Perspective Of Medicine Research Articles

N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and their Pharmacological Implication: A Medicinal Chemistry-oriented Perspective Outline.

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc.). Additionally, reported NMDA antagonists from different sources, such as synthetic, semisynthetic, and natural resources, are explained by their mechanism of action and pharmacological role. The comprehensive report also addresses the chemical spacing of NMDA inhibitors and in-vivo and in-vitro models to test NMDA antagonists. Since the Blood-Brain Barrier (BBB) is the primary membrane that prevents the penetration of a wide variety of drug molecules, we also elaborate on the medicinal chemistry approach to improve the effectiveness of their antagonists.

Protein-protein interactions in cGAS-STING pathway: a medicinal chemistry perspective.

Protein-protein interactions (PPIs) play pivotal roles in biological processes and are closely linked with human diseases. Research on small molecule inhibitors targeting PPIs provides valuable insights and guidance for novel drug development. The cGAS-STING pathway plays a crucial role in regulating human innate immunity and is implicated in various pathological conditions. Therefore, modulators of the cGAS-STING pathway have garnered extensive attention. Given that this pathway involves multiple PPIs, modulating PPIs associated with the cGAS-STING pathway has emerged as a promising strategy for modulating this pathway. In this review, we summarize an overview of recent advancements in medicinal chemistry insights into cGAS-STING PPI-based modulators and propose alternative strategies for further drug discovery based on the cGAS-STING pathway.

Update of the German guideline on chronic and poorly healing peripheral wounds - a geriatric medicine perspective

Update of the German guideline on chronic and poorly healing peripheral wounds - a geriatric medicine perspective

Lessons learned from navigating the COVID pandemic in a health sciences university: a disaster medicine perspective

Lessons learned from navigating the COVID pandemic in a health sciences university: a disaster medicine perspective

Cognitive Impairment from Breast Cancer Chemotherapy in the Perspective of Traditional Chinese Medicine

In recent years, the incidence of breast cancer has been on the rise globally and in China. The conventional treatment methods for breast cancer include surgery, radiotherapy, chemotherapy, endocrine therapy, targeted therapy, traditional Chinese medicine, and other biological immunotherapy. In the treatment of breast cancer, the status of chemotherapy drugs is unshakable, and the related toxic side effects have gradually attracted people's attention. Doxorubicin is an anthracycline drug, which is the cornerstone drug for adjuvant chemotherapy for breast cancer. It exerts anti-tumor effects by inserting DNA and inhibiting topoisomerase II, but it can also cause severe neurotoxicity by crossing the blood-brain barrier, clinically manifested as memory and executive function decline, etc., which has a huge impact on the patient's work and life. With the development of modern medicine, the advantages of traditional Chinese medicine in preventing and treating adverse reactions related to breast cancer and improving patients' quality of life are increasingly being recognized. Traditional Chinese medicine classifies chemotherapy-induced cognitive impairment into related diseases such as "dementia", "brain marrow depletion", and "forgetfulness" based on its main clinical symptoms, and achieves the therapeutic effect of improving chemotherapy-induced cognitive impairment through clinical differentiation and coordinating relevant therapies, providing a scientific basis for the treatment of adverse reactions related to malignant tumors by traditional Chinese medicine in radiotherapy and chemotherapy.

Gender bias in generative artificial intelligence text-to-image depiction of medical students

Introduction: In Australia, 54.3% of medical students are women yet they remain under-represented in stereotypical perspectives of medicine. While potentially transformative, generative artificial intelligence (genAI) has the potential for errors, misrepresentations and bias. GenAI text-to-image production could reinforce gender biases making it important to evaluate DALL-E 3 (the text-to-image genAI supported through ChatGPT) representations of Australian medical students. Method: In March 2024, DALL-E 3 was utilised via GPT-4 to generate a series of individual and group images of medical students, specifically Australian undergraduate medical students to eliminate potential confounders. Multiple iterations of images were generated using a variety of prompts. Collectively, 47 images were produced for evaluation of which 33 were individual characters and the remaining 14 images were comprised of multiple (5 to 67) characters. All images were independently analysed by three reviewers for apparent gender and skin tone. Consequently, 33 feature individuals were evaluated and a further 417 characters in groups were evaluated ( N = 448). Discrepancies in responses were resolved by consensus. Results: Collectively (individual and group images), 58.8% ( N = 258) of medical students were depicted as men, 39.9% ( N = 175) as women, 92.0% ( N = 404) with a light skin tone, 7.7% ( N = 34) with mid skin tone and 0% with dark skin tone. The gender distribution was a statistically significant variation from that of actual Australian medical students for individual images, for group images and for collective images. Among the images of individual medical students ( N = 25), DALL-E 3 generated 92% ( N = 23) as men and 100% were of light skin tone ( N = 25). Conclusion: This evaluation reveals the gender associated with genAI text-to-image generation using DALL-E 3 among Australian undergraduate medical students. Generated images included a disproportionately high proportion of white male medical students which is not representative of the diversity of medical students in Australia. The use of DALL-E 3 to produce depictions of medical students for education or promotion purposes should be done with caution.

Application framework and model of Jingjin therapy in rehabilitation medicine

The Jingjin therapy and rehabilitation medicine share commonalities and complement each other. The application of Jingjin therapy from a rehabilitation perspective can broaden the development path of traditional Chinese medicine (TCM) rehabilitation. This paper, based on relevant literature and research findings, elaborates on the connection between Jingjin syndrome differentiation acupuncture and rehabilitation assessment and treatment. It discusses the application framework of Jingjin's preventive treatment theory in disease prevention and rehabilitation, and forecasts the research model of Jingjin rehabilitation medicine from an integrative perspective of Chinese and western medicine. This study aims to improve the rehabilitation application thinking of Jingjin therapy and enrich the application methods and treatment approaches of TCM rehabilitation medicine.

Leonurine improves atherosclerosis by activating foam cell autophagy and metabolic remodeling via METTL3-mediated AKT1S1 mRNA stability modulation

BackgroundAtherosclerosis (AS) is the most prevalent cardiovascular disease and remains the major contributor to death and mortality globally. Leonurine (LEO) is a unique alkaloid compound with protective effects on the cardiovascular system. However, the exact mechanisms underlying its cardiovascular-protecting action are still not fully elucidated. The methyltransferase 3 (METTL3), the catalytic core of the N6-methyladenosine modification (m6A) methyltransferase complex, has been shown to inhibit autophagy and exacerbate the process of AS via regulation of m6A modification of mRNA. PurposeWe aimed to determine whether the inhibited effect of LEO on AS is related to METTL3-mediated AKT1S1 stability. MethodsThe apolipoprotein E (ApoE) knockout mice was subjected to a high-fat diet (HFD), and THP-1 derived macrophages was exposed to oxidized low-density lipoprotein (ox-LDL), to establish the animal and cellular models of AS, respectively. ResultsWe found that LEO effectively improved AS and reduced the plaque area and inflammation via diminishing macrophage lipid accumulation and remodeling the lipid metabolism profile. LEO activated ox-LDL-induced macrophage autophagy, enhancing lipid metabolism decrease, according to the lipidomic and molecular biology analyses. Additionally, LEO caused a marked increase in autophagy marker levels in mouse models with advanced AS. Furthermore, we found that LEO reactivated autophagy and reversed lipid accumulation by suppressing METTL3 expression. The m6A-seq from ox-LDL-induced macrophages showed that a total of five autophagy-related mRNA transcripts (AKT1S1, AKT1, RB1CC1, CFLAR, and MTMR4) were altered, and AKT1S1 was significantly upregulated by LEO. Mechanistically, LEO-mediated regulation of METTL3 decreased AKT1S1 expression by attenuating its mRNA stability. Silencing AKT1S1 inhibited LEO-METTL3 axis-mediated autophagy and enhanced lipid accumulation in ox-LDL-induced macrophages. ConclusionThe study first revealed that LEO exerts anti-atherosclerotic effect by activating METTL3-mediated macrophage autophagy in vivo and in vitro. The mechanism of LEO was further found to be the enhancement of METTL3-mediated AKT1S1 stability to activate autophagy thereby reducing lipid accumulation. This study provides a new perspective of natural medicines on the treatment of AS via an epigenetic manner.

The Human OCTN Sub-Family: Gene and Protein Structure, Expression, and Regulation.

OCTN1 and OCTN2 are membrane transport proteins encoded by the SLC22A4 and SLC22A5 genes, respectively. Even though several transcripts have been predicted by bioinformatics for both genes, only one functional protein isoform has been described for each of them. Both proteins are ubiquitous, and depending on the physiopathological state of the cell, their expression is regulated by well-known transcription factors, although some aspects have been neglected. A plethora of missense variants with uncertain clinical significance are reported both in the dbSNP and the Catalogue of Somatic Mutations in Cancer (COSMIC) databases for both genes. Due to their involvement in human pathologies, such as inflammatory-based diseases (OCTN1/2), systemic primary carnitine deficiency (OCTN2), and drug disposition, it would be interesting to predict the impact of variants on human health from the perspective of precision medicine. Although the lack of a 3D structure for these two transport proteins hampers any speculation on the consequences of the polymorphisms, the already available 3D structures for other members of the SLC22 family may provide powerful tools to perform structure/function studies on WT and mutant proteins.

Exploring Ayurvedic Nutritional Medicine Perspective: The Benefits and Clinical Significance of Millets

The science of nutrition may be enriched as well as deficiency and over nutritional disorders can be managed in a better way by incorporating Ayurvedic nutritional medicine measures in form of different diets and dietary regulation The millets are referred to in Ayurveda as Kudhanya, Kshudra Dhanya, and Trin Dhanya under the category Dhanya Varga (group of fried grains). Aim & Objectives: To explore Ayurvedic nutritional medicine perspective and clinical significance of millets. Material and Methods: The research methodology used for the study comprises a review of relevant academic articles and Ayurvedic literature. Using the search engines Google Scholar, Scopus, Web of Science and PubMed (MEDLINE). Results: Millets are economical, nutritional and gluten free. Millets are best advised in Kaphaja Roga (diseases due to Kapha) and other Santarpanajanya Vyadhi (diseases brought on by over nutrition of one or more tissues). When it comes to Vataja Roga (diseases caused by Vata), millets should be avoided as they exacerbate the ailment. Conclusion: It has been stated in Ayurveda classics that being thin is preferable to being obese, and the Laghu (lightness), Lekhaniya (therapeutic scrapping) property of millets, with low glycemic content and the added benefit of long-term satiety, making it an excellent choice as a Ayurvedic Nutritional Medicine. Additionally, it is Ruksha (dry) with Lekhana (therapeutic scrapping) and Kledashoshana (dries up excess moisture) actions which makes it effective for treating Santapanajanya Vyadhi (diseases brought on by over nutrition of one or more tissues), such as Prameha (excessive urination), Sthaulya (obesity) etc.

Analyzing unmanned aerial vehicle (drone) attacks; a disaster medicine perspective

IntroductionUnmanned aerial vehicles (UAVs), more commonly known as drones, have rapidly become more diverse in capabilities and utilization through technology advancements and affordability. While drones have had significant positive impact on healthcare and consumer delivery particularly in remote and austere environments, Violent Non-State Actors (VNSAs) have increasingly used drones as weapons in planning and executing terrorist attacks resulting in significant morbidity and mortality. We aim to analyze drone-related attacks globally against civilians and critical infrastructure for more effective hospital and prehospital care preparedness. MethodsWe retrospectively reviewed the Global Terrorism Database (GTD) from 1970 to 2020 to analyze the worldwide prevalence of drone-related attacks against civilians and critical infrastructure. Cases were excluded if they had insufficient information regarding a drone involvement, and if attacks were conducted by the government entities. The trends in the number of attacks per month, as well as the number of fatalities and injuries, were examined using time series and trend analysis. ResultsThe database search yielded 253 drone-related incidents, 173 of which met inclusion criteria. These incidents resulted in 92 fatalities and 215 injuries with civilian targets most commonly attacked by drones (76 events, 43.9%), followed by military (46 events, 26.5-%). The Middle East region was most affected (168 events, 97% of attacks) and the Islamic state of Iraq was the most common perpetrator (106 events, 61.2%). Almost all attacks were by explosive devices attached to drones (172 events, 99.4%). Time series with linear trend analyses suggested an upward trends of drone attacks by VNSAs, resulting in a greater number of injuries and fatalities, that became more frequent over the years. ConclusionsOvertime, there were upward trends of drone attacks, with higher lethality and morbidity. There were more injuries compared to fatalities. Most common region affected was the Middle East, and most common type of weapon employed by drone technology was explosive weapon. Investment in medical personnel training, security, and research is crucial for an effective mass-casualty incident response after the drone attacks.

Effects of Microplastics on Animal Health and Nutrition

Macro plastics are defined as plastics that are larger than 20 cm. Plastics that measure between 5-20 cm are referred to as mesoplastics, while those between 1-5 mm are known as large microplastics. Plastics that measure between 1-1000 μm are called small micro plastics, and those that are smaller than 1000 μm are referred to as nano-plastics. Microplastics are particles that result from the degradation of plastic products or are specifically produced in the form of small pieces. They are considered to be less than 5 μm in size. Micro plastics have come to the fore in re-cent years and are pollutants of major concern to the environment. Plastic materials are commonly used on farms, but they can have negative effects on farm animals. Ruminants such as cattle, sheep and goats require cellulolytic micro-organisms for fiber digestion in their diet. The micro biota of the digestive system varies according to dietary habits. The digestive system and other organs can be adversely affected by sudden changes and damage to the micro biota. The ingestion of large plastic materials causes rumen complications such as rumen atony, indigestion and tympani in livestock. Ingested plastic fragments degrade in the digestive tract, increasing the number of small particles likely to be ingested. In a recent study, the presence of low-density micro plastics in sheep feces suggests that animals can ingest micro and macro plastics from their environment and feed. The increase in demand for the consumption of plastics worldwide is increasing the production of plastics. This situation causes the presence of micro plastics to increase rap-idly day by day. Even if the production of plastics decreases, the continuous degradation of plastic waste in the earth will continue the formation of micro plastics and cause environmental pollution. The effects of microplastics in our coun-try should be investigated by conducting detailed studies from the perspective of veterinary medicine.

Medicinal perspectives, molecular docking and structure activity relationship of benzothiazole derived thiazole-based bis-benzohydrazide as potential anti-Alzheimer agents

A new series of benzothiazole derived thiazole-based bis-benzohydrazide hybrid (1–20) analogs were synthesized. Initially, the product confirmation was identified by employing TLC and the basic skeleton of the new hybrid synthesized compounds was further confirmed through spectroscopic techniques such as 13CNMR, 1HNMR and HREI-MS. Moreover, the synthesized analogs were tested for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. In the whole series, compounds 1, 2, 3 and 6 were found with potent activity against acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE). Molecular docking inveatigation of the potent compounds was performed within the active site of acetylcholinesterase and butyrylcholinesterase revealing compounds 1, 2, 3 and 6 showing promising binding orientations against both enzymes as compared to reference drug donepezil with their IC50 values 1(2.20 ± 1.40 and 3.18 ± 0.45 μM), 2 (2.89 ± 1.25 and 2.78 ± 1.49 μM), 3 (2.94 ± 1.10 and 3.07 ± 1.23 μM), 6 (5.83 ± 1.45 and 6.03 ± 3.08 μM), respectively, and reference drug (IC50 = 8.73 ± 2.68 and 9.30 ± 2.60 μM for acetylcholinesterase and butyrylchlinesterase, respectively. In addition, ADME studies were conducted to gain a deeper understanding of the functional mechanisms of a drug on a living organism. It is considered that benzothiazole derived thiazole based bis-benzohydrazide hybrid analogs (1, 2, 3, 6) might be better inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes.

District Residency Programme (DRP) for Post-graduates: The Community Medicine Perspective

District Residency Programme (DRP) for Post-graduates: The Community Medicine Perspective

The caregiving role influences Suboptimal Health Status and psychological symptoms in unpaid carers

BackgroundSuboptimal Health Status (SHS) is the physical state between health and disease. This study aimed to fill in the knowledge gap by investigating the prevalence of SHS and psychological symptoms among unpaid carers and to identify SHS-risk factors from the perspective of predictive, preventive and personalised medicine (PPPM).MethodsA cross-sectional study was conducted among 368 participants who were enrolled from Australia, including 203 unpaid carers as cases and 165 individuals from the general population as controls. SHS scores were measured using SHSQ-25 (Suboptimal Health Status Questionnaire-25), whilst psychological symptoms were measured by DASS-21 (Depression, Anxiety and Stress Scale-21). Chi-square was used to measure SHS and psychological symptom prevalence. Spearman correlation analysis was utilised to identify the relationship between SHSQ-25 and DASS-21 scores. Logistic regression analysis was used for multivariate analysis.ResultsThe prevalence of SHS in carers was 43.0% (98/203), significantly higher than the prevalence 12.7% (21/165) in the general population (p < 0.001). In addition, suboptimal health prevalence was higher in female carers (50.3%; 95/189) than females in the general population (12.4%; 18/145). Logistic regression showed that the caregiving role influenced SHS, with carers 6.4 times more likely to suffer from SHS than their non-caring counterparts (aOR = 6.400, 95% CI = 3.751–10.919).ConclusionsUnpaid carers in Australia have a significantly higher prevalence of SHS than that in the general population and experience poorer health. The SHSQ-25 is a powerful tool that can be utilised to screen at-risk individuals to predict their risk of chronic disease development, an essential pillar for shifting the paradigm change from reactive medicine to that of predictive, preventive and personalised medicine (PPPM).

Modern approaches to diagnosing and preventing malignization of peptic ulcer in the practice of the general practitioner from the perspective of evidence-based medicine

Background: Peptic ulcer disease (PUD) is a prevalent gastrointestinal disorder that affects millions globally and has the potential to transform into gastric cancer (GC). GC ranks as the fifth most common cancer and is notably lethal. A significant correlation exists between PUD and Helicobacter pylori infection, which disrupts the stomach lining, leading to ulcers that may become malignant if not properly managed. Methods and Materials: This study employed a systematic analysis and meta-analysis approach, gathering data from multiple medical databases including Medscape, Medline, Scopus, Pubmed, and various gastrointestinal guidelines from regions such as Malaysia, Europe, and the United States. The primary methods involved comparing the risk of malignization between gastric and duodenal ulcers, assessing the sensitivity of different diagnostic methods, and determining optimal prevention strategies. Results: The findings indicate that gastric ulcers have a higher risk of malignization compared to duodenal ulcers. Diagnostic methods such as endoscopic biopsy demonstrated higher sensitivity for early malignization detection. Screening programs, especially those targeting H. pylori eradication, significantly reduce the incidence and mortality rates associated with gastric cancer. Conclusion: Early diagnosis and prevention of PUD malignization are vital for improving patient outcomes. Effective strategies include the use of sensitive diagnostic methods and comprehensive screening programs for H. pylori. Lifestyle modifications and vigilant monitoring by healthcare professionals are also crucial in reducing the risk of peptic ulcer malignization and subsequent gastric cancer development.

Immune Changes in “Hepatitis Inflammation and Cancer Transformation Process” from the Perspective of Traditional Chinese Medicine

Immune Changes in “Hepatitis Inflammation and Cancer Transformation Process” from the Perspective of Traditional Chinese Medicine

Nyeruan: Traditional Medicine of the Sasak Tribe in the Perspective of Islam, Medicine and Legislation in Indonesia

This research aims to understand the history of the emergence of the traditional nyeruan healing tradition, how the treatment procession is carried out, how this treatment is in the view of Islam and modern health science. This research lasted for six months using qualitative methods with a phenomenological approach. Determining informants in this study used snowball sampling. The data collection techniques use participant-observation techniques, interviews, documentation, and also triangulation. Data analysis in this research uses the Social Construction theory of Peter L. Berger and Tomas Luckman, and Herbert Blumer's Symbolic Intractionism theory. Based on the research results, it shows that the traditional healing tradition of nyeruan does not violate the laws and regulations in Indonesia, so the practice is still being preserved, especially among the Sasak community

Консенсус експертів Всеукраїнської асоціації кардіологів України і Всеукраїнської асоціації фахівців із серцевої недостатності щодо нового індивідуалізованого підходу до лікування пацієнтів із прогресуючим перебігом хронічної серцевої недостатності

From the perspective of evidence-based medicine, it is recommended that each patient receive all the components of guideline-directed medical therapy (GDMT) that have been proven to have a positive impact on morbidity and mortality. Individualization of treatment is considered a useful tool for achieving GDMT in patients with tolerability issues. Tailoring the treatment approach to the individual characteristics of patients with progressive chronic heart failure (CHF), as well as incorporating innovative strategies targeting different pathways of CHF with vericiguat, can lead to improved prognosis in patients with CHF. The VICTORIA algorithm was developed to identify patients with advanced HF for whom vericiguat may be most effective. The core concept of the VICTORIA algorithm is that most patients with HF are elderly individuals with multiple comorbidities who require pharmacotherapy, leading to a significant increase in the risk of side effects, tolerability issues, and drug interactions. Consequently, the majority of patients are not prescribed drugs at target doses. In such cases, vericiguat will be the drug of choice to either replace or supplement the current treatment.

Research Progress in the Treatment of Subacute Thyroiditis by Traditional Chinese Medicine

Subacute thyroiditis (SAT) is a self-limiting thyroid disease. At present, Western medicine mainly relies on the use of glucocorticoids and a variety of non-steroidal anti-inflammatory drugs in the treatment of SAT. Although the condition has been alleviated to a certain extent, its efficacy still needs to be further improved. Traditional Chinese medicine has unique advantages in the treatment of SAT. From the perspective of traditional Chinese medicine, this paper analyzed the understanding of traditional Chinese medicine in the etiology, pathogenesis and syndrome differentiation of SAT in recent years, and also reviewed the application of traditional Chinese medicine in the treatment of swelling with SAT, providing new insights and strategies for the clinical diagnosis and treatment of SAT.