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Twin-screw melt granulation (TSMG) relies on the dispersive and distributive mixing at the kneading zone for granule growth to happen highlighting the critical role played by the kneading elements in TSMG. Despite extensive research conducted on the impact of screw geometry in melt compounding, there is not enough literature for TSMG. Disc width for the kneading elements was 2 mm, contrary to the standard 5 mm. The objective of this study was to evaluate if varying overflight clearance (OC) can alter the paradigm for TSMG. The new elements reduce the peak shear at kneading zone however a higher barrel temperature and degree of fill (DoF) is required to compensate to attain similar granule attributes. The change in DoF was achieved through a combination of modified screw configuration to pre-densify powders before kneading and processing at a lower screw speed. Despite the higher barrel temperature, process optimization of thermally unstable gabapentin was carried out. Using the new elements, compressible granules (Tensile strength > 2 MPa) with low % GABA-L content were manufactured despite increasing OC to 0.4 mm. Granule stability at 40 °C, ambient humidity for 6 months indicated gabapentin was stable (% GABA-L ≪0.4 %) despite a high barrel temperature of 120 °C., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Feng Zhang reports financial support was provided by Ashland Specialty Ingredients GP. Feng Zhang reports that some of the co-authors on this paper, viz. Charlie Martin, Brian Haight, are the employees of Leistritz, the supplier of the extruder used in this study and provided technical support by providing the new kneading elements. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Structural domains and domain walls, inherent in single crystalline perovskite oxides, can significantly influence the properties of the material and therefore must be considered as a vital part of the design of the epitaxial oxide thin films. We employ 4D-STEM combined with machine learning (ML) to comprehensively characterize domain structures at both high spatial resolution and over a significant spatial extent. Using orthorhombic LaFeO 3 as a model system, we explore the application of unsupervised and supervised ML in domain mapping, which demonstrates robustness against experiment uncertainties. The results reveal the consequential formation of multiple domains due to the structural degeneracy when LaFeO 3 film is grown on cubic SrTiO 3 . In situ annealing of the film shows the mechanism of domain coarsening that potentially links to phase transition of LaFeO 3 at high temperatures. Moreover, synthesis of LaFeO 3 on DyScO 3 illustrates that a less symmetric orthorhombic substrate inhibits the formation of domain walls, thereby contributing to the mitigation of structural degeneracy. High fidelity of our approach also highlights the potential for the domain mapping of other complicated materials and thin films., (© 2024. The Author(s).)

Hyperstimulation of the cholecystokinin 1 receptor (CCK1R), a G protein-coupled receptor (GPCR), in pancreatic acinar cells is commonly used to induce pancreatitis in rodents. Human pancreatic acinar cells lack CCK1R but express cholinergic receptor muscarinic 3 (M3R), another GPCR. To test whether M3R activation is involved in pancreatitis, a mutant M3R was conditionally expressed in pancreatic acinar cells in mice. This mutant receptor loses responsiveness to its native ligand, acetylcholine, but can be activated by an inert small molecule, clozapine-N-oxide (CNO). Intracellular calcium and amylase were elicited by CNO in pancreatic acinar cells isolated from mutant M3R mice but not WT mice. Similarly, acute pancreatitis (AP) could be induced by a single injection of CNO in the transgenic mice but not WT mice. Compared with the cerulein-induced AP, CNO caused more widespread acinar cell death and inflammation. Furthermore, chronic pancreatitis developed at 4 weeks after 3 episodes of CNO-induced AP. In contrast, in mice with 3 recurrent episodes of cerulein-included AP, pancreas histology was restored in 4 weeks. Furthermore, the M3R antagonist ameliorated the severity of cerulein-induced AP in WT mice. We conclude that M3R activation can cause the pathogenesis of pancreatitis. This model may provide an alternative approach for pancreatitis research.

This study investigates the effects of supercritical CO 2 as a foaming agent on structure and physical properties of hot melt extruded hydroxypropyl methylcellulose acetate succinate (HPMCAS)-itraconazole (ITZ) amorphous solid dispersions (ASDs) with the aim of improving the milling efficiency and tabletability of these ASDs. Two different grades of AFFINISOL TM HPMCAS, the standard grade (Std) and the High Productivity grade (HP) were used. The HP-grade has a lower molecular weight, melt viscosity and wider processing temperature range. Extrudates with different ITZ concentrations (0%, 20% and 40%) and CO 2 injection pressure of 100 and 200 bar were prepared. The cellular microstructure of the foams showed that HP-grade HPMCAS had better affinity with the CO 2 resulting in better distribution of CO 2 . The results of DSC and X-ray diffraction analysis revealed that the supercritical CO 2 did not affect the amorphous state of the API in the extrudates. Milling efficiency of the ASDs was significantly improved up to around 90% increase in the mass recovery. The tabletability of the milled extrudates showed a considerable increase in tablet tensile strength. In addition, foaming considerably improved the supersaturation of HP-grade ASD while showing minimal improvement in dissolution behavior of the Std-grade material., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Chemical degradation of drug substances remains a major drawback of extrusion. Larger-scale extrusion equipment has advantages over smaller equipment due to deeper flight elements and added flexibility in terms of screw design, unit operations, and residence time. In a previous study, we extruded a meloxicam-copovidone amorphous solid dispersion (ASD) on a Nano-16 extruder and achieved 96.7% purity. The purpose of this study is to introduce a strategy for scaling the process to an extruder with dissimilar geometry and to investigate the impact on the purity of the ASD. The formulation previously optimized on the Nano-16, 10:90 meloxicam and copovidone, was used for scale-up. Our approach to scale-up to the ZSE-18, utilized specific mechanical energy input and degree of fill from the Nano-16. Vacuum was added to prevent hydrolysis of meloxicam. Downstream feeding and micronization of meloxicam were introduced to reduce the residence time. In-line monitoring of the solubilization of meloxicam was monitored with a UV probe positioned at the die. We were able to achieve the same purity of meloxicam with the Micro-18 as we achieved with Nano-16. When process conditions alone were not sufficient, meglumine was added to further stabilize meloxicam. In addition to the chemical stability advantage that meglumine provided, we also observed solubility enhancement which allowed for an increase in drug loading to 20% while maintaining 100% purity.

Objective: This randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults., Research Methods and Procedures: Obese adults (body mass index, 30 to 44 kg/m(2)) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10-30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d-deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion., Results: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last-observation-carried-forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent-to-treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting > or =50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of > or =5% regardless of treatment (p < 0.0001). Bupropion SR was well-tolerated., Discussion: Bupropion SR in combination with a 500 kcal/d-deficit diet facilitated weight loss. Weight loss of > or =5% may improve mood in obese patients with depressive symptoms.

This study used a randomized pretest/posttest control group design to test the effectiveness of auricular acupuncture interventions in diminishing psychological and physiological changes associated with cocaine craving in 30 treatment-seeking cocaine-dependent patients. The experimental group received the real auricular acupuncture intervention, insertion of needles into ear point locations specifically targeted for drug withdrawal. The control group received sham or placebo auricular acupuncture, insertion of needles into ear point locations not targeted for any specific therapeutic benefit. Psychological (Cocaine Craving Questionnaire - Now) and physiological (skin conductance activity) changes associated with cocaine craving were measured. Results showed no differences between the control and the experimental group in diminishing psychological and physiological measures associated with craving. There were differences from pre- to posttest on measures of psychological but not physiological craving for the combined experimental and control groups.

To date, there is little information on the therapeutic effects of the life review beyond one year. This analysis followed fifty-two of 256 subjects who lived for at least three years in a nursing home. These participants received either a life review or friendly visit and took part in four repeated testings to determine the lasting effects of the life review at two and three years. Measures of integrity (life satisfaction, psychosocial well being, self-esteem) and despair (depression, hopelessness, and suicide intent) were used as pretest, posttest, and retest. Results showed a trend toward continued and by year three significant improvement over time in those who received the life review on measures of depression (t = -2.20, p < .03), life satisfaction (t = 2.51, p < .02), and self-esteem (t = -2.31, p < .03).

The purpose of this paper is to examine the Maris hypothesis that some people have relevant biographies and life histories that predispose suicidal careers. Using a life history approach, this paper reports differing themes in the lives of two groups of older women recently relocated to a nursing home--those who are satisfied with their lives and those who are not. Twelve women were selected from a sample of 256 by their scores on a life satisfaction index or suicidal intent scale. Seventy-two hours of transcribed life histories were content-analyzed for dominant themes that contributed to either life satisfaction or suicidal intent. Strong overall themes emerged for both groups under the headings of childhood, families, role models, connectedness, confidantes, life involvement, death experience, and memories. However, the most important correlates to contribute to a suicidal career for ideators were dysfunctional families of origin, poor role models, a feeling of isolation, and a pessimistic outlook.

Older Americans, 50 years of age and older, account for 10% of the 400,000 reported cases of AIDS nationwide (Centers for Disease Control and Prevention, 1994). the integrated literature review format in this article examines the published literature on HIV/AIDS in older adults. Most articles are case studies and reports, with only 17% having a research basis. The information reviewed indicates that older adults have different risk factors than younger populations for contracting HIV disease and a different pattern of disease progression. These differences create a need for knowledge of HIV infection and AIDS and its parameters in aging populations so nurses may provide both timely and appropriate care.

Relocation to a nursing home places frail elders at risk for developing depression and suicide ideation. This study followed two hundred and fifty-six newly relocated nursing home residents for five years. Using a Solomon Four research design, participants were divided into four groups, two control and two experimental, one each with pretesting and all with posttesting. Participants in the control groups received a friendly visit and those in the experimental groups received the intervention of life review. Immediate short-term results showed the life review to be an effective preventive intervention for clinical depression (p = .05). Additionally, when looking at long-term effects at one year, there were significant decrease in depression (p = .05), hopelessness (p = .01), and psychological well-being (p = .02) with measurable increases in life satisfaction (p = .08). These findings support the hypothesis that life review prevents despair in frail elders newly admitted to a nursing home.

Few nursing schools include in their curriculum home care work; fewer still include coursework in geropsychiatric issues. Yet this is a vital area of knowledge, particularly for home care nurses. What might such courses cover, and how important are they?

1. A part of the commitment to holistic nursing care is meeting the mental health needs of its clients. 2. There exists a great need to deal with both mental and physical problems in older persons. Moreover, geropsychiatry is greatly lacking in the policy and practice of nursing education. 3. Graduate-level courses must focus on both mental health promotion and disease prevention, particularly for the older persons who are consumers.

The literature is replete with diverse studies about gerontological nursing education on the attitudes of nursing students. This study examined the effect of a 3-year curriculum on ageism over all 3 years. Students were exposed first to well elderly subjects, then hospitalized older subjects, then severely ill older subjects. They were tested with the Kogan's Old People Scale and a semantic differential scale to see how their attitudes towards older people changed according to their experiences. The Kogan scale was most sensitive and showed that older students and those with grandparent role models had better attitudes towards older adults. Also, there were great increases in positive attitudes towards ageing in year 1 that slowly decreased by the end of year 3.

Gerontological literature in general, and gerontological nursing literature specifically, does not clearly differentiate two important therapeutic interventions for older people: reminiscence and life review. However, practitioners often implement both interventions in a variety of settings. Because of the confusion regarding the interventions, this paper explains the differences between reminiscence and life review, and offers protocols to improve the effectiveness of both interventions. The three protocols include one-to-one reminiscence therapy, group reminiscence, and one-to-one life review.

In this article, the authors describe a program created by a nursing inservice department to address the graying of America's hospital patients. The increased number of aging patients presents a challenge that hospitals must confront. Elderly patients who take longer to get well and consume more resources make unprecedented demands on nursing staff members. Because basic nursing education programs fail to address the problem, the task of preparing nursing personnel to care for aging patients falls to the hospital's department of staff development.

Students participating in this clinical exercise learned to critically evaluate problems occurring in their practice areas. In addition, they learned ways of addressing problems through nursing diagnosis. They experienced research as they conducted surveys, calculated results, and listed characteristics. The students had the opportunity to create a product. Unfortunately, as students graduated and became busy with their new positions, they no longer pursued the academic activity of getting a diagnosis accepted by NANDA. The acceptance process seemed particularly formidable after the initial rejection. An even more serious loss exists for graduates who work in gerontological nursing--that of not having these existent problems readily identified and labeled.

Although the terms reminiscence and life review continue to be used interchangeably in the literature, they are separate interventions. This article describes the differences, similarities, and commonalities in these two nursing interventions by highlighting differences in goals, theory base, the nurse's role, and the client's role. The implementation process and the desired outcomes are also differentiated to move forward nurse's understanding of these two important nursing interventions.

Gerontological nurses are currently using life review and reminiscence with clients. The terms are used interchangeably in practice and in the literature as though both were the same modality. Much confusion has resulted from lack of definitions of the modalities. Therefore, potentially effective nursing interventions are neither clearly understood nor correctly operationalized. This paper presents an analysis of each modality in an effort to clarify differences and further elucidate the current usage of them as concepts in nursing practice.

Twenty nurse experts participated in a four-round Delphi study to identify topics requiring clinical nursing research in long-term care. The Delphi strategy elaborated 265 items grouped in seven categories, with 73 items under the category of clinical practice. After four rounds, participants ranked the top-rated 50 items overall in serial importance. Nineteen of the 50 items were clinical practice items. A weighted rank than identified the top 10 items requiring investigation. Of these 10, the item deemed most important was patient-centered outcomes, an item subsuming all clinical nursing research.

This article offers basic instructions for performing a life review and running a reminiscence therapy group. The differences between the two modalities become apparent with the descriptions of the separate processes. Each use recall and memory to function. It is hoped that the descriptions and directions described will clarify the differences in reminiscence group therapy and life review and provide direction for gerontological nurses in clinical practice.

This study examined the underlying variables of selected reminiscing processes to determine those that contributed to well-being. Two hundred and forty subjects randomly selected from nursing homes and high-rises participated in one of 10 different reminiscing modalities for eight weeks. Measures of life satisfaction (LSI-A), psychological well being (ABS), self-esteem (SES), and depression (BDI) were given pre- and postintervention to determine the most therapeutic treatment modalities. Results showed the most therapeutic way to reminisce was through a structured, evaluative life review performed on an individual basis. Thus, three variables contributed to successful reminiscing: individuality (one-to-one reminiscing), evaluation (a personal valuing of events), and structure (covering the whole life span).

This integrated review presents the state of the art in reminiscing and life review as derived from a review of the literature from 1960-1990. Reports, reviews, and research are categorized and critiqued with the purpose of clarifying the use of reminiscing for practice. Out of ninety-seven published articles describing reminiscing, only seven report negative outcomes; the remainder are either positive or nonevaluative. As a result, the author concludes that clinicians should use reminiscing in their practice, and researchers should continue to define the variables that lead to successful reminiscing.