An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Genetic trends in CIMMYT's tropical maize breeding pipelines.

Fostering a culture of continuous improvement through regular monitoring of genetic trends in breeding pipelines is essential to improve efficiency and increase accountability. This is the first global study to estimate genetic trends across the International Maize and Wheat Improvement Center (CIMMYT) tropical maize breeding pipelines in eastern and southern Africa (ESA), South Asia, and Latin America over the past decade. Data from a total of 4152 advanced breeding trials and 34,813 entries, conducted at 1331 locations in 28 countries globally, were used for this study. Genetic trends for grain yield reached up to 138 kg ha-1 yr-1 in ESA, 118 kg ha-1 yr-1 South Asia and 143 kg ha-1 yr-1 in Latin America. Genetic trend was, in part, related to the extent of deployment of new breeding tools in each pipeline, strength of an extensive phenotyping network, and funding stability. Over the past decade, CIMMYT's breeding pipelines have significantly evolved, incorporating new tools/technologies to increase selection accuracy and intensity, while reducing cycle time. The first pipeline, Eastern Africa Product Profile 1a (EA-PP1a), to implement marker-assisted forward-breeding for resistance to key diseases, coupled with rapid-cycle genomic selection for drought, recorded a genetic trend of 2.46% per year highlighting the potential for deploying new tools/technologies to increase genetic gain.

Undiagnosed and Uncontrolled Hypertension and Access to Health Care among Residents of an Urban Area of Eastern Nepal: a Cross-sectional Study.

Background The burden and complication of hypertension is increasing as most of the people living with hypertension are unaware of their condition and those who are already diagnosed with it do not have their blood pressure under control. Objective To assess the prevalence of undiagnosed and uncontrolled hypertension among residents of Itahari sub metropolitan city of eastern Nepal, along with its associated socio demographic and behavioral risk factors and access to health care services. Method Cross sectional study was conducted in five wards of Itahari, among 1161 participants, using population proportionate to sample size sampling technique. Face to face interview was conducted with participants for data collection applying semi- structured questionnaire and physical measurement like blood pressure, weight and height. Result Prevalence of hypertension was 26.5% includingundiagnosed 11.0% and previously diagnosed 15.5%. Among diagnosed, 76.6% had uncontrolled blood pressure and 56.70% were taking anti-hypertensive medicine, and 7.8% were under Ayurvedic medicine. More than 70% participants preferred private health facility for treatment and 22.7% had faced financial barrier to seek healthcare. About 64% of participants did not visit health services or had visited only once in past six months. Increasing age, Body Mass Index (BMI), smoking status and positive family history were found to be significantly associated with hypertension at < 0.05 level. Conclusion Prevalence of hypertension is high and awareness regarding available health services in local primary health center and its utilization is lacking among participants. Regular screening program for hypertension and awareness program to disseminate the knowledge of availability of primary health center should be conducted.

Andrographolide - A prospective remedy for chikungunya fever and viral arthritis.

AIM: Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms. MATERIALS AND METHODS: Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases. RESULTS AND DISCUSSION: The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis. CONCLUSION: The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517).

Re-exposure to alarmin HMGB1 and cytokine IL-1 beta induces differential innate immune response generation in mouse brain.

Innate immune memory, a crucial mechanism of epigenetically mediated myeloid cell plasticity, alters subsequent immune responses majorly by two types of immunological imprinting, training, and tolerance. Recent pioneer studies provided proof-of-principle for generation of both types of innate immune memory in brain macrophage, microglial cells. This novel study was designed to investigate whether the pattern of immune response generation, induced by peripheral administration of recombinant alarmin HMGB1, alone and in combination with other recombinant cytokines, is affected by prior exposure. The experimental outcomes revealed that full length recombinant HMGB1 exposure for seven consecutive days exhibit inflammatory response as evidenced by enhanced expression of inflammatory biomarkers and neurodegeneration. In contrary, combined doses of HMGB1 and IL-1ß, for three and seven consecutive days, exhibited lower inflammatory state compared to its alone HMGB1 counterpart. The immune tolerance state was evident by microglial polarization towards non-reactive M2 state, lower astrocyte activation, epigenetic reprogramming, and decreased neurodegeneration. This is the first demonstration that HMGB1 and IL-1ß priming can differentially affect inflammation in the brain when a host is confronted with a second, third stimulus or so on. The findings were further validated by suppressing major regulators of epigenetic reprogramming, by intranasal delivery of specific siRNAs targeting those regulators. These results may provide new evidence for the involvement of recombinant endogenous cytokine induced generation of innate immune tolerance within microglial cells and indicated the possible potential role in mediating cognitive and behavioural alterations during inflammatory diseases.

Genetic gains with rapid-cycle genomic selection for combined drought and waterlogging tolerance in tropical maize (Zea mays L.).

Rapid cycle genomic selection (RC-GS) helps to shorten the breeding cycle and reduce the costs of phenotyping, thereby increasing genetic gains in terms of both cost and time. We implemented RC-GS on two multi-parent yellow synthetic (MYS) populations constituted by intermating ten elite lines involved in each population, including four each of drought and waterlogging tolerant donors and two commercial lines, with proven commercial value. Cycle 1 (C1 ) was constituted based on phenotypic selection and intermating of the top 5% of 500 S2 families derived from each MYS population, test-crossed and evaluated across moisture regimes. C1 was advanced to the next two cycles (C2 and C3 ) by intermating the top 5% selected individuals with high genomic estimated breeding values (GEBVs) for grain yield under drought and waterlogging stress. To estimate genetic gains, population bulks from each cycle were test-crossed and evaluated across locations under different moisture regimes. Results indicated that the realised genetic gain under drought stress was 0.110 t ha-1 yr-1 and 0.135 t ha-1 yr-1 , respectively, for MYS-1 and MYS-2. The gain was less under waterlogging stress, where MYS-1 showed 0.038 t ha-1 yr-1 and MYS-2 reached 0.113 t ha-1 yr-1 . Genomic selection for drought and waterlogging tolerance resulted in no yield penalty under optimal moisture conditions. The genetic diversity of the two populations did not change significantly after two cycles of GS, suggesting that RC-GS can be an effective breeding strategy to achieve high genetic gains without losing genetic diversity.

Andrographolide attenuates complete freund's adjuvant induced arthritis via suppression of inflammatory mediators and pro-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional plant-derived medicines have enabled the mankind in curing the wide spectrum of diseases throughout the ages. Andrographis paniculata (Burm.f.) Nees, is one of the traditional plant used as a folk medicine for the management of inflammation, arthritis, viral-bacterial infections and other ailments in India, China, Malaysia and other South-East Asian countries. Its major bioactive compound; andrographolide, a diterpenoid, also exerts cytoprotective properties and is reported to be effective in neuroprotection, hepatoprotection, etc. AIM: The study is aimed to explore the role of andrographolide in treatment of complete freund's adjuvant (CFA) induced arthritis. MATERIALS AND METHODS: The influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days. RESULTS: The in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1ß and IL-6 involved in arthritis. CONCLUSION: The study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.

Harmonia sedecimnotata (F.): Predatory potential, biology, life table, molecular characterization, and field evaluation against Aphis gossypii Glover.

The ladybird beetle, Harmonia sedecimnotata (F.) was studied in biology, life table, consumption rates, molecular characterization, and field evaluation. The net reproductive rate (R0), based on the age-stage and two-sex life table, was 43.2 eggs/individual. The female adults lived longer (68.1 d) than the male adults (62.9 d). The rate of consumption increased with progress in each stage of development. Compared to the other larval stages of the predator, the fourth stadium consumed most quantities of Aphis gossypii Glover nymphs (Hemiptera: Aphididae) (200.4). Both female (2214.6) and male (1792.4) consumed more prey (nymphs) than larvae. The net rate of consumption was 1458.92 nymphs of melon aphids. There was no variation in the sequences of the two nucleotides out of 583 bp, H sedecimnotata China (EU392410) and India (MG720024). Our investigations demonstrated that inoculative release of 30 or 40 or 50 adults per 100 m2 attained high reduction of aphids (>90%). Thus, it may be recommended the release rate of 40 adults per 100 m2 to suppress the eggplant aphid population. H. sedecimnotata is therefore one of the most promising biological control agents for cotton aphids that can be achieved for instant control through an inoculative release of adults.

Extended spectrum beta-lactamase producing Shiga-toxin producing-Escherichia coli in piglets, humans and water sources in North East region of India.

Extended spectrum ß-lactamases (ESBL) producing Shiga toxin producing E. coli (STEC) are posing a constant threat to public health throughout the world leading to serious infections and raising key therapeutic issues. A total of 219 fecal samples were collected from piglets with diarrheoa, pig farmers and water sources in North East India; and were processed for isolation of Escherichia coli. The isolates were screened for antimicrobial resistance and suspected isolates for ESBLs production by double-disk synergy test (DDST). Escherichia coli isolates positive for DDST were subjected for detection of selected ESBL/beta-lactamase genes and virulence associated genes by PCR. By DDST, 337 (67·94%) E. coli isolates were detected as ESBLs producer, of which 211 (66·98%), 117 (70·91%) and 9 (56·25%) isolates were from piglets, humans and water sources respectively. A total of 64 (12·90%) isolates were recorded as STEC, of which 48 (9·68%), 6 (1·21%) and 10 (2·02%) were from human, piglets and water respectively. Majority of the STEC isolates (64·06%) possessed multiple virulence genes, of which 59·38% also harboured ESBL/beta-lactamase genes with 32·81% STEC isolates being positive for multiple ESBL/beta-lactamase genes. SIGNIFICANCE AND IMPACT OF THE STUDY: Multidrug resistant (MDR) enteric bacteria are global concern. Association of MDR traits in STEC isolates are another rising issue in human and animal health perspective. The interaction of such organisms among the human, domestic animals and adjoining water sources require to be analysed systematically. The present study exhibited the possible transmission of MDR-STEC among the human, domestic animals and water sources in the North eastern states of India. To the best of our knowledge, this is the first report of such kind in India.

CXCR7: A key neuroprotective molecule against alarmin HMGB1 mediated CNS pathophysiology and subsequent memory impairment.

High mobility group box 1 (HMGB1) is an endogenous alarmin that drives the pathogenesis of neurodegenerative disorders including cognitive decline. Therefore, HMGB1 is thought to be a common biomarker as well as promising therapeutic target for neuroinflammation associated with neurocognitive disorders. Here, for the first time, we have unmasked the potential inhibitory effect of a novel receptor of HMGB1-CXCL12 complex; atypical chemokine receptor 3 (ACKR3/CXCR7) on HMGB1 induced glial phenotype switching, neuroinflammation, and subsequent memory loss. Upregulation of CXCR7 inhibits HMGB1-CXCL12 complex induced peripheral immune cells infiltration to CNS by regulating blood-brain barrier (BBB) integrity in HMGB1 induced dementia model of mice. Whereas, gene knockdown study by RNA interference (non-invasive intranasal delivery to animal model) shows CXCR7 ablation aggravates inflammatory responses in hippocampus region and immune cell infiltration to CNS tissue by breached BBB. This study also indicates the important role of CXCR7 molecule in maintaining CNS homeostasis by balancing M1/M2 microglia, A1/A2 astrocytes, long term potentiation/long term depression markers which ultimately ameliorates HMGB1 induced neurodegeneration, synaptic depression and memory loss (assessed by both radial arm maze and Morris water maze) in male mice model of dementia. Overall, the study summarizes several significant protective functions afforded by CXCR7 against HMGB1 induced disbalance in neuroimmunological axis, neurodegeneration and memory loss and thereby provides a new paradigm for strategic development of novel therapeutics against neurodegenerative diseases with dementia as a common symptom.

Diversity and functional analysis of salivary microflora of Indian Antarctic expeditionaries.

Introduction: The human oral microbiota continues to change phenotype by many factors (environment, diet, genetics, stress, etc.), throughout life with a major impact on human physiology, psychology, metabolism and immune system. Amongst one such factor with unique and extreme environmental conditions is Antarctica. The sea voyage to Antarctica has many risks than at station for expedition members. In this study, we investigated the influence of Antarctic sea voyage and stay at the Indian Antarctic station Maitri, on the health of Indian expedition members by using a metagenomic approach to explore oral biodiversity. Methods: Saliva samples were collected from 12 expedition members, at 3 different time points viz. before the start of the ship voyage, after the completion of the voyage and at the end of the stay at Antarctica. Samples were analyzed for whole genome and 16S rRNA sequencing. Result: The oral microbial diversity of the expedition members was significantly changed, during the days of sailing and after the stay at Antarctica. The oral microbiota comprised mainly of the phyla Firmicutes (46%, 29% & 36%); Proteobacteria (40%, 48%, & 44%), Bacteroidetes (10%, 22%, &14%), Fusobacterium and Actinobacteria (5%-1%) and Unclassified (17%, 25% & 23%), at three time points, respectively. Further, the differential analysis of microbes across all the phyla revealed 89, 157 and 157 OTUs genera. The altered microbiota indicated changes in amino acid, lipid and carbohydrate metabolism. Conclusion: Study suggests that understanding the compositional and functional differences in the oral microbiota of Antarctic expedition members, can lay the foundation to relate these differences to their health status. It will further demonstrate the need for providing improved management during ship voyage and stay in Antarctica.

Temporal and Spatial Changes in Glial Cells During Chronic Hypobaric Hypoxia: Role in Neurodegeneration.

Ascend to high altitude results in a drastic change in the environmental conditions an individual is exposed to. As the altitude increases there is a decrease in partial pressure of oxygen leading to a unique condition known as hypobaric hypoxia (HH). Brain is highly vulnerable to hypoxia and it has been well established that hypobaric hypoxia leads to neurodegeneration in different brain regions. However, the response of glial cells during hypobaric hypoxia needs to be explored yet. The present study was aimed to understand the role of glial cells viz. astrocytes, microglia and oligodendrocytes in HH-induced neuronal death. The study aims to understand the effect of HH exposure on glial physiology in a time-dependent (0, 1, 3, 7 and 14 days of HH exposure) and region-dependent (CA1, CA3 and DG regions of hippocampus) manner. We examined the morphological changes and activation of glial cells along with pro-inflammatory cytokine levels. Results indicated that chronic hypobaric hypoxia (7 and 14 days exposure) causes activation of both astrocytes (GFAP-positive cells) and microglia (IBA-1-positive cells) but oligodendrocytes (M-PLP-positive cells) expression was found to be significantly reduced. The results obtained were found to be more profound in the CA1 region of hippocampus, indicating its vulnerability to hypoxia. Neuroinflammation was suggested by elevated IL-ß1, IL-6 and TNF-α cytokine levels upon chronic HH. The study also explored the role of microglia and A1 astrocyte interplay in HH-induced neurodegeneration and demyelination. This study explores the shift in role of glial cell toward neurodegeneration under chronic hypobaric hypoxia stress. Chronic stress results in glial activation which leads to neuroinflammation a plausible factor in HH-induced neurodegeneration.

Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia.

Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene. Here, we implicate Mac-1 scavenger receptor in microglial phenotype switching, neurodegeneration in prefrontal cortex, hippocampus and working memory impairment. RNA mediated silencing of Mac-1 in both in vitro and in vivo model showed significant impact of it on hypoxia induced altered expression of Mac-1 endogenous ligand, signaling cascade proteins, transcription factors and NADPH oxidase pathway. Efficient degradation of Mac-1 mRNA suppressed expression of M1 phenotypic markers, inflammatory chemokines, and cytokines, but on the other hand, it upregulated M2 phenotypic markers and anti-inflammatory cytokines. Neuronal viability and synaptic plasticity markers were also modulated significantly by this strategy. Behavioral study revealed significant downregulation in the number of working memory errors at a time-dependent manner after silencing the Mac-1 gene during continuous hypoxic exposure. The novel findings of this study for the very first time, unmasked the role of Mac-1 receptor in neurodegenerative disease progression under hypoxic condition and at the same time indicated the potential therapeutic value of this non-invasive siRNA delivery approach for treating working memory loss.

2D Effective Electron Mass at the Fermi Level in Accumulation and Inversion Layers of MOSFET Nano Devices.

In this paper an attempt is made to study the 2D Fermi Level Mass (FLM) in accumulation and inversion layers of nano MOSFET devices made of nonlinear optical, III-V, ternary, Quaternary, II-VI, IV-VI, Ge and stressed materials by formulating 2D carrier dispersion laws on the basis of k → ⋅ p → ⋅ formalism and considering the energy band constants of a particular material. It is observed taking accumulation and inversion layers of Cd3As2, CdGeAs2, InSb, Hg1-xCdxTe and In1-xGaxAsyP1-y lattice matched to InP, CdS, GaSb and Ge as examples that the FLM depends on sub band index for nano MOSFET devices made of Cd3As2 and CdGeAs2 materials which is the characteristic features such 2D systems. Besides, the FLM depends on the scattering potential in all the cases and the same mass changes with increasing surface electric field. The FLM exists in the band gap which is impossible without heavy doping.

Adjuvant activity of ethanol extract of Hippophae rhamnoides leaves with inactivated rabies virus antigen.

CONTEXT: Hippophae rhamnoides L. (Elaeagnaceae), commonly known as seabuckthorn (SBT), is known for its medicinal and nutritional properties. OBJECTIVE: Evaluation of in vivo adjuvant activity of SBT leaf extract (SBTE) with inactivated rabies virus antigen (Rb). MATERIALS AND METHODS: Swiss albino mice were immunized with aqueous-alcoholic SBTE (100 mg/kg body weight) or algel (aluminium hydroxide gel) with or without Rb (5% v/v). After priming, booster was administered on day 14. Rabies virus neutralizing antibody (RVNA) titers were estimated by rapid fluorescent focus inhibition test in sera samples collected on days 7, 14, 21, 28 and 35. Effect of adjuvant administration on cytotoxic T lymphocytes (CTLs), memory T cells, plasma and CD11c+ cells was studied by flow cytometry. In vitro hemolysis was assayed in human RBC. RESULTS: RVNA titers were significantly enhanced (p < 0.05) after booster administration in mice immunized with SBTE + Rb as compared to the controls. In combination, SBTE, algel and Rb, enhanced the RVNA titers. CTLs significantly increased (p < 0.05) in SBTE + Rb immunized mice. Memory T cells and plasma cells were 27.9 and 15.9%, respectively, in SBTE + Rb immunized mice as compared to that of 20.3 and 11.3%, respectively, in Rb immunized group. SBTE + Rb enhanced peritoneal CD11c+ cells (25.8%) as compared to 9.4% cells in Rb immunized mice, showed 3.2-fold increment in LPS induced IL-1ß. No RBC hemolysis was observed with SBTE. CONCLUSIONS: This study demonstrates the potential adjuvant activity of SBTE with Rb by increasing RVNA titers and CTL response.

Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment.

Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1ß. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment.

A Modified Mean Gray Wolf Optimization Approach for Benchmark and Biomedical Problems.

A modified variant of gray wolf optimization algorithm, namely, mean gray wolf optimization algorithm has been developed by modifying the position update (encircling behavior) equations of gray wolf optimization algorithm. The proposed variant has been tested on 23 standard benchmark well-known test functions (unimodal, multimodal, and fixed-dimension multimodal), and the performance of modified variant has been compared with particle swarm optimization and gray wolf optimization. Proposed algorithm has also been applied to the classification of 5 data sets to check feasibility of the modified variant. The results obtained are compared with many other meta-heuristic approaches, ie, gray wolf optimization, particle swarm optimization, population-based incremental learning, ant colony optimization, etc. The results show that the performance of modified variant is able to find best solutions in terms of high level of accuracy in classification and improved local optima avoidance.

Cardiovascular involvement in severe malaria: A prospective study in Ranchi, Jharkhand.

BACKGROUND & OBJECTIVES: Malaria is considered as the most important parasitic disease of humans, causing seri- ous illness that can be fatal, if not diagnosed and treated immediately. It is a multisystem disorder affecting nearly every system of the body. The aim of the present study was to evaluate the involvement of cardiovascular system in severe malaria using non-invasive methods. METHODS: This prospective study was conducted on patients of severe malaria who were admitted between June and November 2015 in the Department of Medicine, Rajendra Institute of Medical Sciences and Hospital, Ranchi, Jharkhand, India. A total of 27 cases (18 males and 9 females; age ranging between 15 and 70 yr) of severe malaria (P. falciparum 24; P. vivax 1; mixed 2) were diagnosed by microscopic examination of peripheral blood smear and bivalent rapid diagnostic test (RDT) kit. The assessment of cardiovascular system was done by clinical examination, chest X-ray, ECG and transthoracic echocardiography. RESULTS: In all, 7 (26%) patients were found to be suffering from circulatory failure, out of which one was P. vivax case and rest were cases of P. falciparum infection with high parasite density. One patient died due to cardiovascular collapse. ECG revealed sinus bradycardia [Heart rate (HR): 40-60] in 7% of the cases, extreme tachycardia (HR: 120-150) in 3.7% of cases and premature arterial ectopic with tachycardia in 3.7% of patients (p <0.05). The echo- cardiographic findings were global hypokinesia with decreased left ventricular ejection fraction (<55%) in 11.1%, grade 1 left ventricular diastolic dysfunction in 3.7%, mild tricuspid regurgitation (TR) with mild pulmonary artery hypertension (PAH) in 3.7% and mild pericardial effusion in 3.7% of the cases. The ECG and echocardiography changes indicated myocardial involvement in severe malaria. INTERPRETATION & CONCLUSION: The present study indicated involvement of cardiovascular system in severe malaria as evidenced from ECG and echocardiography. The study also revealed that cardiovascular instabilities are common in falciparum malaria, but can also be observed in vivax malaria.

A New Hybrid MGBPSO-GSA Variant for Improving Function Optimization Solution in Search Space.

In this article, a newly hybrid nature-inspired approach (MGBPSO-GSA) is developed with a combination of Mean Gbest Particle Swarm Optimization (MGBPSO) and Gravitational Search Algorithm (GSA). The basic inspiration is to integrate the ability of exploitation in MGBPSO with the ability of exploration in GSA to synthesize the strength of both approaches. As a result, the presented approach has the automatic balance capability between local and global searching abilities. The performance of the hybrid approach is tested on a variety of classical functions, ie, unimodal, multimodal, and fixed-dimension multimodal functions. Furthermore, Iris data set, Heart data set, and economic dispatch problems are used to compare the hybrid approach with several metaheuristics. Experimental statistical solutions prove empirically that the new hybrid approach outperforms significantly a number of metaheuristics in terms of solution stability, solution quality, capability of local and global optimum, and convergence speed.