Hypogammaglobulinemia in children: a warning sign to look deeply? Melo, Karina Mescouto; Moraes‐Pinto, Maria Isabel; Andrade, Luís E. C. ...
APMIS : acta pathologica, microbiologica et immunologica Scandinavica,
October 2017, 2017-Oct, 2017-10-00, 20171001, Letnik:
125, Številka:
10
Journal Article
Recenzirano
This study investigated phenotypic and functional characteristics of lymphocytes in children with common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH), as well as ...B‐cell subsets in non‐consanguineous parents. Blood samples of 30 children, CVID (n = 9), UH (n = 9), healthy donors HD (n = 12), and 19 adults (parents and controls) were labeled by a combination of surface markers to identify CD4, CD8 T‐cell and B‐cell subpopulations. T‐cell cytokine production in children was analyzed in vitro after stimulation with phytohemagglutinin (PHA) and tetanus toxoid. We observed low percentages of switched memory B cells in children with CVID, increase in total CD4+ T‐cell counts, and high percentages of transitional B cells only in UH group. Analysis of T‐cell immunity showed that CVID children had decreased percentages of CD8+ IFN‐γ‐producing cells after stimulation with PHA and tetanus toxoid. Parent of children with CVID had low percentages of naive B cell and increased percentages of memory B cells in comparison with controls. These results suggest that (i) early combined immune defect in children with CVID and (ii) a possible familial B‐cell disturbance in pediatric CVID.
Abstract This study aims to develop a nano-sized fluoridated layered double hydroxide (LDH)-based release system via hydrothermal treatment for the controlled delivery of fluoride (F-) ions in the ...oral environment. The synthesis of conventional LDH-type (C-LDH) precursor nanomaterials was conducted using a co-precipitation method at constant pH, and the nanoparticulate-LDH (N-LDH) was synthesized by a hydrothermal procedure. Fluoride LDH (F-LDH) products were obtained through indirect synthesis using the precursor ion-exchange technique by varying the agitation time (2 and 24 h) and temperature (25 and 40 °C) to produce 12 material samples. The materials were characterized by energy dispersive x-ray, hexamethyldisilazane, digital radiography x-ray, Fourier-transform infrared, thermogravimetric analysis, and scanning electron microscopy. Additionally, the F-release kinetic profile was evaluated for 21 d in neutral and acid media with mathematical model analysis. Products with varying F-quantities were obtained, revealing specific release profiles. In general, there was a higher F-release in the acid medium, with emphasis on F-LDH-8. Fluoride-LDH and controlled fluoride delivery was successfully obtained, proving the potential of these nanomaterials as alternative anti-caries agents.
To describe the characteristics of opportunistic infections in pediatrics regarding their clinical aspects, as well as the diagnostic strategy and treatment.
Non-systematic review of literature ...studies in the PubMed database.
Opportunistic infections caused by non-tuberculous mycobacteria, fungi, Herpesvirae, and infections affecting individuals using immunobiological agents are analyzed. Because these are severe diseases with a rapid evolution, diagnostic suspicion should be early, associated with the patient's clinical assessment and history pointing to opportunistic infections. Whenever possible, samples of secretions, blood, and other fluids and tissues should be collected, with early therapy implementation.
Despite the improved diagnosis of opportunistic infections in recent years, they remain a challenge for pediatricians who are not used to these infections. They should raise the suspicion and start treating the case, but should also resort to specialists in the management of these infections to provide a better outcome for these patients, who still have high mortality.
Descrever as características das infecções oportunistas em pediatria em seus aspectos clínicos, bem como a estratégia diagnóstica e o tratamento.
Revisão de trabalhos de literatura de forma não sistemática na base de dados Pubmed.
São apresentadas as infecções oportunistas causadas por micobactérias não tuberculosas, fungos, herpervírus e as infecções que acometem indivíduos em uso de imunobiológicos. Por se tratar de doenças graves e de evolução rápida, a suspeita diagnóstica deve ser precoce, associada à clínica do paciente e aos dados de história que apontam para infecções oportunistas. Sempre que possível, amostras de secreções, sangue e outros fluidos e de tecidos devem ser coletadas, com instituição precoce de terapia.
Apesar da melhoria do diagnóstico de infecções oportunistas nos últimos anos, elas ainda são um desafio para o pediatra pouco habituado a essas infecções. Ele deve fazer a suspeita e iniciar a condução do caso, mas recorrer a especialistas com prática no manejo dessas infecções de modo a propiciar um melhor desfecho para esses pacientes que ainda apresentam alta mortalidade.
The objective of this study was to develop an active nanocomposite gelatin-based film in an automatic spreader in order to improve production, which is normally done by casting. The study was divided ...in two steps: (1) first, the effect of a nanocomposite-forming solution formulation on the rheological properties and on some physical properties of gelatin-based nanocomposite films (GNF) was evaluated using a response surface methodology (RSM); (2) then, the effect of potassium sorbate concentration on some GNF properties, previously chosen by RSM, was assessed. RSM, a 23+α factorial design, was used to study and to optimize the effect of three important variables, gelatin concentration (CG), plasticizer concentration (CP) and montmorillonite concentration (CN), on the rheological properties of a nanocomposite-forming solution, and on the properties of the films (mechanical and barrier properties). Films were prepared by casting in an automatic spreader. According to the results of the analysis of variance (ANOVA), in general, nanoparticle incorporation improved the mechanical properties of GNF. However, this improvement was not always proportional to the addition of the nanoparticles, since there is a maximum concentration limit. From the results obtained in the first step of the study, it was possible to optimize a formulation in order to study the effect of potassium sorbate concentration on GNF properties. At the range of concentration studied (5–15%), incorporation of the antimicrobial agent potassium sorbate in the GNF produced significant changes in the mechanical properties and solubility in water of the films. However, despite the hydrophilic characteristic of the antimicrobial compound, moisture content of the films was not affected. It could be concluded that potassium sorbate presented a plasticizer effect in the films, enabling greater molecular chain mobility and, therefore, affecting mechanical properties and solubility in water. The study of the quality of nanoparticle dispersion in the biopolymer matrix is a key strategy that may help researchers to better understand the effect of nanoparticle addition in biopolymer matrices. Spreading technique produced films similar to those produced by casting.
•Gelatin-based nanocomposite films were produced by casting in an automatic spreader.•Nanoparticle incorporation improved the mechanical properties of films.•Incorporation of potassium sorbate produced significant changes in films properties.•Spreading technique produced films similar to those produced by casting.
The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost ...immune responses.
RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer–BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18–60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR–9nn3scw.
Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8–30·1) in adults aged 18–60 years and 8·9% (4·2–16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67–88) for Ad26.COV2-S, 152 (134–173) for BNT162b2, 90 (77–104) for ChAdOx1 nCoV-19, and 12 (11–14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8–7·7) for Ad26.COV2-S, 13·4 (11·6–15·3) for BNT162b2, and 7·0 (6·1–8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9–12·9) for Ad26.COV2-S vaccine, 21·5 (14·5–31·9) for BNT162b2, and 10·6 (7·2–15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home.
Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection.
Ministry of Health, Brazil.
Structure-function relationships of biological macromolecules, in particular proteins, provide crucial insights for fundamental biochemistry, medical research and early drug discovery. However, ...production of recombinant proteins, either for structure determination, functional studies, or to be used as biopharmaceutical products, is often hampered by their instability and propensity to aggregate in solution
. Protein samples of poor quality are often associated with reduced reproducibility as well as high research and production expenses. Several biophysical methods are available for measuring protein aggregation and stability. Yet, discovering and developing means to improve protein behaviour and structure-function integrity remains a demanding task. Here, we discuss workflows that are made possible by adapting established biophysical methods to high-throughput screening approaches. Rapid identification and optimisation of conditions that promote protein stability and reduce aggregation will support researchers and industry to maximise sample quality, stability and reproducibility, thereby reducing research and development time and costs.
Simple Summary: Chlamydia is an infamous sexually transmitted bacterium that also has a less well-known role in human respiratory infections, which has evolved a unique cell structure to enable its ...survival within the body. Covering the surface of this infectious cell is a strong mesh-like network made up of many different proteins which protects the cell against damage. This research focussed on the most abundant protein within this mesh, the Major Outer Membrane Protein (MOMP), and introduced a series of mutations designed to prevent the mesh from forming completely. The effect of the mutations was visualised by adding a bright fluorescent dye to each MOMP, which was then examined with a high-resolution fluorescence microscope capable of showing us each individual cell and the MOMPs at their surface. With statistical analysis, we observed that certain mutations disrupted the connections between MOMPs, giving us greater insight into how Chlamydia forms these interactions. Chlamydia is an extremely prevalent disease amongst the global population, and whilst treatable, there is currently no available vaccine. By researching Chlamydia's biology and its method of evading our immune system, we can not only further our understanding of this complex bacterium, but also develop novel therapeutics for its treatment and prevention.
Neonates born to transplanted mothers are exposed to immunosuppressive drugs during gestation and have a higher risk of being born prematurely and small for gestational age than the general ...population. We have prospectively followed up 27 children born to renal transplanted mothers from a single center and 31 healthy children born at term with adequate weight for gestational age. Comparisons of weight and length measurements were made at birth, 1 month (±0.9), 3 months (±1.0), 6 months (±1.0), 9 months (±1.5), and 12 months (±1.49) of age. There were a high rate of prematurity (51.9%) and neonates small for gestational age (40.7%) in the transplant group. At birth, in the transplant group, 28% of neonates had subnormal
z
-scores for weight and 40%, low
z
-scores for length. However, at 6 months of age, no significant differences were noticed in mean weight-for-age
z
-scores between groups (weight −0.43 vs −0.03; length −0.53 vs −0.08). At 12 months of age, comparable mean length-for-age
z
-scores were observed in both groups (weight 0.01 vs 0.27; length −0.07 vs 0.26).
Conclusion
: Despite high rates of premature births and neonates small for gestational age in the transplant group, there was a good recovery of growth during the first year..
What is Known:
•
Children born to renal transplanted mothers are exposed to immunosuppressive drugs during gestation
4
.
•
They have high risk of premature birth and fetal growth restriction, immune alterations at birth, and risk of hospitalization for infection in the first months of life
5
.
What is New:
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Despite high rates of premature birth and neonates small for gestational age, these infants had good growth recovery by 1 year of age.
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