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1.
Geriatr Nurs ; 57: 179-187, 2024.
Article in English | MEDLINE | ID: mdl-38663186

ABSTRACT

Caregivers of people living with dementia face strain, reduced self-care, and poorer health status. However, research examining the links among those outcomes is limited. We explored the association between caregiver strain and the impact of caregiving on health status and identified the mediating role of self-care difficulty in this association. In the national caregiving dataset "Caregiving in the U.S. 2020," we included 312 caregivers in this study. Demographics, caregiving characteristics, a composite scale for caregiver strain, and single-item questions for the impact of caregiving on health status and self-care difficulty were used. Descriptive statistics and mediation analysis were conducted. Results revealed that higher caregiver strain was associated with higher self-care difficulty (OR 2.054, p < .001) and negative health changes due to caregiving (OR 2.719, p < .001). Self-care difficulty partially mediated this association. These results indicated the need to explore interventions or resources to offer caregivers to encourage their self-care awareness and activities.


Subject(s)
Caregivers , Dementia , Self Care , Humans , Male , Female , Cross-Sectional Studies , Caregivers/psychology , Aged , Dementia/nursing , Surveys and Questionnaires , Middle Aged , Health Status , Stress, Psychological/psychology , United States
2.
BMC Nurs ; 23(1): 230, 2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38584253

ABSTRACT

BACKGROUND: Virtual simulation-based education for healthcare professionals has emerged as a strategy for dealing with infectious disease disasters, particularly when training at clinical sites is restricted due to the risk of infection and a lack of personal protective equipment. This research evaluated a virtual simulation-based education program intended to increase nurses' perceived competence in providing psychological support to patients affected by infectious disease disasters. METHODS: The efficacy of the program was evaluated via a randomized controlled trial. We recruited 104 nurses for participation in the study and allocated them randomly and evenly to an experimental group and a control group. The experimental group was given a web address through which they could access the program, whereas the control group was provided with a web address that directed them to text-based education materials. Data were then collected through an online survey of competence in addressing disaster mental health, after which the data were analyzed using the Statistical Package for the Social Sciences(version 23.0). RESULTS: The analysis showed that the experimental group's disaster mental health competence (F = 5.149, p =.026), problem solving process (t = 3.024, p =.003), self-leadership (t = 2.063, p =.042), learning self-efficacy (t = 3.450, p =.001), and transfer motivation (t = 2.095, p =.039) significantly statistically differed from those of the control group. CONCLUSIONS: A virtual nursing simulation-based education program for psychological support can overcome limitations of time and space. The program would also be an effective learning resource during infectious disease outbreaks. CLINICAL TRIAL REGISTRATION: This Korean clinical trial was retrospectively registered (21/11/2023) in the Clinical Research Information Service ( https://cris.nih.go.kr ) with trial registration number KCT0008965.

3.
Clin Nurse Spec ; 38(2): 107-109, 2024.
Article in English | MEDLINE | ID: mdl-38364072

ABSTRACT

PURPOSE/OBJECTIVES: We aim to explore Current Procedural Terminology (CPT) codes for caregiving training services and their potential impacts on caregivers of people living with dementia. DESCRIPTION OF THE PROJECT/PROGRAM: In response to the growing need for support for caregivers of people living with physical and mental health issues, CPT codes for caregiving training services will be activated for the calendar year 2024. These codes cover (1) family group behavior management and modification training services and (2) caregiver training for techniques to help patients maintain their quality of life. Caregivers will access such training support through the CPT codes provided by treating practitioners. The duration of training will vary by code. OUTCOME: Implementing CPT codes for caregiver training services highlights the vital role of caregivers in patient care. This support may improve their skills and communication with healthcare providers. However, timing and accessibility in care delivery need clarification, especially for caregivers of people living with dementia. Regular skill assessment and culturally competent care are essential. Before providing the service, provider training may also promote person-centered care, benefiting patients and their caregivers. CONCLUSION: Activating CPT codes for caregiving training services may enhance caregivers' support and skills, including dementia care.


Subject(s)
Caregivers , Dementia , Humans , Caregivers/psychology , Dementia/psychology , Quality of Life , Health Personnel , Power, Psychological
4.
Appl Psychophysiol Biofeedback ; 48(3): 259-274, 2023 09.
Article in English | MEDLINE | ID: mdl-37314616

ABSTRACT

Posttraumatic stress disorder (PTSD) encompasses various psychological symptoms and a high early dropout rate due to treatment unresponsiveness. In recent years, neurofeedback has been implemented to control PTSD's psychological symptoms through physiological brain regulation. However, a comprehensive analysis concerning its efficacy is lacking. Therefore, we conducted a systematic review and meta-analysis to determine neurofeedback's effect on reducing PTSD symptoms. We analyzed randomized and non-randomized controlled trials (RCTs) from 1990 to July 2020, evaluating neurofeedback treatments for those diagnosed with PTSD and their symptoms. In addition, we calculated the standardized mean difference (SMD)using random-effects models to estimate effect sizes. We assessed ten articles comprising 276 participants, with a - 0.74 SMD (95% confidence interval = - 0.9230, - 0.5567), 42% I2, moderate effect size, and - 1.40 to -0.08 prediction intervals (PI). Neurofeedback was more effective for complex trauma PTSD patients than single trauma. Increasing and lengthening sessions are more effective than fewer, condensed ones. Neurofeedback positively affected arousal, anxiety, depression, and intrusive, numbing, and suicidal thoughts. Therefore, neurofeedback is a promising and effective treatment for complex PTSD.


Subject(s)
Cognitive Behavioral Therapy , Neurofeedback , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/therapy , Stress Disorders, Post-Traumatic/psychology , Anxiety Disorders/therapy , Anxiety
5.
Int J Nurs Stud Adv ; 5: 100141, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38746574

ABSTRACT

Background: The number of people living with dementia continues to grow, increasing the demands on unpaid caregivers of people living with dementia. Caregiving can be emotionally and mentally distressing. In response, numerous interventions have been developed and tested to improve mental health in caregivers of people living with dementia. However, the effects of self-guided interventions on mental health in this population have remained understudied. Objective: We systematically examined the effects of self-guided interventions on stress, burden, and mental health of unpaid caregivers of people living with dementia. Design and Data Sources: A systematic review method following PRISMA guideline was used. PubMed, CINAHL, PsycINFO, Scopus, and Embase databases were searched using relevant search terms for the study aims from September to November 2022. The search was limited to peer-reviewed articles written in English. This review included articles that examined 1) unpaid caregivers of people living with dementia; 2) a self-guided, self-directed, or self-facilitated intervention; and 3) intervention to improve psychological or mental health as an outcome of interest. The exclusion criteria were: 1) secondary data analysis research based on an intervention study, 2) systematic reviews or meta-analyses, or 3) articles that evaluated only the acceptability or feasibility of a program. The collected data were synthesized using descriptive analysis with tabular summaries. The quality of each paper included was assessed by using JBI Quality Assessment tools. Results: A total of 16 articles and 1,182 unpaid caregivers of people living with dementia were included in this review. Stress, burden, depressive symptoms, anxiety, quality of life, self-efficacy, positive aspects of caregiving, social support, and personal relationship were measured in at least three articles. Depressive symptoms and burden were the most frequently measured outcomes. Stress was generally reduced after the interventions. However, the results of burden and mental health from each intervention were mixed and inconsistent. Interestingly, interventions that lasted less than 3 months were more likely to have better efficacy. Conclusions: Although the results of self-guided interventions are mixed, this is a potentially useful tool in improving emotional well-being for unpaid caregivers of people living with dementia due to low time burden, ease-to-access, and affordability. Future direction in intervention development should include identifying the optimal length and components of self-guided interventions and collaboration with clinicians for wider distribution to unpaid caregivers of people living with dementia. Registration: This review was not registered at the PROSPERO, and a review protocol was not prepared.

6.
J Prof Nurs ; 41: 65-74, 2022.
Article in English | MEDLINE | ID: mdl-35803661

ABSTRACT

Mentorship is important for doctoral education and development. Students in Doctor of Philosophy (PhD) in Nursing programs traditionally receive formal mentorship from more experienced faculty mentors, creating a top-down, mentor-mentee relationship. Peer mentorship, characterized by a mentor-mentee relationship between peers in similar career stages, provides unique opportunities for career development and socialization. The emergence of the COVID-19 pandemic limited in-person interactions and introduced new, complex challenges to peer mentorship. The authors, current and recently graduated PhD in Nursing students, were forced to create new ways of connecting with peers and sought to explore how other PhD in Nursing students experienced and maintained peer mentorship in their respective programs during the pandemic. In this article, the authors share their personal experiences with peer mentorship during the pandemic, their process of creating a formal peer mentor model, and findings from a national, cross-sectional survey on COVID-related, peer mentorship experiences among PhD in Nursing students from other academic institutions. Most respondents were able to maintain peer mentorship throughout the pandemic, however, less than half reported receiving faculty support to do so. Recommendations for PhD in Nursing program administrators are provided, based on the experiences of the authors and survey results from PhD in Nursing students across the United States.


Subject(s)
COVID-19 , Students, Nursing , Cross-Sectional Studies , Humans , Mentors , Pandemics , United States
7.
Integr Cancer Ther ; 21: 15347354221089605, 2022.
Article in English | MEDLINE | ID: mdl-35446180

ABSTRACT

BACKGROUND: Fatigue and lymphatic pain are the most common and debilitating long-term adverse effects of breast cancer treatment. Fatigue and pain independently have negative effects on quality of life, physical functions, and cancer recurrence-free survival. The interactions between fatigue and pain may aggravate their negative effects. OBJECTIVES: Examine the effects of co-occurring fatigue and lymphatic pain on activities of daily living (ADLs), emotional distress, and overall health of breast cancer patients. METHODS: A cross-sectional and observational design was used to enroll 354 breast cancer patients. Valid and reliable instruments were used to assess fatigue, lymphatic pain, ADLs, emotional distress, and overall health. Descriptive statistics and multivariable regression models were used for data analysis. RESULTS: After controlling for demographic and clinical factors, patients with co-occurring fatigue and lymphatic pain had higher odds of having impaired ADLs (OR = 24.43, CI = [5.44-109.67], P < .001) and emotional distress (OR = 26.52, CI = [9.64-72.90], P < .001) compared to patients with only fatigue and only lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had 179% increase in impaired ADL scores (B = 8.06, CI = [5.54-10.59]) and 211% increase in emotional distress scores (B = 9.17, CI = [5.52-12.83]) compared to those without co-occurring fatigue and lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had a 34% decrease (B = -26.29, CI = [-31.90 to -20.69]) and patients with only fatigue had a 33% decrease in overall health scores (B = -25.74, 95% CI = [-34.14 to -17.33]), indicating poor overall health. CONCLUSIONS: Fatigue and lymphatic pain affected 66.4% of breast cancer patients. Findings from this study suggest that co-occurring fatigue and lymphatic pain have negative effects on breast cancer patients' ADLs, emotional distress, and overall health. The synergistic interactions between fatigue and lymphatic pain incrementally aggravated their negative effects on ADLs and emotional distress. Findings of the study highlight the need to evaluate the underlying mechanisms for co-occurring fatigue and lymphatic pain and develop interventions that target both fatigue and lymphatic pain to improve breast cancer patients' the quality of life.


Subject(s)
Breast Neoplasms , Psychological Distress , Activities of Daily Living , Breast Neoplasms/complications , Breast Neoplasms/psychology , Cross-Sectional Studies , Fatigue/etiology , Fatigue/therapy , Female , Humans , Pain , Quality of Life/psychology
8.
Nat Mater ; 21(8): 890-895, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35484329

ABSTRACT

Moiré superlattices formed by stacking two-dimensional crystals have reinvigorated the pursuit for emergent functionalities of engineered superlattices. Unique optical characteristics can be realized from the interplay between the electronic excitations and the atomic rearrangements owing to their intrinsic softness. Although large-scale reconstructions have been identified at small twist angles, they have been treated as being rigid at large twist angles. Here, we report that moiré superlattices made from single layers of MoS2 and WSe2 exhibit a pair of torsional strains with opposite chirality irrespective of the twist angle. The whirlpool-shaped periodic lattice distortions introduce fuzziness in the Raman spectra and universal redshifts to the intralayer excitons for all twist angles. We show that both of these modulations become weaker as the twist angle increases but do not disappear, whereas they are turned off when the constituent layers are not tightly coupled, thus establishing an essential structure-property relationship for moiré superlattices.

9.
Sci Rep ; 12(1): 5101, 2022 Mar 24.
Article in English | MEDLINE | ID: mdl-35332178

ABSTRACT

Owing to unique fundamental physics and device applications, twisted moiré physics in two-dimensional (2D) van der Waals (vdW) layered magnetic materials has recently received particular attention. We investigate magnetic vdW Fe3GeTe2 (FGT)/CrGeTe3 (CGT) moiré heterobilayers with twist angles of 11° and 30° from first-principles. We show that the moiré heterobilayer is a ferromagnetic metal with an n-type CGT layer due to the dominant spin-majority electron transfer from the FGT layer to the CGT layer, regardless of various stacked structures. The spin-majority hybridized bands between Cr and Fe bands crossing the Fermi level are found regardless of stacking. The band alignment of the CGT layer depends on the effective potential difference at the interface. We show that an external electric field perpendicular to the in-plane direction modulates the interface dipole and band edges. Our study reveals a deeper understanding of the effects of stacking, spin alignment, spin transfer, and electrostatic gating on the 2D vdW magnetic metal/semiconductor heterostructure interface.

10.
Lymphat Res Biol ; 20(5): 525-532, 2022 10.
Article in English | MEDLINE | ID: mdl-35089817

ABSTRACT

Background: Breast cancer survivors who report chronic pain in the affected ipsilateral upper limb or body are nearly twice as likely to develop lymphedema. Little is known about lymphatic pain, defined as co-occurring pain and swelling in the affected ipsilateral upper limb or body. The study aimed to examine the predictors and effects of lymphatic pain on breast cancer survivors' activities of daily living (ADLs). Materials and Methods: A sample of 568 patients was recruited in a metropolitan cancer center in the United States. Demographic and clinical data were collected. Body mass index (BMI) and limb volume were measured using infra-red perometer. Lymphatic pain and ADLs were measured by the Lymphedema and Breast Cancer Symptom Experience Index. Parametric and nonparametric tests and generalized linear models were used to analyze data. Results: Lymphatic pain affected 33% of survivors. Significant predictors of lymphatic pain included younger age, higher BMI, financial hardship, and a diagnosis of lymphedema. Patients with a diagnosis of lymphedema had 9.68 odds (confidence interval [CI]: 5.78-16.63; p < 0.001) and those with financial hardship had 4.64 odds (CI: 1.99-11.32; p = 0.001) of experiencing lymphatic pain. Patients with lymphatic pain had more impairments in ADLs (p < 0.001) compared to patients with only pain, only swelling, and no symptoms. Significantly more patients with lymphatic pain had a limb volume difference of >5% and >10% compared to patients with only pain and no symptom. Conclusion: This study is the first to report that in a large sample of patients, 33.1% experienced lymphatic pain and that lymphatic pain was associated with significant impairments in ADLs. Findings suggest that lymphatic pain may be due to abnormal accumulation of lymph fluid. Research is needed to ascertain the physiological mechanisms that underlie lymphatic pain and determine whether strategies to prevent and treat lymphedema can decrease lymphatic pain.


Subject(s)
Breast Neoplasms , Cancer Survivors , Lymphedema , Humans , Female , Breast Neoplasms/complications , Breast Neoplasms/therapy , Activities of Daily Living , Quality of Life , Lymphedema/diagnosis , Lymphedema/epidemiology , Lymphedema/etiology , Survivors , Pain/diagnosis , Pain/etiology
11.
Disaster Med Public Health Prep ; 17: e55, 2021 10 22.
Article in English | MEDLINE | ID: mdl-34674792

ABSTRACT

OBJECTIVE: The study aimed to examine the experience of disaster healthcare workers with simulation training using the Psychological First Aid (PFA) mobile app. METHODS: This study was designed using qualitative research methodology with focus group interviews. The participants were 19 disaster healthcare workers from community mental health service centers who attended disaster simulation training in flood, fire, or leakage of hazardous chemicals. Before the simulation, participants were provided the PFA mobile app and allowed to practice the PFA techniques to apply them during the simulation. Data were collected through focus group interviews and qualitatively analyzed using the content analysis method. RESULTS: The findings were divided into 6 categories: experience in realistic disaster situations, satisfaction with education methods using a mobile app, effectiveness of the PFA app in disaster relief, confidence in disaster relief by integrating experience and knowledge of the PFA app, self-reflection as a disaster healthcare worker, and identifying limitations and making developmental suggestions. CONCLUSIONS: Based on the participants' developmental proposals in this study, the disaster simulation training, incorporating improvements in the disaster simulation training and the PFA app features, will serve as a new framework for disaster support education and systematic mental health services to survivors by disaster healthcare workers.


Subject(s)
Disasters , Mobile Applications , Simulation Training , Humans , Psychological First Aid , Health Personnel/psychology , First Aid
12.
Biomedicines ; 9(7)2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34356882

ABSTRACT

Lymphatic pain and swelling due to lymph fluid accumulation are the most common and debilitating long-term adverse effects of cancer treatment. This study aimed to quantify the effects of obesity on lymphatic pain, arm, and truncal swelling. Methods: A sample of 554 breast cancer patients were enrolled in the study. Body mass index (BMI), body fat percentage, and body fat mass were measured using a bioimpedance device. Obesity was defined as a BMI ≥ 30 kg/m2. The Breast Cancer and Lymphedema Symptom Experience Index was used to measure lymphatic pain, arm, and truncal swelling. Multivariable logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (CI) to quantify the effects of obesity. Results: Controlling for clinical and demographic characteristics as well as body fat percentage, obesity had the greatest effects on lymphatic pain (OR 3.49, 95% CI 1.87-6.50; p < 0.001) and arm swelling (OR 3.98, 95% CI 1.82-4.43; p < 0.001). Conclusions: Obesity is a significant risk factor for lymphatic pain and arm swelling in breast cancer patients. Obesity, lymphatic pain, and swelling are inflammatory conditions. Future study should explore the inflammatory pathways and understand the molecular mechanisms to find a cure.

13.
Int J Geriatr Psychiatry ; 36(11): 1732-1738, 2021 11.
Article in English | MEDLINE | ID: mdl-34216505

ABSTRACT

OBJECTIVES: This study aimed to investigate the effect of depression on suicidal behavior among older adults and identify the mediating effect of life satisfaction on the relationship between depression and suicidal behavior. The moderated mediating effects of social support through life satisfaction were also verified in the relationship between depression and suicidal behavior among older adults. METHODS: A total of 1375 people aged 65 years or older living in J city, South Korea, were recruited to complete a survey on depression, life satisfaction, suicidal behavior, and social support. Data were analyzed using SPSS24.0 and SPSS PROCESS Macro. RESULTS: The results showed that the effect of depression on suicidal behavior was mediated by life satisfaction, and the effect of life satisfaction on suicidal behavior varied according to the level of social support. Moreover, depression negatively affected life satisfaction, increasing the risk of suicidal behavior, and social support decreased suicidal behavior. Finally, the mediating effect of depression leading to suicidal behavior through life satisfaction was moderated by social support. CONCLUSIONS: These findings suggest that it is necessary not only to find interventions for older adults to increase their physical, mental, and socioeconomical satisfaction with life, but also to build social networks that increase social support for them.


Subject(s)
Personal Satisfaction , Suicidal Ideation , Aged , Depression , Humans , Republic of Korea , Social Support
14.
Sci Rep ; 11(1): 14639, 2021 07 19.
Article in English | MEDLINE | ID: mdl-34282172

ABSTRACT

Nonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676-0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724-0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.


Subject(s)
Circulating MicroRNA/blood , Non-alcoholic Fatty Liver Disease/diagnosis , Adult , Biomarkers/blood , Circulating MicroRNA/analysis , Diagnosis, Differential , Fatty Liver/blood , Fatty Liver/diagnosis , Female , Humans , Male , MicroRNAs/blood , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Predictive Value of Tests , Sensitivity and Specificity
15.
Integr Cancer Ther ; 20: 15347354211026757, 2021.
Article in English | MEDLINE | ID: mdl-34160294

ABSTRACT

BACKGROUND: The-Optimal-Lymph-Flow (TOLF) intervention aims to promote lymph flow through therapeutic lymphatic exercises to relieve lymphatic pain, swelling, lymphedema symptoms, and to decrease lymph fluid levels among breast cancer survivors. To enhance the efficacy of the TOLF intervention, an innovative, intelligent, Kinect-enhanced lymphatic exercise intervention (Kinect-TOLF) was developed to teach patients to perform the lymphatic exercises correctly. OBJECTIVES: This feasibility trial aimed to determine the feasibility, usability, and effects of the Kinect-TOLF on lymphatic pain, swelling, lymphedema symptoms, and lymph fluid levels. METHODS: A single-arm feasibility trial with a pre- and post-test design was employed to recruit 30 breast cancer survivors with persistent lymphatic pain or swelling. Patients received a single training session to learn how to perform the lymphatic exercises using the Kinect-TOLF program. Descriptive statistics, Wilcoxon signed-rank tests, t-test, Spearman's rank correlation coefficients, linear regressions, and Cohen's d were performed for data analysis. Qualitative data were assessed for common themes. RESULTS: The Kinect-TOLF was effective in training patients to perform the lymphatic exercises correctly with high user satisfaction. Significant reductions were found in scores of lymphatic pain (MedΔ = -1.00, CI = [-1.5, -0.1], P = .004), arm/hand swelling (MedΔ = -1.00, CI = [-1.5, -0.5], P = .004), total swelling (MedΔ = -1.5, CI = [-2.0, -1.0], P = .003), number of lymphedema symptoms (MΔ = -3.8, CI = [-5.5, -2.1], P < .001), and lymphedema symptom severity (MΔ = -5.3, CI = [-9.5, -1.1], P = .016). A significant reduction in lymph fluid levels was found in mean L-Dex scores (MΔ = -2.68, CI = [-4.67, -0.69], P = .010). Greater decrease in mean L-Dex scores were found in patients with abnormal lymph fluid levels (L-Dex ≥ 7.1) (MΔ = -5.19, CI = [-1.75, -8.63], P = .008). Patients' qualitative feedback supported the results of the study. CONCLUSIONS: The Kinect-TOLF is safe, feasible, and effective in reducing lymphatic pain, swelling, lymphedema symptoms, and in decreasing lymph fluid levels. Future research should focus on a randomized clinical trial to confirm the unique or synergistic efficacy of the Kinect-TOLF in comparison with current lymphedema treatment and other forms of exercises or movement therapy. This study was registered in ClinicalTrials.gov with US ClinicalTrials.gov Identifier: NCT03999177.


Subject(s)
Breast Neoplasms , Lymphedema , Edema , Exercise Therapy , Female , Humans , Lymphedema/therapy , Pain
16.
J Med Chem ; 64(9): 5905-5930, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33904304

ABSTRACT

There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclinical candidate for VL and, herein, we report on the medicinal chemistry program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with in vivo efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chemistry design, in silico profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships.


Subject(s)
Drug Design , Proteasome Endopeptidase Complex/metabolism , Proteasome Inhibitors/chemistry , Protozoan Proteins/metabolism , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/metabolism , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Binding Sites , Cell Line , Drug Evaluation, Preclinical , Half-Life , Humans , Leishmania donovani/drug effects , Leishmania donovani/metabolism , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/parasitology , Mice , Molecular Dynamics Simulation , Proteasome Endopeptidase Complex/chemistry , Proteasome Inhibitors/metabolism , Proteasome Inhibitors/pharmacology , Proteasome Inhibitors/therapeutic use , Protein Subunits/chemistry , Protein Subunits/metabolism , Protozoan Proteins/chemistry , Pyridines/chemistry , Pyridines/metabolism , Pyridines/pharmacology , Pyridines/therapeutic use , Solubility , Structure-Activity Relationship
17.
J Adv Nurs ; 77(5): 2519-2529, 2021 May.
Article in English | MEDLINE | ID: mdl-33576064

ABSTRACT

AIM: The aim of this study is to develop a Smarthealth system of monitoring, modelling, and interactive recommendation solutions (for caregivers) for in-home dementia patient care that focuses on caregiver-patient relationships. DESIGN: This descriptive study employs a single-group, non-randomized trial to examine functionality, effectiveness, feasibility, and acceptability of the novel Smarthealth system. METHODS: Thirty persons with Alzheimer's Disease or related dementia and their family caregivers (N = 30 dyads) will receive and install Smarthealth technology in their home. There will be a 1-month observation phase for collecting baseline mood states and a 2-month implementation phase when caregivers will receive stress management techniques for each detected, negative mood state. Caregivers will report technique implementation and usefulness, sent via Ecological Momentary Assessment system to the study-provided smartphone. Caregivers will provide daily, self-reported mood and health ratings. Instruments measuring caregiver assessment of disruptive behaviours and their effect on caregivers; caregiver depressive symptoms, anxiety and stress; caregiver strain; and family functioning will be completed at baseline and 3 months. The study received funding in 2018 and ethics board approval in 2019. DISCUSSION: This study will develop and test novel in-home technology to improve family caregiving relationships. Results from this study will help develop and improve the Smarthealth recommendation system and determine its usefulness, feasibility, and acceptability for persons with dementia and their family caregiver. IMPACT: The Smarthealth technology discussed will provide in-home stress reduction resources at a time when older adults may be experiencing increasingly high rates of isolation and anxiety and caregiver dyads may be experiencing high levels of relationship strain. TRIAL REGISTRATION: This study was registered with Clinical Trials.gov (Identifier NCT04536701).


Subject(s)
Alzheimer Disease , Dementia , Aged , Anxiety , Caregivers , Humans , Technology
18.
Lymphat Res Biol ; 19(3): 261-268, 2021 06.
Article in English | MEDLINE | ID: mdl-33185515

ABSTRACT

Background: Breast cancer-related lymphedema (BCRL) limits the movements of patients' limbs, which leads to a diminished ability to achieve essential activities of daily living (ADLs). The purpose of this study was to examine the associations between limb volume changes from the baseline before breast cancer surgery and self-reported difficulty in performing ADLs at 12 months following cancer surgery. We hypothesized that a positive association existed between limb volume changes from the baseline and self-reported difficulty in performing ADLs at 12 months following breast cancer surgery. Methods and Results: The data of the present study were part of a larger study with 140 breast cancer patients recruited before breast cancer surgery and followed up during their first year of treatment. Patients with more than 10% limb volume increase reported more frequent distress in performing 13 ADL items, compared with patients whose limb volume increased by 5%-10%. Regression analysis showed a significant increase in the odds ratio of reporting difficulty in ADLs compared with the group with less than 5% limb volume increase. Conclusion: Overall, patients with a greater limb volume increase underwent more difficulty performing ADLs. Patients reported more difficulty in performing ADLs even with 5%-10% limb volume increase. Currently, there is no standardized guideline to diagnose BCRL, although previous evidence suggests a limb volume increase greater than 10% as a criterion for BCRL. The findings from the present study suggest a more precise and clinically meaningful criteria for diagnosing BCRL to accommodate those with 5%-10% increase in limb volume.


Subject(s)
Breast Cancer Lymphedema , Breast Neoplasms , Lymphedema , Activities of Daily Living , Breast Neoplasms/complications , Breast Neoplasms/surgery , Female , Humans , Mastectomy , Prospective Studies
19.
Article in English | MEDLINE | ID: mdl-32325983

ABSTRACT

This study was conducted to explore nursing students' emotional experiences during simulations, and to develop a debriefing model for psychological safety in nursing simulations by qualitatively analyzing data. Data were collected through face-to-face in-depth interviews with 23 undergraduate nursing students in South Korea. Via content analysis, nine categories were derived: fear of evaluation, burden of being observed, unfamiliarity with new ways of learning, sensitivity to interpersonal relationships, physical and emotional exhaustion, utilization of supportive relationships, decline in learning satisfaction, positive acceptance of stress, and attempts to relieve stress. On the basis of these insights, we developed the Share-Explore-Notice-Support-Extend (SENSE) debriefing model, which includes stress management and emotional support, as a strategy for effective simulation practices to reduce the negative experiences of stress in nursing students in simulation-based learning.


Subject(s)
Education, Nursing, Baccalaureate , Models, Psychological , Simulation Training , Students, Nursing , Female , Humans , Learning , Male , Occupational Stress , Qualitative Research , Republic of Korea
20.
ACS Infect Dis ; 6(5): 1044-1057, 2020 05 08.
Article in English | MEDLINE | ID: mdl-32275825

ABSTRACT

Methionyl-tRNA synthetase (MetRS) is a chemically validated drug target in kinetoplastid parasites Trypanosoma brucei and Leishmania donovani. To date, all kinetoplastid MetRS inhibitors described bind in a similar way to an expanded methionine pocket and an adjacent, auxiliary pocket. In the current study, we have identified a structurally novel class of inhibitors containing a 4,6-diamino-substituted pyrazolopyrimidine core (the MetRS02 series). Crystallographic studies revealed that MetRS02 compounds bind to an allosteric pocket in L. major MetRS not previously described, and enzymatic studies demonstrated a noncompetitive mode of inhibition. Homology modeling of the Trypanosoma cruzi MetRS enzyme revealed key differences in the allosteric pocket between the T. cruzi and Leishmania enzymes. These provide a likely explanation for the lower MetRS02 potencies that we observed for the T. cruzi enzyme compared to the Leishmania enzyme. The identification of a new series of MetRS inhibitors and the discovery of a new binding site in kinetoplastid MetRS enzymes provide a novel strategy in the search for new therapeutics for kinetoplastid diseases.


Subject(s)
Allosteric Site , Methionine-tRNA Ligase/chemistry , Protozoan Proteins/chemistry , Trypanosoma brucei brucei/enzymology , Methionine
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