Tuberculosis control strategies: Challenges to health management research

The rapid expansion of RNTCP implementation in this vast and diverse county with quality maintenance demands proactive involvement of policy makers, programme managers, researchers and health functionaries. Mid-term goal for the programme have to be defined. Problems in achieving these objectives have to be identified and a research agenda needs to be formulated to answer the constrains identified. Research, by being linked to the constrains and objectives, will always be relevant to TB control programme and the findings would influence policy and practice. Operational research should become an integral component of the programme management

VIRTUAL SCREENING OF PHYTOCHEMICALS OF MORINDA CITRIFOLIA AS ANTI-INFLAMMATORY AND ANTI-ALZHEIMER AGENTS USING MOLEGRO VIRTUAL DOCKER ON p38-α MITOGEN ACTIVATED PROTEIN KINASE ENZYME

Objective: Pharmacological and genetic inhibition of p38α mitogen-activated protein kinase (p38α MAPK) has potential in the treatment of humandiseases such as autoimmune diseases, heart failure, Alzheimer disease, and Parkinsonism. Our aim is to do in-silico screening of phytochemicals ofMorinda citrifolia for p38α MAPK inhibitory property by docking method.Methods: We did docking of various phytochemicals present in M. citrifolia against p38α MAPK enzyme extracted from Protein Data Bank (ID-4F9Y),by utilizing the Molegro virtual docker Software. The docking scores of phytochemicals were compared with the scores of native reference ligandspresent in the crystal structure 4F9Y.Results: Isoprincepin and balanophonin show better docking scores when compared to reference ligands in the protein. Isoprincepin has potentialto act in a highly selective manner on p38α MAPK as it binds to Met 109 in the phylogenetically conserved kinase hinge region and thereby induces aconformational change known as glycine flip phenomenon. Balanophonin has favorable physiochemical properties for blood-brain barrier penetrationand can act on p38α MAPK in the brain.Conclusion: Some of the phytochemicals present in M. citrifolia have p38α MAPK binding and possible inhibitory potential.Keywords: p38α mitogen-activated protein kinase, Isoprincepin, Balanophonin, Molegro virtual docker

TimeWeaver: Opportunistic One Way Delay Measurement via NTP

One-way delay (OWD) between end hosts has important implications for Internet applications, protocols, and measurement-based analyses. We describe a new approach for identifying OWDs via passive measurement of Network Time Protocol (NTP) traffic. NTP traffic offers the opportunity to measure OWDs accurately and continuously from hosts throughout the Internet. Based on detailed examina- tion of NTP implementations and in-situ behavior, we develop an analysis tool that we call TimeWeaver, which enables assessment of precision and accuracy of OWD measurements from NTP. We apply TimeWeaver to a ~1TB corpus of NTP traffic collected from 19 servers located in the US and report on the characteristics of hosts and their associated OWDs, which we classify in a precision/accuracy hierarchy. To demonstrate the utility of these measurements, we apply iterative hard-threshold singular value decomposition to estimate OWDs between arbitrary hosts from the high- est tier in the hierarchy. We show that this approach results in highly accurate estimates of OWDs, with average error rates on the order of less than 2%. Finally, we outline a number of applications---in particular, IP geolocation, network operations and management---for hosts in lower tiers of the precision hierarchy that can benefit from TimeWeaver, offering directions for future work.Comment: 14 page

VIRTUAL SCREENING OF PHYTOCHEMICALS FOR METHOTREXATE LIKE DIHYDROFOLATE REDUCTASE AND AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOTIDE (AICAR) TRANSFORMYLASE INHIBITORY PROPERTY USING MOLEGRO VIRTUAL DOCKER

Objective: Methotrexate is an effective treatment for autoimmune diseases like Rheumatoid arthritis, vasculitis, and Psoriasis. Our aim is to do in silico screening of various phytochemicals present in common medicinal plants used in India for arthritis and fever for possible Dihydrofolate reductase (DHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) Transformylase inhibitory property similar to methotrexate (MTX) using molecular docking method.Methods: We did docking of 142 phytochemicals against DHFR and AICAR Transformylase domain of ATIC (AICAR Transformylase/Inosine monophosphate cyclohydrolase) enzyme structures extracted from Protein Data Bank (4M6K, 1P4R respectively), by utilizing the Molegro virtual docker Software. The docking scores of phytochemicals were compared with the scores of respective native reference ligands present in the crystal structures.Results: Compounds, dicrocin, melianone, calotropin, uscharidin and mauritine A showed more negative moldoc and rerank scores compared to folic acid and MTX when docked in the folate-binding pocket of DHFR. Dicrocin, melianone and hecogenin showed more negative moldoc and rerank scores compared to scores of AICAR and MTX, when docked in the cavity in AICAR Transformylase, which binds AICAR.Conclusion: The protein-ligand interaction plays a significant role in structural based drug designing. The present analysis shows that Melianone and dicrocin could be the potential lead molecules for the inhibition of both DHFR and AICAR transformylase like MTX. Uscharidin, calotropin, and mauritine A may be the potential DHFR inhibitor lead molecules and Hecogenin could be the potential lead molecule for inhibition of AICAR transformylase.Keywords: Dihydrofolate reductase, AICAR Transformylase, Melianone, Hecogenin, Mauritine

Comparison of Aquatic-Insect Habitat and Diversity Above and Below Road Crossings in Low-Order Streams

The effects of road crossings on fish communities have been extensively studied; yet little attention has been given to macroinvertebrate communities. This study evaluated physical stream characteristics, water quality, and aquatic-insect richness from above and below road crossings of low-order streams in the Ouachita National Forest in Arkansas. Fifteen road crossings were sampled during October and November 2005. Erosion was significantly higher below road crossings than above. Sites downstream of road crossings had significantly lower pH and significantly higher turbidity than sites upstream of road crossings. Despite differences in water quality and habitat, there was no apparent difference in aquatic-insect richness from above and below road crossings based on the EPT index, suggesting that road crossings did not act as barriers to insect movement. The water-quality differences observed were well within acceptable limits and likely not biologically important

Computational Notebooks as Co-Design Tools: Engaging Young Adults Living with Diabetes, Family Carers, and Clinicians with Machine Learning Models

Engaging end user groups with machine learning (ML) models can help align the design of predictive systems with people’s needs and expectations. We present a co-design study investigating the benefits and challenges of using computational notebooks to inform ML models with end user groups. We used a computational notebook to engage young adults, carers, and clinicians with an example ML model that predicted health risk in diabetes care. Through codesign workshops and retrospective interviews, we found that participants particularly valued using the interactive data visualisations of the computational notebook to scaffold multidisciplinary learning, anticipate benefits and harms of the example ML model, and create fictional feature importance plots to highlight care needs. Participants also reported challenges, from running code cells to managing information asymmetries and power imbalances. We discuss the potential of leveraging computational notebooks as interactive co-design tools to meet end user needs early in ML model lifecycles

Modulation of CD4+and CD8+T-Cell Function by Interleukin 19 and Interleukin 24 During Filarial Infections

Interleukin 19 (IL-19) and interleukin 24 (IL-24) are cytokines that are highly expressed in filarial infections. To study the role of IL-19 and IL-24 in regulating T-cell responses, we examined the frequency of T-helper type 1 (Th1)/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, Th22/Tc22, and Tr1 cells in 26 filariae-infected individuals stimulated with filarial antigen following IL-19 or IL-24 neutralization. IL-19 or IL-24 neutralization resulted in significantly enhanced frequencies of Th1/Tc1 and/or Th17/Tc17 cells and significantly reduced frequencies of Th2/Tc2, Tr1, and/or Th9/Tc9 cells. Thus, we demonstrate that IL-19 and IL-24 are associated with the modulation of T-cell responses in filarial infections

Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in Strongyloides stercoralis Infection

Chronic helminth infections are known to be associated with modulation of antigen - specific CD4(+) T responses. However, the role of CD4(+) T cell responses in human infection with Strongyloides stercoralis (Ss) is not well-defined. To examine the role of CD4(+) T cells expressing Th1, Th2 and Th17 cytokines in strongyloidiasis, we compared the frequency of these subsets in infected individuals (INF) to frequencies (F(o)) in Ss-uninfected (UN) individuals. INF individuals exhibited a significant decrease in the spontaneous and antigen specific F(o) of both mono - and dual functional Th1 cells compared to UN. Similarly, INF individuals also exhibited significantly decreased F(o) of mono - and dual - functional Th17 cells upon antigen - stimulation compared to UN. In contrast, both the spontaneous and antigen - induced F(o) of mono- and dual - functional Th2 cells was significantly increased in INF compared to UN individuals. This differential T cell response was predominantly antigen - specific since it was abrogated upon control antigen or mitogen stimulation. The regulation of Th1, Th2 and Th17 cells was pre-dominantly dependent on IL-10, while the regulation of Th2 but not Th1 or Th17 cells was also dependent on TGFβ. In addition, treatment of Ss infection significantly increased the antigen - specific F(o) of Th1 and Th17 cells and decreased the F(o) of Th2 cells in INF individuals. Thus, Ss infection is characterized by a parasite - antigen dependent regulation of mono- and dual - functional Th1, Th2 and Th17 cells, a regulation also reversible by anti-helminthic treatment

Computational Notebooks as Co-Design Tools:Engaging Young Adults Living with Diabetes, Family Carers, and Clinicians with Machine Learning Models

Engaging end user groups with machine learning (ML) models can help align the design of predictive systems with people's needs and expectations. We present a co-design study investigating the benefits and challenges of using computational notebooks to inform ML models with end user groups. We used a computational notebook to engage young adults, carers, and clinicians with an example ML model that predicted health risk in diabetes care. Through co-design workshops and retrospective interviews, we found that participants particularly valued using the interactive data visualisations of the computational notebook to scaffold multidisciplinary learning, anticipate benefits and harms of the example ML model, and create fictional feature importance plots to highlight care needs. Participants also reported challenges, from running code cells to managing information asymmetries and power imbalances. We discuss the potential of leveraging computational notebooks as interactive co-design tools to meet end user needs early in ML model lifecycles