Early detection and metabolic pathway identification of T cell activation by in-process intracellular mass spectrometry.

BACKGROUND AIMS: In-process monitoring and control of biomanufacturing workflows remains a significant challenge in the development, production, and application of cell therapies. New process analytical technologies must be developed to identify and control the critical process parameters that govern ex vivo cell growth and differentiation to ensure consistent and predictable safety, efficacy, and potency of clinical products. METHODS: This study demonstrates a new platform for at-line intracellular analysis of T-cells. Untargeted mass spectrometry analyses via the platform are correlated to conventional methods of T-cell assessment. RESULTS: Spectral markers and metabolic pathways correlated with T-cell activation and differentiation are detected at early time points via rapid, label-free metabolic measurements from a minimal number of cells as enabled by the platform. This is achieved while reducing the analytical time and resources as compared to conventional methods of T-cell assessment. CONCLUSIONS: In addition to opportunities for fundamental insight into the dynamics of T-cell processes, this work highlights the potential of in-process monitoring and dynamic feedback control strategies via metabolic modulation to drive T-cell activation, proliferation, and differentiation throughout biomanufacturing.

The application of electrosprayed minocycline-loaded PLGA microparticles for the treatment of glioblastoma.

The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi-synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87-MG) cells. The results from this study demonstrated that solvent mixture of dicholoromethane (DCM) and methanol is the optimal solvent combination for minocycline and larger amount of methanol (i.e., 70:30) resulted in a higher drug loading. All three solvent ratios of DCM:methanol tested produced microparticles that were both spherical and smooth, all in the micron size range. The electrosprayed microparticles were able to elicit a cytotoxic response in U87-MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work provides proof of concept to the hypothesis that electrosprayed minocycline-loaded PLGA microparticles can be a promising agent for the treatment of GBM and could have potential application for cancer therapies.

Longitudinal two-dimensional gas chromatography mass spectrometry as a non-destructive at-line monitoring tool during cell manufacturing identifies volatile features correlative to cell product quality.

BACKGROUND AIMS: Cell therapies have emerged as a potentially transformative therapeutic modality in many chronic and incurable diseases. However, inherent donor and patient variabilities, complex manufacturing processes, lack of well-defined critical quality attributes and unavailability of in-line or at-line process or product analytical technologies result in significant variance in cell product quality and clinical trial outcomes. New approaches for overcoming these challenges are needed to realize the potential of cell therapies. METHODS: Here the authors developed an untargeted two-dimensional gas chromatography mass spectrometry (GC×GC-MS)-based method for non-destructive longitudinal at-line monitoring of cells during manufacturing to discover correlative volatile biomarkers of cell proliferation and end product potency. RESULTS: Specifically, using mesenchymal stromal cell cultures as a model, the authors demonstrated that GC×GC-MS of the culture medium headspace can effectively discriminate between media types and tissue sources. Headspace GC×GC-MS identified specific volatile compounds that showed a strong correlation with cell expansion and product functionality quantified by indoleamine-2,3-dioxygenase and T-cell proliferation/suppression assays. Additionally, the authors discovered increases in specific volatile metabolites when cells were treated with inflammatory stimulation. CONCLUSIONS: This work establishes GC×GC-MS as an at-line process analytical technology for cell manufacturing that could improve culture robustness and may be used to non-destructively monitor culture state and correlate with end product function.

Mesenchymal Stromal Cell (MSC) Functional Analysis-Macrophage Activation and Polarization Assays.

Stem cell-based therapies have evolved to become a key component of regenerative medicine approaches to human pathologies. Exogenous stem cell transplantation takes advantage of the potential of stem cells to self-renew, differentiate, home to sites of injury, and sufficiently evade the immune system to remain viable for the release of anti-inflammatory cytokines, chemokines, and growth factors. Common to many pathologies is the exacerbation of inflammation at the injury site by proinflammatory macrophages. An increasing body of evidence has demonstrated that mesenchymal stromal cells (MSCs) can influence the immunophenotype and function of myeloid lineage cells to promote therapeutic effects. Understanding the degree to which MSCs can modulate the phenotype of macrophages within an inflammatory environment is of interest when considering strategies for targeted cell therapies. There is a critical need for potency assays to elucidate these intercellular interactions in vitro and provide insight into potential mechanisms of action attributable to the immunomodulatory and polarizing capacities of MSCs, as well as other cells with immunomodulatory potential. However, the complexity of the responses, in terms of cell phenotypes and characteristics, timing of these interactions, and the degree to which cell contact is involved, have made the study of these interactions challenging. To provide a research tool to study the direct interactions between MSCs and macrophages, we developed a potency assay that directly co-cultures MSCs with naïve macrophages under proinflammatory conditions. Using this assay, we demonstrated changes in the macrophage secretome and phenotype, which can be used to evaluate the abilities of the cell samples to influence the cell microenvironment. These results suggest the immunomodulatory effects of MSCs on macrophages while revealing key cytokines and phenotypic changes that may inform their efficacy as potential cellular therapies. Key features • The protocol uses monocytes differentiated into naïve macrophages, which are loosely adherent, have a relatively homogeneous genetic background, and resemble peripheral blood mononuclear cells-derived macrophages. • The protocol requires a plate reader and a flow cytometer with the ability to detect six fluorophores. • The protocol provides a quantitative measurement of co-culture conditions by the addition of a fixed number of freshly thawed or culture-rescued MSCs to macrophages. • This protocol uses assessment of the secretome and cell harvest to independently verify the nature of the interactions between macrophages and MSCs.

The use of complementary and traditional medicine for the treatment of patients with COVID-19: A systematic review.

OBJECTIVE: The aim of this study was to evaluate the use and effectiveness of non-pharmacological therapies as part of the treatment of COVID-19 and its complications, either combined or not with the usual treatment. METHODS: A systematic review was conducted between August and October 2021 using PubMed, Scopus, CINAHL and Web of Science databases. From a total of 204 articles identified, 33 were included in the final sample (15 clinical trials and 18 quasi-experimental studies). The methodological evaluation was carried out using STROBE and CONSORT guidelines. RESULTS: There is a growing literature on the use of CAM for COVID-19. Most studies have shown positive findings, particularly for the use of TCM, other herbal therapies and acupuncture. Nevertheless, most studies were carried out in Asia and relied on quasi-experimental designs. The current evidence is available for physical outcomes (mortality rate, pneumonia resolution and other symptoms, negative PCR test, and hospitalization and ICU admissions) and for mental health outcomes. CONCLUSION: Despite a positive role of CAM on COVID-19 outcomes, the evidence is still mostly based on quasi-experimental studies. More robust clinical trials are needed in order to generate better evidence in this area.

Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists.

Lung-resident and circulatory lymphoid, myeloid, and stromal cells, expressing various pattern recognition receptors (PRRs), detect pathogen- and danger-associated molecular patterns (PAMPs/DAMPs), and defend against respiratory pathogens and injuries. Here, we report the early responses of murine lungs to nanoparticle-delivered PAMPs, specifically the retinoic acid-inducible gene I (RIG-I) agonist poly-U/UC (PUUC), with or without the TLR4 agonist monophosphoryl lipid A (MPLA). Using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we characterized the responses at 4 and 24 h after intranasal administration. Within 4 h, ribosome-associated transcripts decreased in both stromal and immune cells, followed by widespread interferon-stimulated gene (ISG) expression. Using RNA velocity, we show that lung-neutrophils dynamically regulate the synthesis of cytokines like CXCL-10, IL-1α, and IL-1ß. Co-delivery of MPLA and PUUC increased chemokine synthesis and upregulated antimicrobial binding proteins targeting iron, manganese, and zinc in many cell types, including fibroblasts, endothelial cells, and epithelial cells. Overall, our results elucidate the early PAMP-induced cellular responses in the lung and demonstrate that stimulation of the RIG-I pathway, with or without TLR4 agonists, induces a ubiquitous microbial defense state in lung stromal and immune cells. Nanoparticle-delivered combination PAMPs may have applications in intranasal antiviral and antimicrobial therapies and prophylaxis.

Mesenchymal stromal cells for bone trauma, defects, and disease: Considerations for manufacturing, clinical translation, and effective treatments.

Bone is a complex tissue capable of natural repair to injury, however, the healing process is often impaired by the untoward effects of trauma, defects, and disease. Thus, therapeutic modalities, including the use of cells involved in the body's natural healing processes, are investigated to promote or complement natural bone repair. Herein, several modalities and innovative approaches for using mesenchymal stromal cells (MSCs) to treat bone trauma, defects, and diseases are discussed. Given the evidence that supports the promising potential of MSCs, we highlight important considerations for advancing the clinical use of MSCs including the standardization of procedures from the harvest to delivery to patients and realized solutions to manufacturing. A better understanding of the current approaches implemented to address the challenges of using therapeutic MSCs will help improve study designs and, ultimately, achieve effective outcomes for restoring bone health.

A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, which are essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters could overcome the shortcomings of parenteral vaccines and enhance pre- existing systemic immunity. Here we present a new protein subunit nanovaccine using multiadjuvanted (e.g. RIG-I: PUUC, TLR9: CpG) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL- NPs, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lung, and showed robust systemic humoral immunity. Interestingly, as a purely intranasal vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. Our data suggest that PUUC+CpG PAL-NP subunit vaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine.

Despite success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability remain. Molecular adjuvants targeting pattern recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulates various PRRs, including toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. We hypothesized that targeting PRRs using molecular adjuvants on nanoparticles (NPs) along with a stabilized spike protein antigen could stimulate broad and efficient immune responses. Adjuvants targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer NPs were combined with the S1 subunit of spike protein and assessed in vitro with isogeneic mixed lymphocyte reactions (isoMLRs). For in vivo studies, the adjuvant-NPs were combined with stabilized spike protein or spike-conjugated NPs and assessed using a two-dose intranasal or intramuscular vaccination model in mice. Combination adjuvant-NPs simultaneously targeting TLR and RIG-I receptors (MPLA+PUUC, CpG+PUUC, and R848+PUUC) differentially induced T cell proliferation and increased proinflammatory cytokine secretion by APCs in vitro. When delivered intranasally, MPLA+PUUC NPs enhanced CD4+CD44+ activated memory T cell responses against spike protein in the lungs while MPLA NPs increased anti-spike IgA in the bronchoalveolar (BAL) fluid and IgG in the blood. Following intramuscular delivery, PUUC NPs induced strong humoral immune responses, characterized by increases in anti-spike IgG in the blood and germinal center B cell populations (GL7+ and BCL6+ B cells) in the draining lymph nodes (dLNs). MPLA+PUUC NPs further boosted spike protein-neutralizing antibody titers and T follicular helper cell populations in the dLNs. These results suggest that protein subunit vaccines with particle-delivered molecular adjuvants targeting TLR4 and RIG-I could lead to robust and unique route-specific adaptive immune responses against SARS-CoV-2.

Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine.

Despite recent success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability, remain. Although mRNA, pDNA, and viral-vector based vaccines are being administered, no protein subunit-based SARS-CoV-2 vaccine is approved. Molecular adjuvants targeting pathogen-recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulate various PRRs, including toll-like receptors (TLRs) and retinoic-acid-inducible gene I-like receptors (RIG-I). We hypothesized that targeting the same PRRs using adjuvants on nanoparticles along with a stabilized spike (S) protein antigen could provide broad and efficient immune responses. Formulations targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer-nanoparticles (NPs) were combined with the S1 subunit of S protein and assessed in vitro with isogeneic mixed lymphocyte reactions (iso-MLRs). For in vivo studies, the adjuvanted nanoparticles were combined with stabilized S protein and assessed using intranasal and intramuscular prime-boost vaccination models in mice. Combination NP-adjuvants targeting both TLR and RIG-I (MPLA+PUUC, CpG+PUUC, or R848+PUUC) differentially increased proinflammatory cytokine secretion (IL-1ß, IL-12p70, IL-27, IFN-ß) by APCs cultured in vitro, and induced differential T cell proliferation. When delivered intranasally, MPLA+PUUC NPs enhanced local CD4+CD44+ activated memory T cell responses while MPLA NPs increased anti-S-protein-specific IgG and IgA in the lung. Following intramuscular delivery, PUUC-carrying NPs induced strong humoral immune responses, characterized by increases in anti-S-protein IgG and neutralizing antibody titers and germinal center B cell populations (GL7+ and BCL6+ B cells). MPLA+PUUC NPs further boosted S-protein-neutralizing antibody titers and T follicular helper cell populations in draining lymph nodes. These results suggest that SARS-CoV-2-mimicking adjuvants and subunit vaccines could lead to robust and unique route-specific adaptive immune responses and may provide additional tools against the pandemic.

Nursing Education during the SARS-CoV-2 Pandemic: Assessment of Students' Satisfaction with e-Learning Environment.

The disease caused by the SARS-CoV-2 coronavirus led to the disruption of normality with respect to education, public healthcare and new technologies. Education is a fundamental pillar to increase the knowledge and morale of people. However, due to the lockdown implemented to protect the population from an infection of unknown aetiology, the education system decided to switch from face-to-face education to virtual education. This modality has affected the teaching-learning process in the Degree of Nursing, since its competencies and knowledge demand in-presence learning. The aim of this study was to evaluate the impact that telematic education had on students of the Degree of Nursing who were studying in the final year of said degree, which involves their imminent entry into the labour market. We used the client satisfaction questionnaire of Bob Hayes to gather data and analyse the satisfaction level of the nursing students. As a result, a considerable amount of information was obtained about teaching, which shows the absence of practical activities and the lack of information about safety and protection measures related to the pandemic. Most educators themselves were struggling to understand the implications of the virus and implement appropriate safety measures, since there was quite a bit of conflicting information relating to the effectiveness of personal protective safety equipment and the lifespan of the virus on various media outside of the host. It is, therefore, not surprising that education for students in this regard was lacking. In general, most of the students showed dissatisfaction with the virtual education they received.

[Attention to speed and guide traffic signs with eye movements]. / Atención a señales de velocidad y de orientación mediante movimientos oculares.

The goal of this research is to describe the visual search patterns for diverse traffic signs. Twelve drivers of both genders and different driving experience levels took part in real driving research with an instrumented car provided with an eye-tracking system. Looking at signs has a weak relation with speed reduction in cases where actual driving speed was higher. Nevertheless, among the people who looked at the sign, the percentage of those who reduce the speed below the limit is greater than of those who do not look at the sign. Guide traffic signs, particularly those mounted over the road, are more frequently glanced at than speed limit signs, with a glance duration of more than one second, in sequences of more than two consecutive fixations. Implications for driving and the possibilities and limitations of eye movement analysis for traffic sign research are discussed.

Theranostic nanocarriers combining high drug loading and magnetic particle imaging.

We report preparation of theranostic nanocarriers loaded with up to 50 wt% of the anticancer drug doxorubicin that contain magnetic nanoparticles which enable Magnetic Particle Imaging (MPI), an emerging technology for quantitative and unambiguous imaging of the nanocarriers. The nanocarriers, coated with poly(ethylene glycol)-block-poly(lactic acid) (PEG4.9kD-b-PLA6kD) block copolymer for colloidal stability, are composed of a hydrophobic core of precipitated hydrolysable doxorubicin prodrug (proDox) and magnetic nanoparticles. Transmission electron microscopy (TEM) shows evidence of precipitated proDox for nanocarriers with high drug loading of up to 50 wt%. MPI measurements show that the nanocarriers can be quantitatively imaged. The nanocarriers are internalized by MDA-MB-231 cells and their IC50 value via metabolic assay is 1.1 µM, compared to 0.21 µM for free doxorubicin. The release rate from the nanocarriers was dependent on environmental pH. These nanocarriers with high drug loading and quantitative imaging are promising candidates for future applications.

[Serial dependence in the estimation of a car's arrival time]. / Dependencia serial en la estimación del tiempo de llegada de un coche.

Serial dependence of a car's arrival time. We have studied the sequential structure of data in the arrival- time estimations. Forty participants estimated the arrival-time of a vehicle under two experimental conditions: real car and video-image. Various time series regression models were fit to our data, and residuals autocorrelations were computed. For each serial-dependence model, data were fit to three functions, namely, power, logarithmic, and linear. In both experimental conditions, the response magnitude (R) on a given trial in t was a function of the stimulus intensity (S) in such a trial (t) and of the S and R on t-1 and t-2. Assimilation effect to the previous responses and contrast effect to the previous stimuli has been found.

Hispanic health in the USA: a scoping review of the literature.

Hispanics are the largest minority group in the USA. They contribute to the economy, cultural diversity, and health of the nation. Assessing their health status and health needs is key to inform health policy formulation and program implementation. To this end, we conducted a scoping review of the literature and national statistics on Hispanic health in the USA using a modified social-ecological framework that includes social determinants of health, health disparities, risk factors, and health services, as they shape the leading causes of morbidity and mortality. These social, environmental, and biological forces have modified the epidemiologic profile of Hispanics in the USA, with cancer being the leading cause of mortality, followed by cardiovascular diseases and unintentional injuries. Implementation of the Affordable Care Act has resulted in improved access to health services for Hispanics, but challenges remain due to limited cultural sensitivity, health literacy, and a shortage of Hispanic health care providers. Acculturation barriers and underinsured or uninsured status remain as major obstacles to health care access. Advantageous health outcomes from the "Hispanic Mortality Paradox" and the "Latina Birth Outcomes Paradox" persist, but health gains may be offset in the future by increasing rates of obesity and diabetes. Recommendations focus on the adoption of the Health in All Policies framework, expanding access to health care, developing cultural sensitivity in the health care workforce, and generating and disseminating research findings on Hispanic health.

Local 3D matrix confinement determines division axis through cell shape.

How the division axis is determined in mammalian cells embedded in three-dimensional (3D) matrices remains elusive, despite that many types of cells divide in 3D environments. Cells on two-dimensional (2D) substrates typically round up completely to divide. Here, we show that in 3D collagen matrices, mammalian cells such as HT1080 human fibrosarcoma and MDA-MB-231 breast cancer cells exhibit division modes distinct from their Counterparts on 2D substrates, with a markedly higher fraction of cells remaining highly elongated through mitosis in 3D matrices. The long axis of elongated mitotic cells accurately predicts the division axis, independently of matrix density and cell-matrix interactions. This 3D-specific elongated division mode is determined by the local confinement produced by the matrix and the ability of cells to protrude and locally remodel the matrix via ß1 integrin. Elongated division is readily recapitulated using collagen-coated microfabricated channels. Cells depleted of ß1 integrin still divide in the elongated mode in microchannels, suggesting that 3D confinement is sufficient to induce the elongated cell-division phenotype.

G-protein alpha-subunit levels in hippocampus and entorhinal cortex of brains staged for Alzheimer's disease neurofibrillary and amyloid pathologies.

G-protein alpha-subunits (Galphao, Galphai, Galphas, Galphaq) and adenylyl cyclase (AC) I and II isoforms were quantified in hippocampus and entorhinal cortex from 22 cases staged for Alzheimer's disease (AD) pathologies according to Braak and Braak. Hippocampal Galphai levels declined significantly with neurofibrillary staging, whereas AC I levels in this region increased. Significant amyloid stage-related reductions of Galphai were seen in both the hippocampus and entorhinal cortex. The hippocampus also showed a significant reduction of Galphao with amyloid staging. It is concluded that levels of inhibitory G-protein subunits Galphao, and in particular Galphai, decrease in parallel to the extent of AD pathology.

Cáncer de laringe y sinunasal en Cali, Colombia 1962 ­ 2015 / Sinonasal and laryngeal carcinoma in Cali, Colombia 1962 ­ 2015

Introducción: El cáncer es una enfermedad de alta incidencia, con múltiples factores etiológicos y diferentes características evolutivas. Objetivo: Describir la supervivencia y la tendencia de las tasas de incidencia y mortalidad por cáncer de laringe y senos paranasales en Cali (Colombia) durante el periodo 1962 a 2015. Diseño: Estudio observacional descriptivo. Métodos: La información de incidencia, durante el periodo 1962 a 2012, se obtuvo en el RPCC y la mortalidad entre 1984-2015 de la SSPM. El comportamiento de la tendencia se evaluó con el porcentaje de cambio anual (APC) y la supervivencia relativa se estimó con el método de Ederer II. La estadificación se realizó con la AJCC. Resultados: Durante 1962 a 2012, se diagnosticaron 1623 casos nuevos de cáncer, 85.2% (1383 casos) fueron de laringe y 14.8% (240 casos) sinunasal 76% fueron hombres y el CCE fue el tipo histológico más frecuente 84.1% y 59.6% en laringe y sinunasal respectivamente. Se observó una disminución significativa del riesgo de cáncer de laringe en ambos sexos, siendo mayor la disminución en hombres (APC=-1,1*(ICD95%: -1,6; -0,7)). La disminución en la tasa de incidencia de cáncer de laringe CEC fue mayor en hombres (APC=-1,1*(ICD95%: -1,6; -0,6)) durante 1962-2012. Las tasas de mortalidad disminuyeron significativamente (APC=- 2,5*(ICD95%:-3,6 -1,5)). La supervivencia relativa a 5 años durante el periodo 2008- 2012, 43,5%; 93 pacientes se estadificaron con supervivencia: T3-T4 (41,5%) y T1- T2 (55,0%). Conclusiones: El riesgo del cáncer de laringe y sinunasal escamocelular asociado al tabaquismo disminuyó de manera significativa en hombres y mujeres de Cali durante los últimos 53 años.

Introduction: Cancer is disease with high incidence, multiple etiological factors and different characteristics. Objective: To describe the survival and trend of the incidence and mortality rates for cancer of the larynx and paranasal sinuses in Cali (Colombia) during the period 1962 to 2015. Design: Descriptive observational study. Methods: Incidence information, during the period 1962 to 2012, was obtained in the RPCC and mortality between 1984-2015 of the SSPM. The behavior of the trend was evaluated with the percentage of annual change (APC) and the relative survival was estimated with the method of Ederer II. The arrangement was made with the AJCC. Results: During 1962 to 2012, 1623 new cases of cancer were diagnosed, 85.2% (1383 cases) were laryngeal and 14.8% (240 cases) sinunasal 76% were men and the CCE was the most frequent histological type 84.1% and 59.6% in larynx and sinunasal respectively. A significant decrease in the risk of laryngeal cancer was observed in both sexes, with a greater decrease in men (APC = -1.1 * (ICD95%: -1.6, -0.7)). The decrease in the incidence rate of laryngeal cancer CEC was higher in men (APC = -1.1 * (ICD95%: -1.6, -0.6)) during 1962-2012. Mortality rates decreased significantly (APC = -2.5 * (ICD95%: - 3.6 -1.5)). The 5-year relative survival rate during the period 2008-2012 was 43.5%; 93 patients were stratified with survival: T3-T4 (41.5%) and T1-T2 (55.0%). Conclusions: The risk of laryngeal and squamous cell sinonasal cancer associated to smoking decreased significantly in men and women of Cali during the last 53 years.

Three-dimensional self-assembling of gold nanorods with controlled macroscopic shape and local smectic B order.

We describe a method of controlled evaporation on a textured substrate for self-assembling and shaping gold-nanorod-based materials. Tridimensional wall features are formed over areas as large as several square millimeters. Furthermore, analyses by small-angle X-ray scattering and scanning electron microscopy techniques demonstrate that colloids are locally ordered as a smectic B phase. Such crystallization is in fact possible because we could finely adjust the nanoparticle charge, knowledge that additionally enables tuning the lattice parameters. In the future, the type of ordered self-assemblies of gold nanorods we have prepared could be used for amplifying optical signals.