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Roberto C Cerrud-Rodriguez,1 Syed Muhammad Ibrahim Rashid,1 Karlo A Wiley,1 Maday Gonzalez,1 Valeriia A Kosmacheva,1 Isabella Castillero-Norato,2 Cornelia Rivera,1 Pedro Villablanca,3 Jose Wiley1 1Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA; 2Facultad de Medicina, Universidad de Panamá, Campus Octavio Méndez Pereira, Panama City, Republic of Panama; 3Department of Medicine, Division of Cardiology, Henry Ford Hospital, Detroit, MI, USACorrespondence: Roberto C Cerrud-RodriguezMontefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY, 10467, USATel +1 718-920-7929Email robertocerrud@gmail.comBackground: Complete revascularization (CR) of hemodynamically stable STEMI improves outcomes when compared to culprit-only PCI. However, the optimal timing for CR (CR during index PCI [iCR] versus staged PCI [sCR]) is unknown. sCR is defined as revascularization of non-culprit lesions not done during the index procedure (mean 31.5± 24.6 days after STEMI). Our goal was to determine whether iCR was the superior strategy when compared to sCR.Methods: A systematic review of Medline, Cochrane, and Embase was performed for RCTs reporting outcomes of stable STEMI patients who had undergone CR. Only RCTs with a clearly defined timing of CR, for the classification into iCR and sCR, and a follow-up of at least 12 months were included. Seven RCTs comprising 6647 patients (mean age:62.9± 1.4 years, male sex:79.4%) met these criteria and were included.Results: After a mean follow-up of 25.1± 9.4 months, iCR was associated with a significant reduction in cardiovascular mortality (risk ratio [RR] 0.48, 95% confidence interval [CI] 0.26– 0.90, p=0.02, relative risk reduction [RRR] 52%) and non-fatal reinfarctions (RR 0.42, 95% CI 0.25– 0.70, p=0.001, RRR: 58%). sCR showed a significant reduction in non-fatal reinfarctions only (RR 0.68, 95% CI 0.54– 0.85, p=0.0008, RRR: 32%). There was no difference in the safety outcome of contrast-induced nephropathy between groups.Conclusion: iCR of stable STEMI patients is associated with a significant reduction in cardiovascular death and a trend towards reduction in all-cause mortality. These benefits are not seen in sCR. Both strategies are associated with a reduction in non-fatal reinfarctions.Keywords: ST-segment elevation myocardial infarction, STEMI, percutaneous coronary intervention, PCI, staged revascularization, complete revascularization.

This study is dedicated to a comprehensive exploration aimed at advancing our understanding of stability within dynamic systems. The focus is particularly on the intricate domain of delayed systems characterized by gapped gamma distributions. The primary objective of this investigation revolves around evaluating the pragmatic application and efficacy of Jensen's integral inequality in combination with the powerful analytical tools provided by Linear Matrix Inequalities (LMIs). This evaluation is crucial for rigorously assessing exponential stability within these complex systems. Central to our investigative framework is the strategic deployment of augmented Lyapunov functions. These functions play a crucial role in unraveling the intricate stability properties of delayed systems featuring gapped gamma distributions, allowing for a nuanced examination of their inherent stability characteristics under various conditions. The mathematical formulation crafted in this exploration intricately captures the interplay between the distinctive attributes of the gapped gamma distribution and the complex dynamics of the loop traffic flow model within the overarching delayed system. This interconnection serves as the fundamental basis for the stability analysis, providing insights into the interdependence of these key elements. The noteworthy contribution of this study lies in the systematic construction of a robust analytical framework explicitly tailored for stability assessment. A comprehensive investigation is undertaken to elucidate critical aspects, including the convergence rate and the attainment of asymptotic stability within the considered delayed system. Additionally, a dedicated simulation section, focusing on Vehicle Active Suspension Control, has been incorporated to further validate and showcase the applicability of the proposed methodology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author.)

Tumors have posed significant threats to human health for over 250 years, emerging as the foremost cause of death. While chemotherapeutic drugs are effective in treating tumors, their side effects can sometimes be challenging to manage during therapy. Nonetheless, there is growing interest in exploring natural compounds as alternatives, which potentially achieve therapeutic outcomes comparable to conventional chemotherapeutics with fewer adverse effects. Paeoniflorin (PF), a monoterpene glycoside derived from the root of Paeonia lactiflora , has garnered significant attention lately due to its promising anti-cancer properties. This review offers an updated outline of the molecular mechanisms underlying PF's anti-tumor function, with a focus on its modulation of various signaling pathways. PF exerts its anti-tumor activity by regulating crucial cellular processes including apoptosis, angiogenesis, proliferation, and metastasis. We explored the multifaceted impact of PF while modulating through signaling pathways, encompassing nuclear factor kappa B, NOTCH, caspase cascade, transforming growth factor-β, NEDD4, P53/14-3-3, STAT 3, MAPK, MMP-9, and SKP2 signaling pathways, highlighting its versatility in targeting diverse malignancies. Furthermore, we discuss future research directions aimed at exploring innovative and targeted cancer therapies facilitated by PF., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Journal of Biological Methods, All rights reserved.)

The central nervous system (CNS) is widely recognized as the only organ system without lymphatic capillaries to promote the removal of interstitial metabolic by-products. Thus, the newly identified glymphatic system which provides a pseudolymphatic activity in the nervous system has been focus of latest research in neurosciences. Also, findings reported that, sleep stimulates the elimination actions of glymphatic system and is linked to normal brain homeostatis. The CNS is cleared of potentially hazardous compounds via the glymphatic system, particularly during sleep. Any age-related alterations in brain functioning and pathophysiology of various neurodegenerative illnesses indicates the disturbance of the brain's glymphatic system. In this context, β-amyloid as well as tau leaves the CNS through the glymphatic system, it's functioning and CSF discharge markedly altered in elderly brains as per many findings. Thus, glymphatic failure may have a potential mechanism which may be therapeutically targetable in several neurodegenerative and age-associated cognitive diseases. Therefore, there is an urge to focus for more research into the connection among glymphatic system and several potential brain related diseases. Here, in our current review paper, we reviewed current research on the glymphatic system's involvement in a number of prevalent neurodegenerative and neuropsychiatric diseases and, we also discussed several therapeutic approaches, diet and life style modifications which might be used to acquire a more thorough performance and purpose of the glymphatic system to decipher novel prospects for clinical applicability for the management of these diseases., (© 2024 John Wiley & Sons Ltd.)

Colorectal cancer (CRC) is the third highest frequent malignancy and ultimate critical source of cancer-associated mortality around the world. Regardless of latest advances in molecular and surgical targeted medicines that have increased remedial effects in CRC patients, the 5-year mortality rate for CRC patients remains dismally low. Evidence suggests that microRNAs (miRNAs) execute an essential part in the development and spread of CRC. The miRNAs are a type of short non-coding RNA that exhibited to control the appearance of tumor suppressor genes and oncogenes. miRNA expression profiling is already being utilized in clinical practice as analytical and prognostic biomarkers to evaluate cancer patients' tumor genesis, advancement, and counteraction to drugs. By modulating their target genes, dysregulated miRNAs are linked to malignant characteristics (e.g., improved proliferative and invasive capabilities, cell cycle aberration, evasion of apoptosis, and promotion of angiogenesis). This review presents an updated summary of circulatory miRNAs, tumor-suppressive and oncogenic miRNAs, and the potential reasons for dysregulated miRNAs in CRC. Further we will explore the critical role of miRNAs in CRC drug resistance., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Clinical decision support systems have been widely deployed to guide healthcare decisions on patient diagnosis, treatment choices, and patient management through evidence-based recommendations. These recommendations are typically derived from clinical practice guidelines created by clinical specialties or healthcare organizations. Although there have been many different technical approaches to encoding guideline recommendations into decision support systems, much of the previous work has not focused on enabling system generated recommendations through the formalization of changes in a guideline, the provenance of a recommendation, and applicability of the evidence. Prior work indicates that healthcare providers may not find that guideline-derived recommendations always meet their needs for reasons such as lack of relevance, transparency, time pressure, and applicability to their clinical practice., Results: We introduce several semantic techniques that model diseases based on clinical practice guidelines, provenance of the guidelines, and the study cohorts they are based on to enhance the capabilities of clinical decision support systems. We have explored ways to enable clinical decision support systems with semantic technologies that can represent and link to details in related items from the scientific literature and quickly adapt to changing information from the guidelines, identifying gaps, and supporting personalized explanations. Previous semantics-driven clinical decision systems have limited support in all these aspects, and we present the ontologies and semantic web based software tools in three distinct areas that are unified using a standard set of ontologies and a custom-built knowledge graph framework: (i) guideline modeling to characterize diseases, (ii) guideline provenance to attach evidence to treatment decisions from authoritative sources, and (iii) study cohort modeling to identify relevant research publications for complicated patients., Conclusions: We have enhanced existing, evidence-based knowledge by developing ontologies and software that enables clinicians to conveniently access updates to and provenance of guidelines, as well as gather additional information from research studies applicable to their patients' unique circumstances. Our software solutions leverage many well-used existing biomedical ontologies and build upon decades of knowledge representation and reasoning work, leading to explainable results., (© 2023. The Author(s).)

Medical research has been revolutionized after the publication of the full human genome. This was the major landmark that paved the way for understanding the biological functions of different macro and micro molecules. With the advent of different high-throughput technologies, biomedical research was further revolutionized. These technologies constitute genomics, transcriptomics, proteomics, metabolomics, etc. Collectively, these high-throughputs are referred to as multi-omics technologies. In the biomedical field, these omics technologies act as efficient and effective tools for disease diagnosis, management, monitoring, treatment and discovery of certain novel disease biomarkers. Genotyping arrays and other transcriptomic studies have helped us to elucidate the gene expression patterns in different biological states, i.e. healthy and diseased states. Further omics technologies such as proteomics and metabolomics have an important role in predicting the role of different biological molecules in an organism. It is because of these high throughput omics technologies that we have been able to fully understand the role of different genes, proteins, metabolites and biological pathways in a diseased condition. To understand a complex biological process, it is important to apply an integrative approach that analyses the multi-omics data in order to highlight the possible interrelationships of the involved biomolecules and their functions. Furthermore, these omics technologies offer an important opportunity to understand the information that underlies disease. In the current review, we will discuss the importance of omics technologies as promising tools to understand the role of different biomolecules in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This decade has seen the beginning of ground-breaking conceptual shifts in the research of Alzheimer's disease (AD), which acknowledges risk elements and the evolving wide spectrum of complicated underlying pathophysiology among the range of diverse neurodegenerative diseases. Significant improvements in diagnosis, treatments, and mitigation of AD are likely to result from the development and application of a comprehensive approach to precision medicine (PM), as is the case with several other diseases. This strategy will probably be based on the achievements made in more sophisticated research areas, including cancer. PM will require the direct integration of neurology, neuroscience, and psychiatry into a paradigm of the healthcare field that turns away from the isolated method. PM is biomarker-guided treatment at a systems level that incorporates findings of the thorough pathophysiology of neurodegenerative disorders as well as methodological developments. Comprehensive examination and categorization of interrelated and convergent disease processes, an explanation of the genomic and epigenetic drivers, a description of the spatial and temporal paths of natural history, biological markers, and risk markers, as well as aspects about the regulation, and the ethical, governmental, and sociocultural repercussions of findings at a subclinical level all require clarification and realistic execution. Advances toward a comprehensive systems-based approach to PM may finally usher in a new era of scientific and technical achievement that will help to end the complications of AD.

Rheumatoid arthritis (RA) is an immunocompromised disorder characterized by a marked increase in the synthesis of inflammatory molecules that stimulates the destruction of bones and cartilage. The conventional treatment modalities for RA are associated with adverse side effects and lack sensitivity, suggesting an immediate demand for alternate beneficial therapeutic remedies. The current study sought to understand more about zerumbone's anti-inflammatory properties in diagnosing collagen-induced arthritis (CIA) in experimental animals. The current study observed that zerumbone reduced clinical severity in CIA-induced animals compared to healthy animals. Zerumbone administration significantly decreased ( p < 0.001) the concentration of SOD, CAT, GR, and GSH in treatment groups. Zerumbone administration drove down significantly ( p < 0.001) the concentration of inflammatory cytokine molecules. Zerumbone was effective in bringing significant changes in levels of MPO, NO, LDH, MMP-8, and ELA. The therapeutic potential of zerumbone was found to be associated with reduced joint destruction and restored normal histology in the cartilage and tissue. Adsorption, distribution, metabolism, excretion, and toxicity studies were used to determine the druglike properties of zerumbone. ProTox-II studies revealed that zerumbone did not possess toxic properties like hepatotoxicity, immunotoxicity, carcinogenicity, mutagenicity, and cytotoxicity. Therefore, the present study evaluated the therapeutic properties of zerumbone in CIA animal models., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD), Parkinson disease (PD), and Huntington disease (HD) represent a major socio-economic challenge in view of their high prevalence yet poor treatment outcomes affecting quality of life. The major challenge in drug development for these NDs is insufficient clarity about the mechanisms involved in pathogenesis and pathophysiology. Mitochondrial dysfunction, oxidative stress and inflammation are common pathways that are linked to neuronal abnormalities and initiation of these diseases. Thus, elucidating the shared initial molecular and cellular mechanisms is crucial for recognizing novel remedial targets, and developing therapeutics to impede or stop disease progression. In this context, use of multifunctional compounds at early stages of disease development unclogs new avenues as it acts on act on multiple targets in comparison to single target concept. In this review, we summarize overview of the major findings and advancements in recent years focusing on shared mechanisms for better understanding might become beneficial in searching more potent pharmacological interventions thereby reducing the onset or severity of various NDs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bovine milk is an important food component in the human diet due to its nutrient-rich metabolites. However, bovine subclinical mastitis alters the composition and quality of milk. In present study, California mastitis testing, somatic cell count, pH, and electrical conductivity were used as confirmatory tests to detect subclinical mastitis. The primary goal was to study metabolome and identify major pathogens in cows with subclinical mastitis. In this study, 29 metabolites were detected in milk using gas chromatography−mass spectrometry. Volatile acidic compounds, such as hexanoic acid, hexadecanoic acid, lauric acid, octanoic acid, n-decanoic acid, tricosanoic acid, tetradecanoic acid, and hypogeic acid were found in milk samples, and these impart good flavor to the milk. Metaboanalyst tool was used for metabolic pathway analysis and principal component estimation. In this study, EC and pH values in milk were significantly increased (p < 0.0001), whereas fat (p < 0.04) and protein (p < 0.0002) significantly decreased in animals with subclinical mastitis in comparison to healthy animals. Staphylococcus aureus was the predominant pathogen found (n = 54), followed by Escherichia coli (n = 30). Furthermore, antibiotic sensitivity revealed that Staphylococcus aureus was more sensitive to gentamicin (79.6%), whereas Escherichia coli showed more sensitivity to doxycycline hydrochloride (80%)., Competing Interests: The authors declare no conflicts of interest.

The objective of the study was to evaluate the sustainability of the grazing and feeding resources of the sheep in Kashmir, India. The study was conducted in the Ganderbal District of Kashmir to evaluate sustainability, along with the scenario of grazing pattern and feeding system of the sheep during the non-migratory period. The district was divided into three production zones based on altitude, i.e., zone I (high altitude), zone II (medium altitude), and zone III (low altitude). A total of 360 sheep farmers were interviewed from the three zones that consist of 9 blocks, with 40 sheep farmers interviewed from each block. Majority of the sheep farmers (75.00%) follow a semi-migratory type of production system, use forest, and low-mountain areas for grazing purposes (48.88%) and were having medium to high availability of grazing lands. The main feeding source available to majority of the sheep farmers (60.00%) was found to be crop residues and fodder grasses, with local markets (60.00%) and fellow farmers (71.11%) being the main source of procuring concentrates and fodders. Hybrid entropy and TOPSIS method were used for the evaluation of sustainability of grazing and feeding system in the area. The most influencing factors for sustainability of grazing pattern and feeding source were found to be production system followed and the major feed sources available respectively. Most of the variables included in the grazing system were ideally best in zone I and of feeding system were found to be ideally best in zone III. There is a need for improvement in the parameters of the grazing pattern in zone III, i.e., in low-altitude areas or planes where grazing lands are shrinking at an alarming rate. The parameters under the feeding system need due consideration in zone I, i.e., in the high altitudes where the socio-economic situation of the people is comparatively poor than the other two zones., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To compare the effects of neuromuscular training (NMT) to a quadriceps strength training (QT) program on co-contraction index (CCI) of knee muscles in patients with knee osteoarthritis (OA)., Methods: Sixty-six knee OA patients with varus malalignment were recruited from the physiotherapy outpatient department of the university. After baseline measurements, they were randomly assigned into two groups: NMT (n = 33) and QT (n = 33). Patients in NMT group received neuromuscular exercises whereas QT group received conventional strengthening exercises for a period of 12 weeks, three times per week. Electromyographic (EMG) activity of quadriceps, hamstring and gastrocnemius muscle was evaluated during treadmill walking before and after 12 weeks of intervention period and CCI of medial quadriceps-medial hamstring (med QH), lateral quadriceps-lateral hamstring (lat QH), medial quadriceps-medial gastrocnemius (med QG) and, lateral quadriceps and lateral gastrocnemius (lat QG) was calculated., Results: There was a significantly greater reduction in CCI of med QH (p = 0.02) and lat QH (p = 0.01) in the NMT group than the QT group. Whereas both NMT and QT led to statistically similar reductions in CCI of med QG (p = 0.08) and lat QG (p = 0.66)., Conclusion: Findings of this study suggest that NMT led to a greater reduction in CCI of knee muscles than QT which indicates that enhanced sensori-motor control attained by NMT could reduce knee loading in knee OA patients with varus malalignment., (© 2022. The Author(s).)

Purpose:  The current investigation was carried out to evaluate the efficacy of myricetin in ethanol-induced liver toxicity in Wistar rats.  Research Design:  Twenty-four rats were randomly divided into four groups with six animals per group. Group-I animals were administered with vehicle (distilled water), Group II, III, and IV were treated orally with sequential (per week) increase in the dose of ethanol (5, 8, 10, and 12 g/kg b wt per week in each group) for 28 days. Myricetin was treated orally to Group-III and IV animals at the respective doses of 25 mg/kg b wt. and 50 mg/kg b wt.  Results:  Our results showed that myricetin prevented hepatotoxicity by modulating the production of free radicals, ethanol metabolizing enzymes, and inflammatory markers in vivo. Myricetin also helped maintain lipid membrane integrity, oxidant-antioxidant status, and histoarchitecture. Ethanol administration caused elevation in XO, ADH, and CYP2E1 in hepatic tissue, which significantly normalized with myricetin administration. After ethanol administration, there was a steep increase in the hepatotoxicity biomarkers, including ALT, MDA, and AST. The level of cytotoxicity marker LDH also increased after ethanol administration; myricetin administration decreased the level of all these markers. Moreover, myricetin treatment also reduced ethanol-induced inflammatory markers such as NF-κB and IL-6.  Conclusion:  Findings from the current study demonstrate that myricetin administration prevents alcohol-induced hepatic injury by influencing the metabolism of ethanol, inhibiting oxidative stress, maintaining lipid profile, and suppressing inflammatory markers.

Cancer has been generally related to the possession of numerous mutations which interrupt important signaling pathways. Nevertheless, deregulated immunological signaling is considered as one of the key factors associated with the development and progression of cancer. The signaling pathways operate as modular network with different components interacting in a switch-like fashion with two proteins interplaying between each other leading to direct or indirect inhibition or stimulation of down-stream factors. Genetic, epigenetic, and transcriptomic alterations maintain the pathological conduit of different signaling pathways via affecting diverse mechanisms including cell destiny. At present, immunotherapy is one of the best therapies opted for cancer treatment. The cancer immunotherapy strategy includes harnessing the specificity and killing mechanisms of the immunological system to target and eradicate malignant cells. Targeted therapies utilizing several little molecules including Galunisertib, Astragaloside-IV, Melatonin, and Jervine capable of regulating key signaling pathways can effectively help in the management of different carcinomas., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Coronavirus Disease 2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations, and pathogenesis. Nearly 0.4 million mutations have been identified so far among the ∼60,000 SARS-CoV-2 genomic sequences. In this study, we compared a total of 371 SARS-CoV-2 published whole genomes reported from different parts of Bangladesh with 467 sequences reported globally to understand the origin of viruses, possible patterns of mutations, and availability of unique mutations. Phylogenetic analyses indicated that SARS-CoV-2 viruses might have transmitted through infected travelers from European countries, and the GR clade was found as predominant in Bangladesh. Our analyses revealed 4604 mutations at the RNA level including 2862 missense mutations, 1192 synonymous mutations, 25 insertions and deletions and 525 other types of mutation. In line with the global trend, D614G mutation in spike glycoprotein was predominantly high (98 %) in Bangladeshi isolates. Interestingly, we found the average number of mutations in ORF1ab, S, ORF3a, M, and N were significantly higher (p < 0.001) for sequences containing the G614 variant compared to those having D614. Previously reported frequent mutations, such as R203K, D614G, G204R, P4715L and I300F at protein levels were also prevalent in Bangladeshi isolates. Additionally, 34 unique amino acid changes were revealed and categorized as originating from different cities. These analyses may increase our understanding of variations in SARS-CoV-2 virus genomes, circulating in Bangladesh and elsewhere., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epilepsy is an intricate neurological disease where the neurons are severely affected, leading to the mortality of millions worldwide. Status epilepticus (SE), induced by lithium chloride (LiCl) and pilocarpine, is the most accepted model for epilepsy. The current work aims to unravel the mechanisms underlying the anti-epileptic efficacy of zingerone (an active ingredient of ginger), which has beneficial pharmacological activities on seizure-induced behavioral, histological, neurochemical, and molecular patterns in mice. Zingerone restored cognitive function by diminishing seizure activity, escape latency, and subsequent hippocampal damage manifested in histology. Seizures are associated with local inflammation, redox imbalance, and neural loss, confirmed by the present study of SE, and was attenuated by zingerone treatment. Nuclear factor-kappa B and its downstream signaling molecules (TNF-α, IL-1β, IL-6, NO, MPO) were activated in the LiCl-and-pilocarpine-induced group leading to inflammatory signaling, which was substantially ameliorated by zingerone treatment. The intrinsic apoptotic process was triggered subsequent to SE, as demonstrated by augmentation of cleaved caspase-3, downregulation of Bcl-2. However, zingerone treatment downregulated caspase-3 and upregulated Bcl-2, increasing cell survival and decreasing hippocampal neural death, deciphering involvement of apoptosis in SE. Therefore, zingerone plays an essential role in neuroprotection, probably by precluding oxidative stress, inflammation, and obstructing the mitochondrial pathway of apoptosis.

Study Design: Prospective Study., Objectives: To describe a unique site-specific injury mechanism for spinal cord injury: incidents involving ox-carts., Setting: Main referral hospital for North-eastern Tanzania., Methods: A prospective cohort study on Spinal Cord Injury (SCI) in a tertiary referral center in North-eastern Tanzania was examined for accidents related to the use of ox-carts, a major means of transport in a rugged rural area where the economy is largely based on agricultural practices., Results: Five out of a total of 163 individuals admitted with SCI were injured in incidents directly related to the use of ox-carts. On admission each of the five individuals had different neurological level and corresponding injury severity as follows; C4 (American Spinal Injury Association Impairment Scale) AIS A), C5 (AIS D), C7 (AIS C), T1 (AIS C) and L1 (AIS D). Two out of the five patients developed secondary complications during their hospital stay., Conclusion: The nature of these injuries highlights the influence of one's environment and social circumstances on the risk of sustaining a SCI. Such cases also serve to illustrate the need for tailored prevention, rehabilitation, and reintegration into society.

Colon cancer is the most common cancer in men and women globally, killing millions of people annually. Though there widespread development has been made in the management of colorectal cancer, still there is an urgent need to find novel targets for its effective treatment. Piperine is an alkaloid found in black pepper having anticancer, anti-inflammatory activities, safe and nutritive for human consumption. Nuclear factor-erythroid 2-kelch-like ECH-associated protein 1(Nrf-2/Keap-1)/Heme-oxygenase1 (HO-1) signaling pathway plays a vital part in shielding cells from intracellular oxidative stress and inflammation. A potential cross-talk between the Nrf-2 and NF-κB pathways is recognized during cancerous growth and expansion. We studied this pathway extensively in the present study to discover novel targets in the prevention of chemically induced colon cancer with piperine to simulate human colon cancer pathology. Animals were divided into four groups. Groups1 and 2 were used as a negative control and positive control where 1,2-Dimethylhydrazine, DMH was administered in group 2, while group 3 and 4 were prevention groups where piperine at two different doses was given two weeks prior to DMH and continued until end of experiment. We found that piperine inhibited NF-κB by the activation of Nrf-2, blocking downstream inflammatory mediators/cytokines (TNF-α, IL-6, IL-1β, Cox-2, PGE-2, iNOS, NO, MPO), triggering an antioxidant response machinery (HO-1, NQO-1, GSH, GR, GPx, CAT, SOD), scavenging ROS, and decreasing lipid peroxidation. Histological findings further validated our molecular findings. It also downregulates CEA, MDF and ACF, markers of precancerous lesions in colon, alleviates infiltration of mast cells and depletes the mucous layer. Our results indicate that piperine may be an effective molecule for the prophylactic treatment of colon carcinogenesis by targeting the NF-κB/Nrf-2/Keap-1/HO-1 pathway as a progressive strategy in the preclusion and effective treatment of colorectal cancer.

It is common practice for data providers to include text descriptions for each column when publishing datasets in the form of data dictionaries. While these documents are useful in helping an end-user properly interpret the meaning of a column in a dataset, existing data dictionaries typically are not machine-readable and do not follow a common specification standard. We introduce the Semantic Data Dictionary, a specification that formalizes the assignment of a semantic representation of data, enabling standardization and harmonization across diverse datasets. In this paper, we present our Semantic Data Dictionary work in the context of our work with biomedical data; however, the approach can and has been used in a wide range of domains. The rendition of data in this form helps promote improved discovery, interoperability, reuse, traceability, and reproducibility. We present the associated research and describe how the Semantic Data Dictionary can help address existing limitations in the related literature. We discuss our approach, present an example by annotating portions of the publicly available National Health and Nutrition Examination Survey dataset, present modeling challenges, and describe the use of this approach in sponsored research, including our work on a large NIH-funded exposure and health data portal and in the RPI-IBM collaborative Health Empowerment by Analytics, Learning, and Semantics project. We evaluate this work in comparison with traditional data dictionaries, mapping languages, and data integration tools.

Doxorubicin (Dox) is an operational and largely used anticancer drug, used to treat an array of malignancies. Nonetheless, its beneficial use is constrained due to its renal and hepatotoxicity dose dependently. Numerous research findings favor the use of antioxidants may impact Dox-induced liver injury/damage. In the current study, Wistar rats were given naringenin (50 and 100 mg/kg b.wt.) orally for 20 days as prophylactic dose, against the hepatotoxicity induced by single intraperitoneal injection of Dox (20 mg/kg b.wt.). Potency of naringenin against the liver damage caused by Dox was assessed by measuring malonyl aldehyde (MDA) as a by-product of lipid peroxidation, biochemical estimation of antioxidant enzyme system, reactive oxygen species (ROS) level, and inflammatory mediators. Naringenin-attenuated ROS production, ROS-induced lipid peroxidation, and replenished reduced antioxidant armory, namely, catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). Naringenin similarly diminished expression of Cox-2 and levels of NF-κB and other inflammatory molecules induced by the Dox treatment. Histology added further evidence to the defensive effects of naringenin on Dox-induced liver damage. The outcomes of the current study reveal that oxidative stress and inflammation are meticulously linked with Dox-triggered damage, and naringenin illustrates the potential effect on Dox-induced hepatotoxicity probably through diminishing the oxidative stress and inflammation.

Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-β. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.

Introduction: Surviving a traumatic cervical Spinal Cord Injury (SCI) has an immense effect on an individual's physical function and independence. It also predisposes them to financial, social, psychological and several medical complications throughout their life. In high-income countries, improved multidisciplinary care has led to better long term outcomes, however in low-income countries, the burden of the condition and its associated mortality remain high. The aim of this study was to illustrate the sociodemographic and clinical characteristics of cervical level Traumatic Spinal Cord Injuries (TSCIs) at Kilimanjaro Christian Medical Centre (KCMC) in northern Tanzania., Methods: This was a retrospective hospital-based study of 105 cervical TSCI cases admitted to KCMC from January 2012 to December 2016., Results: We included 105 patients in the study cohort, with a male preponderance of 86.7%, giving a male-to-female ratio of 6.5:1. The mean age at injury was 44.1 years. Overall, 65.7% were farmers and 69 patients were from within the Kilimanjaro region. Road Traffic Crashes (RTCs) accounted for 47.6% of the injuries, 17.9% had associated injuries, 38.1% sustained complete TSCIs and 45.7% developed secondary complications during the ward stay. The mortality rate before discharge from hospital care was 35.2%., Conclusion: The majority of patients were males from a low socioeconomic background and the most common cause of injury was RTCs. The secondary complication rates and mortality rates before discharge from hospital care are high., Competing Interests: The authors declare no competing interests.

Objective: The purpose of this study was to compare the effects of neuromuscular training (NMT) and quadriceps training (QT) on the altered gait patterns and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index in patients with knee osteoarthritis (OA) and varus malalignment., Methods: Sixty-six patients with knee pain ≥2 on 100-mm visual analog scale, radiographic knee OA changes ≥2 on Kellgren-Lawrence grading scale, and genu varum were allocated randomly into either the neuromuscular training group or quadriceps training group. Twelve weeks of supervised exercise protocol was given to the participants of both groups, which included 3 sessions per week. Primary outcomes were gait variables and self-reported physical function (WOMAC index)., Results: Of 66 knee OA patients, only 31 (94%) in the NMT group and 28 (84.8%) in the QT group completed the exercise protocol and were included in the analysis. There was a significant improvement in gait velocity ( P = .022), stride length ( P = .009), and global WOMAC index ( P = .011) in the NMT group compared to the QT group. However, the scores of cadence ( P = .226), gait cycle ( P = .332), and double limb support ( P = .054) were not found significant in the NMT group compared with the QT group., Conclusion: The NMT group showed improvement in some of the gait parameters as well as improvement in pain, stiffness, and functional limitation compared with conventional QT. No additional improvement was found in cadence, gait cycle, and double limb support in patients who received NMT.

Nature has bestowed mankind with surplus resources (natural products) on land and water. Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. These natural products have been experimentally documented to possess various biological properties such as antioxidant, anti-inflammatory and anti-apoptotic activities. In vitro and in vivo studies have further established the usefulness of natural products in various preclinical models of neurodegenerative disorders. Natural products include phytoconstituents, like polyphenolic antioxidants, found in herbs, fruits, nuts, vegetables and also in marine and freshwater flora. These phytoconstituents may potentially suppress neurodegeneration and improve memory as well as cognitive functions of the brain. Also, they are known to play a pivotal role in the prevention and cure of different neurodegenerative diseases, such as Alzheimer's disease, epilepsy, Parkinson's disease and other neuronal disorders. The large-scale neuro-pharmacological activities of natural products have been documented due to the result of either the inhibition of inflammatory processes, or the up-regulation of various cell survival proteins or a combination of both. Due to the scarcity of human studies on neuroprotective effects of natural products, this review focuses on the various established activities of natural products in in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications using the available knowledge in the literature., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Accidental or intentional poisoning is a public health concern requiring intervention. The current study designs to evaluate the types of poisoning exposure calls received by the Malaysia National Poison Centre (NPC) over a 10-year period., Settings and Data Sources: The poisoning enquiries database (2006-2015) from the Malaysia NPC was used for the analysis., Participants: The NPC records all telephone calls that it manages using a validated and standardised form. Demographics and types of the poisoning exposure calls were extracted and descriptive analysis was applied., Primary and Secondary Outcomes: The primary outcome of this study is to evaluate NPC data for trends in the poisoning exposure calls based on the types and modes of poisoning over a 10-year period. The secondary outcome is to evaluate the characteristics of human exposure cases based on the calls received by the NPC., Results: There was a notable increase in the number of poisoning exposure calls noticed during the 10-year period but dropped significantly in 2012. The highest number of poisoning exposure calls came from Selangor (21.0%), Perak (18.0%) and Negeri Sembilan (9.8%). More than half of the exposure was intentional (53.8%) involving more women (50.3%) as compared with men (41.9%), and in the 20-29 years age group category (33.5%). Exposure mostly occurred at home (96%) through the ingestion route (94.1%). Pharmaceutical products (40.5%), pesticides (31.7%) and household products (20.1%) were the common agents implicated for intentional exposure., Conclusions: There is an increasing trend in enquiries on poisoning exposure calls made to the NPC. Most of the intentional poisoning exposures occurred among younger women and involved pharmaceuticals, pesticides or household products. Poisoning safety education and other interventions are needed to curb poisoning incidents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Down Syndrome (DS)-also referred to as Trisomy 21-is associated with multiple deformities affecting various systems of the body. Joint laxity resulting in unstable atlanto-occipital and atlanto-axial joints-with an increased susceptibility to fatal cord injuries-is a recognized phenomenon in patients with DS., Case Presentation: We report on a 30-year-old man with DS from Tanzania with no previous neck complaints, who presented with a 5-week progressive history of paraparesis that evolved into a quadriparesis. During his initial presentation, the patient reported that 5 months ago he had been involved in a headlock during a playground encounter., Discussion: Primary prevention of the traumatic spinal cord injuries is an important public health measure and a heightened emphasis should be placed to prevent such injuries in high risk populations-including DS patients., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Colon cancer is a world-wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chinese's traditional medicine because of its exceptional pharmacological properties and non-toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3-5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH-induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF-κB-p65, COX-2, i-NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF-α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin., (© 2018 Wiley Periodicals, Inc.)

This study was designed to assess the potential antifibrotic effect of D-Limonene-a component of volatile oils extracted from citrus plants. D-limonene is reported to have numerous therapeutic properties. CCl 4 -intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl 4 -intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D-Limonene. Also, CCl 4 -intoxication caused depletion of glutathione and other antioxidant enzymes while D-Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl 4 treatment while D-Limonene prevented these alterations. Levels of TNF-α, TGF-β, and α-SMA were also assessed; CCl 4 increased the expression of α-SMA, NF-κB and other downstream inflammatory cascade while D-Limonene co-treatment inhibited them. Collectively these findings indicate that D-Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti-inflammatory properties., (© 2017 Wiley Periodicals, Inc.)

Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Study Design: Retrospective study., Objectives: To describe the epidemiology of traumatic spinal cord injury (TSCI) in Northern Tanzania., Setting: Main referral hospital for Northern Tanzania., Methods: A retrospective review of 125 TSCI cases admitted to Kilimanjaro Christian Medical Centre (KCMC) over a period of 5 years., Results: We included 125 patients in the sample size, with a male majority of 107 (85.6%), giving a male-to-female ratio of 5.9:1. The mean age at injury was 39.9 (±16.0) years. Overall, 66 (52.8%) were farmers and an overwhelming majority (109 (87.2%)) were referrals from peripheral medical centres. Fall injuries accounted for 65 (52.0%) of the admissions and 49 (39.2%) were injured due to a Road Traffic Accident (RTA). Severity of injury was classified according to the American Spinal Injury Association Impairment Scale (AIS) and 57 (45.6%) injuries were categorised as AIS A and 68 (54.4%) as AIS BCD. Cervical level injuries (59 (47.2%)) were the most frequent among the cohort. The in-hospital mortality rate was 24.1%., Conclusion: The majority of patients affected by TSCIs were young males and the most common cause was fall injuries. Cervical level injuries were the most common and in-hospital mortality was high., Competing Interests: The authors declare no conflict of interest.