Induction maintenance concept for HAART as initial treatment in HIV infected infants

<p>Abstract</p> <p>Background</p> <p>Early initiated antiretroviral therapy (ART) in HIV infected infants leads to improved long-term viral suppression and survival. Guidelines recommend initiating therapy with a triple ART consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either one additional non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Compared to older children and adults, viral relapse is seen more frequently in infants receiving triple ART. We now address the possibility of a more potent ART with a quadruple induction and triple maintenance therapy.</p> <p>Methods</p> <p>We examine the longitudinal course in four HIV infected infants, who were referred from other centers and could not be recruited to multicentre trials. We introduced ART initially consisting of two NRTIs, one NNRTI and one PI and later discontinued the PI at the age of 12 months maintaining a triple regime consisting of two NRTIs and one NNRTI.</p> <p>Results</p> <p>Provided that therapy adherence was maintained we observed an effective sustained decline of viral load and significant CD4 cell reconstitution even after switching to a triple regime. No drug associated toxicity was seen.</p> <p>Conclusion</p> <p>We suggest that a four drug therapy might be a possible initial therapy option in HIV infected infants, at least in those with a high viral load, followed by a maintenance triple regime after 12 months of therapy.</p

The impact of interventions to promote healthier ready-to-eat meals (to eat in, to take away or to be delivered) sold by specific food outlets open to the general public: a systematic review.

INTRODUCTION: Ready-to-eat meals sold by food outlets that are accessible to the general public are an important target for public health intervention. We conducted a systematic review to assess the impact of such interventions. METHODS: Studies of any design and duration that included any consumer-level or food-outlet-level before-and-after data were included. RESULTS: Thirty studies describing 34 interventions were categorized by type and coded against the Nuffield intervention ladder: restrict choice = trans fat law (n = 1), changing pre-packed children's meal content (n = 1) and food outlet award schemes (n = 2); guide choice = price increases for unhealthier choices (n = 1), incentive (contingent reward) (n = 1) and price decreases for healthier choices (n = 2); enable choice = signposting (highlighting healthier/unhealthier options) (n = 10) and telemarketing (offering support for the provision of healthier options to businesses via telephone) (n = 2); and provide information = calorie labelling law (n = 12), voluntary nutrient labelling (n = 1) and personalized receipts (n = 1). Most interventions were aimed at adults in US fast food chains and assessed customer-level outcomes. More 'intrusive' interventions that restricted or guided choice generally showed a positive impact on food-outlet-level and customer-level outcomes. However, interventions that simply provided information or enabled choice had a negligible impact. CONCLUSION: Interventions to promote healthier ready-to-eat meals sold by food outlets should restrict choice or guide choice through incentives/disincentives. Public health policies and practice that simply involve providing information are unlikely to be effective

Universality and exactness of Schrodinger geometries in string and M-theory

We propose an organizing principle for classifying and constructing Schrodinger-invariant solutions within string theory and M-theory, based on the idea that such solutions represent nonlinear completions of linearized vector and graviton Kaluza-Klein excitations of AdS compactifications. A crucial simplification, derived from the symmetry of AdS, is that the nonlinearities appear only quadratically. Accordingly, every AdS vacuum admits infinite families of Schrodinger deformations parameterized by the dynamical exponent z. We exhibit the ease of finding these solutions by presenting three new constructions: two from M5 branes, both wrapped and extended, and one from the D1-D5 (and S-dual F1-NS5) system. From the boundary perspective, perturbing a CFT by a null vector operator can lead to nonzero beta-functions for spin-2 operators; however, symmetry restricts them to be at most quadratic in couplings. This point of view also allows us to easily prove nonrenormalization theorems: for any Sch(z) solution of two-derivative supergravity constructed in the above manner, z is uncorrected to all orders in higher derivative corrections if the deforming KK mode lies in a short multiplet of an AdS supergroup. Furthermore, we find infinite classes of 1/4 BPS solutions with 4-,5- and 7-dimensional Schrodinger symmetry that are exact.Comment: 31 pages, plus appendices; v2, minor corrections, added refs, slight change in interpretation in section 2.3, new Schrodinger and Lifshitz solutions included; v3, clarifications in sections 2 and 3 regarding existence of solutions and multi-trace operator

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

In vivo biofunctional evaluation of hydrogels for disc regeneration

Purpose Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. Methods In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Results Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. Conclusions None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioningThis work was supported by the EU-project Disc Regeneration (NMP3-LA-2008-213904). Technical assistance of Iris Baum and the whole animal surgery team of the Institute of Orthopaedic Research and Biomechanics, Ulm, are gratefully acknowledged. DDAHA hydrogels were kindly provided by Cristina Longinotti (DDAHA, Anika Therapeutics, Abano Therme, Italy)

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Fermions and Type IIB Supergravity On Squashed Sasaki-Einstein Manifolds

We discuss the dimensional reduction of fermionic modes in a recently found class of consistent truncations of type IIB supergravity compactified on squashed five-dimensional Sasaki-Einstein manifolds. We derive the lower dimensional equations of motion and effective action, and comment on the supersymmetry of the resulting theory, which is consistent with N=4 gauged supergravity in $d=5$, coupled to two vector multiplets. We compute fermion masses by linearizing around two $AdS_{5}$ vacua of the theory: one that breaks N=4 down to N=2 spontaneously, and a second one which preserves no supersymmetries. The truncations under consideration are noteworthy in that they retain massive modes which are charged under a U(1) subgroup of the $R$-symmetry, a feature that makes them interesting for applications to condensed matter phenomena via gauge/gravity duality. In this light, as an application of our general results we exhibit the coupling of the fermions to the type IIB holographic superconductor, and find a consistent further truncation of the fermion sector that retains a single spin-1/2 mode.Comment: 43 pages, 2 figures, PDFLaTeX; v2: added references, typos corrected, minor change

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Nucleon structure functions and light front dynamics

We present a quark-parton model to describe polarized and unpolarized nucleon structure functions. The twist-two matrix elements for the QCD evolution analysis of lepton-hadron scattering are calculated within a light-front covariant quark model. The relativistic effects in the three-body wave function are discussed for both the polarized and unpolarized cases. Predictions are given for the polarized gluon distributions as will be seen in future experiments

Homoeologous gene silencing in tissue cultured wheat callus

Abstract Background In contrast to diploids, most polyploid plant species, which include the hexaploid bread wheat, possess an additional layer of epigenetic complexity. Several studies have demonstrated that polyploids are affected by homoeologous gene silencing, a process in which sub-genomic genomic copies are selectively transcriptionally inactivated. This form of silencing can be tissue specific and may be linked to developmental or stress responses. Results Evidence was sought as to whether the frequency of homoeologous silencing in in vitro cultured wheat callus differ from that in differentiated organs, given that disorganized cells are associated with a globally lower level of DNA methylation. Using a reverse transcription PCR (RT-PCR) single strand conformation polymorphism (SSCP) platform to detect the pattern of expression of 20 homoeologous sets of single-copy genes known to be affected by this form of silencing in the root and/or leaf, we observed no silencing in any of the wheat callus tissue tested. Conclusion Our results suggest that much of the homoeologous silencing observed in differentiated tissues is probably under epigenetic control, rather than being linked to genomic instability arising from allopolyploidization. This study reinforces the notion of plasticity in the wheat epi-genome.</p