{"title":"Development of a Predictive Statistical Pharmacological Model for Local Anesthetic Agent Effects with Bayesian Hierarchical Model Parameter Estimation.","authors":"Toshiaki Ara, Hiroyuki Kitamura","doi":"10.3390/medicines10110061","DOIUrl":"10.3390/medicines10110061","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Potential of Chatbots in Critical Care Nephrology.","authors":"Supawadee Suppadungsuk, Charat Thongprayoon, Jing Miao, Pajaree Krisanapan, Fawad Qureshi, Kianoush Kashani, Wisit Cheungpasitporn","doi":"10.3390/medicines10100058","DOIUrl":"10.3390/medicines10100058","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10608511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan Lai, Erik Almazan, Thomas Le, Matthew T Taylor, Jihad Alhariri, Shawn G Kwatra
{"title":"Demographics, Cutaneous Manifestations, and Comorbidities Associated with Progressive Cutaneous Sarcoidosis: A Retrospective Cohort Study.","authors":"Jonathan Lai, Erik Almazan, Thomas Le, Matthew T Taylor, Jihad Alhariri, Shawn G Kwatra","doi":"10.3390/medicines10100057","DOIUrl":"10.3390/medicines10100057","url":null,"abstract":"<p><p><b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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, <i>p</i> = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (<i>p</i> = 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). <b>Conclusions</b>: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10608652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
José C De La Flor, Maribel Monroy-Condori, Jacqueline Apaza-Chavez, Iván Arenas-Moncaleano, Francisco Díaz, Xavier E Guerra-Torres, Jorge L Morales-Montoya, Ana Lerma-Verdejo, Edna Sandoval, Daniel Villa, Coca-Mihaela Vieru
{"title":"Monoclonal Gammopathy of Renal Significance with Deposits of Infrequent Morphology: Two Case Reports of Light and Heavy Chain Deposition Disease with Atypical Presentation and Literature Review.","authors":"José C De La Flor, Maribel Monroy-Condori, Jacqueline Apaza-Chavez, Iván Arenas-Moncaleano, Francisco Díaz, Xavier E Guerra-Torres, Jorge L Morales-Montoya, Ana Lerma-Verdejo, Edna Sandoval, Daniel Villa, Coca-Mihaela Vieru","doi":"10.3390/medicines10100055","DOIUrl":"10.3390/medicines10100055","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Case presentation: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10608252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swagatika Das, Praveen K Roayapalley, Sarvesh C Vashishtha, Umashankar Das, Jonathan R Dimmock
{"title":"Anticonvulsant Properties of 1-Diethylamino-3-phenylprop-2-en-1-one.","authors":"Swagatika Das, Praveen K Roayapalley, Sarvesh C Vashishtha, Umashankar Das, Jonathan R Dimmock","doi":"10.3390/medicines10090054","DOIUrl":"https://doi.org/10.3390/medicines10090054","url":null,"abstract":"<p><p>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 (<b>2</b>) 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 (<b>2</b>) 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 (<b>2</b>) 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 (<b>2</b>) is an important lead molecule in the quest for novel structures to combat epilepsy.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effects of Mindfulness on Glycemic Control in People with Diabetes: An Overview of Systematic Reviews and Meta-Analyses.","authors":"Hidetaka Hamasaki","doi":"10.3390/medicines10090053","DOIUrl":"10.3390/medicines10090053","url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jamir Pitton Rissardo, Ursula Medeiros Araujo de Matos, Ana Letícia Fornari Caprara
{"title":"Gabapentin-Associated Movement Disorders: A Literature Review.","authors":"Jamir Pitton Rissardo, Ursula Medeiros Araujo de Matos, Ana Letícia Fornari Caprara","doi":"10.3390/medicines10090052","DOIUrl":"https://doi.org/10.3390/medicines10090052","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Two reviewers identified and assessed relevant reports in six databases without language restriction between 1990 and 2023.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Myoclonus (GRADE A) and dyskinesia (GRADE C) were the most common movement disorders associated with GBP.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histological Alterations in Hashimoto's Disease: A Case-Series Ultrastructural Study.","authors":"Eleni Avramidou, Antonios Gkantaras, Iasonas Dermitzakis, Konstantinos Sapalidis, Maria Eleni Manthou, Paschalis Theotokis","doi":"10.3390/medicines10090051","DOIUrl":"https://doi.org/10.3390/medicines10090051","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina E Larder, Michèle M Iskandar, Stan Kubow
{"title":"Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis.","authors":"Christina E Larder, Michèle M Iskandar, Stan Kubow","doi":"10.3390/medicines10090050","DOIUrl":"https://doi.org/10.3390/medicines10090050","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common joint disorder, with a social and financial burden that is expected to increase in the coming years. Currently, there are no effective medications to treat it. Due to limited treatment options, patients often resort to supplements, such as collagen hydrolysates (CHs). CHs are products with low molecular weight (MW) peptides, often between 3 and 6 kDa, and are a result of industrialized processed collagen. Collagen extraction is often a by-product of the meat industry, with the main source for collagen-based products being bovine, although it can also be obtained from porcine and piscine sources. CHs have demonstrated positive results in clinical trials related to joint health, such as decreased joint pain, increased mobility, and structural joint improvements. The bioactivity of CHs is primarily attributed to their bioactive peptide (BAP) content. However, there are significant knowledge gaps regarding the digestion, bioavailability, and bioactivity of CH-derived BAPs, and how different CH products compare in that regard. The present review discusses CHs and their BAP content as potential treatments for OA.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"10 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}