Search Results (687)

Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC₅₀ for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins. Full article

Background: Hypoxia is a well-recognized characteristic of the tumor microenvironment of solid cancers. This study aimed to analyze hypoxia-related genes shared by groups based on tumor location. Methods: A total of 9 hypoxia-related pathways from the Kyoto Encyclopedia of Genes and Genomes database or the Reactome database were selected, and 850 hypoxia-related genes were analyzed. Based on their anatomical locations, 14 tumor types were categorized into 6 groups. The group-specific genetic risk score was classified as high- or low-risk based on mRNA expression, and survival outcomes were evaluated. Results: The risk scores in the Female Reproductive group and the Lung group were internally and externally validated. In the Female Reproductive group, CDKN2A, FN1, and ITGA5 were identified as hub genes associated with poor prognosis, while IL2RB and LEF1 were associated with favorable prognosis. In the Lung group, ITGB1 and LDHA were associated with poor prognosis, and GLS2 was associated with favorable prognosis. Functional enrichment analysis showed that the Female Reproductive group was enriched in relation to cilia and skin, while the Lung group was enriched in relation to cytokines and defense. Conclusions: This analysis may lead to better understanding of the mechanisms of cancer progression and facilitate establishing new biomarkers for prognosis prediction. Full article

Heart failure (HF) presents an increasingly significant problem as the population ages. The cause of HF plays a significant role in determining treatment options and outcomes. It is worth noting that several studies have identified gender disparities in both morbidity and mortality, which may suggest differing causes of HF. The purpose of this research is to investigate the influence of various factors, including demographics and comorbidities, on ejection fraction (EF). The objectives of this study involve implementing preventive measures, ensuring timely diagnosis, and implementing interventions that target risk factors and specific comorbidities. These efforts aim to improve the prognosis for individuals affected by heart failure. The main method consists of linear regression. The demographic factors under scrutiny are gender and education, while the comorbidities of interest encompass valvulopathy, ischemia, smoking, obesity, high cholesterol, and diabetes. The main results consist of the fact that high education is associated with a 12.8% better EF on average, while among the factors with a negative role analyzed, ischemia is the most harmful, being 12.8% lower on average. Factors with a smaller impact are smoking, obesity, and high cholesterol. Diabetes does not seem to affect EF. Full article

Background: Malnutrition in cardiovascular disease is associated with poor prognosis, especially in patients with heart failure and acute coronary syndrome (ACS). High bleeding risk is also linked to coronary artery disease prognosis, including ACS. However, whether the extent of malnutrition and high bleeding risk have a cumulative impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention remains unclear. Methods: We analyzed 275 patients with ACS treated with percutaneous coronary intervention. The Controlling Nutritional Status score and Japanese version of the Academic Research Consortium for High Bleeding Risk criteria (J-HBR) were retrospectively evaluated. The primary and secondary outcomes were adjusted using the inverse probability treatment weighting method. Results: The prevalence of moderate or severe malnutrition in this cohort was 16%. Kaplan–Meier analysis showed a significantly higher incidence of major adverse cardiovascular and cerebrovascular events in patients who were moderately or severely malnourished than in those who were not. Notably, the incidence of these major events was similar between severely malnourished patients with J-HBR and those without. Conclusion: Moderate or severe malnutrition has a significant impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention. Full article

As an alternative to animal use, computer simulations are useful for predicting pharmacokinetics and cardiovascular activities. For this purpose, we constructed a statistical model to simulate the effects of local anesthetic agents. To train the model, animal experiments were performed on 6-week-old male Hartley guinea pigs. Firstly, the guinea pigs’ backs were shaved, then local anesthetic agents were subcutaneously injected, with subsequent stimulation of the anesthetized site with a needle six times at regular intervals. The number of reactions (score value) was counted. In this statistical model, the probability of reacting to needle stimulation was calculated using the elapsed time, type of local anesthetic agent, and presence or absence of adrenaline. Score values were assumed to follow a binomial distribution at the calculated probability. Parameters were estimated using the Bayesian hierarchical model and Hamiltonian Monte Carlo method. The predicted curves using the estimated parameters fitted well the observed animal values. When score values were predicted using randomly generated parameters, the median of duration was similar between animal experiments and simulations (Procaine: 55 min vs. 50 min, Lidocaine: both 60 min, and Mepivacaine: both 85 min). This approach effectively modeled the effects of local anesthetic agents. It is possible to create the simulator using the parameter values estimated in this study. Full article

Background: There is a high prevalence of sleep disorders in Japan, and they are a factor in a decreased quality of life. The main objective of this study was to clarify the background factors of sleep disorders that affect sleep duration, such as subjective symptoms and working hours. Methods: We performed a cross-sectional study on the Japanese national statistics data. Answers from a household questionnaire were used to analyze risk factors for decreases in sleep duration. The subjects were a total of 3972 men and women aged 40–59 years, the age group that forms the core of the working population. For the analysis, a univariate analysis (contingency table) between sleep duration (two groups: sleep duration ≥ 6 h and <6 h) and 42 subjective symptoms was carried out. A multivariate analysis (binomial logistic regression) was conducted using sleep duration and subjective health assessment as objective variables, and odds ratios (ORs) adjusted for sex, working hours, and other factors were obtained. Results: The univariate analysis by subjective symptom showed significant ORs for eight symptoms, including poor sleep quality (OR: 2.24), constipation (OR: 2.24), and dizziness (OR: 1.77). In the multivariate analysis, the model with sleep duration as the objective variable showed significantly adjusted ORs for four variables, including constipation (1.72) and poor sleep quality (1.66). The model with subjective health assessment as the objective variable showed significantly adjusted ORs for eight variables, including dizziness (4.18), while poor sleep quality (1.45) was not significant. Conclusions: The present results suggest the presence of subjective symptoms that may be inferred to be related to decreases in sleep duration. Full article

Background: Early detection of elderly patients with COVID-19 who are at high risk of mortality is vital for appropriate clinical decisions. We aimed to evaluate the risk factors associated with all-cause in-hospital mortality among elderly patients with COVID-19. Methods: In this retrospective study, the medical records of elderly patients aged over 60 who were hospitalized with COVID-19 at Thammasat University Hospital from 1 July to 30 September 2021 were reviewed. Multivariate logistic regression was used to identify independent predictors of mortality. The sum of weighted integers was used as a total risk score for each patient. Results: In total, 138 medical records of patients were reviewed. Four identified variables based on the odds ratio (age, respiratory rate, glomerular filtration rate and history of stroke) were assigned a weighted integer and were developed to predict mortality risk in hospitalized elderly patients. The AUROC of the scoring system were 0.9415 (95% confidence interval, 0.9033–0.9716). The optimized scoring system was developed and a risk score over 213 was considered a cut-off point for high mortality risk. Conclusions: A simple predictive risk score provides an initial assessment of mortality risk at the time of admission with a high degree of accuracy among hospitalized elderly patients with COVID-19. Full article

The exponential growth of artificial intelligence (AI) has allowed for its integration into multiple sectors, including, notably, healthcare. Chatbots have emerged as a pivotal resource for improving patient outcomes and assisting healthcare practitioners through various AI-based technologies. In critical care, kidney-related conditions play a significant role in determining patient outcomes. This article examines the potential for integrating chatbots into the workflows of critical care nephrology to optimize patient care. We detail their specific applications in critical care nephrology, such as managing acute kidney injury, alert systems, and continuous renal replacement therapy (CRRT); facilitating discussions around palliative care; and bolstering collaboration within a multidisciplinary team. Chatbots have the potential to augment real-time data availability, evaluate renal health, identify potential risk factors, build predictive models, and monitor patient progress. Moreover, they provide a platform for enhancing communication and education for both patients and healthcare providers, paving the way for enriched knowledge and honed professional skills. However, it is vital to recognize the inherent challenges and limitations when using chatbots in this domain. Here, we provide an in-depth exploration of the concerns tied to chatbots’ accuracy, dependability, data protection and security, transparency, potential algorithmic biases, and ethical implications in critical care nephrology. While human discernment and intervention are indispensable, especially in complex medical scenarios or intricate situations, the sustained advancements in AI signal that the integration of precision-engineered chatbot algorithms within critical care nephrology has considerable potential to elevate patient care and pivotal outcome metrics in the future. Full article

Background: Sarcoidosis is a multisystem granulomatous disease with a wide variety of presentations and clinical courses. Cutaneous manifestations and comorbidities associated with sarcoid prognosis remain understudied. Methods: An EPIC query was run for patients age 18+ at the Johns Hopkins Hospital with a diagnosis of sarcoidosis of the skin according to the ICD-10-CM code D86.3. Data were obtained from a population-based sample of 240 patients from 2015 to 2020. Results: A total of 240 patients were included in the cohort study. The mean (SD) age was 43.76 (11.72) years, and 30% of participants were male; 76.25% of patients identified as black, 19.58% as white, and 4.17% as other. The average age of onset in remissive patients was significantly higher than progressive (47 ± 12 vs. 40 ± 10, p = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (p = 0.028). Progressive disease was associated with the presence of lupus pernio (aOR = 3.29, 95% CI, 1.60–6.77) and at least one autoimmune comorbidity (aOR 6.831, 95% CI 1.819–11.843). Conclusions: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis. Full article

Background: Cognitive impairment is poorly addressed in G8 screening. The aim of the present study was to evaluate the additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores. Methods: Seventy-four consecutive urogeriatric patients aged 75 and above were evaluated. All patients underwent G8 and Mini-Cog© screening. Patients with a G8 score above 14 were considered geriatric “healthy or fit”. A Mini-Cog© from four to five points was considered inconspicuous in screening for cognitive impairment. The additional information of a Mini-Cog© screening during G8 screening was evaluated by looking at G8 “fit and healthy” patients who had conspicuous Mini-Cog© tests and vice versa. Additionally, the results of the neuropsychological subitem “E” of the G8 score were compared with the results of the Mini-Cog© screening. Results: The mean age of the patients was 83 y (min. 75–max. 102). Sixty-one of the patients were males, and 13 were females. Twenty-nine of the patients had a normal G8 score and were considered “healthy or fit”, and 45 were not. Forty-three of the patients had an inconspicuous Mini-Cog©, and 31 had a conspicuous Mini-Cog© of less than four points. The majority of G8 “healthy or fit” patients (n = 24/29) had an inconspicuous Mini-Cog© test. However, of them, five patients had a Mini-Cog© of less than four points, which is suspicious for cognitive disorders. Furthermore, of the 43 patients with a normal G8 subscore in item “E” of two points, 6 patients had a conspicuous Mini-Cog© of less than four points. Conclusions: As shown by the present study, the Mini-Cog© might extend the G8 screening with regard to the detection of cognitive functional impairments that are not detected by the G8 screening alone. It can be easily added to G8 screening. Full article

Background: Monoclonal immunoglobulin deposition disease (MIDD) includes three entities: light chain deposition disease (LCDD), heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LHCDD). The renal presentation can manifest with varying degrees of proteinuria and/or nephrotic syndrome, microhematuria, and often leads to end-stage renal disease. Given the rarity of LHCDD, therapeutic approaches for this condition remain inconclusive, as clinical trials are limited. Case presentation: We report two male patients with underlying monoclonal gammopathy of renal significance (MGRS) associated with LHCDD lesions. Both cases had non-nephrotic proteinuria, moderately impaired renal function, and normal levels of C3 and C4. Light microscopy of the renal biopsies in both patients did not show lesions of nodular glomerulosclerosis. Immunofluorescence showed a staining pattern with interrupted linear IgA-κ in patient #1 and IgA-λ in patient #2 only along the glomerular basement membrane (GBM). Electron microscopy of patient #1 revealed electrodense deposits in the subendothelial and mesangial areas only along the GBM. Discussion: In this case series, we discuss the clinical, analytical, and histopathological findings of two rare cases of LHCDD. Both patients exhibited IgA monoclonality and were diagnosed with monoclonal gammopathy of undetermined significance (MGUS) by the hematology department at the time of renal biopsy. Treatment with steroids and cytotoxic agents targeting the clone cells responsible for the deposition disease resulted in a favorable renal and hematologic response. Full article

There is a need for novel antiepileptic agents whose modes of action differ from those of current antiepileptic drugs. The objective of this study was to determine whether 1-diethylamino-3-phenylprop-2-en-1-one (2) could prevent or at least diminish convulsions caused by different mechanisms. This amide afforded protection in the maximal electroshock and subcutaneous pentylenetetrazole screens when given intraperitoneally to both mice and rats. A number of specialized tests in mice were conducted and are explained in the text. They revealed (2) to have efficacy in the 6 Hz psychomotor seizure test, the corneal kindling model, the mouse temporal epilepsy screen and a peripheral neuronal transmission test using formalin. Three screens in rats were undertaken, which revealed that (2) blocked chloride channels, inhibited peripheral neuronal transmission (tested using sciatic ligation and von Frey fibres) and afforded protection in the lamotrigine-resistant kindled rat model. The biodata generated reveal that (2) is an important lead molecule in the quest for novel structures to combat epilepsy. Full article

Background: Previous research has demonstrated the effectiveness of mindfulness interventions in improving glycemic control. By enhancing attention control, emotion regulation, and self-awareness, mindfulness shows promise in managing the lifestyle factors associated with cardiovascular disease risk. However, the impact of mindfulness on glycemic control in people with diabetes remains unclear. This overview aims to summarize the current evidence of the impact of mindfulness interventions on glycemic control in people with diabetes and propose suggestions for future research. Methods: The author searched electronic databases (PubMed/MEDLINE, Embase, and Cochrane Library) to identify relevant systematic reviews and meta-analyses. The current evidence regarding the effects of mindfulness on glycemic control in people with diabetes was summarized. Results: This review evaluated a total of five systematic reviews and meta-analyses of randomized controlled trials (RCTs). Mindfulness interventions show potential for improving glycemic control as measured by hemoglobin A1c (HbA1c) levels, as well as reducing stress, depression, and anxiety in people with diabetes. Four out of five systematic reviews and meta-analyses reported a significant reduction in HbA1c levels by approximately 0.3%. However, the available studies lacked adequate description of key characteristics of study subjects, such as body mass index, medication, and disease conditions, which are essential for assessing the impact of mindfulness on glycemic control. Moreover, there was significant heterogeneity in the intervention methods employed across the included RCTs. Conclusions: Mindfulness interventions are effective in improving glycemic control in people with type 2 diabetes. However, the overall quality of the reviewed studies raises uncertainty regarding the effectiveness of mindfulness as a treatment for people with diabetes. Further research is necessary to elucidate the biological effects of mindfulness on physiological, neurological, and endocrinological functions in humans. Full article

Background: Gabapentin (GBP)-induced movement disorders (MDs) are under-recognized adverse drug reactions. They are commonly not discussed with patients, and their sudden occurrence can lead to misdiagnosis. This literature review aims to evaluate the clinical–epidemiological profile, pathological mechanisms, and management of GBP-associated MD. Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between 1990 and 2023. Results: A total of 99 reports of 204 individuals who developed a MD associated with GBP were identified. The MDs encountered were 135 myoclonus, 22 dyskinesias, 7 dystonia, 3 akathisia, 3 stutterings, 1 myokymia, and 1 parkinsonism. The mean and median ages were 54.54 (SD: 17.79) and 57 years (age range: 10–89), respectively. Subjects were predominantly male (53.57%). The mean and median doses of GBP when the MD occurred were 1324.66 (SD: 1117.66) and 1033 mg/daily (GBP dose range: 100–9600), respectively. The mean time from GBP-onset to GBP-associated MD was 4.58 weeks (SD: 8.08). The mean recovery time after MD treatment was 4.17 days (SD: 4.87). The MD management involved GBP discontinuation. A total of 82.5% of the individuals had a full recovery in the follow-up period. Conclusions: Myoclonus (GRADE A) and dyskinesia (GRADE C) were the most common movement disorders associated with GBP. Full article

Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease exhibiting stromal fibrosis and follicular cell destruction due to lymphoplasmacytic infiltration. Besides deprecated analyses, histopathological approaches have not employed the use of electron microscopy adequately toward delineating subcellular-level interactions. Methods: Biopsies for ultrastructural investigations were obtained from the thyroids of five patients with HT after a thyroidectomy. Transmission electron microscopy (TEM) was utilized to study representative tissue specimens. Results: Examination indicated interstitial extravasated blood cells and a plethora of plasma cells, based on their subcellular identity landmarks. These antibody-secreting cells were profoundly spotted near follicular cells, fibroblasts, and cell debris entrenched in collagenous areas. Pathological changes persistently affected subcellular components of the thyrocytes, including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and other intracellular vesicles. Interestingly, significant endothelial destruction was observed, specifically in the larger blood vessels, while the smaller vessels appeared comparatively unaffected. Conclusions: Our TEM findings highlight the immune-related alterations occurring within the thyroid stroma. The impaired vasculature component and remodeling have not been described ultrastructurally before; thus, further exploration is needed with regards to angiogenesis in HT in order to achieve successful prognostic, diagnostic, and treatment-monitoring strategies. Full article