Pharmacological and Toxicological Study of Coumarinolignoids from Cleome viscosa in Small Animals for the Management of Rheumatoid Arthritis.

This study aims to explore the possible pharmacological potential of Cleome viscosa Linn (Cleomaceae), an annual weed, into therapeutic value-added products. In the present study, we have explored the pharmacological and toxicological profile of coumarinolignoids isolated from Cleome viscose for the management of rheumatoid arthritis and related complications in a small animal model. To avoid the biasness during experiments on animals, we have coded the isolated coumarinolignoids as CLIV-92 to perform the experimental pharmacological study. CLIV-92 was orally administrated (30,100, 300 mg/kg) to animal models of collagen-induced arthritis (CIA), carrageenan-induced acute inflammation, thermal and chemical-induced pain, and Brewer's yeast-induced pyrexia. Oral administration of CLIV-92 significantly decreases the arthritis index, arthritis score, and increases the limb withdrawal threshold in the CIA model in experimental rats. The anti-arthritis studies revealed that the anti-inflammatory effect of CLIV-92 was associated with inhibition of the production of inflammatory mediators like TNF-α, IL-6, IL-17A, MMP-1, MMP-9, Nitric oxide, and C-RP in CIA rat's serum, and also reduced the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue of CIA rats, in a dose-dependent manner. Further individual experiments related to arthritis-related complications in experimental animals demonstrated the analgesic, anti-inflammatory, and antipyretic potential of CLIV-92 in a dose-dependent manner. Further, an in-vivo acute oral toxicity study concluded that CLIV-92 is safe in experimental animals up to 2,000 mg/kg dose. The results of this study suggested that the oral administration of CLIV-92 may be a therapeutic candidate for further investigation in the management of rheumatoid arthritis and related complications.

Cerebral visual impairment in children: Multicentric study determining the causes, associated neurological and ocular findings, and risk factors for severe vision impairment.

Purpose: To evaluate the causes, associated neurological and ocular findings in children with cerebral visual impairment (CVI), and to identify risk factors for severe vision impairment. Methods: A multicenter, retrospective, cross-sectional analysis was carried out from January 2017 to December 2019 on patients less than 16 years of age with a diagnosis of CVI. Results: A total of 405 patients were included of which 61.2% were male and 38.8% were female. The median age at presentation was 4 years (range 3 months to 16 years). Antenatal risk factors were present in 14% of the cases. The most common cause of CVI was hypoxic-ischemic encephalopathy (35.1%), followed by seizure associated with brain damage (31.3%). The most common neurological finding was seizure (50.4%), followed by cerebral palsy (13.6%). Associated ophthalmological findings were significant refractive error (63.2%), esotropia (22.2%), exotropia, (38%), nystagmus (33.3%), and optic nerve atrophy (25.9%). Severe visual impairment (<20/200) was associated with optic atrophy (odds ratio: 2.9, 95% confidence interval: 1.4-6.0; P = 0.003) and seizure disorder (odds ratio: 1.9, 95% confidence interval: 1.2-3.3; P = 0.012). Conclusion: The various ophthalmic, neurological manifestations and etiologies could guide the multidisciplinary team treating the child with CVI in understanding the visual impairment that affects the neuro development of the child and in planning rehabilitation strategies.

Design and Implementation of Advanced Machine Learning Management and Its Impact on Better Healthcare Services: A Multiple Regression Analysis Approach (MRAA).

In the current information and technology era, business enterprises are focusing in performing the process effectively by reducing the waiting time in completing the work, reduce latency and deploy the resources effectively so as to service the patient, medical practitioners, societies, and other stakeholders in an efficient manner. Hence, several organisations are using the emerging technologies so as to obtain high performance and enhance competitive edge. The advancement in machine learning, deep learning, business analytics, etc. enables the health care industry to identify the patterns based on the data collected and create a pivotal position and enhance revenues and profits in a sustainable manner. Machine learning models are considered as computational algorithms which will enable in collected the data, analyze them, and provide the necessary reports to the experts and management in order to make informed decision making. The application of advanced machine learning enables the organisation to process the image effectively, recognize the voice and enable in servicing the customers, process the available data, and identify the patterns so as to make informed decision making. The basic purpose of the study is to analyze the overall implementation of advanced machine learning approaches towards health care services for providing enhanced services, better patient engagement, and support in creating better life for them, the researchers intend to collect the closed-ended questionnaire from employees in different medical centers covering: apprehend the nature of designing and implementation of machine learning approaches in the organisation and understand the effectiveness of these tools in enhancing the sustainable growth and development of the organisation.

Preventive factors, diagnosis, and management of injection-related endophthalmitis: a literature review.

BACKGROUND: Intravitreal medication injections represent the gold standard treatment for a variety of potentially blinding chorioretinal vascular diseases. Despite their excellent safety profile, they are associated with the feared complication of injection-related endophthalmitis (IRE). Though the overall incidence of IRE is low, due to the ever-increasing number of injections being performed, it is a complication that all retina specialists are likely to encounter. This article reviews various factors that could potentially influence the risk of IRE and discusses evidence-based strategies for management. METHOD: PubMed was searched for keywords "intravitreal injection" and "endophthalmitis" from the period of 1995-2021. Relevant articles were reviewed and selected articles were analyzed with respect to the incidence, potential preventive factors, clinical presentation, microbial profile, management, and outcomes for IRE. RESULTS: There is strong consensus supporting the use of povidone iodine topical antiseptic, eyelid retraction away from the injection site, and avoiding treatment of eyes with active surface or eyelid disease, but there is less agreement on the use of face masks versus "no-talking" policies and optimal anesthetic technique. Current evidence comparing tap and inject or early vitrectomy for treatment of IRE is inadequate to determine an optimal treatment strategy. CONCLUSION: Intravitreal injections are sight saving, but even using established prophylactic measures there remains a small but real risk of infectious injection-related complications. Further investigations comparing tap and inject versus vitrectomy may help to establish optimal treatment, although the rarity of IRE makes designing adequately powered prospective trials a difficult task.

Assessment of antidiabetic effect of 4-HIL in type 2 diabetic and healthy Sprague Dawley rats.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and insulin resistance. 4-hydroxyisoleucine (4-HIL) is a non-proteinogenic amino acid isolated from the fenugreek seeds and has enormous pharmacological activities. The present study was undertaken to investigate the antihyperglycemic effect of 4-HIL in streptozotocin (STZ)-induced diabetic rats. Moreover, its toxicity was evaluated in vitro and in vivo employing human embryonic kidney cells (HEK-293) and healthy rats, respectively. In experiment 1, STZ-induced diabetic male rats were subjected to an oral treatment of 4-HIL (100 mg/kg), while experiment 2 deals with the effects of 4-HIL on healthy male and female rats following oral administration. The treatment (experiment 1) declined the elevated blood glucose level, feed intake, and increased body weight(s). Additionally, blood glucose impairment was improved as observed by OGTT and IPGT tests. Pancreatic histopathology revealed mild changes in the 4-HIL group. Moreover, experiment 2 showed increased body weight, normal blood glucose levels (male-106.06 ± 7.49 mg/dl and female-100.06 ± 14.69 mg/dL), hematological parameters, and histopathological profiles in the treatment group. 4-HIL did not affect the viability of HEK-293 cells, and no signs of toxicity were observed in healthy rats. Therefore, the study concludes that 4-HIL has potential antihyperglycemic activity without any toxic effects.

A drug-free strategy to combat bacterial infections with magnetic nanoparticles biosynthesized in bacterial pathogens.

The extensive and indiscriminate use of antibiotics in the ongoing COVID-19 pandemic might significantly contribute to the growing number of multiple drug resistant (MDR) bacteria. With the dwindling pipeline of new and effective antibiotics, we might soon end up in a post-antibiotic era, in which even common bacterial infections would be a challenge to control. To prevent this, an antibiotic-free strategy would be highly desirable. Magnetic nanoparticle (MNP)-mediated hyperthermia-induced antimicrobial therapy is an attractive option as it is considered safe for human use. Given that iron and zinc are critical for bacterial virulence, we evaluated the response of multiple pathogenic bacteria to these elements. Treatment with 1 mM iron and zinc precursors resulted in the intracellular biosynthesis of MNPs in multiple Gram-positive and Gram-negative disease-causing bacteria. The superparamagnetic nanoparticles in the treated bacteria/biofilms, generated heat upon exposure to an alternating magnetic field (AMF), which resulted in an increase in the temperature (5-6 °C) of the milieu with a subsequent decrease in bacterial viability. Furthermore, we observed for the first time that virulent bacteria derived from infected samples harbour MNPs, suggesting that the bacteria had biosynthesised the MNPs using the metal ions acquired from the host. AMF treatment of the bacterial isolates from the infected specimens resulted in a strong reduction in viability (3-4 logs) as compared to vancomycin/ciprofloxacin treatment. The therapeutic efficacy of the MNPs to induce bacterial death with AMF alone was confirmed ex vivo using infected tissues. Our proposed antibiotic-free approach for killing bacteria using intracellular MNPs is likely to evolve as a promising strategy to combat a wide range of bacterial infections.

SARS-CoV-2 and tissue damage: current insights and biomaterial-based therapeutic strategies.

The effect of SARS-CoV-2 infection on humanity has gained worldwide attention and importance due to the rapid transmission, lack of treatment options and high mortality rate of the virus. While scientists across the world are searching for vaccines/drugs that can control the spread of the virus and/or reduce the risks associated with infection, patients infected with SARS-CoV-2 have been reported to have tissue/organ damage. With most tissues/organs having limited regenerative potential, interventions that prevent further damage or facilitate healing would be helpful. In the past few decades, biomaterials have gained prominence in the field of tissue engineering, in view of their major role in the regenerative process. Here we describe the effect of SARS-CoV-2 on multiple tissues/organs, and provide evidence for the positive role of biomaterials in aiding tissue repair. These findings are further extrapolated to explore their prospects as a therapeutic platform to address the tissue/organ damage that is frequently observed during this viral outbreak. This study suggests that the biomaterial-based approach could be an effective strategy for regenerating tissues/organs damaged by SARS-CoV-2.

Recent advances in nanotherapeutic strategies that target nitric oxide pathway for preventing cartilage degeneration.

Nitric oxide (NO) is an important inflammatory mediator involved in the development and progression of osteoarthritis (OA). Increased production of NO in the affected joints promote cartilage damage. As NO synthesis is catalysed by the inducible NO synthase (iNOS) enzyme, iNOS inhibition serves as an attractive therapeutic target to prevent NO release. Despite a number of direct and indirect iNOS inhibitor molecules demonstrating chondro-protective effect, none have reached the clinic. Its limited bioavailability and adverse side effects served as a deterrent for pursuing clinical trials in OA patients. With the advent of nanotechnology, interest in targeting NO for preventing cartilage degeneration has revived. In this article, we discuss the limitations of the existing molecules and provide an insight on recent nanotechnology-based strategies that have been explored for the diagnosis and inhibition of NO in OA. These approaches hold promise in reviving the hitherto under explored potential of targeting NO to address OA.

POWERDRESS-mediated histone deacetylation is essential for thermomorphogenesis in Arabidopsis thaliana.

Ambient temperature affects plant growth and even minor changes can substantially impact crop yields. The underlying mechanisms of temperature perception and response are just beginning to emerge. Chromatin remodeling, via the eviction of the histone variant H2A.Z containing nucleosomes, is a critical component of thermal response in plants. However, the role of histone modifications remains unknown. Here, through a forward genetic screen, we identify POWERDRESS (PWR), a SANT-domain containing protein known to interact with HISTONE DEACETYLASE 9 (HDA9), as a novel factor required for thermomorphogenesis in Arabidopsis thaliana. We show that mutations in PWR impede thermomorphogenesis, exemplified by attenuated warm temperature-induced hypocotyl/petiole elongation and early flowering. We show that inhibitors of histone deacetylases diminish temperature-induced hypocotyl elongation, which demonstrates a requirement for histone deacetylation in thermomorphogenesis. We also show that elevated temperature is associated with deacetylation of H3K9 at the +1 nucleosomes of PHYTOCHROME INTERACTING FACTOR4 (PIF4) and YUCCA8 (YUC8), and that PWR is required for this response. There is global misregulation of genes in pwr mutants at elevated temperatures. Meta-analysis revealed that genes that are misregulated in pwr mutants display a significant overlap with genes that are H2A.Z-enriched in their gene bodies, and with genes that are differentially expressed in mutants of the components of the SWR1 complex that deposits H2A.Z. Our findings thus uncover a role for PWR in facilitating thermomorphogenesis and suggest a potential link between histone deacetylation and H2A.Z nucleosome dynamics in plants.

Fatigue in Type 2 Diabetes: Impact on Quality of Life and Predictors.

Fatigue is a persistent symptom, impacting quality of life (QoL) and functional status in people with type 2 diabetes, yet the symptom of fatigue has not been fully explored. The purpose of this study was to explore the relationship between fatigue, QoL functional status and to investigate the predictors of fatigue. These possible predictors included body mass index (BMI), Hemoglobin A1C (HbA1C), sleep quality, pain, number of complications from diabetes, years since diagnosis and depression. Forty-eight individuals with type 2 diabetes (22 females, 26 males; 59.66±7.24 years of age; 10.45 ±7.38 years since diagnosis) participated in the study. Fatigue was assessed by using Multidimensional Fatigue Inventory (MFI-20). Other outcomes included: QoL (Audit of Diabetes Dependent QoL), and functional status (6 minute walk test), BMI, HbA1c, sleep (Pittsburg sleep quality index, PSQI), pain (Visual Analog Scale), number of complications, years since diagnosis, and depression (Beck's depression Inventory-2). The Pearson correlation analysis followed by multivariable linear regression model was used. Fatigue was negatively related to quality of life and functional status. Multivariable linear regression analysis revealed sleep, pain and BMI as the independent predictors of fatigue signaling the presence of physiological (sleep, pain, BMI) phenomenon that could undermine health outcomes.

Genetic Architecture of Natural Variation in Thermal Responses of Arabidopsis.

Wild strains of Arabidopsis (Arabidopsis thaliana) exhibit extensive natural variation in a wide variety of traits, including response to environmental changes. Ambient temperature is one of the major external factors that modulates plant growth and development. Here, we analyze the genetic architecture of natural variation in thermal responses of Arabidopsis. Exploiting wild accessions and recombinant inbred lines, we reveal extensive phenotypic variation in response to ambient temperature in distinct developmental traits such as hypocotyl elongation, root elongation, and flowering time. We show that variation in thermal response differs between traits, suggesting that the individual phenotypes do not capture all the variation associated with thermal response. Genome-wide association studies and quantitative trait locus analyses reveal that multiple rare alleles contribute to the genetic architecture of variation in thermal response. We identify at least 20 genomic regions that are associated with variation in thermal response. Further characterizations of temperature sensitivity quantitative trait loci that are shared between traits reveal a role for the blue-light receptor CRYPTOCHROME2 (CRY2) in thermosensory growth responses. We show the accession Cape Verde Islands is less sensitive to changes in ambient temperature, and through transgenic analysis, we demonstrate that allelic variation at CRY2 underlies this temperature insensitivity across several traits. Transgenic analyses suggest that the allelic effects of CRY2 on thermal response are dependent on genetic background suggestive of the presence of modifiers. In addition, our results indicate that complex light and temperature interactions, in a background-dependent manner, govern growth responses in Arabidopsis.

Safety of aerobic exercise in people with diabetic peripheral neuropathy: single-group clinical trial.

BACKGROUND: Exercise is recommended for people with diabetes, but little is known about exercise in people with diabetic peripheral neuropathy (DPN). OBJECTIVE: The primary purpose of this preliminary study was to examine adverse events (AEs) during moderate-intensity, supervised aerobic exercise in people with DPN. The secondary purpose was to examine changes in fatigue, aerobic fitness, and other outcomes after intervention. DESIGN: This was a single-group preliminary study. SETTING: The setting was an academic medical center. PARTICIPANTS: Participants were 18 people who were sedentary and had type 2 diabetes and peripheral neuropathy (mean age=58.1 years, SD=5). INTERVENTION: The intervention was a supervised 16-week aerobic exercise program (3 times per week at 50% to >70% oxygen uptake reserve). MEASUREMENTS: Adverse events were categorized as related or unrelated to the study, anticipated or unanticipated, and serious or not serious. Outcomes included fatigue (Multidimensional Fatigue Inventory), cardiovascular fitness (peak oxygen uptake), body composition (dual-energy x-ray absorptiometry), sleep quality, plasma metabolic markers, and peripheral vascular function. RESULTS: During the study, 57 nonserious AEs occurred. Improvements were found in general fatigue (mean change=-3.5; 95% confidence interval [95% CI]=-1.3, -5.3), physical fatigue (mean change=-3.1; 95% CI=-1.2, -5.0), peak oxygen uptake (mean change=1.1 mL·kg(-1)·min(-1); 95% CI=0.2, 1.9), total body fat (mean change=-1%; 95% CI=-0.3, -1.7), fat mass (mean change=-1,780 g; 95% CI=-616.2, -2,938.7), and peripheral blood flow (mean change=2.27%; 95% CI=0.6, 4.0). LIMITATIONS: This was a small-scale, uncontrolled study. A future randomized controlled trial is needed to fully assess the effects of exercise on the outcomes. CONCLUSIONS: This study provides new support for supervised aerobic exercise in people with DPN. However, it is important for physical therapists to carefully prescribe initial exercise intensity and provide close monitoring and education to address the anticipated AEs as people who are sedentary and have DPN begin an exercise program.

A SNP (g.358A > T) at intronic region of CD9 molecule of crossbred bulls may associate with spermatozoal motility.

The surface expression of CD9 (cluster-of-differentiation antigen-9) in sperms of certain mammalian species has been attributed to its fusion with the egg and thereby dictating the fertility of species. In the present study, we investigated the association of CD9 with crossbred bull sperm quality and quantity trait was analyzed using a total of 96 Frieswal (HF × Sahiwal) crossbred. A single nucleotide polymorphism (g.358A > T) in intron 6 was significantly associated with sperm concentration (P < 0.05) and motility percentage (P < 0.01). mRNA was extracted from good (progressive motility > 50%) and motility impaired (progressive motility < 50%) bull semen. The mRNA expression and seminal plasma protein concentration of CD9 was significantly (P < 0.05) higher among good quality bull semen than motility impaired ones. Our results thus may indicate that, mutation in the intronic region may be responsible for the instability of RNA and the subsequent functional protein expression.

Association of breast arterial calcification with stroke and angiographically proven coronary artery disease: a meta-analysis.

OBJECTIVE: We conducted a meta-analysis of the current literature to deduce the strength of association between breast arterial calcification (BAC) and coronary artery disease (CAD) and/or stroke. METHODS: PubMed, Google Scholar, ClinicalTrials.gov, and Ovid were searched for English-language literature up to August 2013 using the terms "breast arterial calcification," "breast vascular calcification," "coronary artery disease," "coronary heart disease," "cardiovascular disease," "abnormal coronary angiography," and "stroke." A hand search of the reference lists of key articles was performed to supplement the literature search. Our literature search revealed 75 articles for further abstract review. Limiting our search to articles that quantitatively assessed the correlation between BAC and stroke or angiographically proven CAD, we reviewed 35 full manuscripts. Of these articles, 14 were included in the final analysis. RESULTS: We analyzed 10 cross-sectional studies (n = 3,952) with CAD as the primary outcome (diagnosed by coronary angiography). The odds ratio (95% CI) for CAD in those with BAC versus those without BAC is 3.86 (3.25-4.59) (P < 0.0001). For stroke, six cross-sectional studies were analyzed (n = 18,888). The odds ratio (95% CI) for stroke in those with BAC versus those without BAC is 1.54 (1.25-1.90) (P < 0.0001). CONCLUSIONS: These results suggest that BAC is significantly associated with both CAD and stroke. Although more prospective studies are warranted to clarify whether BAC is truly a predictor of the future development of CAD and stroke, the concept that BAC is a benign finding is waning.

Development of a tetra-primer ARMS PCR-based assay for detection of a novel single-nucleotide polymorphism in the 5' untranslated region of the bovine ITGB6 receptor gene associated with foot-and-mouth disease susceptibility in cattle.

ITGB6 is known to be one of the major receptor components involved in host tropism of foot-and-mouth disease (FMD) virus in cattle. A competitive PCR technique called ARMS PCR was adapted to identify a single-nucleotide polymorphism (SNP), G29A, db SNP Id: rs109075046, in the 5' untranslated region (5'UTR) of the bovine ITGB6 gene. Genotype profiling identified three kinds of genetic variation within the targeted SNP among Frieswal crossbred cattle. The occurrence of FMD in the three genotypes was further evaluated, revealing a clear role in the incidence of FMD in the studied population.

Fatigue and related factors in people with type 2 diabetes.

PURPOSE: The purpose of this study was to examine the presence and severity of fatigue in people with type 2 diabetes. METHODS: The Fatigue Severity Scale (FSS), Fatigue Assessment Scale (FAS), and Visual Analog Fatigue Scale (VAFS) were administered by anonymous survey of 37 individuals with and 33 individuals without diabetes to assess the presence of fatigue. Data on age, gender, weight, height, year of diagnosis, and number/type of complications were also collected. Nonparametric tests tested for differences in fatigue measures between the groups, and distribution characteristics of the FAS, FSS, and VAFS scores were examined. Spearman rank correlation coefficients examined the relationships between the variables. RESULTS: People with diabetes scored higher on all 3 fatigue assessment scales as compared to controls (FAS: 25.11 vs 19.94, P = .001; FSS: 4.30 vs 2.59, P = .000; VAFS: 4.64 vs 1.75, P = .000). Data were normally distributed for FSS in the group with diabetes and the group without diabetes, and scores of FAS, FSS, and VAFS showed no ceiling effects. A positive correlation was noted between fatigue measures and number of complications (r = .482; P = .003). CONCLUSIONS: Higher levels of fatigue were noted in people with type 2 diabetes as compared to healthy age-matched control; however, the cause and impact of these changes remain unclear. FSS is a recommended tool for measuring fatigue in this population. Further studies are needed to explore the contributing factors to fatigue in those with diabetes.

The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy.

UNLABELLED: Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. METHODS: A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. RESULTS: Significant reductions in pain (-18.1±35.5 mm on a 100 mm scale, P=.05), neuropathic symptoms (-1.24±1.8 on MNSI, P=.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, P=.008) from a proximal skin biopsy were noted following the intervention. CONCLUSIONS: This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies.

Circadian cycle and chronotherapeutics: recent trend for the treatment of various biological disorders.

Chronotherapeutics is a novel approach in the treatment of various biological disorders. Circadian rhythms are the important factor in the biological cycle through which the drug dosing should be matched with the rhythms of the diseases for the successful treatment of the illness or the disorder. Through this review it shows that different chronotherapeutic approaches have been successfully employed for treating different biological disorders through different formulation methods, and discussion of recent patents.