The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1.

Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from Brachyury-positive multipotent cells in the posterior-proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite being expressed in the postimplantation epiblast. Using a dual transgene system for controlled expression at postimplantation stages, we found that Nanog blocks primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. Accordingly, Nanog-deficient embryonic stem cells are prone to erythropoietic differentiation. Moreover, Nanog expression in adults prevents the maturation of erythroid cells. By analysis of previous data for NANOG binding during stem cell differentiation and CRISPR/Cas9 genome editing, we found that Tal1 is a direct NANOG target. Our results show that Nanog regulates primitive hematopoiesis by directly repressing critical erythroid lineage specifiers.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Reflections on the Biology of Cell Culture Models: Living on the Edge of Oxidative Metabolism in Cancer Cells.

Nowadays, the study of cell metabolism is a hot topic in cancer research. Many studies have used 2D conventional cell cultures for their simplicity and the facility to infer mechanisms. However, the limitations of bidimensional cell cultures to recreate architecture, mechanics, and cell communication between tumor cells and their environment, have forced the development of other more realistic in vitro methodologies. Therefore, the explosion of 3D culture techniques and the necessity to reduce animal experimentation to a minimum has attracted the attention of researchers in the field of cancer metabolism. Here, we revise the limitations of actual culture models and discuss the utility of several 3D culture techniques to resolve those limitations.

The microRNA-29/PGC1α regulatory axis is critical for metabolic control of cardiac function.

Different microRNAs (miRNAs), including miR-29 family, may play a role in the development of heart failure (HF), but the underlying molecular mechanisms in HF pathogenesis remain unclear. We aimed at characterizing mice deficient in miR-29 in order to address the functional relevance of this family of miRNAs in the cardiovascular system and its contribution to heart disease. In this work, we show that mice deficient in miR-29a/b1 develop vascular remodeling and systemic hypertension, as well as HF with preserved ejection fraction (HFpEF) characterized by myocardial fibrosis, diastolic dysfunction, and pulmonary congestion, and die prematurely. We also found evidence that the absence of miR-29 triggers the up-regulation of its target, the master metabolic regulator PGC1α, which in turn generates profound alterations in mitochondrial biogenesis, leading to a pathological accumulation of small mitochondria in mutant animals that contribute to cardiac disease. Notably, we demonstrate that systemic hypertension and HFpEF caused by miR-29 deficiency can be rescued by PGC1α haploinsufficiency, which reduces cardiac mitochondrial accumulation and extends longevity of miR-29-mutant mice. In addition, PGC1α is overexpressed in hearts from patients with HF. Collectively, our findings demonstrate the in vivo role of miR-29 in cardiovascular homeostasis and unveil a novel miR-29/PGC1α regulatory circuitry of functional relevance for cell metabolism under normal and pathological conditions.

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

Autotransplantation of a surgically removed canine using a customised 3D-printed surgical template.

Autotransplantation is a treatment option with high reported survival rates to replace failing teeth in the anterior maxilla. This treatment requires a multidisciplinary approach from orthodontists, paediatric dentists, restorative dentists, and oral and maxillofacial surgeons to achieve successful outcomes. Success is dependent on many factors including stage of root development, handling of the periodontal ligament, extra-alveolar time and splinting. This case report presents the novel use of digitally designed and three-dimensional (3D) printed surgical templates to aid intraoperatively and reduce the extra-alveolar time. A preoperative cone-beam computed tomography scan allowed digital planning and construction of surgical templates that replicated the exact root dimensions of impacted maxillary canines. These templates were subsequently 3D printed in resin, sterilised and utilised intraoperatively to aid socket preparation before the surgical autotransplantation.

Progress in vaccination towards hepatitis B control and elimination in the Region of the Americas.

BACKGROUND: Over recent decades, the Region of the Americas has made significant progress towards hepatitis B elimination. We summarize the countries/territories' efforts in introducing and implementing hepatitis B (HB) vaccination and in evaluating its impact on HB virus seroprevalence. METHODS: We collected information about HB vaccination schedules, coverage estimates, and year of vaccine introduction from countries/territories reporting to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF Joint Reporting Form on Immunization. We obtained additional information regarding countries/territories vaccination recommendations and strategies through communications with Expanded Program on Immunization (EPI) managers and national immunization survey reports. We identified vaccine impact studies conducted and published in the Americas. RESULTS: As of October 2016, all 51 countries/territories have included infant HB vaccination in their official immunization schedule. Twenty countries, whose populations represent over 90% of the Region's births, have included nationwide newborn HB vaccination. We estimated at 89% and 75%, the regional three-dose series and the birth dose HB vaccination coverage, respectively, for 2015. The impact evaluations of infant HB immunization programs in the Region have shown substantial reductions in HB surface antigen (HBsAg) seroprevalence. CONCLUSION: The achievements of vaccination programs in the Americas suggest that the elimination of perinatal and early childhood HB transmission could be feasible in the short-term. Moreover, the data gathered indicate that the Region may have already achieved the 2020 WHO goal for HB control.

Attenuation of the physiological response to infection on adults over 65 years old admitted to the emergency room (ER).

It has been considered that the elderly have clinical manifestations different from the ones observed in middle-age adults during an injury event. This hypothesis has not been extensively explored in sepsis and bacterial infections. Secondary analysis of two prospective studies including 2611 patients over 18 years of age admitted to the emergency room with confirmed or probable bacterial infections and sepsis. The outcome measures were heart rate, respiratory rate, systolic blood pressure, temperature, Glasgow Coma Scale, creatinine, PaO2/FiO2 and platelets daily during the first week. Compared to survivors younger than 65, the deceased under 65 had an average heart rate of 12.5 beats per minute per day higher (95% CI 9.32; 15.61), while patients over 65 who died barely had an average 5.7 beats per minute per day higher than the same reference group (95% CI 3.45; 8.06). The systolic blood pressure had a significant decreased in those who died younger than 65, compared to survivors with the same age, in both cohorts (-5.2 mmHg, 95% CI -8.17; -2.23 and -8.5 mmHg, 95% CI -13.48; -3.54, respectively), while those older than 65 who died had a nonsignificant increase (+1.6 mmHg, 95% CI -1.33; 4.62 and +0.1, 95% CI -6.48; 6.72, respectively) compared to the same reference group. The behavior of most clinical and laboratory variables suggests a less pronounced response of subjects above 65 years of age who died 28 days after being diagnosed with sepsis.

Progress towards a comprehensive approach to maternal and neonatal immunization in the Americas.

Maternal and neonatal immunization (MNI) is a core component of the new immunization model in the Americas, which transitioned from immunization of children to that of the entire family. Immunization during pregnancy protects the mother and the fetus by providing the neonate with maternal antibodies against disease. It has the potential to impact early childhood morbidity and mortality, and thus MNI has gained visibility and priority on the global health agenda. The Region of the Americas is a leader in MNI, as seen by its elimination of congenital rubella syndrome in 2015 and the progress made toward neonatal tetanus elimination. In the Americas, 31 countries currently target pregnant women for influenza vaccination; and 21 countries-over 90% of the Region's birth cohort-have nationwide newborn hepatitis B vaccination. This paper describes the status of MNI in the Americas and identifies gaps in the evidence, obstacles to optimal implementation, and opportunities for future improvements. Catalysts for MNI in the Region have been political commitment, endorsement by scientific societies, an established "culture of vaccination," widespread access to antenatal care, and context-specific communications; however, universal and equitable access for pregnant women and their newborns continues to be a formidable challenge, and additional vaccine safety and effectiveness evidence is needed. Continued efforts to integrate MNI with maternal and child health services will be critical to furthering the MNI platform as well.

La inmunización materna y neonatal es un componente central del nuevo modelo de inmunización en la Región de las Américas, que pasó de la inmunización infantil a la de toda la familia. La inmunización durante el embarazo protege a la madre y el feto dando al recién nacido los anticuerpos maternos contra las enfermedades. Tiene el potencial de repercutir en la morbilidad y la mortalidad en la primera infancia, por lo que la inmunización materna y neonatal ha adquirido visibilidad y prioridad en la agenda mundial de salud.La Región de las Américas ocupa una posición de liderazgo en materia de inmunización materna y neonatal, como lo demuestra la eliminación del síndrome de rubéola congénita en el 2015 y los avances logrados para la eliminación del tétanos neonatal. Actualmente en 31 países de la Región se da prioridad a las embarazadas para que reciban vacunación antigripal y en 21 países ­más de 90% de la cohorte de nacimiento de la Región­ se incluye la vacunación de los recién nacidos contra la hepatitis B a nivel nacional.En este documento se describe la situación de la inmunización materna y neonatal en la Región de las Américas y se señalan las lagunas en la evidencia, los obstáculos a la implementación óptima y las oportunidades para las mejoras futuras. Los catalizadores de la inmunización materna y neonatal en la Región han sido el compromiso político, el aval de las sociedades científicas, una "cultura de vacunación" establecida, el acceso generalizado a la atención prenatal y las comunicaciones específicas para cada contexto; sin embargo, el acceso universal y equitativo de las embarazadas y los recién nacidos sigue siendo un reto enorme y se necesitan más datos científicos sobre la seguridad y efectividad de las vacunas. La continuación de los esfuerzos para integrar la inmunización materna y neonatal en los servicios de salud maternoinfantil será fundamental para promover también la plataforma a favor de esta inmunización.

A imunização materna e neonatal é peça fundamental do novo modelo de imunização nas Américas, com a transição da vacinação de crianças à vacinação de toda a família. A vacinação da gestante protege a mãe e o feto ao proporcionar ao recém-nascido anticorpos maternos contra doenças. A imunização materna e neonatal possivelmente repercute na primeira infância reduzindo a morbidade e a mortalidade e, portanto, ganhou visibilidade sendo considerada prioritária na agenda global de saúde.A Região das Américas é líder em imunização materna e neonatal, tendo alcançado a eliminação da síndrome da rubéola congênita em 2015 e avançado para a eliminação do tétano neonatal. Existem atualmente programas de vacinação contra influenza para gestantes em 31 países e programas nacionais de vacinação contra hepatite B para recém-nascidos em 21 países (com uma cobertura superior a 90% da coorte de nascidos vivos na Região).Este artigo apresenta um panorama da imunização materna e neonatal nas Américas, destaca as lacunas nas evidências científicas e os obstáculos à implementação ideal dos programas de vacinação e aponta oportunidades futuras para melhorias. Entre os fatores responsáveis pelo incentivo à imunização materna e neonatal na Região estão o compromisso político, o endosso das sociedades científicas, uma "cultura de vacinação" estabelecida, o amplo acesso à assistência pré-natal e a comunicação contextualizada. Porém, o acesso universal e equitativo das gestantes e seus recémnascidos à vacinação é ainda um grande desafio e se fazem necessárias mais evidências sobre a segurança e a efetividade das vacinas. Além disso, é imprescindível o empenho contínuo para integrar a imunização materna e neonatal aos serviços de saúde materno-infantil e seguir promovendo a plataforma de imunização materna e neonatal.

The evolution of Vaccination Week in the Americas.

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.

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 contribuir a alcanzar la cobertura universal de salud.

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 sealcançar 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.

[Bulimia Nervosa]. / Bulimia nerviosa.

In our society a huge tension is caused by three types of contradictory messages in relation to our body structure: medical message, aesthetic message and gastronomic message. The abundance of food, some very attractive, together with the social "order" of having to be slim to be accepted, originates very complicated internal situations that lead predisposed people to develop an eating disorder. In concrete, bulimia nervosa is a disorder nobody spoke about three decades ago, and there are only some detailed references about it in the last 80 years. In 1979, Rusell coined the name of bulimia nervosa and considered it as a variation of the anorexia. From the 80s on, it has been noticed how the incidence of the bulimia nervosa has increased, with an important quantitative variability, being a reason for concern among health professionals and our society in general, and for the families who suffer its consequences in particular. Not likely to be a new disorder, since the references to excesses with food and to vomiting are so old that they cannot be traced in time. The origin of this disorder is multifactorial and although personality factors and environmental elements are implied, it is also true that there is a genetic predisposition that is not still well known. The individuals with bulimia nervosa show a wide range of functional limitations that are linked to the disorder, being the social field the one which can probably be affected more negatively. For all this, nowadays the deployment of resources and efforts has been increased by the health authorities, in order to implement therapeutic procedures, to boost ways of prevention and to reinforce the rehabilitation of all the aspects implied in the disorder.

Vaccination Week in the Americas, 2011: an opportunity to assess the routine vaccination program in the Bolivarian Republic of Venezuela.

BACKGROUND: Vaccination Week in the Americas (VWA) is an annual initiative in countries and territories of the Americas every April to highlight the work of national expanded programs on immunization (EPI) and increase access to vaccination services for high-risk population groups. In 2011, as part of VWA, Venezuela targeted children aged less than 6 years in 25 priority border municipalities using social mobilization to increase institution-based vaccination. Implementation of social communication activities was decentralized to the local level. We conducted a survey in one border municipality of Venezuela to evaluate the outcome of VWA 2011 and provide a snapshot of the overall performance of the routine EPI at that level. METHODS: We conducted a coverage survey, using stratified cluster sampling, in the Venezuelan municipality of Bolivar (bordering Colombia) in August 2011. We collected information for children aged <6 years through caregiver interviews and transcription of vaccination card data. We estimated each child's eligibility to receive a specific vaccine dose during VWA 2011 and whether or not they were actually vaccinated during VWA activities. We also estimated baseline vaccination coverage, timeliness and 95% confidence intervals (CI), and used chi-square tests to compare coverage across age cohorts, taking into account the sampling design. RESULTS: We surveyed 839 children from 698 households; 93% of children had a vaccination card. Among households surveyed, 216 (31%) caregivers reported having heard about a vaccination activity during April or May 2011. Of the 528 children eligible to receive a vaccine during VWA, 24% received at least one dose, while 13% received all doses due. Overall, baseline coverage with routine vaccines, as measured by the survey, was >85%, with a few exceptions. CONCLUSION: Low levels of VWA awareness among caregivers probably contributed to the limited vaccination of eligible children during the VWA activities in Bolivar in 2011. However, vaccine coverage for most EPI vaccines was high. Additionally, high vaccination card availability and high participation in VWA among those caregivers aware of it in 2011 suggest public trust in the EPI program in the municipality. Health authorities have used survey findings to inform changes to the routine EPI and better VWA implementation in subsequent years.

Pilot to evaluate the feasibility of measuring seasonal influenza vaccine effectiveness using surveillance platforms in Central-America, 2012.

BACKGROUND: Since 2004, the uptake of seasonal influenza vaccines in Latin America and the Caribbean has markedly increased. However, vaccine effectiveness (VE) is not routinely measured in the region. We assessed the feasibility of using routine surveillance data collected by sentinel hospitals to estimate influenza VE during 2012 against laboratory-confirmed influenza hospitalizations in Costa-Rica, El Salvador, Honduras and Panama. We explored the completeness of variables needed for VE estimation. METHODS: We conducted the pilot case-control study at 23 severe acute respiratory infections (SARI) surveillance hospitals. Participant inclusion criteria included children 6 months-11 years and adults ≥60 years targeted for vaccination and hospitalized for SARI during January-December 2012. We abstracted information needed to estimate target group specific VE (i.e., date of illness onset and specimen collection, preexisting medical conditions, 2012 and 2011 vaccination status and date, and pneumococcal vaccination status for children and adults) from SARI case-reports and for children ≤9 years, inquired about the number of annual vaccine doses given. A case was defined as an influenza virus positive by RT-PCR in a person with SARI, while controls were RT-PCR negative. We recruited 3 controls per case from the same age group and month of onset of symptoms. RESULTS: We identified 1,186 SARI case-patients (342 influenza cases; 849 influenza-negative controls), of which 994 (84 %) had all the information on key variables sought. In 893 (75 %) SARI case-patients, the vaccination status field was missing in the SARI case-report forms and had to be completed using national vaccination registers (36 %), vaccination cards (30 %), or other sources (34 %). After applying exclusion criteria for VE analyses, 541 (46 %) SARI case-patients with variables necessary for the group-specific VE analyses were selected (87 cases, 236 controls among children; 64 cases, 154 controls among older adults) and were insufficient to provide precise regional estimates (39 % for children and 25 % for adults of minimum sample size needed). CONCLUSIONS: Sentinel surveillance networks in middle income countries, such as some Latin American and Caribbean countries, could provide a simple and timely platform to estimate regional influenza VE annually provided SARI forms collect all necessary information.

Access to optically pure ß-hydroxy esters via non-enzymatic kinetic resolution by a planar-chiral DMAP catalyst.

The development of new approaches to obtain optically pure ß-hydroxy esters is an important area in synthetic organic chemistry since they are precursors of other high value compounds. Herein, the kinetic resolution of racemic ß-hydroxy esters using a planar-chiral DMAP derivative catalyst is presented. Following this procedure, a range of aromatic ß-hydroxy esters was obtained in excellent selectivities (up to s = 107) and high enantiomeric excess (up to 99% ee). Furthermore, the utility of the present method was demonstrated in the synthesis of (S)-3-hydroxy-N-methyl-3-phenylpropanamide, a key intermediate for bioactive molecules such as fluoxetine, tomoxetine or nisoxetine, in its enantiomerically pure form.

Tablet-based Augmented reality and 3D printed templates in fully guided Microtia Reconstruction: a clinical workflow.

BACKGROUND: Microtia is a congenital malformation of the auricle that affects approximately 4 of every 10,000 live newborns. Radiographic film paper is traditionally employed to bidimensionally trace the structures of the contralateral healthy ear in a quasi-artistic manner. Anatomical points provide linear and angular measurements. However, this technique proves time-consuming, subjectivity-rich, and greatly dependent on surgeon expertise. Hence, it's susceptible to shape errors and misplacement. METHODS: We present an innovative clinical workflow that combines 3D printing and augmented reality (AR) to increase objectivity and reproducibility of these procedures. Specifically, we introduce patient-specific 3D cutting templates and remodeling molds to carve and construct the cartilaginous framework that will conform the new ear. Moreover, we developed an in-house AR application compatible with any commercial Android tablet. It precisely guides the positioning of the new ear during surgery, ensuring symmetrical alignment with the healthy one and avoiding time-consuming intraoperative linear or angular measurements. Our solution was evaluated in one case, first with controlled experiments in a simulation scenario and finally during surgery. RESULTS: Overall, the ears placed in the simulation scenario had a mean absolute deviation of 2.2 ± 1.7 mm with respect to the reference plan. During the surgical intervention, the reconstructed ear was 3.1 mm longer and 1.3 mm wider with respect to the ideal plan and had a positioning error of 2.7 ± 2.4 mm relative to the contralateral side. Note that in this case, additional morphometric variations were induced from inflammation and other issues intended to be addressed in a subsequent stage of surgery, which are independent of our proposed solution. CONCLUSIONS: In this work we propose an innovative workflow that combines 3D printing and AR to improve ear reconstruction and positioning in microtia correction procedures. Our implementation in the surgical workflow showed good accuracy, empowering surgeons to attain consistent and objective outcomes.

Vaccination Week in the Americas: an opportunity to integrate other health services with immunization.

Vaccination Week in the Americas (VWA) is an initiative of the countries and territories of the Americas that works to advance equity and access to vaccination. The initiative focuses on reaching populations with limited access to regular health services and promotes solidarity among countries. As the Expanded Program on Immunization is one of the world's best-established health programs, integrating other interventions with immunization services has been highly promoted. Using data available from the Pan American Health Organization, we explored the extent of integration of other interventions with immunization in Latin American and Caribbean (LAC) countries as part of VWA. At least 14 countries or territories have integrated other interventions with immunization during VWA. The most common integrated intervention is vitamin A supplementation, followed by deworming. However, a variety of other interventions have been integrated, such as educational activities, supplementation with vitamins and minerals, and provision of health services. Data on coverage of integrated interventions are limited. Integration of other interventions with immunization in LAC countries is widespread, and its impact and lessons learned merit further examination.

Non-enzymatic dynamic kinetic resolution of secondary aryl alcohols: planar chiral ferrocene and ruthenium catalysts in cooperation.

"Ruth" helps iron! A novel method for the non-enzymatic dynamic kinetic resolution (DKR) of secondary aryl alcohols by the use of the planar chiral ferrocene derivative (+)-1 in combination with the ruthenium racemization catalyst 2 yields acetylated alcohols in high enantioselectivity and yield. This development opens opportunities for new developments in the field of non-enzymatic dynamic kinetic resolution.

Stakeholder Perspectives on the Current and Future of Additive Manufacturing in Healthcare.

Additive manufacturing (AM) technologies have disrupted many supply chains by making new designs and functionalities possible. The opportunity to realize complex customized structures has led to significant interest within healthcare; however, full utilization critically requires the alignment of the whole supply chain. To offer insights into this process, a survey was conducted to understand the views of different medical AM stakeholders. The results highlighted an agreement between academics, designers, manufacturers, and medical experts, that personalization and design control are the main benefits of AM. Interestingly, surface finish was consistently identified as an obstacle. Nevertheless, there was a degree of acceptance that post-processing was necessary to achieve appropriate quality control. Recommendations were made for extending the use of in situ process monitoring systems to support improved reproducibility. Variations in the future vision of AM were highlighted between stakeholder groups and areas of interest for development noted for each stakeholder. Collectively, this survey indicates that medical stakeholders agree on the capabilities of AM but have different priorities for its implementation and progression. This highlights a degree of disconnection among the supply chain at a ground level; thus, collaboration on AM specific standards and enhancement of communication between stakeholders from project inception is recommended.

Giant cell arteritis presenting as scalp necrosis.

The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness.