Broad-Spectrum Virus Trapping with Heparan Sulfate-Modified DNA Origami Shells.

Effective broadband antiviral platforms that can act on existing viruses and viruses yet to emerge are not available, creating a need to explore treatment strategies beyond the trodden paths. Here, we report virus-encapsulating DNA origami shells that achieve broadband virus trapping properties by exploiting avidity and a widespread background affinity of viruses to heparan sulfate proteoglycans (HSPG). With a calibrated density of heparin and heparan sulfate (HS) derivatives crafted to the interior of DNA origami shells, we could encapsulate adeno, adeno-associated, chikungunya, dengue, human papilloma, noro, polio, rubella, and SARS-CoV-2 viruses or virus-like particles, in one and the same HS-functionalized shell system. Additional virus-type-specific binders were not needed for the trapping. Depending on the relative dimensions of shell to virus particles, multiple virus particles may be trapped per shell, and multiple shells can cover the surface of clusters of virus particles. The steric occlusion provided by the heparan sulfate-coated DNA origami shells can prevent viruses from further interactions with receptors, possibly including those found on cell surfaces.

Care to female adolescents victims of sexual violence at a referral service in Brazil from 2011 to 2018.

OBJECTIVE: To evaluate the characteristics of aggression, care, and follow-up of sexual violence in adolescent women at a university service in Campinas, São Paulo, Brazil. METHODS: In a retrospective cohort study from 2011 to 2018, we assessed sociodemographic characteristics, type and form of sexual violence perpetration, background and perception of the victim about violence, and characteristics of care and social/legal support during follow-up. RESULTS: Of 521 adolescents 242 (46.5%) were aged 10-14 years, 354 (68%) had not started sexual life, 465 (89%) perceived the violence and they had low prevalence of alcohol (71, 16%) and other psychoactive substance consumption (25, 6%), and 24 (4.6%) had an intellectual disability. Intimidation through physical force, acute abuse, vaginal penetration, acquaintance aggressor, being approached in a public place, and family/acquaintance residence were the most prevalent characteristics of aggression. In the 2017-2018 biennium, we observed a decrease in the prevalence of adolescents who were students (P < 0.001), an increase in the number of acquaintance aggressors (P = 0.008), and medical care after 72 hours (P < 0.033). CONCLUSION: Adolescents were victims of severe sexual violence. There was a decrease in prophylactic treatments and half of the adolescents did not complete outpatient follow-up. The economic worsening over the last decade may have contributed to these results.

Highly Transparent Covalent Mucin Coatings Improve the Wettability and Tribology of Hydrophobic Contact Lenses.

A stable, good coverage of the corneal tissue by the tear film is essential for protecting the eye. Contact lenses, however, constitute a foreign body that separates the tear film into two thinner layers, which are then more vulnerable toward disruption. This effect is even more pronounced if the contact lenses possess an insufficient surface wettability, which, in addition to friction, is suggested to be linked to discomfort and damage to the ocular surface. In this study, we establish covalent surface coatings with mucin macromolecules to overcome this issue for pure silicone contact lenses. This material class, which outperforms state-of-the-art silicone hydrogels in terms of oxygen permeability, is not yet used for commercial contact lens applications, which is due to its strongly hydrophobic surface characteristics. The applied process stably attaches a transparent mucin layer onto the contact lenses and thereby establishes hydrophilic surfaces that not only prevent lipid adsorption but also interact very well with liquid environments. Most importantly, however, we show that those mucin coatings are indeed able to prevent wear formation on corneal tissue that is subjected to the tribological stress applied by a contact lens. Our results open up great possibilities for a variety of hydrophobic materials that are, to date, not suitable for a contact lens application. Furthermore, the ability of mucin coatings to reduce wear in a tissue/synthetic material contact might be also beneficial for other biomedical applications.

Consecutive Use of the 52 mg Levonorgestrel-releasing Intrauterine System: Variations in Bleeding Patterns.

OBJECTIVE: Changes in bleeding patterns could influence the decisions of healthcare professionals to change the levonorgestrel-releasing intrauterine system (LNG-IUS) before 7 years of use, the recommended period of extended use. We evaluated changes in the bleeding patterns of users of the 52 mg LNG-IUS at the end of use of the first (IUS-1) and during the second device (IUS-2) use. METHODS: We performed an audit of the medical records of all women who used two consecutive LNG-IUSs at the Family Planning clinic. We evaluated the sociodemographic/gynecological variables, the length of use, and the bleeding patterns reported in the reference periods of 90 days before removal of the IUS-1 and at the last return in use of IUS-2. We used the McNemar test to compare bleeding patterns. Statistical significance was established at p < 0.05. RESULTS: We evaluated 301 women aged (mean ± SD) 32 (±6.1) years, with lengths of use of 68.9 (±16.8) and 20.3 (±16.7) months for the IUS-1 and IUS-2, respectively. No pregnancies were reported. Bleeding patterns varied significantly among women who used the IUS-2 for ≥ 7 months to 6 years when compared the bleeding patterns reported in IUS-1 use. Eighty-nine out of 221 (40%) women maintained amenorrhea and infrequent bleeding; 66 (30%) evolved to bleeding patterns with light flow, and 66 (30%) maintained or evolved to heavy flow patterns (p = 0.012). No differences were observed among the 80 women with ≤ 6 months of use. CONCLUSION: Changes in bleeding patterns occur during the use of LNG-IUS and should not be decisive for the early replacement of the device.

OBJETIVO: Variações no padrão de sangramento podem afetar a decisão de troca do sistema intrauterino de levonorgestrel (SIU-LNG) antes do período de uso estendido recomendado de 7 anos. Nós avaliamos mudanças no padrão de sangramento de usuárias ao final do uso do primeiro SIU-LNG 52 mg (SIU-1) e durante o uso do segundo dispositivo (SIU-2). MéTODOS: Revisamos os prontuários de todas as mulheres que inseriram consecutivamente o SIU-LNG no ambulatório de Planejamento Familiar. Foram avaliadas as variáveis sociodemográficas/ginecológicas, o tempo de uso, e os padrões de sangramento relatados nos períodos de referência de 90 dias antes da remoção do SIU-1 e no último retorno em uso do SIU-2. Usamos o teste de McNemar para comparar os padrões de sangramento. A significância estatística foi estabelecida em p < 0,05. RESULTADOS: Analisamos os dados de 301 mulheres com idade (média ± desvio padrão [DP]) de 32 (±6,1) anos e tempo de uso de 68,9 (±16,8) e 20,3 (±16,7) meses para o SIU-1 e SIU-2, respectivamente. Nenhuma gravidez foi relatada. Os padrões de sangramento variaram significativamente durante o uso do SIU-2 (≥ 7 meses a 6 anos) em relação ao padrão relatado no SIU-1. Oitenta e nove das 221 (40%) mulheres mantiveram amenorreia e sangramento infrequente; 66 (30%) evoluíram para padrões de sangramento com fluxo leve e 66 (30%) mantiveram ou evoluíram para padrões de fluxo intenso (p = 0,012). Não foram observadas diferenças entre as 80 mulheres que utilizavam o SIU-2 há ≤ 6 meses. CONCLUSãO: Mudanças nos padrões de sangramento ocorrem durante o uso do LNG-IUS e não devem ser decisivas para a troca precoce do dispositivo.

Consecutive use of the 52 mg levonorgestrel-releasing intrauterine system: variations in bleeding patterns / Uso consecutivo do sistema intrauterino de levonorgestrel 52 mg: variações no padrão de sangramento

Abstract Objective Changes in bleeding patterns could influence the decisions of healthcare professionals to change the levonorgestrel-releasing intrauterine system (LNG-IUS) before 7 years of use, the recommended period of extended use. We evaluated changes in the bleeding patterns of users of the 52 mg LNG-IUS at the end of use of the first (IUS-1) and during the second device (IUS-2) use. Methods We performed an audit of the medical records of all women who used two consecutive LNG-IUSs at the Family Planning clinic. We evaluated the sociodemographic/gynecological variables, the length of use, and the bleeding patterns reported in the reference periods of 90 days before removal of the IUS-1 and at the last return in use of IUS-2. We used the McNemar test to compare bleeding patterns. Statistical significance was established at p < 0.05. Results We evaluated 301 women aged (mean ± SD) 32 (±6.1) years, with lengths of use of 68.9 (±16.8) and 20.3 (±16.7) months for the IUS-1 and IUS-2, respectively. No pregnancies were reported. Bleeding patterns varied significantly among women who used the IUS-2 for ≥ 7 months to 6 years when compared the bleeding patterns reported in IUS-1 use. Eighty-nine out of 221 (40%) women maintained amenorrhea and infrequent bleeding; 66 (30%) evolved to bleeding patterns with light flow, and 66 (30%) maintained or evolved to heavy flow patterns (p = 0.012). No differences were observed among the 80 women with ≤ 6 months of use. Conclusion Changes in bleeding patterns occur during the use of LNG-IUS and should not be decisive for the early replacement of the device.

Resumo Objetivo Variações no padrão de sangramento podem afetar a decisão de troca do sistema intrauterino de levonorgestrel (SIU-LNG) antes do período de uso estendido recomendado de 7 anos. Nós avaliamos mudanças no padrão de sangramento de usuárias ao final do uso do primeiro SIU-LNG 52 mg (SIU-1) e durante o uso do segundo dispositivo (SIU-2). Métodos Revisamos os prontuários de todas as mulheres que inseriram consecutivamente o SIU-LNG no ambulatório de Planejamento Familiar. Foram avaliadas as variáveis sociodemográficas/ginecológicas, o tempo de uso, e os padrões de sangramento relatados nos períodos de referência de 90 dias antes da remoção do SIU-1 e no último retorno em uso do SIU-2. Usamos o teste de McNemar para comparar os padrões de sangramento. A significância estatística foi estabelecida em p < 0,05. Resultados Analisamos os dados de 301 mulheres com idade (média ± desvio padrão [DP]) de 32 (±6,1) anos e tempo de uso de 68,9 (±16,8) e 20,3 (±16,7) meses para o SIU-1 e SIU-2, respectivamente. Nenhuma gravidez foi relatada. Os padrões de sangramento variaram significativamente durante o uso do SIU-2 (≥ 7 meses a 6 anos) em relação ao padrão relatado no SIU-1. Oitenta e nove das 221 (40%) mulheres mantiveram amenorreia e sangramento infrequente; 66 (30%) evoluíram para padrões de sangramento com fluxo leve e 66 (30%) mantiveram ou evoluíram para padrões de fluxo intenso (p = 0,012). Não foram observadas diferenças entre as 80 mulheres que utilizavam o SIU-2 há ≤ 6 meses. Conclusão Mudanças nos padrões de sangramento ocorrem durante o uso do LNG-IUS e não devem ser decisivas para a troca precoce do dispositivo.

Eyepass Glaucoma Implant in Open-Angle Glaucoma After Failed Conventional Medical Therapy: Clinical Results of a 5-Year-Follow-up.

PURPOSE OF THE STUDY: The purpose of the study was to evaluate the long-term safety and intraocular pressure (IOP) lowering effect of the Eyepass glaucoma implant (GMP Vision Solutions, Inc.). PATIENTS AND METHODS: The prospective study included 15 patients (16 eyes) with primary open-angle glaucoma who underwent an implantation of the Y-shaped Eyepass glaucoma implant. This shunt diverts aqueous from the anterior chamber directly into Schlemm's canal to increase outflow and to lower the IOP. IOP, visual acuity, potential complications and the number of antiglaucomatous medications were monitored over a period of 5 years. RESULTS: The implant was successfully inserted in 14 of 16 eyes. Mean IOP was reduced from 26.4±8.1 mm Hg (SD) to 16.4±5.3 mm Hg (P=0.032) at the end of the follow-up. Mean number of antiglaucomatous medications dropped from 2.1±1.2 (SD) to 0.9±1.2 (SD). In 5 cases, no pressure-lowering medications were necessary 5 years after surgery. Mean best-corrected visual acuity did not change significantly (P>0.05). In all cases, filtering blebs were observed and sustained using antimetabolites. The most common complication was temporary ocular hypotony. Two patients required a revision surgery due to implant malposition. CONCLUSIONS: The Eyepass glaucoma implant seems to be a safe and effective treatment option for patients with primary open-angle glaucoma. The use of this device resulted in a significant decrease of IOP.

[Winnicott's arabesques. The wit of a psychotherapeutic technique]. / Winnicotts Arabesken. Vom Witz einer psychotherapeutischen Praxis.

This article analyzes Winnicott's technique of the so-called "squiggle game". Its basic principle can be traced back to early attempts in psychiatry at using patients' drawings and paintings as diagnostic tools around 1900. Winnicott's technique, however, by being rooted in his theory of "transition phemomena", is conducive to a new relationship between patient and therapist.

Drawing cure: children's drawings as a psychoanalytic instrument.

This essay deals with the special case of drawings as psychoanalytical instruments. It aims at a theoretical understanding of the specific contribution made by children's drawings as a medium of the psychical. In the influential play technique developed by Melanie Klein, drawing continuously interacts with other symptomatic (play) actions. Nonetheless, specific functions of drawing within the play technique can be identified. The essay will discuss four crucial aspects in-depth: 1) the strengthening of the analysis's recursivity associated with the graphic artifact; 2) the opening of the analytic process facilitated by drawing; 3) the creation of a genuinely graphic mode of producing meaning that allows the child to develop a "theory" of the workings of his own psychic apparatus; and 4) the new possibilities of symbolization associated with the latter. In contrast to classical definitions of the psychological instrument, the child's drawing is a weakly structured tool that does not serve to reproduce psychic processes in an artificial, controlled setting. The introduction of drawing into the psychoanalytic cure is by no means interested in replaying past events, but in producing events suited to effecting a transformation of the synchronic structures of the unconscious.

IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses.

IC31, the combination of a novel immunostimulatory oligodeoxynucleotide containing deoxy-Inosine/deoxy-Cytosine (ODN1a) and the antimicrobial peptide KLKL(5)KLK, represents a promising novel adjuvant signaling via the TLR9/MyD88-dependent pathway of the innate immune system. In mice, IC31 induces potent peptide-specific type 1 cellular immune responses, as well as mainly type 1 dominated protein-specific cellular and humoral immune responses. In addition, cytotoxic T lymphocytes were induced, able to kill efficiently target cells in vivo. Activation of murine dendritic cells by IC31 induced efficiently proliferation of naïve CD4(+) TCR transgenic T cells (DO.11.10) as well as their differentiation into IFN-gamma- and IL-4-producing T cells in vitro.

Vaccination with poly-L-arginine as immunostimulant for peptide vaccines: induction of potent and long-lasting T-cell responses against cancer antigens.

Vaccines that induce high numbers of sustained T cell responses are urgently needed for the treatment of numerous diseases including cancer. Antigen-presenting cells (APCs), the most important of which are dendritic cells, orchestrate antigen-dependent T cell responses in that they present antigens to T cells in an appropriate environment. Here we present evidence that after vaccination with a simple mixture of the cationic poly-amino acid poly-L-arginine and tumor antigen-derived peptide antigens, large numbers of antigen-specific T cells are induced and APCs mediate the generation of T lymphocytes. We observe that after s.c. injection, MHC class II(+) cells infiltrate injection sites and are loaded with large amounts of antigen in vivo under the influence of poly-L-arginine. Consequently, numerous antigen-charged APCs can be detected in draining lymph nodes of vaccinated animals. Antigen-specific T cell responses induced are systemic and were readily detected more than 4 months after the last vaccination, the latest time point we measured. By contrast, even after repeat injections, we were consistently unable to detect antibody responses against poly-L-arginine, allowing this compound to be used for numerous booster injections. Clinical trials in cancer patients using poly-L-arginine as immunostimulant will be carried out in the near future.