Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix.

Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices (ECMs) on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D ECMs. Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlight the importance of tumor mechanics and invasion.

Correlative cryo-soft X-ray tomography and cryo-structured illumination microscopy reveal changes to lysosomes in amyloid-ß-treated neurons.

Protein misfolding is common to neurodegenerative diseases (NDs) including Alzheimer's disease (AD), which is partly characterized by the self-assembly and accumulation of amyloid-beta in the brain. Lysosomes are a critical component of the proteostasis network required to degrade and recycle material from outside and within the cell and impaired proteostatic mechanisms have been implicated in NDs. We have previously established that toxic amyloid-beta oligomers are endocytosed, accumulate in lysosomes, and disrupt the endo-lysosomal system in neurons. Here, we use pioneering correlative cryo-structured illumination microscopy and cryo-soft X-ray tomography imaging techniques to reconstruct 3D cellular architecture in the native state revealing reduced X-ray density in lysosomes and increased carbon dense vesicles in oligomer treated neurons compared with untreated cells. This work provides unprecedented visual information on the changes to neuronal lysosomes inflicted by amyloid beta oligomers using advanced methods in structural cell biology.

The correlation between sub-epidermal moisture measurement and other early indicators of pressure ulcer development-A prospective cohort observational study. Part 1. The correlation between sub-epidermal moisture measurement and ultrasound.

The correlation between sub-epidermal moisture (SEM) and other early indicators of pressure ulcer (PU) development is yet to be determined. This three-part series aims to bridge this knowledge gap, through investigating SEM and its correlation with evidence-based technologies and assessments. This article focuses on the correlation between SEM and ultrasound. A prospective cohort observational study was undertaken between February and November 2021. Patients undergoing three surgery types were consecutively enrolled to the study following informed consent. Assessments were performed prior to and following surgery for 3 days at the sacrum, both heels and a control site, using a SEM scanner and high-frequency ultrasound scanner (5-15 MHz). Spearman's rank (rs ) explored the correlation between SEM and ultrasound. A total of 60 participants were included; 50% were male with a mean age of 58 years (±13.46). A statistically significant low to moderately positive correlation was observed between SEM and ultrasound across all anatomical sites (rs range = 0.39-0.54, p < 0.05). The only exception was a correlation between SEM and ultrasound on day 0 at the right heel (rs = 0.23, p = 0.09). These results indicate that SEM and ultrasound agreed in the presence of injury; however, SEM was able to identify abnormalities before ultrasound.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix.

Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D extracellular matrices (EMCs). Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlights the importance of tumor mechanics and invasion.

Providing person-centred dementia care on general hospital wards.

Dementia is caused by conditions that result in a progressive loss of brain function. People with dementia often have complex multimorbidity which increases their risk of admission to hospital. However, care in acute hospitals is often not adapted to patients with dementia, who have reported negative experiences of their hospital stay from admission to discharge. Person-centred care has been shown to make a positive difference to how well people with dementia cope in hospital. This article discusses how nurses working on general hospital wards can enhance the experiences of people with dementia and improve their outcomes by providing person-centred care.

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

BACKGROUND: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. OBJECTIVES: The authors aimed to determine factors associated with survival in a large cohort of such individuals. METHODS: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). RESULTS: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. CONCLUSIONS: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.

Time to Hemostasis After Trauma and Transfusion by Patient Blood Type.

BACKGROUND: Although evidence supports an increased risk of mortality after major trauma among patients with type O blood, the relationship between patient blood type and clinical outcomes aside from mortality has not been fully elucidated. OBJECTIVE: To examine the relationship between patient blood type and time to hemostasis after trauma and massive transfusion. METHODS: A secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was performed (N = 544). Blood type was dichotomized into type O versus non-type O. It was hypothesized that patients with non-type O blood would achieve hemostasis more quickly owing to the theoretical presence of increased clotting factors. Bivariate analysis and multiple Cox regression were conducted to test this assumption. RESULTS: No significant difference was found in time to hemostasis between patients with type O blood and those with non-type O blood. However, mechanism of injury, diastolic blood pressure, and international normalized ratio affected the time to hemostasis in these trauma patients. CONCLUSION: This study showed no significant difference in time to hemostasis by blood type.

Managing myocarditis in a patient with newly diagnosed dermatomyositis.

A woman in her 20s presented with chest pain, dyspnoea, arthralgia, muscle weakness and skin discolouration. She was diagnosed with dermatomyositis. During her admission, she developed pleuritic chest pain and shortness of breath accompanied by a significant troponin I rise. Her echocardiogram showed a hyperdynamic left ventricle with a trivial pericardial effusion; there were no regional wall motion abnormalities. Gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI showed extensive myocarditis. She was started on corticosteroids and azathioprine which led to an improvement of symptoms and biochemical markers.

Asthma diagnosis: into the fourth dimension.

Asthma is the most common chronic respiratory disease in the UK; however, the misdiagnosis rate is substantial. The lack of consistency in national guidelines and the paucity of data on the performance of diagnostic algorithms compound the challenges in asthma diagnosis. Asthma is a highly rhythmic disease, characterised by diurnal variability in clinical symptoms and pathogenesis. Asthma also varies day to day, seasonally and from year to year. As much as it is a hallmark for asthma, this variability also poses significant challenges to asthma diagnosis. Almost all established asthma diagnostic tools demonstrate diurnal variation, yet few are performed with standardised timing of measurements. The dichotomous interpretation of diagnostic outcomes using fixed cut-off values may further limit the accuracy of the tests, particularly when diurnal variability straddles cut-off values within a day, and careful interpretation beyond the 'positive' and 'negative' outcome is needed. The day-to-day and more long-term variations are less predictable and it is unclear whether performing asthma diagnostic tests during asymptomatic periods may influence diagnostic sensitivities. With the evolution of asthma diagnostic tools, home monitoring and digital apps, novel strategies are needed to bridge these gaps in knowledge, and circadian variability should be considered during the standardisation process. This review summarises the biological mechanisms of circadian rhythms in asthma and highlights novel data on the significance of time (the fourth dimension) in asthma diagnosis.

Night shift work is associated with an increased risk of asthma.

INTRODUCTION: Shift work causes misalignment between internal circadian time and the external light/dark cycle and is associated with metabolic disorders and cancer. Approximately 20% of the working population in industrialised countries work permanent or rotating night shifts, exposing this large population to the risk of circadian misalignment-driven disease. Analysis of the impact of shift work on chronic inflammatory diseases is lacking. We investigated the association between shift work and asthma. METHODS: We describe the cross-sectional relationship between shift work and prevalent asthma in >280000 UK Biobank participants, making adjustments for major confounding factors (smoking history, ethnicity, socioeconomic status, physical activity, body mass index). We also investigated chronotype. RESULTS: Compared with day workers, 'permanent' night shift workers had a higher likelihood of moderate-severe asthma (OR 1.36 (95% CI 1.03 to 1.8)) and all asthma (OR 1.23 (95% CI 1.03 to 1.46)). Individuals doing any type of shift work had higher adjusted odds of wheeze/whistling in the chest. Shift workers who never or rarely worked on nights and people working permanent nights had a higher adjusted likelihood of having reduced lung function (FEV1 <80% predicted). We found an increase in the risk of moderate-severe asthma in morning chronotypes working irregular shifts, including nights (OR 1.55 (95% CI 1.06 to 2.27)). CONCLUSIONS: The public health implications of these findings are far-reaching due to the high prevalence and co-occurrence of both asthma and shift work. Future longitudinal follow-up studies are needed to determine if modifying shift work schedules to take into account chronotype might present a public health measure to reduce the risk of developing inflammatory diseases such as asthma.

AZD1775 induces toxicity through double-stranded DNA breaks independently of chemotherapeutic agents in p53-mutated colorectal cancer cells.

AZD1775 is a small molecule WEE1 inhibitor used in combination with DNA-damaging agents to cause premature mitosis and cell death in p53-mutated cancer cells. Here we sought to determine the mechanism of action of AZD1775 in combination with chemotherapeutic agents in light of recent findings that AZD1775 can cause double-stranded DNA (DS-DNA) breaks. AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC50 from 9.3 µM to 3.5 µM. Flow cytometry showed a significant increase in the mitotic marker pHH3 (3.4% vs. 56.2%) and DS-DNA break marker γH2AX (5.1% vs. 50.7%) for combination therapy compared with 5-FU alone. Combination therapy also increased the amount of caspase-3 dependent apoptosis compared with 5-FU alone (4% vs. 13%). The addition of exogenous nucleosides to combination therapy significantly rescued the increased DS-DNA breaks and caspase-3 dependent apoptosis almost to the levels of 5-FU monotherapy. In conclusion, AZD1775 enhances 5-FU cytotoxicity through increased DS-DNA breaks, not premature mitosis, in p53-mutated colorectal cancer cells. This finding is important for designers of future clinical trials when considering the optimal timing and duration of AZD1775 treatment.

Music therapy for children and adolescents with behavioural and emotional problems: a randomised controlled trial.

BACKGROUND: Although music therapy (MT) is considered an effective intervention for young people with mental health needs, its efficacy in clinical settings is unclear. We therefore examined the efficacy of MT in clinical practice. METHODS: Two hundred and fifty-one child (8-16 years, with social, emotional, behavioural and developmental difficulties) and parent dyads from six Child and Adolescent Mental Health Service community care facilities in Northern Ireland were randomised to 12 weekly sessions of MT plus usual care [n = 123; 76 in final analyses] or usual care alone [n = 128; 105 in final analyses]. Follow-up occurred at 13 weeks and 26 weeks postrandomisation. Primary outcome was improvement in communication (Social Skills Improvement System Rating Scales) (SSIS) at 13 weeks. Secondary outcomes included social functioning, self-esteem, depression and family functioning. RESULTS: There was no significant difference for the child SSIS at week 13 (adjusted difference in mean 2.4; 95% CI -1.2 to 6.1; p = .19) or for the guardian SSIS (0.5; 95% CI -2.9 to 3.8; p = .78). However, for participants aged 13 and over in the intervention group, the child SSIS communication was significantly improved (6.1, 95% CI 1.6 to 10.5; p = .007) but not the guardian SSIS (1.1; 95% CI -2.9 to 5.2; p = .59). Overall, self-esteem was significantly improved and depression scores were significantly lower at week 13. There was no significant difference in family or social functioning at week 13. CONCLUSIONS: While the findings provide some evidence for the integration of music therapy into clinical practice, differences relating to subgroups and secondary outcomes indicate the need for further study. ISRCTN Register; ISRCTN96352204.

The evolution of Vaccination Week in the Americas / La evolución de la Semana de Vacunación en las Américas / Evolução da Semana de Vacinação nas Américas

ABSTRACT This report covers the background and evolution of Vaccination Week in the Americas (VWA), an initiative that started as a coordinated response to a 2002 measles outbreak in Colombia and Venezuela, and evolved into the model for other regions and World Immunization Week (WIW). VWA focuses on the work of national immunization programs, with special efforts to reach the unreached. This paper offers examples of how countries have leveraged VWA to implement a diverse array of vaccination activities, strengthening overall health services by integrating with other preventive health interventions, and bolstering "Pan-Americanism" and health diplomacy. The opportunities offered by this global initiative were clearly demonstrated in April 2016 when the successful global switch from the trivalent oral polio vaccine to the bivalent vaccine was synchronized with WIW. Going forward, VWA and WIW can help close the gaps in access to immunization and other health services, contributing to achieve universal health coverage.(AU)

RESUMEN Este informe incluye los antecedentes y la evolución de la Semana de Vacunación en las Américas, una iniciativa que comenzó como una respuesta coordinada a un brote de sarampión en Colombia y Venezuela en el 2002, y evolucionó hasta convertirse en modelo para otras regiones y para la Semana Mundial de la Inmunización. La Semana de Vacunación en las Américas se centra en el trabajo de los programas nacionales de inmunización, con esfuerzos especiales para llegar a las personas que todavía no estén cubiertas. En el presente trabajo se dan ejemplos de cómo los países han aprovechado la Semana de Vacunación para realizar diversas actividades relacionadas con la vacunación, fortalecer los servicios de salud en general mediante la integración con otras intervenciones preventivas y fomentar el "panamericanismo" y la diplomacia en torno a la salud. Las oportunidades que ofrece esta iniciativa mundial quedaron claramente evidenciadas en abril del 2016 con el éxito obtenido en la sustitución de la vacuna oral trivalente contra la poliomielitis por la vacuna bivalente, sincronizada con la Semana Mundial de la Inmunización. En el futuro, la Semana de Vacunación en las Américas y la Semana Mundial de Inmunización pueden ayudar a subsanar la brecha en el acceso a la inmunización y otros servicios de salud, y contribui(AU)

RESUMO Este artigo narra os antecedentes e a evolução da Semana de Vacinação nas Américas (SVA), uma iniciativa que nasceu da resposta coordenada ao surto de sarampo na Colômbia e na Venezuela em 2002 e evoluiu como um modelo para as outras regiões e para a Semana Mundial da Imunização. A SVA põe ênfase no trabalho dos programas nacionais de vacinação e, principalmente, nos esforços para se alcançar quem ainda está inalcançado. São ilustrados exemplos de como os países têm aproveitado a SVA para implementar várias atividades de vacinação, fortalecendo os serviços de saúde em geral ao integrá-la a outras intervenções preventivas e reforçando o pan-americanismo e a diplomacia da saúde. As oportunidades criadas por esta iniciativa global ficaram bem evidentes em abril de 2016 com a bem-sucedida transição em nível mundial da vacina oral contra poliomielite trivalente à bivalente, em sincronia com a Semana Mundial da Imunização. Prosseguindo adiante, a SVA e a Semana Mundial da Imunização podem contribuir para sanar as lacunas no acesso à imunização e a outros serviços de saúde e alcançar a cobertura universal de saúde.(AU)

Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic.

BACKGROUND: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. METHODS: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). RESULTS: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact. CONCLUSION: Following the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps.

Educational professionals' understanding of childhood traumatic brain injury.

PRIMARY OBJECTIVES: To determine the understanding of educational professionals around the topic of childhood brain injury and explore the factor structure of the Common Misconceptions about Traumatic Brain Injury Questionnaire (CM-TBI). RESEARCH DESIGN: Cross-sectional postal survey. METHODS AND PROCEDURES: The CM-TBI was posted to all educational establishments in one region of the UK. One representative from each school was asked to complete and return the questionnaire (n = 388). MAIN OUTCOMES AND RESULTS: Differences were demonstrated between those participants who knew someone with a brain injury and those who did not, with a similar pattern being shown for those educators who had taught a child with brain injury. Participants who had taught a child with brain injury demonstrated greater knowledge in areas such as seatbelts/prevention, brain damage, brain injury sequelae, amnesia, recovery and rehabilitation. Principal components analysis suggested the existence of four factors and the discarding of half the original items of the questionnaire. CONCLUSIONS: In the first European study to explore this issue, it is highlighted that teachers are ill-prepared to cope with children who have sustained a brain injury. Given the importance of a supportive school environment in return to life following hospitalization, the lack of understanding demonstrated by teachers in this research may significantly impact on a successful return to school.

Music in mind, a randomized controlled trial of music therapy for young people with behavioural and emotional problems: study protocol.

AIMS: This article is a report of a trial protocol to determine if improvizational music therapy leads to clinically significant improvement in communication and interaction skills for young people experiencing social, emotional or behavioural problems. BACKGROUND: Music therapy is often considered an effective intervention for young people experiencing social, emotional or behavioural difficulties. However, this assumption lacks empirical evidence. STUDY DESIGN: Music in mind is a multi-centred single-blind randomized controlled trial involving 200 young people (aged 8-16 years) and their parents. Eligible participants will have a working diagnosis within the ambit of international classification of disease 10 mental and behavioural disorders and will be recruited over 15 months from six centres within the Child and Adolescent Mental Health Services of a large health and social care trust in Northern Ireland. Participants will be randomly allocated in a 1:1 ratio to receive standard care alone or standard care plus 12 weekly music therapy sessions delivered by the Northern Ireland Music Therapy Trust. Baseline data will be collected from young people and their parents using standardized outcome measures for communicative and interaction skills (primary endpoint), self-esteem, social functioning, depression and family functioning. Follow-up data will be collected 1 and 13 weeks after the final music therapy session. A cost-effectiveness analysis will also be carried out. DISCUSSION: This study will be the largest trial to date examining the effect of music therapy on young people experiencing social, emotional or behavioural difficulties and will provide empirical evidence for the use of music therapy among this population. Trial registration. This study is registered in the ISRCTN Register, ISRCTN96352204. Ethical approval was gained in October 2010.

Pandemic influenza vaccination: lessons learned from Latin America and the Caribbean.

In April 2009, the World Health Organization (WHO) reported the emergence of a new influenza (H1N1) virus which led to the first pandemic declaration of the 21st century. Most countries in Latin America and the Caribbean (LAC) had a national preparedness plan in place at this time; however, the vaccination component of such plans was largely undeveloped. Nevertheless, countries were able to capitalize on the infrastructure of their immunization programs and widespread experience utilizing the seasonal influenza vaccine to prepare rapidly, developing H1N1 vaccination plans targeting individuals with chronic disease, pregnant women and health care workers, among others. In LAC vaccine was acquired through three mechanisms: the Pan American Health Organization's Revolving Fund, direct manufacturer purchase, and WHO donations. Vaccine access was not equitable both in quantity of vaccine available and timeless of vaccine availability. As of December 2010, an estimated 145 million doses had been administered in LAC. Despite high regional coverage, there were large variations in coverage at the national level; pregnant women had the lowest coverage, despite their high risk for morbidity and mortality. The number of severe adverse events reported in LAC was similar to those expected with the seasonal influenza vaccine. Risk communication was one of the key challenges countries faced, mainly due to concerns and misinformation spread regarding vaccine safety. Countries and the international community need to learn from the experiences gained during H1N1 vaccination in order to be better prepared for the next pandemic.

The first avian Ig-like Fc receptor family member combines features of mammalian FcR and FCRL.

Homologues of almost all mammalian Ig-like immunoregulatory receptor families have been found in the chicken, except the Fc receptor (FcR) family. In addition to classical FcRs that specifically bind antibodies and mediate their effector functions, this family includes "Fc receptor-like" (FCRL) proteins for which ligands have yet to be identified. We have cloned and expressed a full-length chicken monocyte transcript that encodes an avian homologue of the mammalian FcR family. We have termed it chFcR/L as it possesses characteristics of both mammalian FcR and FCRL, but is phylogenetically distinct from either. chFcR/L is a transmembrane protein with four extracellular Ig-like domains and a short cytoplasmic tail. It can be expressed on the cell surface only in the presence of an accessory molecule, chFcRgamma, through which it acquires signalling potential.