Stress and Allostatic Load in Patients With Primary Open Angle Glaucoma.

PRCIS: This study evaluated the allostatic load (AL) in primary open angle glaucoma (POAG) patients and reported that the AL score was significantly higher in glaucoma patients compared with age-matched controls. PURPOSE: To evaluate the AL in patients with POAG. METHODS: This case-control study comprised 50 POAG (glaucoma patients) and 50 age-matched controls without glaucoma (controls). AL was estimated based on 13 variables: systolic blood pressure (BP), diastolic BP, homocysteine, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, body mass index, serum cortisol, glycosylated hemoglobin, albumin, creatinine clearance, and C-reactive protein. High-risk thresholds were determined based on biological cutoffs of each biomarker. One point was assigned for each biomarker reading above cutoff and were summated to obtain AL score; score ≥4 was considered high. RESULTS: Mean age of glaucoma patients was 60.82±6.26 and 60.14±6.72 years in controls ( P =0.602). All components of AL score (except C-reactive protein) had higher values in glaucoma patients. There was a statistically significant difference in homocysteine ( P =0.001), total cholesterol ( P =0.037), high-density lipoprotein ( P =0.005), and glycosylated hemoglobin ( P =0.003). Mean AL score was 4.68±2.09 in glaucoma patients and 3.32±1.34 in controls ( P <0.001). There was significant association of high AL score with older age ( P =0.006), low socioeconomic status ( P =0.020), and glaucoma severity ( P =0.001). Negative correlation was seen between AL and retinal nerve fiber layer thickness (Right Eye: r =-0.37, P <0.001; Left Eye: r =-0.298, P <0.001) and visual field mean deviation (Right Eye: r =-0.469, P <0.001; Left Eye: r =-0.520, P <0.001). CONCLUSIONS: Glaucoma patients exhibited allostatic overload indicating physiological dysregulation to chronic stress although additional research is required to establish causality. A holistic approach with lifestyle modifications to reduce chronic stress should be an integral part of managing glaucoma patients as it would serve both to possibly reduce or prevent disease progression and improve overall health outcomes.

Therapeutic targeting of the tumor microenvironments with cannabinoids and their analogs: Update on clinical trials.

Cancer is a major global public health concern that affects both industrialized and developing nations. Current cancer chemotherapeutic options are limited by side effects, but plant-derived alternatives and their derivatives offer the possibilities of enhanced treatment response and reduced side effects. A plethora of recently published articles have focused on treatments based on cannabinoids and cannabinoid analogs and reported that they positively affect healthy cell growth and reverse cancer-related abnormalities by targeting aberrant tumor microenvironments (TMEs), lowering tumorigenesis, preventing metastasis, and/or boosting the effectiveness of chemotherapy and radiotherapy. Furthermore, TME modulating systems are receiving much interest in the cancer immunotherapy field because it has been shown that TMEs have significant impacts on tumor progression, angiogenesis, invasion, migration, epithelial to mesenchymal transition, metastasis and development of drug resistance. Here, we have reviewed the effective role of cannabinoids, their analogs and cannabinoid nano formulations on the cellular components of TME (endothelial cells, pericytes, fibroblast and immune cells) and how efficiently it retards the progression of carcinogenesis is discussed. The article summarizes the existing research on the molecular mechanisms of cannabinoids regulation of the TME and finally highlights the human studies on cannabinoids' active interventional clinical trials. The conclusion outlines the need for future research involving clinical trials of cannabinoids to demonstrate their efficacy and activity as a treatment/prevention for various types of human malignancies.

Presence of potent inhibitors of bacterial biofilm associated proteins is the key to Citrus limon's antibiofilm activity against pathogenic Escherichia coli.

In an era of antibiotic resistance where natural antibiotic substitutes are considered essential, the antimicrobial and antibiofilm activities of Citrus limon extract on strains of pathogenic Escherichia coli isolated from pork were evaluated. The strains which form biofilms were more resistant (MIC50 = 2.5 mgml-1) compared to non-biofilm forming strains (MIC50 = 1.25 mgml-1). Use of C. limon extract at 20 mgml-1 concentration has resulted in inhibition of biofilm formation by 53.96%. Cyclobarbital, 5, 8-dimethoxycumarin, orotic acid and 3-methylsalicylhydrazide were the major phytochemicals in C. limon extract with highest docking affinities against the biofilm associated proteins in E. coli. The results of simulation studies have clearly illustrated the energy stability of the protein-ligand complexes. Absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles revealed that the phytochemicals in C. limon could be used in the drug design studies to preferentially target the specific receptors to combat biofilms associated with E. coli.

Molecular Docking and Network Pharmacology Interaction Analysis of Gingko Biloba (EGB761) Extract with Dual Target Inhibitory Mechanism in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative dementia affecting people in their later years of life. The AD prevalence rate has significantly increased due to a lack of early detection technology and low therapeutic efficacy. Despite recent scientific advances, some aspects of AD pathological targets still require special attention. Certain traditionally consumed phytocompounds have been used for thousands of years to treat such pathologies. The standard extract of Gingko biloba (EGB761) is a combination of 13 macro phyto-compounds and various other micro phytocompounds that have shown greater therapeutic potential against the pathology of AD. OBJECTIVE: Strong physiological evidence of cognitive health preservation has been observed in elderly people who keep an active lifestyle. According to some theories, consuming certain medicinal extracts helps build cognitive reserve. We outline the research employing EGB761 as a dual target for AD. METHODS: This study investigates various inhibitory targets against AD using computational approaches such as molecular docking, network pharmacology, ADMET (full form), and bioactivity prediction of the selected compounds. RESULTS: After interaction studies were done for all the phytoconstituents of EGB761, it was concluded that all four of the phytocompounds (kaempferol, isorhamnetin, quercetin, and ginkgotoxin) showed the maximum inhibitory activity against acetylcholinesterase (AChE) and GSK3ß. CONCLUSION: The highly active phytocompounds of EGB761, especially quercetin, kaempferol, and isorhamnetin, have better activity against AChE and GSK3ß than its reported synthetic drug, according to molecular docking and network pharmacology research. These compounds may act on multiple targets in the protein network of AD. The AChE theory was primarily responsible for EGB761's therapeutic efficacy in treating AD.

Imaging Patients with Kidney Failure.

The approach to imaging a patient with kidney failure continues to evolve. Overstatement of the risk of iodinated contrast material-induced (ie, contrast-induced) acute kidney injury and new guidelines for administration of gadolinium-based contrast media affect screening and the choice of contrast material. Treatment of kidney failure requires dialysis or a kidney transplant. Pretransplant imaging includes assessment for the feasibility of performing a transplant and evaluation for underlying malignancy and peripheral vascular disease. Patients with kidney failure are at high risk for renal cell carcinoma. Subtypes that occur exclusively or more commonly in patients with kidney failure, such as acquired cystic kidney disease, renal cell carcinoma, and clear cell papillary renal cell carcinoma, have specific clinical-pathologic characteristics, with indolent behavior. Performing US for dialysis planning increases the success of placement of an arteriovenous fistula, while postoperative US evaluation is essential in assessment of access dysfunction. Systemic manifestations in patients with kidney failure are multifactorial and may relate to the underlying cause of renal failure or may be secondary to treatment effects. Disturbances in mineral and bone metabolism and soft-tissue and vascular calcifications are seen in patients with chronic kidney disease and mineral bone disorder. Neurologic and cardiothoracic complications are also common. The authors provide a comprehensive overview of imaging considerations for patients with kidney failure, including the appropriate use of CT, MRI, and US with their respective contrast agents; the use of imaging in transplant workup and dialysis assessment; and the common renal and extrarenal manifestations of kidney failure. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Dereplication approach for the first time isolation of tatarinowin a and pentadecanoic acid from Acorus calamus L. by using GC-MS.

In the present study, we report herein the isolation of cadinane-type sesquiterpenoid, tatarinowin A (ACH-6), and pentadecanoic acid (ACH-8) from petroleum ether extract of rhizome of Acorus calamus L. (Acoraceae) along with 6 other known compounds in this species. It is pertinent to mention here that this is the first report to stain these compounds in which dereplication approach based on GC-MS was applied to target unknown compounds ACH-6 and ACH-8 in A. calamus L. Derelpication approaches based on GC-MS is very useful technique in the area of drug discovery and have eminence potential to identify known and unknown compounds present in extracts of medicinal important plants. This technique can be used to expedite the process of purification of unknown compounds from different matrixes. The isolated compounds were identified with the help of inbuilt library search which reveals the presence of 17 known and 4 unknown compounds. Further, the structure elucidation of all isolated compounds was done using spectroscopy techniques. Also, the structure of ACH-6 was further confirmed by using the single-crystal X-ray diffraction technique.

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Effect of integrated people-centred eye care (IPEC) model on eye care seeking behaviour of community.

Background: World report on vision makes integrated people-centered eye care as care model of choice. Integrating eye care with the existing public health system makes services available, accessible, affordable, and sustainable. Being from the community, Accredited Social Health Activists (ASHAs) are better suited to improve people's eye health-seeking behavior. Objectives: This study aims to assess the eye care-seeking behavior of community and to understand their response toward the approach of integrated vision centers (VC) with ASHA involvement. Methods: A cross-sectional descriptive study was conducted in South Delhi district where integrated VC were functional for more than a year. These centers were supervised by medical officer in-charge, under whom ophthalmic assistants, ASHAs, auxiliary nurse midwives, and pharmacist work. ASHAs were trained in community-based primary eye care. The community survey was conducted on eye health-seeking behavior and utilization of VC services. Descriptive statistics were used for data analysis. Results: Out of 1571 study participants, 998 reported any ophthalmic illness in family in the past 6 months as against 1302 who reported nonophthalmic illness in family. The majority (1461, 90%) were aware about integrated VC and half of them (748, 51.2%) visited it. Of them, 64.2% were motivated through ASHAs. ASHAs spread awareness about eye diseases, eye treatment facility, and referred patients from the community. The majority (93%) were happy with the integrated VC and 87.8% were happy with ASHAs. Conclusion: Integrated VC with ASHA engagement could pave the way for universal eye health. Understanding people's needs and engaging community would increase the demand for eye care.

Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks.

Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of multiple sclerosis (MS) symptoms, which has also shown beneficial effects against Alzheimer's (AD) and Parkinson's (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling-based quantitative mass-spectrometric approach to investigate the mechanism of action of Fingolimod. This study identified 6749 and 6319 proteins in CB and FC, respectively, and returned 2609 and 3086 differentially expressed proteins in mouse CB and FC, respectively, between Fingolimod treated and control groups. Subsequent bioinformatics analyses indicated a metabolic reprogramming in both brain regions of the Fingolimod treated group, where oxidative phosphorylation was upregulated while glycolysis and pentose phosphate pathway were downregulated. In addition, modulation of neuroinflammation in the Fingolimod treated group was indicated by upregulation of retrograde endocannabinoid signaling and autophagy pathways, and downregulation of neuroinflammation related pathways including neutrophil degranulation and the IL-12 mediated signaling pathway. Our findings suggest that Fingolimod may exert its protective effects on the brain by inducing metabolic reprogramming and neuroinflammation pathway modulation.

Biochemical Characterization of Different Chemical Components of Parthenium hysterophorus and Their Therapeutic Potential against HIV-1 RT and Microbial Growth.

Parthenium hysterophorus possesses certain allelochemicals responsible for their medicinal effects. The presence of oils, polyphenols, alkaloids, terpenes, pseudoguaianolides, and histamines in P. hysterophorus has been shown to exhibit medicinal properties. However, the systematic biomedical properties of this plant are still unexplored. The extracts of leaves, stem, and flower of P. hysterophorus, both at low and high temperatures (equivalent to boiling points of different solvents) were prepared. The extracts prepared in hexane, ethylacetate, methanol, and water were analyzed spectrophotometrically and colorimetrically and resolved on TLC for the presence of phytochemicals. The analyses of the free radical quenching potential of plant extracts were done by DPPH assay. The total antioxidant capacity was determined by phosphomolybdate assay and the ferric reducing antioxidant power (FRAP) assay was used to determine the reduction potential of the extracts. The spectrophotometric and qualitative analysis of plant extracts demonstrated the presence of alkaloids, terpenoids, carbohydrates, and cardiac glycosides. The occurrence of more than one Rf values for extracts determined by TLC indicated the presence of more than one phytochemical compound. The P. hysterophorus extracts contained strong antioxidant activity. These extracts exhibited strong antimicrobial activity against Staphylococcus epidermis, Salmonela typhi, Neisseria gonococci or gonococci, Citrobacter, and Shigella flexineri. The evaluation of the antimicrobial potential of P. hysterophorus extracts was done by the disc diffusion method. These extracts also showed significant inhibition against HIV-1 RT activity. The anti-HIV-1 RT activity was done using Roche Kit. The P. hysterophorus extracts displayed the presence of many phytochemicals with strong antioxidant, antimicrobial, and anti-HIV-1 RT properties.

Pharmacological Chemistry and Biomedical Implications of Chemical Ingredients from Parthenium hysterophorus.

Parthenium hysterophorus L. belonging to the family Asteraceae is a noxious weed infestation with allelopathic effects with its lower economic value. It poses a serious risk to its surroundings. The presence of oils, polyphenols, flavones, flavonoids, alkaloids, terpenes, pseudoguaianolides, and histamines in P. hysterophorus makes it important and beneficial due to its medicinal properties. This review article is focused on the history, geographical distribution, chemical composition, and molecular structure of some phytochemicals and ethanopharmacological aspects of P. hysterophorus. The harmful effects of this weed have also been included. The information available from the existing literature revealed that P. hysterophorus is rich in various phytochemicals with different pharmacological activities. However, the complete analysis of different phytoconstituents isolated from P. hysterophorus and their specific properties are not fully understood. The sporadic information published in some journals suggests that this plant could be exploited to develop new drugs against certain diseases, including cancer, HIV-1 infection, and immunological disorders. The structure and mode of action of some compounds such as parthenin and stigmasterol were also discussed. Though the current information on P. hysterophorus indicates the ethnopharmacological implications of extracts of this plant, more systematic and extensive studies are still required to properly understand the contribution of its specific chemical constituents responsible for their various medicinal properties.

Treatment of chronic airway diseases using nutraceuticals: Mechanistic insight.

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.

A Proteomic View of Cellular and Molecular Effects of Cannabis.

Cannabis (Cannabis sativa), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease, schizophrenia and glaucoma; these have prompted changes in medicinal cannabis legislation. The relaxation of legal restrictions and increased socio-cultural acceptance has led to its increase in both medicinal and recreational usage. Several biochemically active components of cannabis have a range of effects on the biological system. There is an urgent need for more research to better understand the molecular and biochemical effects of cannabis at a cellular level, to understand fully its implications as a pharmaceutical drug. Proteomics technology is an efficient tool to rigorously elucidate the mechanistic effects of cannabis on the human body in a cell and tissue-specific manner, drawing conclusions associated with its toxicity as well as therapeutic benefits, safety and efficacy profiles. This review provides a comprehensive overview of both in vitro and in vivo proteomic studies involving the cellular and molecular effects of cannabis and cannabis-derived compounds.

Efficacy of two siddha polyherbal decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with standard allopathy treatment in the management of mild to moderate symptomatic COVID-19 patients-a double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIM: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success to date. Indian traditional medicines, especially polyherbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine, have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. METHODS: The study was a double-blind, placebo-controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020-Dec 2020). Participants were randomized into 3 arms; placebo-decaffeinated tea in Arm I, NVK in Arm II, and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough, and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR), liver function test (LFT), renal function test (RFT), and electrolytes and electrocardiogram (ECG) at baseline (day 0) and days 3, 6, and 10. Post-treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. RESULTS: The results revealed that when compared to patients in the placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to the intensive care unit (ICU) and three patients from Arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years, respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from the placebo group on that day. The hospital stay time for patients in Arm I was significantly longer (mean [SD]=8.4 [2.0] days) as compared to the Arms II and III (mean [SD]=4.7 [1.5] and 4.2 [1.5] days, respectively (Kruskal-Wallis test, P=0.0001). Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean of 2.5 and 1.7 days, respectively, Arm I, patients took a mean of 4.2 days (Kruskal-Wallis test, P=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhea lasting a day in Arm I and Arm II, respectively. The mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, placebo=4.0, P=0.02). The other blood biochemical parameters like C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer that were analyzed at the baseline and at the time of discharge from the hospital, were not significantly different in the three arms. CONCLUSION: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea). The primary outcome measures of the KSK arm were significantly better than those in the NVK arm.

Euglena Species: Bioactive Compounds and their Varied Applications.

Euglena, a microalga, has gained a great attention as it contains several bioactive compounds including food supplements, drugs and biofuels. The genus Euglena includes >300 species of unicellular, fresh water flagellates. The objective of this review article concerns the presentation of updated information on pharmacological and therapeutic properties and industrial implications of molecules isolated from Euglena species. A bibliographic search of scientific literature published till March, 2020 was made from scientific databases using different search engines. Euglena produces several antioxidant molecules, such as ß-carotene, L-ascorbic acid, polymers of unsaturated fatty acids and phytotoxins useful in manufacturing many pharmaceutical, cosmetics, and nutraceutical compounds. It is a rich source of antimicrobial, anticancer, immunomodulatory compounds. Though, several studies have indicated its therapeutic applications, extensive research is needed to explore its efficacy against many pathophysiological conditions including toxicity assessment of compound(s). Nevertheless, the biotechnological influence on industrial production of Euglena has been less exploited.

Edge-enhancing gradient echo with multi-image co-registration and averaging (EDGE-MICRA) for targeting thalamic centromedian and parafascicular nuclei.

BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus is an effective treatment for multiple neurological disorders. The centromedian and parafascicular nuclei are recently emerging targets for multiple conditions, such as epilepsy and Tourette syndrome; however, their limited visibility on conventional magnetic resonance imaging sequences has been a major obstacle. The goal of this study was to demonstrate the feasibility of a high-resolution and high-contrast targeting sequence for centromedian-parafascicular deep brain stimulation using a recently described magnetic resonance imaging sequence, three-dimensional edge-enhancing gradient echo. METHODS: The three-dimensional edge-enhancing gradient echo sequence was performed on a normal volunteer for a total of six acquisitions. Multi-image co-registration and averaging was performed by first co-registering each of the six scans and then averaging to produce an edge-enhancing gradient echo-multi-image co-registration and averaging scan. The averaging was also performed for two, three, four and five scans to assess the change in the signal-to-noise ratio and identify the ideal balance of image quality and scan time. RESULTS: The edge-enhancing gradient echo-multi-image co-registration and averaging scan allowed clear boundary delineation of the centromedian and parafascicular nuclei. The signal-to-noise ratio increased as a function of increasing scan number, but the added gain was small beyond four scans for the imaging parameters used in this study. CONCLUSIONS: The recently described three-dimensional edge-enhancing gradient echo sequence provides an easily implementable approach, using widely available magnetic resonance imaging technology without complex post-processing techniques, to delineate centromedian and parafascicular nuclei for deep brain stimulation targeting.

A double blinded placebo controlled comparative clinical trial to evaluate the effectiveness of Siddha medicines, Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy treatment in the management of symptomatic COVID 19 patients - a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The primary objectives of the study are to determine the effectiveness of the Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy Treatment to compared with Placebo (Decaffeinated Tea) with standard Allopathy Treatment in the management of Symptomatic COVID 19 patients and also in reduction of Hospital Stay Time & Changes in Immunological (IL6) and Bio Chemical Markers (Ferritin, CRP, D-Dimer and LDH). The secondary objectives are to evaluate the safety of the trial medicines and their effects in the reduce the risks of the disease. In addition, to document the profile of Symptomatic COVID 19 patients as per Siddha Principles. TRIAL DESIGN: A Double Blinded, Three arm, Single Centre, Placebo Controlled, Exploratory and comparative Randomized Controlled Trial PARTICIPANTS: Patients who were admitted to the COVID Care Centre at Govt. Institute of Medical Sciences. Noida in India will be recruited. These will be patients with Mild and Moderate symptoms with laboratory confirmed COVID 19 (RT - PCR Tested Positive) aged 18-65, willing and consenting to participate. INTERVENTION AND COMPARATOR: Arm I: Decaffeinated Tea (Placebo - similar in taste and appearance to the other Two Decoctions), 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm II: Nilavembu Kudineer (The Siddha Medicines which is used as a standard Anti-Viral drug for the past Pandemics by Siddha Physicians) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm III: Kaba Sura Kudineer (The Siddha Medicine which is proposed to be used as a Treatment for COVID 19 based on Siddha Literature) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. The investigational drugs are registered products under the Govt.of India and bought from GMP Certified Manufacturing Units. MAIN OUTCOMES: Primary outcomes: 1. Reduction in Viral load of SARS-CoV-2 at the end of treatment (10 days). 2. Time taken to convert Patient from symptomatic to Asymptomatic based on Reduction in clinical symptoms (10 days). 3. Effect of drugs inflammatory markers (IL6,) at the end of treatment (10 days). 4. Reduction in hospital stay time (20 days follow up). (Based on RT PCR CT Value 3rd, 6th if needed 10th day). (Based on IL 6 Value needed 10th day or IL6 value on turning negative. (entry level/exit level). Secondary outcomes (10 days): 1. Reduction in use of Intensive Supportive Care. 2. Reduction in incidence of complications (Acute Respiratory Distress Syndrome, other systemic complications). 3. MuLBSTA score for viral pneumonia (multinodular infiltration, hypo-lymphocytosis, bacterial co infection, Total Leucocyte Count (TLC ≤ 0.8 x 109/L), smoking history, hyper-tension and age) score. 4. Laboratory markers (Haematological & Biochemical Markers). 5. Adverse events/effects Siddha-based measurements. 6. Siddha Udaliyal assessment by using Yakkai Ilakkanam (YI) Tool to diagnose body condition for covid-19 patients. RANDOMISATION: The assignment of the participants into 3 Groups will be allocated in 1:1:1 Ratio through randomization Blocks in Microsoft Excel by a Statistician who is not involved in the study. The allocation scheme will be made by another statistician by using a closed envelope after the assessment of eligibility and Informed consent procedures. The groups will be balanced for age and sex with 3:1 Ratio in each group for mild: severe COVID-19 symptoms. BLINDING: The Study is Double Blinded. Participants and Investigators were blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Sample size could not be calculated, Since there are no prior trials on KSK and NVK as a comparative trial. In addition, there are no prior trials on KSK and NVK in this region. A total Number of 120 Patients, 40 each in 3 groups will be recruited in 1:1:1 Ratio. TRIAL STATUS: Protocol Number : SCRUND GIMS Noida Study 1,Version: 2.0 Protocol Date : 20.08.2020 The recruitment period is completed for the trial. The Trial started its recruitment on 22.8.2020. We anticipate study including data analysis will finish in January 2021. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. TRIAL REGISTRATION: The trial protocol was registered with CTRI (Clinical Trial Registry of India) and number is CTRI/2020/08/027286 on 21.08.2020 FULL PROTOCOL: The full Protocol is attached as an additional file, Accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated. This letter serves as a summary of the key elements of the full protocol. The Study protocol has been reported in accordance with the SPIRIT guidelines.

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment.

Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates.

BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.

Anti-Inflammatory and Antioxidative Potential of Aloe vera on the Cartap and Malathion Mediated Toxicity in Wistar Rats.

Aloe vera has been the most useful medicinal herb in the world since ancient times due to its vast biological effects. The presence of high content of bioactive compounds make Aloe vera a promising complementary and alternative agent in disease prevention. The effectiveness of A. vera-based medicines against pesticide toxicity has never been evaluated. It was therefore envisaged to develop an A. vera-based strategy to protect the non-target animals from adverse effects of the pesticides. This article illustrates the ameliorating effect of aqueous extract (AE) of A. vera leaves against the cartap and malathion toxicity. To evaluate the protective impact of A. vera against cartap (Ctp), malathion (Mtn) and a mixture of both pesticides, the animals were divided in eight groups, each containing six rats: Group 1- C (control), Group 2- AE + C, Group 3- Ctp, Group 4- Mtn, Group 5- Ctp + Mtn, Group 6- AE + Ctp, Group 7- AE + Mtn, Group 8- AE + Ctp + Mtn. Wistar rats exposed to Ctp, Mtn and Ctp + Mtn, displayed significant change in body weight. It was observed that the WBC level increased significantly in Mtn and Ctp + Mtn challenged groups. The contents of TNF-α and IL-6 in serum increased expressively in the Ctp, Mtn and Ctp + Mtn challenged groups. Rats treated with Ctp, Mtn and Ctp + Mtn displayed significant alterations in the levels of antioxidative indices (MDA, GSH, GST, GPx, SOD and CAT). Significant alterations were recorded in the activities of AST, ALT, ACP and ALP in Ctp, Mtn and Ctp + Mtn challenged groups. The histopathological results of liver supported the biochemical data. The pre-treatment of rats with the aqueous extract of A. vera leaves significantly protected them from the toxicity of pesticides. These results suggested that A. vera extract may be used as a promising natural agent for the management of pesticide induced toxicity.