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Asian Pacific Journal of Cancer... Jun 2024Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A Randomized Single-Blinded Phase II Trial Comparing Efficacy and Quality of Life of Topical Aloe Vera Gel Plus Urea Cream Versus Urea Cream Alone for Prevention of Hand Foot Syndrome in Cancer Patients Receiving Capecitabine.
INTRODUCTION
Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively co-prescribed, even though its efficacy is doubtful. Aloe vera gel with urea cream might potentiate each other. This trial was intended to prove the efficacy of this combination.
MATERIALS AND METHODS
The investigators conducted a randomized single-blinded phase II study. The participants were randomized 1:1 to receive the combination of aloe vera gel and 10% urea cream (n = 30), the experimental A+U arm and 10% urea cream alone (n = 31), the U arm. The sample size was calculated to have 90% power to show the significant 20% reduction in the incidence of HFS grade 2-3 of the combination therapy with alpha level = 0.05. Both the CTCAE criteria version 5 and the dermatology life quality index (DLQI) were assessed to determine the severity of HFS and quality of life, respectively.
RESULTS
Most of the participants had rectal cancer (A+U: 43.3%; U: 41.9%). In the A+U group, 86.7% had grade 0-1 HFS and 13.3% had grade 2-3 HFS. In the U group, 64.5% had grade 0-1 HFS and 35.5% had grade 2-3 HFS (Mann-Whitney U test, p = 0.045). Grade 2-3 HFS was significantly lower in the combination group.
CONCLUSION
Combination of aloe vera gel and 10% urea cream ameliorated the severity of HFS in participants taking capecitabine; however, no significant difference in DLQI between the groups was demonstrated.
Topics: Humans; Capecitabine; Female; Male; Middle Aged; Quality of Life; Hand-Foot Syndrome; Urea; Antimetabolites, Antineoplastic; Single-Blind Method; Plant Preparations; Prognosis; Follow-Up Studies; Adult; Administration, Topical; Aged; Neoplasms; Skin Cream; Aloe
PubMed: 38918684
DOI: 10.31557/APJCP.2024.25.6.2203 -
Microbiology Spectrum Jun 2024The discovery of antimicrobials with novel mechanisms of action is crucial to tackle the foreseen global health crisis due to antimicrobial resistance. Bacterial...
UNLABELLED
The discovery of antimicrobials with novel mechanisms of action is crucial to tackle the foreseen global health crisis due to antimicrobial resistance. Bacterial two-component signaling systems (TCSs) are attractive targets for the discovery of novel antibacterial agents. TCS-encoding genes are found in all bacterial genomes and typically consist of a sensor histidine kinase (HK) and a response regulator. Due to the conserved Bergerat fold in the ATP-binding domain of the TCS HK and the human chaperone Hsp90, there has been much interest in repurposing inhibitors of Hsp90 as antibacterial compounds. In this study, we explore the chemical space of the known Hsp90 inhibitor scaffold 3,4-diphenylpyrazole (DPP), building on previous literature to further understand their potential for HK inhibition. Six DPP analogs inhibited HK autophosphorylation and had good antimicrobial activity against Gram-positive bacteria. However, mechanistic studies showed that their antimicrobial activity was related to damage of bacterial membranes. In addition, DPP analogs were cytotoxic to human embryonic kidney cell lines and induced the cell arrest phenotype shown for other Hsp90 inhibitors. We conclude that these DPP structures can be further optimized as specific disruptors of bacterial membranes providing binding to Hsp90 and cytotoxicity are lowered. Moreover, the X-ray crystal structure of resorcinol, a substructure of the DPP derivatives, bound to the HK CheA represents a promising starting point for the fragment-based design of novel HK inhibitors.
IMPORTANCE
The discovery of novel antimicrobials is of paramount importance in tackling the imminent global health crisis of antimicrobial resistance. The discovery of novel antimicrobials with novel mechanisms of actions, e.g., targeting bacterial two-component signaling systems, is crucial to bypass existing resistance mechanisms and stimulate pharmaceutical innovations. Here, we explore the possible repurposing of compounds developed in cancer research as inhibitors of two-component systems and investigate their off-target effects such as bacterial membrane disruption and toxicity. These results highlight compounds that are promising for further development of novel bacterial membrane disruptors and two-component system inhibitors.
PubMed: 38917423
DOI: 10.1128/spectrum.00146-24 -
PloS One 2024Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from UVATS, is a novel surgical approach for VATS and carries out micro-innovation for lung...
OBJECTIVES
Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from UVATS, is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach.
METHODS
The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected, and analyzed. According to whether applied Lu's approach during the VATS operation, patients were divided into the LVATS group and the UVATS group. The propensity score (PS) matching method was used to reduce selection bias by creating two groups. After generating the PSs, 1:1 ratio and nearest-neighbor score matching was completed. Perioperative variables, including the operation time, intraoperative blood loss, lymph node stations dissected, total drainage volume, drainage duration, postoperative hospital stay, pain score (VAS, Visual Analogue Scale) on the postoperative first day (POD1) and third day (POD3), and incidence of postoperative complications, were compared between the two groups. The data were analyzed statistically with P<0.05 defined as statistically significant.
RESULTS
A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144)min, P <0.001), less intraoperative blood loss(20 (20, 30) VS 25 (20, 50)ml, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50)cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600)ml, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected(5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4)days, P = 0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6)days, P = 0.608), VAS on the POD1(4 (4, 4) VS 4 (4, 4), P = 0.058)and POD3 (3 (3, 4) VS 4 (3, 4), P = 0.219), and incidence of postoperative complications (P = 0.521) between the two groups.
CONCLUSIONS
Lu's approach is a safe and feasible approach for video-assisted thoracoscopic surgery for the lobectomy of NSCLC. This approach can shorten surgical time, reduce incision length and intraoperative blood loss.
Topics: Humans; Thoracic Surgery, Video-Assisted; Male; Female; Middle Aged; Lung Neoplasms; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Aged; Postoperative Complications; Operative Time; Length of Stay; Pneumonectomy; Propensity Score; Treatment Outcome
PubMed: 38917144
DOI: 10.1371/journal.pone.0300632 -
JAMA Network Open Jun 2024Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.
OBJECTIVE
To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.
DESIGN, SETTING, AND PARTICIPANTS
Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.
INTERVENTION
Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.
MAIN OUTCOMES AND MEASURES
Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.
RESULTS
Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.
CONCLUSIONS AND RELEVANCE
In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02651584.
Topics: Humans; Opioid-Related Disorders; Fentanyl; Male; Female; Administration, Sublingual; Adult; Double-Blind Method; Buprenorphine; Middle Aged; Delayed-Action Preparations; Injections, Subcutaneous; Narcotic Antagonists; Analgesics, Opioid; Opiate Substitution Treatment; Buprenorphine, Naloxone Drug Combination; Treatment Outcome
PubMed: 38916892
DOI: 10.1001/jamanetworkopen.2024.17377 -
Reumatismo Jun 2024There is no study comparing knee and spine osteoarthritis. The purpose of the study is to examine the effects of pain and disability on quality of life (QoL) and the... (Comparative Study)
Comparative Study
OBJECTIVE
There is no study comparing knee and spine osteoarthritis. The purpose of the study is to examine the effects of pain and disability on quality of life (QoL) and the factors affecting QoL in patients with knee osteoarthritis and spondylosis.
METHODS
This cross-sectional study included 114 patients with spondylosis and 126 patients with knee osteoarthritis. Demographic data were recorded. The visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Roland Morris Questionnaire (RMQ), and the Short Form Health Questionnaire (SF-36) were filled out.
RESULTS
Statistically, patients with spondylosis and knee osteoarthritis did not differ significantly in terms of gender, age, body mass index, number of concomitant conditions, marital status, years of schooling, pain scores, or SF-36 characteristics. SF-36 physical function, vitality, and mental health assessments were lower in women than men, while VAS scores were higher. There was no correlation between marital status, educational level, and QoL subscales. WOMAC and RMQ scores were negatively correlated with the SF-36 subscales. RMS scores were not related to mental health.
CONCLUSIONS
Spondylosis and knee osteoarthritis affect all subscales of QoL in the same way. The management of patients with spondylosis and knee osteoarthritis should focus on pain and functionality to improve QoL.
Topics: Humans; Quality of Life; Osteoarthritis, Knee; Male; Female; Cross-Sectional Studies; Middle Aged; Spondylosis; Chronic Pain; Aged; Pain Measurement; Surveys and Questionnaires; Disability Evaluation
PubMed: 38916166
DOI: 10.4081/reumatismo.2024.1660 -
Clinical Case Reports Jul 2024Neuroendocrine tumors, rare and slow-growing, primarily affect the gastrointestinal tract, causing symptoms due to hormone secretion or mass effect. This case image...
KEY CLINICAL MESSAGE
Neuroendocrine tumors, rare and slow-growing, primarily affect the gastrointestinal tract, causing symptoms due to hormone secretion or mass effect. This case image described postprandial abdominal pain as an atypical initial presentation of abdominal neuroendocrine tumor recurrence in a middle-aged male.
ABSTRACT
Neuroendocrine tumors are a group of rare, slow-growing neoplasms, most commonly affecting the gastrointestinal tract. Clinical presentations include symptoms related to the mass or hypersecretion of hormones, such as flushing, diarrhea, or bronchoconstriction. Postprandial abdominal pain is most commonly related to chronic mesenteric ischemia from atherosclerotic changes but is rarely linked to external mass compression, including gastrointestinal tumors. Hereby, the authors highlight an uncommon presentation of NET, which is very challenging to diagnose and demands a high index of suspicion.
PubMed: 38915930
DOI: 10.1002/ccr3.9113 -
Frontiers in Endocrinology 2024The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or...
OBJECTIVE
The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients.
METHODS
We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model.
RESULTS
For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR.
CONCLUSION
Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.
Topics: Humans; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Machine Learning; Male; Female; Middle Aged; Aged; Biomarkers; Metabolomics; Carnitine; Cohort Studies; Diabetic Nephropathies
PubMed: 38915893
DOI: 10.3389/fendo.2024.1279034 -
BioRxiv : the Preprint Server For... Jun 2024Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their...
UNLABELLED
Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their gender identity. During peripubertal growth, connective tissues such as tendon rapidly adapt to applied mechanical loads (e.g., exercise) yet if and how tendon adaptation is influenced by sex and gender affirming hormone therapy during growth remains unknown. The goal of this study was to understand the how pubertal suppression influences the structural and functional properties of the Achilles tendon using an established mouse model of transmasculine gender affirming hormone therapy. C57BL/6N female-born mice were assigned to experimental groups to mimic gender-affirming hormone therapy in human adolescents, and treatment was initiated prior to the onset of puberty (at postnatal day 26, P26). Experimental groups included controls and mice serially treated with gonadotropin release hormone analogue (GnRHa), delayed Testosterone (T), or GnRHa followed by T. We found that puberty suppression using GnRHa, with and without T, improved the overall tendon load capacity in female-born mice. Treatment with T resulted in an increase in the maximum load that tendon can withstand before failure. Additionally, we found that GnRHa, but not T, treatment resulted in a significant increase in cell density at the Achilles enthesis.
NEW & NOTEWORTHY
These findings demonstrate that puberty suppression or testosterone does not negatively influence tendon structural or functional properties in a mouse model of transmasculine gender affirming care. In all treatment groups, the ability of the tendon to withstand load was significantly increased. Puberty suppression with GnRHa significantly increased enthesis cell density, suggesting an extended growth phase. These findings elucidate the effects of gender affirming care on the structural and functional properties of the tendon and enthesis.
PubMed: 38915724
DOI: 10.1101/2024.06.10.598308 -
BioRxiv : the Preprint Server For... Jun 2024We introduce an adaptor-based strategy for regulating fluorescein-binding synthetic Notch (SynNotch) receptors using ligands based on conjugates of fluorescein isomers...
We introduce an adaptor-based strategy for regulating fluorescein-binding synthetic Notch (SynNotch) receptors using ligands based on conjugates of fluorescein isomers and analogs. To develop a versatile system, we evaluated the surface expression and activities of multiple constructs containing distinct extracellular fluorescein-binding domains. Using an optimized receptor, we devised ways to regulate signaling via fluorescein-based chemical transformations, including an approach based on a bio-orthogonal chemical ligation and a spatially controllable strategy via the photo-patterned uncaging of an -nitrobenzyl-caged fluorescein conjugate. We further demonstrate that fluorescein-conjugated extracellular matrix (ECM)-binding peptides can regulate SynNotch activity depending on the folding state of collagen-based ECM networks. Treatment with these conjugates enabled cells to distinguish between folded versus denatured collagen proteins and enact dose-dependent gene expression responses depending on the nature of the signaling adaptors presented. To demonstrate the utility of these tools, we applied them to control the myogenic conversion of fibroblasts into myocytes with spatial and temporal precision and in response to denatured collagen-I, a biomarker of multiple pathological states. Overall, we introduce an optimized fluorescein-binding SynNotch as a versatile tool for regulating transcriptional responses to extracellular ligands based on the widely used and clinically-approved fluorescein dye.
PubMed: 38915575
DOI: 10.1101/2024.06.12.598538 -
BioRxiv : the Preprint Server For... Jun 2024With the increased reliance on multi-omics data for bulk and single cell analyses, the availability of robust approaches to perform unsupervised analysis for clustering,...
MOTIVATION
With the increased reliance on multi-omics data for bulk and single cell analyses, the availability of robust approaches to perform unsupervised analysis for clustering, visualization, and feature selection is imperative. Joint dimensionality reduction methods can be applied to multi-omics datasets to derive a global sample embedding analogous to single-omic techniques such as Principal Components Analysis (PCA). Multiple co-inertia analysis (MCIA) is a method for joint dimensionality reduction that maximizes the covariance between block- and global-level embeddings. Current implementations for MCIA are not optimized for large datasets such such as those arising from single cell studies, and lack capabilities with respect to embedding new data.
RESULTS
We introduce nipalsMCIA , an MCIA implementation that solves the objective function using an extension to Non-linear Iterative Partial Least Squares (NIPALS), and shows significant speed-up over earlier implementations that rely on eigendecompositions for single cell multi-omics data. It also removes the dependence on an eigendecomposition for calculating the variance explained, and allows users to perform out-of-sample embedding for new data. nipalsMCIA provides users with a variety of pre-processing and parameter options, as well as ease of functionality for down-stream analysis of single-omic and global-embedding factors.
AVAILABILITY
nipalsMCIA is available as a BioConductor package at https://bioconductor.org/packages/release/bioc/html/nipalsMCIA.html , and includes detailed documentation and application vignettes. Supplementary Materials are available online.
PubMed: 38915554
DOI: 10.1101/2024.06.07.597819