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To counteract host antiviral responses, influenza A virus triggers a global reduction of cellular gene expression, a process termed "host shutoff." A key effector of influenza A virus host shutoff is the viral endoribonuclease PA-X, which degrades host mRNAs. While many of the molecular determinants of PA-X activity remain unknown, a previous study found that N-terminal acetylation of PA-X is required for its host shutoff activity. However, it remains unclear how this co-translational modification promotes PA-X activity. Here, we report that PA-X N-terminal acetylation has two functions that can be separated based on the position of the acetylation, i.e. on the first amino acid, the initiator methionine, or the second amino acid following initiator methionine excision. Modification at either site is sufficient to ensure PA-X localization to the nucleus. However, modification of the second amino acid is not sufficient for host shutoff activity of ectopically expressed PA-X, which specifically requires N-terminal acetylation of the initiator methionine. Interestingly, during infection N-terminal acetylation of PA-X at any position results in host shutoff activity, which is in part due to a functional interaction with the influenza protein NS1. This result reveals an unexpected role for another viral protein in PA-X activity. Our studies uncover a multifaceted role for PA-X N-terminal acetylation in regulation of this important immunomodulatory factor.

Objectives: Loneliness and chronic stress are prevalent issues for older adults that have been linked to adverse health outcomes. We conducted a remote resilience and self-compassion intervention targeting loneliness and chronic stress., Methods: This study utilized a multiple-phase-change single-case experimental design with three consecutive 6-week phases: control, intervention, follow-up. Assessments and biomarker collection (blood pressure, inflammation, sleep actigraphy) were conducted at each phase. Participants completed a 6-week remotely-administered resilience and self-compassion intervention using techniques from cognitive behavioral therapy and resilience training. Repeated measures ANOVAs were conducted over the 12-week period from control (week 0) to intervention completion (week 12) and over the 18-week period from control (week 0) to follow-up (week 18) in supplemental analyses., Results: Participants reported a reduction in stress ( p  < 0.001; η p 2  = 0.15), depression ( p  =  0.02; η p 2  = 0.08), and loneliness ( p  = 0.003; η p 2  = 0.18), and an increase in self-compassion ( p   =  0.01; η p 2  = 0.13) from control to intervention completion (weeks 0-12). Post-hoc tests revealed that stress reduced significantly during the intervention phase (weeks 6-12) and loneliness reduced significantly during the control phase (weeks 0-6). Some improvements in blood pressure, inflammation, and sleep quality were noted in a subsample of participants., Conclusion: Findings indicate that our remote resilience and self-compassion intervention for older adults targeting loneliness and chronic stress was efficacious.

Objective: Older adults are vulnerable to perceived stress and loneliness, exacerbated by the COVID-19 pandemic. We previously reported inverse relationships between loneliness/perceived stress and wisdom/resilience. There are few evidence-based tele-health interventions for older adults. We tested a new remotely-administered manualized resilience- and wisdom-focused behavioral intervention to reduce perceived stress and loneliness in older adults., Methods: This pilot controlled clinical trial used a multiple-phase-change single-case experimental design, with three successive 6-week phases: control, intervention, and follow-up periods. The intervention included six once-a-week one-hour sessions. Participants were 20 adults >65 years, without dementia., Results: All 20 participants completed every session. The study indicated feasibility and acceptability of the intervention. While the sample was too small for demonstrating efficacy, there was a reduction (small-to-medium effect size) in perceived stress and loneliness, and increase in resilience, happiness, and components of wisdom and positive perceptions of aging., Conclusion: These preliminary data support feasibility, acceptability, and possible efficacy of a remotely-administered resilience- and wisdom-focused intervention in older adults to reduce stress and loneliness., (Copyright © 2022 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Persons with serious mental illnesses experience high rates of medical comorbidity, especially diabetes. This study examined initial implementation feasibility, acceptability, and appropriateness of a new 6-month Multicomponent Intervention for Diabetes risk reduction in Adults with Serious mental illnesses (MIDAS) among persons in residential care facilities (RCFs). We conducted a mixed-methods study using four types of quantitative and qualitative data sources (administrative data; structured facility-level observations; resident assessments including blood-based biomarkers, 24-h dietary recalls, and self-report physical activity; and focus groups/interviews with staff and participants), to assess evidence of and factors affecting intervention feasibility, acceptability, and appropriateness. It was feasible to provide a high percentage of MIDAS class sessions (mean 50 of 52 intended sessions delivered) and make nutrition-related RCF changes (substitutions for healthier food items and reduced portion sizes). Class attendance rates and positive feedback from residents and staff provided evidence of MIDAS acceptability and appropriateness for addressing identified health needs. The residents who attended ≥ 85% of the sessions had greater improvement in several desired outcomes compared to others. Implementing a fully integrated MIDAS model with more extensive changes to facilities and more fundamental health changes among residents was more challenging. While the study found evidence to support feasibility, acceptability, and appropriateness of individual MIDAS components, some challenges for full implementation and success in obtaining immediate health benefits were also apparent. The study results highlight the need for improving health among RCF populations and will inform MIDAS adaptations designed to improve intervention fit and effectiveness outcomes., (© 2022. The Author(s).)

We investigated subjective cognitive complaints (SCCs), as well as physical and mental health factors, in adults and older adults. U.S. residents ( N = 2,962) were recruited via the Amazon Mechanical Turk platform and completed a 90-item survey. Overall, 493/1930 (25.5%) of younger adults and 278/1032 (26.9%) of older adults endorsed SCCs. Analyses revealed worse physical and mental health characteristics in the SCC+ compared to the SCC- group, with primarily medium (Cohen's d = 0.50) to large (0.80) effect sizes. Age did not moderate relationships between SCCs and physical/mental health. Results suggest that SCCs are associated with a diverse set of negative health characteristics such as poor sleep and high body mass index, and lower levels of positive factors, including happiness and wisdom. Effect sizes of psychological correlates were at least as large as those of physical correlates, indicating that mental health is critical to consider when evaluating SCCs.

Herein, we establish a method to quantitatively monitor a metal-organic framework (MOF)-catalyzed, biomedically relevant reaction directly in blood plasma, specifically, the generation of nitric oxide (NO) from the endogenous substrate S -nitrosoglutathione (GSNO) catalyzed by H 3 [(Cu 4 Cl) 3 -(BTTri) 8 ] (CuBTTri). The reaction monitoring method uses UV-vis and 1 H NMR spectroscopies along with a nitric oxide analyzer (NOA) to yield the reaction stoichiometry and catalytic rate for GSNO to NO conversion catalyzed by CuBTTri in blood plasma. The results show 100% loss of GSNO within 16 h and production of 1 equiv. of glutathione disulfide (GSSG) per 2 equiv. of GSNO. Only 78 ± 10% recovery of NO(g) was observed, indicating that blood plasma can scavenge the generated NO before it can escape the reaction vessel. Significantly, to best apply and understand reaction systems with biomedical importance, such as NO release catalyzed by CuBTTri, methods to study the reaction directly in biological solvents must be developed.

Herpes simplex viruses (HSV-1 and HSV-2) encode up to 16 envelope proteins, four of which are essential for entry. However, whether these four proteins alone are sufficient to dictate the broad cellular tropism of HSV-1 and the selection of different cell type-dependent entry routes is unknown. To begin addressing this, we previously pseudotyped vesicular stomatitis virus (VSV), lacking its native glycoprotein G, with only the four essential entry glycoproteins of HSV-1: gB, gH, gL, and gD. This novel VSVΔG-BHLD pseudotype recapitulated several important features of HSV-1 entry: the requirement for gB, gH, gL, gD, and a cellular receptor and sensitivity to anti-gB and anti-gH/gL neutralizing antibodies. However, due to the use of a single cell type in that study, the tropism of the VSVΔG-BHLD pseudotype was not investigated. Here, we show that the cellular tropism of the pseudotype is severely limited compared to that of wild-type HSV-1 and that its entry pathways differ from the native HSV-1 entry pathways. To test the hypothesis that other HSV-1 envelope proteins may contribute to HSV-1 tropism, we generated a derivative pseudotype containing the HSV-1 glycoprotein C (VSVΔG-BHLD-gC) and observed a gC-dependent increase in entry efficiency in two cell types. We propose that the pseudotyping platform developed here has the potential to uncover functional contributions of HSV-1 envelope proteins to entry in a gain-of-function manner. IMPORTANCE Herpes simplex viruses (HSV-1 and HSV-2) contain up to 16 different proteins in their envelopes. Four of these, glycoproteins gB, gD, gH, and gL, are termed essential with regard to entry, whereas the rest are typically referred to as nonessential based on the entry phenotypes of the respective single genetic deletions. However, the single-gene deletion approach, which relies on robust loss-of-function phenotypes, may be confounded by functional redundancies among the many HSV-1 envelope proteins. We have developed a pseudotyping platform in which the essential four entry glycoproteins are isolated from the rest, which can be added back individually for systematic gain-of-function entry experiments. Here, we show the utility of this platform for dissecting the contributions of HSV envelope proteins, both the essential four and the remaining dozen (using gC as an example), to HSV entry., (Copyright © 2021 Hilterbrand et al.)

Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo 2 -lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies., (Published by Elsevier Inc.)

Objective: Wisdom has gained increasing interest among researchers as a personality trait relevant to well-being and mental health. We previously reported development of a new 24-item San Diego Wisdom Scale (SD-WISE), with good to excellent psychometric properties, comprised of six subscales: pro-social behaviors, emotional regulation, self-reflection (insight), tolerance for divergent values (acceptance of uncertainty), decisiveness, and social advising. There is controversy about whether spirituality is a marker of wisdom. The present cross-sectional study sought to address that question by developing a new SD-WISE subscale of spirituality and examining its associations with various relevant measures., Methods: Data were collected from a national-level sample of 1,786 community-dwelling adults age 20-82 years, as part of an Amazon M-Turk cohort. Participants completed the 24-item SD-WISE along with several subscales of a commonly used Brief Multidimensional Measure of Religiousness/Spirituality, along with validated scales for well-being, resilience, happiness, depression, anxiety, loneliness, and social network., Results: Using latent variable models, we developed a Spirituality subscale, which demonstrated acceptable psychometric properties including a unidimensional factor structure and good reliability. Spirituality correlated positively with age and was higher in women than in men. The expanded 28-item, 7-subscale SD-WISE total score (called the Jeste-Thomas Wisdom Index or JTWI) demonstrated acceptable psychometric properties. The Spirituality subscale was positively correlated with good mental health and well-being, and negatively correlated with poor mental health. However, compared to other components of wisdom, the Spirituality factor showed weaker (i.e., small-to-medium vs. medium-to-large) association with the SD-WISE higher-order Wisdom factor (JTWI)., Conclusion: Similar to other components as well as overall wisdom, spirituality is significantly associated with better mental health and well-being, and may add to the predictive utility of the total wisdom score. Spirituality is, however, a weaker contributor to overall wisdom than components like pro-social behaviors and emotional regulation. Longitudinal studies of larger and more diverse samples are needed to explore mediation effects of these constructs on well-being and health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Loneliness is a prevalent and serious public health problem due to its effects on health, well-being, and longevity. Understanding correlates of loneliness is critical for guiding efforts toward the development of evidence-based strategies for prevention and intervention. Considering that patterns of association between age and loneliness vary, the present study sought to examine age-related differences in risk and protective factors for loneliness., Methods: Correlates of loneliness were examined through a large web-based survey of 2,843 participants (aged 20-69 years) from across the United States from April 10, 2019, through May 10, 2019. Participants completed the 4-item UCLA Loneliness Scale, San Diego Wisdom Scale (with the following subscales measuring components of wisdom: Prosocial Behaviors, Emotional Regulation, Self-Reflection, Acceptance of Divergent Values, Decisiveness, and Social Advising), and other scales measuring psychosocial variables. Multivariate regression analyses were conducted to identify the best model of loneliness and examine potential age-related differences., Results: Age demonstrated a nonlinear quadratic relationship with loneliness (Wald statistic = 5.48, P = .019); levels were highest in the 20s and lowest in the 60s with another peak in the mid-40s. Across all decades, loneliness was associated with not having a spouse or partner (P < .001), sleep disturbance (P < .02), lower prosocial behaviors (P < .001), and smaller social network (P < .001). Lower social self-efficacy (P < .001) and higher anxiety (P < .005) were associated with worse loneliness in all age decades, except the 60s. Loneliness was uniquely associated with decisiveness in the 50s (P = .012) and with education (P = .046) and memory complaints (P = .013) in the 60s., Conclusions: Our findings identify several potentially modifiable targets related to loneliness, including several aspects of wisdom and social self-efficacy. Differential predictors at different decades suggest a need for a personalized and nuanced prioritizing of prevention and intervention targets., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Objective: Although 25% of people with bipolar disorder (BD) are over age 60, there is a dearth of research on older age bipolar disorder (OABD). This report describes an initial effort to create an integrated OABD database using the U.S. National Institute of Mental Health Data Archive (NDA). Goals were to: 1) combine data from three BD studies in the United States that included overlapping data elements; 2) investigate research questions related to aims of the original studies; and 3) take an important first step toward combining existing datasets relevant to aging and BD., Methods: Data were prepared and uploaded to the NDA, with a focus on data elements common to all studies. As appropriate, data were harmonized to select or collapse categories suitable for cross-walk analysis. Associations between age, BD symptoms, functioning, medication load, medication adherence, and medical comorbidities were assessed. The total sample comprised 451 individuals, mean age 57.7 (standard deviation: 13.1) years., Results: Medical comorbidity was not significantly associated with either age or functioning and there did not appear to be an association between medication load, comorbidity, age, and adherence. Men and African-Americans were significantly more likely to have poor adherence. Both BD mania and depression symptoms were associated with functioning, but this differed across studies., Conclusion: Despite limitations including heterogeneity in study design and samples and cross-sectional methodology, integrated datasets represent an opportunity to better understand how aging may impact the presentation and evolution of chronic mental health disorders across the lifespan., (Copyright © 2019 American Association for Geriatric Psychiatry. All rights reserved.)

This paper aims to compare mental and physical health, cognitive functioning, and selected biomarkers of aging reflecting metabolic pathology and inflammation, in outpatients with schizophrenia from two residential settings: residential care facilities (RCFs) and living with someone in a house/apartment. This cross-sectional study examined community-dwelling adults with schizophrenia either in RCFs (N = 100) or in a house/apartment with someone (N = 76), recruited for two NIH-funded studies in San Diego. Assessments included measures of mental/physical health, cognitive function, and metabolic (glycosylated hemoglobin, cholesterol) and inflammatory (C-Reactive Protein, Tumor Necrosis Factor-alpha, Interleukin-6) biomarkers of aging. General logistic models were used to analyze factors associated with residential status. RCF residents had several indicators of worse prognosis (never being married, higher daily antipsychotic dosages, increased comorbidities and higher Framingham risk for coronary heart disease) than individuals living with someone. However, RCF residents had better mental well-being and lower BMI, as well as comparable biomarkers of aging as those living with someone. While the cross-sectional nature of the study does not allow us to infer causality, it is possible that the supportive environment of RCFs may have a positive impact on mental and physical health of persons with schizophrenia. Longitudinal follow-up studies are needed to test this hypothesis., (Copyright © 2019. Published by Elsevier B.V.)

Higher prevalence of physical comorbidity and premature mortality in persons with schizophrenia (PwS) results primarily from heightened cardiovascular and metabolic risks. The literature suggests that insulin resistance precedes the development of obesity, smoking, and use of antipsychotic medications, although these likely play a compounding role later in the course of the disorder. It is thus important to discover the clinical characteristics of PwS with high insulin resistance, as these individuals may represent an etiopathologically distinct subgroup with a distinct course and treatment needs. We conducted a cross-sectional study and compared insulin resistance between 145 PwS and 140 nonpsychiatric comparison (NC) participants, similar in age, sex, and race distribution. In addition, we examined correlates of insulin resistance in PwS. As expected, PwS had higher levels of insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)] and body mass index (BMI) compared to the NC participants. HOMA-IR in the PwS was most associated with negative symptoms, BMI, and non-White race/ethnicity. The mechanistic relationships between insulin resistance and negative symptoms in schizophrenia patients warrant further investigation, and future studies should examine outcomes of PwS with this cluster of physical and mental symptoms and determine how management of insulin resistance might improve health of these individuals.

Intestinal microbiome and gut-brain axis have been receiving increasing attention for their role in the regulation of brain/behavior and possible biological basis of psychiatric disorders. Several recent clinical studies have linked the microbiome with neuropsychiatric conditions, although the literature on schizophrenia is quite limited. This study investigated gut microbiome composition in 50 individuals, including 25 persons with chronic schizophrenia and 25 demographically-matched non-psychiatric comparison subjects (NCs). Stool samples were collected and assayed using 16S rRNA sequencing of the V4 region. Examination of unweighted UniFrac and Bray-Curtis dissimilarity revealed significant community-level separation in microbiome composition between the two subject groups. At the phylum level, Proteobacteria were found to be relatively decreased in schizophrenia subjects compared to NCs. At the genus level, Anaerococcus was relatively increased in schizophrenia while Haemophilus, Sutterella, and Clostridium were decreased. Within individuals with schizophrenia, abundance of Ruminococcaceae was correlated with lower severity of negative symptoms; Bacteroides was associated with worse depressive symptoms; and Coprococcus was related to greater risk for developing coronary heart disease. Our findings provide evidence of altered gut microbial composition in persons with chronic schizophrenia and suggest a need for larger and longitudinal studies of microbiome in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Wisdom is an ancient concept that has gained new interest among clinical researchers as a complex trait relevant to well-being and healthy aging. As the empirical data regarding wisdom have grown, several measures have been used to assess an individual's level of wisdom. However, none of these measures has been based on a construct of wisdom with neurobiological underpinnings. We sought to develop a new scale, the San Diego Wisdom Scale (SD-WISE), which builds upon recent gains in the understanding of psychological and neurobiological models of the trait. Data were collected from 524 community-dwelling adults age 25-104 years as part of a structured multi-cohort study of adult lifespan. Participants were administered the SD-WISE along with two existing measures of wisdom that have been shown to have good psychometric properties. Factor analyses confirmed the hypothesized measurement model. SD-WISE total scores were reliable, demonstrated convergent and discriminant validity, and correlated, as hypothesized, negatively with emotional distress, but positively with well-being. However, the magnitudes of these associations were small, suggesting that the SD-WISE is not just a global measure of mental state. The results support the reliability and validity of SD-WISE scores. Study limitations are discussed. The SD-WISE, with good psychometric properties, a brief administration time, and a measurement model that is consistent with commonly cited content domains of wisdom based on a putative neurobiological model, may be useful in clinical practice as well as in bio-psycho-social research, especially investigations into the neurobiology of wisdom and experimental interventions to enhance wisdom., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age., Methods: We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years., Results: Overall, LTL was inversely associated with age (t(249) = -6.2, p < 0.001), and a gender effect on the rate of LTL decrease with age was found (t(249) = 2.20, p = 0.029), with men declining more rapidly than women. No significant overall effect of diagnosis on the rate of decline was detected. However, at the average sample age (48 years), there was a significant gender effect in both schizophrenia and HC groups (t(249) = 2.48, p = 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) = 2.43, p = 0.016) - at the average sample age, women with schizophrenia had shorter LTL than HC women., Discussion: Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women., (Published by Elsevier Ltd.)

Schizophrenia is characterized by physical (mainly metabolic and cardiovascular) comorbidity and shortened lifespan. High sensitivity C-reactive protein (hs-CRP), an inflammatory marker of hepatic origin linked to metabolic and cardiovascular diseases and mortality in the general population, has been reported to be elevated in people with schizophrenia. However, the relationship of hs-CRP to psychiatric and medical risk factors, after controlling for potentially confounding variables such as smoking, is not well established in schizophrenia. We assessed hs-CRP levels along with various demographic, psychiatric, and metabolic measures in 88 clinically stable outpatients with schizophrenia or schizoaffective disorder and 71 age epoch-matched comparison subjects with no history of a major psychiatric illness. hs-CRP levels were significantly higher in individuals with schizophrenia than in comparison subjects. Higher hs-CRP levels in the schizophrenia group were associated with female gender, more severe negative symptoms, greater medical comorbidity, and worse metabolic risk factors including BMI, fasting glucose, and hemoglobin A1c levels. hs-CRP was not related to age, race, education, smoking status, antipsychotic dosage, or cognitive impairment. Longitudinal studies are needed to investigate the relationship between hs-CRP and long-term health outcomes including metabolic syndrome, cardiovascular disease, and mortality in schizophrenia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: This study examined the differential prevalence of substance and alcohol use disorders among European Americans, African Americans, and Latinos with schizophrenia (n = 6424) who received public mental health services in San Diego County during fiscal year 2002-2003., Methods: Data were obtained from the public mental health database used by the San Diego County Mental Health System. Chi-Square analyses and stepwise logistic regression analyses were used to examine differences regarding the prevalence of substance and alcohol use among clients with schizophrenia and schizoaffective disorder, and to analyze the sociodemographic variables associated with this co-morbidity., Results: Significant differences in the prevalence of diagnosed co-morbidity were found across the ethnic groups. Rates of co-morbid diagnosis among African Americans (25%) were significantly higher than those among European Americans (22%) and Latinos (19%). Logistic regression results revealed ethnicity was a significant predictor of co-morbid substance and alcohol use, as was being homeless and male. Among Latinos, language preference was also a significant predictor. Latinos who denoted English as their primary language were 1.7 times more likely to be diagnosed with co-morbid substance or alcohol use disorders than Latinos who denoted Spanish., Conclusions: Among people with schizophrenia, there were significant differences in prevalence rates and predictors of diagnosed co-morbid substance and alcohol use disorders. Future research is needed to examine the relationship among language preference, level of acculturation, and subsequent diagnosing barriers for Latinos. Among African Americans, the reasons behind increased co-morbidity rates need to be examined, and homelessness should be carefully addressed among all three ethnic groups.

A Zymate II robotic dissolution system was modified by addition of a liquid chromatography (LC) system equipped with an Isco ISIS autosampler. Using the Concurrent EasyLab programming language, operation of this LC system was integrated into the main robotic dissolution procedure. This enabled simultaneous dissolution sampling and LC analysis of standard and pre-pulled sample solutions. The resulting dual-tasking system effects considerable efficiency of operation and results in significant time savings. Comparison of the robotic and non-robotic data indicate good correlation and statistically insignificant differences at the 95% confidence level. Validation studies confirm linearity and precision of the quantitative LC method, accuracy and precision of volume and temperature measurements and negligible vessel-to-vessel carryover.

A reversed-phase high-performance liquid chromatography method for the assay of erythromycins in pharmaceutical preparations is described. Detailed experimental procedures and results are given. The major erythromycins are well separated, very good recoveries were obtained and detection limits for erythromycins B and C were estimated.

An ion-pair reversed-phase high-pressure liquid chromatographic assay is developed that allows simultaneous quantitation of guaifenesin, dextromethorphan hydrobromide, and sodium benzoate in an expectorant syrup. The method is rapid and accurate. Average recoveries of 99.6, 99.8, and 99.7% with relative standard deviations of 0.5, 0.9, and 0.2% are obtained for guaifenesin, dextromethorphan hydrobromide, and sodium benzoate, respectively, from laboratory prepared samples. Chromatographic conditions are selected to afford a pH that provides adequate separation of guaifenesin, dextromethorphan hydrobromide, sodium benzoate, and sodium saccharin and a detection wavelength that effectively compensates for the great disparity in quantity between guaifenesin and dextromethorphan hydrobromide present in syrups. The relationships between the retention volume of dextromethorphan hydrobromide and the alkyl chain length as well as the concentration of the counterion are studied. The retention profiles for sodium saccharin, guaifenesin, sodium benzoate, and dextromethorphan hydrobromide in the apparent pH range of 2.5 to 6.6 are established.

A stabilized compressed nitroglycerin tablet, containing microocrystalline cellulose NF and providone NF as stabilizing agents, was formulated. Bioavailability and physical tests were conducted on the compressed tablet and two leading brands of molded tablets. There was no difference in the mean pulse rate between a molded tablet formulation and the compressed tablet in a crossover study using 10 human volunteers and three tablet strengths, 0.3, 0.4, and 0.6 mg. The compressed tablet was most uniform when tested according to the USP method for weight variation and content uniformity. Various tests for nitroglycerin loss due to volatility, i.e., open dish test, thermogravimetric analysis, and simulated in-use test, all indicated that the stabilized compressed tablet was substantially more stable than partially stabilized or unstabilized molded tablets.

A selective titrimetric method for the determination of benzoyl peroxide in lotions and creams was developed. It is based on the work of Horner and Jürgens, in which diacylperoxides, dialkylperoxides, peracids, and alkylhydroperoxides can be determined selectively by iodometry and acidimetry. The proposed assay is stability indicating with respect to peracids. Good recovery data were obtained.