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Future Medicinal Chemistry Jul 2024This study aimed to enhance the aqueous dissolution of SRPK inhibitor -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). A complex with...
This study aimed to enhance the aqueous dissolution of SRPK inhibitor -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). A complex with -sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines. The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, ∼50% for Nalm6 and Jurkat, and ∼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.
PubMed: 38949866
DOI: 10.1080/17568919.2024.2366690 -
Journal of Medical Internet Research Jul 2024Virtual reality (VR) is a well-researched digital intervention that has been used for managing acute pain and anxiety in pediatric patients undergoing various medical...
Exploring Relations Between Unique Patient Characteristics and Virtual Reality Immersion Level on Anxiety and Pain in Patients Undergoing Venipuncture: Secondary Analysis of a Randomized Control Trial.
BACKGROUND
Virtual reality (VR) is a well-researched digital intervention that has been used for managing acute pain and anxiety in pediatric patients undergoing various medical procedures. This study focuses on investigating the role of unique patient characteristics and VR immersion level on the effectiveness of VR for managing pediatric pain and anxiety during venipuncture.
OBJECTIVE
The purpose of this study is to determine how specific patient characteristics and level of immersion during a VR intervention impact anxiety and pain levels for pediatric patients undergoing venipuncture procedures.
METHODS
This study is a secondary data analysis of 2 combined, previously published randomized control trials on 252 pediatric patients aged 10-21 years observed at Children's Hospital Los Angeles from April 12, 2017, to July 24, 2019. One randomized clinical trial was conducted in 3 clinical environments examining peripheral intravenous catheter placement (radiology and an infusion center) and blood draw (phlebotomy). Conditional process analysis was used to conduct moderation and mediation analyses to assess the impact of immersion level during the VR intervention.
RESULTS
Significant moderation was found between the level of immersion and anxiety sensitivity when predicting postprocedural anxiety (P=.01). Patients exhibiting the highest anxiety sensitivity within the standard of care yielded a 1.9 (95% CI 0.9-2.8; P<.001)-point elevation in postprocedural anxiety relative to individuals with high immersion levels. No other significant factors were found to mediate or moderate the effect of immersion on either postprocedural anxiety or pain.
CONCLUSIONS
VR is most effective for patients with higher anxiety sensitivity who report feeling highly immersed. Age, location of the procedure, and gender of the patient were not found to significantly impact VR's success in managing levels of postprocedural pain or anxiety, suggesting that immersive VR may be a beneficial intervention for a broad pediatric population.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04268901; https://clinicaltrials.gov/study/NCT04268901.
PubMed: 38949862
DOI: 10.2196/53196 -
Journal of Agricultural and Food... Jul 2024Corn ear rot and fumonisin caused by pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity...
Corn ear rot and fumonisin caused by pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The bioassay results indicated that compound showed broad-spectrum activity with EC values falling from 3.51 to 24.10 μg/mL against and , which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
PubMed: 38949855
DOI: 10.1021/acs.jafc.4c02848 -
Blood Transfusion = Trasfusione Del... Jun 2024
Analysis of HLA matching between deceased organ donors and cord blood units from a national bank network as a basis for potential platforms for chimerism-based immune tolerance after solid organ transplantation.
PubMed: 38949850
DOI: 10.2450/BloodTransfus.759 -
Diabetes Care Jul 2024To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2...
OBJECTIVE
To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As).
RESEARCH AND METHODS
Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin.
RESULTS
Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028).
CONCLUSIONS
These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.
PubMed: 38949847
DOI: 10.2337/dc24-0573 -
Pharmeuropa Bio & Scientific Notes 2024The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by...
Determination of procoagulant activity in human normal immunoglobulin preparations for therapeutic use by FXIa chromogenic assay: Evaluation of test kit sensitivity, reference standard performance and product formulation effects on the FXIa assay.
The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by the European Pharmacopoeia (Ph. Eur.) that requires 2 control reference reagents. The World Health Organization (WHO) positive control International Reference Reagent (IRR; 02/228) with a nominal titre of 8 defines the highest acceptable titre, while the negative control preparation (02/226) has a nominal titre of <2. Working reference preparations (04/132 and 04/140) were subsequently established as Biological Reference Preparations (BRPs) for the Ph. Eur., and for distribution by the United States Food and Drug Administration (US FDA) and the National Institute for Biological Standards and Control (NIBSC). Due to diminishing stocks of these working reference preparations across the 3 institutions, a joint international study was organised to establish harmonised replacement batches. Sixteen laboratories contributed data to the study to evaluate positive and negative candidate replacement batches (13/148 and 12/300, respectively) against the WHO positive and negative control IRRs and the current working reference preparations (BRPs). The results show that the candidate reference preparations (13/148 and 12/300) are indistinguishable from the corresponding IRRs and current BRPs. The candidate preparations 13/148 and 12/300 were adopted by the Ph. Eur. Commission as Immunoglobulin (anti-D antibodies test) BRP batch 2 and Immunoglobulin (anti-D antibodies test negative control) BRP batch 2 with nominal haemagglutination titres of 8 and <2, respectively. The same materials were also adopted as NIBSC and US FDA reference preparations, thus ensuring full harmonisation.
Topics: Humans; Reference Standards; Immunoglobulins, Intravenous; Rho(D) Immune Globulin; Chemistry, Pharmaceutical
PubMed: 38949845
DOI: No ID Found -
Physiological Reports Jul 2024This study compared the joint kinematics between the front squat (FS) conducted in the upright (natural gravity) position and in the supine position on a short arm human... (Comparative Study)
Comparative Study
This study compared the joint kinematics between the front squat (FS) conducted in the upright (natural gravity) position and in the supine position on a short arm human centrifuge (SAHC). Male participants (N = 12) with no prior experience exercising on a centrifuge completed a FS in the upright position before (PRE) and after (POST) a FS exercise conducted on the SAHC while exposed to artificial gravity (AG). Participants completed, in randomized order, three sets of six repetitions with a load equal to body weight or 1.25 × body weight for upright squats, and 1 g and 1.25 g at the center of gravity (COG) for AG. During the terrestrial squats, the load was applied with a barbell. Knee (left/right) and hip (left/right) flexion angles were recorded with a set of inertial measurement units. AG decreased the maximum flexion angle (MAX) of knees and hips as well as the range of motion (ROM), both at 1 and 1.25 g. Minor adaptation was observed between the first and the last repetition performed in AG. AG affects the ability to FS in naïve participants by reducing MAX, MIN and ROM of the knees and hip.
Topics: Humans; Male; Range of Motion, Articular; Biomechanical Phenomena; Adult; Centrifugation; Knee Joint; Exercise; Young Adult; Hip Joint; Posture; Gravity, Altered
PubMed: 38949844
DOI: 10.14814/phy2.16034 -
Journal of Homosexuality Jul 2024Mental healthcare for LGBTQIA+ populations in rural areas remains unequal, despite societal progress toward inclusivity. This review examines the specific obstacles...
Mental healthcare for LGBTQIA+ populations in rural areas remains unequal, despite societal progress toward inclusivity. This review examines the specific obstacles faced in rural areas, such as limited services, workforce deficiencies, and travel burdens for treatment, which exacerbate existing mental health inequities. By following the Joanna Briggs Institute methodology, an exploration of SCOPUS, EBSCO Host (All), and Ovid databases yielded 2373 articles. After careful screening, 21 articles from five countries were selected, primarily using qualitative interviews and quantitative online surveys. Analysis through the Lévesque framework reveals the complex challenges faced by LGBTQIA+ individuals in rural mental healthcare. Discrepancies in approachability, acceptability, availability, affordability, and appropriateness were identified. Geographical isolation, discrimination, and a lack of LGBTQIA+-attuned professionals further compound these issues. Societal stigma, discrimination, and economic constraints hinder individuals from accessing and engaging in mental health services. This study highlights the need for purposeful interventions to improve rural mental health access for sexual and gender minorities.
PubMed: 38949842
DOI: 10.1080/00918369.2024.2373798 -
JAMA Internal Medicine Jul 2024The resting electrocardiogram (ECG) is commonly performed for cardiovascular disease (CVD) screening purposes in Japan. However, evidence is limited regarding the...
IMPORTANCE
The resting electrocardiogram (ECG) is commonly performed for cardiovascular disease (CVD) screening purposes in Japan. However, evidence is limited regarding the prognostic significance of ECG in clinical practice settings.
OBJECTIVE
To investigate the association between ECG abnormalities and CVD outcomes in a working-age population.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide cohort study included individuals aged 35 to 65 years from the Japan Health Insurance Association database, which covers approximately 40% (30 million) of the working-age population in Japan. Data from April 1, 2015, to March 31, 2022, were included, and analysis was conducted from October 1, 2022, to April 11, 2024.
EXPOSURES
Baseline ECG status (normal, 1 minor abnormality, ≥2 minor abnormalities, or major abnormality).
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of overall death and CVD hospital admission due to myocardial infarction, stroke, or heart failure. The secondary outcome was developing a new major ECG abnormality over the years of screening.
RESULTS
Of 3 698 429 individuals enrolled in the nationwide annual health check program (mean [SD] age, 47.1 [8.5] years; 66.6% male), 623 073 (16.8%) had 1 minor ECG abnormality, 144 535 (3.9%) had 2 or more minor ECG abnormalities, and 56 921 (1.5%) had a major ECG abnormality. During a median follow-up of 5.5 (IQR, 3.4-5.7) years, baseline ECG abnormality was independently associated with an increased incidence of the composite end points of overall death and CVD admission compared with normal ECG (incidence rates per 10 000 person-years: 92.7 [95% CI, 92.2-93.2] for normal ECG, 128.5 [95% CI, 127.2-129.9] for 1 minor ECG abnormality, 159.7 [95% CI, 156.6-162.9] for ≥2 minor ECG abnormalities, and 266.3 [95% CI, 259.9-272.3] for a major ECG abnormality; adjusted hazard ratios: 1.19 [95% CI, 1.18-1.20] for 1 minor ECG abnormality, 1.37 [95% CI, 1.34-1.39] for ≥2 minor ECG abnormalities, and 1.96 [95% CI, 1.92-2.02] for a major ECG abnormality). Furthermore, the presence and number of minor ECG abnormalities were associated with an increased incidence of developing new major ECG abnormalities (incidence rates per 10 000 person-years: 85.1 [95% CI, 84.5-85.5] for normal ECG, 217.2 [95% CI, 215.5-219.0] for 1 minor ECG abnormality, and 306.4 [95% CI, 302.1-310.7] for ≥2 minor ECG abnormalities; and adjusted hazard ratios: 2.52 [95% CI, 2.49-2.55] for 1 minor ECG abnormality and 3.61 [95% CI, 3.55-3.67] for ≥2 minor ECG abnormalities). Associations were noted regardless of baseline CVD risk.
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that the potential role of routine ECG screening for early prevention of CVD events, along with the optimal follow-up strategy, should be examined in future studies.
PubMed: 38949831
DOI: 10.1001/jamainternmed.2024.2270 -
Leukemia & Lymphoma Jul 2024This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was...
This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart ( = .031) and brain leukostasis ( = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.
PubMed: 38949830
DOI: 10.1080/10428194.2024.2372408