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International Journal of General... 2024Dementia is a common neurogenerative disease among older adults. Therefore, they are more prone to potentially inappropriate medication (PIM), which is medication that...
BACKGROUND
Dementia is a common neurogenerative disease among older adults. Therefore, they are more prone to potentially inappropriate medication (PIM), which is medication that causes more harm rather than protecting the health of an individual. Hence, the American Geriatrics Society (AGS) has recognized the risk of certain medication classes on this population and released PIM according to Beers criteria, which is a helpful guide for clinicians to ensure the safety of medication before it is prescribed. The aim of this study is to assess the prevalence of PIM use among older adults with dementia as a risk factor in comparison to other older adults without dementia.
METHODS
A retrospective study was conducted in an outpatient setting in a tertiary hospital targeting elderly patients aged 65 years old or over from January 2020 to September 2022. A total of 598 patients were screened, and 270 patients met the inclusion criteria. The eligible patients were then divided into two groups: 168 were in a non-dementia group and 102 were in a dementia group.
RESULTS
PIM use was reported in patients with and without dementia. The most inappropriate medication that was prescribed comprised atypical antipsychotics PIM for both patients with and without dementia. However, the prevalence was higher in the dementia group for quetiapine (75% vs 24% respectively), olanzapine (82% vs 17% respectively) or risperidone (92% vs 7%, respectively). Anticholinergics were highly prescribed in older adult without dementia as compared to dementia patient and was statistically significant for solifenacin (96% vs.3.6% respectively) and amitriptyline (88% vs 11% respectively).
CONCLUSION
Among elderly patients in outpatient care settings, the prevalence of PIM use is considered high in dementia patients for antipsychotics, while a higher use of benzodiazepine and anticholinergics was found in non-dementia patients.
PubMed: 38912331
DOI: 10.2147/IJGM.S456091 -
Annals of Translational Medicine Jun 2024Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of...
BACKGROUND
Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of sex, is the infrapatellar fat pad (IFP). We previously demonstrated that removal of the IFP had short-term beneficial effects for a cohort of male Dunkin-Hartley guinea pigs. The present project was designed to elucidate the influence of IFP removal in females of this OA-prone strain. It was hypothesized that resection of the IFP would reduce the development of OA in knees of a rodent model predisposed to the disease.
METHODS
Female guinea pigs (n=16) were acquired at an age of 2.5 months. Surgical removal of the IFP and associated synovium complex (IFP/SC) was executed at 3 months of age. One knee had the IFP/SC resected; a comparable sham surgery was performed on the contralateral knee. All animals were subjected to voluntary enclosure monitoring and dynamic weight-bearing, as well as compulsory treadmill-based gait analysis monthly; baseline data was collected prior to surgery. Guinea pigs were euthanized at 7 months. Knees from eight animals were evaluated via histology, mRNA expression, and immunohistochemistry (IHC); knees from the remaining eight animals were allocated to microcomputed tomography (microCT), biomechanical analyses (whole joint testing and indentation relaxation testing), and atomic absorption spectroscopy (AAS).
RESULTS
Fibrous connective tissue (FCT) replaced the IFP/SC. Mobility/gait data indicated that unilateral IFP/SC removal did not affect bilateral hindlimb movement. MicroCT demonstrated that osteophytes were not a significant feature of OA in this sex; however, trabecular thickness (TbTh) in medial femorae decreased in knees containing the FCT. Histopathology scores were predominantly influenced by changes in the lateral tibia, which demonstrated that histologic signs of OA were increased in knees containing the native IFP/SC versus those with the FCT. Similarly, indentation testing demonstrated higher instantaneous and equilibrium moduli in the lateral tibial articular cartilage of control knees with native IFPs. AAS of multiple tissue types associated with the knee revealed that zinc was the major trace element influenced by removal of the IFP/SC.
CONCLUSIONS
Our data suggest that the IFP/SC is a significant component driving knee OA in female guinea pigs and that resection of this tissue prior to disease has short-term benefits. Specifically, the formation of the FCT in place of the native tissue resulted in decreased cartilage-related OA changes, as demonstrated by reduced Osteoarthritis Research Society International (OARSI) histology scores, as well as changes in transcript, protein, and cartilage indentation analyses. Importantly, this model provides evidence that sex needs to be considered when investigating responses and associated mechanisms seen with this intervention.
PubMed: 38911554
DOI: 10.21037/atm-23-1886 -
Journal of Cancer 2024Skin cutaneous melanoma (SKCM) is a highly malignant tumor that is prone to immune escape and distant metastasis. Immunotherapy is considered to be the best treatment...
Skin cutaneous melanoma (SKCM) is a highly malignant tumor that is prone to immune escape and distant metastasis. Immunotherapy is considered to be the best treatment for patients with SKCM. However, not all patients benefit from it. We observed a significant differential expression of the lncRNA CYTOR in patients with SKCM based on single-cell and bulk RNA sequencing data mining results. The results showed that compared to normal tissue lncRNA CYTOR expression was significantly upregulated in SKCM tissue. Subsequently, we validated this finding in clinical samples, and we also found that the expression of lncRNA CYTOR in SKCM was higher as it progressed. lncRNA CYTOR was differentially expressed in patients who responded to immunotherapy, suggesting that it may serve as a biomarker to predict the efficacy of SKCM immunotherapy. In-depth analysis revealed that lncRNA CYTOR expression was strongly correlated with immune cell infiltration, immune response, and immune checkpoint expression. Meanwhile, our experiments revealed that CYTOR affects SKCM cell invasion and clone formation and is associated with the activation of the EMT pathway. In summary, our findings illustrate, for the first time, the value of CYTOR as a potential prognostic and immunotherapeutic response marker in SKCM.
PubMed: 38911384
DOI: 10.7150/jca.94823 -
Frontiers in Pediatrics 2024Multiple-breath washout (MBW) is a sensitive method for assessing lung volumes and ventilation inhomogeneity in infants, but remains prone to artefacts (e.g., sighs)....
BACKGROUND
Multiple-breath washout (MBW) is a sensitive method for assessing lung volumes and ventilation inhomogeneity in infants, but remains prone to artefacts (e.g., sighs). There is a lack of tools for systematic retrospective analysis of existing datasets, and unlike N-MBW in older children, there are few specific quality control (QC) criteria for artefacts in infant SF-MBW.
AIM
We aimed to develop a computer-based tool for systematic evaluation of visual QC criteria of SF-MBW measurements and to investigate interrater agreement and effects on MBW outcomes among three independent examiners.
METHODS
We developed a software package for visualization of raw Spiroware (Eco Medics AG, Switzerland) and signal processed WBreath (ndd Medizintechnik AG, Switzerland) SF-MBW signal traces. Interrater agreement among three independent examiners (two experienced, one novice) who systematically reviewed 400 MBW trials for visual artefacts and the decision to accept/reject the washin and washout were assessed.
RESULTS
Our tool visualizes MBW signals and provides the user with (i) display options (e.g., zoom), (ii) options for a systematic QC assessment [e.g., decision to accept or reject, identification of artefacts (leak, sigh, irregular breathing pattern, breath hold), and comments], and (iii) additional information (e.g., automatic identification of sighs). Reviewer agreement was good using pre-defined QC criteria (κ 0.637-0.725). Differences in the decision to accept/reject had no substantial effect on MBW outcomes.
CONCLUSION
Our visual quality control tool supports a systematic retrospective analysis of existing data sets. Based on predefined QC criteria, even inexperienced users can achieve comparable MBW results.
PubMed: 38910962
DOI: 10.3389/fped.2024.1393291 -
NPJ Science of Food Jun 2024Silkworm pupae as widely consumed insect products are good biosources of protein and micronutrients. Silkworm rearing throughout the year can be achieved by feeding them...
Silkworm pupae as widely consumed insect products are good biosources of protein and micronutrients. Silkworm rearing throughout the year can be achieved by feeding them an artificial diet instead of native plants, facilitating extensive pupa production. However, artificial diets are prone to spoilage caused by bacterial contamination. Here, we evaluated the antiseptic effect of ethylparaben (EP, chemical preservative) and medium-chain fatty acids (MCFA, natural preservative) in a silkworm artificial diet. Results showed that both preservatives effectively inhibited pathogenic bacterial growth. Furthermore, the addition of EP or MCFA did not negatively impact the production capacity of silkworms and the homeostasis of gut microbiota. However, the expression of genes involved in detoxification such as Ugt2, and immune response such as Cecropin B, were upregulated after EP consumption. Therefore, natural preservative MCFA emerges as a suitable option from a safety perspective. These findings highlight future directions for improving insect artificial diet formulation.
PubMed: 38909075
DOI: 10.1038/s41538-024-00284-9 -
Asian Nursing Research Jun 2024The prevalence of psychological distress is frequently observed among old adults with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However,...
A structural equation model of the relationship between symptom burden,psychological resilience, coping styles, social support and psychological distress in elderly patients with acute exacerbation chronic obstructive pulmonary disease in China.
The prevalence of psychological distress is frequently observed among old adults with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, current researches are insufficient to clarify the correlation among these relevant factors. This study examined the effects of symptom burden, psychological resilience, coping styles and socialsupporton psychological distress METHODS: 255 elderly patients with AECOPD were conveniently selected in Taian, Shandong Province. The General Information Questionnaire, Distress Thermometer, The Revised Memorial Symptom Assessment Scale, Connor-Davidson Resilience Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale were used to investigate. The relationship among factors was estimated by using a structural equation model RESULTS: Psychological distress score of elderly patients with AECOPD was (5.25±1.01); coping styles, psychological resilience, symptom burden, social support directly affected psychological distress (the direct effects were -0.934, 0.174, 0.169 and -0.086); coping styles had the largest total effect on psychological distress (the total effect was -0.934); psychological resilience indirectly affected psychological distress through coping styles (the indirect effect was -0.743); symptom burden indirectly affected psychological distress through psychological resilience (the indirect effect was 0.254); social support indirectly affected psychological distress through symptom burden, psychological resilience, and coping styles (the indirect effect was -0.799) CONCLUSION: The psychological distress of elderly patients with AECOPD is at a moderate level; coping styles, psychological resilience and social support have positive effects on alleviating the psychological distress of elderly patients with AECOPD; symptom burden is negatively correlated with psychological distress. Healthcare professionals should pay more attention to elderly patients with AECOPD who are particularly prone to experiencing higher levels of psychological distress, especially in the presence of low coping style, limited psychological resilience, inadequate levels of social support, and high symptom burden.
PubMed: 38908429
DOI: 10.1016/j.anr.2024.06.003 -
Journal of Biomechanics Jun 2024Arteriovenous fistula (AVF) is the optimal form of vascular access for most haemodialysis dependant patients; however, it is prone to the formation of stenoses that...
Arteriovenous fistula (AVF) is the optimal form of vascular access for most haemodialysis dependant patients; however, it is prone to the formation of stenoses that compromise utility and longevity. Whilst there are many factors influencing the development of these stenoses, pathological flow-related phenomena may also incite the formation of intimal hyperplasia, and hence a stenosis. Repeated CFD-derived resistance was calculated for six patient who had a radiocephalic AVF, treated with an interwoven nitinol stent around the juxta-anastomotic region to address access dysfunction. A three-dimensional freehand ultrasound system was used to obtain patient-specific flow profiles and geometries, before performing CFD simulations to replicate the flow phenomena in the AVF, which enabled the calculation of CFD-derived resistance. We presented six patient cases who were examined before and after treatment and our results showed a 77% decrease in resistance, recorded after a surgical intervention to address access dysfunction. Problematic AVFs were found to have high resistance, particularly in the venous segment. AVFs with no reported clinical problems, and clinical patency, had low resistance in the venous segment. There did not appear to be any relationship with clinical problems/patency and resistance values in the arterial segment. Identifying changes in resistance along the circuit allowed stenoses to be identified, independent to that determined using standard sonographic criteria. Our exploratory study reveals thatCFD-derived resistance is a promising metric that allows for non-invasive identification of diseased AVFs. The pipeline analysis enabled regular surveillance of AVF to be studied to aid with surgical planning and outcome, further exhibiting its clinical utility.
PubMed: 38908106
DOI: 10.1016/j.jbiomech.2024.112203 -
Scientific Reports Jun 2024In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and...
In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient's position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.
Topics: Humans; Female; Breast Neoplasms; Prone Position; Supine Position; Organs at Risk; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiometry; Patient Positioning; Lung; Middle Aged; Radiotherapy, Intensity-Modulated; Heart
PubMed: 38907042
DOI: 10.1038/s41598-024-65461-y -
Lupus Science & Medicine Jun 2024Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is...
OBJECTIVE
Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear.
METHODS
MRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice.
RESULTS
ZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1β in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys.
CONCLUSION
RIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.
Topics: Animals; Lupus Erythematosus, Systemic; Mice, Inbred MRL lpr; Receptor-Interacting Protein Serine-Threonine Kinases; Mice; Mice, Inbred C57BL; Disease Models, Animal; Graft vs Host Disease; Cytokines; Female; Antibodies, Antinuclear; Lupus Nephritis; T-Lymphocytes; Spleen
PubMed: 38906550
DOI: 10.1136/lupus-2024-001146 -
The Journal of Nutrition Jun 2024The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) (NCT00179777) found no difference type 1 diabetes risk between hydrolyzed and regular infant formula....
High levels of immunoglobulin G against cow's milk proteins and frequency of cow milk consumption are associated with the development of islet autoimmunity and type 1 diabetes - the TRIGR study.
BACKGROUND
The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) (NCT00179777) found no difference type 1 diabetes risk between hydrolyzed and regular infant formula. However, cow's milk consumption during childhood is consistently linked to type 1 diabetes risk in prospective cohort studies.
OBJECTIVE
Our primary aim was to study whether humoral immune responses to cow's milk and cow's milk consumption are associated with type 1 diabetes in TRIGR children.
METHODS
TRIGR comprised 2159 children with genetic susceptibility to type 1 diabetes born between 2002-2007 in 15 countries. Children were randomized into groups receiving extensively hydrolyzed casein or a regular cow's milk formula and followed until age 10. Type 1 diabetes related autoantibodies and antibodies to cow's milk proteins were analyzed. Infant formula intake was measured by structured dietary interviews and milk consumption with a food frequency questionnaire. Associations of milk antibodies and milk consumption with the risk to develop type 1 diabetes were analysed by Cox survival model.
RESULTS
Cow's milk antibody levels both in cord blood [HR for islet autoimmunity 1.30 (95% CI 1.05-1.61); type 1 diabetes 1.32 (1.02-1.71)] and longitudinally from birth to 3 years [islet autoimmunity 1.39 (1.07-1.81); type 1 diabetes 1.43 (1.04-1.96)] were associated with increased risk of developing type 1 diabetes. The amount of regular infant formula was associated with a reduced islet autoimmunity risk in the regular infant formula group [0.92 (0.85-0.99)]. Furthermore, frequent liquid milk consumption after infancy was associated with an increased risk of islet autoimmunity or type 1 diabetes.
CONCLUSIONS
Elevated cow's milk antibody levels and high consumption of liquid milk after infancy are related to type 1 diabetes development in children with an increased genetic susceptibility to type 1 diabetes. Enhanced antibody levels to cow's milk may provide a biomarker of immune system prone to develop islet autoimmunity.
TRIAL REGISTRY NUMBER
NCT00179777.
PubMed: 38906178
DOI: 10.1016/j.tjnut.2024.06.005