Environmental laws and policies related to periodic flooding and sedimentation in the Lake Victoria Basin (LVB) of East Africa

What should a community of three states with diverse historical profiles of legal and regulatory frameworks do when a common ecological resource is threatened any yet is critical in the sustenance of communities around it? This is the challenge that East African States faced with dealing with Lake Victoria Basin (LVB) in East Africa (Uganda, Kenya, Tanzania, Rwanda and Burundi). Given the various ecological, land and demographic changes in the LVB, various institutions have attempted to address the negative changes and contribute towards poverty reduction and environmental restoration. This paper analyzed the existing laws and policies on periodic flooding and sedimentation of wetlands, rivers and flood plains, which is timely and important for improved management and utilisation of resources of LVB. The paper argues that the lack of community level policy models relating to land and water use affects soil management and ultimately affects the water used in the LVB. These area-specific policies and models all over the LVB will go a long way in dealing with the negative effects of periodic flooding and sedimentation.Key words: Lake Victoria, Basin, East Africa, sedimentation, periodic flooding, environment, law

Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant inheritance of germline mutations in the bone morphogenetic protein receptor type 2 (<it>BMPR2</it>) gene are a major risk factor for pulmonary arterial hypertension (PAH). While previous studies demonstrated a difference in severity between <it>BMPR2 </it>mutation carriers and noncarriers, it is likely disease severity is not equal among <it>BMPR2 </it>mutations. We hypothesized that patients with missense <it>BMPR2 </it>mutations have more severe disease than those with truncating mutations.</p> <p>Methods</p> <p>Testing for <it>BMPR2 </it>mutations was performed in 169 patients with PAH (125 with a family history of PAH and 44 with sporadic disease). Of the 106 patients with a detectable <it>BMPR2 </it>mutation, lymphocytes were available in 96 to functionally assess the nonsense-mediated decay pathway of RNA surveillance. Phenotypic characteristics were compared between <it>BMPR2 </it>mutation carriers and noncarriers, as well as between those carriers with a missense versus truncating mutation.</p> <p>Results</p> <p>While there was a statistically significant difference in age at diagnosis between carriers and noncarriers, subgroup analysis revealed this to be the case only for females. Among carriers, there was no difference in age at diagnosis, death, or survival according to exonic location of the <it>BMPR2 </it>mutation. However, patients with missense mutations had statistically significant younger ages at diagnosis and death, as well as shorter survival from diagnosis to death or lung transplantation than those with truncating mutations. Consistent with this data, the majority of missense mutations were penetrant prior to age 36 years, while the majority of truncating mutations were penetrant after age 36 years.</p> <p>Conclusion</p> <p>In this cohort, <it>BMPR2 </it>mutation carriers have more severe PAH disease than noncarriers, but this is only the case for females. Among carriers, patients with missense mutations that escape nonsense-mediated decay have more severe disease than those with truncating mutations. These findings suggest that treatment and prevention strategies directed specifically at <it>BMPR2 </it>pathway defects may need to vary according to the type of mutation.</p

Novel insights into the genomic basis of citrus canker based on the genome sequences of two strains of Xanthomonas fuscans subsp. aurantifolii

Background: Citrus canker is a disease that has severe economic impact on the citrus industry worldwide. There are three types of canker, called A, B, and C. The three types have different phenotypes and affect different citrus species. The causative agent for type A is Xanthomonas citri subsp. citri, whose genome sequence was made available in 2002. Xanthomonas fuscans subsp. aurantifolii strain B causes canker B and Xanthomonas fuscans subsp. aurantifolii strain C causes canker C. Results: We have sequenced the genomes of strains B and C to draft status. We have compared their genomic content to X. citri subsp. citri and to other Xanthomonas genomes, with special emphasis on type III secreted effector repertoires. In addition to pthA, already known to be present in all three citrus canker strains, two additional effector genes, xopE3 and xopAI, are also present in all three strains and are both located on the same putative genomic island. These two effector genes, along with one other effector-like gene in the same region, are thus good candidates for being pathogenicity factors on citrus. Numerous gene content differences also exist between the three cankers strains, which can be correlated with their different virulence and host range. Particular attention was placed on the analysis of genes involved in biofilm formation and quorum sensing, type IV secretion, flagellum synthesis and motility, lipopolysacharide synthesis, and on the gene xacPNP, which codes for a natriuretic protein. Conclusion: We have uncovered numerous commonalities and differences in gene content between the genomes of the pathogenic agents causing citrus canker A, B, and C and other Xanthomonas genomes. Molecular genetics can now be employed to determine the role of these genes in plant-microbe interactions. The gained knowledge will be instrumental for improving citrus canker control.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientIfico e Tecnologico (CNPq)Coordenacao para Aperfeicoamento de Pessoal de Ensino Superior (CAPES)Fundo de Defesa da Citricultura (FUNDECITRUS

Pharmacogenomics in pulmonary arterial hypertension: Toward a mechanistic, target-based approach to therapy

Pharmacogenomics is the study of how genetic variations influence the response to drugs, by correlating gene expression with the drug's efficacy and toxicity. This concept has recently been successfully applied in oncology. To test its applicability to PAH, we examined two experimental models of the disease: mice with deletion of the Vasoactive Intestinal Peptide gene (VIP- /-); and rats injected with monocrotaline (MCT). Since the two models express comparable phenotypic features, we analyzed their particular gene alterations, with special reference to genes related to pulmonary vasoconstriction, vascular remodeling, and inflammation. We then compared the phenotypic and genotypic responses in each model to treatment with the same drug, VIP. In untreated VIP-/- mice there was over-expression of almost all genes promoting vasoconstriction/ proliferation, as well as inflammation, and under-expression of all vasodilator/anti-proliferative genes. As expected, treatment with VIP fully corrected both the key PAH features, and all gene expression alterations. MCT-treated rats showed two distinct sets of alterations. One, similar to that in VIP- /- mice, i.e., tended to promote vascular remodeling and inflammation, e.g., up-regulation of myosin polypeptides, procollagen, and some inflammatory genes. The other was a set of opposite alterations that suggested an effort to modulate the PAH, e.g., up-regulation of the VIP and NOS3 genes. In this model, VIP treatment failed to correct many of the genotypic abnormalities, and, in parallel, incompletely corrected the phenotypic changes as well. This preliminary proof-of-concept study demonstrates the importance of genomic information in determining therapeutic outcome, and thus in selecting personalized therapy. Full validation of the merits of pharmacogenomics must await studies of lungs from patients with different forms of PAH

A Regional Health System Journey from Volume to Value: Roadmap to the Recognition as a 15 Top Health System in the USA for Quality Excellence

Nidal H Harb,1,2 Patricia A Said,1 Shirley L Gusta,1 Amanda M Wesson,1 Jordan D Brautigam,1 Jon H Lemke,1 Stephen T DeLessio,1 Douglas P Cropper,1 Nicolas W Shammas1,3 1Quality and Safety Department, Genesis Health System, Davenport, IA, USA; 2Cardiovascular Division, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 3Cardiology Research Unit, Midwest Cardiovascular Research Foundation, Davenport, IA, USACorrespondence: Nicolas W Shammas, Midwest Cardiovascular Research Foundation, 630 E 4th Street, Davenport, IA, 52801, USA, Tel +1 563-320-0263, Email [email protected]: The 15 Top Health System program, an IBM Watson study, objectively measures health systems’ performance overall on an annual basis using publicly reported data available from the Center for Medicare and Medicaid Services (CMS) and state data banks. Genesis Health System was recognized as an IBM Watson Health 15 Top Health System for two consecutive years in 2020 and 2021. A system-based approach with a “physician-lead, professionally-managed” framework, led to accomplishing the 15 Top Health System. The steps needed included adoption of the IBM Watson database to determine current status of certain key performance indicators, establishing a clinical effectiveness program and governance structure, and adopting Lean methodologies to analyze and determine appropriate interventions with long-term solution. The desire and willingness to accomplish this ambitious goal start with adoption by the Board and the administration of the health system while supplying appropriate financial and human resources that are dedicated to the success of the journey. In this manuscript, we describe the journey and steps implemented to accomplish the outcomes that led to the recognition as a 15 Top Health System for quality excellence.Keywords: 15 Top Health System, physician lead, clinical effectiveness, Lean methodology, Value of car