Washington Global Health Alliance Discovery Series
Robert Sinden, PhD
July 28, 2008
'Understanding Malaria Development in the Mosquito, and its Pivotal Role in the Formulation of Effective Control Strategies'
Novel research aimed at finding a cure for AIDS requires animal models responding to human antiretroviral drugs. However, there have been few antiretrovirals cross-active against the simian viruses. In this study, we expanded the arsenal of drugs active against the simian retrovirus SIVmac251 and showed that this virus is inhibited by the protease inhibitor, darunavir, and the CCR5 blocker, maraviroc. Administration of these two drugs in combination with the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the integrase inhibitor, raltegravir, resulted in prolonged plasma viral loads below assay detection limits, and, surprisingly, restricted the viral reservoir, a marker of which is viral DNA. We then decided to employ this multidrug regimen (termed “highly intensified ART”) in order to increase the potency of a previous strategy based on the gold drug auranofin, which recently proved able to restrict the viral reservoir in vivo. A short course of highly intensified ART following the previous treatment resulted, upon therapy suspension, in a remarkably spontaneous control of the infection, that may pave the way to a persistent suppression of viremia in the absence of ART. These results corroborate the robustness of the macaque AIDS model as a vanguard for potentially future treatments for HIV in humans.
Sanja Selak of Intercell AG, Vienna, Austria, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Intercell develops vaccines for the prevention and treatment of infectious diseases
Gene Olinger, USAMRIID, Fort Detrick USA, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Protective Immune Reponses to Ebola Virus
mRNA rather than DNA may become the nucleotide framework for new classes of drugs and vaccines. Exciting preclinical results in prophylaxis and initial clinical data in oncology suggest that mRNA technology could be translated into improvements in lung cancer and other diseases.
This document summarizes information about malaria vaccines. It discusses how malaria is caused by Plasmodium parasites and transmitted by mosquitoes. Four species can infect humans. Current vaccines target different stages of the parasite's life cycle, including pre-erythrocytic, blood, and sexual stages. Challenges to vaccine development include the parasite's ability to evade the immune system through antigenic variation. Several candidate vaccines are discussed that target different stages, but none have achieved high levels of efficacy and durability.
This study found that rat tissues from farms in the Netherlands tested positive for the pla gene, which is a marker for Yersinia pestis. The pla gene sequences from rats were nearly identical to Y. pestis pla but further analysis identified adjacent sequences similar to bacterial replication genes. Attempts to culture or detect other Y. pestis markers from rat tissues were unsuccessful. The findings suggest there are unknown bacteria in rats that contain a pla homolog, which could produce false positive results in Y. pestis detection assays that only target the pla gene. Methods to confirm the presence of Y. pestis should include additional gene targets.
Novel research aimed at finding a cure for AIDS requires animal models responding to human antiretroviral drugs. However, there have been few antiretrovirals cross-active against the simian viruses. In this study, we expanded the arsenal of drugs active against the simian retrovirus SIVmac251 and showed that this virus is inhibited by the protease inhibitor, darunavir, and the CCR5 blocker, maraviroc. Administration of these two drugs in combination with the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the integrase inhibitor, raltegravir, resulted in prolonged plasma viral loads below assay detection limits, and, surprisingly, restricted the viral reservoir, a marker of which is viral DNA. We then decided to employ this multidrug regimen (termed “highly intensified ART”) in order to increase the potency of a previous strategy based on the gold drug auranofin, which recently proved able to restrict the viral reservoir in vivo. A short course of highly intensified ART following the previous treatment resulted, upon therapy suspension, in a remarkably spontaneous control of the infection, that may pave the way to a persistent suppression of viremia in the absence of ART. These results corroborate the robustness of the macaque AIDS model as a vanguard for potentially future treatments for HIV in humans.
Sanja Selak of Intercell AG, Vienna, Austria, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Intercell develops vaccines for the prevention and treatment of infectious diseases
Gene Olinger, USAMRIID, Fort Detrick USA, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Protective Immune Reponses to Ebola Virus
mRNA rather than DNA may become the nucleotide framework for new classes of drugs and vaccines. Exciting preclinical results in prophylaxis and initial clinical data in oncology suggest that mRNA technology could be translated into improvements in lung cancer and other diseases.
This document summarizes information about malaria vaccines. It discusses how malaria is caused by Plasmodium parasites and transmitted by mosquitoes. Four species can infect humans. Current vaccines target different stages of the parasite's life cycle, including pre-erythrocytic, blood, and sexual stages. Challenges to vaccine development include the parasite's ability to evade the immune system through antigenic variation. Several candidate vaccines are discussed that target different stages, but none have achieved high levels of efficacy and durability.
This study found that rat tissues from farms in the Netherlands tested positive for the pla gene, which is a marker for Yersinia pestis. The pla gene sequences from rats were nearly identical to Y. pestis pla but further analysis identified adjacent sequences similar to bacterial replication genes. Attempts to culture or detect other Y. pestis markers from rat tissues were unsuccessful. The findings suggest there are unknown bacteria in rats that contain a pla homolog, which could produce false positive results in Y. pestis detection assays that only target the pla gene. Methods to confirm the presence of Y. pestis should include additional gene targets.
This document discusses using molecular genotyping methods to investigate the genetic diversity of Mycobacterium tuberculosis strains in Taiwan. It provides background on M. tuberculosis and describes several genotyping methods including restriction fragment length polymorphism (RFLP), spoligotyping, variable number tandem repeats (VNTR), and mycobacterial interspersed repetitive units (MIRU). The study aims to evaluate the genotyping efficiency of these methods, select appropriate genetic markers, and establish high-throughput protocols. Preliminary results on 479 samples from Taiwan show discrimination of strains by region, age, gender and genotype. Locus discrimination power and Hunter-Gaston discrimination index are also reported for different genotyping methods.
This research article demonstrates the use of Wavelength Modulated Raman Spectroscopy (WMRS) to identify major immune cell subsets in an unlabeled and non-fixed state. Using WMRS, the researchers were able to distinguish between CD4+ T lymphocytes, CD8+ T lymphocytes, and CD56+ Natural Killer cells from multiple donors with up to 96% specificity. They also distinguished between CD303+ plasmacytoid and CD1c+ myeloid dendritic cell subsets. This label-free method opens new opportunities for analyzing immune systems and developing diagnostic technologies without altering or damaging the cells.
Presentation by adrian hill [university of oxford]Pamoja
Malaria is a major global health problem, killing over 700,000 people annually. Developing an effective vaccine is challenging due to the parasite's complex life cycle and ability to evade the immune system. Current vaccine approaches include protein-adjuvant vaccines targeting specific stages, viral vectored vaccines to induce cellular immunity, and whole parasite vaccines. Significant progress has been made, but partial efficacy has required unprecedented immunogenicity. A multi-component vaccine targeting multiple stages may be needed for high efficacy.
ProImmune Antigen Characterization Summit Paul Mossamandacturner
This document summarizes research on the immune response to cytomegalovirus (CMV) and cancer-testis antigens (CTAgs). It discusses how CMV elicits a massive immune response, occupying up to 40% of CD8+ T cells. This response declines with immunosuppression. It also explores using CMV-specific T cells for immunotherapy after stem cell transplantation. The document then examines CTAgs, which are expressed in cancers and elicit anti-tumor immune responses, but challenges remain in understanding their efficacy.
Dr. David Mooney - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
1) The study investigated how Gram-negative bacterial lipopolysaccharide (LPS), a component of bacteria like Chlamydia and Neisseria that cause STIs, affects expression of HIV receptors in cervical epithelial cells.
2) The results showed that LPS increased expression of the CCR5 HIV co-receptor and other alternative receptors in cervical cells through activation of EGFR, ERK1/2, and COX-2 signaling pathways.
3) This suggests that STIs have the potential to enhance susceptibility to HIV infection in women by regulating expression of HIV receptors in cervical epithelial cells through an inflammatory response.
Transglutaminase 2 (TG2) expression was examined in macrophages in response to Toxoplasma gondii infection and stress. TG2 was expressed in RAW macrophages and intestinal epithelial cells. TG2 expression increased at 3 hours post-infection but decreased at 8 hours. TG2 expression was induced by the stress hormone corticosterone, norepinephrine, and T. gondii infection, with maximum expression observed when infection and norepinephrine were combined. Increased TG2 expression may be detrimental to the host by decreasing anti-inflammatory transforming growth factor beta from macrophages and exacerbating inflammation.
1) Researchers studied the internal ribosomal entry site (IRES) in the 5' untranslated region of the canine dicistrovirus (CDV-A) genome.
2) Using computational prediction and SHAPE analysis, they determined the secondary structure of the CDV-A 5'UTR IRES, which resembles the poliovirus IRES structure.
3) In vitro translation assays in rabbit reticulocyte lysate showed that the CDV-A 5'UTR IRES can direct cap-independent translation, and requires the initiation factor eIF4A.
A brief exploration of the way some modern viruses act and ancient viruses have acted to benefit their hosts - particularly humans - today and through evolutionary history, by various means (such as targeted destruction of pathogenic bacteria and introduction of new genetic material).
This document summarizes a study that identified genes in the extracellular matrix that regulate the susceptibility of cultured cells to prion infection. The study compared gene expression in prion-susceptible and resistant cell lines. They identified 9 genes, including fibronectin 1 and integrin α8, that were upregulated in resistant cells. Knockdown of these genes increased susceptibility by altering the extracellular matrix structure and deposition of prion proteins. The results suggest the extracellular matrix plays a key role in controlling prion infection by influencing how prion proteins interact and convert forms.
Candidemia in HIV-positive patients in Dschang District Hospital (West Region...Claude Nangwat
Candidemia has been identified as a public health problem in HIV-infected patients. The evaluation of CD4 count, transaminases and blood glucose, are being used as a means to monitor the health of HIV-infected patients, without excluding the diagnosis of candidemia and other opportunistic infections. In order to contribute in improving the care of HIV-infected patients attending Dschang District Hospital and later on, in other hospitals in Cameroon, we conducted from June to September 2014 a cross-sectional study, with general objective; to determine the association between candidemia and selected biochemical and haematological parameter changes in HIV-infected patients, as a possible indicator in monitoring HIV disease progression.
To do this, blood samples were collected from HIV-infected patients assigned to the UPEC of Dschang District Hospital for follow up, and haemogram report, CD4 counts, ALAT level, ASAT level, and glucose level in blood were evaluated by cytometric and spectrophotometric assays. Candida species were isolated from some blood samples, and then identified using CHROMagar Candida culture medium. The broth microdilution method was afterwards used to test the susceptibility of the fungal isolates vis-a-vis three conventional antifungal agents.
Mycological analysis of blood samples showed that eight (08) patients had candidemia, a prevalence of 6.11%. Eight (08) isolates were obtained from these eight (08) candidemic HIV-infected patients; this consisted of 4(50%) Candida albicans, 3(37.5%) Candida parapsilosis and 1(12.5%) Candida glabrata. All these isolates were resistant (MICs ranged from 2 to >256 µg/mL) to the antifungals used, that is, ketoconazole, amphotericin B and nystatin.
A significant correlation was found between candidemia and white blood cell count, with a correlation coefficient of r = 0.240 (p < 0.05). Based on the results obtained, the systematic diagnosis of candidemia should be performed in patients infected with HIV in Cameroon in order to improve on their care.
Key words: Candidemia, HIV, biochemical parameters, hematological parameters, Antifungals activities.
This document compares the allele frequencies of 15 Plasmodium falciparum merozoite antigen genes in malaria infections sampled in Kenya in 2007 and 2008. It finds fluctuating allele frequencies in codons 147 and 148 of the reticulocyte-binding homologue 5 (Rh5) gene over this period in uncomplicated malaria infections. However, the dominant YH haplotype was stable over multiple years in asymptomatic and complicated infections. A regression analysis found the chance of the less common HD haplotype decreased over time from 2007 to 2009 in uncomplicated and asymptomatic infections.
Molecular biomarkers can be used for several purposes in infectious disease research and clinical practice. These include detecting pathogens, measuring antibody responses, identifying markers of virulence, resistance, and disease severity, and understanding human immune responses and genetic susceptibility. Challenges include lack of sensitivity, mobile genetic elements, and changes in RNA sequences. Whole genome sequencing allows investigation of microbial phylogeny, evolution, and virulence factors.
- The mRNA-1273 vaccine induced robust antibody and neutralizing responses against SARS-CoV-2 in all participants after the first dose. A second dose led to even stronger responses, especially in the 100 μg and 250 μg groups. Systemic side effects were mostly mild or moderate. This interim report provides support for mRNA-1273 as a promising COVID-19 vaccine candidate warranting further development and evaluation.
This document summarizes information presented about Mycobacterium tuberculosis and tuberculosis. It discusses that M. tuberculosis grows slowly, doubling every 24 hours, and takes 3-4 weeks to culture. It also notes that tuberculosis infects around 2 billion people globally and causes 1.6 million deaths per year. The document also mentions that multidrug resistant tuberculosis is emerging worldwide and there are an estimated 50 million people infected with multidrug resistant strains.
The mechani smof t ransl at i on i ni t i at i on on t he genomi c RNA of Cadi ci vi rus A: a nat ural l y occurri ng di ci st roni c pi cornavi rus and t ype member of t he novel genus Di ci pi vi rus. The document discusses the discovery of Canine dicistronic picornavirus (Cadicivirus A, CDV-A) and aims to characterize the mechanism of translation initiation on its genomic RNA through predicting the secondary structure of its 5'UTR using SHAPE analysis and studying its activity in rabbit reticulocyte lysate using various constructs. Toe-printing
1) The study characterized the internal ribosomal entry site (IRES) of Canine dicistronic picornavirus (Cadicivirus A), a naturally occurring dicistronic picornavirus.
2) Predictive modeling and SHAPE analysis were used to predict the secondary structure of the 5'UTR IRES and confirm its predicted folding.
3) Comparisons showed similarities between domains of the Cadicivirus IRES and domains of the poliovirus IRES, but also differences that may influence structure and function.
4) IRESs can be studied in vitro using rabbit reticulocyte lysate to determine their ability to independently initiate translation of a downstream cistron.
The document describes malaria immunology and epidemiology studies conducted in Papua New Guinea between 2004-2017. It involved several cohort and intervention studies with observational cohorts of approximately 500-2000 individuals. The studies aimed to understand immunity targets and mechanisms to malaria in order to rationalize vaccine development. They examined both antibody and cellular immune responses. Key findings included that γδ T cells are a major source of IFNγ response and certain NK cell receptors are associated with risk of high density infections.
2015 Detection of Leishmania Parasites via Flow Cytometry ReviseAnaliese Wenger
This document describes a study that used flow cytometry to detect Leishmania parasites inside infected macrophages. Leishmania are single-celled parasites that infect humans and cause diseases like cutaneous and visceral leishmaniasis. The study infected mouse macrophages with L. major and L. infantum and used an anti-Leishmania antibody with fluorescent tagging to detect the parasites via flow cytometry. The results showed that the antibody attached to the surface of both parasite species and flow cytometry could distinguish between infected and uninfected macrophages, though separation was incomplete. This technique has potential for detecting Leishmania infection.
Malaria is caused by parasites of the Plasmodium type, which are transmitted via the bites of infected Anopheles mosquitoes. The parasites multiply in the liver and then infect red blood cells. Symptoms of malaria include fever, chills, and flu-like illness. Malaria most commonly occurs in subtropical and tropical areas of Africa, Asia, and South America. While the disease can be treated with antimalarial drugs, prevention through mosquito bite avoidance and antimalarial prophylaxis is most effective.
RAD: Christian J. Stockert Jr, Junmin Liuniranabey
The Penn Experience with MAGE-TAB involved loading 22 studies from various species including human, mouse, Plasmodium, and Toxoplasma into their local database using MAGE-TAB over the past year. They generated MAGE-TAB from templates and downloaded studies. Lessons learned included that providing templates with fillable areas colored was helpful for submitters, but biologists found the format difficult to understand without assistance. Their tools help with validation, loading, and visualization of MAGE documents.
This document discusses using molecular genotyping methods to investigate the genetic diversity of Mycobacterium tuberculosis strains in Taiwan. It provides background on M. tuberculosis and describes several genotyping methods including restriction fragment length polymorphism (RFLP), spoligotyping, variable number tandem repeats (VNTR), and mycobacterial interspersed repetitive units (MIRU). The study aims to evaluate the genotyping efficiency of these methods, select appropriate genetic markers, and establish high-throughput protocols. Preliminary results on 479 samples from Taiwan show discrimination of strains by region, age, gender and genotype. Locus discrimination power and Hunter-Gaston discrimination index are also reported for different genotyping methods.
This research article demonstrates the use of Wavelength Modulated Raman Spectroscopy (WMRS) to identify major immune cell subsets in an unlabeled and non-fixed state. Using WMRS, the researchers were able to distinguish between CD4+ T lymphocytes, CD8+ T lymphocytes, and CD56+ Natural Killer cells from multiple donors with up to 96% specificity. They also distinguished between CD303+ plasmacytoid and CD1c+ myeloid dendritic cell subsets. This label-free method opens new opportunities for analyzing immune systems and developing diagnostic technologies without altering or damaging the cells.
Presentation by adrian hill [university of oxford]Pamoja
Malaria is a major global health problem, killing over 700,000 people annually. Developing an effective vaccine is challenging due to the parasite's complex life cycle and ability to evade the immune system. Current vaccine approaches include protein-adjuvant vaccines targeting specific stages, viral vectored vaccines to induce cellular immunity, and whole parasite vaccines. Significant progress has been made, but partial efficacy has required unprecedented immunogenicity. A multi-component vaccine targeting multiple stages may be needed for high efficacy.
ProImmune Antigen Characterization Summit Paul Mossamandacturner
This document summarizes research on the immune response to cytomegalovirus (CMV) and cancer-testis antigens (CTAgs). It discusses how CMV elicits a massive immune response, occupying up to 40% of CD8+ T cells. This response declines with immunosuppression. It also explores using CMV-specific T cells for immunotherapy after stem cell transplantation. The document then examines CTAgs, which are expressed in cancers and elicit anti-tumor immune responses, but challenges remain in understanding their efficacy.
Dr. David Mooney - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
1) The study investigated how Gram-negative bacterial lipopolysaccharide (LPS), a component of bacteria like Chlamydia and Neisseria that cause STIs, affects expression of HIV receptors in cervical epithelial cells.
2) The results showed that LPS increased expression of the CCR5 HIV co-receptor and other alternative receptors in cervical cells through activation of EGFR, ERK1/2, and COX-2 signaling pathways.
3) This suggests that STIs have the potential to enhance susceptibility to HIV infection in women by regulating expression of HIV receptors in cervical epithelial cells through an inflammatory response.
Transglutaminase 2 (TG2) expression was examined in macrophages in response to Toxoplasma gondii infection and stress. TG2 was expressed in RAW macrophages and intestinal epithelial cells. TG2 expression increased at 3 hours post-infection but decreased at 8 hours. TG2 expression was induced by the stress hormone corticosterone, norepinephrine, and T. gondii infection, with maximum expression observed when infection and norepinephrine were combined. Increased TG2 expression may be detrimental to the host by decreasing anti-inflammatory transforming growth factor beta from macrophages and exacerbating inflammation.
1) Researchers studied the internal ribosomal entry site (IRES) in the 5' untranslated region of the canine dicistrovirus (CDV-A) genome.
2) Using computational prediction and SHAPE analysis, they determined the secondary structure of the CDV-A 5'UTR IRES, which resembles the poliovirus IRES structure.
3) In vitro translation assays in rabbit reticulocyte lysate showed that the CDV-A 5'UTR IRES can direct cap-independent translation, and requires the initiation factor eIF4A.
A brief exploration of the way some modern viruses act and ancient viruses have acted to benefit their hosts - particularly humans - today and through evolutionary history, by various means (such as targeted destruction of pathogenic bacteria and introduction of new genetic material).
This document summarizes a study that identified genes in the extracellular matrix that regulate the susceptibility of cultured cells to prion infection. The study compared gene expression in prion-susceptible and resistant cell lines. They identified 9 genes, including fibronectin 1 and integrin α8, that were upregulated in resistant cells. Knockdown of these genes increased susceptibility by altering the extracellular matrix structure and deposition of prion proteins. The results suggest the extracellular matrix plays a key role in controlling prion infection by influencing how prion proteins interact and convert forms.
Candidemia in HIV-positive patients in Dschang District Hospital (West Region...Claude Nangwat
Candidemia has been identified as a public health problem in HIV-infected patients. The evaluation of CD4 count, transaminases and blood glucose, are being used as a means to monitor the health of HIV-infected patients, without excluding the diagnosis of candidemia and other opportunistic infections. In order to contribute in improving the care of HIV-infected patients attending Dschang District Hospital and later on, in other hospitals in Cameroon, we conducted from June to September 2014 a cross-sectional study, with general objective; to determine the association between candidemia and selected biochemical and haematological parameter changes in HIV-infected patients, as a possible indicator in monitoring HIV disease progression.
To do this, blood samples were collected from HIV-infected patients assigned to the UPEC of Dschang District Hospital for follow up, and haemogram report, CD4 counts, ALAT level, ASAT level, and glucose level in blood were evaluated by cytometric and spectrophotometric assays. Candida species were isolated from some blood samples, and then identified using CHROMagar Candida culture medium. The broth microdilution method was afterwards used to test the susceptibility of the fungal isolates vis-a-vis three conventional antifungal agents.
Mycological analysis of blood samples showed that eight (08) patients had candidemia, a prevalence of 6.11%. Eight (08) isolates were obtained from these eight (08) candidemic HIV-infected patients; this consisted of 4(50%) Candida albicans, 3(37.5%) Candida parapsilosis and 1(12.5%) Candida glabrata. All these isolates were resistant (MICs ranged from 2 to >256 µg/mL) to the antifungals used, that is, ketoconazole, amphotericin B and nystatin.
A significant correlation was found between candidemia and white blood cell count, with a correlation coefficient of r = 0.240 (p < 0.05). Based on the results obtained, the systematic diagnosis of candidemia should be performed in patients infected with HIV in Cameroon in order to improve on their care.
Key words: Candidemia, HIV, biochemical parameters, hematological parameters, Antifungals activities.
This document compares the allele frequencies of 15 Plasmodium falciparum merozoite antigen genes in malaria infections sampled in Kenya in 2007 and 2008. It finds fluctuating allele frequencies in codons 147 and 148 of the reticulocyte-binding homologue 5 (Rh5) gene over this period in uncomplicated malaria infections. However, the dominant YH haplotype was stable over multiple years in asymptomatic and complicated infections. A regression analysis found the chance of the less common HD haplotype decreased over time from 2007 to 2009 in uncomplicated and asymptomatic infections.
Molecular biomarkers can be used for several purposes in infectious disease research and clinical practice. These include detecting pathogens, measuring antibody responses, identifying markers of virulence, resistance, and disease severity, and understanding human immune responses and genetic susceptibility. Challenges include lack of sensitivity, mobile genetic elements, and changes in RNA sequences. Whole genome sequencing allows investigation of microbial phylogeny, evolution, and virulence factors.
- The mRNA-1273 vaccine induced robust antibody and neutralizing responses against SARS-CoV-2 in all participants after the first dose. A second dose led to even stronger responses, especially in the 100 μg and 250 μg groups. Systemic side effects were mostly mild or moderate. This interim report provides support for mRNA-1273 as a promising COVID-19 vaccine candidate warranting further development and evaluation.
This document summarizes information presented about Mycobacterium tuberculosis and tuberculosis. It discusses that M. tuberculosis grows slowly, doubling every 24 hours, and takes 3-4 weeks to culture. It also notes that tuberculosis infects around 2 billion people globally and causes 1.6 million deaths per year. The document also mentions that multidrug resistant tuberculosis is emerging worldwide and there are an estimated 50 million people infected with multidrug resistant strains.
The mechani smof t ransl at i on i ni t i at i on on t he genomi c RNA of Cadi ci vi rus A: a nat ural l y occurri ng di ci st roni c pi cornavi rus and t ype member of t he novel genus Di ci pi vi rus. The document discusses the discovery of Canine dicistronic picornavirus (Cadicivirus A, CDV-A) and aims to characterize the mechanism of translation initiation on its genomic RNA through predicting the secondary structure of its 5'UTR using SHAPE analysis and studying its activity in rabbit reticulocyte lysate using various constructs. Toe-printing
1) The study characterized the internal ribosomal entry site (IRES) of Canine dicistronic picornavirus (Cadicivirus A), a naturally occurring dicistronic picornavirus.
2) Predictive modeling and SHAPE analysis were used to predict the secondary structure of the 5'UTR IRES and confirm its predicted folding.
3) Comparisons showed similarities between domains of the Cadicivirus IRES and domains of the poliovirus IRES, but also differences that may influence structure and function.
4) IRESs can be studied in vitro using rabbit reticulocyte lysate to determine their ability to independently initiate translation of a downstream cistron.
The document describes malaria immunology and epidemiology studies conducted in Papua New Guinea between 2004-2017. It involved several cohort and intervention studies with observational cohorts of approximately 500-2000 individuals. The studies aimed to understand immunity targets and mechanisms to malaria in order to rationalize vaccine development. They examined both antibody and cellular immune responses. Key findings included that γδ T cells are a major source of IFNγ response and certain NK cell receptors are associated with risk of high density infections.
2015 Detection of Leishmania Parasites via Flow Cytometry ReviseAnaliese Wenger
This document describes a study that used flow cytometry to detect Leishmania parasites inside infected macrophages. Leishmania are single-celled parasites that infect humans and cause diseases like cutaneous and visceral leishmaniasis. The study infected mouse macrophages with L. major and L. infantum and used an anti-Leishmania antibody with fluorescent tagging to detect the parasites via flow cytometry. The results showed that the antibody attached to the surface of both parasite species and flow cytometry could distinguish between infected and uninfected macrophages, though separation was incomplete. This technique has potential for detecting Leishmania infection.
Malaria is caused by parasites of the Plasmodium type, which are transmitted via the bites of infected Anopheles mosquitoes. The parasites multiply in the liver and then infect red blood cells. Symptoms of malaria include fever, chills, and flu-like illness. Malaria most commonly occurs in subtropical and tropical areas of Africa, Asia, and South America. While the disease can be treated with antimalarial drugs, prevention through mosquito bite avoidance and antimalarial prophylaxis is most effective.
RAD: Christian J. Stockert Jr, Junmin Liuniranabey
The Penn Experience with MAGE-TAB involved loading 22 studies from various species including human, mouse, Plasmodium, and Toxoplasma into their local database using MAGE-TAB over the past year. They generated MAGE-TAB from templates and downloaded studies. Lessons learned included that providing templates with fillable areas colored was helpful for submitters, but biologists found the format difficult to understand without assistance. Their tools help with validation, loading, and visualization of MAGE documents.
1. The document discusses population genetics concepts as they relate to infectious diseases, including effective population size within individual hosts and within epidemics.
2. It explains that epidemics begin when the basic reproductive number (R0) is greater than 1, meaning each infected individual spreads the disease to more than one other person on average.
3. Methods for calculating R0 are presented, involving factors such as new infections caused, disease-related deaths, recoveries, and non-disease deaths.
El documento trata sobre la historia, diagnóstico y tratamiento de la leucemia y las anemias. Explica que la leucemia fue descubierta hace casi 200 años y originalmente se trataba con arsénico. Luego, en el siglo 20, se empezó a usar la terapia de radiación y quimioterapia. Describe los métodos de diagnóstico como exámen físico y análisis de sangre, así como los tratamientos como quimioterapia, terapia dirigida, radioterapia y trasplante de
Este documento presenta un seminario sobre biología molecular relacionado con el parásito Plasmodium y la enzima tioredoxina peroxidasa. Los autores Daniel González y Juan José Garcés buscan encontrar nuevos métodos de diagnóstico para la malaria mediante el uso de anticuerpos monoclonales unidos a esta enzima. El documento describe las especies de Plasmodium que infectan humanos, el ciclo de vida del parásito, y los métodos utilizados en el estudio como ELISA, SDS-PAGE, inmunocromatografía y Western Blot.
1. The evolutionary relationships between malaria parasite species have been controversial due to past studies relying on visible traits rather than molecular data and issues like taxon bias.
2. Different genes are suitable for phylogenetic analysis, with some like rRNA being problematic due to paralogs. Studies using multiple genes from different genomic compartments provide better resolution.
3. The origin of P. falciparum, which causes the most virulent human malaria, has been debated, with evidence it may have recently switched hosts from gorillas rather than co-diverging with humans. Further sampling of ape malarias is needed to resolve this.
Antigen variation is common in protozoan parasites to evade the host immune system. Plasmodium falciparum, the parasite that causes malaria, utilizes antigen variation through expression of different var genes encoding PfEMP1 proteins on the surface of infected red blood cells. Only one var gene is expressed at a time through epigenetic and nuclear architectural mechanisms to ensure low and coordinated switching of antigens and avoid immune clearance. PfEMP1 promotes adhesion of infected cells, causing microvascular obstruction and malaria pathogenesis.
Malaria is caused by plasmodium parasites transmitted via mosquito bites. The document discusses the life cycle and species of malaria parasites, which includes P. falciparum, P. vivax, P. malariae, and P. ovale. It then covers the pathogenesis of malaria, including the hepatic and erythrocytic phases. Finally, it outlines the clinical features of malaria like febrile paroxysms, splenomegaly, hepatomegaly, anemia, and complications of P. falciparum malaria such as cerebral malaria. Diagnostic methods for malaria are also summarized, including microscopy, fluorescent microscopy, and rapid diagnostic tests.
Malaria is caused by the intracellular protozoan parasite Plasmodium, which is transmitted through the bites of infected female Anopheles mosquitoes. The parasite invades and reproduces within human red blood cells. During invasion, merozoites release contents from organelles like micronemes and rhoptries, which help in binding and entry into red blood cells. The parasite then modifies red blood cell surface by forming knob-like protrusions to evade immune detection and adhere to blood vessel walls, preventing clearance by the spleen. This sequestration can lead to complications in multiple organs. Diagnosis involves microscopic examination of blood smears to identify various parasite stages.
BCC4: Pierre Janin on 4 Newer Agents for Hepatitis CSMACC Conference
Janin speaks on the dawn of a revolution for treating Hepatitis C. This was recorded at Bedside Critical Care Conference 4. Full postings can be found at www.intensivecarenetwork.com
molecular markers for antimalarial drug resistanceAnil kumar
this presentation deals with the drugs for choice for malaria, their mode of action, resistance development and its distribution, how to evaluate resistance development and reasons for developing resistance.
Drug Repurposing Against Infectious Diseases Philip Bourne
This document discusses challenges in drug repurposing against infectious diseases and proposes an integrated computational approach using chemical genomics and structural systems biology. It presents an algorithm called geneSAR that improves prediction of drug-target interactions. Case studies demonstrate how the approach identified selective estrogen receptor modulators as potential anti-virulence agents against Pseudomonas aeruginosa and how targets of compounds from an open access malaria box could enable drug repurposing and optimization. The integrated computational pipeline generates testable hypotheses for improving treatments of infectious diseases.
Malaria is a life-threatening disease caused by Plasmodium parasites transmitted via the bites of infected Anopheles mosquitoes. It is a major public health issue in many developing countries, especially in sub-Saharan Africa. The most severe and deadly form is caused by P. falciparum. Symptoms include fevers, chills, and flu-like illness. Without prompt treatment, P. falciparum malaria can progress to severe complications and death. Diagnosis is by microscopy of blood films to detect the parasites. Treatment depends on the parasite species, but may include chloroquine, quinine, artemesinin or antifolate combinations. Prevention focuses on mosquito avoidance, control,
The Grand Canyon separates two populations of squirrels, the Albert and Kaibab squirrels. The canyon acts as a geographic barrier that has led to allopatric speciation as the squirrel populations evolved independently on either side over time with limited gene flow between them.
Mechanisms of Evolution: Population Selection and ChangePaulVMcDowell
The document discusses several key mechanisms of evolution:
1. Mutations introduce new genetic variations within populations.
2. Natural selection leads to changes in populations over generations as certain traits increase chances of survival and reproduction.
3. Gene flow spreads variations between populations through migration and interbreeding.
4. Genetic drift causes random fluctuations in allele frequencies that can accumulate over time, especially in small, isolated populations.
Hepatitis C is a major global public health problem that infects approximately 180 million people worldwide. It is a leading cause of liver disease and death, with more than 350,000-500,000 people dying each year from hepatitis C related liver disease. The virus predominantly causes chronic infection in 70-85% of cases and can lead to cirrhosis, liver failure, and hepatocellular carcinoma over time if left untreated. New direct acting antiviral regimens have revolutionized treatment and now offer cure rates over 95% with shorter, better tolerated courses of therapy.
My presentation in the "CME on Sickle Cell Disease" at Government Medical College, Akola, Maharashtra, India on 19th December 2012 organized by MMC-CME Committee of GMC, Akola and the Department of Pediatrics, GMC, Akola.
The document discusses the RTS,S/AS01 malaria vaccine candidate. It provides details on the development of RTS,S from initial designs incorporating the circumsporozoite protein to clinical trials demonstrating safety and efficacy. Phase 3 trials in African children showed RTS,S/AS01 reduced clinical malaria by approximately 50% and severe malaria by approximately 50% over 12 months. While the vaccine provided benefit, it also caused some adverse side effects and deaths. Ongoing research continues to improve vaccine design and development for a highly effective malaria vaccine.
Host-pathogen Interactions, Molecular Basis and Host Defense: Pathogen Detect...QIAGEN
Host–pathogen interactions are strikingly complex during infection. This slidedeck provides an overview of the molecular basis of these intricate interactions: the impact of microbiota on innate and adaptive immunity, metabolism, and insulin resistance and host defense mechanisms. Various research tools will be introduced to simplify and streamline each step of studying the host response, enabling detection of pathogens, analysis of gene expression and regulation, epigenetic modification, genotyping and signal transduction pathway activation.
Conferencia de la Dra. Ana María Roa, Bióloga Molecular, sobre Epigenética, impartida en la Universidad Popular Carmen de Michelena de Tres Cantos el 1 de marzo de 2013.
Más información en:
http://www.universidadpopularc3c.es/index.php/actividades/conferencias/event/448-conferencia-una-revision-de-los-conocimientos-fundamentales-de-la-biologia-de-la-celula-la-epigenetica
Target validation of the inosine monophosphate dehydrogenase (IMPDH) gene in ...Therese Horn
This document summarizes research using a yeast-two hybrid system and Phylomer peptide library to identify peptides that interact with and potentially inhibit the inosine monophosphate dehydrogenase (IMPDH) enzyme in Cryptosporidium. IMPDH is a potential drug target as Cryptosporidium relies solely on purine salvage and IMPDH is essential for DNA synthesis. A Phylomer peptide library was screened against IMPDH from C. parvum and C. hominis, identifying 38 unique interacting peptides. 12 peptides were synthesized and 2 showed significant growth inhibition of C. parvum in vitro. One peptide consistently interacted with C. parvum and C. hominis IMPDH but not human
STD Prevalence in World, USA and Iran, and Neisseria gonorrhoeaeMeisam Ruzbahani
The document discusses sexually transmitted infections (STIs). It provides lists of common bacterial, fungal, viral and parasitic infections including Neisseria gonorrhoeae, Chlamydia trachomatis, HIV, HPV, and Trichomonas vaginalis. It notes that STIs can cause complications like pelvic inflammatory disease and increase the risk of HIV transmission. Global statistics on new curable STI cases are provided, with the highest numbers in South and Southeast Asia. The document also discusses how STIs differently impact women, including increased risk of infertility and passing infections to babies.
Microbial Biotechnology Scope, Technique and Examples in Therapeutics Zohaib HUSSAIN
Genetic engineering enables us to produce a large number of proteins in bacterial cell that were originally encoded by human genes. For example a landmark in this case is production of insulin in bacterial cell in 1982. It is first case of genetically engineered therapeutic protein used for clinical purposes. Insulin produced in this way is widely used in curing diabetes and is same in all forms as compared to original insulin
Martin Chang, MBBE final report, 2012_08_21Martin Chang
This document summarizes key information about developing an effective blood-stage malaria vaccine, including:
1) Existing vaccines like RTS,S have shown only partial effectiveness, so more effective vaccines are still needed.
2) The malaria parasite has different life stages, and vaccines target different stages. This report focuses on blood-stage vaccines.
3) Effective immune mechanisms against blood-stage parasites include antibody-dependent cellular inhibition (ADCI) and antibody-dependent respiratory burst (ADRB), but these have not been fully induced by existing vaccines.
Immunocompromised patients are susceptible to infections from bacteria, fungi and viruses that a healthy immune system would usually fight off. Their weakened immune systems may be due to cancer treatments, transplants, or inherited/acquired immune disorders. These patients are at risk of infections from common organisms like Staphylococcus and Pseudomonas, as well as opportunistic pathogens like Candida, Aspergillus, Cryptococcus, and Acanthamoeba. Diagnosis involves cultures, antigen tests and imaging. Treatment requires appropriate antifungal or antibacterial drugs.
Intracellular highways in the plants: the role of the cytoskeleton in camv i...CIAT
The document discusses research on the intracellular movement of Cauliflower Mosaic Virus (CaMV) particles. It finds that the CaMV P6 protein forms motile inclusion bodies that traffic along the plant cell's actin microfilaments and stabilize microtubules. The P6 inclusion bodies are hypothesized to function as "virion factories" where CaMV particles assemble before being transported to plasmodesmata for movement between cells. A yeast two-hybrid screen identified the host protein CHUP1, which mediates chloroplast movement along microfilaments, as interacting with P6. Silencing CHUP1 reduced the rate of CaMV lesion development, supporting its role in P6 inclusion body movement.
A novel marker, ARM58, confers antimony resistance to Leishmania spp.Carola Schäfer
This document describes the identification of a novel genetic marker, LbrARM58, that confers antimony resistance to Leishmania species. Using a functional cloning strategy with genomic DNA libraries from antimony-resistant and sensitive L. braziliensis clinical isolates, researchers repeatedly selected a region on chromosome 20. This region contains the gene LbrM20.0210, which when overexpressed increases resistance to antimony (SbIII) in L. braziliensis and L. infantum in vitro and enhances parasite survival inside macrophages under antimony pressure. LbrM20.0210 encodes a previously uncharacterized protein with four repeats of a domain of unknown function that is unique to the Leishmania genus.
Alan Lesniewicz Memorial Lecture at UIC - July 2015Cassandra Quave
This is the keynote lecture given at the University of Illinois at Chicago Garden Walk event in the department of Pharmacognosy. The objectives of the talk were:
·Discuss the role of medical ethnobotany in drug discovery efforts
·Explore state-of-the-art research techniques that examine the activity of botanical natural products with next generation antibiotic discovery efforts focused on “alternative targets”, such as bacterial communication systems
·Provide examples of current research underway by her group both in the field (especially through fieldwork in the Mediterranean) and the lab (natural product research on multidrug resistant bacteria).
tansgenic mice:methodology and applicationtinasingh30
This document discusses the generation and applications of transgenic mice. It describes four main methods for generating transgenic mice: retroviral vector method, microinjection method, engineered embryonic stem cell method, and yeast artificial chromosome transgenesis. Transgenic mice can be used as disease models and to study the biological basis of human diseases. They have been made for conditions like Alzheimer's disease and cystic fibrosis. Transgenic mice are also used as test systems to evaluate potential therapies.
Schistosomiasis is caused by a parasitic flatworm and affects over 200 million people worldwide. It is transmitted through contaminated water. The most common drug used to treat it, praziquantel, is losing effectiveness due to the emergence of resistant strains. This study identifies a new compound that shows promising potential as an alternative drug. The compound was found to be effective against all life stages of the parasite, including the three main species that infect humans. It had lower cytotoxicity than praziquantel and was equally or more effective at reducing worm burden in mice. Further testing is still needed to fully evaluate its efficacy and safety profile prior to clinical use in humans.
Clinical Manifestations of Plasmodium bergheiANKA Infection in Juvenile Mice:...AI Publications
Malaria is an important health and development challenge in Africa, Animalmodels most particularly mice, have long been employedto study malaria pathogenesis. Clinical manifestations due to Plasmodium bergheiANKA infection in juvenile mice as a model for understanding the complications ofcongenital malaria in neonates.Forty-five juvenile mice (5-7 days old) were acquired from University College Hospital, Ibadan and injected with 2 x 107 (0.2ml) Plasmodium berghei ANKA parasitized red blood cells (PRBCs). Mice were transported to the study site, kept in well ventilated cages and fed daily with a balanced ration. Every day after post-P. berghei infection, mice were monitored for mortality. Clinical manifestations ofexperimental cerebral malaria (ECM) was assessed and confirmed if at leastruffled fur, hunching, wobbly gait, limb paralysis, convulsions, or coma was observed. Each sign was given a score of 1. Animals with scores ≥4 were considered to have severe ECM.20 (44%) micewerelost due to natural cause (i.e. stress) at day 2 of the experiment. Between day 4 and 9, 25 (56%) of the studymice presented clinical signs of ECM which includes; ruffled fur 25(100%), hunching 21 (84%), wobbly gait 17 (68%), limb paralysis 20 (80%), convulsions 25 (100%) and subsequently died. Survival rate and severity of ECM in the mice differs, 22 (88.0%) had severe ECM and 3(12.0%) had mild ECM.This study has shown that parasite establishment and malaria complications can manifest as early as 4 days’postP. berghei infection in 5-7 days old mice.
This study analyzed loss of heterozygosity (LOH) in papillary thyroid carcinoma (PTC) by examining microsatellite markers in the M6P/IGFIIR gene region and three loci on chromosome 11 in 98 PTC tumor and normal tissue samples. The samples showed 49-63% heterozygosity for the markers analyzed. However, LOH was not detected in any of the informative heterozygous samples, indicating that LOH did not contribute to PTC development in these patients for the regions studied.
Immunotoxins are being developed to specifically target and destroy cancer cells. The document summarizes research from Professor Rama Verma's lab on developing humanized immunotoxins as alternatives to bacterial/toxin-based immunotoxins that can cause toxicity. The lab has created immunotoxins linking GM-CSF to DFF40 to target leukemia cells and IL2 to TRAIL to target leukemia patients' samples. These humanized immunotoxins induce apoptosis in cancer cells with less toxicity than traditional immunotoxins. The lab is also exploring targeting cancer stem cells, which can cause cancer recurrence after treatment.
Gene drives are being explored for alleviating vector-borne infectious diseases however, the risks of employing them need to be understood. This Slidedoc assesses the potential use of gene drives in India by performing a stage-wise risk assessment of deploying gene drive.
Gene drive mosquitoes are an application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. The application is to develop mosquitoes that decrease the incidence of mosquito-borne diseases.
Research into gene drives should be promoted however, there are risks associated with their potential use in India. Given the nature of the technology, it is recommended that robust monitoring mechanisms for disease incidence, mosquito burden and ecological impact be implemented before deploying these mosquitoes.
Data driven decisions on identifying the type of gene drive and deployment locations will ensure effective use of the technology.
This document summarizes a seminar on the role of effectors in plant-fungal interactions. It discusses how fungi secrete effectors to suppress plant immunity and facilitate infection. Effectors can target the plant apoplast or cytoplasm. Apoplastic effectors inhibit antifungal enzymes and proteins or suppress chitin-triggered immunity. Cytoplasmic effectors interfere with hormone signaling or alter protein stability. The seminar also examines how plants have evolved resistance proteins that recognize specific effectors. Effectoromics uses high-throughput screening of effectors to identify new plant resistance genes and their corresponding fungal avirulence genes.
Similar to WGHA Discovery Series: Robert Sinden (20)
This document summarizes a needs assessment conducted in Bangkok, Thailand to inform diabetes prevention efforts. Surveys found exercise was the top perceived need, with 28.9% reporting no exercise. However, participants noted a lack of community spaces and access barriers to physical activity. While organizers were concerned about a lack of cooperation and commitment to community-centered programs. The needs assessment identifies structural and participation barriers to address to effectively promote diabetes prevention in the community.
This document summarizes strategies used to undermine public acceptance of climate change science and discusses ways to more effectively engage the public on this issue. It notes that corporate interests have funded front groups and think tanks to manufacture doubt about climate science and make lack of certainty a political issue. As a result, news media often portray climate science as a two-sided controversy when there is actually a scientific consensus. It suggests joining online networks for information and action, developing new communication strategies, and promoting a values-based debate around climate solutions rather than perpetuating manufactured controversies.
The document discusses accountability for global health efforts. It asks if governments of poor countries are accountable for not spending more on domestic health and if so, to whom. It also asks if international organizations like the IMF and World Bank are accountable for policies that discourage health spending and if rich country governments are accountable for not providing more international health aid. It notes challenges to mutual accountability given both national and international responsibilities for health.
Understanding the Effect of the GAVI Initiative on Reported Vaccination Cover...UWGlobalHealth
This document discusses the critical role of health metrics and evaluation in ensuring accountability, transparency and reducing corruption in global health. It provides two examples: tracking childhood immunization coverage shows investments have increased coverage gradually over 20 years but initiatives can lead to over-reporting; India's conditional cash transfer program for facility births increased coverage and likely reduced mortality, but quality issues remain. Overall, independent monitoring of health indicators and evaluation of programs is needed to show resources are having their intended impact.
Foreign funding to NGOs in Nicaragua has undermined their accountability to grassroots organizations and limited their ability to catalyze social change. Due to short-term funding cycles tied to donor priorities, NGOs are more accountable to foreign donors than the communities they are meant to serve. This has contributed to a façade of civil society dominated by urban NGO elites rather than empowered grassroots organizations. As a result, NGOs have had minimal policy impact and have demobilized, rather than empowered, the people. Long-term funding structures that strengthen accountability to local constituencies may help NGOs better support grassroots organizations and social movements.
The Power of Numbers- Communities Use Government Budget Data to Advocate for ...UWGlobalHealth
The International Budget Partnership provides concise summaries of documents in 3 sentences or less:
The document outlines the work of the International Budget Partnership (IBP), including building budget literacy, training on fiscal analysis, and monitoring government budgets and expenditures. IBP partners with civil society organizations around the world to increase budget transparency and hold governments accountable. The document also describes IBP's role in providing funding, capacity building, information sharing, and networking opportunities to support its partners' budget work.
Perspectives and Controversies surrounding human rightsUWGlobalHealth
This document discusses the right to health from a human rights perspective. It begins by defining key concepts like health, human rights, and the relationship between health and human rights. It then examines how the right to health is established under international law through conventions like the International Covenant on Economic, Social and Cultural Rights. The document also summarizes commentary on the right to health from the UN Committee on Economic, Social and Cultural Rights. Finally, it discusses some controversies and challenges regarding a human rights-based approach to health, such as issues of universality and developing appropriate indicators.
Politics and Health Reform:Lessons From a Year in Washington, D.C.UWGlobalHealth
This document summarizes the history of health reform efforts in the United States from the late 19th century to 2009. It discusses how a national health insurance system has been proposed since the 1880s but consistently opposed by groups like the AMA and insurance industry. The US now spends over twice as much per capita on healthcare as other OECD countries but has lower life expectancy and more administrative waste. Creating a universal, publicly financed system could reduce costs while improving access and outcomes.
"What Will It Take To Control TB?" Richard Chaisson, MDUWGlobalHealth
Dr. Richard Chaisson, Professor of Medicine, Epidemiology and International Health and Director of the Center for Tuberculosis Research at the Johns Hopkins University in Baltimore was the keynote Jan. 19 as part of the Washington Global Health Discovery Series. His talk was on ""What Will It Take To Control TB?"
This document discusses health as a societal right. It begins by discussing how health has traditionally been viewed as an individual responsibility but argues that there are no biological reasons why entire populations cannot be healthy. It then explores how health can be considered a societal or human right. The document examines how determinants of health are influenced by societal factors like inequality and poverty rather than just individual behaviors or access to healthcare. Overall, it promotes a view of health as a societal issue that governments should aim to improve and protect for entire populations, rather than just an individual concern.
"The Aid Enclave: Mapping and Emerging Geography of Global Health"UWGlobalHealth
The document discusses how global health initiatives have led to the emergence of "aid enclaves" - self-contained areas focused on health research and aid that become isolated from their surroundings. It describes how these enclaves develop through economic, political, and ethical processes. Economically, they exist as tax-free zones that offer higher pay and privileges to foreigners compared to locals. Politically, they represent a return to colonial-style projects. Ethically, they position themselves as spaces of biomedical and moral correctness but may marginalize local healing practices. The document critiques how enclaves can act as "parasites" detached from the communities they aim to serve.
1) The US ranks last among seven countries in overall health system performance and ranks last or near last on most measures of health care quality, access, efficiency, and equity.
2) While the US spends much more per capita on health care than other countries, it has poorer population health outcomes and shorter life expectancies.
3) Rising health care costs are consuming an increasing share of family budgets in the US. The percentage of families spending over 10% and over 25% of pre-tax income on health care doubled from 2000 to 2008.
"The Health System and Aid Effectives: Sudan's Experience"UWGlobalHealth
The document summarizes Sudan's health system and aid effectiveness. It provides background on Sudan's location and history as a 4000 year old civilization. It then discusses Sudan's socio-economic context, including its potentially rich natural resources and decentralization of services. The health delivery system is described as providing free healthcare, with increasing expenditures over time. Main health issues are outlined and data is given on international NGO presence and beneficiaries across regions. The document concludes with some of the challenges facing Sudan's health system.
The IHOP program allows medical students to spend 8 weeks in a developing country to learn about global health challenges. Students conduct a community health assessment and partner with local organizations to address health needs. The experience aims to provide cultural immersion and help students understand how to incorporate global health into their careers. Students are responsible for costs of $3,000-$5,000 and must complete assignments while abroad and after returning. Strong applicants have a genuine interest in global health and experience with underserved populations.
The document summarizes health reforms in Mexico from 1943-2004, with a focus on the 2004 reform that established the Health Social Protection System. It overviews declining mortality rates and increasing life expectancy over time. Key aspects of the 2004 reform included establishing universal health care coverage, separating financing from service provision, defining an essential benefits package, and increasing accountability through performance measurement. The reform reorganized Mexico's health system to improve access, quality, and financial protection for all citizens.
The document discusses health care systems and funding in Mozambique. It outlines the various sectors involved in health including public, private, NGOs, and traditional/alternative care. It also describes the types of funding for health care including vertical, horizontal, and diagonal funding. Vertical funding for specific diseases has increased from organizations like PEPFAR, Global Fund, and foundations. While this funding has increased dramatically, questions remain about whether NGOs effectively strengthen health systems or divert resources and can fragment services.
The document summarizes research into how NGOs are implementing a voluntary Code of Conduct for Health Systems Strengthening. Interviews found that while most signatories are aware of the Code and value its principles, they still face challenges adhering to provisions around hiring health workers from ministries of health and matching government salaries. Some promising practices discussed include building workforce capacity through training, advocating for improved public sector opportunities, and coordinating hiring and compensation policies among NGOs. Overall, signatories are committed to the Code's goals but continuing to test practical solutions for balancing them with operational needs.
The document discusses the erosion of public sector health systems and increased privatization. It argues that without strong public sectors, healthcare will be inequitable and exclude the poor, rural communities, and marginalized groups. Public health measures also risk being neglected. It examines factors driving privatization like international financial institutions and private sector interests, and argues the private sector did not compensate for declines in public investment as hoped.
The document discusses PATH's approach to collaborating with private sector partners to advance global health technologies. It focuses on PATH bringing expertise in developing country health systems and strategic relationships, while partners contribute product development expertise, intellectual property, and distribution systems. The collaboration aims to improve availability, accessibility, and affordability of important health products for public health programs.
How to Make a Field Mandatory in Odoo 17Celine George
In Odoo, making a field required can be done through both Python code and XML views. When you set the required attribute to True in Python code, it makes the field required across all views where it's used. Conversely, when you set the required attribute in XML views, it makes the field required only in the context of that particular view.
Leveraging Generative AI to Drive Nonprofit InnovationTechSoup
In this webinar, participants learned how to utilize Generative AI to streamline operations and elevate member engagement. Amazon Web Service experts provided a customer specific use cases and dived into low/no-code tools that are quick and easy to deploy through Amazon Web Service (AWS.)
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
Healing can occur in two ways: Regeneration and Repair
There are 4 phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This document also describes the mechanism of wound healing. Factors that affect healing include infection, uncontrolled diabetes, poor nutrition, age, anemia, the presence of foreign bodies, etc.
Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
"Learn about all the ways Walmart supports nonprofit organizations.
You will hear from Liz Willett, the Head of Nonprofits, and hear about what Walmart is doing to help nonprofits, including Walmart Business and Spark Good. Walmart Business+ is a new offer for nonprofits that offers discounts and also streamlines nonprofits order and expense tracking, saving time and money.
The webinar may also give some examples on how nonprofits can best leverage Walmart Business+.
The event will cover the following::
Walmart Business + (https://business.walmart.com/plus) is a new shopping experience for nonprofits, schools, and local business customers that connects an exclusive online shopping experience to stores. Benefits include free delivery and shipping, a 'Spend Analytics” feature, special discounts, deals and tax-exempt shopping.
Special TechSoup offer for a free 180 days membership, and up to $150 in discounts on eligible orders.
Spark Good (walmart.com/sparkgood) is a charitable platform that enables nonprofits to receive donations directly from customers and associates.
Answers about how you can do more with Walmart!"
Communicating effectively and consistently with students can help them feel at ease during their learning experience and provide the instructor with a communication trail to track the course's progress. This workshop will take you through constructing an engaging course container to facilitate effective communication.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptxEduSkills OECD
Iván Bornacelly, Policy Analyst at the OECD Centre for Skills, OECD, presents at the webinar 'Tackling job market gaps with a skills-first approach' on 12 June 2024
IGCSE Biology Chapter 14- Reproduction in Plants.pdf
WGHA Discovery Series: Robert Sinden
1. Understanding malaria development in the mosquito, and its pivotal role in the formulation of effective control strategies. R.E.Sinden DSc, FMedSci. The Malaria Research Centre Imperial College London
10. Malaria-Vector Control Works! Environmental House position House screens --Bednets Breeding site-- elimination DDT ( 19 50 s -60 s ) Synthetic Pyrethroid s/ ITN : Permethrin, Deltamethrin ( since 19 80 s ) Biological Control Bacillus thuringiensis israelensis (Bti) ( since 1980s ) Insecticidal
11. Reducing malaria profile (2001-2006) Source WHO Reports from countries Francis Omaswa, ITN’s; Drugs; Societal change
12. Why attacking (malaria in) the mosquito is an essential component of eradication Ro- the basic reproductive rate, is defined as the number of secondary cases derived from one individual. For malaria this can be as high as 200, but must be <1 to reduce the number of persons infected. ma 2 bp n r(-log e p) R o =
13. ma 2 bp n r(-log e p) R o = Mosquito:man ratio Mosquito biting rate Proportion of mosquitoes that are infectious Mosquito daily survival rate The daily proportion of infected people who become non-infectious to the mosquito Days taken for parasite in mosquito to become infective What factors determine the value of Ro?
14. ma 2 bp n r(-log e p) R o = Environment mgmt Insecticides Larvicides SIT/RIDL Biological control GM-sex ratio Housing Clothing Repellents Deterrents ITN GM-Olfaction mutants GM-Biological clocks GM-Parasite/vector interactions GM-Vector immunity Sporontocidal drugs ‘ Terminator’ genes ITN/IRS Gametocytocidal drugs Transmission-blocking vaccines and drugs L iver/ABS drugs/vaccines… only if they reduce infectivity to vector
16. Biology of Plasmodium development in the mosquito 8-20 day 1 hour 12 hour 24-36 hour 15 min Gametocytes Gametes Zygote Ookinete Oocyst Sporozoite
24. Ookinete Invasion of PTM and Midgut Cells Vlachou et al, Midgut R.Moon Bloodmeal PTM Midgut
25. Target parasite energy metabolism in ookinete? Vertebrate Invertebrate Oxidative phosphorylation Mitochondrial transport TCA cycle Glycolysis Atovaquone very active vs ookinete and oocyst Glycolysis and conversion of pyruvate to L-lactate TCA cycle Oxidative Phosphorylation Other mitochondrial proteins ABS Gct Okn
26.
27. Impact of anti-gamete (P230) antibody on microgametes Control Anti-230 SEM Ferritin -TEM
28.
29. Expression of FusM fragments in E.coli N C TM 1 828 680 708 33 N C MBP - 40 kDa TVMV TEV His 6 FusM polypeptide 37 kDa 25 kDa 1 2 3 4 5
30. Anti-HAP2 rabbit sera inhibits P.berghei ookinete development in vitro Currently evaluating transmission-blocking ability of sera in vivo using SMFA. Affinity purification on rProtein 37 kDa 25 kDa 1 2
32. Defining the ookinete/mosquito interactome 184 6 518 Includes : hypotheticals with protease or carbohydrate binding domains and botulinum neurotoxin-related homologies (regulated pathway) Includes : known vaccine candidates P25, P28 (default pathway) WARP and 3 hypotheticals ‘ Surface’ Proteome Bioinformatics Micronemes 4 3 90 26 POSH Etramp Pepsinogen
33. Proteomics: Understanding the Ookinete….Surface (Vaccine discovery) 1985 2005 2007 R. Sinden et al. -of micronemal origin
34. Surface/secreted molecules with known roles in gamete-ookinete-oocyst development P230 P48/45 HAP2* P47 P25 P28 Chitinase WARP MAOP CTRP PPLP5* Fertilization Ookinete ‘ Epithelial’ invasion
35. Standard Membrane Feeding Assay for transmission-blocking vaccines. Blood containing gametocytes + test antiserum Artificial or Natural Membrane Jacket for warm water Infected mosquito gut 6 days post feed Cultured P.f gametocytes + transmission blocking antibodies give reduced numbers of oocysts per mosquito and fewer infected mosquitoes ( An. stephensi and An. gambiae )
36. Human trials of Pv25 vaccine If 80% of the gametocyte carriers immunised vaccination would result in 33% reduction in transmission in the field Malkin et al; Vaccine, 2005 Medley et al; Parasitology, 1993 Antibody Activity (ELISA units) Percent blockade of oocyst intensity
37. Modelling transmission Sporozoites in bite Emma Dawes in Sinden et al PLoS Pathogens 2007 Hyperbolic No. of Macrogametocytes No. of Ookinetes Sigmoid No. of Ookinetes No. of Oocysts Sigmoid ? Hyperbolic
38.
39. 1. Modelling:- Implications A vaccine that kills 90% of the parasites will have markedly different impacts upon transmission ( i.e rendering each mosquito incapable of transmitting malaria) dependent upon the initial parasite burden Sinden et al PLoS Pathogens 2007 Percent reduction in infected mosquitoes Initial parasite number in mosquito Low transmission High transmission
41. Number of P. falciparum oocysts per positive mosquito in Simbock, Cameroon Frequency Number of Oocysts 30% of infected mosquito population have just one oocyst Mean infection intensity 2.2 oocysts Annan at al. 2005
42. Malaria Research Centre Current Research Collaborations Malaria Research Centre Institute for Systems Biology FILM Imaging Centre Scripps Research Institute (Proteomics) Metabolomics Research Biomalpar NoE Sanger Institute IRDC/IRSS Burkina Faso Malaria Research Centre Centre for Bioinformatics
43.
44. Gene expression during ookinete development DNA replication Meiosis Gametocyte activation 0 1h 24h Fertilisation 3h 8h Midgut Invasion 10d www.lumc.nl www.lumc.nl What essential function do aspartyl protease and the LAPs fulfil so early in development, and yet the phenotype is visible so late? Maternal transcription, gametic translation e.g p28, p25 Maternal transcription, ??????? translation e.g AP essential function phenotype Pre-zygotic maternal t/t/function e.g LAPs Zygotic (m/f) gene activation e.g. CTRP
45. Gene disruption (double crossover) studies were carried out in the rodent malaria model P.berghei. Plasmodial (and C. reinhardtii) HAP2 KO male gametes exflagellate normally, retain the ability to form tight, pre-fusion membrane attachments with female macrogametes, but are unable to fertilise normally, blocking the transmission of the parasite in the mosquito. IFAs using tagged transgenic parasites, and genetic crosses using male (CDPK4 KO) and female (NEK4 KO) deficient strains of P.berghei demonstrate that HAP2 functions is located (and essential) on the male gametocyte/gamete:
46. Binding of Pv25 to Mab Fragment Heavy chain Light chain GPI- anchor Mike Sternberg