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"Ultra-Processed Adolescence"
No full textAn animated short accompanied by three sculpturesPurchase College SUNYNew MediaBachelor of ArtsMcKay, Jo
Alcohol use in Early Midlife: Findings from the Age 37 Follow-Up Assessment of the FinnTwin12 Cohort
Get PDFThis paper provides an overview of the most recent assessment, collected in early midlife, of the FinnTwin12 cohort, a population-based study of Finnish twins born in 1983-1987. The twins were invited to complete an online survey assessing a range of variables, including physical and mental health, alcohol use and problems, other substance use, and early midlife environments (e.g., parenthood). In total, 2,085 individuals (~ 40% of the original sample) completed the survey (551 complete twin pairs, 58.7% female, 37.3% monozygotic, Mage = 37.2 years, SD = 1.47 years, age range = 34-39 years). Individuals who participated were more likely to be female, monozygotic, and have higher parental education and less hyperactivity/impulsivity and aggression at age 12 when compared to individuals who were invited but did not participate. Parental alcohol misuse and the twins' alcohol use and misuse at age 14 were not related to study retention. Alcohol misuse in early midlife was positively associated with nicotine dependence, lifetime use of cannabis and other drugs, trauma exposure, and depressive symptoms, and negatively associated with physical health and having biological children. These new data expand upon the wealth of measures collected as part of previous assessments, expanding the scope of work on the etiology and correlates of alcohol misuse within a longitudinal, genetically-informed framework. In addition to these new survey measures, we are planning an in-person assessment to collect physiological measurements and conduct additional in-depth phenotyping on a subset of twins who have been more intensively studied over the years.National Center for Advancing Translational SciencesVoRSUNY DownstatePsychiatry and Behavioral SciencesN/
Assessing the Therapeutic Role of Rehabilitation Programs in Chemotherapy-Induced Peripheral Neuropathy (CIPN)—A Scoping Review
No full textBackground: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients' quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O'Malley's framework and Levac et al.'s refinements, was conducted to assess rehabilitation programs for CIPN. Searches across six databases were performed, with inclusion and exclusion criteria focusing on studies with physical rehabilitation interventions. Data were charted, detailing interventions, demographics, and outcomes. Results were synthesized descriptively and presented narratively with tables. Results: The review included 24 studies covering diverse cancer types and treatments, involving a total of 1167 participants. Various interventions for CIPN were assessed, and results were thematically categorized according to exercise category. Physical modalities like ultrasound and exercise showed promise in symptom relief for colorectal and breast cancer patients. No distinct advantage was found in the timing of exercise interventions. Complementary therapies such as acupuncture and yoga demonstrated effectiveness in managing CIPN symptoms. Conclusions: This review highlights the effectiveness of diverse physical and complementary interventions in managing CIPN, advocating for their integration into standard protocols. It emphasizes the need for holistic, patient-centered approaches that combine exercises, physical therapy, and complementary therapies to improve patient outcomes. These findings set a direction for future research and clinical practices focused on comprehensive and personalized CIPN management strategies.VoRSUNY DownstateMedicineN/
Protein-S-Nitrosylation of Viral Proteins is A Universal Anti-Viral Mechanism
No full textInnate immune pathways like the cGAS/STING pathway are essential in the production of interferons to inhibit viral infections. DNA viruses have evolved measures to counteract our innate immune pathways. Common DNA viruses like Human Cytomegalovirus (HCMV), Human-Papillomavirus (HPV) and Adenovirus (AdV) each encode proteins that limit innate immunity. HCMV encoded pp71 and pp65 antagonize STING and cGAS, respectively. HPV encoded E7 and AdV encoded E1A both antagonize STING and diminish interferon response. However, the infected host cell has developed countermeasures to limit the activity of these pro-viral proteins. These mechanisms include the direct modification of viral proteins by post-translational modifications (PTMs). Herein, we postulate that a potent but relatively understudied PTM, called protein-S-nitrosylation, may serve as a universal anti-viral mechanism. We previously reported that protein-S-nitrosylation of pp71 undermines its ability to antagonize STING activation. Here we report that pp65 which undermines the cGAS/STING pathway is protein-S-nitrosylated, and this PTM limits the functions of this HCMV virulence factor. Mutations of the amino acids for protein-S-nitrosylation on pp65 from serine to cysteine thus blocking this PTM, resulted in the viral protein inhibiting the induction of the STING pathway with higher efficiency compared to WT. Further, nitrosylation deficient pp65 expression resulted in a reduced ability to phosphorylate IRF3 and TBK1 which led to a decrease in interferon beta secretion. This suggests protein-S-nitrosylation may function as a potent countermeasure to HCMV infection.
To determine if nitrosylation is a universal inhibitory mechanism for viruses beyond HCMV, we developed stable cell lines that express WT and serine mutant AdV E1A and HPV E7. We confirmed that E1A and E7 are both protein-S-nitrosylated and observed that nitrosylation deficient isoforms of these proteins result in diminished levels of interferon beta and a reduction in IRF3 phosphorylation upon STING induction. Further these proteins can complement the STING dependent inhibition of a pp71 HCMV. In sum out data suggests that protein-S-nitrosylation of viral proteins may serve as a universal anti-viral mechanism in viral infection and highlights the need to understand nitrosylation as an anti-viral mechanism for the development of novel therapeutics.NAUpstate Medical UniversityMicrobiology & ImmunologyPhDMurphy, Eai
Stress, Survival, and Death in Metabolically Compromised Lung Cancer Cells
No full textLung cancer is the leading cause of cancer-related deaths; thus, newer therapeutic approaches are urgently needed. In recent years, several studies have shown that tumors, including lung cancers, undergo metabolic rewiring for continuous growth and survival. This reprogramming, influenced by oncogenic mutations and nutrients, is believed to promote cancer progression. Consequently, therapeutic approaches to target cancer metabolism is a viable approach. Here we report that CB-839 (glutaminase-1 inhibitor) and metformin (anti-diabetic drug) induce metabolic stress and also inhibit human lung cancer cell growth.
The effects of these agents were tested in three human lung cancer cell lines, namely H460, A549, and H1299. Our results revealed that these agents did not considerably affect cell cycle regulation. However, they induced cell death in H460 and A549 cells through upregulation and stabilization of Death Receptor 5 (DR5) protein. These agents did not considerably upregulate DR5 in H1299 cells. However, H1299 cells activated autophagy instead, a survival mechanism triggered under metabolic stress. Inhibition of autophagy using 3-methyladenine in H1299 cells resulted in metabolic stress-mediated upregulation of DR5 and cell death, suggesting autophagy plays a protective role in these cells.
Our findings show that these three lung cancer lines exhibit variable sensitivity to CB-839 and metformin. In H460 and A549 cells, which harbor mutant K-Ras, these agents promote apoptosis by activating the DR5-dependent extrinsic pathway. By contrast, in wild-type K-Rass carrying H1299 cells, autophagy is activated with minimal effect on DR5 regulation. Therefore, we also investigated whether the status of K-Ras affected the sensitivity of these cells to metabolic stress. Accordingly, we utilized a pan-K-Ras inhibitor and noted that inhibition of mutant K-Ras in H460 and A549 cells decreased sensitivity to CB-839 and metformin. These findings led us to conclude mutant K-Ras to be one of the underlying reasons for the increased susceptibility of H460 and A549 lung cancer cells to CB-839 and metformin-induced growth inhibition.
Collectively, our findings suggest that CB-839 and Metformin have the potential to become components of novel therapeutic strategies for managing lung cancer.NAUpstate Medical UniversityPharmacologyPhDSheikh, M. Saee
Sex differences in α4βδ GABAA receptor-regulated synaptic pruning in the primary motor cortex during adolescence and its role in motor learning flexibility
Get PDFBackground: Both human and mouse studies report sex differences in motor learning flexibility.
While males are capable of motor learning, after puberty, reports suggest that they struggle with
behavioral flexibility in motor learning compared to females. α4βδ GABAA receptor (GABAR)
regulated adolescent synaptic pruning of mushroom spines in CA1 hippocampus has been shown
to be necessary for learning flexibility of spatial tasks. I believe this deficit in motor learning
flexibility is caused by the spatial limitations and higher energy cost caused by increased
dendritic spine density in our α4 -/- mice. Since learning of motor skills causes an initial increase
in dendritic spines in the primary motor cortex (M1), I predicted that differences in α4βδ
GABAR triggered mushroom spine pruning M1 would play a role in this sex difference.
However,, the role that motor activity would have on adolescent synaptic pruning in M1 is
unclear. While running wheel activity is reported to increase spines in M1, it is unclear how
motor activity will interact with adolescent synaptic pruning of mushroom spines in this area or
its afferent input from prelimbic prefrontal cortex (PL PFC) which also undergoes pruning.
Methods: I measured the mushroom spine density in the basilar dendrites of layer (L) 5 M1 pyramidal cells in pubertal and post-pubertal C57Bl/6J mice of both sexes to determine if there
was a sex difference in mushroom spine pruning. If male and/or female mice exhibited
mushroom spine pruning, I measured mushroom spine density in α4 -/- mice of the
corresponding sex to determine if α4βδ GABAR played a role in this process. To assess the
effects motor activity had on adolescent synaptic pruning, I exposed all groups that experienced
this process to a voluntary running wheel during puberty and measured mushroom spine density.
To assess motor learning flexibility in relevant groups I taught mice how to perform a constant speed rotarod test initially (“learning”) and assessed performance on an accelerating speed
rotarod test the following day (“learning flexibility”).
Results: Only female wild-type mice exhibited synaptic pruning of mushroom spines in the
proximal region of basilar dendrites of L5 M1 pyramidal cells (>60% pubertal: 2.23 ± 0.21
spines/10 μm; post-pubertal: 0.81 ± 0.14 spines/10 μm, P < 0.001). Mushroom spine density of
the distal dendrites was unchanged for both sexes. This decrease in mushroom spines was not
observed in female α4 -/- mice, implicating α4βδ GABARs as the mechanism. Pubertal
expression of α4 was greater in female M1, a likely reason for the sex difference in pruning.
Motor activity offset pruning in female L5 M1 (control mice: 0.98±0.40 spines/10μm, running
wheel mice:1.87±0.77 spines/10μm, P = 0.0405) and increased mushroom spines in L5 PL PFC
(control mice: 0.79±0.37 spines/10μm, running wheel mice: 1.41±0.45 spines/10μm, P =
0.0140). The mushroom spine pruning of female wild-type M1 was associated with improved
motor learning flexibility compared to the groups with no pruning (male wild-type, female α4 -/) on the accelerating speed rotarod test (P = 0.006).
Discussion: My results demonstrate sex differences in adolescent synaptic pruning
corresponding with sex differences in motor learning flexibility. Adolescent synaptic pruning
was triggered by the α4βδ GABARs which emerge at puberty. This process appears to be offset
by motor activity in M1 and PL PFC but the implications of this on motor learning flexibility are
unclear. Studying synaptic pruning has important implications in the application of drugs that
target pruning of mushroom spine pruning because sub populations of people with autism
spectrum disorder have a functional knockdown of the α4βδ GABAR and impaired behavioral
flexibility.VoRSUNY DownstateProgram in Neural and Behavioral SciencePhDSmith, Shery
Longitudinal Engagement in Modifiable Lifestyle Behaviors and Racial–Ethnic Differences in Dementia Risk
Get PDFThis study was ethically approved by the Institutional Review Board for the Protection of Human Subjects at SUNY Upstate Medical University under project number 2161653-1.Objectives
The objective was to examine racial–ethnic differences in longitudinal engagement for lifestyle behaviors and moderating role of race–ethnicity between lifestyle behaviors and dementia risk.
Methods
We analyzed 2011–2021 National Health and Aging Trends Study data, a nationally representative U.S. sample of 6155 White, Black, Hispanic, and Asian older adults aged 65+. Cox models regressed dementia on the interaction between lifestyle behaviors (physical activity, smoking, and social contacts) and race–ethnicity.
Results
Only smoking was associated with about a 45% higher dementia risk (aHR = 1.45, 95% CI = 1.11–1.89). On average, Black and Hispanic respondents exhibited less frequent physical activity and social contacts, along with more frequent smoking. There was one significant interaction; more social contacts were associated with lower dementia risk among Asian respondents (aHR = 0.16, 95% CI = 0.05–0.55).
Discussion
Racial–ethnic differences in lifestyle behaviors should be considered when addressing dementia disparities. Future research needs to explore the relationship between social contacts and lower dementia risk among Asian older adults.National Institute on Aging (R36 AG061426).
The Johns Hopkins Alzheimer’s Disease Resource Center for Minority Aging Research (P30 AG059298)AMUpstate Medical UniversityPublic Health and Preventive MedicineN/
From Brussels to Budapest: Capturing a Continent's Ideological Shift Right
Get PDFSUNY OswegoGlobal and International Studie