Technetium-99m-labeled ceftizoxime loaded long-circulating and pH-sensitive liposomes used to identify osteomyelitis

Osteomyelitis is an infectious disease located in the bone or bone marrow. Long-circulating and pH-sensitive liposomes containing a technetium-99m-labeled antibiotic, ceftizoxime, (SpHL-(99m)Tc-CF) were developed to identify osteomyelitis foci. Biodistribution studies and scintigraphic images of bone infection or non infection-bearing rats that had been treated with these liposomes were performed. A high accumulation in infectious foci and high values in the target-non target ratio could be observed. These results indicate the potential of SpHL-(99m)Tc-CF as a potential agent for the diagnosis of bone infections.     

A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection

There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection.     

Definition of minimal domains of interaction within the recombination-activating genes 1 and 2 recombinase complex

During V(D)J recombination, recognition and cleavage of the recombination signal sequences (RSSs) requires the coordinated action of the recombination-activating genes 1 and 2 (RAG1/RAG2) recombinase complex. In this report, we use deletion mapping and site-directed mutagenesis to determine the minimal domains critical for interaction between RAG1 and RAG2. We define the active core of RAG2 required for RSS cleavage as aa 1-371 and demonstrate that the C-terminal 57 aa of this core provide a dominant surface for RAG1 interaction. This region corresponds to the last of six predicted kelch repeat motifs that have been proposed by sequence analysis to fold RAG2 into a six-bladed beta-propeller structure. Residue W317 within this sixth repeat is shown to be critical for mediating contact with RAG1 and concurrently for stabilizing binding and directing cleavage of the RSS. We also show that zinc finger B (aa 727-750) of RAG1 provides a dominant interaction domain for recruiting RAG2. In all, the data support a model of RAG2 as a multimodular protein that utilizes one of its six faces for establishing productive contacts with RAG1.     

Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos

The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system.     

Multilevel Effects of Wealth on Women's Contraceptive Use in Mozambique

Objective

This paper analyzes the impact of wealth on the use of contraception in Mozambique unmixing the contextual effects due to community wealth from the individual effects associated with the women''s situation within the community of residence.

Methods

Data from the 2011 Mozambican Demographic and Health Survey on women who are married or living together are analyzed for the entire country and also for the rural and urban areas separately. We used single level and multilevel probit regression models.

Findings

A single level probit regression reveals that region, religion, age, previous fertility, education, and wealth impact contraceptive behavior. The multilevel analysis shows that average community wealth and the women’s relative socioeconomic position within the community have significant positive effects on the use of modern contraceptives. The multilevel framework proved to be necessary in rural settings but not relevant in urban areas. Moreover, the contextual effects due to community wealth are greater in rural than in urban areas and this feature is associated with the higher socioeconomic heterogeneity within the richest communities.

Conclusion

This analysis highlights the need for the studies on contraceptive behavior to specifically address the individual and contextual effects arising from the poverty-wealth dimension in rural and urban areas separately. The inclusion in a particular community of residence is not relevant in urban areas, but it is an important feature in rural areas. Although the women''s individual position within the community of residence has a similar effect on contraceptive adoption in rural and urban settings, the impact of community wealth is greater in rural areas and smaller in urban areas.     

Myotonic dystrophytype 1 – report of non-24-h sleep-wake disorder with excessive daytime sleepiness

ABSTRACT

Myotonic dystrophy (MD) is a neuromuscular disease with myotonia, progressive weakness, and involvement of CNS, heart, and gastrointestinal system. Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (MD1) is related to sleep breathing diseases, restless leg syndrome, periodic limb movements during sleep and narcoleptic-like phenotype. However, authors highlight a central dysfunction of sleep regulation.

We describe a 26-year-old, female, MD1 patient with EDS. Sleep diary/actigraphy evidenced two different circadian periods with values of 1442 and 1522 min. Agomelatine, 50 mg at night, was prescribed with improvement of the circadian rhythm and complaints of sleepiness.

The identification of unanticipated causes of EDS, such as circadian rhythm disorders permits an appropriated treatment. As we know, it is the first relate of non-24-h sleep-wake disorder in patient with MD1. Sleep diary and actigraphy could be good options to investigate sleep-wake cycle disorder in patients with MD and EDS.     

Persistence and space preemption explain species‐specific founder effects on the organization of marine sessile communities

Community assembly may not follow predictable successional stages, with a large fraction of the species pool constituted by potential pioneering species and successful founders defined through lottery. In such systems, priority effects may be relevant in the determination of trajectories of developing communities and hence diversity and assemblage structure at later advanced states. In order to assess how different founder species may trigger variable community trajectories and structures, we conducted an experimental study using subtidal sessile assemblages as model. We manipulated the identity of functionally different founders and initial colony size (a proxy of the time lag before the arrival of later species), and followed trajectories. We did not observe any effects of colony size on response variables, suggesting that priority effects take place even when the time lag between the establishment of pioneering species and late colonizers is very short. Late community structure at experimental panels that started either with the colonial ascidian Botrylloides nigrum, or the arborescent bryozoan Bugula neritina, was similar to control panels allowed natural assembling. In spite of high potential for fast space domination, and hence negative priority effects, B. nigrum suffered high mortality and did not persist throughout succession. Bugula neritina provided complex physical microhabitats through conspecific clustering that have enhanced larval settlement of late species arrivals, but no apparent facilitation was observed. Differently, panels founded by the encrusting bryozoan Schizoporella errata led to different and less diverse communities compared to naturally assembled panels, evidencing strong negative priority effects through higher persistence and space preemption. Schizoporella errata founder colonies inhibited further conspecific settlement, which may greatly relax intraspecific competition, allowing resource allocation to colony growth and space domination, thus reducing the chances for the establishment of other species.     

The influence of ammonia on the growth and photosynthesis of Ruppia drepanensis Tineo from Doñana National Park (SW Spain)

In a laboratory experiment, Ruppia drepanensis Tineo seedlings from a brackish marsh in Southern Spain were grown at 20 and 30 °C, at three different nitrogen levels. These levels were obtained by the addition of a slow release fertilizer (23% NH₄NO₃ by weight) to a sediment mixture of sand and clay (3:1). Several morphometric parameters were recorded during the first five weeks of the experiment, and photosynthesis and respiration were measured after 7 weeks of growth. Results showed a significant reduction of growth and development with increasing nitrogen and temperature levels. Dark respiration increased strongly at high nitrogen levels. At the same time, net photosynthesis at 250 and 500 µE m^-2 s^-1, Pm, Km and LCP were not affected by either factor. We attribute these phenomena to ammonia toxicity, since relatively high total ammonia (NH₃ + NH_f4 ^p+) levels were found in the interstitial water.     

Stress distribution of three-unit fixed partial prostheses (conventional and pontic) supported by three or two implants: 3D finite element analysis of ductile materials

In implantology, when financial or biological feasibility limitations appear, it is necessary to use prostheses with geometries that deviate from the conventional, with a pontic in the absence of an intermediate implant. The aim of this study was analyze and understand the general differences in the stresses generated in implants, components and infrastructures according to the configuration of the prosthesis over three or two implants. Thus, this paper analyzes the von Mises equivalent stresses (VMES) of ductile materials on their external surfaces. The experimental groups: Regular Splinted Conventional Group (RCG), which had conventional infrastructures on 3 regular-length Morse taper implants (4x11?mm); Regular Splinted Pontic Group (RPG), which had infrastructures with intermediate pontics on 2 regular-length Morse taper implants (4x11?mm). The simulations of the groups were created with Ansys Workbench 10.0 software. The results revealed that the RPG presented greater areas of possible fragility due to higher stress concentrations, for example, in the cervical area of the union between the implant and component the top platform of the abutment, as well as greater coverage of the stress by the cervical implant threads. The RPG infrastructure was also more affected by stresses in the connection areas between the prostheses and on the occlusal surface. There is an advantage to using prostheses supported by a greater number of implants (RCG) because this decreases the stress in the analyzed structures and consequently improves stress dissipation to the supporting bone, which would preserve the system.