RESUMO
Homophobic and transphobic beliefs that lead to bias-based harassment remain a critical concern for young people in the USA. The aim of the present study was to examine the impact of an inclusive comprehensive sex education program (High School FLASH) on homophobic and transphobic beliefs. Data from this study come from a randomized controlled trial that evaluated the impact of High School FLASH on students' sexual behaviors and related outcomes with 20 schools in two U.S. regions (Midwest and South). Following the baseline survey, the 20 schools were randomly assigned to receive FLASH or a comparison curriculum. Ninth and 10th grade students completed follow-up surveys 3 and 12 months after the instructional period. We examined changes in homophobic beliefs using multilevel linear regression models in the full sample and two sub-groups: straight cisgender young people versus those who identified as not straight or cisgender. Mean scores on the homophobic and transphobic beliefs scale were statistically significantly lower among young people receiving FLASH relative to the comparison at both the 3- and 12-month timepoints (p-values for adjusted mean differences were < 0.01, n = 1357 and 1275, respectively). Specifically, FLASH's positive impact on reducing homophobic and transphobic beliefs was statistically significant for straight and cisgender youth at both survey follow-ups (p < 0.01, n = 1144 and p = 0.05, n = 1078, respectively); the effects for the LGBTQ sub-group reached statistical significance at only the final follow-up (p = 0.01, n = 197). Our results show that carefully designed, inclusive comprehensive sexual health education programs like High School FLASH can play a role in promoting better school climates for all youth by reducing beliefs that may lead to bullying, violence, and victimization.
Assuntos
Bullying , Minorias Sexuais e de Gênero , Adolescente , Humanos , Educação Sexual , Homofobia/prevenção & controle , Instituições Acadêmicas , CurrículoRESUMO
We examine condom failure and use error experienced by high school youth in two regions of the United States. Data are from a baseline survey of a randomized controlled trial to evaluate FLASH, a sexual health education curriculum for high school students. Participants were 1,597 ninth- or 10th-grade students in health class who had parental consent and who assented to participate in the study. This study examines condom use behavior among students who reported vaginal or anal sex at baseline. Of the 222 participants who reported having vaginal or anal sex in the 3 months prior to baseline survey, 180 of them reported using a condom at least once. Of these youth, 70.6% reported that they did not squeeze the tip of the condom before sex, 25.0% of youth reported that they did not roll the condom all the way down to the base of the penis, and 49.4% reported that they did not hold the base of the penis when pulling out; 36.9% reported experiencing condom breakage or slippage. The frequency of condom error and/or failure reported by young adolescents in this study indicates a need for further education on potential condom use errors with an emphasis on the correct steps for using a condom to prevent condom failure. High rates of error and failure suggest an opportunity for educators to tailor preexisting condom use interventions to further reinforce the skills necessary for effective condom use and to educate on what to do in the event of condom failure.
Assuntos
Comportamento do Adolescente , Preservativos , Adolescente , Feminino , Humanos , Masculino , Instituições Acadêmicas , Comportamento Sexual , Estudantes , Estados UnidosRESUMO
BACKGROUND & AIMS: Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history. METHODS: A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status. RESULTS: AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status. CONCLUSION: As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.
Assuntos
Abdome/fisiopatologia , Fibrose Cística/fisiopatologia , Genótipo , Adolescente , Criança , Pré-Escolar , Fibrose Cística/genética , Fibrose Cística/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Human cytomegalovirus (HCMV) causes significant disease worldwide. Multiple HCMV vaccines have been tested in man but only partial protection has been achieved. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of neutralizing antibodies in HCMV seropositive individuals and raises high titers of neutralizing antibodies in small animals and non-human primates (NHP). Thus, Pentamer is a promising candidate for an effective HCMV vaccine. Development of a Pentamer-based subunit vaccine requires expression of high amounts of a functional and stable complex. We describe here the development of a mammalian expression system for large scale Pentamer production. Several approaches comprising three different CHO-originated cell lines and multiple vector as well as selection strategies were tested. Stable cell pools expressed the HCMV Pentamer at a titer of approximately 60 mg/L at laboratory scale. A FACS-based single cell sorting approach allowed selection of a highly expressing clone producing Pentamer at the level of approximately 400 mg/L in a laboratory scale fed-batch culture. Expression in a 50 L bioreactor led to the production of HCMV Pentamer at comparable titers indicating the feasibility of further scale-up for manufacturing at commercial scale. The CHO-produced HCMV Pentamer bound to a panel of human neutralizing antibodies and raised potently neutralizing immune response in mice. Thus, we have generated an expression system for the large scale production of functional HCMV Pentamer at high titers suitable for future subunit vaccine production.
Assuntos
Células CHO , Vacinas contra Citomegalovirus/imunologia , Expressão Gênica , Proteínas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Cricetulus , Citomegalovirus/genética , Vacinas contra Citomegalovirus/administração & dosagem , Vacinas contra Citomegalovirus/genética , Vacinas contra Citomegalovirus/metabolismo , Camundongos , Multimerização Proteica , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/metabolismo , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Introduction. P. aeruginosa is the primary cause for pulmonary destruction and premature death in cystic fibrosis (CF). Therefore, prevention of airway colonization with the pathogen, ubiquitously present in water, is essential. Infection of CF patients with P. aeruginosa after dentist treatment was proven and dental unit waterlines were identified as source, suggesting prophylactic measures. For their almost regular sinonasal involvement, CF patients often require otorhinolaryngological (ORL) attendance. Despite some fields around ORL-procedures with comparable risk for acquisition of P. aeruginosa, such CF cases have not yet been reported. We present four CF patients, who primarily acquired P. aeruginosa around ORL surgery, and one around dentist treatment. Additionally, we discuss risks and preventive strategies for CF patients undergoing ORL-treatment. Perils include contact to pathogen-carriers in waiting rooms, instrumentation, suction, drilling, and flushing fluid, when droplets containing pathogens can be nebulized. Postsurgery mucosal damage and debridement impair sinonasal mucociliary clearance, facilitating pathogen proliferation and infestation. Therefore, sinonasal surgery and dentist treatment of CF patients without chronic P. aeruginosa colonization must be linked to repeated microbiological assessment. Further studies must elaborate whether all CF patients undergoing ORL-surgery require antipseudomonal prophylaxis, including nasal lavages containing antibiotics. Altogether, this underestimated risk requires structured prevention protocols.
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The impact of transient gene expression approaches (TGE) on the rapid production of recombinant proteins is undisputed, despite that all efforts are currently relying on two host cell families only, namely HEK293 derivatives and CHO cell line(s). Yet, the increasing complexity of biological targets calls for more than two host cell types to meet the challenges of difficult-to-express proteins. For this reason, we evaluated the more recently established novel CAP-T® cell line derived from human amniocytes for its performance and potential in transient gene expression. Upon careful analyses and adaptation of all process parameters we show here that indeed the CAP-T® cells are extremely amenable to transient gene expression and recombinant protein production. Additionally, they possess inherent capabilities to express and secrete complex and difficult target molecules, thus adding an attractive alternative to the repertoire of existing host cell lines used in transient production processes.
Assuntos
Líquido Amniótico/citologia , Líquido Amniótico/metabolismo , Proteínas Recombinantes/biossíntese , Transfecção/métodos , Líquido Amniótico/química , Western Blotting , Linhagem Celular , Expressão Gênica , Humanos , Lipossomos/química , Plasmídeos/genética , Polietilenoimina/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genéticaRESUMO
Streptococcus infantarius subsp. infantarius belongs to the Streptococcus bovis/Streptococcus equinus complex (SBSEC) commonly associated with human and animal infections. We elucidated the lactose metabolism of S. infantarius subsp. infantarius predominant in African fermented milk products. S. infantarius subsp. infantarius isolates (n = 192) were identified in 88% of spontaneously fermented camel milk suusac samples (n = 24) from Kenya and Somalia at log10 8.2-8.5 CFU mL⻹. African S. infantarius isolates excreted stoichiometric amounts of galactose when grown on lactose, exhibiting a metabolism similar to Streptococcus thermophilus and distinct from their type strain. African S. infantarius subsp. infantarius CJ18 harbors a regular gal operon with 99.7-100% sequence identity to S. infantarius subsp. infantarius ATCC BAA-102(T) and a gal-lac operon with 91.7-97.6% sequence identity to S. thermophilus, absent in all sequenced SBSEC strains analyzed. The expression and functionality of lacZ was demonstrated in a ß-galactosidase assay. The gal-lac operon was identified in 100% of investigated S. infantarius isolates (n = 46) from suusac samples and confirmed in Malian fermented cow milk isolates. The African S. infantarius variant potentially evolved through horizontal gene transfer of an S. thermophilus-homologous lactose pathway. Safety assessments are needed to identify any putative health risks of this novel S. infantarius variant.
Assuntos
Produtos Fermentados do Leite/microbiologia , DNA Bacteriano/isolamento & purificação , Lactose/metabolismo , Streptococcus thermophilus/genética , Streptococcus/genética , Animais , Camelus , DNA Bacteriano/genética , Galactose/metabolismo , Genótipo , Quênia , Óperon Lac , Fenótipo , Análise de Sequência de DNA , Somália , Streptococcus/isolamento & purificação , Streptococcus/metabolismo , Streptococcus thermophilus/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismoRESUMO
BACKGROUND: Prevention and control of ovine enzootic abortion (OEA) can be achieved by application of a live vaccine. In this study, five sheep flocks with different vaccination and infection status were serologically tested using a competitive enzyme-linked immunosorbent assay (cELISA) specific for Chlamydophila (Cp.) abortus over a two-year time period. RESULTS: Sheep in Flock A with recent OEA history had high antibody values after vaccination similar to Flock C with natural Cp. abortus infections. In contrast, OEA serology negative sheep (Flock E) showed individual animal-specific immunoreactions after vaccination. Antibody levels of vaccinated ewes in Flock B ranged from negative to positive two and three years after vaccination, respectively. Positive antibody values in the negative control Flock D (without OEA or vaccination) are probably due to asymptomatic intestinal infections with Cp. abortus. Excretion of the attenuated strain of Cp. abortus used in the live vaccine through the eye was not observed in vaccinated animals of Flock E. CONCLUSION: The findings of our study indicate that, using serology, no distinction can be made between vaccinated and naturally infected sheep. As a result, confirmation of a negative OEA status in vaccinated animals by serology cannot be determined.
Assuntos
Aborto Animal/microbiologia , Anticorpos Antibacterianos/biossíntese , Vacinas Bacterianas/imunologia , Infecções por Chlamydophila/veterinária , Chlamydophila/imunologia , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/microbiologia , Aborto Animal/epidemiologia , Aborto Animal/imunologia , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Chlamydophila/genética , Infecções por Chlamydophila/epidemiologia , Infecções por Chlamydophila/imunologia , Infecções por Chlamydophila/prevenção & controle , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Reação em Cadeia da Polimerase/veterinária , Gravidez , RNA Ribossômico 23S/química , RNA Ribossômico 23S/genética , Estudos Soroepidemiológicos , Ovinos , Doenças dos Ovinos/epidemiologia , Suíça/epidemiologia , Vacinas Atenuadas/imunologiaRESUMO
UNLABELLED: Adding a small dose of ketamine to opioids may increase the analgesic effect and prevent opioid-induced hyperalgesia and acute tolerance to opioids. In this randomized, double-blinded, placebo-controlled crossover study, we investigated the effect of remifentanil combined with small concentrations of ketamine on different experimental pain models. Pain detection thresholds to single and repeated IM electrical stimulation and to repeated transcutaneous electrical stimulation, pressure pain tolerance threshold, and sedative, respiratory, and cardiovascular side effects were assessed in 14 healthy volunteers. Saline, remifentanil alone, and remifentanil combined with ketamine at target plasma concentrations of 50 or 100 ng/mL were administered in four study sessions. The ketamine infusion was started after baseline testing at a constant target concentration. Remifentanil was started after testing with ketamine alone at an initial target concentration of 1 ng/mL and then increased to 2 ng/mL and decreased to 1 ng/mL. The last test series were started 10 min after discontinuation of remifentanil. Acute remifentanil-induced hyperalgesia and tolerance were detected only by the pressure pain test and were not suppressed by ketamine. Remifentanil alone induced significant analgesia with all pain tests. Ketamine further increased the remifentanil effect only on IM electrical pain. Remifentanil at a 2 ng/mL target concentration induced a slight respiratory depression that was antagonized by ketamine. We conclude that ketamine effects on opioid analgesia are pain-modality specific. IMPLICATIONS: Coadministration of ketamine and morphine for pain relief is still controversial. Our experimental pain study with volunteers showed that ketamine enhances opioid analgesia without increasing sedation and reduces respiratory depression. Opioid-induced hyperalgesia and tolerance were not affected by ketamine and depended on the type of nociceptive stimulus. This may explain the conflicting results on opioid tolerance in previous studies.