of bioenergetics capacity would be associated with cognitive function at SOMMA’s baseline. MRI-based ATPMAX and muscle fiber respirometry-based max OXPHOS were correlated with scores on the MoCA (mean: 24.0; SD: 3.2); Trails B (mean: 138 seconds; SD: 73) and the Digit Symbol Coding Tests (mean: 50.8; SD: 14.9). The spearman correlations between ATPmax and the three measures were: 0.10 (p=0.29); -0.20 (p=0.03) and 0.16 (p=0.09), respectively. The association between max OXPHOS were: 0.18 (p=0.02); -0.20 (p&lt;0.01) and 0.11 (p=0.13), respectively. Some associations appeared stronger in men than women. Gender interactions and whether energetics mediate some of the association between cognitive function and gait speed will be explored in the full baseline sample.

Mental health and behavioural difficulties in adopted children: A systematic review of post-adoption risk and protective factors

Previous research suggests that adopted children are at a greater risk of experiencing psychological and behavioural difficulties or accessing mental health services than non-adopted peers and that post-adoption variables are significant risk and protective factors producing this situation. This review seeks to summarise the post-adoption variables associated with adopted children’s mental health or behavioural difficulties to inform future research and shape interventions. A search for publications that assess associated risk and protective factors using Web of Science, Psychinfo, Medline and Sociological Abstracts identified 52 studies that met rigorous methodological criteria. Children’s and adolescents’ mental health and behavioural outcomes were associated with parent, parent–child and wider family factors and by contextual variables. The findings highlight the importance of focusing on the multitude of systemic factors surrounding a child following adoption. Clinical implications and direction for future research are discussed.

Involvement of Different Nerve Branches in Trigeminal Neuralgia on Right and Left Sides- A Retrospective Study

One of the most common symptoms in the orofacial region is pain. Trigeminal neuralgia is characterized by pain affecting the trigeminal nerve and its related areas of distribution and is known to have significant impact on the quality of life. Misdiagnosis of trigeminal neuralgia has been reported by dentists in several previous studies in the literature. With this rationale, the aim of the present study is to determine the most commonly involved nerve branch and the side affected in trigeminal neuralgia patients. The present retrospective study involved 72 patients diagnosed with trigeminal neuralgia who reported from October 2013 to October 2014. Data regarding the age of onset, gender, side of involvement was analyzed from their clinical records. Out of the 72 patients, males were 42(58.3%) and females were 30(41.7%). In our study, a total of 56 % (i.e., 40) patients showed involvement on the right and 44% (i.e., 32) (i.e, 32) patients on the left side of the face. In this retrospective study, ophthalmic branch (V1) was affected only in 3 patients. Mandibular nerve (V3) alone was involved in 24 patients. Involvement of all the three divisions V1, V2 and V3 was seen in 16(22.3%) of patients. Clinical similarities of trigeminal neuralgia that have an impact on different populations were demonstrated in this study. Detailed history and proper identification of involved nerve branch play an important role in the diagnostic accuracy and treatment satisfaction. Most involved branch in our study was the mandibular (V3) branch and the most affected side was the right side. Correlation of systemic factors with trigeminal neuralgia can be attempted in future research.

Binge Drinking and Heavy Drinking Among Older Military Veterans: Applying the Theory of Intersectionality

The post-service impact of military experiences include post-traumatic stress disorder, depression, substance misuse and several other adverse outcomes that persist well into older adulthood. As such, older military veterans are at risk of developing alcohol dependency and those with existing stressors from other identities are at the highest risk of engaging in binge drinking or heavy drinking. This study used the theory of intersectionality to examine alcohol misuse by veteran status and age, veteran status and race and veteran status and sex. Data were derived from the 2016, 2017 and 2018 Brief Risk Factor Surveillance System (BRFSS) from the Centers for Disease Control and Prevention (CDC). The BRFSS is an annual survey conducted over the phone in all 50 states and territories. Survey-weighted logistic regression models were used to examine alcohol misuse among adults aged 65+ by veteran status and the intersection between age, race, and sex. Results showed no interaction between veteran status and age, and no interaction between veteran status and sex. However, there was a significant interaction between veteran status and race, in that Black/Other race veterans were more likely to engage in both binge drinking and heavy drinking compared to White veterans, White nonveterans and nonveterans of the same race. Interventions geared towards this population should therefore engage culturally sensitive approaches that consider the historical and systemic factors that contribute to these disparities in rates of alcohol misuse among older military veterans.