Diseases of Despair and Social Capital: Findings from a Population-Based Survey on Opioid Misuse among Adolescents.

BACKGROUND: Deaths related to opioid overdose have increased substantially in the past few years, raising concerns about how to combat this public health emergency. Objectives: We investigated the association of family, school, and community social capital with opioid misuse in the adolescent population. In addition, we examined if adolescents' depressive symptoms have any mediating effects on opioid misuse. Methods: We used the 2018 National Survey on Drug Use and Health (NSDUH) data, and two substantive models with binary logistic regressions. Three social capital variables were added to the full model with control for sociodemographic and health status variables. A mediation analysis was estimated for family and school social capital, major depressive episodes in the past year, and opioid misuse. Results: We found statistically significant relationships between adolescent opioid misuse and family and school social capital. Adolescents' odds of opioid misuse decreased 10% with each additional family situation where they felt supported. Not knowing students in their grade who drank alcohol or used marijuana/hashish decreased the odds of misusing opioids 42% (p < .01). Experience of depressive episodes acted as a mediator for the social capital effects on adolescents' opioid misuse. Conclusions: Our findings lend support that opioid misuse is associated with despair, and therefore, opioid prevention programs need to incorporate strategies to address mental health issues as well. Our findings also underscore the need for focusing on increasing parental awareness and involvement as well as scaling up prevention efforts in high schools where substance abuse is relatively higher.

Perceptions of Successful Aging among Older Adults in Bangladesh: An Exploratory Study.

To analyze older adults' definitions of successful aging in Bangladesh. The purposively selected study sample comprised twelve participants who were aged over 60. Interviews using in-depth semi-structured questionnaires were conducted based on participants' chosen mode, either face-to-face, or by phone. Findings of this study support that successful aging is multidimensional - that is - for Bangladeshis successful aging encompasses dimensions such as adaptation to an aging body, financial security, family and intergenerational care, and social participation. Older adults' emphases on all these dimensions were qualitatively different from those relevant in western societies. Bangladeshis see disease and disability as a normal part of aging and do not emphasize freedom from disease or longevity as much as North Americans and the US-focused successful aging discourses do. Family care is a key component of successful aging in Bangladesh. While in western models functional independence has been emphasized, for Bangladeshi older adults' adaptations to changing body, co-residing with children, being financially, physically, and emotionally dependent on family and receiving their care are viewed as normal and appropriate. Cross-cultural comparisons in this study suggest that what it means and entails to age well differ across cultures. This study highlights the need among health professionals to understand Bangladeshi culture, with its specific beliefs and values, as it relates to the views of aging well.

Social Capital and Sexual Risk-Taking Behaviors Among Older Adults in the United States.

Using the General Social Survey (GSS) 2012, a national household-based probability sample of non-institutionalized U.S. adults, this study examined the association of social capital and sexual risk behaviors among older adults aged 55 years and older. Of the 547 respondents, 87% reported not using condoms during their last intercourse, and nearly 15% reported engaging in sexual risk behaviors, such as casual sex, paid sex, male to male sex, and drug use. Binary logistic regression results showed that age, gender, marital status, education, race, sexual orientation, and sexual frequencies were significant predictors of older adults' unprotected sex. Social capital was not a predictor of unprotected sex but was positively associated with other human immunodeficiency virus/sexually transmitted disease (HIV/STD) risk behaviors such as sex with strangers, having multiple sex partners, injecting drugs, and having male to male sex. Findings of this study highlight the importance of HIV/STD prevention programs for older adults.

Eldercare in the transnational setting: insights from Bangladeshi transnational families in the United States.

Little is known about the emotional impact of caregiving for elderly parents on migrant child in the transnational setting. To address this gap in the literature, this study examines the stressors, mediators, and outcomes of eldercare in the transnational context. Data were collected from 21 Bangladeshi immigrant men and women living in the United States who had living parents in Bangladesh over 60 years old. Despite the geographic distance, the migrants provide care to their parents such as emotional support, financial assistance, and arranging for care. While the health status of the care recipients contributed to primary objective stressors, none of the transnational caregivers' narratives reflected the presence of any subjective stressors such as role overload, role captivity, and relational deprivation. Distance and depending on others for hands-on caregiving resulted in feelings of loss of control over the caregiving process. Caregivers experienced a range of emotions from guilt, excessive worrying, and distress over the unpredictability and uncertainty of their circumstances. Kin networks, communicative technologies, and a cultural norm of filial piety contributed to mediating stress. The findings underscore the importance of supportive institutional policies such as visa and travel policies, employment leave, and counseling services for caregivers who provide care for their elderly parents transnationally.

Pattern recognition-informed feedback for nanopore detector cheminformatics.

Pattern recognition-informed (PRI) feedback using channel current cheminformatics (CCC) software is shown to be possible in "real-time" experimental efforts. The accuracy of the PRI classification is shown to inherit the high accuracy of our offline classifier: 99.9% accuracy in distinguishing between terminal base pairs of two DNA hairpins. The pattern recognition software consists of hidden Markov model (HMM) feature extraction software, and support vector machine (SVM) classification/ clustering software that is optimized for data acquired on a nanopore channel detection system. For general nanopore detection, the distributed HMM and SVM processing used here provides a processing speedup that allows pattern recognition to complete within the time frame of the signal acquisition - where the sampling is halted if the blockade signal is identified as not in the desired subset of events (or once recognized as nondiagnostic in general). We demonstrate that Nanopore Detection with PRI offers significant advantage when applied to data acquisition on antibody-antigen system, or other complex biomolecular mixtures, due to the reduction in wasted observation time on eventually rejected "junk" (nondiagnostic) signals.

Nanopore current transduction analysis of protein binding to non-terminal and terminal DNA regions: analysis of transcription factor binding, retroviral DNA terminus dynamics, and retroviral integrase-DNA binding.

BACKGROUND: Synthetic transcription factors (STFs) promise to offer a powerful new therapeutic against Cancer, AIDS, and genetic disease. Currently, 10% of drugs are of this type, including salicylate and tamoxifen. STFs that can appropriately target (and release) their transcription factor binding sites on native genomic DNA provide a means to directly influence cellular mRNA production. An effective mechanism for screening amongst transcription factor (TF) candidates would itself be highly valued, and such may be possible with nanopore cheminformatics methods. RESULTS: It is hypothesized that binding targets on channel-captured molecules, that are well away from the channel-captured region, can be monitored insofar as their binding status, or history, is concerned. The first set of experiments we perform to explore this "transduction" hypothesis involve non-terminal dsDNA binding to protein (DNA TATA box receptor binding to TBP), where we show new experimental results and application of a new cheminformatics data analysis method. In the second series of experiments to explore the transduction hypothesis we examine terminal (blunt-ended) dsDNA binding to protein. We show experimental results before and after introduction of HIV's DNA integrase to a solution of bifunctional "Y" shaped aptamers that have an HIV consensus terminus exposed for interaction. CONCLUSION: X-ray crystallographic studies have guided our understanding of DNA structure for almost a century. It is still difficult, however, to translate the sequence-directed curvature information obtained through these tools to actual systems found in solution. With a nanopore detector the sequence-dependent conformation kinetics of DNA, especially at the DNA terminus, can be studied in a new way while still in solution and on a single molecule basis.

Preliminary nanopore cheminformatics analysis of aptamer-target binding strength.

BACKGROUND: Aptamers are nucleic acids selected for their ability to bind to molecules of interest and may provide the basis for a whole new class of medicines. If the aptamer is simply a dsDNA molecule with a ssDNA overhang (a "sticky" end) then the segment of ssDNA that complements that overhang provides a known binding target with binding strength adjustable according to length of overhang. RESULTS: Two bifunctional aptamers are examined using a nanopore detector. They are chosen to provide sensitive, highly modulated, blockade signals with their captured ends, while their un-captured regions are designed to have binding moieties for complementary ssDNA targets. The bifunctional aptamers are duplex DNA on their channel-captured portion, and single-stranded DNA on their portion with binding ability. For short ssDNA, the binding is merely to the complementary strand of DNA, which is what is studied here - for 5-base and 6-base overhangs. CONCLUSION: A preliminary statistical analysis using hidden Markov models (HMMs) indicates a clear change in the blockade pattern upon binding by the single captured aptamer. This is also consistent with the hypothesis that significant conformational changes occur during the annealing binding event. In further work the objective is to simply extend this ssDNA portion to be a well-studied approximately 80 base ssDNA aptamer, joined to the same bifunctional aptamer molecular platform.

Nanopore-based kinetics analysis of individual antibody-channel and antibody-antigen interactions.

BACKGROUND: The UNO/RIC Nanopore Detector provides a new way to study the binding and conformational changes of individual antibodies. Many critical questions regarding antibody function are still unresolved, questions that can be approached in a new way with the nanopore detector. RESULTS: We present evidence that different forms of channel blockade can be associated with the same antibody, we associate these different blockades with different orientations of "capture" of an antibody in the detector's nanometer-scale channel. We directly detect the presence of antibodies via reductions in channel current. Changes to blockade patterns upon addition of antigen suggest indirect detection of antibody/antigen binding. Similarly, DNA-hairpin anchored antibodies have been studied, where the DNA linkage is to the carboxy-terminus at the base of the antibody's Fc region, with significantly fewer types of (lengthy) capture blockades than was observed for free (un-bound) IgG antibody. The introduction of chaotropic agents and its effects on protein-protein interactions have also been observed. CONCLUSION: Nanopore-based approaches may eventually provide a direct analysis of the complex conformational "negotiations" that occur upon binding between proteins.

Cheminformatics methods for novel nanopore analysis of HIV DNA termini.

BACKGROUND: Channel current feature extraction methods, using Hidden Markov Models (HMMs) have been designed for tracking individual-molecule conformational changes. This information is derived from observation of changes in ionic channel current blockade "signal" upon that molecule's interaction with (and occlusion of) a single nanometer-scale channel in a "nanopore detector". In effect, a nanopore detector transduces single molecule events into channel current blockades. HMM analysis tools described are used to help systematically explore DNA dinucleotide flexibility, with particular focus on HIV's highly conserved (and highly flexible/reactive) viral DNA termini. One of the most critical stages in HIV's attack is the binding between viral DNA and the retroviral integrase, which is influenced by the dynamic-coupling induced high flexibility of a CA/TG dinucleotide positioned precisely two base-pairs from the blunt terminus of the duplex viral DNA. This suggests the study of a family of such CA/TG dinucleotide molecules via nanopore measurement and cheminformatics analysis. RESULTS: HMMs are used for level identification on the current blockades, HMM/EM with boosted variance emissions are used for level projection pre-processing, and time-domain FSAs are used to parse the level-projected waveform for kinetic information. The observed state kinetics of the DNA hairpins containing the CA/TG dinucleotide provides clear evidence for HIV's selection of a peculiarly flexible/interactive DNA terminus.