C-reactive protein and procalcitonin: As predictor biomarkers of severity and outcome in children with community-acquired pneumonia.

Our cohort study aimed to compare serum C-reactive protein (CRP) and procalcitonin (PCT) levels in children with community-acquired pneumonia defined by WHO. The former differentiated between pneumonia and severe pneumonia while the latter was better for the outcome of pneumonia.

Pulmonary mucormycosis diagnosed by ultrasound guided percutaneous biopsy: A case series.

Pulmonary mucormycosis is a rare but highly lethal fungal infection, usually affecting immunocompromised patients. Pulmonary mucormycosis was also a critical problem that complicated the later part of the clinical course of COVID-19 in India. Early diagnosis of the disease, combined with aggressive treatment, is crucial for patient survival. Fibreoptic bronchoscopy is a useful procedure for diagnosis of pulmonary mucormycosis, but image-guided percutaneous biopsy efficiently samples lesions abutting the chest wall. Biopsy is more yielding than cultures and imaging guided biopsy is required for lesions that cannot be microbiologically confirmed by fibreoptic bronchoscopy. We present a case series of four patients of pulmonary mucormycosis in whom ultrasound guided biopsy clinched the diagnosis. All the four patients were poor surgical candidates and underwent medical management with antifungal agents, and had successful clinical recovery and radiological resolution. Our case series illustrates the utility of ultrasound guided percutaneous biopsy as a diagnostic tool for sampling cavitatory disease due to pulmonary mucormycosis, when fibreoptic bronchoscopy failed to yield a diagnosis and the beneficial role antifungal agents as salvage therapy in poor surgical candidates.

Multifaceted approach toward mapping out the anticancer properties of small molecules via in vitro evaluation on melanoma and nonmelanoma skin cancer cells, and in silico target fishing.

Melanoma and nonmelanoma skin cancers are among the most prevalent and most lethal forms of skin cancers. To identify new lead compounds with potential anticancer properties for further optimization, in vitro assays combined with in-silico target fishing and docking have been used to identify and further map out the antiproliferative and potential mode of action of molecules from a small library of compounds previously prepared in our laboratory. From screening these compounds in vitro against A375, SK-MEL-28, A431, and SCC-12 skin cancer cell lines, 35 displayed antiproliferative activities at the micromolar level, with the majority being primarily potent against the A431 and SCC-12 squamous carcinoma cell lines. The most active compounds 11 (A431: IC50 = 5.0 µM, SCC-12: IC50 = 2.9 µM, SKMEL-28: IC50 = 4.9 µM, A375: IC50 = 6.7 µM) and 13 (A431: IC50 = 5.0 µM, SCC-12: IC50 = 3.3 µM, SKMEL-28: IC50 = 13.8 µM, A375: IC50 = 17.1 µM), significantly and dose-dependently induced apoptosis of SCC-12 and SK-MEL-28 cells, as evidenced by the suppression of Bcl-2 and upregulation of Bax, cleaved caspase-3, caspase-9, and PARP protein expression levels. Both agents significantly reduced scratch wound healing, colony formation, and expression levels of deregulated cancer molecular targets including RSK/Akt/ERK1/2 and S6K1. In silico target prediction and docking studies using the SwissTargetPrediction web-based tool suggested that CDK8, CLK4, nuclear receptor ROR, tyrosine protein-kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, might be prospective targets for the two most active compounds. Further validation of these targets by western blot analyses, revealed that ROCK/Fyn and its associated Hedgehog (Hh) pathways were downregulated or modulated by the two lead compounds. In aggregate, these results provide a strong framework for further validation of the observed activities and the development of a more comprehensive structure-activity relationship through the preparation and biological evaluation of analogs.

The Role of Outpatient Physical Medicine and Rehabilitation in a Multidisciplinary Prehabilitation Program for Older Adults before Allogeneic Hematopoietic Stem Cell Transplant.

INTRODUCTION: Physical rehabilitation is increasingly incorporated throughout the allogeneic hematopoietic stem cell transplant (allo-HSCT) journey for older adults. OBJECTIVE: This study aimed to describe physical medicine and rehabilitation (PM&R)-related diagnoses, exercise barriers, and management recommendations for older adults before allo-HSCT. DESIGN: Fifty PM&R consults as part of the Enhanced Recovery-Stem Cell Transplant (ER-SCT) multidisciplinary prehabilitation program at a comprehensive cancer center were retrospectively reviewed. RESULTS: Many PM&R-related diagnoses (173), exercise barriers (55), and management recommendations (112) were found. Common diagnoses were musculoskeletal dysfunction (more commonly back, shoulder, then knee) (n = 39, 23%) and fatigue (n = 36, 21%). Common exercise barriers were also musculoskeletal dysfunction (more commonly back, knee, then shoulder) (total n = 20, 36%) and fatigue (n = 20, 36%). Most patients (n = 32, 64%) had 1 or more exercise barriers. Common PM&R management recommendations were personalized exercise counseling (n = 37, 33%), personalized nutrition management (n = 19, 17%), body composition recommendations (n = 17, 15%), medications (n = 15, 13%), and orthotics and durable medical equipment (n = 8, 7%). CONCLUSION: Routine PM&R referral of older allo-HSCT patients for prehabilitation resulted in the identification of many rehabilitative needs and substantial additional management recommendations. Increased early, collaborative prehabilitation efforts between PM&R and allo-HSCT teams to optimize care for these patients is recommended.

The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds.

The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, and vitiligo, and is associated with poor treatment outcomes. Improved comprehension of the consequences of the dysregulated PI3K/Akt/mTOR pathway in patients with inflammatory dermatoses has resulted in the development of novel therapeutic approaches. Nonetheless, more studies are necessary to validate the regulatory role of this pathway and to create more effective preventive and treatment methods for a wide range of inflammatory skin diseases. Several studies have revealed that certain natural products and synthetic compounds can obstruct the expression/activity of PI3K/Akt/mTOR, underscoring their potential in managing common and persistent skin inflammatory disorders. This review summarizes recent advances in understanding the role of the activated PI3K/Akt/mTOR pathway and associated components in immune-mediated inflammatory dermatoses and discusses the potential of bioactive natural products, synthetic scaffolds, and biologic agents in their prevention and treatment. However, further research is necessary to validate the regulatory role of this pathway and develop more effective therapies for inflammatory skin disorders.

Knowledge, attitudes, and beliefs of oncology trainees on function and cancer rehabilitation medicine.

BACKGROUND: Improved function is associated with reduced morbidity and mortality in patients with cancer. Cancer rehabilitation medicine (CRM) is a subspecialty of physical medicine and rehabilitation (PM&R) that focuses on improving function in patients with cancer. One of the barriers to patients accessing CRM services is the lack of referrals from oncology providers. Understanding the knowledge, attitudes and beliefs of oncology trainees regarding the importance of function and the role of CRM is essential to reducing educational gaps and improving patients' access to essential rehabilitation services. OBJECTIVE: To determine oncology trainees' knowledge, attitude and beliefs about the importance of function and the role of CRM in the care of patients with cancer. SETTING: The study was conducted at a comprehensive cancer center in the United States. INTERVENTION: Descriptive survey study was administered to postgraduate oncology trainees who spent at least 1 day a week providing patient care. MAIN OUTCOME: Participants' report of their knowledge, attitudes, and beliefs on the importance of function and CRM in the care of patients with cancer. RESULTS: The survey was sent to 197 oncology trainees with a response rate of 67% (n = 132) and 126 were ultimately included. All participants believed that function is important in the care of patients with cancer. The majority believed that better function improves treatment tolerance (94%) and survival (84%). Most reported that having CRM physicians (80%) and an inpatient rehabilitation unit (88%) in the oncological setting is important; however, most participants reported that they refer fewer than 25% of their patients to CRM services. Participants with prior exposure to PM&R were significantly more likely to consult PM&R compared to those without exposure (p = .005). Most oncology trainees (81%) believed that education in CRM should be part of their oncology training. CONCLUSION: This study demonstrates that oncology trainees believe that function is important. They also believe that access to CRM would improve treatment tolerance and survival, but most report that they rarely refer patients to CRM services. Most trainees desire increased exposure to CRM during oncology training.

Non-permitted food colorants induced neurotoxicity in cerebellum of rat brain.

Food colorants are important food additives that not only enhance the appearance of food but also appetite. These can be obtained from natural and synthetic sources, but synthetic sources are more popular, efficient, and potential. Non-permitted food colorants (NPFCs) are banned, but their injudicious use in developing countries associated with various adverse health effects. They have potentially toxic effects on the body organs like the brain, liver, kidney, spleen, gut, etc. In view of their toxicity pattern, the present study aims to investigate the effect of three NPFCs (MY: Metanil yellow; MG: Malachite green; SIII: Sudan III) on oxidative stress, mitochondrial complexes, neurochemicals, and histological changes in the cerebellum of rats. Rats treated with MY (430 mg/kg), MG (13.75 mg/kg), SIII (250 mg/kg), and their mixtures (YGR) (MY 143.33 + MG 4.52 + SIII 83.33 mg/kg) p.o. for 60 days showed a significant increase in lipid peroxidation and decreased level of reduced glutathione, superoxide dismutase, and catalase activity as compared to controls. An increase in the activity of acetylcholinesterase (AChE) and a significant decrease in the activity of monoamine oxidase-B (MAO-B) and mitochondrial complex I and II was also observed in NPFCs treated rats as compared to controls. Further, the histological study also revealed the loss of Purkinje neurons in the cerebellum of the rat brain. The results of the present study indicate that NPFCs exposure to rats enhances oxidative stress and alters the activity of neurochemicals and mitochondrial complexes which could further lead to neuronal loss and behavioral dysfunctions.

Implementation of the Uttarakhand Tobacco Free Initiative in Schools, India, 2016.

PURPOSE AND OBJECTIVES: A process evaluation, the Uttarakhand Tobacco Free Initiative (UTFI), was conducted in 49 public high schools and colleges in the state of Uttarakhand, India, to measure program implementation, provide feedback to school administrators, and identify barriers to tobacco control. INTERVENTION APPROACH: UTFI aims to 1) raise awareness and provide education and tools for teachers and school administrators about the dangers of tobacco use and secondhand smoke, 2) encourage participation in student-led activities to promote tobacco-free initiatives, and 3) enforce tobacco-free school policies in the state of Uttarakhand. EVALUATION METHODS: We used the CDC evaluation framework to document key components and lessons learned from the UTFI. We distributed questionnaires to 71 teachers and principals in December 2016, to assess awareness of school activities and policies related to the initiative. Descriptive statistics were computed for quantitative data, and a thematic content analysis was used for qualitative data. RESULTS: Of the 71 participants, 66 (92.9%) were aware of tobacco use policies in schools, and 63 (88.7%) agreed policies were enforced. Sixty-six participants (93.0%) said that they taught tobacco prevention-related topics, and 41 of 70 respondents (58.6%) reported that a student-led group helped to enforce tobacco-free policies in their schools. Of 69 respondents, almost all (n = 66) reported satisfaction with UTFI implementation. Challenges identified were related to tobacco products being readily accessible near school premises, lack of tobacco prevention materials, and tobacco use by school staff. IMPLICATIONS FOR PUBLIC HEALTH: Successes of UTFI were documented by measuring different components of the process, including implementation of program activities and teacher and principal satisfaction. Results might help enhance key processes for the initiative and highlight some barriers to implementation, such as enforcing tobacco control policy off school premises. Continued efforts are needed to prevent tobacco use among young people.

Exercise Barriers and Adherence to Recommendations in Patients With Cancer.

PURPOSE: The American College of Sports Medicine exercise guidelines for cancer survivors encourage a combination of 150 minutes of moderate-intensity aerobic activity and 2-3 weekly sessions of strength training. Cancer survivors often experience more barriers to meeting recommended guidelines because of side effects from cancer treatments. Our aim was to measure the cancer survivors' adherence and barriers with these recommendations. METHODS: Two hundred adult cancer survivors completed surveys (Stanford Patient Education Research Center Exercise Behaviors Survey and an exercise barrier scale) reporting their physical activity, barriers to physical activity, and symptom assessment. RESULTS: A total of 68/200 participants (34%) reported adhering to the recommended physical activity guidelines of 150 minutes or more per week. Those who adhered to the guidelines reported fewer barriers to exercise (mean of 2.44 compared with 4.15 barriers, P < .0001). Female participants (P = .01), higher number of barriers, and feeling of poor well-being were less likely to report at least 60 or 150 minutes of exercise time. Lack of interest (P = .003) and self-discipline (P = .001) were reported as barriers. These participants were more likely to report high symptom burden of pain (P = .007) and fatigue (P = .005). Participants who reported < 60 minutes of exercise reported lack of enjoyment (P = .03), lack of equipment (P = .01), and symptoms of poor appetite, poor well-being, and increased dyspnea. CONCLUSION: Although recommendations are given for exercise, adherence to recommendations is low. Issues of motivation, including lack of interest and self-discipline, and symptoms of pain and fatigue were some of the main reported barriers to adhering to the recommended exercise guidelines. Therefore, interventions aimed at increasing motivation and treating symptoms could improve cancer survivor adherence to recommended exercise guidelines.

Surprising phenotypic diversity of cancer-associated mutations of Gly 34 in the histone H3 tail.

Sequencing of cancer genomes has identified recurrent somatic mutations in histones, termed oncohistones, which are frequently poorly understood. Previously we showed that fission yeast expressing only the H3.3G34R mutant identified in aggressive pediatric glioma had reduced H3K36 trimethylation and acetylation, increased genomic instability and replicative stress, and defective homology-dependent DNA damage repair. Here we show that surprisingly distinct phenotypes result from G34V (also in glioma) and G34W (giant cell tumors of bone) mutations, differentially affecting H3K36 modifications, subtelomeric silencing, genomic stability; sensitivity to irradiation, alkylating agents, and hydroxyurea; and influencing DNA repair. In cancer, only 1 of 30 alleles encoding H3 is mutated. Whilst co-expression of wild-type H3 rescues most G34 mutant phenotypes, G34R causes dominant hydroxyurea sensitivity, homologous recombination defects, and dominant subtelomeric silencing. Together, these studies demonstrate the complexity associated with different substitutions at even a single residue in H3 and highlight the utility of genetically tractable systems for their analysis.

Cancer Rehabilitation Providers and Oncology Patient Expectations for Functional Outcomes after Inpatient Rehabilitation.

BACKGROUND: Cancer rehabilitation is a valued resource for patients and oncologists. Cancer rehabilitation providers are seeing increasing numbers of referrals for inpatient rehabilitation as the number of cancer survivors grows. However, cancer rehabilitation providers, oncologists, therapists, patients, and caregivers may not always clearly communicate the goals of care, which can lead to different expectations for inpatient rehabilitation. OBJECTIVE: To determine the difference in expectations of function after an acute inpatient rehabilitation stay between cancer patients and cancer rehabilitation providers and how they align with achieved goals after treatment. DESIGN: Prospective survey study. SETTING: Quaternary academic medical center inpatient rehabilitation unit. PARTICIPANTS: Out of 194 eligible patients, 132 were enrolled and completed admission surveys, and 110 completed the discharge survey. Twelve cancer rehabilitation providers completed the surveys. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Barthel Index. RESULTS: Patients estimated their expected functional status as a median (interquartile range) score of 19 points (18, 20) using the Barthel Index, compared to cancer rehabilitation providers, who estimated a median score of 17 points (15, 19) (P < .001). Actual functional status upon discharge was a median score of 16 points (13, 18) using the Barthel Index, which was three points lower than expected by patients (P < .001). CONCLUSIONS: Oncology patients and cancer rehabilitation providers significantly overestimate functional goals for acute inpatient rehabilitation. This overestimation was clinically significant for oncology patients and statistically but not clinically significant for cancer rehabilitation providers. Increased communication may allow for a more realistic expectation of functional status upon discharge.

An Exploratory Study on Physical Function in Stem Cell Transplant Patients Undergoing Corticosteroid Treatment for Acute Graft-Versus-Host-Disease.

ABSTRACT: Acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation is treated with corticosteroids, placing patients at risk for steroid myopathy. In this single-arm cohort study, 23 patients who were started on high-dose corticosteroids for acute graft-versus-host disease underwent a series of functional tests (baseline and days 14, 28, and 56): 6-min walk test, hip flexor and knee extensor strength via dynamometry, five times sit-to-stand, Brooke scale for myopathy, modified Adult Myopathy Assessment Tool, and manual muscle testing. Participants were prescribed home exercises including walking and resistance exercises, with low adherence. Fifteen (63%) participants were male and median (range) age was 60 (36-70) yrs. Median (range) corticosteroid duration and cumulative equivalent methylprednisolone dose were 66 (22-165) days and 3625 (1020-11720) mg, respectively. At day 14, there was a significant decline in five times sit-to-stand (P = 0.0132), knee extensor (P = 0.0182), and manual muscle testing (P = 0.0466). Functional tests negatively associated with cumulative corticosteroid dose included 6-min walk test distance (P = 0.0103), hip flexor strength (P = 0.0262), knee extensor strength (P = 0.0369), and manual muscle testing strength (P = 0.0319). Five times sit-to-stand was positively associated with corticosteroid dose (P = 0.0003). In conclusion, stem cell transplant patients receiving high-dose corticosteroids for acute graft-versus-host disease are at risk for weakness detected as early as day 14. Increasing adherence to exercise may mitigate these changes.

Differentiating benign from malignant pancreatic cysts on computed tomography.

PURPOSE: It is important to identify features on computed tomography (CT) that can distinguish between benign and premalignant or malignant pancreatic cysts to avoid unnecessary surgeries. This study investigated the preoperative diagnostic evaluation of cystic pancreatic lesions to determine how advanced imaging and clinical factors should guide management. METHODS: In total, 53 patients with 27 benign and 26 premalignant or malignant cysts were enrolled. CT features of the cysts were compared using univariate and multivariate analyses. RESULTS: On univariate analysis, a solid component (p < 0.01), septation (p < 0.01), location (p < 0.01), border (p < 0.01), wall enhancement (p = 0.01), lesion margins (p < 0.01), pancreatic atrophy (p = 0.04), and a cystic wall (p < 0.01) were all significantly different between benign and premalignant or malignant cysts. On multivariate analysis, only a solid component (p < 0.01) and septation (p < 0.01) were significant. CONCLUSION: A thin cystic wall, uniform homogeneity, a clear border, the presence of septation, pancreatic atrophy, and the absence of both wall enhancements and solid components were more frequently seen in benign cysts. A thick wall, lack of homogeneity, the presence of wall enhancements and solid components, absence of septation, only a small degree of pancreatic atrophy, and unclear borders were more frequent among premalignant or malignant cysts. The only CT features to differentiate benign from premalignant or malignant cysts were a solid component and septation.

CAR T cell therapy: newer approaches to counter resistance and cost.

The genetically engineered Chimeric Antigen Receptor bearing T-cell (CAR T cell) therapy has been emerged as the new paradigm of cancer immunotherapy. However, recent studies have reported an increase in the number of relapsed haematological malignancies. This review provides newer insights into how the efficacy of CAR T cells might be increased by the application of new genome editing technologies, monitoring the complexity of tumor types and T cells sub-types. Next, tumor mutation burden along with tumormicroenvironment and epigenetic mechanisms of CAR T cell as well as tumor cell may play a vital role to tackle the cancer resistance mechanisms. These studies highlight the need to consider traditional cancer therapy in conjunction with CAR T cell therapy for relapsed or cases unresponsive to treatment. Of note, this therapy is highly expensive and requires multi-skill for successful implementation, which results in reduction of its accessibility/affordability to the patients. Here, we also propose a model for cost minimization of CAR T cell therapy by a collaboration of academia, hospitals and industry.

Neuroprotective effects of mitochondria-targeted curcumin against rotenone-induced oxidative damage in cerebellum of mice.

The present study investigated the protective effect of curcumin and mitochondrial-targeted curcumin (MTC) in rotenone-induced cerebellar toxicity in mice. Treatment of rotenone in mice significantly shortened the stride length for both forelimb and hind-limb and increased fore-paws and hind-limb base width. Co-treatment of curcumin and MTC with rotenone improved the walking pattern. A significant increase in lipid peroxidation, nitric oxide and decreased activity of AChE, reduced glutathione, superoxide dismutase and catalase were observed in rotenone-treated mice while co-treatment of curcumin and MTC with rotenone significantly increased AChE activity and protected against rotenone-induced oxidative damage. Rotenone exposed mice showed irregular, damaged Purkinje cells and perineuronal vacuolation while co-treatment of curcumin and MTC with rotenone protected against rotenone-induced cellular damage in these cells. The result exhibits that both curcumin and MTC showed protective effects against rotenone-induced cerebellar toxicity in mice and MTC is more effective than curcumin.

A Survey Regarding the Knowledge, Attitudes, and Beliefs of Graduates of Cancer Rehabilitation Fellowship Program.

Currently there are limited options for physiatrists to further subspecialize in cancer rehabilitation. Since 2007, few cancer rehabilitation fellowship programs have been started. There is currently absolutely no information about such training programs and their graduates. This study is the first to survey a small number of graduates from two cancer rehabilitation fellowship programs. The purpose of this study was to report characteristics, attitudes, and beliefs of cancer rehabilitation fellowship graduates. Graduates of cancer rehabilitation fellowship programs from 2008 through 2015 responded to a 26-question survey. Information collected included exposure to cancer rehabilitation prior to fellowship training, usefulness of fellowship training program, information about current practice, and suggested areas of improvement. The setting of the study is online survey. Participants were graduates of two cancer rehabilitation fellowship programs from 2008 through 2015. Participants were contacted via email about completion of an online survey and information was collected anonymously. Primary outcome measure was satisfaction of respondents with their fellowship training program in meeting the rehabilitation needs of their cancer patients. Sixteen responses, with a response rate of 89%, were recorded. Sixty-three percent of the respondents had exposure to cancer rehabilitation prior to post-graduate year 3 (PGY-3). Majority of graduates had practice involving at least 50% of care to cancer patients. Fifty percent indicated that their position was specifically created after their job interview. Career development was one of the major areas of suggested improvement in training. Graduates of cancer rehabilitation fellowship programs strongly value their training. Majority of the graduates were able to continue their career into jobs that were primarily cancer rehabilitation related. Further work needs to be done to define this subspecialty further and incorporate building practice as part of this training.

Changing Paradigms in the Rehabilitation of Inpatients with Brain Tumors.

Neurologic tumors account for over 50% of American acute inpatient rehabilitation facility cancer admissions. WHO Grade IV astrocytoma (also known as glioblastoma multiforme, high grade glioma or GBM) is the most common primary brain tumor in adults and is invariably fatal. The majority of primary brain tumor patients experience neurologic deficits. However, under-referral from oncology to rehabilitation has been reported. This brief narrative review article covers functional, medical and regulatory considerations when rehabilitating brain tumor inpatients.

Liquid biopsy in pancreatic cancer: the beginning of a new era.

With dismal survival rate pancreatic cancer remains one of the most aggressive and devastating malignancy. Predominantly, due to the absence of a dependable methodology for early identification and limited therapeutic options for advanced disease. However, it takes over 17 years to develop pancreatic cancer from initiation of mutation to metastatic cancer; therefore, if diagnosed early; it may increase overall survival dramatically, thus, providing a window of opportunity for early detection. Recently, genomic expression analysis defined 4 subtypes of pancreatic cancer based on mutated genes. Hence, we need simple and standard, minimally invasive test that can monitor those altered genes or their associated pathways in time for the success of precision medicine, and liquid biopsy seems to be one answer to all these questions. Again, liquid biopsy has an ability to pair with genomic tests. Additionally, liquid biopsy based development of circulating tumor cells derived xenografts, 3D organoids system, real-time monitoring of genetic mutations by circulating tumor DNA and exosome as the targeted drug delivery vehicle holds lots of potential for the treatment and cure of pancreatic cancer. At present, diagnosis of pancreatic cancer is frantically done on the premise of CA19-9 and radiological features only, which doesn't give a picture of genetic mutations and epigenetic alteration involved. In this manner, the current diagnostic paradigm for pancreatic cancer diagnosis experiences low diagnostic accuracy. This review article discusses the current state of liquid biopsy in pancreatic cancer as diagnostic and therapeutic tools and future perspectives of research in the light of circulating tumor cells, circulating tumor DNA and exosomes.

The anti-epileptogenic and cognition enhancing effect of novel 1-[4-(4-benzo [1, 3] dioxol-5-ylmethyl-piperazin-1-yl)-phenyl]-3-phenyl-urea (BPPU) in pentylenetetrazole induced chronic rat model of epilepsy.

Epilepsy is a chronic neurological disorder which affects 65 million worldwide population and characterized by recurrent seizure in epileptic patients. Recently, we reported a novel piperonylpiperazine derivative, BPPU "1-[4-(4-benzo [1,3]dioxol-5-ylmethyl-piperazin-1-yl)- phenyl]-3-phenyl-urea'' as a potent anticonvulsant agent. BPPU has shown excellent anticonvulsant activity in various in-vivo seizure models along with good anti-depressant activity. In this report, we have deeply examined the anti-epileptogenic potential of BPPU in pentylenetetrazole (PTZ) induced kindling model and BPPU effectively reduced seizure episodes in kindled animals upto 35 days. Further, neuroprotective potential of BPPU against PTZ induced neurodegeneration has also been evaluated in hippocampus as well as cortex region by histopathological and immunohistochemical studies. Epileptic patients generally suffer from a range of cognitive impairments. Therefore, the cognition enhancing effect of BPPU was also measured by using well known social recognition test, novel object recognition test, light/dark test and open field test in kindled rat model as well as scopolamine induced memory deficit mice model. Results indicated that BPPU successfully improved cognition deficits in both models. Thus, BPPU appeared as a potent anti-epileptic agent which has also capability to improve cognition decline associated with epilepsy.

PI3K/Akt/GSK3ß induced CREB activation ameliorates arsenic mediated alterations in NMDA receptors and associated signaling in rat hippocampus: Neuroprotective role of curcumin.

Protective efficacy of curcumin in arsenic induced NMDA receptor dysfunctions and PI3K/Akt/ GSK3ß signalling in hippocampus has been investigated in vivo and in vitro. Exposure to sodium arsenite (in vivo - 20 mg/kg, body weight p.o. for 28 days; in vitro - 10 µM for 24 h) and curcumin (in vivo - 100 mg/kg body weight p.o. for 28 days; in vitro - 20 µM for 24 h) was carried out alone or simultaneously. Treatment with curcumin ameliorated sodium arsenite induced alterations in the levels of NMDA receptors, its receptor subunits and synaptic proteins - pCaMKIIα, PSD-95 and SynGAP both in vivo and in vitro. Decreased levels of BDNF, pAkt, pERK1/2, pGSK3ß and pCREB on sodium arsenite exposure were also protected by curcumin. Curcumin was found to decrease sodium arsenite induced changes in hippocampus by modulating PI3K/Akt/GSK3ß neuronal survival pathway, known to regulate various cellular events. Treatment of hippocampal cultures with pharmacological inhibitors for ERK1/2, GSK3ß and Akt individually inhibited levels of CREB and proteins associated with PI3K/Akt/GSK3ß pathway. Simultaneous treatment with curcumin was found to improve sodium arsenite induced learning and memory deficits in rats assessed by water maze and Y-maze. The results provide evidence that curcumin exercises its neuroprotective effect involving PI3K/Akt pathway which may affect NMDA receptors and downstream signalling through TrKß and BDNF in arsenic induced cognitive deficits in hippocampus.