Management Of Multiple Diseases Research Articles

Multiplex PCR for Early Generation Identification of Tomato Segregants Carrying Ty-2, Ty-3 and Ph-3 Resistance Alleles Against Leaf Curl and Late Blight Diseases.

Deployment of different natural disease resistance alleles is the most sustainable and eco-friendly way for multiple disease management in tomato. Diagnostic molecular markers are indispensible in this effort as they offer early generation identification of resistance alleles in an environment-independent manner. Moreover, optimized multiplex polymerase chain reaction (PCR) for detecting different disease resistance alleles in a single reaction can speed-up the selection process with cost and labour-effectiveness. Here we report the optimized multiplex detection and stacking of leaf curl disease resistance alleles Ty-2 and Ty-3 along with late blight disease resistance allele Ph-3 in tomato genotypes and F2 segregants. The triplex assay could be replaced by a duplex assay (for Ty-2 and Ty-3 resistance alleles) followed by analysis at Ph-3 locus to achieve further cost-effectiveness. We identified two plants in F2 populations derived from the Arka Samrat (F1) x Kashi Chayan combination to carry the Ty-2, Ty-3 and Ph-3 resistance alleles in homozygous condition. Early generation genotyping also allowed us to identify a few morphologically better segregants, where further marker assisted selection (MAS) should identify superior multiple disease resistant lines. Thus we advocate the utility of multiplex PCR in MAS to address multiple disease resistance breeding in tomato.

Help sought for gout sufferers: A historical look at the treatment of gout in the New Kingdom of Granada

IntroductionDuring the colonial period, despite scarce knowledge and resources, doctors and apothecaries developed medical prescriptions mainly of vegetable origin for the management of multiple diseases, including gout. ObjectiveTo contextualise and describe the use of medical prescription in the early 19th century in the New Kingdom of Granada for the treatment of gout. Material and methodsA documentary search of medical prescription was carried out in the Cipriano Rodríguez Santamaría Historical Archive of the Octavio Arizmendi Posada Library of the University of La Sabana. Subsequently, an open literature review was carried out in the ScienceDirect, ClinicalKey, and Scielo databases in English and Spanish. ResultsPistacia lentiscus, the basis of the recipe described, has a high content of terpenes, tannins, flavonoids, and coumarins, which generate anti-inflammatory, antimicrobial, antioxidant, antibiotic, antiviral, and anti-atherogenic effects, among others. ConclusionMastic, one of the components of these recipes, possesses anti-inflammatory and antioxidant properties, which could explain its relative efficacy in the treatment of gout in the 19th century.

Mast Cells as a Potential Target of Molecular Hydrogen in Regulating the Local Tissue Microenvironment.

Knowledge of the biological effects of molecular hydrogen (H2), hydrogen gas, is constantly advancing, giving a reason for the optimism in several healthcare practitioners regarding the management of multiple diseases, including socially significant ones (malignant neoplasms, diabetes mellitus, viral hepatitis, mental and behavioral disorders). However, mechanisms underlying the biological effects of H2 are still being actively debated. In this review, we focus on mast cells as a potential target for H2 at the specific tissue microenvironment level. H2 regulates the processing of pro-inflammatory components of the mast cell secretome and their entry into the extracellular matrix; this can significantly affect the capacity of the integrated-buffer metabolism and the structure of the immune landscape of the local tissue microenvironment. The analysis performed highlights several potential mechanisms for developing the biological effects of H2 and offers great opportunities for translating the obtained findings into clinical practice.

Evaluation of the Phytochemistry-Therapeutic Activity Relationship for Grape Seeds Oil.

Seeds' abundant biologically active compounds make them a suitable primary platform for the production of natural extracts, innovative foods, medicines, and cosmetics. High levels of industrial and agricultural residues and byproducts are generated during the processing of grapes, although some parts can also be repurposed. This paper examines the phytochemical composition, manufacturing processes, and health-improving attributes of many varieties of grape oil derived using various extraction methods. Since the results are influenced by a range of factors, they are expressed differently among studies, and the researchers employ a variety of measuring units, making it difficult to convey the results. The primary topics covered in most papers are grape seed oil's lipophilic fatty acids, tocopherols, and phytosterols. In addition, new methods for extracting grape seed oil should therefore be designed; these methods must be affordable, energy-efficient, and environmentally friendly in order to increase the oil's quality by extracting bioactive components and thereby increasing its biological activity in order to become part of the overall management of multiple diseases.

Microgreens: A Next Generation Nutraceutical for Multiple Disease Management and Health Promotion

Microgreens: A Next Generation Nutraceutical for Multiple Disease Management and Health Promotion

Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis

The role of microneedle array patches (MAPs) and, in particular, dissolving MAPs in transdermal drug delivery has increased exponentially over the last decade. MAPs are able to form drug depots in the viable skin from where poorly soluble drugs dissolve in a long-acting fashion, showing promise in the management of multiple diseases. The manufacture of these systems can present some challenges, including the presence of bubbles in the baseplates and consequent lack of uniformity in microneedle formation and drug content. Here, we present a simple method based on ring inserts to produce tip-loaded MAPs using the antiretroviral drug cabotegravir sodium (CAB). The obtained MAPs presented a high uniformity in terms of microneedle formation, and a suitable insertion capability, as per the mechanical characterisation performed. An optimisation based on design of experiments revealed that centrifugation parameters had a significant impact on the skin deposition of the MAPs in excised neonatal porcine skin using Franz cells, with values ranging from 62.24 ± 47.13 µg to 174.13 ± 41.10 µg of CAB. Pharmacokinetic studies carried out in rats evidenced the capacity of the MAPs to maintain therapeutic plasma levels of CAB for 14 days, with Tmax values reached between 5 and 8 days.

Flaxseed Bioactive Compounds: Chemical Composition, Functional Properties, Food Applications and Health Benefits-Related Gut Microbes.

Flaxseed (Linum usitatissimum L.) has gained worldwide recognition as a health food because of its abundance in diverse nutrients and bioactive compounds such as oil, fatty acids, proteins, peptides, fiber, lignans, carbohydrates, mucilage, and micronutrients. These constituents attribute a multitude of beneficial properties to flaxseed that makes its use possible in various applications, such as nutraceuticals, food products, cosmetics, and biomaterials. The importance of these flaxseed components has also increased in modern times because of the newer trend among consumers of greater reliance on a plant-based diet for fulfilling their nutritional requirements, which is perceived to be hypoallergenic, more environmentally friendly, sustainable, and humane. The role of flaxseed substances in the maintenance of a healthy composition of the gut microbiome, prevention, and management of multiple diseases has recently been elucidated in various studies, which have highlighted its importance further as a powerful nutritional remedy. Many articles previously reported the nutritive and health benefits of flaxseed, but no review paper has been published reporting the use of individual flaxseed components in a manner to improve the techno-functional properties of foods. This review summarizes almost all possible applications of flaxseed ingredients in food products from an extensive online literature survey; moreover, it also outlines the way forward to make this utilization even better.

To Wean or Not to Wean: A Practical Patient Focused Guide to Ventilator Weaning.

Since the inception of critical care medicine and artificial ventilation, literature and research on weaning has transformed daily patient care in intensive care units (ICU). As our knowledge of mechanical ventilation (MV) improved, so did the need to study patient-ventilator interactions and weaning predictors. Randomized trials have evaluated the use of protocol-based weaning (vs. usual care) to study the duration of MV in ICUs, different techniques to conduct spontaneous breathing trials (SBT), and strategies to eventually extubate a patient whose initial SBT failed. Despite considerable milestones in the management of multiple diseases contributing to reversible respiratory failure, in the application of early rehabilitative interventions to preserve muscle integrity, and in ventilator technology that mitigates against ventilator injury and dyssynchrony, major barriers to successful liberation from MV persist. This review provides a broad encompassing view of weaning classification, causes of weaning failure, and evidence behind weaning predictors and weaning modes.

Impact of Calonectria Diseases on Ornamental Horticulture: Diagnosis and Control Strategies.

Diseases caused by fungi in the genus Calonectria pose a significant threat to the ornamental horticulture industries in Europe and the United States. Calonectria spp. are particularly challenging pathogens to manage in ornamental production systems and the urban landscape for multiple reasons. A high level of species diversity and poorly resolved taxonomy in the genus makes proper pathogen identification and disease diagnosis a challenge, though recent molecular phylogenetic studies have made significant advances in species delimitation. From a disease management perspective, Calonectria spp. produce long-lived survival structures (microsclerotia) that contaminate nursery production systems and can survive multiple years in the absence of a susceptible plant host. Latent infection of plant material is poorly understood but likely contributes to long-distance dissemination of these fungal pathogens, including the clonal Calonectria spp. responsible for the global emergence of boxwood blight. Breeding for disease resistance represents a sustainable strategy for managing Calonectria diseases but is challenging due to the perennial nature of many ornamental plants and high levels of susceptibility in commercial cultivars. Ultimately, long-term sustainable management of Calonectria diseases will require an improved understanding of pathogen biology as well as integration of multiple disease management strategies.

A Review on Oxadiazoles as a Pharmacologically Active Nucleus

The structure of the oxadiazole skeleton is a biologically and biochemically active nucleus that has a multiple number of biological activities. The oxadiazole structure is a five-membered aromatic ring that has been used in numerous studies and molecules synthesised in laboratories. The principle structure of the Oxadiazole ring with a pair of Pyridine-type nitrogen atoms has been confirmed to be valuable for Oxadiazole analogues for having efficacious protein interactions with a large number of enzyme proteins and receptor proteins present in the organ system of the human body through different types of interactions, like Vander Wall interactions, thereby producing a huge variety of biological activities or pharmacological properties. Due to the variety in the pharmacological activity of Oxadiazole and their derivatives and analogues, they have been termed as one of the important pharmacological aspects to study. Multiple numbers of oxadiazole related synthetic compounds possessing high potent action and therapeutic activity are being widely incorporated for treatment and management of multiple diseases and disorders, giving immeasurable progression and establishment value. Oxadiazole derivatives express a multiple number of pharmacological activities like antimicrobial, anti-inflammatory, analgesic, antifungal, antipyretic, antidepressant, anti-tubercular, anticonvulsant, anticholinesterase, antihypertensive, antidiabetic, antitumor/anticancer, anti-HIV, antioxidant, etc. The history of 1,3,4-Oxadiazole is also very interesting. It shows that it attracted many chemists, researchers, and scientists to explore the Oxadiazole nucleus as a biologically active molecule having promising potency. This review article mainly focuses on the pharmacological profile of 1,3,4-Oxadiazole with various activities and examples (in the form of figures and structures). Expectations are that this article will be like a path showing torch to help and serve as guidance for new innovations/ideas along the progression of research for the evolution of more active/potent and less poisonous/toxic Oxadiazole-based derivatives.

Auxilios que se imploran favorables a los gotosos: una mirada histórica al tratamiento de la gota en el Nuevo Reino de Granada

IntroductionDuring the colonial period, despite scarce knowledge and resources, doctors and apothecaries developed medical prescriptions mainly of vegetable origin for the management of multiple diseases, including gout. ObjectiveTo contextualise and describe the use of medical prescription in the early 19th century in the New Kingdom of Granada for the treatment of gout. Material and methodsA documentary search of medical prescription was carried out in the Cipriano Rodríguez Santamaría Historical Archive of the Octavio Arizmendi Posada Library of the University of La Sabana. Subsequently, an open literature review was carried out in the ScienceDirect, ClinicalKey, and Scielo databases in English and Spanish. ResultsPistacia lentiscus, the basis of the recipe described, has a high content of terpenes, tannins, flavonoids, and coumarins, which generate anti-inflammatory, antimicrobial, antioxidant, antibiotic, antiviral, and anti-atherogenic effects, among others. ConclusionMastic, one of the components of these recipes, possesses anti-inflammatory and antioxidant properties, which could explain its relative efficacy in the treatment of gout in the 19th century.

Detection of transdermal biomarkers using gradient-based colorimetric array sensor

Accurate assessment of dietary macronutrients intake is critical for the effective management of multiple diseases, such as obesity, diabetes, cardiovascular disease, metabolic disease, and cancer. Conventional self-reporting method is burdensome, inaccurate, and often biased. Though blood analysis and breath analysis can provide evidence-based information, they are either invasive or subject to human errors. Here we reported a wearable transdermal volatile biomarkers detection system based on novel colorimetric sensing technology for dietary macronutrients intake assessment. This technique quantifies the emission rates of transdermal volatile biomarkers via a gradient-based colorimetric array sensor (GCAS). The optical system of the GCAS device tracks the localized color development associated with the chemical reaction between the volatile biomarkers and the porous sensing probes, and determines the biomarkers emission rates through image processing algorithms. The localized chemical reaction and the image-based signal processing also make the GCAS capable for multiplexed detection of multiple analytes simultaneously. The GCAS sensor has been applied for transdermal acetone detection on 5 subjects in a keto diet intervention. The study indicates that the transdermal acetone increases after the subjects consuming keto diets and it decreases to basal level after intaking carb-rich diets. The transdermal acetone response from the GCAS sensor correlates well with breath acetone concentration in the range between 0 and 40 ppm and the correlation factor (R2) is as high as 0.8877. This method provides a noninvasive, low-cost, and wearable tool for assessing dietary macronutrients intake outside of lab or hospital settings. It could be widely applied in disease management, weight control, and nutrition management.

Phytochemical Screening and Hepatoprotective Potential of Sida cordata

Sida cordata (Burn. f.) Borss. Waalk is highly distributed in entire part of India. The various parts of the plant are used in folklore medicine for the management of multiple diseases. So,the present study was performed to examine the hepatoprotective activity study of ethanolic extract of S. cordata leaves (SCLE) on alcohol mediated hepatotoxicity in a rat model. Ethanol intoxicated rats showed noteworthy elevation of liver weight and volume. Further, ethanol insulted rats also showed significant elevation in the level of biochemical markers such as AST, ALT, TG, TB, and DB) and marked variation in the histological structure of liver. Oral administration of SCLE at the dose of 200 and 400 mg/kg for 30 days) significantly reduced the liver weight, hepatic markers level and restored the histological changes annoyed by ethanol thus indicating its hepatoprotective potential. Furthermore, HPTLC analysis was performed for the identification and quality estimation of S. cordata leaves.

Biosimilars are becoming indispensable in the management of multiple diseases although concerns still exist

Abstract Not Available
 Bangladesh Journal of Medical Science Vol.20(1) 2021 p.5-10

Multiple Disease Hotspot Mining for Public Health Informatics in Resource Starved Settings: Study of Communicable Diseases in Punjab, Pakistan

Communicable diseases remain a significant challenge for public health management. In particular, for resource scarce settings, it is important to understand the linkages and dynamics of multiple diseases that share common resources, space or time. We develop a framework, called Multiple Disease Management Framework (MDMF) based on machine learning approach for managing multiple diseases occurring in close space and time to identify locations that experience high disease burden rates. We use 8 water related disease incidence data in Punjab, Pakistan from year 2013 to 2019 to investigate interactions among hotspots of different diseases. However, the model is scalable and can be applied to any number of diseases. The hotspot analysis involves multi-level clustering and tagging of individual disease incidence streams that generates a distance based graph over a geographical area and is then integrated into a single stream in the framework to identify final sensitive locations called cluster alarms. The initial individual disease clustering yielded number of clusters as high as 24 clusters for each disease with up to 16 neighboring clusters of other diseases of similar sizes. The cluster tagging and multi-level clustering process was able to identify as low as 19 locations of cluster alarms across the whole province of 38 districts. The identification of high disease hotspots and their dynamics with the neighboring hotspots of multiple diseases allows identification of locations with higher need of related public health resources. This identification is very critical for national health agencies for optimal allocation of resources and devising an effective intervention programs.

Mucopolysaccharidoses I and II: Brief Review of Therapeutic Options and Supportive/Palliative Therapies.

Purpose. Mucopolysaccharidoses (MPS) are group of inherited lysosomal storage diseases caused by mutations of enzymes involved in catalyzing different glycosaminoglycans (GAGs). MPS I and MPS II exhibit both somatic and neurological symptoms with a relatively high disease incidence. Hematopoietic stem cell therapy (HSCT) and intravenous enzyme replacement therapy (ERT) have had a significant impact on the treatment and comprehension of disease. This review is aimed at providing a comprehensive evaluation of the pros and cons of HSCT and ERT, as well as an up-to-date knowledge of new drugs under development. In addition, multiple disease management strategies for the uncontrollable manifestations of MPS I and MPS II to improve patients' quality of life are presented. Findings. Natural history of MPS I and MPS II shows that somatic and neurological symptoms occur earlier in severe forms of MPS I than in MPS II. ERT increases life expectancy and alleviates some of the somatic symptoms, but musculoskeletal, ophthalmological, and central nervous system (CNS) manifestations are not controlled. Additionally, life-long treatment burdens and immunogenicity restriction are unintended consequences of ERT application. HSCT, another treatment method, is effective in controlling the CNS symptoms and hence has been adopted as the standard treatment for severe types of MPS I. However, it is ineffective in MPS II, which can be explained by the relatively late diagnosis. In addition, several factors such as transplant age limits or graft-versus-host disease in HSCT have limited its application for patients. Novel therapies, including BBB-penetrable-ERT, gene therapy, and substrate reduction therapy, are under development to control currently unmanageable manifestations. BBB-penetrable-ERT is being studied comprehensively in the hopes of being used in the near future as a method to effectively control CNS symptoms. Gene therapy has the potential to “cure” the disease with a one-time treatment rather than just alleviate symptoms, which makes it an attractive treatment strategy. Several clinical studies on gene therapy reveal that delivering genes directly into the brain achieves better results than intravenous administration in patients with neurological symptoms. Considering new drugs are still in clinical stage, disease management with close monitoring and supportive/palliative therapy is of great importance for the time being. Proper rehabilitation therapy, including physical and occupational therapy, surgical intervention, or medications, can benefit patients with uncontrolled musculoskeletal, respiratory, ophthalmological, and neurological manifestations.

Genetic links between endometriosis and cancers in women.

Endometriosis is a chronic disease occurring during the reproductive stage of women. Although there is only limited association between endometriosis and gynecological cancers with regard to clinical features, the molecular basis of the relationship between these diseases is unexplored. We conducted a systematic study by integrating literature-based evidence, gene expression and large-scale cancer genomics data in order to reveal any genetic relationships between endometriosis and cancers in women. We curated 984 endometriosis-related genes from 3270 PubMed articles and then conducted a meta-analysis of the two public gene expression profiles related to endometriosis which identified Differential Expression of Genes (DEGs). Following an overlapping analysis, we identified 39 key endometriosis-related genes common in both literature and DEG analysis. Finally, the functional analysis confirmed that all the 39 genes were associated with the vital processes of tumour formation and cancer progression and that two genes (PGR and ESR1) were common to four cancers of women. From network analysis, we identified a novel linker gene, C3AR1, which had not been implicated previously in endometriosis. The shared genetic mechanisms of endometriosis and cancers in women identified in this study provided possible new avenues of multiple disease management and treatments through early diagnosis.

A Small-Molecule Pan-Id Antagonist Inhibits Pathologic Ocular Neovascularization

SUMMARYId helix-loop-helix (HLH) proteins (Id1–4) bind E protein bHLH transcription factors, preventing them from forming active transcription complexes that drive changes in cell states. Id proteins are primarily expressed during development to inhibit differentiation, but they become re-expressed in adult tissues in diseases of the vasculature and cancer. We show that the genetic loss of Id1/Id3 reduces ocular neovascularization in mouse models of wet age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). An in silico screen identifies AGX51, a small-molecule Id antagonist. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduced viability. AGX51 is well-tolerated in mice and phenocopies the genetic loss of Id expression in AMD and ROP models by inhibiting retinal neovascularization. Thus, AGX51 is a first-in-class compound that antagonizes an interaction formerly considered undruggable and that may have utility in the management of multiple diseases.

Baicalein Inhibits Dextran Sulfate Sodium-induced Mouse Colitis.

BackgroundBaicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized.MethodsThe experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured.ResultsBaicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric.ConclusionsProtective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.

Mining co-occurrence and sequence patterns from cancer diagnoses in New York State.

The goal of this study is to discover disease co-occurrence and sequence patterns from large scale cancer diagnosis histories in New York State. In particular, we want to identify disparities among different patient groups. Our study will provide essential knowledge for clinical researchers to further investigate comorbidities and disease progression for improving the management of multiple diseases. We used inpatient discharge and outpatient visit records from the New York State Statewide Planning and Research Cooperative System (SPARCS) from 2011-2015. We grouped each patient’s visit history to generate diagnosis sequences for seven most popular cancer types. We performed frequent disease co-occurrence mining using the Apriori algorithm, and frequent disease sequence patterns discovery using the cSPADE algorithm. Different types of cancer demonstrated distinct patterns. Disparities of both disease co-occurrence and sequence patterns were observed from patients within different age groups. There were also considerable disparities in disease co-occurrence patterns with respect to different claim types (i.e., inpatient, outpatient, emergency department and ambulatory surgery). Disparities regarding genders were mostly found where the cancer types were gender specific. Supports of most patterns were usually higher for males than for females. Compared with secondary diagnosis codes, primary diagnosis codes can convey more stable results. Two disease sequences consisting of the same diagnoses but in different orders were usually with different supports. Our results suggest that the methods adopted can generate potentially interesting and clinically meaningful disease co-occurrence and sequence patterns, and identify disparities among various patient groups. These patterns could imply comorbidities and disease progressions.