Intravitreal implants manufactured by supercritical foaming for treating retinal diseases

Chronic retinal diseases, such as age-related macular degeneration (AMD), are a major cause of global visual impairment. However, current treatment methods involving repetitive intravitreal injections pose financial and health burdens for patients. The development of controlled drug release systems, particularly for biological drugs, is still an unmet need in prolonging drug release within the vitreous chamber. To address this, green supercritical carbon dioxide (scCO2) foaming technology was employed to manufacture porous poly(lactic-co-glycolic acid) (PLGA)-based intravitreal implants loaded with dexamethasone. The desired implant dimensions were achieved through 3D printing of customised moulds. By varying the depressurisation rates during the foaming process, implants with different porosities and dexamethasone release rates were successfully obtained. These implants demonstrated controlled drug release for up to four months, surpassing the performance of previously developed implants. In view of the positive results obtained, a pilot study was conducted using the monoclonal antibody bevacizumab to explore the feasibility of this technology for preparing intraocular implants loaded with biologic drug molecules. Overall, this study presents a greener and more sustainable alternative to conventional implant manufacturing techniques, particularly suited for drugs that are susceptible to degradation under harsh conditionsI.S.-V. acknowledges Consellería de Cultura, Educación e Universidade for her Postdoctoral Fellowship (Xunta de Galicia, Spain; ED481B-2021-019). Work supported by MICINN [PID2022-142350OB-C21] and [PID2020-120010RB-I00], Xunta de Galicia [ED431C 2020/17], Agencia Estatal de Investigación [AEI] and FEDER funds. Authors would like to thank the use of RIAIDT-USC analytical facilities.S

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

In Vitro Antileishmanial Activity of Aloe Vera Leaf Exudate: A Potential Herbal Therapy in leishmaniasis

Aloe vera has wide spread use in health products, and despite several reports on the whole plant and inner gel, little work has been performed on the leaf exudate. Our aim was to evaluate the in vitro efficacy of Aloe vera leaf exudate (AVL) in leishmaniasis. Irrespective of the disease manifestation, promastigotes from strains responsible for cutaneous, mucocutaneous, and visceral leishmaniasis were susceptible to AVL and their IC50 ranged from 100 to 180 μg/ml. In axenic amastigotes cultured from a L. donovani strain 2001 responsible for visceral leishmaniasis, the IC50 was 6.0 μg/ml. AVL caused activation of host macrophages evident by an increased release of members of reactive oxygen species that was attenuated by preincubation with free radical scavengers. Collectively, our data indicates that AVL, via its direct leishmanicidal activity which can be further enhanced by activation of host macrophages, isan effective antileishmanial agent meriting further pharmacological investigations

UDP-Gal: N-acetylglucosamine β 1–4 galactosyltransferase expressing live attenuated parasites as vaccine for visceral leishmaniasis

As compared to cutaneous leishmaniasis, vaccination against visceral leishmaniasis (VL) has received limited attention. In this study, we demonstrate for the first time that an UDP-Galactose: N-acetylglucosamine β 1–4 galactosyltransferase (GenBank Accession No. EF159943) expressing attenuated LD clonal population (A-LD) is able to confer protection against the experimental challenge with the virulent LD AG83 parasite. A-LD was also effective in established leishmania infection. The vaccinated animals showed both cell mediated (in vitro T-cell proliferation, and DTH response) and humoral responses (Th1 type). These results demonstrate the potential of the attenuated clones as an immunotherapeutic and immunoprophylactic agent against visceral leishmaniasis

Fish consumption in mid-childhood and its relationship to neuropsychological outcomes measured in 7–9 year old children using a NUTRIMENTHE neuropsychological battery

Background Long-chain polyunsaturated fatty acids (LCPUFA), particularly n-3 LCPUFA, play a central role in neuronal growth and the development of the human brain. Fish is the main dietary source of n-3 LCPUFA. To assess the relation between fish consumption, estimated dietary n-3 LCPUFA intake and cognition and behaviour in childhood in a multi-centre European sample. Methods Children from 2 European studies, CHOP and NUHEAL, were assessed at 8 and 7.5 years of age, respectively. Different outcomes of neuropsychological development (assessed with the standardized NUTRIMENTHE Neuropsychological Battery (NNB) consisting of 15 subtests) were related with outcomes from a food-frequency questionnaire (FFQ) focussing on the consumption of fish. Results A total of 584 children completed the FFQ and the neuropsychological tests. We found no associations with calculated DHA or EPA intakes for any of the neuropsychological domains. Children who consumed 2 fish meals per week including one of fatty fish, showed no substantive differences in the cognitive domains from the children who did not. However negative associations with fatty fish consumption were found for social problems (p\ua0=\ua00.019), attention problems (p\ua0=\ua00.012), rule-breaking problems (p\ua0=\ua00.019) and aggressive behaviour problems (p\ua0=\ua00.032). No association was observed with internalizing problems. Higher levels of externalizing problems (p\ua0=\ua00.018) and total problems (p\ua0=\ua00.018) were associated with eating less fatty fish. Conclusions Children who consumed 2 fish meals per week including one of fatty fish were less likely to show emotional and behavioural problems than those who did not

SuperB Progress Reports -- Physics

SuperB is a high luminosity e+e- collider that will be able to indirectly probe new physics at energy scales far beyond the reach of any man made accelerator planned or in existence. Just as detailed understanding of the Standard Model of particle physics was developed from stringent constraints imposed by flavour changing processes between quarks, the detailed structure of any new physics is severely constrained by flavour processes. In order to elucidate this structure it is necessary to perform a number of complementary studies of a set of golden channels. With these measurements in hand, the pattern of deviations from the Standard Model behavior can be used as a test of the structure of new physics. If new physics is found at the LHC, then the many golden measurements from SuperB will help decode the subtle nature of the new physics. However if no new particles are found at the LHC, SuperB will be able to search for new physics at energy scales up to 10-100 TeV. In either scenario, flavour physics measurements that can be made at SuperB play a pivotal role in understanding the nature of physics beyond the Standard Model. Examples for using the interplay between measurements to discriminate New Physics models are discussed in this document. SuperB is a Super Flavour Factory, in addition to studying large samples of B_{u,d,s}, D and tau decays, SuperB has a broad physics programme that includes spectroscopy both in terms of the Standard Model and exotica, and precision measurements of sin^2theta_W. In addition to performing CP violation measurements at the Y(4S) and phi(3770), SuperB will test CPT in these systems, and lepton universality in a number of different processes. The multitude of rare decay measurements possible at SuperB can be used to constrain scenarios of physics beyond the Standard Model

SuperB Progress Reports - Physics

SuperB is a high luminosity e+e- collider that will be able to indirectly probe new physics at energy scales far beyond the reach of any man made accelerator planned or in existence. Just as detailed understanding of the Standard Model of particle physics was developed from stringent constraints imposed by flavour changing processes between quarks, the detailed structure of any new physics is severely constrained by flavour processes. In order to elucidate this structure it is necessary to perform a number of complementary studies of a set of golden channels. With these measurements in hand, the pattern of deviations from the Standard Model behavior can be used as a test of the structure of new physics. If new physics is found at the LHC, then the many golden measurements from SuperB will help decode the subtle nature of the new physics. However if no new particles are found at the LHC, SuperB will be able to search for new physics at energy scales up to 10-100 TeV. In either scenario, flavour physics measurements that can be made at SuperB play a pivotal role in understanding the nature of physics beyond the Standard Model. Examples for using the interplay between measurements to discriminate New Physics models are discussed in this document. SuperB is a Super Flavour Factory, in addition to studying large samples of B_{u,d,s}, D and tau decays, SuperB has a broad physics programme that includes spectroscopy both in terms of t he Standard Model and exotica, and precision measurements of sin^2theta_W. In addition to performing CP violation measurements at the Y(4S) and phi(3770), SuperB will test CPT in these systems, and lepton universality in a number of different processes. The multitude of rare decay measurements possible at SuperB can be used to constrain scenarios of physics beyond the Standard Model. ..