Engineering modular half-antibody conjugated nanoparticles for targeting CD44v6-expressing cancer cells

Gastric cancer (GC) remains a major cause of death worldwide mainly because of the late detection in advanced stage. Recently, we proposed CD44v6 as a relevant marker for early detection of GC, opening new avenues for GC-targeted theranostics. Here, we designed a modular nanoscale system that selectively targets CD44v6-expressing GC cells by the site-oriented conjugation of a new-engineered CD44v6 half-antibody fragment to maleimide-modified polystyrene nanoparticles (PNPs) via an efficient bioorthogonal thiol-Michael addition click chemistry. PNPs with optimal particle size (200 nm) for crossing a developed biomimetic CD44v6-associated GC stromal model were further modified with a heterobifunctional maleimide crosslinker and click conjugated to the novel CD44v6 half-antibody fragment, obtained by chemical reduction of full antibody, without affecting its bioactivity. Collectively, our results confirmed the specific targeting ability of CD44v6-PNPs to CD44v6-expressing cells (1.65-fold higher than controls), highlighting the potential of CD44v6 half-antibody conjugated nanoparticles as promising and clinically relevant tools for the early diagnosis and therapy of GC. Additionally, the rational design of our nanoscale system may be explored for the development of several other nanotechnology-based disease-targeted approaches.This work was supported by Norte Portugal Regional Operational Programme (NORTE2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF) projects Norte-01-0145-FEDER-000012 and NORTE-07-0124-FEDER-000029, through COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI) Portugal 2020 and Portuguese Foundation for Science and Technology (FCT) in the framework of the projects POCI-01-0145-FEDER-007274, POCI-01-0145-FEDER-016390, and PTDC/CTMNAN/120958/2010, B.N.L. doctoral grant (SFRH/BD/87400/2012) and postdoctoral grant (PTDC/MEC-GIN/29232/2017). R.F.P. was supported by Institute of Network Bioengineering for Healthy Aging (0245_IBEROS_1_E)

Effects of therapeutic and aerobic exercise programs in temporomandibular disorder-associated headaches

Objective: To assess the effects of three 8-week exercise programs on the frequency, intensity, and impact of headaches in patients with headache attributed to temporomandibular disorder (TMD). Methodology: Thirty-six patients diagnosed with headache attributed to TMD participated in the study and were divided into three groups of 12 patients: a therapeutic exercise program (G1, mean age: 26.3±5.6 years), a therapeutic and aerobic exercise program (G2, mean age: 26.0±4.6 years), and an aerobic exercise program (G3, 25.8±2.94 years). Headache frequency and intensity were evaluated using a headache diary, and the adverse headache impact was evaluated using the Headache Impact Test (HIT-6). The intensity was reported using the numerical pain rating scale. These parameters were evaluated twice at baseline (A01/A02), at the end of the 8-week intervention period (A1), and 8-12 weeks after the end of the intervention (A2). Results: At A1, none of the G2 patients reported having headaches, in G1, only two patients reported headaches, and in G3, ten patients reported headache. The headache intensity scores (0.3 [95% CI: -0.401, 1.068]), (0.0 [95% CI: -0.734, 0.734]) and HIT-6 (50.7 [95% CI: 38.008, 63.459]), (49.5 [95% CI: 36.808, 62.259]), significantly decreased in G1 and G2 at A1. At A2 headache intensity scores (0.5 [95% CI: -0.256, 1.256]), (0.0 [95% CI: -0.756, 0.756]) and HIT-6 (55.1 [95% CI: 42.998, 67.268]), (51.7 [95% CI: 39.532, 63.802]) in G1 and G2 haven't change significantly. The effects obtained immediately after the completion of the intervention programs were maintained until the final follow-up in all groups. Conclusion: The programs conducted by G1 (therapeutic exercises) and G2 (therapeutic and aerobic exercise) had significant results at A1 and A2.info:eu-repo/semantics/publishedVersio

A Fast Alternative to Soft Lithography for the Fabrication of Organ-on-a-Chip Elastomeric-Based Devices and Microactuators

Organ-on-a-chip technology promises to revolutionize how pre-clinical human trials are conducted. Engineering an in vitro environment that mimics the functionality and architecture of human physiology is essential toward building better platforms for drug development and personalized medicine. However, the complex nature of these devices requires specialized, time consuming, and expensive fabrication methodologies. Alternatives that reduce design-to-prototype time are needed, in order to fulfill the potential of these devices. Here, a streamlined approach is proposed for the fabrication of organ-on-a-chip devices with incorporated microactuators, by using an adaptation of xurography. This method can generate multilayered, membrane-integrated biochips in a matter of hours, using low-cost benchtop equipment. These devices are capable of withstanding considerable pressure without delamination. Furthermore, this method is suitable for the integration of flexible membranes, required for organ-on-a-chip applications, such as mechanical actuation or the establishment of biological barrier function. The devices are compatible with cell culture applications and present no cytotoxic effects or observable alterations on cellular homeostasis. This fabrication method can rapidly generate organ-on-a-chip prototypes for a fraction of cost and time, in comparison to conventional soft lithography, constituting an interesting alternative to the current fabrication methods.C.O. and P.L.G. contributed equally to this work as co‐senior authors. This work was supported by Fundação para a Ciência e Tecnologia (FCT) and Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences (BiotechHealth Programme; ref. PD/00016/2012), by Programa Operacional Potencial Humano (POPH), and SkinChip project (PTDC/BBB‐BIO/1889/2014). The work has been also financed by: 1) Fundo Europeu de Desenvolvimento (FEDER) Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI‐01‐0145‐FEDER‐007274), 3DChroMe (PTDC/BTM‐TEC/30164/2017); Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) for projects NORTE‐01‐0145‐FEDER‐000029 and DOCnet (NORTE‐01‐0145‐FEDER‐000003). D.A.F. acknowledges FCT for his support through a FCT/BiotechHealth PhD Programme grant, ref. PD/BD/105976/2014. J.P.C. acknowledges funding from the European Structural and Investment funds through the Compete Programme (Grant #: LISBOA‐01‐0145‐FEDER‐016405) and from National funds through FCT (SAICTPAC/0019/2015) via the research project POINT4PAC, and FCT funding through INESC MN (Unidade ID 5367). The authors would also like to thank: Jorge Ferreira (Chromosome Instability Group, i3S/IBMC) for granting access to the plasma cleaner equipment and for the insightful scientific support; i3S Scientific Platform (Biointerfaces and Nanotechnology core facility, i3S/INEB), member of the national infrastructure PPBI – Portuguese Platform of Bioimaging (PPBI‐POCI‐01‐0145‐FEDER‐022122), in particular Maria Lázaro for support and access to the SP5 confocal microscope; Aureliana Sousa (Biofabrication Group at i3S/INEB) for scientific support and discussion; Dina Leitão (Centro Hospitalar e Universitário São João) for providing access to the normal gastric mucosa specimens; Celso Reis for kindly providing the antibody against Mucin‐1. C.O. and P.L.G. contributed equally to this work as co-senior authors. This work was supported by Funda??o para a Ci?ncia e Tecnologia (FCT) and Doctoral Programme on Cellular and Molecular Biotechnology Applied to?Health Sciences (BiotechHealth Programme; ref.?PD/00016/2012),?by Programa Operacional Potencial Humano (POPH), and SkinChip project (PTDC/BBB-BIO/1889/2014). The work has been also financed by: 1) Fundo Europeu de Desenvolvimento (FEDER) Regional funds through the COMPETE 2020 ? Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT/Minist?rio da Ci?ncia, Tecnologia e Inova??o in the framework of the projects ?Institute for Research and Innovation in Health Sciences? (POCI-01-0145-FEDER-007274), 3DChroMe (PTDC/BTM-TEC/30164/2017); Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) for projects NORTE-01-0145-FEDER-000029 and DOCnet (NORTE-01-0145-FEDER-000003). D.A.F. acknowledges FCT for his support through a FCT/BiotechHealth PhD Programme grant, ref. PD/BD/105976/2014. J.P.C. acknowledges funding from the European Structural and Investment funds through the Compete Programme (Grant #: LISBOA-01-0145-FEDER-016405) and from National funds through FCT (SAICTPAC/0019/2015) via the research project POINT4PAC, and FCT funding through INESC MN (Unidade ID 5367). The authors would also like to thank: Jorge Ferreira (Chromosome Instability Group, i3S/IBMC) for granting access to the plasma cleaner equipment and for the insightful scientific support; i3S Scientific Platform (Biointerfaces and Nanotechnology core facility, i3S/INEB), member of the national infrastructure PPBI ? Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122), in particular Maria L?zaro for support and access to the SP5 confocal microscope; Aureliana Sousa (Biofabrication Group at i3S/INEB) for scientific support and discussion; Dina Leit?o (Centro Hospitalar e Universit?rio S?o Jo?o) for providing access to the normal gastric mucosa specimens; Celso Reis for kindly providing the antibody against Mucin-1

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

Crystallization and preliminary X-ray study of haem-binding protein from the bloodsucking insect Rhodnius prolixus

Rhodnius haem-binding protein (RHBP) from the bloodsucking insect Rhodnius prolixus, a 15 kDa protein, has been crystallized using polyethylene glycol as a precipitant. X-ray diffraction data have been collected at a synchrotron source. The crystals belong to the space group P4(1(3))2(1)2, with unit-cell parameters a = b = 64.98, c = 210.68 Angstrom, and diffract beyond 2.6 Angstrom resolution.57686086

VISCERAL LEISHMANIASIS IN PETROLINA, STATE OF PERNAMBUCO, BRAZIL, 2007-2013

Visceral leishmaniasis is a life-threatening disease of great public health relevance in Brazil. The municipality of Petrolina is an endemic area in the State of Pernambuco, Brazil. This study was designed to assess the recent expansion of VL in the municipality ofPetrolina, Pernambuco. Patients data were obtained from the Brazilian National Information System for Notifiable Diseases (SINAN). A total of 111 records from 2007 to 2013 were investigated, of which 69 were residents in Petrolina. The disease has predominantly affected 1-4 year old children (34.8%). Most of the patients were males (59.4%). Co-infection with human immunodeficiency virus occurred in 14.5% of the cases. The criterion most frequently used was the clinical and epidemiological confirmation (59.4%), with clinical cure in 78.3% of cases and one fatal outcome. Visceral leishmaniasis is endemic in Petrolina with transmission levels varying from moderate to high. The present study has shown the precariousness of the use of diagnostic tests in primary healthcare units, and this misuse has interfered with the diagnosis and treatment of cases

Produção orgânica de rabanete em plantio direto sobre cobertura morta e viva.

O objetivo deste trabalho foi avaliar o uso de plantas espontâneas e cobertura viva de amendoim forrageiro(Arachis pintoi), associado à aplicação de composto orgânico na produção orgânica do rabanete em plantio direto. O experimento foi instalado na Universidade Federal do Acre, em Rio Branco-AC, de 15/06 a 14/07/2007. O delineamento experimental utilizado foi em blocos casualizados com parcelas subdivididas 4x3, em quatro repetições. As parcelas corresponderam ao sistema de plantio direto com cobertura viva de amendoim forrageiro, cobertura viva de planta espontânea, cobertura morta de planta espontânea e sistema de plantio em canteiro com solo descoberto. As subparcelas foram compostas pelas doses de composto orgânico de 5, 10 e 15 t ha-1 (base seca). O plantio direto na palha de plantas espontâneas teve desempenho semelhante ao preparo convencional do solo, ambos superiores ao plantio sobre as coberturas vivas. A produtividade do rabanete cv. Cometo, não foi afetada pelas doses crescentes de composto orgânico, podendo aplicar-se apenas 5 t ha-1, enquanto em preparo convencional do solo, o aumento da produtividade ultrapassa o plantio direto na palha apenas na dose maior de composto (15 t ha-1)