Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni

Members of the genus Campylobacter are frequently responsible for human enteric disease, often through consumption of contaminated poultry products. Bacteriophages are viruses that have the potential to control pathogenic bacteria, but understanding their complex life cycles is key to their successful exploitation. Treatment of Campylobacter jejuni biofilms with bacteriophages led to the discovery that phages had established a relationship with their hosts typical of the carrier state life cycle (CSLC), where bacteria and bacteriophages remain associated in equilibrium. Significant phenotypic changes include improved aerotolerance under nutrient-limited conditions that would confer an advantage to survive in extra-intestinal environments, but a lack in motility eliminated their ability to colonize chickens. Under these circumstances, phages can remain associated with a compatible host and continue to produce free virions to prospect for new hosts. Moreover, we demonstrate that CSLC host bacteria can act as expendable vehicles for the delivery of bacteriophages to new host bacteria within pre-colonized chickens. The CSLC represents an important phase in the ecology of Campylobacter bacteriophage

Transposixión [2,3]-sigmatrópica de 3-sulfinil dihidropiranos: aproximaciones sintéticas a la Disiherbatina y al ácido Pseudomónico B

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 17-10-200

Economic and Humanistic Burden of Moderate and Severe Hemophilia A and B in Spain: Real-World Evidence Insights from the CHESS II Study

Background: Hemophilia is a congenital disorder characterized by deficiency or absence of clotting factor VIII in hemophilia A (HA) or clotting factor IX in hemophilia B (HB), resulting in frequent, repeated, and prolonged spontaneous or traumatic bleeding into joints or soft tissue. Severity is classified by the patient’s baseline level of clotting factor activity as mild (>5%-40%), moderate (1%-5%), or severe (<1%). In Spain, there is limited information on the societal economic burden of disease. Objective: To estimate the economic and humanistic burden of disease in adult patients with non-inhibitor moderate and severe HA and HB in Spain. Methods: Spanish data from the CHESS II study (2018-2020) on patients’ clinical characteristics, health-related quality of life (HRQoL) and hemophilia-related healthcare resource utilization were analyzed. Economic burden was determined by estimating condition-related annual per-patient direct (medical and nonmedical) and indirect costs, stratified according to hemophilia type and severity and presented as 2022 Euros. HRQoL was assessed via the EQ-5D-5L. Results: Of 341 patients in the Spanish CHESS II cohort, 288 patients met the inclusion criteria: 181 had HA (37% [n = 66] moderate and 63% [n=115] severe) and 107 had HB (26% [n = 28] moderate and 74% [n = 79] severe). Mean annual direct cost was higher in HB than in HA, and higher in severe than in moderate patients, resulting in an annual cost/patient of €17 251 (moderate HA), €17 796 (moderate HB), €116 767 (severe HA) and €206 996 (severe HB). The main direct cost component in all groups except moderate HA was factor replacement therapy. Mean per-patient indirect cost was €4089 (moderate HA), €797 (moderate HB), €8633 (severe HA) and €8049 (severe HB). Finally, the mean total cost (direct and indirect) for moderate and severe patients were €91 017 (HA) and €163 924 (HB). EQ-5D-5L [SD] scores were lower in patients with severe HA (0.77 [0.18]) and severe HB (0.70 [0.22]) compared with patients with moderate HA (0.81 [0.15]) and moderate HB (0.86 [0.17]). Conclusions: Independently of the type of hemophilia, greater condition severity was associated with increased costs and a decrease in HRQoL

The Distribution of Tetrahymena pyriformis 1

This paper is a brief account of both amicronucleate and sexually active strains of Tetrahymena pyriformis and their distribution with some comments on their possible evolution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72276/1/j.1550-7408.1970.tb02348.x.pd

Healthcare-associated pneumonia: a prospective study in Spain

Objective: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). Methods: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. Results: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. Conclusions: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.Objetivo: Describir las características epidemiológicas y factores relacionados con la neumonía asociada a cuidados sanitarios (NACS) causada por Streptococcus pneumoniae y Staphylococcus aureus resistente a meticilina (SARM). Pacientes y métodos: Estudio epidemiológico observacional prospectivo de casos a 3 años en siete hospitales españoles. Se recogieron las características microbiológicas y de los pacientes y sus resultados y se clasificaron en función del patógeno causante en 4 categorías: ?S. pneumoniae?, ?SARM?, ?Otros? y ?Desconocido?. Al alta, se realizó un seguimiento de 30 días. Resultados: Se incluyeron 258 (84,6%) pacientes (170 hombres [65.9%]; edad media 72,4 años ± 15 años (95% IC [70,54-74,25]). La etiología de la neumonía se identificó en 73 casos (28,3%):S. pneumoniae en 35 pacientes (13,6%), SARM en 8 (3,1%) y otros microorganismos en 30 pacientes (11,6%). Hubo diferencias significativas en tasas de enfermedad pulmonar obstructiva crónica (p < 0,05), tratamiento antibiótico previo (p < 0,05), otras enfermedades respiratorias crónicas, corticoides inhalados (p < 0,01) y linfoma (p < 0,05) entre los cuatro grupos. Los pacientes con NACS causada por SARM recibieron tratamiento antibiótico previo en mayor medida (87,5%). Treinta y tres (12,8%) pacientes murieron durante la hospitalización; en 27 (81,2%) debido a la neumonía. Conclusiones: Se identificó la etiología de la NACS en solo un cuarto de los pacientes, siendo S. pneumoniae el patógeno más frecuente. En los pacientes con enfermedades respiratorias crónicas fue más frecuente la NACS causada por SARM. La muerte tras el alta hospitalaria se relacionó con la neumonía en la mayoría de los casos

A Quarter Century Exploring Tetrahymena *

In reviewing 25 years of work on Tetrahymena , the author describes early difficulties experienced by himself and others in developing a chemically-defined medium and in defining the taxonomy of T. pyriformis. With identification of its essential requirements, a variety of nutritional studies revealed the close resemblance between the metabolic pathways of this ciliate and those of the chick and rat. This suggested studies on the effects of gamma radiation and the effect of antibiotics. Attention then turned to the puzzle of the absence of conjugation in all strains of T. pyriformis then maintained in laboratories. The observation that these strains were all amicronucleate led to the discovery of mating types (with D. F. Gruchy). This brought up the problem of what constitutes a species and how it might be solved in T. pyriformis where clearly defined groups are set off from other similar groups (varieties) by a breeding barrier. Another problem is whether a life cycle exists in this ciliate and if so, the role amicronucleate strains play in this cycle. The origin and obvious evolutionary success of these “genetically dead” strains are other problems that are considered. The search for nutritional markers for genetic experiments inspired large-scale collections, including some from tropical habitats. Strains were found which differed in serine and pyridoxine requirements. Genetic analysis was hindered by the high lethality following conjugation, unsatisfactory mating behavior in some clones, and the complete absence of autogamy, the latter making it difficult to obtain homozygous clones. The use of x-radiation yielded haploid individuals; when these were mated with diploid clones the resulting haploid progeny proved that the genes controlling mating type and pyridoxine synthesis resided in the micronucleus. Genetic analysis of the serine and pyridoxine mutants supports the idea that T. pyriformis is more of an outbreeder than an inbreeder. Left for the future is an extension of our knowledge of the breeding system of T. pyriformis and ultimately to examine critically the factors responsible for the success of this ubiquitous ciliate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71977/1/j.1550-7408.1959.tb03918.x.pd

The roles of B vitamins in phytoplankton nutrition: new perspectives and prospects

B vitamins play essential roles in central metabolism. These organic water-soluble molecules act as, or as part of, coenzymes within the cell. Unlike land plants, many eukaryotic algae are auxotrophic for certain B vitamins. Recent progress in algal genetic resources and environmental chemistry have promoted a renewal of interest in the role of vitamins in governing phytoplankton dynamics, and illuminated amazing versatility in phytoplankton vitamin metabolism. Accumulating evidence demonstrates metabolic complexity in the production and bioavailability of different vitamin forms, coupled with specialized acquisition strategies to salvage and remodel vitamin precursors. Here, I describe recent advances and discuss how they redefine our view of the way in which vitamins are cycled in aquatic ecosystems and their importance in structuring phytoplankton communities

Defining Life: The Virus Viewpoint

Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition