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.

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.

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.

In vitro immunomodulatory activity of ruthenium complexes.

OBJECTIVE AND DESIGN: We have explored the in vitro immunomodulatory effects of pure ruthenium red and a series of pyridine and imidazole substituted ruthenium complexes (RCs). MATERIAL: Human peripheral blood lymphocytes and purified T cells were used in these studies along with various cell lines. METHODS: Cells were treated with dilutions of RCs and assessed in various assays of immune function, cytotoxicity and cell cycle progression. RESULTS: RCs efficiently blocked T cell receptor (TCR)-mediated stimulation (IC(50)'s in the low nM range) of human peripheral blood lymphocytes (hPBL) by various agents, including tetanus toxoid, alloantigens, superantigens, and receptor-specific antibodies. RCs are not cytotoxic to T cells. Antiproliferative activity was also observed for B cells. Some non-lymphoid cell lines or primary cultures showed sensitivity to the RCs, but only at higher concentrations. The inhibitory effect on human T cells was assessed and demonstrated at the level of proliferation (DNA synthesis), IL-2 secretion, and IL-2 receptor (CD25) upregulation. RCs also inhibited IL-2-mediated proliferation of antigen-induced T-cell blasts and the IL-2-dependent T cell line Kit-225. Cell cycle analysis indicates that RCs inhibit the progression of activated T cells from G(0)/G(1) to S phase. CONCLUSIONS: Since the mechanism of T cell inhibition by RCs appears to be different than that of rapamycin (RAP) or cyclosporin A (CsA), they may provide a new tool to investigate intracellular signaling in T cells, and may present novel opportunities for immunosuppression

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.

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.

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.

Characterization of the African swine fever virion protein j18L.

The African swine fever virus (ASFV) open reading frame (ORF) that is named jl8L in the Malawi (LIL20/1) isolate and E199L in the Ba71V isolate encodes a cysteine rich protein of 195 amino acids with a predicted molecular mass of 21.7 kDa and a hydrophobic domain near the C terminus. There are several possible motifs for glycosylation, phosphorylation and myristoylation. Rabbit antisera and monoclonal antibodies raised against a recombinant ASFV j18L protein expressed as a fusion protein with glutathione S-transferase (GST) identified proteins of 19.0-20 kDa in cells infected with different ASFV strains and with a recombinant vaccinia virus expressing j18L. The monoclonal antibodies detected a protein of 20.0 kDa whereas rabbit antisera detected two proteins with relative molecular masses of 15.0 and 20.0 kDa in purified extracellular ASF virions. In ASFV-infected cells, the j18L protein was expressed late post-infection and was localized mainly in the viral factories.

Naphthalene sulfonate polymers with CD4-blocking and anti-human immunodeficiency virus type 1 activities.

PIC 024-4 and PRO 2000 are naphthalene sulfonate polymers that bind to CD4 with nanomolar affinity and block binding of gp120. Both have activity against human immunodeficiency virus type 1 in H9 cells, peripheral blood mononuclear cells, and primary monocyte/macrophages, are synergistic with zidovudine, and do not inhibit tetanus toxoid-stimulated T-cell proliferation at anti-human immunodeficiency virus type 1 concentrations.

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.

The effects of skills and intentions to use drugs on posttreatment drug use of adolescents.

The present study examines the relationship between (a) social, cognitive, and behavioral skills; (b) self-reported intentions to use drugs and alcohol following treatment; and (c) later drug and alcohol use for a sample of 130 adolescents. Social, problem solving, self-control, and drug and alcohol avoidance skills were significantly related to marijuana use, variety and severity of drug use, and to the number of drug-free months for female subjects at 12-month follow-up. These skills did not have a statistically significant direct effect on any measured drug outcomes for males. However, skills did lower male subjects' intentions to use drugs or alcohol. Decreased intentions to use, in turn, were associated with less drug and alcohol use, suggesting an indirect relationship between skills and reductions in drug and alcohol use among males at 12-month follow-up. Implications for the treatment of adolescents who engage in drug and alcohol use are discussed.

Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis.

It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.

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.

Purification and characterization of the bombesin/gastrin-releasing peptide receptor from Swiss 3T3 cells.

The bombesin/gastrin-releasing peptide (GRP) receptor was solubilized from Swiss mouse 3T3 cell membranes in an active form and was purified about 90,000-fold to near homogeneity by a combination of wheat germ agglutinin-agarose and ligand affinity chromatography. The purified receptor displayed a single diffuse band with a Mr of 75,000-100,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After treatment of the receptor with N-glycanase, removing N-linked oligosaccharide moieties, the protein yielded a Mr = 38,000 band. These results agree with the Mr value estimated for the GRP receptor that was labeled on Swiss 3T3 cells by cross-linking to 125I-GRP1-27. GRP1-27 bound to the purified receptor with a Kd of 0.038 +/- 0.019 nM. By comparison, the soluble receptor in unfractionated extracts and intact membranes displayed a Kd for GRP1-27 of 0.036 +/- 0.003 nM and 0.13 +/- 0.04 nM, respectively. The relative potencies of a series of GRP analogs for the soluble receptor and intact membranes indicated that the extraction procedure did not significantly alter the receptor's ligand binding specificity. However coupling of the receptor to its guanyl nucleotide regulatory protein was not maintained in the soluble extract, and a G-protein did not co-purify with the receptor. Physiological concentrations of NaCl greatly inhibited the binding of some GRP analogs to the receptor, while the binding of other analogs was not affected. A domain on the GRP molecule involving Lys-13 or Arg-17 was identified which promoted binding to the GRP receptor under conditions of low ionic strength. These findings aided the development of an effective ligand affinity resin for the purification of the GRP receptor.

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.