Autoimmune hepatitis: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management.

Protocol for the isolation of mouse muscle stem cells using fluorescence-activated cell sorting.

Muscle stem cells (MuSCs) are the building blocks for regenerating skeletal muscle after trauma. If we intend to maximize the therapeutic potential of MuSCs, we must further study their molecular and functional properties. Here, we present a protocol for the isolation of mouse MuSCs via a two-step enzymatic and mechanical dissociation of skeletal muscle coupled with fluorescence-activated cell sorting (FACS). FACS-isolated MuSCs can be used for various downstream applications including cell culture, cell transduction, immunofluorescence, and gene expression assays. For complete details on the use and execution of this protocol, please refer to Almada et al. (2021).1.

Chromium Recovery from Chromium-Loaded Cupressus lusitanica Bark in Two-Stage Desorption Processes.

Hexavalent chromium (Cr(VI)) contamination poses serious health and environmental risks. Chromium biosorption has been employed as an effective means of eradicating Cr(VI) contamination. However, research on chromium desorption from chromium-loaded biosorbents is scarce despite its importance in facilitating industrial-scale chromium biosorption. In this study, single- and two-stage chromium desorption from chromium-loaded Cupressus lusitanica bark (CLB) was conducted. Thirty eluent solutions were evaluated first; the highest single-stage chromium desorption efficiencies were achieved when eluent solutions of 0.5 M NaOH, 0.5 M H2SO4, and 0.5 M H2C2O4 were used. Subsequently, two-stage kinetic studies of chromium desorption were performed. The results revealed that using 0.5 M NaOH solution in the first stage and 0.5 M H2C2O4 in the second stage enabled the recovery of almost all the chromium initially bound to CLB (desorption efficiency = 95.9-96.1%) within long (168 h) and short (3 h) desorption periods at each stage. This study clearly demonstrated that the oxidation state of the recovered chromium depends on the chemical nature and concentration of the eluent solution. The results suggest the possible regeneration of chromium-loaded CLB for its subsequent use in other biosorption/desorption cycles.

A stimulus-contingent positive feedback loop enables IFN-ß dose-dependent activation of pro-inflammatory genes.

Type I interferons (IFN) induce powerful antiviral and innate immune responses via the transcription factor, IFN-stimulated gene factor (ISGF3). However, in some pathological contexts, type I IFNs are responsible for exacerbating inflammation. Here, we show that a high dose of IFN-ß also activates an inflammatory gene expression program in contrast to IFN-λ3, a type III IFN, which elicits only the common antiviral gene program. We show that the inflammatory gene program depends on a second, potentiated phase in ISGF3 activation. Iterating between mathematical modeling and experimental analysis, we show that the ISGF3 activation network may engage a positive feedback loop with its subunits IRF9 and STAT2. This network motif mediates stimulus-specific ISGF3 dynamics that are dependent on ligand, dose, and duration of exposure, and when engaged activates the inflammatory gene expression program. Our results reveal a previously underappreciated dynamical control of the JAK-STAT/IRF signaling network that may produce distinct biological responses and suggest that studies of type I IFN dysregulation, and in turn therapeutic remedies, may focus on feedback regulators within it.

Improved charge-transfer resonance in graphene oxide/ZrO2 substrates for plasmonic-free SERS determination of methyl parathion.

This work reports a sensitive SERS substrate based on graphene oxide (GO) and quantum-sized ZrO2 nanoparticles (GO/ZrO2) for label-free determination of the organophosphate pesticide methyl parathion (MP). The enhanced light-matter interactions and the consequent SERS effect in these substrates resulted from the effective charge transfer (CT) mechanism attributed to synergistic contributions of three main factors: i) the strong molecular adherence of the MP molecules and the ZrO2 surface which allows the first layer-effect, ii) the relatively abundant surface defects in low dimensional ZrO2 semiconductor NPs, which act as intermediate electronic states that reduce the large bandgap barrier, and iii) the hindered charge recombination derived from the transference of the photoinduced holes to the GO layer. This mechanism allowed an enhancement factor of 8.78 × 104 for GO/ZrO2-based substrates, which is more than 5-fold higher than the enhancement observed for platforms without GO. A detection limit of 0.12 µM was achieved with an outstanding repeatability (variation ≤4.5%) and a linear range up to 10 µM, which is sensitive enough to determine the maximal MP concentration permissible in drinking water according to international regulations. Furthermore, recovery rates between 97.4 and 102.1% were determined in irrigation water runoffs, strawberry and black tea extracts, demonstrating the reliability of the hybrid GO/ZrO2 substrate for the organophosphate pesticides quantification in samples related to agri-food sectors and environmental monitoring.

Marketplace and Literature Review of Spanish Language Mental Health Apps.

Language differences between patients and providers remains a barrier to accessing health care, especially mental health services. One potential solution to reduce inequities for patients that speak different languages and improve their access to care is through the delivery of healthcare through mobile technology. Given that the Latinx community serves as the largest ethnic minority in the United States, this two-phased review examines Spanish app development, feasibility and efficacy. Phase 1 explored the commercial marketplace for apps available in Spanish, while phase 2 involved a literature review of published research centered around the creation, functions, and usability of these apps using the PubMed and Google Scholar electronic databases. Of the apps available on the database, only 14.5% of them had Spanish operability. The literature search uncovered 629 results, of which 12 research articles that tested or described 10 apps met the inclusion criteria. Of the 10 apps studied in this literature review, only four apps were translated to Spanish. Our study reveals that despite increasing interest in Spanish-language apps to address mental health, the commercial marketplace is not currently meeting the demand.

Corncob as an effective, eco-friendly, and economic biosorbent for removing the azo dye Direct Yellow 27 from aqueous solutions.

The corncob is an agricultural waste generated in huge quantities during corn processing. In this paper, we tested the capacity of corncob particles for water purification by removing the azo dye Direct Yellow 27 (DY27) via biosorption. The biosorption process was investigated in terms of the kinetics, equilibria, and thermodynamics. Batch biosorption studies showed that the biosorption performance has strong inverse correlations to the solution pH and the corncob particle size, and it increases quickly with increasing contact time and initial dye concentration. The pseudo-second-order kinetic model provides the best fit to the experimental data, whereas the Redlich-Peterson isotherm model is most suitable for describing the observed equilibrium biosorption. The biosorption process is exothermic, spontaneous, and physisorption in character. Fourier transform infrared (FTIR) spectroscopy and confocal scanning laser microscopy (CSLM) studies suggest that lignocellulose and proteins play key roles in the biosorption of DY27 from aqueous solutions by corncob. Furthermore, after biosorption onto the corncob, the dye can be effectively desorbed using 0.1 M NaOH solution. Therefore, the corncob can be used as a promising biosorbent to remediate DY27-contaminated water and wastewater.

[Statement of the Advisory Immunization Committee of the Chilean Society of Infectious Diseases on the emergence of serotype 19A pneumococcal infection and the use of pneumococcal conjugated vaccine in Chilean children]. / Opinión del Comité Consultivo de Inmunizaciones Sociedad Chilena de Infectología: Vacuna neumocóccica conjugada en niños y la emergencia de serotipo 19A.

Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.

Opinión del Comité Consultivo de Inmunizaciones Sociedad Chilena de Infectología: Vacuna neumocóccica conjugada en niños y la emergencia de serotipo 19A / Statement of the Advisory Immunization Committee of the Chilean Society of Infectious Diseases on the emergence of serotype 19A pneumococcal infection and the use of pneumococcal conjugated vaccine in Chilean children

La incorporación de la vacuna conjugada antineumocóc-cica 10 valente (PCV10) en lactantes en Chile el año 2011 ha permitido reducir las hospitalizaciones y muertes por neumonía en este grupo etario. Sin embargo, se ha observado desde entonces un aumento progresivo de los aislados de Streptococcus pneumoniae del serotipo 19A no incluido en la vacuna en uso (de < 5% del total de cepas recibidas en el Laboratorio de Referencia Nacional del Instituto de Salud Pública para vigilancia de infecciones invasores causadas por S. pneumoniae hasta el año 2010, a 12-23% en los años 2014-2015). En lactantes, el serotipo 19A representaba 4 a 8% de los aislados en la era pre vacuna, porcentaje que se incrementa a 25% el 2014. Este aumento ha ocurrido en dos terceras partes de las regiones administrativas del país. Cepas del serotipo 19A de pacientes menores de 5 años, muestran 25% de resistencia a penicilina para aislados extra-meníngeos y casi 100% para aislados de meningitis. El análisis genético de las cepas del serotipo 19A ha demostrado que 48% pertenecen al complejo clonal 320 de carácter pandémico y asociado a resistencia antimicrobiana. Además, casi todas las infecciones invasoras por serotipo 19A en niños se han dado en pacientes con esquema completo de vacunación PCV10. Los cambios epidemiológicos presentados indican la emergencia de infecciones invasoras por el serotipo 19A y la necesidad de controlar este problema con el cambio de la vacuna PCV10 a la vacuna PCV13 que contiene el serotipo 19A.

Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.

Chromium Biosorption from Cr(VI) Aqueous Solutions by Cupressus lusitanica Bark: Kinetics, Equilibrium and Thermodynamic Studies.

The present study investigated the kinetics, equilibrium and thermodynamics of chromium (Cr) ion biosorption from Cr(VI) aqueous solutions by Cupressus lusitanica bark (CLB). CLB total Cr biosorption capacity strongly depended on operating variables such as initial Cr(VI) concentration and contact time: as these variables rose, total Cr biosorption capacity increased significantly. Total Cr biosorption rate also increased with rising solution temperature. The pseudo-second-order model described the total Cr biosorption kinetic data best. Langmuir´s model fitted the experimental equilibrium biosorption data of total Cr best and predicted a maximum total Cr biosorption capacity of 305.4 mg g(-1). Total Cr biosorption by CLB is an endothermic and non-spontaneous process as indicated by the thermodynamic parameters. Results from the present kinetic, equilibrium and thermodynamic studies suggest that CLB biosorbs Cr ions from Cr(VI) aqueous solutions predominantly by a chemical sorption phenomenon. Low cost, availability, renewable nature, and effective total Cr biosorption make CLB a highly attractive and efficient method to remediate Cr(VI)-contaminated water and wastewater.

Natural decrease of dissolved arsenic in a small stream receiving drainages of abandoned silver mines in Guanajuato, Mexico.

Arsenic release from the abandoned mines and its fate in a local stream were studied. Physicochemical parameters, metals/metalloids and arsenic species were determined. One of the mine drainages was found as a point source of contamination with 309 µg L(-1) of dissolved arsenic; this concentration declined rapidly to 10.5 µg L(-1) about 2 km downstream. Data analysis confirmed that oxidation of As(III) released from the primary sulfide minerals was favored by the increase of pH and oxidation reduction potential; the results obtained in multivariate approach indicated that self-purification of water was due to association of As(V) with secondary solid phase containing Fe, Mn, Ca.

Persistence of antibodies in adolescents 18-24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine.

We previously demonstrated the immunogenicity and tolerability of the serogroup B meningococcal vaccine, 4CMenB (Bexsero), in 11-17 y-olds randomized to receive 1, 2, or 3 doses at 1, 2, or 6 mo intervals. Participants in this extension study provided an additional blood sample 18-24 mo after last vaccine dose, to assess persistence of serum bactericidal activity with human complement (hSBA), and to compare with age-matched 4CMenB-naïve controls. In the original study, one month after one 4CMenB dose, 93% of subjects had seroprotective hSBA titers (≥4) against indicator serogroup B strains for individual vaccine antigens (fHbp, NadA and NZOMV), increasing to ~100% after two or three doses. After 18-24 mo, 62-73% of subjects given one dose had titers ≥4 against the three antigens, significantly lower rates than after two (77-94%) or three (86-97%) doses. Only proportions with titers ≥ 4 against NZOMV were significantly different between the two (77%) and three (90%, p < 0.0001) dose groups. These results confirm that two doses of 4CMenB, administered 1 to 6 mo apart, provide good levels of bactericidal activity against serogroup B meningococci, which were sustained at least 18-24 mo in over 64% of adolescents for all three tested vaccine-related antigens.

[Modification of pertussis vaccination schedule in Chile, immunization of special groups and control strategies: Commentary from the Consultive Committee of Immunizations of The Chilean Society of Infectious Diseases]. / Modificación en el esquema de vacunación antipertussis en Chile, vacunación en grupos especiales y estrategias de control: Comentario del Comité Consultivo de Inmunizaciones (CCI) de la Sociedad Chilena de Infectología.

In Chile, an increased number of notifications of cases of whooping cough was detected at the beginning of October 2010, and maintained through 2012. Accumulated cases during 2011 were 2,581 (15.0 per 100,000), which is greater than the number of cases registered during the period 2008-2010 (2,460 cases). On the other hand, the local sanitary authority introduced a modification of pertussis vaccination schedule (starting 2012), which consists in the replacement of the second booster of pertussis vaccine (DTwP, administered to 4-year-old children) as well as diphtheria-tetanus toxoid (dT, administered to second grade scholars) for an acellular pertussis vaccine with reduced antigenic content (dTpa), which will be administrated to first grade scholars. The Consultive Committee of Immunizations considers that the modification is adequate, since it extends the age of protection, reducing at least in theory the infection in older scholars and adolescents -who are significant sources of transmission of Bordetella pertussis to infants- using an adequate vaccine formulation (acellular pertussis vaccine). The available evidence regarding vaccination in special groups (adolescents and adults, health-care workers and pregnant women) and cocooning strategy are commented.

Modificación en el esquema de vacunación antipertussis en Chile, vacunación en grupos especiales y estrategias de control: Comentario del Comité Consultivo de Inmunizaciones (CCI) de la Sociedad Chilena de Infectología / Modification of pertussis vaccination schedule in Chile, immunization of special groups and control strategies: Commentary from the Consultive Committee of Immunizations of The Chilean Society of Infectious Diseases

In Chile, an increased number of notifications of cases of whooping cough was detected at the beginning of October 2010, and maintained through 2012. Accumulated cases during 2011 were 2,581 (15.0 per 100,000), which is greater than the number of cases registered during the period 2008-2010 (2,460 cases). On the other hand, the local sanitary authority introduced a modification of pertussis vaccination schedule (starting 2012), which consists in the replacement of the second booster of pertussis vaccine (DTwP, administered to 4-year-old children) as well as diphtheria-tetanus toxoid (dT, administered to second grade scholars) for an acellular pertussis vaccine with reduced antigenic content (dTpa), which will be administrated to first grade scholars. The Consultive Committee of Immunizations considers that the modification is adequate, since it extends the age of protection, reducing at least in theory the infection in older scholars and adolescents -who are significant sources of transmission of Bordetella pertussis to infants- using an adequate vaccine formulation (acellular pertussis vaccine). The available evidence regarding vaccination in special groups (adolescents and adults, health-care workers and pregnant women) and cocooning strategy are commented.

En Chile, a comienzos del mes de octubre de 2010 se detectó un aumento en la notiicación de casos de coqueluche, dinámica que se ha mantenido a la fecha (abril 2012). El número de casos acumulados durante 2011 ascendió a 2.581 (15,0/100.000 hab.), cifra superior al número de casos registrados durante el período 2008-2010 (2.460 casos). Por su parte, a partir de 2012 la autoridad sanitaria introdujo una modiicación en el esquema de vacunación anti-pertussis, consistente en el reemplazo del segundo refuerzo de vacuna antipertussis (DTwP, administrada a los 4 años) y del refuerzo de toxoide diftérico-tetánico (dT, administrado en segundo básico) por la vacuna anti-pertussis acelular de contenido antigénico reducido (dTpa), a ser administrada en primero básico. El Comité Consultivo de Inmunizaciones considera la modificación adecuada, por cuanto permite extender el tiempo de protección, reduciendo al menos en teoría la infección en escolares mayores y adolescentes -quienes son importantes fuente de contagio de Bordetella pertussis para los lactantes- utilizando una adecuada formulación de vacuna (vacuna antipertussis acelular). Se comenta la evidencia disponible sobre vacunación anti-pertussis en grupos especiales (adolescentes y adultos, funcionarios de la salud y mujeres embarazadas), y la estrategia de vacunación de capullo.

Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

BACKGROUND: Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. METHODS: We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. FINDINGS: Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (p<0·0145) and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose; seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified. INTERPRETATION: On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys. FUNDING: Novartis Vaccines and Diagnostics.

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries.

To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used.