Leveraging seasonal influenza health worker vaccination programmes for COVID-19 vaccine Introduction: A global qualitative analysis.

BACKGROUND: Health worker vaccination programmes can help to safeguard both health workers (HWs) and their patients and enhance vaccine uptake more broadly in local communities and society. This study's objective was to increase global understanding of how existing HW vaccination programmes were leveraged for emergency COVID-19 vaccine introduction. METHODS: This qualitative study included 13 in-depth group interviews with 38 key informants with expertise in vaccine programme implementation from eleven countries in five WHO regions: Albania, Armenia, Bhutan, Lao PDR, Maldives, Mongolia, Oman, Timor Leste, the United Kingdom, Vietnam, and Zimbabwe in addition to WHO regional focal points from all six regions. These interviews were transcribed, coded, and thematically analyzed. Key informants reviewed the initial results and validated the key findings. RESULTS: Informants characterized key components of both routine and seasonal influenza vaccination programmes that were leveraged for the emergency vaccination of HWs during the COVID-19 pandemic. We identified a set of cross-cutting factors that were used for COVID-19 vaccine roll out: 1) pre-existing occupational health policies, 2) adequate human resources, 3) well-functioning data information systems and vaccine delivery platforms, and 4) established communication channels. Across the eleven countries and six regions interviewed, the ability to adapt existing influenza or other health worker vaccination infrastructure was beneficial for their pandemic response. CONCLUSIONS: Our findings suggest a strong justification for enhanced investment in vaccination of health workers, particularly against seasonal influenza, through country-wide programmes as a foundation for pandemic preparedness and response.

Artifactual Orthologs and the Need for Diligent Data Exploration in Complex Phylogenomic Datasets: A museomic case study from the Andean flora.

The Andes mountains of western South America are a globally important biodiversity hotspot, yet there is a paucity of resolved phylogenies for plant clades from this region. Filling an important gap to our understanding of the World's richest flora, we present the first phylogeny of Freziera (Pentaphylacaceae), an Andean-centered, cloud forest radiation. Our dataset was obtained via yrid-enriched target sequence capture of Angiosperms353 universal loci for 50 of the ca. 75 spp., obtained almost entirely from herbarium specimens. We identify high phylogenomic complexity in Freziera, including the presence of data artifacts. Via by-eye observation of gene trees, detailed examination of warnings from recently improved assembly pipelines, and gene tree filtering, we identified that artifactual orthologs (i.e., the presence of only one copy of a multi-copy gene due to differential assembly) were an important source of gene tree heterogeneity that had a negative impact on phylogenetic inference and support. These artifactual orthologs may be common in plant phylogenomic datasets, where multiple instances of genome duplication are common. After accounting for artifactual orthologs as source of gene tree error, we identified a significant, but non-specific signal of introgression using Patterson's D and f4 statistics. Despite phylogenomic complexity, we were able to resolve Freziera into nine well-supported subclades whose evolution has been shaped by multiple evolutionary processes, including incomplete lineage sorting, historical gene flow, and gene duplication. Our results highlight the complexities of plant phylogenomics, which are heightened in Andean radiations, and show the impact of filtering data processing artifacts and standard filtering approaches on phylogenetic inference.

Curium(III) speciation in the presence of microbial cell wall components.

Trivalent actinides such as Cm(III) are able to strongly interact with microbes and especially with bacterial cell walls. However, detailed knowledge of the influence of different cell wall components is somewhat lacking. For this investigation, we studied the formation of aqueous Cm(III) complexes with cell wall components (e.g., lipopolysaccharide, peptidoglycan, and plasma membranes) using time-resolved laser-induced fluorescence spectroscopy (TRLFS). For all systems, two specific Cm(III) complexes with the biomacromolecules were observed as a function of pH. Specifically, Cm(III) was found to bind to phosphate and carboxyl groups present in the structure of the biomacromolecules. Stability constants and luminescence parameters of the specific Cm(III) complexes were determined and are presented. The pH of the surrounding aqueous solution, the plasma membrane concentration, and proteins included in the crude plasma membrane fraction were found to significantly impact the complexation of Cm(III). The Cm(III) luminescence spectra with plasma membranes, cell wall polymers, as well as Gram-negative (Sporomusa sp. MT-2.99 and Pseudomonas fluorescens) and Gram-positive (Paenibacillus sp. MT-2.2) bacteria will be explained by linear combination fitting using the investigated components.

Phylogeny, classification, and character evolution of tribe Citharexyleae (Verbenaceae).

PREMISE: As a family of Neotropical origin and primarily Neotropical distribution, the Verbenaceae are a good but understudied system with which to understand Neotropical evolution. Tribe Citharexyleae comprises three genera: Baillonia, Citharexylum-one of the largest genera in Verbenaceae-and Rehdera. A molecular phylogenetic approach was taken to resolve intergeneric relationships in Citharexyleae and infrageneric relationships in Citharexylum. The phylogeny is used to elucidate character evolution in a widespread, morphologically diverse Neotropical genus. METHODS: Seven plastid regions, two nuclear ribosomal spacers, and six low-copy nuclear loci were analyzed for 64 species of Citharexyleae. Phylogenetic analyses were conducted using maximum likelihood, Bayesian inference, and multispecies coalescent approaches. Habit, presence or absence of thorns, inflorescence architecture, flower color, fruit color, and geography were examined to identify diagnostic character states for clades within Citharexylum. RESULTS: Rehdera is resolved as sister to Citharexylum, and Baillonia nested within Citharexylum. Two species, C. oleinum and C. tetramerum, are not closely related to tribe Citharexyleae, but may be related to members of tribe Duranteae instead. Seven clades within Citharexylum are inferred, each characterized by a combination of geography, fruit color and/or maturation, and inflorescence architecture. There is evidence of correlated evolution between habit, axillary inflorescences, and flower number per inflorescence. Shrubs with reduced inflorescences have evolved repeatedly. CONCLUSIONS: A subgeneric classification for Citharexylum is proposed. Although suites of associated traits are found, character morphology has been labile throughout Citharexylum's evolutionary history. Morphological diversity may be related to adaptation to differing mesic and xeric habitats.

Investigation of The Usefulness of Serum Amyloid A in Characterizing Selected Disease Forms of Equine Herpesvirus-1 Infection.

The objective of this study was to study the SAA response of horses with various forms of EHV-1 infection. Archived serum samples from 153 horses with various disease forms of EHV-1 infection (48 healthy non-infected horses, 48 subclinically infected horses, 40 horses with respiratory EHV-1 infection and 17 horses with neurological EHV-1 infection) were available for SAA testing. SAA values ranged from 0 to 31 µg/mL (median 0 µg/mL) in healthy horses, from 0 to 2,416 µg/mL (median 8.5 µg/mL) in subclinically infected horses, from 0 to 3,000 µg/mL (median 597 µg/mL) in horse with respiratory EHV-1 infection and from 0 to 1,640 µg/mL (median 58 µg/mL) in horse with neurological EHV-1 disease. Infected horses had significantly higher SAA values compared to healthy, non-infected horses. While SAA was elevated in the majority of horses with evidence of EHV-1 infection, a single point in time SAA test was unable to consistently support infection in horses with subclinical disease.

What is the relationship between post-traumatic stress disorder, extreme appraisals of internal state and symptoms in bipolar disorder?

BACKGROUND: It is important to understand the factors associated with more severe mood symptoms in bipolar disorder. The integrative cognitive model of bipolar disorder proposes that extreme appraisals of changes to internal states maintain and exacerbate mood symptoms. AIMS: The current study aimed to investigate if post-traumatic stress disorder (PTSD) is related to current depressive and manic bipolar symptoms, and whether this relationship is mediated by appraisals of internal state. METHOD: Participants with bipolar disorder (n = 82) from a randomized controlled trial of cognitive therapy for bipolar disorder (the TEAMS trial) completed self-reported questionnaires assessing appraisals of internal state, generalized anxiety symptoms, and self-reported and observer-rated depressive and manic symptoms. Clinical interviews assessed PTSD co-morbidity. RESULTS: Participants with bipolar and co-morbid PTSD (n = 27) had higher depressive symptoms and more conflicting appraisals than those without PTSD. Regression analyses found PTSD to be associated with depressive symptoms but not manic symptoms. Conflicting appraisals were found to be associated only with manic symptoms meaning that the planned mediation analysis could not be completed. CONCLUSIONS: Findings provide partial support for the integrative cognitive model of bipolar disorder and highlight the need for transdiagnostic treatments in bipolar disorder due to the prevalence and impact of trauma and co-morbidity. Working on trauma experiences in therapy may impact on depressive symptoms for those with bipolar disorder and co-morbid PTSD.

Cooperative Function of TraJ and ArcA in Regulating the F Plasmid tra Operon.

The F plasmid tra operon encodes most of the proteins required for bacterial conjugation. TraJ and ArcA are known activators of the tra operon promoter PY, which is subject to H-NS-mediated silencing. Donor ability and promoter activity assays indicated that PY is inactivated by silencers and requires both TraJ and ArcA for activation to support efficient F conjugation. The observed low-level, ArcA-independent F conjugation is caused by tra expression from upstream alternative promoters. Electrophoretic mobility shift assays showed that TraJ alone weakly binds to PY regulatory DNA; however, TraJ binding is significantly enhanced by ArcA binding to the same DNA, indicating cooperativity of the two proteins. Analysis of binding affinities between ArcA and various DNA fragments in the PY regulatory region defined a 22-bp tandem repeat sequence (from -76 to -55 of PY) sufficient for optimal ArcA binding, which is immediately upstream of the predicted TraJ-binding site (from -54 to -34). Deletion analysis of the PY promoter in strains deficient in TraJ, ArcA, and/or H-NS determined that sequences upstream of -103 are required by silencers including H-NS for PY silencing, whereas sequences downstream of -77 are targeted by TraJ and ArcA for activation. TraJ and ArcA appear not only to counteract PY silencers but also to directly activate PY in a cooperative manner. Our data reveal the cooperativity of TraJ and ArcA during PY activation and provide insights into the regulatory circuit controlling F-family plasmid-mediated bacterial conjugation.IMPORTANCE Conjugation is a major mechanism for dissemination of antibiotic resistance and virulence among bacterial populations. The tra operon in the F family of conjugative plasmids encodes most of the proteins involved in bacterial conjugation. This work reveals that activation of tra operon transcription requires two proteins, TraJ and ArcA, to bind cooperatively to adjacent sites immediately upstream of the major tra promoter PY The interaction of TraJ and ArcA with the tra operon not only relieves PY from silencers but also directly activates it. These findings provide insights into the regulatory circuit of the F-family plasmid-mediated bacterial conjugation.

Using Systems Thinking to train future leaders in global health.

Systems Thinking provides a useful set of concepts and tools that can be used to train students to be effective and innovative global health leaders in an ever-changing and often chaotic world. This paper describes an experiential, multi-disciplinary curriculum that uses Systems Thinking to frame and analyse global health policies and practices. The curriculum uses case studies and hands-on activities to deepen students' understanding of the following concepts: complex adaptive systems, dynamic complexity, inter-relationships, feedback loops, policy resistance, mental models, boundary critique, leverage points, and multi-disciplinary, multi-sectoral, and multi-stakeholder thinking and action. A sample of Systems Thinking tools for analysing global health policies and practices are also introduced.

Origins of North American arid-land Verbenaceae: More than one way to skin a cat.

PREMISE OF THE STUDY: Verbenaceae originated and initially diversified in South America in wet forest habitats. They have diversified extensively in arid habitats in both South and North America. This study aims to understand the origin of the North American arid-land members of Verbenaceae. METHODS: A phylogenetic approach is used to examine four genera (Aloysia, Citharexylum, Glandularia, Verbena) in three distinct clades with representatives in North American deserts and disjunct South and North American distributions. Phylogenetic analyses were conducted using maximum likelihood and Bayesian approaches. Analyses included both plastid and nuclear DNA regions and include the first study of Citharexylum and an expanded sampling of tribe Verbeneae (Glandularia and Verbena). Ancestral areas were reconstructed for each group. KEY RESULTS: North American desert species of Aloysia and Glandularia were likely derived from ancestors in arid temperate South America, perhaps by long-distance dispersal. The pattern for Verbena was less clear, with evidence from plastid DNA implicating an Andean dispersal route to the North American clade, whereas nuclear data suggest that the Andean and North American species resulted from independent dispersals from southern South America. A previously unrecognized clade of Andean Verbeneae was discovered, raising the possibility of an Andean origin of Verbena or Verbena and Glandularia. North American desert species of Citharexylum represent multiple, independent origins from mesic habitat ancestors in Mesoamerica. CONCLUSIONS: North American arid-zone Verbenaceae are derived from South and Central American ancestors via multiple avenues, including long-distance, amphitropical dispersal, Andean migration corridors, and in situ evolution of desert-adapted species.

Annotation of plasmid genes.

Good annotation of plasmid genomes is essential to maximise the value of the rapidly increasing volume of plasmid sequences. This short review highlights some of the current issues and suggests some ways forward. Where a well-studied related plasmid system exists we recommend that new annotation adheres to the convention already established for that system, so long as it is based on sound principles and solid experimental evidence, even if some of the new genes are more similar to homologues in different systems. Where a well-established model does not exist we provide generic gene names that reflect likely biochemical activity rather than overall purpose particularly, for example, where genes clearly belong to a type IV secretion system but it is not known whether they function in conjugative transfer or virulence. We also recommend that annotators use a whole system naming approach to avoid ending up with an illogical mixture of names from other systems based on the highest scoring match from a BLAST search. In addition, where function has not been experimentally established we recommend using just the locus tag, rather than a function-related gene name, while recording possible functions as notes rather than in a provisional name.

PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4.

The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1). DNA and RNA immuno-FISH reveal that PML NBs are closely associated with actively transcribed DDIT4 loci, implicating these bodies in regulation of basal DDIT4 expression. Although PML silencing did reduce the sensitivity of U2OS cells to metabolic stress induced by metformin, PML loss did not inhibit the upregulation of DDIT4 in response to metformin, hypoxia-like (CoCl2) or genotoxic stress. Analysis of publicly available cancer data also revealed a significant correlation between PML and DDIT4 expression in several cancer types (e.g. lung, breast, prostate). Thus, these findings uncover a novel mechanism by which PML loss may contribute to mTOR activation and cancer progression via dysregulation of basal DDIT4 gene expression.

Decreased eIF3e Expression Can Mediate Epithelial-to-Mesenchymal Transition through Activation of the TGFß Signaling Pathway.

UNLABELLED: The eIF3e protein is a component of the multisubunit eIF3 complex, which is essential for cap-dependent translation initiation. Decreased eIF3e expression is often observed in breast and lung cancer and has been shown to induce epithelial-to-mesenchymal transition (EMT) in breast epithelial cells by an unknown mechanism. Here, we study the effect of decreased eIF3e expression in lung epithelial cells by creating stable clones of lung epithelial cells (A549) that express an eIF3e-targeting shRNA. Our data indicate that decreased eIF3e expression in lung epithelial cells leads to EMT, as it does in breast epithelial cells. Importantly, we show that decreased eIF3e expression in both lung and breast epithelial cells leads to the overproduction of the TGFß cytokine and that inhibition of TGFß signaling can reverse eIF3e-regulated EMT in lung epithelial cells. In addition, we discovered that several mRNAs that encode important EMT regulators are translated by a cap-independent mechanism when eIF3e levels are reduced. These findings indicate that EMT mediated by a decrease in eIF3e expression may be a general phenomenon in epithelial cells and that it requires activation and maintenance of the TGFß signaling pathway. IMPLICATIONS: These results indicate that inhibition of TGFß signaling could be an efficient way to prevent metastasis in patients with NSCLC that display reduced eIF3e expression.

The FinO family of bacterial RNA chaperones.

Antisense RNAs have long been known to regulate diverse aspects of plasmid biology. Here we review the FinOP system that modulates F plasmid gene expression through regulation of the F plasmid transcription factor, TraJ. FinOP is a two component system composed of an antisense RNA, FinP, which represses TraJ translation, and a protein, FinO, which is required to stabilize FinP and facilitate its interactions with its traJ mRNA target. We review the evidence that FinO acts as an RNA chaperone to bind and destabilize internal stem-loop structures within the individual RNAs that would otherwise block intermolecular RNA duplexing. Recent structural studies have provided mechanistic insights into how FinO may facilitate interactions between FinP and traJ mRNA. We also review recent findings that two other proteins, Escherichia coli ProQ and Neisseria meningitidis NMB1681, may represent FinO-like RNA chaperones.

The Contribution of Melanoregulin to Microtubule-Associated Protein 1 Light Chain 3 (LC3) Associated Phagocytosis in Retinal Pigment Epithelium.

A main requisite in the phagocytosis of ingested material is a coordinated series of maturation steps which lead to the degradation of ingested cargo. Photoreceptor outer segment (POS) renewal involves phagocytosis of the distal disk membranes by the retinal pigment epithelium (RPE). Previously, we identified melanoregulin (MREG) as an intracellular cargo-sorting protein required for the degradation of POS disks. Here, we provide evidence that MREG-dependent processing links both autophagic and phagocytic processes in LC3-associated phagocytosis (LAP). Ingested POS phagosomes are associated with endogenous LC3 and MREG. The LC3 association with POSs exhibited properties of LAP; it was independent of rapamycin pretreatment, but dependent on Atg5. Loss of MREG resulted in a decrease in the extent of LC3-POS association. Studies using DQ-BSA suggest that loss of MREG does not compromise the association and fusion of LC3-positive phagosomes with lysosomes. Furthermore, the mechanism of MREG action is likely through a protein complex that includes LC3, as determined by colocalization and immunoprecipitation in both RPE cells and macrophages. We posit that MREG participates in coordinating the association of phagosomes with LC3 for content degradation with the loss of MREG leading to phagosome accumulation.

Mechanistic basis of plasmid-specific DNA binding of the F plasmid regulatory protein, TraM.

The conjugative transfer of bacterial F plasmids relies on TraM, a plasmid-encoded protein that recognizes multiple DNA sites to recruit the plasmid to the conjugative pore. In spite of the high degree of amino acid sequence conservation between TraM proteins, many of these proteins have markedly different DNA binding specificities that ensure the selective recruitment of a plasmid to its cognate pore. Here we present the structure of F TraM RHH (ribbon-helix-helix) domain bound to its sbmA site. The structure indicates that a pair of TraM tetramers cooperatively binds an underwound sbmA site containing 12 base pairs per turn. The sbmA is composed of 4 copies of a 5-base-pair motif, each of which is recognized by an RHH domain. The structure reveals that a single conservative amino acid difference in the RHH ß-ribbon between F and pED208 TraM changes its specificity for its cognate 5-base-pair sequence motif. Specificity is also dictated by the positioning of 2-base-pair spacer elements within sbmA; in F sbmA, the spacers are positioned between motifs 1 and 2 and between motifs 3 and 4, whereas in pED208 sbmA, there is a single spacer between motifs 2 and 3. We also demonstrate that a pair of F TraM tetramers can cooperatively bind its sbmC site with an affinity similar to that of sbmA in spite of a lack of sequence similarity between these DNA elements. These results provide a basis for the prediction of the DNA binding properties of the family of TraM proteins.

Transcriptional control of floral anthocyanin pigmentation in monkeyflowers (Mimulus).

A molecular description of the control of floral pigmentation in a multi-species group displaying various flower color patterns is of great interest for understanding the molecular bases of phenotypic diversification and pollinator-mediated speciation. Through transcriptome profiling, mutant analyses and transgenic experiments, we aim to establish a 'baseline' floral anthocyanin regulation model in Mimulus lewisii and to examine the different ways of tinkering with this model in generating the diversity of floral anthocyanin patterns in other Mimulus species. We find one WD40 and one bHLH gene controlling anthocyanin pigmentation in the entire corolla of M. lewisii and two R2R3-MYB genes, PELAN and NEGAN, controlling anthocyanin production in the petal lobe and nectar guide, respectively. The autoregulation of NEGAN might be a critical property to generate anthocyanin spots. Independent losses of PELAN expression (via different mechanisms) explain two natural yellow-flowered populations of M. cardinalis (typically red-flowered). The NEGAN ortholog is the only anthocyanin-activating MYB expressed in the M. guttatus flowers. The mutant lines and transgenic tools available for M. lewisii will enable gene-by-gene replacement experiments to dissect the genetic and developmental bases of more complex floral color patterns, and to test hypotheses on phenotypic evolution in general.

Success factors for reducing maternal and child mortality.

Reducing maternal and child mortality is a priority in the Millennium Development Goals (MDGs), and will likely remain so after 2015. Evidence exists on the investments, interventions and enabling policies required. Less is understood about why some countries achieve faster progress than other comparable countries. The Success Factors for Women's and Children's Health studies sought to address this knowledge gap using statistical and econometric analyses of data from 144 low- and middle-income countries (LMICs) over 20 years; Boolean, qualitative comparative analysis; a literature review; and country-specific reviews in 10 fast-track countries for MDGs 4 and 5a. There is no standard formula--fast-track countries deploy tailored strategies and adapt quickly to change. However, fast-track countries share some effective approaches in addressing three main areas to reduce maternal and child mortality. First, these countries engage multiple sectors to address crucial health determinants. Around half the reduction in child mortality in LMICs since 1990 is the result of health sector investments, the other half is attributed to investments made in sectors outside health. Second, these countries use strategies to mobilize partners across society, using timely, robust evidence for decision-making and accountability and a triple planning approach to consider immediate needs, long-term vision and adaptation to change. Third, the countries establish guiding principles that orient progress, align stakeholder action and achieve results over time. This evidence synthesis contributes to global learning on accelerating improvements in women's and children's health towards 2015 and beyond.

La réduction de la mortalité maternelle et infantile est une priorité des objectifs du Millénaire pour le développement (OMD) et le restera probablement après l'échéance de 2015. Il existe des données sur les investissements, les interventions et les politiques habilitantes nécessaires. On comprend mal pourquoi certains pays ont réalisé des progrès plus rapidement que d'autres pays comparables. Les Facteurs de réussite des études sur la santé des femmes et des enfants ont cherché à combler ce manque de connaissances en utilisant les analyses statistiques et économétriques des données provenant de 144 pays à faible revenu et à revenu intermédiaire et recueillies depuis 20 ans: une analyse comparative qualitative booléenne; une étude bibliographique et des études spécifiques à chaque pays pour les 10 pays à progression rapide pour les points 4 et 5a des OMD. Il n'existe pas de formule standard ­ les pays à progression rapide ont déployé des stratégies personnalisées et se sont adaptés rapidement aux changements. Cependant, ces pays ont en commun des approches efficaces visant 3 grands axes afin de réduire la mortalité maternelle et infantile. Premièrement, ils impliquent de nombreux secteurs pour traiter les facteurs déterminants et cruciaux pour la santé. Près de la moitié de la réduction de la mortalité infantile dans les pays à faible revenu et à revenu intermédiaire depuis 1990 résulte des investissements dans le secteur de la santé, l'autre moitié étant attribuée aux investissements réalisés dans les secteurs extérieurs à la santé. Deuxièmement, ces pays utilisent des stratégies pour mobiliser les partenaires dans la société, en utilisant des données solides et opportunes pour la prise de décisions et la responsabilisation, ainsi qu'une approche de planification triple pour prendre en considération les besoins immédiats, la vision à long terme et l'adaptation aux changements. Troisièmement, ces pays établissent des principes directeurs qui orientent les progrès, harmonisent les actions des parties prenantes et génèrent des résultats dans le temps. Cette synthèse de données contribue à l'ensemble des connaissances requises pour accélérer les améliorations sur la santé des femmes et des enfants en vue de l'échéance de 2015 et au-delà.

La reducción de la mortalidad materna e infantil es una prioridad en los Objetivos de Desarrollo del Milenio (ODM), y probablemente lo seguirá siendo después de 2015. Existen evidencias sobre las inversiones, las intervenciones y las políticas necesarias, pero se sabe menos acerca de por qué algunos países logran un progreso más rápido que otros países comparables. Los estudios relativos a los Factores de Éxito en la Salud de las Mujeres y los Niños han tratado de abordar esta brecha de conocimiento por medio de análisis estadísticos y econométricos de datos de 144 países de ingresos bajos y medianos (PIBM) a lo largo de más de 20 años, análisis comparativos cualitativos booleanos, revisión de la literatura y revisiones específicas de cada país en 10 países bien encarrilados para los ODM 4 y 5a. No existe una fórmula estándar, estos países despliegan estrategias a medida y se adaptan rápidamente a los cambios. Sin embargo, comparten ciertos enfoques eficaces a la hora de abordar tres áreas principales para reducir la mortalidad materna e infantil. En primer lugar, involucran a numerosos sectores para hacer frente a los factores sanitarios decisivos. Alrededor de la mitad de la reducción de la mortalidad infantil en los PIBM desde 1990 es el resultado de inversiones en el sector de la salud, y la otra mitad se atribuye a las inversiones realizadas en sectores fuera del ámbito sanitario. En segundo lugar, estos países utilizan estrategias para movilizar a socios a través de la sociedad, utilizando evidencias oportunas y sólidas para la toma de decisiones y la rendición de cuentas, así como un enfoque de planificación triple para considerar las necesidades inmediatas, la visión a largo plazo y la adaptación al cambio. En tercer lugar, los países establecen principios rectores que orientan el progreso, armonizan las acciones de las partes interesadas y logran resultados en el tiempo. Este compendio de evidencias contribuye al aprendizaje global sobre cómo acelerar las mejoras en la salud de mujeres y niños hacia el 2015 y más adelante.

Autophagy in the eye: implications for ocular cell health.

Autophagy, a catabolic process by which a cell "eats" itself, turning over its own cellular constituents, plays a key role in cellular homeostasis. In an effort to maintain normal cellular function, autophagy is often up-regulated in response to environmental stresses and excessive organelle damage to facilitate aggregated protein removal. In the eye, virtually all cell types from those comprising the cornea in the front of the eye to the retinal pigment epithelium (RPE) providing a protective barrier for the retina at the back of the eye, rely on one or more aspects of autophagy to maintain structure and/or normal physiological function. In the lens autophagy plays a critical role in lens fiber cell maturation and the formation of the organelle free zone. Numerous studies delineating the role of Atg5, Vsp34 as well as FYCO1 in maintenance of lens transparency are discussed. Corneal endothelial dystrophies are also characterized as having elevated levels of autophagic proteins. Therefore, novel modulators of autophagy such as lithium and melatonin are proposed as new therapeutic strategies for this group of dystrophies. In addition, we summarize how corneal Herpes Simplex Virus (HSV-1) infection subverts the cornea's response to infection by inhibiting the normal autophagic response. Using glaucoma models we analyze the relative contribution of autophagy to cell death and cell survival. The cytoprotective role of autophagy is further discussed in an analysis of photoreceptor cell heath and function. We focus our analysis on the current understanding of autophagy in photoreceptor and RPE health, specifically on the diverse role of autophagy in rods and cones as well as its protective role in light induced degeneration. Lastly, in the RPE we highlight hybrid phagocytosis-autophagy pathways. This comprehensive review allows us to speculate on how alterations in various stages of autophagy contribute to glaucoma and retinal degenerations.