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The mitochondrial ATP synthase emerges as key hub of cellular functions controlling the production of ATP, cellular signaling, and fate. It is regulated by the ATPase inhibitory factor 1 (IF1), which is highly abundant in neurons. Herein, we ablated or overexpressed IF1 in mouse neurons to show that IF1 dose defines the fraction of active/inactive enzyme in vivo, thereby controlling mitochondrial function and the production of mitochondrial reactive oxygen species (mtROS). Transcriptomic, proteomic, and metabolomic analyses indicate that IF1 dose regulates mitochondrial metabolism, synaptic function, and cognition. Ablation of IF1 impairs memory, whereas synaptic transmission and learning are enhanced by IF1 overexpression. Mechanistically, quenching the IF1-mediated increase in mtROS production in mice overexpressing IF1 reduces the increased synaptic transmission and obliterates the learning advantage afforded by the higher IF1 content. Overall, IF1 plays a key role in neuronal function by regulating the fraction of ATP synthase responsible for mitohormetic mtROS signaling.
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Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Proteínas/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , ATPases Mitocondriais Próton-Translocadoras/fisiologia , Cultura Primária de Células , Proteínas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proteína Inibidora de ATPaseRESUMO
Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx, MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d-7d for Myogenin. Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry.
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Toxinas Botulínicas Tipo A , Músculos da Mastigação , Adulto , Humanos , Camundongos , Masculino , Animais , Miogenina , Músculo Masseter/patologia , Músculo Masseter/fisiologia , Atrofia Muscular/patologia , RNA MensageiroRESUMO
OBJECTIVE: To know the impact of the educational intervention carried out on the professionals of a basic health area and their community participation group, which make up the intervention group (IG), and to analyze its repercussion on the vaccination coverage achieved for influenza in the risk group (pregnant and puerperal women) comparing it with its neighboring basic zone, which makes up the control group (CG), during the 2019/20 vaccination season. DESIGN: Quasi-experimental study of community intervention. SITE: Two basic health zones belonging to the Elche-Crevillente health department, Spain. PARTICIPANTS: Pregnant and postpartum women from 2 basic health areas and the community participation group. Health professionals directly related to the flu vaccination campaign. INTERVENTIONS: Training session for the IG prior to the 2019/20 flu campaign. MAIN MEASUREMENTS: Attitudes towards influenza vaccination in health professionals through the validated CAPSVA questionnaire and the vaccination coverage of pregnant and postpartum women through the Nominal Vaccine Registry and their acceptance of the vaccine in the midwife's office. RESULTS: The influenza vaccination coverage data recorded in Nominal Vaccine Registry for pregnant and puerperal women was 26.4% (n=207) in the IG and 19.7% (n=144) in the CG (p=0.001), with an incidence ratio of 1.34, thus achieving 34% more vaccination in the IG. Acceptance for vaccination in the midwife's office was also high, with 96.5% immunization in IG vs. 89.0% in CG, with a RR=1.09 (95% CI 1.01-1.62). CONCLUSIONS: Joint training strategies for professionals and community assets improve the results of vaccination coverage.
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Vacinas contra Influenza , Influenza Humana , Feminino , Humanos , Gravidez , Gestantes , Influenza Humana/prevenção & controle , Cobertura Vacinal , Estudos Transversais , VacinaçãoRESUMO
Optimal production of bispecific antibodies (bsAb) requires efficient and tailored co-expression and assembly of two distinct heavy and two distinct light chains. Here, we describe a novel technology to modulate the translational strength of antibody chains via Kozak sequence variants to produce bsAb in a single cell line. In this study, we designed and screened a large Kozak sequence library to identify 10 independent variants that can modulate protein expression levels from approximately 0.2 to 1.3-fold compared with the wild-type sequence in transient transfection. We used a combination of several of these variants, covering a wide range of translational strength, to develop stable single cell Chinese hamster ovary bispecific cell lines and compared the results with those obtained from the wild-type sequence. A significant increase in bispecific antibody assembly with a concomitant reduction in the level of product-related impurities was observed. Our findings suggest that for production of bsAb it can be advantageous to modify translational strength for selected protein chains to improve overall yield and product quality. By extension, tuning of translational strength can also be applied to improving the production of a wide variety of heterologous proteins.
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Anticorpos Biespecíficos/genética , Animais , Células CHO , Cricetulus , Biblioteca Gênica , Biossíntese de Proteínas , Proteínas Recombinantes de Fusão/genética , TransfecçãoRESUMO
Background and Objectives: To describe the knowledge and attitudes related to the acceptance of the flu vaccine during pregnancy in women, from two Health Departments of the Valencian Community (VC), during the 2015-2016 season, after receiving prenatal care. Materials and Methods: A prospective observational study was conducted during the annual vaccine season of women ascribed to prenatal care. A midwife offered flu vaccine advice and afterwards conducted a telephone poll of a representative sample, in order to find out the reason for accepting or rejecting the vaccine. Results: Of the 1017 expectant women who received advice about the vaccine, 77.4% (95% CI: 74.8-79.9%) declared their intention to vaccinate. After the recommendation, the vaccine coverage was 61.6%, with a percentage of accordance of 98.8% (95% CI: 98.0-99.6%) between the coverage declared and the Nominal Vaccination Registry (NVR) of the VC. Additionally, 67.2% of the expectant women were interviewed (n = 683). Most were aware of the recommendation and identified the health center and the midwife as the main sources of information. The internet was a consistent source in favor of vaccination 80.8% (n = 42). The obstetric variables (risk during the pregnancy, end of pregnancy, and feeding the newborn) did not have a statistically significant relationship with the vaccination. The women declared a high adherence to the vaccinations present in the child vaccination calendar, but rejected (31.3%) the flu vaccine, as they had not received it previously and did not want it because of their expectant state. Conclusions: The women positively evaluated the effectiveness and safety of the vaccines. However, with the flu vaccine, "not being previously vaccinated" and the "doubts about its safety" represented more than half of the reasons put forth for its rejection. Ensuring that the flu vaccine is perceived as more effective and acceptable through the messages directed towards the expectant mothers, directly through the midwives or through the communication media and social networks, will result in an increase of vaccine coverage.
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Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Influenza/uso terapêutico , Gestantes/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Gravidez , Estudos Prospectivos , Espanha , Vacinação/psicologiaRESUMO
Previous work has shown that, in cla4Δ cells of budding yeast, where septin ring organization is compromised, the chitin ring at the mother-daughter neck becomes essential for prevention of neck widening and for cytokinesis. Here, we show that it is not the chitin ring per se, but its linkage to ß(1-3)glucan that is required for control of neck growth. When in a cla4Δ background, crh1Δ crh2Δ mutants, in which the chitin ring is not connected to ß(1-3)glucan, grew very slowly and showed wide and growing necks, elongated buds and swollen cells with large vacuoles. A similar behavior was elicited by inhibition of the Crh proteins. This aberrant morphology matched that of cla4Δ chs3Δ cells, which have no chitin at the neck. Thus, this is a clear case in which a specific chemical bond between two substances, chitin and glucan, is essential for the control of morphogenesis. This defines a new paradigm, in which chemistry regulates growth.
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Parede Celular/metabolismo , Saccharomycetales/metabolismo , Parede Celular/ultraestrutura , Quitina/metabolismo , Glucanos/metabolismo , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Microscopia Eletrônica , Morfogênese/genética , Morfogênese/fisiologia , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomycetales/ultraestruturaRESUMO
The mechanical properties of fungal cell walls are largely determined by composition and mutual cross-linking of their macromolecular components. Previous work showed that the Crh proteins are required for the formation of cross-links between chitin and glucan at the Saccharomyces cerevisiae cell wall. In the present study, the proteins encoded by CRH1 and CRH2 were heterologously expressed in Pichia pastoris and a sensitive fluorescence in vitro soluble assay was devised for determination of their transglycosylating activities. Both proteins act as chitin transglycosylases; they use soluble chitin derivatives, such as carboxymethyl chitin, glycol-chitin and/or N-acetyl chito-oligosaccharides of DP (degree of polymerization)≥5 as the oligoglycosyl donors, and oligosaccharides derived from chitin, ß-(1,3)-glucan (laminarin) and ß-(1,6)-glucan (pustulan), fluorescently labelled with sulforhodamine or FITC as acceptors. The minimal number of intact hexopyranose units required by Crh1 and/or Crh2 in the molecule of the acceptor oligosaccharide was two and the effectivity of the acceptor increased with the increasing length of its oligosaccharide chain. Products of the transglycosylation reactions were hybrid molecules composed of the acceptor and portions of carboxymethyl chitin attached to its non-reducing end. Both proteins exhibited a weak chitinolytic activity in different assays whereby the ratio of endo- compared with exo-chitinase activity was approximately 4-fold higher in Crh1 than in Crh2. The pH optimum of both enzymes was 3.5 and the optimum temperature was 37°C. The results obtained in vitro with different fluorescently labelled oligosaccharides as artificial chitin acceptors corroborated well with those observed in vivo.
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Parede Celular/enzimologia , Glicosídeo Hidrolases/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/enzimologia , Catálise , Parede Celular/química , Parede Celular/metabolismo , Quitina/metabolismo , Fluoresceína-5-Isotiocianato/química , Fluorescência , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Concentração de Íons de Hidrogênio , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Temperatura , beta-Glucanas/metabolismoRESUMO
Previous results suggested that the chitin ring present at the yeast mother-bud neck, which is linked specifically to the nonreducing ends of ß(1-3)glucan, may help to suppress cell wall growth at the neck by competing with ß(1-6)glucan and thereby with mannoproteins for their attachment to the same sites. Here we explored whether the linkage of chitin to ß(1-3)glucan may also prevent the remodeling of this polysaccharide that would be necessary for cell wall growth. By a novel mild procedure, ß(1-3)glucan was isolated from cell walls, solubilized by carboxymethylation, and fractionated by size exclusion chromatography, giving rise to a very high-molecular-weight peak and to highly polydisperse material. The latter material, soluble in alkali, may correspond to glucan being remodeled, whereas the large-size fraction would be the final cross-linked structural product. In fact, the ß(1-3)glucan of buds, where growth occurs, is solubilized by alkali. A gas1 mutant with an expected defect in glucan elongation showed a large increase in the polydisperse fraction. By a procedure involving sodium hydroxide treatment, carboxymethylation, fractionation by affinity chromatography on wheat germ agglutinin-agarose, and fractionation by size chromatography on Sephacryl columns, it was shown that the ß(1-3)glucan attached to chitin consists mostly of high-molecular-weight material. Therefore, it appears that linkage to chitin results in a polysaccharide that cannot be further remodeled and does not contribute to growth at the neck. In the course of these experiments, the new finding was made that part of the chitin forms a noncovalent complex with ß(1-3)glucan.
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Quitina/metabolismo , Glucanos/metabolismo , Saccharomyces cerevisiae/metabolismo , Configuração de Carboidratos , Parede Celular/química , Parede Celular/metabolismo , Parede Celular/fisiologia , Fracionamento Químico , Quitina/química , Quitina/isolamento & purificação , Técnicas de Inativação de Genes , Glucana Endo-1,3-beta-D-Glucosidase/química , Glucanos/química , Glucanos/isolamento & purificação , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Peso Molecular , Reprodução Assexuada , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Hidróxido de Sódio/química , Solventes/químicaRESUMO
The eyes are in constant movement to optimize the interpretation of the visual scene by the brain. Eye movements are controlled by complex neural networks that interact with the rest of the brain. The direction of our eye movements could thus be influenced by our cognitive activity (imagination, internal dialogue, memory, etc.). A given cognitive activity could then cause the gaze to move in a specific direction (a brief movement that would be instinctive and unconscious). Neuro Linguistic Programming (NLP), which was developed in the 1970s by Richard Bandler and John Grinder (psychologist and linguist respectively), issued a comprehensive theory associating gaze directions with specific mental tasks. According to this theory, depending on the visual path observed, one could go back to the participant's thoughts and cognitive processes. Although NLP is widely used in many disciplines (communication, psychology, psychotherapy, marketing, etc), to date, few scientific studies have examined the validity of this theory. Using eye tracking, this study explores one of the hypotheses of this theory, which is one of the pillars of NLP on visual language. We created a protocol based on a series of questions of different types (supposed to engage different brain areas) and we recorded by eye tracking the gaze movements at the end of each question while the participants were thinking and elaborating on the answer. Our results show that 1) complex questions elicit significantly more eye movements than control questions that necessitate little reflection, 2) the movements are not random but are oriented in selected directions, according to the different question types, 3) the orientations observed are not those predicted by the NLP theory. This pilot experiment paves the way for further investigations to decipher the close links between eye movements and neural network activities in the brain.
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Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.
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Healthcare professionals must play an exemplary role in the field of vaccinology. It is convenient that they are trained during their time at university. The objective of this study was to determine the acceptability of the vaccines against COVID-19 in health sciences students in Spanish universities. A cross-sectional study was performed regarding the acceptance of the vaccines against COVID-19 in students in the Health Sciences Degrees in Spanish universities was performed on a sample of students of nursing, medicine, and pharmacy during the spring of 2021, via an online questionnaire with 36 questions designed ad hoc, self-administered, anonymized, and standardized. There were 1222 students participating, of Spanish nationality (97.4%), women (80.5%) and with an average age of 22.0 ± 4.8 years old. Of those, 12.3% had had the disease, 44.0% had to quarantine, 70.8% had undergone diagnostic tests, out of which 14.1% were positive. In total, 97.5% of those surveyed indicated their desire of being vaccinated, if possible, with Comirnaty® (74.9%). At the time of the study, 49.6% were already vaccinated. The reasons for vaccination differed according to the degree and the doubts about vaccine safety was the largest reason for reluctance. Some 37.7% suspected that there are unknown adverse effects and 85.6% of those vaccinated experienced some mild effects after injection. Vaccine acceptance and confidence in the recommendations given by health authorities is high in health sciences students.
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COVID-19 , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Infecções por Papillomavirus/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Estudantes , Universidades , Vacinação , Adulto JovemRESUMO
Due to the COVID-19 pandemic, physical therapists have had to adopt a set of specific protection measures, which have had an impact on their clinical activity and economy. The objective was to evaluate the impact of the COVID-19 pandemic on the work of Spanish physical therapists, as well as their attitudes and predisposition to vaccination. An online questionnaire was divided into five sections: (1) demographic and professional data; (2) labor impact; (3) precautions and infection-control measures; (4) economic impact; and (5) vaccine acceptance and adverse effects. Of the 666 participants, 62.1% showed a reduction in their working hours motivated by: fear of infection (p = 0.007), financial issues (p = 0.002) and being in quarantine or isolation (p < 0.001). Of these, 36.4% were forced to close the clinic, 62.7% requested help from the government, but only 12.04% mentioned that it was adequate. The main prevention measures adopted were the use of gels and masks and, in the private sector, disinfection with ozone or ultraviolet light (p < 0.05). The acceptance of the vaccine was high, 87.5%, being lower among the group over 40 years of age, self-employed, widowed or separated. More adverse effects were mentioned after receiving the AstraZeneca-Oxford vaccine, compared to Pfizer-BioNTech or Moderna. In conclusion, this study assessed for the first time that the COVID-19 pandemic in Spain had a negative impact on work and finances of physical therapists. The vaccine was widely accepted, in part by the economic impact that an infection in the work setting could signify.
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COVID-19 , Influenza Humana , Fisioterapeutas , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Influenza Humana/epidemiologia , Pessoa de Meia-Idade , Pandemias , VacinaçãoRESUMO
This study analyses the obstetric−neonatal outcomes of women in labour with symptomatic and asymptomatic COVID-19. A retrospective, multicenter, observational study was carried out between 1 March 2020 and 28 February 2021 in eight public hospitals in the Valencian community (Spain). The chi-squared test compared the obstetric−neonatal outcomes and general care for symptomatic and asymptomatic women. In total, 11,883 births were assisted in participating centers, with 10.9 per 1000 maternities (n = 130) infected with SARS-CoV-2. The 20.8% were symptomatic and had more complications both upon admission (p = 0.042) and during puerperium (p = 0.042), as well as transfer to the intensive care unit (ICU). The percentage of admission to the Neonatal Intensive Care Unit (NICU) was greater among offspring of symptomatic women compared to infants born of asymptomatic women (p < 0.001). Compared with asymptomatic women, those with symptoms underwent less labour companionship (p = 0.028), less early skin-to-skin contact (p = 0.029) and greater mother−infant separation (p = 0.005). The overall maternal mortality rate was 0.8%. No vertical transmission was recorded. In conclusion, symptomatic infected women are at increased risk of lack of labour companionship, mother−infant separation, and admission to the ICU, as well as to have preterm births and for NICU admissions.
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COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , COVID-19/epidemiologia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Estudos Retrospectivos , SARS-CoV-2RESUMO
Vaccine hesitancy has increased in the past few years, influenced by the socio-cultural differences, political populism, or concerns related to the effectiveness and safety of some vaccines, resulting a feeling of distrust. This feeling can become a barrier against the achievement of the immunity necessary to stop the expansion of COVID-19. The aim of this study was to evaluate the acceptance of the vaccine against COVID-19 in Spain, as well as to identify the factors that have an influence on the concerns and attitudes of people against accepting the vaccine in the months prior to the start of vaccination on December 2020. An online questionnaire was created to obtain information about (1) sociodemographic characteristics; (2) concerns and sources of information about vaccines; and (3) attitudes about vaccination and state of health. A multivariate logistic regression was performed to identify the influencing factors. Of the 2501 participants, 1207 (48.3%) would accept the COVID-19 vaccine, 623 (24.9%) were hesitant, and 671 (26.8%) would reject it. The logistic regression showed that being male, older than 60, married, retired, with a high level of education, or with a leftist political inclination, could increase the probability of accepting the COVID-19 vaccine. Disinformation and the lack of political consensus were the main sources of distrust. The patients with hypertension, immunodepression, hypercholesterolemia, or respiratory disease, or were overweight, showed a greater acceptance to the vaccine, while those with cancer took the longest to accept it. A low acceptance of the vaccine against COVID-19 was observed among the Spanish population in the phase prior to its availability, and the main fears of the population were identified. It is necessary to offer correct and transparent information about these vaccines to reduce the concerns and increase the trust of the population, to thereby guarantee the success of the vaccination campaigns.
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Vacinas contra COVID-19 , COVID-19 , Estudos Transversais , Humanos , Masculino , SARS-CoV-2 , Espanha , VacinaçãoRESUMO
Health professionals are the most influential and main sources of information about vaccines for the general population, as they are regarded as role models by patients and society. The objective of the present study was to determine the knowledge and attitudes of a group of university Nursing students about vaccines, as well as their sources of information and their education needs. A cross-sectional study was performed through a questionnaire (55 items) provided to Nursing students at two Spanish universities. A total of 1122 students participated in the study. The mean score obtained for knowledge about vaccines was 44.6 ± 4.3, and for attitudes towards vaccines, it was 37.2 ± 3.9. Hepatitis B (94.7%) and the Flu (89%) are the two main vaccines they should receive as health workers. The main source of information was the family environment (65.6%). Most of them considered that post-graduate education about vaccines should be provided by academic entities (universities, 62.7%). Among the health professionals, Nurses (85.5%) must be better educated and trained on the subject of vaccines. It is therefore necessary to delve into and complete the nurses' training on vaccines, to educate them about the risks at the individual level, and their decisive role as promoters of the vaccination strategy for the general population. Universities must become the leaders in vaccine education and training.
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Estudantes de Enfermagem , Vacinas , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inquéritos e Questionários , Universidades , VacinaçãoRESUMO
A good perception of the vaccines administered during pregnancy favors immunization coverage, which is still not optimal for the influenza vaccine. To understand the predisposition towards vaccination in future pregnancies, a study was performed that evaluated the experiences of women with the vaccine or influenza. A cross-sectional study was conducted through telephone interviews given to a total of 683 postpartum women in two health departments from the Valencia Community (Spain). This interview asked about their intention of becoming vaccinated in future pregnancies and whether they were favor or against vaccination. Most of them, 98.5% (n = 673 [95% CI: 97.6-99.4]) (p < 0.001) declared having received the systematic vaccines throughout their lives. The ones who were vaccinated against influenza, 91.9% (n = 387 [95% CI: 89.2-94.6]) (p < 0.001) manifested they would do so in future pregnancies. The probability of future non-vaccination was modeled, which was related to an unfavorable opinion towards vaccines (OR = 4.07 [95% CI: 2.01-8.24]) (p < 0.001), having suffered from influenza during pregnancy (OR = 3.84 [95% CI: 1.41-10.42]) (p < 0.05), and not having been vaccinated during previous pregnancies (OR = 38.47 [95% CI: 23.58-62.76]) (p < 0.001). Vaccination during pregnancy increases the intent of vaccination in the future.
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Chinese hamster ovary (CHO) cells have been adapted to grow in serum-free media and in suspension culture to facilitate manufacturing needs. Some CHO cell lines, however, tend to form cell aggregates while being cultured in suspension. This can result in reduced viability and capacity for single cell cloning (SCC) via limiting dilution, and process steps to mitigate cell aggregate formation, for example, addition of anti-cell-aggregation agents. In this study, we have identified endothelial intercellular cell adhesion molecule 1 (ICAM-1) as a key protein promoting cell aggregate formation in a production competent CHO cell line, which is prone to cell aggregate formation. Knocking out (KO) the ICAM-1 gene significantly decreased cell aggregate formation in the culture media without anti-cell-aggregation reagent. This trait can simplify the process of transfection, selection, automated clone isolation, and so on. Evaluation in standard cell line development of ICAM-1 KO and wild-type CHO hosts did not reveal any noticeable impacts on titer or product quality. Furthermore, analysis of a derived nonaggregating cell line showed significant reductions in expression of cell adhesion proteins. Overall, our data suggest that deletion of ICAM-1 and perhaps other cell adhesion proteins can reduce cell aggregate formation and improve clonality assurance during SCC.
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Adesão Celular/efeitos dos fármacos , Agregação Celular/genética , Molécula 1 de Adesão Intercelular/genética , Animais , Células CHO/efeitos dos fármacos , Células Clonais/efeitos dos fármacos , Cricetinae , Cricetulus , Meios de Cultura Livres de Soro/farmacologia , Regulação da Expressão Gênica/genética , Técnicas de Inativação de Genes , HumanosRESUMO
OBJECTIVE: To estimate the prevalence of immunity against Hepatitis B virus among all healthcare workers linked to the Departments of Public Health in Torrevieja and Elx-Crevillent,two municipalities in the Valencian Community, Spain. METHODS: Cross-sectional descriptive study of healthcare workers in two different public health departments. Once the sample was obtained, the anti-hepatitis B surface antibody (anti-HBsAb) levels were abstracted based on serological test results recorded in the workers' medical records. Titers of anti-HBsAB ≥10mlU / ml were considered as evience of immunity. The variables analyzed were classified by department, gender, age (18-34; 35-49;≥50 years); professional category (physicians / nursing / other health personnel / nonhealth personnel); service at risk of contagion (Yes / No); immunity (≥10mlU/ml, ã10mlU/ml,missing) and systematic anti-HBs vaccination by date of birth (Yes / No). RESULTS: The study population consisted of 2674 workers. The highest proportions of workers were female(68.8%), between 35 and 49 years of age (52.8%), and employed in nursing,(32.2%). Overall, 74.9% of employees had evidence of hepatitis B immunity, 11.3% had no inmunity, and 13.8% was missing information on serology. Among those employees with serological information (n=2306), lack of immunity was highest among males (17.8%).Protective titers were inversely proportional to age, with the lowest titers being found in the oldest age groups. Non-healthcare personnel and physicians also had lower levels of protection (36.9% and 11.1%, respectively). CONCLUSIONS: Despite identifying high levels of immunity among healthcare workers, the percentages of non-immunized employees and those lacking immunological information underscores the need to implement new communication strategies aimed at these at-risk groups.
OBJETIVO: Estimar la prevalencia de inmunización frente al virus de la Hepatitis B del personal sanitario, vinculado a los Departamentos de Salud de Torrevieja y Elche-Crevillente, de la Comunidad Valenciana. MÉTODOS: Estudio descriptivo transversal en todos los trabajadores sanitarios de dos departamentos de Salud. Obtenida la muestra se identificó los niveles de anticuerpos de superficie del virus de la Hepatitis B a través de los resultados serológicos ubicados en las historias clínicas. Se consideró inmunizado a títulos de anti-HBs ≥10mlU/ml. Las variablesanalizadas fueron categorizadas según: Departamento; Género; Edad (18-34; 35-49; >50años); categoría profesional (facultativos/Enfermería/Otro personal sanitario/Personal no sanitario); Servicio riesgo contagio (Si/No); Inmunidad (≥10mlU/ml / ã10mlU/ml / No Dato) y Vacunacion sistemática anti-HBs según fecha nacimiento (Si/No). RESULTADOS: El personal estudiado ascendió a 2674. Predominó el género femenino 68,8%, el grupo de edad 35-49 años, 52,8%, y la categoría profesional de Enfermería, 32,2%. Un 74,9% de los resultados serológicos identificaron niveles de protección anti-HBs, frente al 11,3% no inmune, y un 13,8% que no disponían de información. Del personal con información serológica (2306), obtuvieron porcentajes de no protección más elevadas la categoría masculina, 17,8%. Los niveles de protección fueron inversamente proporcionales según la variable edad, menor inmunidad a mayor edad. El personal no sanitario y los facultativosarrojaron niveles de protección más bajos, 36,9% y 11,1% respectivamente. CONCLUSIONES: A pesar de identificarse una inmunidad elevada, el porcentaje de no inmunizadosy de ausencia de información inmunológica plantea la necesidad de implementar nuevas estrategias de comunicación dirigidas a este colectivo.
Assuntos
Pessoal de Saúde/estatística & dados numéricos , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Hepatite B/sangue , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Pública , Características de Residência , Espanha/epidemiologia , Adulto JovemRESUMO
Background: Pregnant women should receive two vaccines during pregnancy due to maternal-foetal complications and risks as well as the influenza and pertussis vaccinations. The goal was to evaluate vaccination coverage against influenza and pertussis in pregnant women, following midwife professional advice during the pregnancy follow-up; Methods: Prospective cohort study of 1017 pregnancies during the vaccination campaign in 2015â»2016. To estimate the degree of consistency between the coverage declared by mothers and that registered in the Nominal Vaccination Registry (NVR), we used the Cohen's kappa index (k); Results: 95.4% were registered in the NVR. Vaccination coverage recorded against influenza was 64.2% (95% CI: 61.2â»67.2), and 89.8% (95% CI: 87.9â»91.7) against pertussis. The coverage of the pregnant women interviewed was 61.7% (95% CI: 58.1â»67.3)) for influenza and 92.3% (95% CI: 91.4â»95.3) for pertussis. Subsequent interviews of 67.2% of the women produced a kappa agreement index between the data obtained from interviews and those recorded in the NVR of 0.974 (IC95%: 98.0â»99.6) for influenza, and 0.921 (IC95%: 98.1â»99.7) for pertussis. The women identified midwives as the main source of vaccination information and advice 88.4% (IC95%: 85.8â»90.9); Conclusions: The NVR is an effective platform for estimating immunisation coverage in pregnant women. The degree of agreement between declared vaccinations and registered vaccinations was high for both vaccines.
Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Vacina contra Coqueluche/uso terapêutico , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Cobertura Vacinal/estatística & dados numéricos , Coqueluche/prevenção & controle , Adulto , Feminino , Humanos , Programas de Imunização , Gravidez , Estudos Prospectivos , Sistema de Registros , EspanhaRESUMO
Incidental learning allows us to extract statistical relations between events in our daily lives without the intention to learn them. Whereas anticipation during intentional associative learning has been linked to increased and decreased theta band activity, comparatively little research has focused on incidental learning. The study of such a pervasive mechanism of incidental learning faces the challenge of finding an appropriate paradigm. Similarly, while posterior alpha band activity has been shown to facilitate attention to a predictable target location, it is not clear whether alpha power could mediate attention given other predictive information; e.g., when the only available information provided by the cue is the likelihood of the target outcome. Here we used a stimulus-stimulus associative learning task to investigate whether a cue carries information on its contingent relationship with a target outcome, not only when their relationship is learned intentionally but also when it could be learned incidentally. Moreover, by presenting the target outcome in a visual search task, we were also able to study whether anticipatory attention can be modulated by the intentional or the incidental knowledge of the likelihood of a target outcome given a predictive (or non-predictive) cue. Participants were exposed to streams of cue-target outcome trials, where one of two possible cues and one of two possible outcomes were displayed. Intention to learn was manipulated by asking participants to assess whether one of the target outcomes (the intentional one) was more likely to appear following one of the cues (the intentional one). Any learning regarding the other cue-outcome relationship would be incidental. We found that frontal and temporal theta band activity were sensitive to the predictive value of a cue (predictive cues elicited lower theta power). Moreover, left temporal theta was sensitive to the intention to learn associations (theta activity elicited by intentional learning cues was higher). Alpha power, by contrast, was not modulated by cue predictiveness of the target outcome. These findings suggest that theta band activity carries information about the predictive value of a cue. The topographical differences between theta for intentional and incidental learning suggest distinct cortical networks activated depending on whether the relationship between a cue and an outcome has been learned intentionally or incidentally.