Formative Perceptions of a Digital Pill System to Measure Adherence to Heart Failure Pharmacotherapy: Mixed Methods Study.

BACKGROUND: Heart failure (HF) affects 6.2 million Americans and is a leading cause of hospitalization. The mainstay of the management of HF is adherence to pharmacotherapy. Despite the effectiveness of HF pharmacotherapy, effectiveness is closely linked to adherence. Measuring adherence to HF pharmacotherapy is difficult; most clinical measures use indirect strategies such as calculating pharmacy refill data or using self-report. While helpful in guiding treatment adjustments, indirect measures of adherence may miss the detection of suboptimal adherence and co-occurring structural barriers associated with nonadherence. Digital pill systems (DPSs), which use an ingestible radiofrequency emitter to directly measure medication ingestions in real-time, represent a strategy for measuring and responding to nonadherence in the context of HF pharmacotherapy. Previous work has demonstrated the feasibility of using DPSs to measure adherence in other chronic diseases, but this strategy has yet to be leveraged for individuals with HF. OBJECTIVE: We aim to explore through qualitative interviews the facilitators and barriers to using DPS technology to monitor pharmacotherapy adherence among patients with HF. METHODS: We conducted individual, semistructured qualitative interviews and quantitative assessments between April and August 2022. A total of 20 patients with HF who were admitted to the general medical or cardiology service at an urban quaternary care hospital participated in this study. Participants completed a qualitative interview exploring the overall acceptability of and willingness to use DPS technology for adherence monitoring and perceived barriers to DPS use. Quantitative assessments evaluated HF history, existing medication adherence strategies, and attitudes toward technology. We analyzed qualitative data using applied thematic analysis and NVivo software (QSR International). RESULTS: Most participants (12/20, 60%) in qualitative interviews reported a willingness to use the DPS to measure HF medication adherence. Overall, the DPS was viewed as useful for increasing accountability and reinforcing adherence behaviors. Perceived barriers included technological issues, a lack of need, additional costs, and privacy concerns. Most were open to sharing adherence data with providers to bolster clinical care and decision-making. Reminder messages following detected nonadherence were perceived as a key feature, and customization was desired. Suggested improvements are primarily related to the design and usability of the Reader (a wearable device). CONCLUSIONS: Overall, individuals with HF perceived the DPS to be an acceptable and useful tool for measuring medication adherence. Accurate, real-time ingestion data can guide adherence counseling to optimize adherence management and inform tailored behavioral interventions to support adherence among patients with HF.

Concancvalin A binding proteins of lymphoid cell surface.

A Concanavalin A binding protein of chicken lymphoid cells was isolated by affinity chromatography of intact lymphoid cells. This protein with a mol wt of 160,000 daltons revealed two peptides (30,000 and 20,000 daltons) in SDS-acrylamide gel electrophoresis.

Repetitive transcranial magnetic stimulation for the treatment of postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a common and gravely disabling health concern. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depression and may be a valuable tool in the treatment of PPD. The treatment effect of rTMS is rapid, generally well tolerated, without systemic effects, and without medication exposure to a fetus and/or breastfed infant. METHODS: Six women with PPD received 20 sessions of 10 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) over a 4 week period. Psychiatric rating scales (BDI, EPDS, STATI), cognitive assessments (MMSE, Trails B, List Generation) and breastfeeding practices were surveyed at baseline and post rTMS treatment. BDI and EPDS were obtained weekly, as well as 3 months and 6 months post study conclusion. RESULTS: Average BDI, EPDS, and STAI scores declined over the 4-week duration of rTMS treatment. Of the six patients, four achieved remission as assessed by EPDS and one achieved remission and two responded as assessed by BDI. Mean BDI and EPDS scores at 3 and 6 months follow-up remained below levels at study entry. No evidence of cognitive changes or breastfeeding disruptions. LIMITATIONS: This was an exploratory study with small sample size with no sham control arm. Daily administration of rTMS provides potential for confounding of behavioral activation in the otherwise often isolative postpartum period. CONCLUSIONS: rTMS was safe and well tolerated among participants with evidence of sustained improvements in depression and anxiety scores. This study supports rTMS as a promising non-pharmacologic treatment modality for perinatal depression.

The influence of diet and water on the stable oxygen and hydrogen isotope composition of Chironomidae (Diptera) with paleoecological implications.

Stable oxygen and hydrogen isotope analyses of fossil aquatic organisms, such as the chitinous head capsules of chironomid larvae (Chironomidae: Diptera), are promising proxies for inferring paleoecological conditions. In order for analyses of stable oxygen (delta(18)O) and hydrogen isotope ratios (delta(2)H) of fossil chironomid head capsules to be used effectively in paleoecological research, it is necessary to understand the factors controlling their stable oxygen and hydrogen composition. We cultured chironomid larvae in two isotopically distinct waters under controlled, replicated laboratory conditions. Chironomid larvae were fed on identical diets, to examine the degree to which water and diet influence the delta(18)O and delta(2)H of these organisms. We used a two-end member mixing model to determine the proportional contributions of oxygen and hydrogen from water to the oxygen and hydrogen of chironomid larvae. Our experiment demonstrated that 69.0 +/- 0.4% of oxygen and 30.8 +/- 2.6% of hydrogen in chironomid larvae are derived from habitat water. Our results show that oxygen isotopes from chironomid remains can better constrain past habitat water isotopic changes compared to hydrogen, due to 69% of the chironomid oxygen being influenced by habitat water. Our data add to a small but growing suite of comparative data on the sources of oxygen and hydrogen in animal tissues, and provide the first such analyses from aquatic insects.

Physical-chemical properties of ubiquitin.

The secondary structure of ubiquitin, the environment of its single tyrosine residue and its potential for interacting noncovalently with histone 2A or DNA, have been probed by circular dichroism (CD), ultraviolet absorbance, fluorescence and ancillary techniques. The results indicate that ubiquitin has a stable secondary structure containing only a low percentage of alpha-helix or beta-sheet. The ubiquitin tyrosine has an elevated pKa arising from the influence of a spatially proximate carboxylate which also causes a marked quenching of the tyrosine fluorescence at neutral pH; the influence of this carboxylate is lost when the protein is unfolded in 7 M guanidine. No evidence has been obtained for the presence of allosteric noncovalent interactions between free ubiquitin and either histone 2A or purified unfractionated DNA. The results suggest that one function of ubiquitin (or of the ubiquitin segment of protein A24) may be to interact with a chromatin component other than histone 2A or DNA, and/or that ubiquitin functions within 2A as a steric blocking group of a region of the nucleosome.

The cellular immune recognition of proteins expressed by an African swine fever virus random genomic library.

The cellular immune recognition of peptides expressed by an African swine fever virus (ASFV) random genomic library has been studied. DNA from the Malawi (LIL20/1) ASFV isolate was randomly sheared by sonication, cloned into a plasmid vector downstream of a bacteriophage T7 promoter, and 72 recombinant plasmids were arbitrarily selected. These plasmids were transiently expressed following transfection into major histocompatibility complex (MHC) class I(+) class II(-) matched pig skin cells, which had been co-infected with vTF7-3, a recombinant vaccinia virus encoding bacteriophage T7 RNA polymerase. Such cells served as antigen presenting cells and each recombinant plasmid was screened in a proliferation assay for recognition by CD8(+) lymphocytes from inbred pigs previously exposed to ASFV. This assay was demonstrated to measure CD8(+) T cell proliferation, as predicted by the phenotype of the antigen presenting cell. Of the 72 randomly selected clones, 14 were reproducibly recognised by immune pig lymphocytes and 10 corresponded to non-overlapping and distinct nucleic acid sequences. This high frequency of ASFV encoded antigenic epitopes supports the concept that cellular immunity to the virus may play an important role in resistance to ASF.

Inhalant use among antisocial youth: prevalence and correlates.

The current (2.9%), annual (19.6%), and lifetime (34.3%) prevalence of inhalant use among 475 youth (M age = 15.5; SD = 1.5; 87.4% male) on probation in a western state of the United States was assessed. Inhalant users reported significantly less family support and cohesiveness and lower self-esteem, and significantly more lifetime thoughts of suicide and suicide attempts, neighborhood gang activity, peer and parental substance abuse, intentions to engage in illegal behavior, substance-related criminality, and substance abuse than did nonusers. Ethnicity, self-esteem, suicidality, number of substance-using peers, and extent of substance-related criminality significantly discriminated inhalant users from nonusers in a logistic regression analysis. Multiple linear regression analyses indicated that age, perceived school ability, age at initiation of alcohol use, self-esteem, and substance-related criminality significantly predicted age at onset of inhalant use (R2 = .30). Age at initiation of inhalant use, gang membership, truancy, and substance-related criminality significantly predicted lifetime frequency of inhalant use (R2 = .20). Study findings indicate that inhalant-using delinquents evidence significantly greater antisocial attitudes, personal and familial dysfunction, and substance abuse, than do their non-inhalant-using counterparts.

Delinquents and drug use: a model program for community reintegration.

Evidence indicates that serious and persistent delinquency and the frequent use of illicit drugs emerge from common etiological roots. This suggests that treatment efforts which target risk factors of adolescent drug use and crime may be effective in preventing subsequent antisocial behavior. This paper describes Project ADAPT, a treatment program for juvenile delinquents based on the Social Development Model, which integrates this knowledge of risk factors. Project ADAPT is a 3 1/2-year demonstration project which combines behavioral skill training, supportive network development, and involvement in prosocial activities to facilitate the community reentry of youths following placement in a Washington state correctional facility.

Numerical modeling of atoll island hydrogeology.

We implemented Ayers and Vachers' (1986) inclusive conceptual model for atoll island aquifers in a comprehensive numerical modeling study to evaluate the response of the fresh water lens to selected controlling climatic and geologic variables. Climatic factors include both constant and time-varying recharge rates, with particular attention paid to the effects of El Niño and the associated drought it brings to the western Pacific. Geologic factors include island width; hydraulic conductivity of the uppermost Holocene-age aquifer, which contains the fresh water lens; the depth to the contact with the underlying, and much more conductive, Pleistocene karst aquifer, which transmits tidal signals to the base of the lens; and the presence or absence of a semiconfining reef flat plate on the ocean side. Sensitivity analyses of steady-steady simulations show that lens thickness is most strongly sensitive to the depth to the Holocene-Pleistocene contact and to the hydraulic conductivity of the Holocene aquifer, respectively. Comparisons between modeling results and published observations of atoll island lens thicknesses suggest a hydraulic conductivity of approximately 50 m/d for leeward islands and approximately 400 m/d for windward islands. Results of transient simulations show that lens thickness fluctuations during average seasonal conditions and El Niño events are quite sensitive to island width, recharge rate, and hydraulic conductivity of the Holocene aquifer. In general, the depletion of the lens during drought conditions is most drastic for small, windward islands. Simulation results suggest that recovery from a 6-month drought requires about 1.5 years.

Cultivation of malarial parasites.

The method for continuous cultivation of Plasmodium falciparum has now been successfully applied to several strains from different geographical areas. It has been used for tests of antimalarial drugs, for studies of parasite-host cell interactions with special reference to sickle haemoglobin, and for the production of amounts of parasite sufficient for experimental immunisation of Aotus trivirgatus monkeys.

Youth crime, public policy, and practice in the juvenile justice system: recent trends and needed reforms.

Historically, juvenile justice policy has oscillated between rehabilitative and punitive approaches to managing young offenders. Policy and practice in the 1970s and 1980s emphasized individual treatment for young offenders in nonsecure, community-based programs. An increase in violent youth crime during the past decade has renewed interest in punishing delinquent youths. Cyclic fluctuations in juvenile justice policy and their relationship to policy, practice, and youth crime are examined. Our analysis suggests that overall crime rates have remained relatively stable over the past three decades and are independent of prevailing juvenile justice policies. The findings support the need for targeted prevention efforts addressing the root causes of juvenile crime. Needed policy reforms, public education efforts, and practice approaches are outlined.

Chemical aversion treatment of alcohol dependence. I. Validity of current criticisms.

Current criticisms of chemical aversion therapy are delineated and their validity assessed. Data pertaining to the effectiveness, acceptability, intrusiveness, availability of alternative treatments, cost-effectiveness, and theoretical foundations of chemical aversion therapy are examined. It is concluded that available evidence supports the efficacy of chemical aversion therapy with respect to production of conditioned aversion to alcohol and treatment outcome.

Chemical aversion treatment of alcohol dependence. II. Future research directions for the '90s.

Chemical aversion treatment is one of the most promising modalities currently available for treatment of alcohol dependence. This review highlights potentially fruitful areas for future investigational efforts and poses a number of specific empirical questions. Investigation of issues delineated in this report would advance understanding of pharmacological aversion therapy vis-à-vis utility and mechanisms of action.

NO contributes to proliferative suppression in a murine model of filariasis.

Infection of BALB/c mice with microfilariae (mf) of Brugia pahangi leads to the suppression of antigen (Ag)-specific proliferative responses in the spleen. The proliferative defect is dependent on inducible nitric oxide synthase (iNOS) activity, since inhibition of iNOS with either L-N-monomethyl arginine (L-NMMA) or aminoguanidine reversed defective proliferation. Splenocytes from mf-infected animals produce high levels of gamma interferon (IFN-gamma) upon in vitro restimulation with Ag, and experiments in IFN-gamma receptor-deficient (IFN-gamma R(-/-)) mice demonstrated that signaling via the IFN-gamma R is essential in the induction of NO production and subsequent proliferative suppression. Restimulation of splenocytes from mf-infected animals with an extract of Acanthocheilonema viteae, a related filarial worm which lacks endosymbiotic bacteria, also resulted in NO production and proliferative suppression, demonstrating that lipopolysaccharide of bacterial origin is not essential to the induction of iNOS activity. These results extend previous observations that infection with different life cycle stages of Brugia leads to the development of differentially polarized immune responses and demonstrate one method by which these differences may exert their effects on the proliferative potential of cells from infected animals.

Treatment of adolescent substance abusers: issues for practice and research.

Treatment of adolescent substance abuse poses difficult challenges to social work practitioners. Effective intervention requires awareness of assessment and treatment approaches and knowledge of individual, peer, and family factors that contribute to alcohol or drug use. Social work's emphasis on contextual factors in the etiology and maintenance of addictive disorders is an important contribution to substance abuse treatment. Practitioners are in an excellent position to implement interventions addressing multiple causes of substance abuse. This paper discusses the prevalence of alcohol and drug use among adolescents in the United States. Assessment issues are identified and promising approaches to treating adolescents with substance use problems are noted. Implications for social work practice and research are delineated.

Lysines of histone 1 represent the principal target for covalent binding of microsomally activated benzo[a]pyrene in vitro.

The principal target amino acid residue for covalent binding of metabolically activated [3H]benzo[a]pyrene (B[a]P) to histone 1 (H1) has been identified. Highly purified calf thymus H1 was modified by incubation with [3H]B[a]P in the presence of rat liver microsomes. The relative distribution of [3H]B[a]P versus specific amino acids among the N-bromo-succinimide peptides of H1 suggested that lysine may be the target. This was tested by selectively blocking the nucleophilic amino groups of lysine by amidination prior to [3H]B[a]P binding. Increasing levels of amidination of H1 resulted in corresponding decreases in the reactivity of this histone toward [3H]B[a]P. Amidination of 93% of the lysines blocked 87% of the [3H]B[a]P binding indicating that lysine was the principal target. N-terminal amino acid sequencing of [3H]B[a]P-modified H1 confirmed that lysine residues had bound [3H]B[a]P.