Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease.

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.

Schizophrenia and disruption of circadian rhythms: An overview of genetic, metabolic and clinical signs.

A molecular clock in the suprachiasmatic nucleus of the anterior hypothalamus, which is entrained by the dark-light cycle and controls the sleep-wake cycle, regulates circadian rhythms. The risk of developing mental disorders, such as schizophrenia, has long been linked to sleep abnormalities. Additionally, a common aspect of mental disorders is sleep disturbance, which has a direct impact on the intensity of the symptoms and the quality of life of the patient. This relationship can be explained by gene alterations such as CLOCK in schizophrenia which are also important components of the physiological circadian rhythm. The function of dopamine and adenosine in circadian rhythm should also be noted, as these hypotheses are considered to be the most popular theories explaining schizophrenia pathogenesis. Therefore, determining the presence of a causal link between the two can be key to identifying new potential targets in schizophrenia therapy, which can open new avenues for clinical research as well as psychiatric care. We review circadian disruption in schizophrenia at the genetic, metabolic, and clinical levels. We summarize data about clock and clock-controlled genes' alterations, neurotransmitter systems' impairments, and association with chronotype in schizophrenia patients. Our findings demonstrate that in schizophrenia either homeostatic or circadian processes of sleep regulation are disturbed. Also, we found an insufficient number of studies aimed at studying the relationship between known biological phenomena of circadian disorders and clinical signs of schizophrenia.

Regulatory enforcement of the marketing of fixed-dose combinations in India: a case study of systemic antibiotics.

BACKGROUND: In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market. METHODS: Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008-2020 using PharmaTrac market dataset. RESULTS: The regulatory initiatives permitted 68 formulations to be given de facto approvals ('No Objection Certificates') outside the statutory regime, banned 46 FDCs and restricted one FDC. Market data show that FDCs as a proportion of total antibiotic sales increased from 32.9 in 2008 to 37.3% in 2020. The total number of antibiotic FDC formulations on the market fell from 574 (2008) to 395 (2020). Formulations with a record of prior central approval increased from 86 (2008) to 94 (2020) and their share of the antibiotic FDC sales increased from 32.0 to 55.3%. In 2020, an additional 23 formulations had been permitted de facto approval, accounting for 10.6% of the antibiotic FDC sales. Even in 2020, most marketed formulations (70.4%, 278/395) were unapproved or banned, and comprised a 15.9% share of the antibiotic FDC sales. The share of NLEM-listed antibiotic FDC sales increased from 21.2 (2008) to 26.7% (2020). CONCLUSION: The initiatives had limited impact. Regulatory enforcement has been slow and weak, with many unapproved, and even banned, FDCs remaining on the market.

Comparative use of ultrasound and radiography for the detection of fractures: a systematic review and narrative synthesis.

Background: Traditionally, X-rays have remained the standard modality for bone fracture diagnosis. However, other diagnostic modalities most notably ultrasound have emerged as a simple, radiation-safe, effective imaging tool to diagnose bone fractures. Despite the advantages, there is a prevalent scarcity of literature recognizing its significance in bone trauma management. This review investigates the effectiveness of ultrasound in the diagnosis of various bone fractures when compared to conventional radiography such as X-rays. Methodology: Electronic databases such as PubMed/Medline, SCOPUS, and Web of Science (WOS) were reviewed for observational studies and review articles from the years 2017-2022 utilizing MESH terminology in a broad term search strategy. The search returned a total of 248 articles. After removal of duplicates, abstract, and full-text screening this systematic review ultimately utilized data from 31 articles. All searches were performed and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology and were conducted during August 2022. In accordance with the guidelines for assessing the quality of included systematic reviews, we used the AMSTAR 2020, Supplemental Digital Content 2, http://links.lww.com/MS9/A241 (A Measurement Tool to Assess Systematic Reviews) tool to evaluate the methodological quality of the included studies. A data extraction form based on the Cochrane Consumers and Communication Review group's extraction template for quality assessment and evidence synthesis was used for data extraction. The information extracted included details such as author information, database, journal details, type of study, etc. Studies included will be classified into long bones, short bones, pneumatic bones, irregular bones, ankle and knee, stress fractures, hip fractures, POCUS, and others. All included studies considered bias and ethical criteria and provided valuable evidence to answer the research question. Results: The search returned a total of 248 articles, with 192 articles remaining after the removal of duplicates. Primary screening of the title and abstract articles from the database search and additional sources identified 68 relevant articles for full-text screening. This systematic review ultimately used data from 33 articles of the remaining articles we included all of them because they had more than 70% certainty, using the STROBE tool for observational articles, narrative reviews with the ENTREQ guide, and systematic reviews and meta-analyses with the PRISMA guide; however, two articles were excluded at the eligibility stage because of risk of bias. Conclusion: This systematic review provides insightful evidence on safety and effectiveness of ultrasound in diagnosing fractures when compared to the conventional imaging modalities such as X-rays. This shall promote further large-scale, multi-centre research that can eventually guide clinic practice in diagnosing and managing various bone fractures.

Inequitable access to Ebola vaccines and the resurgence of Ebola in Africa: A state of arts review.

The Ebola virus, a member of the filoviridae family of viruses, is responsible for causing Ebola Virus Disease (EVD) with a case fatality rate as high as 50%. The largest EVD outbreak was recorded in West Africa from March 2013 to June 2016, leading to over 28 000 cases and 11 000 deaths. It affected several countries, including Nigeria, Senegal, Guinea, Liberia, and Sierra Leone. Until then, EVD was predominantly reported in remote villages in central and west Africa close to tropical rainforests. Human mobility, behavioral and cultural norms, the use of bushmeat, burial customs, preference for traditional remedies and treatments, and resistance to health interventions are just a few of the social factors that considerably aid and amplify the risk of transmission. The scale and persistence of recent ebola outbreaks, as well as the risk of widespread global transmission and its ability for bioterrorism, have led to a rethinking of public health strategies to curb the disease, such as the expedition of Ebola vaccine production. However, as vaccine production lags in the subcontinent, among other challenges, the risk of another ebola outbreak is likely and feared by public health authorities in the region. This review describes the inequality of vaccine production in Africa and the resurgence of EVD, emphasizing the significance of health equality.

Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review.

The circadian rhythm (CR) is a fundamental biological process regulated by the Earth's rotation and solar cycles. It plays a critical role in various bodily functions, and its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, and immune response. Immune mediators, cycle proteins, and hormones exhibit circadian oscillations, supporting optimal immune function and defence against pathogens. Sleep deprivation and disruptions challenge the regulatory mechanisms, making immune responses vulnerable. Altered CR pathways have been implicated in diseases such as diabetes, neurological conditions, and systemic autoimmune diseases (SADs). SADs involve abnormal immune responses to self-antigens, with genetic and environmental factors disrupting self-tolerance and contributing to conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Inflammatory Myositis. Dysregulated CR may lead to increased production of pro-inflammatory cytokines, contributing to the systemic responses observed in SADs. Sleep disturbances significantly impact the quality of life of patients with SADs; however, they are often overlooked. The relationship between sleep and autoimmune conditions, whether causal or consequential to CR dysregulation, remains unclear. Chrono-immunology investigates the role of CR in immunity, offering potential for targeted therapies in autoimmune conditions. This paper provides an overview of the connections between sleep and autoimmune conditions, highlighting the importance of recognizing sleep disturbances in SADs and the need for further research into the complex relationship between the CR and autoimmune diseases.

Anti-TNFα induced lupus due to infliximab therapy in a patient with concurrent Crohn's disease.

Anti-TNFα inhibitor-induced Lupus (ATIL) is a rare syndrome characterized by a wide array of symptoms ranging from skin manifestations to organ-specific symptoms such as pleural effusions, pericardial effusions, hepatotoxicity, etc. Infliximab is implicated in most cases, and ATIL usually develops between the first month and 4 years of infliximab application. In this report, we present an interesting case of ATIL that developed rather gradually upon anti-TNFa used to treat Crohn's disease. The patient presented with oral ulcers, photosensitive rash, diffuse alopecia, inflammation of the hands, and pleuritic chest pain. Comprehensive serological testing revealed the presence of antinuclear antibodies and anti-DNA antibodies. During the evaluation, the patient developed headaches, followed by a brain MRI that suggested nonspecific white matter lesions. Given the chronic development of symptoms, invasive examinations such as an arteriogram were performed to exclude CNS vasculitis, which showed no evidence of the vasculitis. Therefore, in the absence of any clear radiographical signs of vasculitis, patients should not undergo invasive studies, including an angiogram. The CNS angiogram can be associated with several side effects, including damage to the blood vessel, bruising or bleeding at the puncture site, and infection, which can further aggravate ATIL. Although rare, ATIL should always be considered while evaluating a patient with suggestive symptoms on infliximab therapy. Further research on identifying the variety of clinical presentations of ATIL and the underlying pathophysiology can help improve health policy and clinical practice by reducing unnecessary examination and allowing early management and better-quality care.

The African cancer burden: what is the potential role of modern oncology innovation in reducing the continent's rapidly rising mortality?

With increasing prevalence and an expected rise in disease burden, cancer is a cause of concern for African healthcare. The cancer burden in Africa is expected to rise to 2.1 million new cases per year and 1.4 million deaths annually by the year 2040. Even though efforts are being made to improve the standard of oncology service delivery in Africa, the current state of cancer care is not yet on par with the rise in the cancer burden. Cutting-edge technologies and innovations are being developed across the globe to augment the battle against cancer; however, many of them are beyond the reach of African countries. Modern oncology innovations targeted to ward Africa would be promising to address the high cancer mortality rates. The innovations should be cost-effective and widely accessible to tackle the rapidly rising mortality rate on the African continent. Though it may seem promising, a multidisciplinary approach is required to overcome the challenges associated with the development and implementation of modern oncology innovations in Africa.

Prospects of evolution-based artificial intelligence models in genome-wide studies to stratify genetic risk variants in nonalcoholic fatty liver disease.

The emergence of genome-wide association studies (GWAS) has identified genetic traits and polymorphisms that are associated with the progression of nonalcoholic fatty liver disease (NAFLD). Phospholipase domain-containing 3 and transmembrane 6 superfamily member 2 are genes commonly associated with NAFLD phenotypes. However, there are fewer studies and replicability in lesser-known genes such as LYPLAL1 and glucokinase regulator (GCKR). With the advent of artificial intelligence (AI) in clinical genetics, studies have utilized AI algorithms to identify phenotypes through electronic health records and utilize convolution neural networks to improve the accuracy of variant identification, predict the deleterious effects of variants, and conduct phenotype-to-genotype mapping. Natural language processing (NLP) and machine-learning (ML) algorithms are popular tools in GWAS studies and connect electronic health record phenotypes to genetic diagnoses using a combination of international classification disease (ICD)-based approaches. However, there are still limitations to machine-learning - and NLP-based models, such as the lack of replicability in larger cohorts and underpowered sample sizes, which prevent the accurate prediction of genetic variants that may increase the risk of NAFLD and its progression to advanced-stage liver fibrosis. This may be largely due to the lack of understanding of the clinical consequence in the majority of pathogenic variants. Though the concept of evolution-based AI models and evolutionary algorithms is relatively new, combining current international classification disease -based NLP models with phylogenetic and evolutionary data can improve prediction accuracy and create valuable connections between variants and their pathogenicity in NAFLD. Such developments can improve risk stratification within clinical genetics and research while overcoming limitations in GWAS studies that prevent community-wide interpretations.

Exploring the effects of adiponectin and leptin in correlating obesity with cognitive decline: a systematic review.

Obesity and cognitive decline including dementia and Alzheimer's Disease (AD) affect millions worldwide. Several studies have shown that obese individuals suffer from cognitive decline. Here, we suggest that adiponectin and leptin, protein hormones secreted by white adipose tissue explain the relationship between obesity and cognitive decline. We systematically searched PubMed and World Health Organization (WHO) websites with the keywords obesity and dementia and compiled literature that explains how adiponectin and leptin impact obesity and cognitive decline. Full-text, free-access articles on PubMed published after 2009 have been included. Whereas articles published before 2009, books, and reports were excluded. We concentrated on mechanisms via which adiponectin and leptin affect energy expenditure, fatty acid catabolism, satiety, hunger, Body Mass Index (BMI), neurogenesis, and brain structures that lead to the development of cognitive dysfunction. Moreover, we hypothesized that adiponectin and leptin hormones explain how obesity and dementia are connected. After compiling the research studies, we summarized that adiponectin and leptin negatively correlate to BMI. Adiponectin arbitrates energy expenditure and fatty acid catabolism to prevent obesity. In the presence of adiponectin, hippocampal cells proliferate, whereas neurogenesis is reduced in its absence. However, leptin prevents obesity by promoting satiety, reducing hunger, and increasing insulin sensitivity. It also has neuroprotective effects thus reducing the risk of developing cognitive decline. So, physical exercise, diet alteration, weight reduction, adiponectin, and leptin supplementation should be carried out to protect against obesity-induced cognitive decline. Therefore, further research studies should be done in this area.

Concerns over cardiovascular manifestations associated with monkeypox immunization: a literature review.

Following the recent surge in monkeypox cases worldwide, vaccines have gained popularity due to their protective role against the disease in the absence of specific pharmacological therapies for the disease. This article explores the possible challenges associated with the treatment and prevention of monkeypox with special emphasis on cardiovascular concerns relating to vaccines, warranting further investigation and research. Methods: Multiple electronic databases from inception till October 2022 were searched to find articles reporting the cardiovascular adverse events associated with monkeypox immunization. Results: Smallpox vaccines ACAM2000, JYNNEOS, and modified vaccinia Ankara have been used for monkeypox. ACAM2000 has been reported to have major cardiovascular adverse events such as myocarditis, dilated cardiomyopathy, and heart failure. Whereas JYNNEOS and modified vaccinia Ankara are associated with minor cardiovascular adverse events such as tachycardia, palpitation, electrocardiogram changes such as T wave inversion, and ST elevation. Conclusions: Despite having cardiovascular issues with the existing vaccines, clinicians and public health experts should measure the risk benefit aspect of smallpox vaccines to decide whether to go for mass immunization or not. Based on the lessons learned from the COVID-19 pandemic, immunization will be a better strategy to halt the monkeypox spread throughout the globe. However, further research is needed to determine the exact incidence and susceptibility to develop cardiovascular complications among monkeypox immunized individuals.

An interesting case of pulmonary hypertension in nephrotic syndrome due to amphetamine use for attention-deficit hyperactivity disorder.

Pulmonary arterial hypertension (PAH) was first associated with stimulants use in the 1960s during an outbreak of amphetamine-like appetite suppressants (anorexigens). To date, various drugs and toxins have been correlated with PAH. Diagnosing PAH in nephrotic syndrome has always remained a challenge due to the overlap of signs and symptoms in clinical presentation between the two entities. Case presentation: In this report, the authors present an interesting case of a 43-year-old male, diagnosed with nephrotic syndrome secondary to minimal change disease, as well as currently presenting with PAH secondary to amphetamine. Clinical discussion and conclusion: Patients with nephrotic syndrome and end-stage renal disease should be regularly followed up and evaluated for comorbidities, complications, as well as adverse events from pharmacological intervention. In patients with end-stage renal disease hypertension control is key, stimulant use can precipitate poor blood pressure control especially in pulmonary arteries resulting in PAH. PAH can result in right ventricular dysfunction and heart failure that can further exacerbate renal dysfunction and vice-versa in a vicious cycle, deteriorating patient condition and quality of life.

Exploring the possible therapeutic role of influenza vaccine in chronic kidney disease patients.

Chronic kidney disease (CKD) is an irreversible change in kidney function and structure with a prevalence of about 9.1% worldwide. Toxins and heavy metal exposure, as well as hypertension and diabetes mellitus, are common causes of CKD. Despite extensive therapeutic options such as renal replacement therapy and renal transplants, most changes in kidney function remain irreversible, causing lifelong morbidity and affecting the quality of life of patients. Increased susceptibility to infections as well as serious complications from influenza, is a major cause of concern in nephrological care. Therefore, it is imperative to consider the protective role of influenza vaccination against seasonal influenza, which can worsen preexisting kidney dysfunction. This commentary explores a possible relationship between the influenza vaccine and patient outcomes in CKD in terms of complications, hospitalization, and possibly prognostic improvements in patient outcomes from CKD.

A critical appraisal on the treatment of acute appendicitis in pediatric population during the COVID-19 pandemic.

Acute appendicitis is one of the most common causes of abdominal pain in children. During the coronavirus disease 2019 (COVID-19) pandemic, a delay in presentation to the emergency department and a higher rate of complicated appendicitis were observed. Traditionally, operative management (laparoscopic or open appendectomy) was thought to be the best treatment strategy for acute appendicitis. However, nonoperative management with antibiotics has gained popularity in managing pediatric appendicitis during the COVID-19 era. The pandemic has posed significant challenges in the management of acute appendicitis. Cancellation of elective appendectomies, delay in seeking care due to fear of contracting COVID-19 infection, and impact of COVID-19 infection in the pediatric population have resulted in higher rates of complications. Furthermore, multiple studies have reported multisystem inflammatory syndrome in children mimicking acute appendicitis, subjecting patients to unnecessary surgery. Therefore, it is imperative to update the treatment guidelines for the management of acute appendicitis in the pediatric population during and after COVID-19 times.

Antibiotic prescriptions for oral diseases in India: evidence from national prescription data.

INTRODUCTION: The key objective of this research was to describe the prescription rate of various antibiotics for dental problems in India and to study the relevance of the prescriptions by analysing antibiotic types associated with different dental diagnoses, using a large-scale nationally representative dataset. METHODS: We used a 12-month period (May 2015 to April 2016) medical audit dataset from IQVIA (formerly IMS Health). We coded the dental diagnosis provided in the medical audit data to the International Statistical Classification of Diseases and Related Health Problems (ICD-11) and the prescribed antibiotics for the diagnosis to the Anatomic Therapeutic Chemical (ATC) -2020 classification of the World Health Organization. The primary outcome measure was the medicine prescription rate per 1,000 persons per year (PRPY1000). RESULTS: Our main findings were-403 prescriptions per 1,000 persons per year in the year 2015 -2016 for all dental ailments. Across all ATC level 1 classification, 'Diseases of hard tissues' made up the majority of the prescriptions. 'Beta-lactam', 'Penicillin,' and 'Cephalosporins' were the most commonly prescribed antibiotics for dental diagnoses followed by 'Macrolides' and 'Quinolones'. 'Dental caries', 'Discoloration of tooth', and 'Toothache' were the most common reasons for 'Beta-Lactams' and 'Penicillin' prescriptions. CONCLUSION: To conclude our study reports first ever country (India) level estimates of antibiotic prescription by antibiotic classes, age groups, and ICD-11 classification for dental ailments.

Effectiveness of artificial intelligence-assisted colonoscopy in early diagnosis of colorectal cancer: a systematic review.

INTRODUCTION: As artificial intelligence (AI)-assisted diagnosis gained immense popularity, it is imperative to consider its utility and efficiency in the early diagnosis of colorectal cancer (CRC), responsible for over 1.8 million cases and 881 000 deaths globally, as reported in 2018. Improved adenoma detection rate, as well as better characterizations of polyps, are significant advantages of AI-assisted colonoscopy (AIC). This systematic review (SR) investigates the effectiveness of AIC in the early diagnosis of CRC as compared to conventional colonoscopy. MATERIALS AND METHODS: Electronic databases such as PubMed/Medline, SCOPUS, and Web of Science were reviewed for original studies (randomized controlled trials, observational studies), SRs, and meta-analysis between 2017 and 2022 utilizing Medical Subject Headings terminology in a broad search strategy. All searches were performed and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and were conducted from November 2022. A data extraction form based on the Cochrane Consumers and Communication Review group's extraction template for quality assessment and evidence synthesis was used for data extraction. All included studies considered for bias and ethical criteria and provided valuable evidence to answer the research question. RESULTS: The database search identified 218 studies, including 87 from PubMed, 60 from SCOPUS, and 71 from Web of Science databases. The retrieved studies from the databases were imported to Rayyan software and a duplicate article check was performed, all duplicate articles were removed after careful evaluation of the data. The abstract and full-text screening was performed in accordance with the following eligibility criteria: Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for observational studies; Preferred Reporting Items for Systematic Reviews and Meta-Analysis for review articles, ENTREQ for narrative studies; and modified JADAD for randomized controlled trials. This yielded 15 studies that met the requirements for this SR and were finally included in the review. CONCLUSION: AIC is a safe, highly effective screening tool that can increase the detection rate of adenomas, and polyps resulting in an early diagnosis of CRC in adults when compared to conventional colonoscopy. The results of this SR prompt further large-scale research to investigate the effectiveness in accordance with sex, race, and socioeconomic status, as well as its influence on prognosis and survival rate.