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Vasovagal Reactions during Interventional Pain Management Procedures—A Review of Pathophysiology, Incidence, Risk Factors, Prevention, and Management -
Polyamine Depletion Strategies in Cancer: Remodeling the Tumor Immune Microenvironment to Enhance Anti-Tumor Responses -
Polyamine and Ethanolamine Metabolism in Bacteria as an Important Component of Nitrogen Assimilation for Survival and Pathogenicity -
The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study -
Predictors of Invasiveness in Adenocarcinoma of Lung with Lepidic Growth Pattern
Journal Description
Medical Sciences
Medical Sciences
is an international, peer-reviewed, open access journal, providing a platform for advances in basic, translational and clinical research, published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within PubMed, PMC, MEDLINE, CAPlus / SciFinder, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 26.5 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in this journal in the first half of 2022).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 11 topical sections.
Latest Articles
Resuming Swallowing and Oral Feeding in Tracheostomized COVID-19 Patients: Experience of a Swiss COVID-Center and Narrative Literature Review
Med. Sci. 2022, 10(4), 57; https://doi.org/10.3390/medsci10040057 - 29 Sep 2022
Abstract
During the COVID-19 pandemic, percutaneous tracheostomy proved to be an effective option in the management of patients with prolonged periods of intubation. In fact, among other things, it allowed early discharge from ICUs and contributed to reducing overcrowding in intensive care settings, a
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During the COVID-19 pandemic, percutaneous tracheostomy proved to be an effective option in the management of patients with prolonged periods of intubation. In fact, among other things, it allowed early discharge from ICUs and contributed to reducing overcrowding in intensive care settings, a central and critical point in the COVID pandemic. As a direct consequence, the management and the weaning of frail, tracheostomized and ventilated patients was diverted to sub-intensive or normal hospitalization wards. One central challenge in this setting is the resumption of swallowing and oral feeding, which require interdisciplinary management involving a phoniatrician, ENT, pneumologist, and speech therapist. With this article, we aim to share the experience of a Swiss COVID-19 Center and to draw up a narrative review on the issues concerning the management of the tracheostomy cannula during swallowing resumption, integrating the most recent evidence from the literature with the clinical experiences of the professionals directly involved in the management of tracheostomized COVID-19 patients. In view of the heterogeneity of COVID-19 patients, we believe that the procedures described in the article are applicable to a larger population of patients undergoing tracheostomy weaning.
Full article
(This article belongs to the Special Issue Lung Lesion: Causes, Diagnosis, and Treatments)
Open AccessArticle
A Pilot Study of Electrocardiographic Features in Patients with Obesity from a Tertiary Care Centre in Southern India (Electron)
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, , , , and
Med. Sci. 2022, 10(4), 56; https://doi.org/10.3390/medsci10040056 - 28 Sep 2022
Abstract
Background: Obesity is associated with increased all-cause mortality and cardiovascular disease (CVD). An electrocardiogram (ECG) may be used to screen for subtle signs of CVD or altered cardiac morphology in the obese. Methodology: This observational cross-sectional analysed ECG changes in patients with obesity
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Background: Obesity is associated with increased all-cause mortality and cardiovascular disease (CVD). An electrocardiogram (ECG) may be used to screen for subtle signs of CVD or altered cardiac morphology in the obese. Methodology: This observational cross-sectional analysed ECG changes in patients with obesity at a tertiary care centre in southern India. Results: One hundred and fifty adult patients with a mean (SD) BMI of 39.9 (6.7) kg/m2 were recruited in the study after excluding those with comorbidities (diabetes mellitus, systemic hypertension) or on chronic medications (ACE inhibitors). The cohort showed a female predominance (69.3%), with a mean (SD) age of 45.4 (11.2) years. Most patients exhibited a sinus rhythm (78%), with one patient showing features of first-degree conduction block. Sinus tachycardia was seen in 32 (21.3%) patients. We observed left and right ventricular hypertrophy in five (3.3%) and three (2%) patients, respectively. Observed ECG patterns included a prolonged QTc in 16 (10.7%) patients, inverted T-waves (mostly in the inferior leads) in 39 (26%) patients and ST-segment depression (predominantly in the lateral leads) in 14 (9.3%) patients. A greater prevalence was noted for morbid obesity. No deaths were reported in our cohort. Conclusions: The predominant ECG variations in this cohort included tachycardia, atrial enlargement, ventricular hypertrophy, conduction defects, LAD, features of ischemia or old infarction and repolarization abnormalities, with a greater prevalence in morbid obesity. Further studies are needed to assess the impact of weight reducing measures on reversibility of these changes and determine the association with outcomes in obese patients.
Full article
(This article belongs to the Section Endocrinology and Metabolic Diseases)
Open AccessArticle
Training-Induced Muscle Fatigue with a Powered Lower-Limb Exoskeleton: A Preliminary Study on Healthy Subjects
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, , , , , and
Med. Sci. 2022, 10(4), 55; https://doi.org/10.3390/medsci10040055 - 26 Sep 2022
Abstract
Powered lower-limb exoskeletons represent a promising technology for helping the upright stance and gait of people with lower-body paralysis or severe paresis from spinal cord injury. The powered lower-limb exoskeleton assistance can reduce the development of lower-limb muscular fatigue as a risk factor
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Powered lower-limb exoskeletons represent a promising technology for helping the upright stance and gait of people with lower-body paralysis or severe paresis from spinal cord injury. The powered lower-limb exoskeleton assistance can reduce the development of lower-limb muscular fatigue as a risk factor for spasticity. Therefore, measuring powered lower-limb exoskeleton training-induced fatigue is relevant to guiding and improving such technology’s development. In this preliminary study, thirty healthy subjects (age 23.2 ± 2.7 years) performed three motor tasks: (i) walking overground (WO), (ii) treadmill walking (WT), (iii) standing and sitting (STS) in three separate exoskeleton-based training sessions of 60 min each. The changes in the production of lower-limb maximal voluntary isometric contraction (MVIC) were assessed for knee and ankle dorsiflexion and extension before and after the three exoskeleton-based trained motor tasks. The MVIC forces decreased significantly after the three trained motor tasks except for the ankle dorsiflexion. However, no significant interaction was found between time (before-, and after-training) and the training sessions except for the knee flexion, where significant fatigue was induced by WO and WT trained motor tasks. The results of this study pose the basis to generate data useful for a better approach to the exoskeleton-based training. The STS task leads to a lower level of muscular fatigue, especially for the knee flexor muscles.
Full article
(This article belongs to the Special Issue Advances in Neurorehabilitation: Robotics, Virtual Reality and Beyond)
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Open AccessBrief Report
Easy Intra-Operative Localization of Pulmonary Nodules during Uniportal Video-Assisted Thoracoscopy: Experience with Hydrogel Plugs at Our Institution
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, , , , and
Med. Sci. 2022, 10(4), 54; https://doi.org/10.3390/medsci10040054 - 23 Sep 2022
Abstract
Background: The diffusion of lung cancer screening programs has increased the detection of both solid and ground-glass opacity (GGO) sub-centimetric lesions, leading to the necessity for histological diagnoses. A percutaneous CT-guided biopsy may be challenging, thus making surgical excision a valid diagnostic alternative.
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Background: The diffusion of lung cancer screening programs has increased the detection of both solid and ground-glass opacity (GGO) sub-centimetric lesions, leading to the necessity for histological diagnoses. A percutaneous CT-guided biopsy may be challenging, thus making surgical excision a valid diagnostic alternative. CT-guided hydrogel plug deployment (BioSentry®) was recently proposed to simplify intraoperative nodule localization. Here, we report our initial experience. Methods: We evaluated 62 patients with single, small, peripheral, non-subpleural pulmonary GGO that was suspicious for cancer. All lesions were preoperatively marked, using CT-guidance, with a hydrogel plug (BioSentry®). Then, a uniportal video-assisted thoracoscopy (uniVATS) wedge resection was performed. If cancer was confirmed at the frozen section, a major lung resection was then performed. The study’s end points were the rates of intraoperative localization and of successful resection. Results: The hydrogel plug was correctly placed in 54 of the 62 cases, leading to an effective resection of the target lesion. In the remaining eight cases, the plug was displaced, and so the identification of pleural erosions due to the previous percutaneous procedure guided the resection. The uniVATS resection success rate was 98.3%. Conclusions: CT-guided hydrogel plug placement allowed for the successful detection of lung GGOs and resection with the uniVATS approach. This device allowed us to obtain lung cancer diagnoses and successfully treat 85.4% of cases.
Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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Open AccessReview
Time to Load Up–Resistance Training Can Improve the Health of Women with Polycystic Ovary Syndrome (PCOS): A Scoping Review
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, , , , , , , and
Med. Sci. 2022, 10(4), 53; https://doi.org/10.3390/medsci10040053 - 22 Sep 2022
Abstract
Background: Guidelines for the management of polycystic ovary syndrome (PCOS) focus on lifestyle changes, incorporating exercise. Whilst evidence suggests that aerobic exercise may be beneficial, less is known about the effectiveness of resistance training (RT), which may be more feasible for those that
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Background: Guidelines for the management of polycystic ovary syndrome (PCOS) focus on lifestyle changes, incorporating exercise. Whilst evidence suggests that aerobic exercise may be beneficial, less is known about the effectiveness of resistance training (RT), which may be more feasible for those that have low fitness levels and/or are unable to tolerate/participate in aerobic exercise. Objectives: To identify the available evidence on RT in women with PCOS and to summarise findings in the context of a scoping review. Eligibility criteria: Studies utilising pre-post designs to assess the effectiveness of RT in PCOS; all outcomes were included. Sources of evidence: Four databases (PubMed, CENTRAL, CINAHL and SportDiscus) were searched and supplemented by hand searching of relevant papers/reference lists. Charting methods: Extracted data were presented in tables and qualitatively synthesised. Results: Searches returned 42 papers; of those, 12 papers were included, relating to six studies/trials. Statistical changes were reported for multiple pertinent outcomes relating to metabolic (i.e., glycaemia and fat-free mass) and hormonal (i.e., testosterone and sex hormone-binding globulin) profiles. Conclusions: There is a striking lack of studies in this field and, despite the reported statistical significance for many outcomes, the documented magnitude of changes are small and the quality of the evidence questionable. This highlights an unmet need for rigorously designed/reported and sufficiently powered trials.
Full article
(This article belongs to the Section Endocrinology and Metabolic Diseases)
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Open AccessReview
Novel Vaccine Strategies and Factors to Consider in Addressing Health Disparities of HPV Infection and Cervical Cancer Development among Native American Women
Med. Sci. 2022, 10(3), 52; https://doi.org/10.3390/medsci10030052 - 13 Sep 2022
Abstract
Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer
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Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer is high and often understudied among Native American communities. While effective HPV vaccines exist, less than 60% of 13- to 17-year-olds in the general population are up to date on their HPV vaccination as of 2020. Vaccination rates are higher among Native American adolescents, approximately 85% for females and 60% for males in the same age group. Unfortunately, the burden of cervical cancer remains high in many Native American populations. In this paper, we will discuss HPV infection, vaccination and the cervicovaginal microbiome with a Native American perspective. We will also provide insight into new strategies for developing novel methods and therapeutics to prevent HPV infections and limit HPV persistence and progression to cervical cancer in all populations.
Full article
(This article belongs to the Special Issue Gynecologic Oncology – Old Controversies and New Strategies)
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Open AccessCommunication
Understanding the Polyamine and mTOR Pathway Interaction in Breast Cancer Cell Growth
Med. Sci. 2022, 10(3), 51; https://doi.org/10.3390/medsci10030051 - 10 Sep 2022
Abstract
The polyamines putrescine, spermidine and spermine are nutrient-like polycationic molecules involved in metabolic processes and signaling pathways linked to cell growth and cancer. One important pathway is the PI3K/Akt pathway where studies have shown that polyamines mediate downstream growth effects. Downstream of PI3K/Akt
[...] Read more.
The polyamines putrescine, spermidine and spermine are nutrient-like polycationic molecules involved in metabolic processes and signaling pathways linked to cell growth and cancer. One important pathway is the PI3K/Akt pathway where studies have shown that polyamines mediate downstream growth effects. Downstream of PI3K/Akt is the mTOR signaling pathway, a nutrient-sensing pathway that regulate translation initiation through 4EBP1 and p70S6K phosphorylation and, along with the PI3K/Akt, is frequently dysregulated in breast cancer. In this study, we investigated the effect of intracellular polyamine modulation on mTORC1 downstream protein and general translation state in two breast cancer cell lines, MCF-7 and MDA-MB-231. The effect of mTORC1 pathway inhibition on the growth and intracellular polyamines was also measured. Results showed that polyamine modulation alters 4EBP1 and p70S6K phosphorylation and translation initiation in the breast cancer cells. mTOR siRNA gene knockdown also inhibited cell growth and decreased putrescine and spermidine content. Co-treatment of inhibitors of polyamine biosynthesis and mTORC1 pathway induced greater cytotoxicity and translation inhibition in the breast cancer cells. Taken together, these data suggest that polyamines promote cell growth in part through interaction with mTOR pathway. Similarly intracellular polyamine content appears to be linked to mTOR pathway regulation. Finally, dual inhibition of polyamine and mTOR pathways may provide therapeutic benefits in some breast cancers.
Full article
(This article belongs to the Special Issue Polyamines: Essential Molecules Regulating Development, Health, and Disease)
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Open AccessReview
Acute Intravesical Capsaicin for the Study of TRPV1 in the Lower Urinary Tract: Clinical Relevance and Potential for Innovation
Med. Sci. 2022, 10(3), 50; https://doi.org/10.3390/medsci10030050 - 10 Sep 2022
Abstract
Capsaicin acts on sensory nerves via vanilloid receptors. TRPV1 has been extensively studied with respect to functional lower urinary tract (LUT) conditions in rodents and humans. We aimed to (1) provide background information on capsaicin and TRPV1 and its mechanisms of action and
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Capsaicin acts on sensory nerves via vanilloid receptors. TRPV1 has been extensively studied with respect to functional lower urinary tract (LUT) conditions in rodents and humans. We aimed to (1) provide background information on capsaicin and TRPV1 and its mechanisms of action and basis for clinical use, (2) review the use of acute intravesical capsaicin instillation (AICI) in rodents to mimic various LUT disorders in which capsaicin sensitive C-fibers are involved and (3) discuss future innovative treatments. A comprehensive search of the major literature databases until June 2022 was conducted. Both capsaicin-sensitive and resistant unmyelinated bladder afferent C-fibers are involved in non-neurogenic overactive bladder/detrusor overactivity (OAB/DO). AICI is a suitable model to study afferent hyperactivity mimicking human OAB. Capsaicin-sensitive C-fibers are also involved in neurogenic DO (NDO) and potential targets for NDO treatment. AICI has been successfully tested for NDO treatment in humans. Capsaicin-sensitive bladder afferents are targets for NDO treatment. TRPV1-immunoreactive nerve fibers are involved in the pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS). The AICI experimental model appears relevant for the preclinical study of treatments targeting bladder afferents for refractory IC/BPS. The activity of capsaicin-sensitive bladder afferents is increased in experimental bladder outlet obstruction (BOO). The AICI model may also be relevant for bladder disorders resulting from C-fiber hyperexcitabilities related to BOO. In conclusion, there is a rationale for the selective blockade of TRPV1 channels for various bladder disorders. The AICI model is clinically relevant for the investigation of pathophysiological conditions in which bladder C-fiber afferents are overexcited and for assessing innovative treatments for bladder disorders based on their pathophysiology.
Full article
(This article belongs to the Section Nephrology and Urology)
Open AccessArticle
Vitamin D Supplementation in the Assessment of Cardiovascular Risk Factors in Overweight and Obese Children
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Med. Sci. 2022, 10(3), 49; https://doi.org/10.3390/medsci10030049 - 05 Sep 2022
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Background: Childhood obesity is associated with cardiovascular-disease (CVD) risk factors, an unfavorable lipid profile and reduced levels of 25(OH)D. The aim of our study is to evaluate whether vitamin D supplementation may play a role in the assessment of the CVD risk factors
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Background: Childhood obesity is associated with cardiovascular-disease (CVD) risk factors, an unfavorable lipid profile and reduced levels of 25(OH)D. The aim of our study is to evaluate whether vitamin D supplementation may play a role in the assessment of the CVD risk factors in overweight/obese children and adolescents. Methods: We performed a retrospective observational study involving children (9–15 years of age) with a known diagnosis of overweight or obesity (BMI > 25) and decreased levels of 25(OH)D (<25 ng/mL), who underwent oral vitamin D supplementation (100,000 UI, one vial/month) for six months. The anthropometric parameters, 25(OH)D, serum lipids and ALT levels were measured at the beginning (T0) and after 6 months (T1). Results: Of the 58 patients recruited, 45 had an increase in the serum 25(OH)D levels after supplementation. Vitamin D supplementation was associated with a decrease in the serum levels of the total cholesterol (p = 0.009), LDL-C (p = 0.005) and ALT (p = 0.005), and an increase in HDL-C (p = 0.03). These results were confirmed when the correction for the body mass index (BMI) was applied. Conclusions: The favorable effect of vitamin D supplementation on the total cholesterol, LDL-C, HDL-C and ALT could transform these values into modifiable risk factors starting in early childhood, with beneficial effects on long-term health.
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Open AccessArticle
Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing
Med. Sci. 2022, 10(3), 48; https://doi.org/10.3390/medsci10030048 - 31 Aug 2022
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The high cost and time for developing a new drug or repositioning a partially-developed drug has fueled interest in “repurposing” drugs. Drug repurposing is particularly of interest for Alzheimer’s disease (AD) or AD-related dementias (ADRD) because there are no unrestricted disease-modifying treatments for
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The high cost and time for developing a new drug or repositioning a partially-developed drug has fueled interest in “repurposing” drugs. Drug repurposing is particularly of interest for Alzheimer’s disease (AD) or AD-related dementias (ADRD) because there are no unrestricted disease-modifying treatments for ADRD. We have designed and pilot tested a 3-Step Medication-Wide Association Study Plus (MWAS+) approach to rigorously accelerate the identification of drugs with a high potential to be repurposed for delaying and preventing AD/ADRD: Step 1 is a hypothesis-free exploration; Step 2 is mechanistic filtering; And Step 3 is hypothesis testing using observational data and prospective cohort design. Our results demonstrated the feasibility of the MWAS+ approach. The Step 1 analysis identified potential candidate drugs including atorvastatin and GLP1. The literature search in Step 2 found evidence supporting the mechanistic plausibility of the statin-ADRD association. Finally, Step 3 confirmed our hypothesis that statin may lower the risk of incident ADRD, which was statistically significant using a target trial design that emulated randomized controlled trials.
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Open AccessArticle
Identification and Characterization of Novel Small-Molecule SMOX Inhibitors
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Med. Sci. 2022, 10(3), 47; https://doi.org/10.3390/medsci10030047 - 30 Aug 2022
Abstract
The major intracellular polyamines spermine and spermidine are abundant and ubiquitous compounds that are essential for cellular growth and development. Spermine catabolism is mediated by spermine oxidase (SMOX), a highly inducible flavin-dependent amine oxidase that is upregulated during excitotoxic, ischemic, and inflammatory states.
[...] Read more.
The major intracellular polyamines spermine and spermidine are abundant and ubiquitous compounds that are essential for cellular growth and development. Spermine catabolism is mediated by spermine oxidase (SMOX), a highly inducible flavin-dependent amine oxidase that is upregulated during excitotoxic, ischemic, and inflammatory states. In addition to the loss of radical scavenging capabilities associated with spermine depletion, the catabolism of spermine by SMOX results in the production of toxic byproducts, including H2O2 and acrolein, a highly toxic aldehyde with the ability to form adducts with DNA and inactivate vital cellular proteins. Despite extensive evidence implicating SMOX as a key enzyme contributing to secondary injury associated with multiple pathologic states, the lack of potent and selective inhibitors has significantly impeded the investigation of SMOX as a therapeutic target. In this study, we used a virtual and physical screening approach to identify and characterize a series of hit compounds with inhibitory activity against SMOX. We now report the discovery of potent and highly selective SMOX inhibitors 6 (IC50 0.54 μM, Ki 1.60 μM) and 7 (IC50 0.23 μM, Ki 0.46 μM), which are the most potent SMOX inhibitors reported to date. We hypothesize that these selective SMOX inhibitors will be useful as chemical probes to further elucidate the impact of polyamine catabolism on mechanisms of cellular injury.
Full article
(This article belongs to the Special Issue Polyamines: Essential Molecules Regulating Development, Health, and Disease)
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Open AccessArticle
Plasma Concentrations of Vinculin versus Talin-1 in Coronary Artery Disease
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Med. Sci. 2022, 10(3), 46; https://doi.org/10.3390/medsci10030046 - 26 Aug 2022
Abstract
Vinculin and talin-1, which are cytoskeletal proteins affecting focal adhesions, were reported to be down-expressed in atherosclerotic lesions. Recently, we reported high concentrations of plasma talin-1 in patients with coronary artery disease (CAD). However, blood vinculin concentrations in CAD patients have not been
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Vinculin and talin-1, which are cytoskeletal proteins affecting focal adhesions, were reported to be down-expressed in atherosclerotic lesions. Recently, we reported high concentrations of plasma talin-1 in patients with coronary artery disease (CAD). However, blood vinculin concentrations in CAD patients have not been clarified. Plasma vinculin concentrations as well as talin-1 were studied in 327 patients in whom coronary angiography was performed. CAD was proven in 177 patients (1-vessel, n = 79; 2-vessel, n = 57; 3-vessel disease, n = 41). However, vinculin concentrations were not markedly different between the CAD(-) and CAD groups (median 122.5 vs. 119.6 pg/mL, p = 0.325) or among patients with CAD(-), 1-, 2-, and 3-vessel diseases (122.5, 112.8, 107.9, and 137.2 pg/mL, p = 0.202). In contrast, talin-1 concentrations were higher in CAD than the CAD(-) group (0.29 vs. 0.23 ng/mL, p = 0.006) and increased stepwise in the number of stenotic vessels: 0.23 in CAD(-), 0.28 in 1-vessel, 0.29 in 2-vessel, and 0.33 ng/mL in 3-vessel disease (p = 0.043). No correlation was observed between vinculin and talin-1 concentrations. In multivariate analysis, vinculin concentrations were not a factor for CAD. In conclusion, plasma vinculin concentrations in patients with CAD were not high and were not associated with the presence or severity of CAD.
Full article
(This article belongs to the Section Cardiovascular Disease)
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Open AccessBrief Report
Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
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, , , and
Med. Sci. 2022, 10(3), 45; https://doi.org/10.3390/medsci10030045 - 25 Aug 2022
Abstract
Polyamines are small organic cations that are essential for many biological processes such as cell proliferation and cell cycle progression. While the metabolism of polyamines has been well studied, the mechanisms by which polyamines are transported into and out of cells are poorly
[...] Read more.
Polyamines are small organic cations that are essential for many biological processes such as cell proliferation and cell cycle progression. While the metabolism of polyamines has been well studied, the mechanisms by which polyamines are transported into and out of cells are poorly understood. Here, we describe a novel role of Chmp1, a vesicular trafficking protein, in the transport of polyamines using a well-defined leg imaginal disc assay in Drosophila melanogaster larvae. We show that Chmp1 overexpression had no effect on leg development in Drosophila, but does attenuate the negative impact on leg development of Ant44, a cytotoxic drug known to enter cells through the polyamine transport system (PTS), suggesting that the overexpression of Chmp1 downregulated the PTS. Moreover, we showed that the addition of spermine did not rescue the leg development in Chmp1-overexpressing leg discs treated with difluoromethylornithine (DFMO), an inhibitor of polyamine metabolism, while putrescine and spermidine did, suggesting that there may be unique mechanisms of import for individual polyamines. Thus, our data provide novel insight into the underlying mechanisms that are involved in polyamine transport and highlight the utility of the Drosophila imaginal disc assay as a fast and easy way to study potential players involved in the PTS.
Full article
(This article belongs to the Special Issue Polyamines: Essential Molecules Regulating Development, Health, and Disease)
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Open AccessArticle
Polyamine-Based Nanostructures Share Polyamine Transport Mechanisms with Native Polyamines and Their Analogues: Significance for Polyamine-Targeted Therapy
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, , , , , and
Med. Sci. 2022, 10(3), 44; https://doi.org/10.3390/medsci10030044 - 22 Aug 2022
Abstract
Polyamines are small polycationic alkylamines involved in many fundamental cellular processes, including cell proliferation, survival, and protection from oxidative stress. Polyamine homeostasis is tightly regulated through coordinated biosynthesis, catabolism, and transport. Due to their continual proliferation, cancer cells maintain elevated intracellular polyamine pools.
[...] Read more.
Polyamines are small polycationic alkylamines involved in many fundamental cellular processes, including cell proliferation, survival, and protection from oxidative stress. Polyamine homeostasis is tightly regulated through coordinated biosynthesis, catabolism, and transport. Due to their continual proliferation, cancer cells maintain elevated intracellular polyamine pools. Both polyamine metabolism and transport are commonly dysregulated in cancer, and as such, polyamine analogues are a promising strategy for exploiting the increased polyamine requirement of cancer cells. One potential polyamine analogue resistance mechanism is the downregulation of the poorly defined polyamine transport system. Recent advances in nanomedicine have produced nanostructures with polyamine analogue-based backbones (nanopolyamines). Similar nanostructures with non-polyamine backbones have been shown to be transported by endocytosis. As these polyamine-based nanoparticles could be a method for polyamine analogue delivery that bypasses polyamine transport, we designed the current studies to determine the efficacy of polyamine-based nanoparticles in cells lacking intact polyamine transport. Utilizing polyamine transport-deficient derivatives of lung adenocarcinoma lines, we demonstrated that cells unable to transport natural polyamines were also resistant to nanopolyamine-induced cytotoxicity. This resistance was a result of transport-deficient cells being incapable of importing and accumulating nanopolyamines. Pharmacological modulation of polyamine transport confirmed these results in polyamine transport competent cells. These studies provide additional insight into the polyamine transport pathway and suggest that receptor-mediated endocytosis is a likely mechanism of transport for higher-order polyamines, polyamine analogues and the nanopolyamines.
Full article
(This article belongs to the Special Issue Polyamines: Essential Molecules Regulating Development, Health, and Disease)
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Open AccessArticle
Multiple Asparaginase Infusions Cause Increasingly Severe Acute Hyperammonemia
Med. Sci. 2022, 10(3), 43; https://doi.org/10.3390/medsci10030043 - 12 Aug 2022
Abstract
Adverse reactions during and shortly after infusing asparaginase for the treatment of acute lymphoblastic leukemia can increase in severity with later doses, limiting further use and increasing relapse risk. Although asparaginase is associated with hyperammonemia, the magnitude of the increase in serum ammonia
[...] Read more.
Adverse reactions during and shortly after infusing asparaginase for the treatment of acute lymphoblastic leukemia can increase in severity with later doses, limiting further use and increasing relapse risk. Although asparaginase is associated with hyperammonemia, the magnitude of the increase in serum ammonia immediately after the infusion and in response to multiple infusions has not been examined. The concurrence of hyperammonemia and infusion reactions was studied using weaned juvenile pigs that received 12 infusions of Erwinia asparaginase (Erwinase; 1250 U/kg) over 28 days, with two 5-day recovery periods without asparaginase after the eighth and eleventh doses. Infusion reactions and prolonged hyperammonemia (>50 µM ammonia 48 h after the infusion) began after the fourth dose and increased with later doses. Dense sampling for 60 min revealed an acute phase of hyperammonemia that peaked within 20 min after starting the first infusion (298 + 62 µM) and lasted less than 1 h, without apparent symptoms. A pronounced acute hyperammonemia after the final infusion (1260 + 250 µM) coincided with severe symptoms and one mortality during the infusion. The previously unrecognized acute phase of hyperammonemia associated with asparaginase infusion coincides with infusion reactions. The juvenile pig is a translational animal model for understanding the causes of acute and chronic hyperammonemia, differentiating from hypersensitivity reactions, and for improving infusion protocols to reduce acute hyperammonemia and to allow the continued use of asparaginase.
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(This article belongs to the Topic Advances in Anti-cancer Drugs)
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Open AccessArticle
Clinicopathological Characteristics and Overall 5-Year Survival of Colorectal Cancer: A Retrospective Study
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Med. Sci. 2022, 10(3), 42; https://doi.org/10.3390/medsci10030042 - 09 Aug 2022
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death. We aimed to investigate the clinicopathological characteristics and 5-year survival in CRC. This retrospective study reviewed King Abdulaziz University Hospital records from 2009 to 2019. Tumor staging was performed using Dukes’ pathological
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Colorectal cancer (CRC) is the third leading cause of cancer-related death. We aimed to investigate the clinicopathological characteristics and 5-year survival in CRC. This retrospective study reviewed King Abdulaziz University Hospital records from 2009 to 2019. Tumor staging was performed using Dukes’ pathological classification. Additionally, we measured the frequency of qualitative data and performed the chi-square and Mann–Whitney U-tests. Kaplan–Meier analysis was performed to calculate overall survival. Of the 574 included patients (age (mean ± standard deviation), 55.51 ± 14.28 years), 43.2% were Saudis, and most were male (58.7%). The rectum was the most common location of CRC (30.8%); 33.1% of patients presented with abdominal pain. The dominant histological variant was mucinous adenocarcinoma (95.5%). Age at diagnosis was significantly associated with Dukes’ staging; 36.3% of individuals aged <50 years had Dukes’ D stage. The 5-year survival rate was 47.9%. Better survival was noted for those of Saudi nationality, those with Dukes’ A stage, and those who were overweight (51.6%, 56.3%, and 46.8%, respectively). Significantly better survival was seen in Saudi patients due to accessible healthcare and in overweight patients due to better treatment tolerance. The outcome of CRC was not related to sex or metformin use in patients with diabetes mellitus.
Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
Open AccessArticle
In-Person or Online? The Effect of Delivery Mode on Team-Based Learning of Clinical Reasoning in a Family Medicine Clerkship
Med. Sci. 2022, 10(3), 41; https://doi.org/10.3390/medsci10030041 - 08 Aug 2022
Abstract
In health professions education, team-based learning (TBL) has been used to help learners develop clinical reasoning and decision-making skills. The COVID-19 pandemic has challenged institutions to move curriculum delivery from largely in-person to online. With the anticipated return to in-person instruction and arguments
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In health professions education, team-based learning (TBL) has been used to help learners develop clinical reasoning and decision-making skills. The COVID-19 pandemic has challenged institutions to move curriculum delivery from largely in-person to online. With the anticipated return to in-person instruction and arguments made in favor of online instruction in certain circumstances, evidence is needed to support decision making in curriculum planning. The purpose of this study was to examine the effect of delivery mode (in-person vs. online) on student learning of clinical reasoning and clinical decision-making (CR/CDM) in the family medicine clerkship. Data from three cohorts of third-year medical students were included in the study: 2018/2019 cohort, in-person; 2019/2020 cohort, half of the cohort in-person, half of the cohort online; 2020/2021 cohort, online. Students’ performance data—individual readiness assurance test (IRAT) and group readiness assurance test (GRAT) scores—were used. The Generalized Estimating Equations (GEE) analysis was performed. As expected, students scored higher in GRAT than IRAT across the three cohorts. No significant IRAT-GRAT differences were observed between in-person and online delivery of TBL sessions. Student learning of CR/CDM in TBL is comparable between the two modes of delivery in the family medicine clerkship. Future research in other clerkships, years of medical education, and professional programs is needed to inform decision making regarding the TBL delivery mode.
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Polyamine and Ethanolamine Metabolism in Bacteria as an Important Component of Nitrogen Assimilation for Survival and Pathogenicity
Med. Sci. 2022, 10(3), 40; https://doi.org/10.3390/medsci10030040 - 29 Jul 2022
Abstract
Nitrogen is an essential element required for bacterial growth. It serves as a building block for the biosynthesis of macromolecules and provides precursors for secondary metabolites. Bacteria have developed the ability to use various nitrogen sources and possess two enzyme systems for nitrogen
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Nitrogen is an essential element required for bacterial growth. It serves as a building block for the biosynthesis of macromolecules and provides precursors for secondary metabolites. Bacteria have developed the ability to use various nitrogen sources and possess two enzyme systems for nitrogen assimilation involving glutamine synthetase/glutamate synthase and glutamate dehydrogenase. Microorganisms living in habitats with changeable availability of nutrients have developed strategies to survive under nitrogen limitation. One adaptation is the ability to acquire nitrogen from alternative sources including the polyamines putrescine, cadaverine, spermidine and spermine, as well as the monoamine ethanolamine. Bacterial polyamine and monoamine metabolism is not only important under low nitrogen availability, but it is also required to survive under high concentrations of these compounds. Such conditions can occur in diverse habitats such as soil, plant tissues and human cells. Strategies of pathogenic and non-pathogenic bacteria to survive in the presence of poly- and monoamines offer the possibility to combat pathogens by using their capability to metabolize polyamines as an antibiotic drug target. This work aims to summarize the knowledge on poly- and monoamine metabolism in bacteria and its role in nitrogen metabolism.
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(This article belongs to the Special Issue Polyamines: Essential Molecules Regulating Development, Health, and Disease)
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Open AccessReview
Vasovagal Reactions during Interventional Pain Management Procedures—A Review of Pathophysiology, Incidence, Risk Factors, Prevention, and Management
by
and
Med. Sci. 2022, 10(3), 39; https://doi.org/10.3390/medsci10030039 - 25 Jul 2022
Abstract
Vasovagal reactions are a benign but common outcome of interventional pain management procedures that can negatively impact patient care, including aborted procedures and fear of future procedures that would otherwise help the patient. Research has been done on the incidence, risk factors, and
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Vasovagal reactions are a benign but common outcome of interventional pain management procedures that can negatively impact patient care, including aborted procedures and fear of future procedures that would otherwise help the patient. Research has been done on the incidence, risk factors, and management of vasovagal reactions resulting from such procedures, but less is known about how to prevent these reactions from occurring. In this paper, we present a literature review of the pathophysiology, incidence, risk factors, prevention, and management of vasovagal reactions during interventional pain management procedures, with an emphasis on the relative lack of research and conflicting advice on preventive measures. We found that moderate sedation and anxiolytics have been used prophylactically to prevent vasovagal reactions, but their side-effect profiles prevent them from being used commonly. Less studied is the prophylactic administration of antimuscarinics and IV fluids, despite the potential benefit of these measures and relatively low side-effect profile. We explore these topics here and offer advice for future research to fill the gaps in our knowledge.
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(This article belongs to the Section Translational Medicine)
Open AccessReview
Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease
Med. Sci. 2022, 10(3), 38; https://doi.org/10.3390/medsci10030038 - 15 Jul 2022
Cited by 1
Abstract
The polyamines spermidine and spermine are positively charged aliphatic molecules. They are critical in the regulation of nucleic acid and protein structures, protein synthesis, protein and nucleic acid interactions, oxidative balance, and cell proliferation. Cellular polyamine levels are tightly controlled through their import,
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The polyamines spermidine and spermine are positively charged aliphatic molecules. They are critical in the regulation of nucleic acid and protein structures, protein synthesis, protein and nucleic acid interactions, oxidative balance, and cell proliferation. Cellular polyamine levels are tightly controlled through their import, export, de novo synthesis, and catabolism. Enzymes and enzymatic cascades involved in polyamine metabolism have been well characterized. This knowledge has been used for the development of novel compounds for research and medical applications. Furthermore, studies have shown that disturbances in polyamine levels and their metabolic pathways, as a result of spontaneous mutations in patients, genetic engineering in mice or experimentally induced injuries in rodents, are associated with multiple maladaptive changes. The adverse effects of altered polyamine metabolism have also been demonstrated in in vitro models. These observations highlight the important role these molecules and their metabolism play in the maintenance of physiological normalcy and the mediation of injury. This review will attempt to cover the extensive and diverse knowledge of the biological role of polyamines and their metabolism in the maintenance of physiological homeostasis and the mediation of tissue injury.
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(This article belongs to the Special Issue Polyamines: Essential Molecules Regulating Development, Health, and Disease)
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