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Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.Medicina (Kaunas, Lithuania) Jun 2024: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and...
: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. : After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. : A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older ( = 0.007) and have a higher prevalence of diabetes ( < 0.001) and hypertension ( = 0.030), higher systolic blood pressure ( = 0.011), and higher endocan levels ( < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (β = 0.405, adjusted R change = 0.152; < 0.001). : The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.
Topics: Humans; Vascular Stiffness; Male; Proteoglycans; Female; Middle Aged; Renal Dialysis; Risk Factors; Neoplasm Proteins; Aged; Adult; Pulse Wave Analysis; ROC Curve; Biomarkers; Logistic Models; Cross-Sectional Studies
PubMed: 38929601
DOI: 10.3390/medicina60060984 -
Medicina (Kaunas, Lithuania) Jun 2024The coronavirus disease 2019 (COVID-19) preventive measures affected various aspects of people's lives, while also representing an important risk factor for people's...
The coronavirus disease 2019 (COVID-19) preventive measures affected various aspects of people's lives, while also representing an important risk factor for people's mental health. In the present study, we examined the negative psychological consequences of the preventive measures on people's mental health and the protective factors that strengthened their mental health and well-being during the pandemic. A study, using a combination of qualitative and quantitative methods based on a Delphi protocol, was conducted with a sample of Slovenian professionals who worked with people from different demographic groups (i.e., children and adolescents, emerging adults, the adult working population, the elderly) during the pandemic. We conducted (i) a qualitative study involving semi-structured interviews with 11 professionals and (ii) a quantitative study where 73 professionals completed a structured online questionnaire. Experts recognized the disruption of informal face-to-face social contacts as the measure with the greatest impact on people's lives across all groups studied, the effect being particularly evident in relation to individuals' development period and socio-demographic characteristics. An individual's ability to adapt to change and emotional support provided by family or other close persons contributed significantly to maintaining mental health and well-being during the pandemic. Considering the interplay of various COVID-19-related risk and protective factors for mental health, enabling and promoting the maintenance and development of social relationships (including through alternative pathways) should be a priority aspect of (mental health) intervention for all demographic groups.
Topics: Humans; COVID-19; Delphi Technique; Mental Health; Adult; Male; Female; Adolescent; Aged; Slovenia; Middle Aged; SARS-CoV-2; Pandemics; Surveys and Questionnaires; Young Adult; Child
PubMed: 38929595
DOI: 10.3390/medicina60060978 -
Medicina (Kaunas, Lithuania) May 2024: The role of surgical extraction of the third molar in patients' sleep quality remains unclear, although it is one of the most common oral surgical procedures. The aim... (Observational Study)
Observational Study
: The role of surgical extraction of the third molar in patients' sleep quality remains unclear, although it is one of the most common oral surgical procedures. The aim of this study is to assess the changes in patient-reported sleep health outcomes after third molar surgery and to investigate any associations between sleep parameters and post-extraction pain. : Young adults without known comorbidities who were in need of mandibular third molar surgical extraction were included. All participants completed a sleep diary, the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS) questionnaires, which were used to assess sleep habits, daytime sleepiness, sleep quality and insomnia severity one week before and after extraction. In addition, a visual analog scale was completed postoperatively to assess the perception of pain. : Out of 75 patients who completed the study protocol, 32 (42.7%) were males and 43 (57.3%) were females, with a mean age of 24.01 (±3.43) years. Postoperatively, statistically significant higher scores were observed for PSQI [4.85 (±2.32) before vs. 5.39 (±2.75) after, = 0.041], AIS [5.56 (±3.23) before vs. 6.91 (±4.06) after, < 0.001] and average weekly number of nocturnal awakenings [2.01 (±3.72) before vs. 4.19 (±5.20) after, < 0.001] but not for ESS, average weekly sleep duration and average weekly sleep onset latency. Pain perception was increased in patients who slept worse on almost all seven postoperative days, although this did not reach statistical significance. : Third molar surgery impacts sleep quality and insomnia severity in the first week after extraction, while there is no effect on daytime sleepiness. The worsening of subjective sleep symptoms after extraction may be associated with an increased perception of pain.
Topics: Humans; Female; Male; Molar, Third; Adult; Tooth Extraction; Young Adult; Surveys and Questionnaires; Sleep Quality; Pain, Postoperative; Sleep Initiation and Maintenance Disorders
PubMed: 38929475
DOI: 10.3390/medicina60060858 -
Children (Basel, Switzerland) Jun 2024The evolutionarily conserved Wnt signaling has a significant and diverse role in maintaining cell homeostasis and tissue maintenance. It is necessary in the regulation... (Review)
Review
The evolutionarily conserved Wnt signaling has a significant and diverse role in maintaining cell homeostasis and tissue maintenance. It is necessary in the regulation of crucial biological functions such as embryonal development, proliferation, differentiation, cell fate, and stem cell pluripotency. The deregulation of Wnt/β-catenin signaling often leads to various diseases, including cancer and non-cancer diseases. The role of Wnt/β-catenin signaling in adult tumors has been extensively studied in literature. Although the Wnt signaling pathway has been well explored and recognized to play a role in the initiation and progression of cancer, there is still a lack of understanding on how it affects pediatric tumors. This review discusses the recent developments of this signaling pathway in pediatric tumors. We also focus on understanding how different types of variations in Wnt signaling pathway contribute to cancer development and provide an insight of tissue specific mutations that lead to clinical progression of these tumors.
PubMed: 38929279
DOI: 10.3390/children11060700 -
International Journal of Environmental... May 2024Acute hypoxemic respiratory failure (ARF) is a common cause for hospital admission. High-flow nasal oxygen (HFNO) is increasingly used as a first-line treatment for... (Review)
Review
Acute hypoxemic respiratory failure (ARF) is a common cause for hospital admission. High-flow nasal oxygen (HFNO) is increasingly used as a first-line treatment for patients with ARF, including in medical wards. Clinical guidance is crucial when providing HFNO, and health services use local health guidance documents (LHGDs) to achieve this. It is unknown what hospital LHGDs recommend regarding ward administration of HFNO. This study examined Australian hospitals' LHGDs regarding ward-based HFNO administration to determine content that may affect safe delivery. A scoping review was undertaken on 2 May 2022 and updated on 29 January 2024 to identify public hospitals' LHGDs regarding delivery of HFNO to adults with ARF in medical wards in two Australian states. Data were extracted and analysed regarding HFNO initiation, monitoring, maintenance and weaning, and management of clinical deterioration. Of the twenty-six included LHGDs, five documents referenced Australian Oxygen Guidelines. Twenty LHGDs did not define a threshold level of hypoxaemia where HFNO use was recommended over conventional oxygen therapy. Thirteen did not provide target oxygen saturation ranges whilst utilising HFNO. Recommendations varied regarding maximal levels of inspired oxygen and flow rates in the medical ward. Eight LHGDs did not specify any system to identify and manage deteriorating patients. Five LHGDs did not provide guidance for weaning patients from HFNO. There was substantial variation in the LHGDs regarding HFNO care for adult patients with ARF in Australian hospitals. These findings have implications for the delivery of high-quality, safe clinical care in hospitals.
Topics: Oxygen Inhalation Therapy; Humans; Australia; Respiratory Insufficiency; Hospitals; Oxygen
PubMed: 38928951
DOI: 10.3390/ijerph21060705 -
International Journal of Environmental... May 2024Multidrug- and artemisinin-resistant (ART-R) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region gene...
Multidrug- and artemisinin-resistant (ART-R) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region gene allows tracking mutations in parasite resistance to artemisinin. The increase in illegal miners in the Roraima Yanomami indigenous land (YIL) could favor ART-R parasites. Thus, this study aimed to investigate ART-R in patients from illegal gold mining areas in the YIL of Roraima, Brazil. A questionnaire was conducted, and blood was collected from 48 patients diagnosed with or mixed malaria (). The DNA was extracted and the gene was amplified by PCR. The amplicons were subjected to DNA-Sanger-sequencing and the entire amplified fragment was analyzed. Among the patients, 96% (46) were from illegal mining areas of the YIL. All parasite samples carried the wild-type genotypes/ART-sensitive phenotypes. These data reinforce the continued use of artemisinin-based combination therapies (ACTs) in Roraima, as well as the maintenance of systematic monitoring for early detection of parasite populations resistant to ART, mainly in regions with an intense flow of individuals from mining areas, such as the YIL. This is especially true when the achievement of falciparum malaria elimination in Brazil is planned and expected by 2030.
Topics: Artemisinins; Brazil; Plasmodium falciparum; Humans; Antimalarials; Drug Resistance; Malaria, Falciparum; Male; Mining; Adult; Female; Middle Aged; Young Adult; Adolescent; Genotype
PubMed: 38928926
DOI: 10.3390/ijerph21060679 -
International Journal of Molecular... Jun 2024All- retinoic acid (ATRA), the major active metabolite of all- retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread... (Review)
Review
All- retinoic acid (ATRA), the major active metabolite of all- retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread influence on processes that are crucial to the growth and differentiation of cells and, in turn, the acquisition of mature cell functions. Therefore, there is considerable potential in the use of retinoids to treat diseases. ATRA binds to the retinoic acid receptors (RAR) which, as activated by ATRA, selectively regulate gene expression. There are three main RAR isoforms, RARα, RARβ, and RARγ. They each have a distinct role, for example, RARα and RARγ regulate myeloid progenitor cell differentiation and hematopoietic stem cell maintenance, respectively. Hence, targeting an isoform is crucial to developing retinoid-based therapeutics. In principle, this is exemplified when ATRA is used to treat acute promyelocytic leukemia (PML) and target RARα within PML-RARα oncogenic fusion protein. ATRA with arsenic trioxide has provided a cure for the once highly fatal leukemia. Recent in vitro and in vivo studies of RARγ have revealed the potential use of agonists and antagonists to treat diseases as diverse as cancer, heterotopic ossification, psoriasis, and acne. During the final drug development there may be a need to design newer compounds with added modifications to improve solubility, pharmacokinetics, or potency. At the same time, it is important to retain isotype specificity and activity. Examination of the molecular interactions between RARγ agonists and the ligand binding domain of RARγ has revealed aspects to ligand binding that are crucial to RARγ selectivity and compound activity and key to designing newer compounds.
Topics: Humans; Retinoic Acid Receptor gamma; Receptors, Retinoic Acid; Animals; Tretinoin; Protein Binding; Leukemia, Promyelocytic, Acute; Antineoplastic Agents
PubMed: 38928275
DOI: 10.3390/ijms25126568 -
International Journal of Molecular... Jun 2024Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; = 395)... (Randomized Controlled Trial)
Randomized Controlled Trial
Molecular Long-Term Analysis of the GMMG-HD4 Trial in Multiple Myeloma-Patterns of Association of Chromosomal Aberrations with Response and Proliferation Determining Survival in Selecting Treatments in View of Limited Resources in Low- and Middle-Income Countries.
Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront "novel agents" in cases of limited resources, e.g., in low- or middle-income countries. Serum parameters and risk factors were assessed in 395 patients. CD138-purified plasma cells were subjected to fluorescence in situ hybridization ( = 354) and gene expression profiling ( = 204). We found chromosomal aberrations to be associated in four patterns with survival, proliferation, and response: deletion (del) del17p13, del8p21, del13q14, (gain) 1q21+, and translocation t(4;14) (all adverse) associate with higher proliferation. Of these, del17p is associated with an response (pattern 1), and 1q21+, t(4;14), and del13q14 with a treatment-dependent response (pattern 2). Hyperdiploidy associates with lower proliferation without impacting response or survival (pattern 3). Translocation t(11;14) has no association with survival but a treatment-dependent adverse response (pattern 4). Significantly fewer patients reach a near-complete response or better with "conventional" (VAD) vs. bortezomib-based treatment after induction or high-dose melphalan. These patients, however, show significantly median progression-free and overall survival. Molecularly, patients responding to the two regimens differ in gene expression, indicating distinct biological properties of the responding myeloma cells. Patients with normal renal function (89.4%), low cytogenetic risk (72.5%), or low proliferation rate (37.9%) neither benefit in progression-free nor overall survival from bortezomib-based upfront treatment. We conclude that response level, the treatment by which it is achieved, and molecular background determine long-term prognosis. Chromosomal aberrations are associated in four patterns with proliferation and treatment-dependent responses. Associations with faster and deeper responses can be deceptive in the case of prognostically adverse aberrations 1q21+ and t(4;14). Far from advocating a return to "outdated" treatments, if resources do not permit state-of-the-art-treatment, normal renal function and/or molecular profiling identifies patient subpopulations doing well without upfront "novel agents".
Topics: Humans; Multiple Myeloma; Chromosome Aberrations; Female; Male; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Prognosis; Adult; Developing Countries; Dexamethasone; Bortezomib; Thalidomide
PubMed: 38928138
DOI: 10.3390/ijms25126431 -
International Journal of Molecular... Jun 2024The prevalence of diabetes is increasing worldwide. Massive death of pancreatic beta-cells causes type 1 diabetes. Progressive loss of beta-cell function and mass... (Review)
Review
The prevalence of diabetes is increasing worldwide. Massive death of pancreatic beta-cells causes type 1 diabetes. Progressive loss of beta-cell function and mass characterizes type 2 diabetes. To date, none of the available antidiabetic drugs promotes the maintenance of a functional mass of endogenous beta-cells, revealing an unmet medical need. Dysfunction and apoptotic death of beta-cells occur, in particular, through the activation of intracellular protein kinases. In recent years, protein kinases have become highly studied targets of the pharmaceutical industry for drug development. A number of drugs that inhibit protein kinases have been approved for the treatment of cancers. The question of whether safe drugs that inhibit protein kinase activity can be developed and used to protect the function and survival of beta-cells in diabetes is still unresolved. This review presents arguments suggesting that several protein kinases in beta-cells may represent targets of interest for the development of drugs to treat diabetes.
Topics: Humans; Insulin-Secreting Cells; Animals; Protein Kinases; Protein Kinase Inhibitors; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Cell Survival; Diabetes Mellitus; Diabetes Mellitus, Type 1
PubMed: 38928130
DOI: 10.3390/ijms25126425 -
Genes Jun 2024Patients with advanced-stage epithelial ovarian cancer (EOC) receive treatment with a poly-ADP ribose-polymerase (PARP) inhibitor (PARPi) as maintenance therapy after...
BACKGROUND
Patients with advanced-stage epithelial ovarian cancer (EOC) receive treatment with a poly-ADP ribose-polymerase (PARP) inhibitor (PARPi) as maintenance therapy after surgery and chemotherapy. Unfortunately, many patients experience disease progression because of acquired therapy resistance. This study aims to characterize epigenetic and genomic changes in cell-free DNA (cfDNA) associated with PARPi resistance.
MATERIALS AND METHODS
Blood was taken from 31 EOC patients receiving PARPi therapy before treatment and at disease progression during/after treatment. Resistance was defined as disease progression within 6 months after starting PARPi and was seen in fifteen patients, while sixteen patients responded for 6 to 42 months. Blood cfDNA was evaluated via Modified Fast Aneuploidy Screening Test-Sequencing System (mFast-SeqS to detect aneuploidy, via Methylated DNA Sequencing (MeD-seq) to find differentially methylated regions (DMRs), and via shallow whole-genome and -exome sequencing (shWGS, exome-seq) to define tumor fractions and mutational signatures.
RESULTS
Aneuploid cfDNA was undetectable pre-treatment but observed in six patients post-treatment, in five resistant and one responding patient. Post-treatment ichorCNA analyses demonstrated in shWGS and exome-seq higher median tumor fractions in resistant (7% and 9%) than in sensitive patients (7% and 5%). SigMiner analyses detected predominantly mutational signatures linked to mismatch repair and chemotherapy. DeSeq2 analyses of MeD-seq data revealed three methylation signatures and more tumor-specific DMRs in resistant than in responding patients in both pre- and post-treatment samples (274 vs. 30 DMRs, 190 vs. 57 DMRs, Χ-test < 0.001).
CONCLUSION
Our genome-wide Next-Generation Sequencing (NGS) analyses in PARPi-resistant patients identified epigenetic differences in blood before treatment, whereas genomic alterations were more frequently observed after progression. The epigenetic differences at baseline are especially interesting for further exploration as putative predictive biomarkers for PARPi resistance.
Topics: Humans; Female; Drug Resistance, Neoplasm; Middle Aged; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Epigenesis, Genetic; Aged; DNA Methylation; Carcinoma, Ovarian Epithelial; Adult; Aneuploidy; Genomics
PubMed: 38927686
DOI: 10.3390/genes15060750