CAR-T Cell Therapy: From the Shop to Cancer Therapy.

Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.

Perceptions of change in the environment caused by the COVID-19 pandemic: Implications for environmental policy.

COVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy.

The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

Changes in the natural killer cell repertoire and function induced by the cancer immune adjuvant candidate IMMUNEPOTENT-CRP.

Natural killer (NK) cells are CD3-, CD16+, CD56+ that play a crucial role in immune response by recognizing and eliminating a variety of virus-infected, malignant, and antibody-coated target cells. We examined activation; repertoire changes and effector functions of human NK cells normal donors treated with IMMUNEPOTENT-CRP (I-CRP), a bovine dialyzable leukocyte extract (DLE) containing a mixture of low molecular weight molecules. I-CRP induces human NK cells activation and increase CD56Dim CD16- subset, without inducing proliferation. Human NK cells showed an increase on NKp30, NKp44, NKp46, NKG2D, NKG2C and KIR receptors, whereas no significant differences on CD160, CD85j and CD226 where observed. I-CRP-treated human NK cells exhibited an increased degranulation activity against K562 target cells, as shown by CD107a assay, and this correlates with cytotoxicity against K562 cells observed in calcein release assay. These results indicate that I-CRP can modify human NK cells receptor repertoire leading to an increased cytotoxic activity, supporting evidence for its use to stimulate NK cells.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Short-term neuropsychiatric outcomes and quality of life in COVID-19 survivors.

BACKGROUND: The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms and QoL in COVID-19 survivors shortly after hospital discharge. METHODS: This was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity and QoL (mental and physical components) was administered by telephone. RESULTS: Of the 229 screened patients, 179 were included in the final analysis. Amongst survivors, the prevalence of moderately impaired immediate verbal memory and learning was 38%, delayed verbal memory (11.8%), verbal fluency (34.6%) and working memory (executive function) (6.1%), respectively. Moreover, 58.7% of patients had neurocognitive impairment in at least one function. Rates of positive screening for anxiety, depression and post-traumatic stress disorder were 29.6%, 26.8% and 25.1%, respectively. In addition, 39.1% of the patients had psychiatric morbidity. Low QoL for physical and mental components was detected in 44.1% and 39.1% of patients respectively. Delirium and psychiatric morbidity were associated with neurocognitive impairment, and female gender was related with psychiatric morbidity. CONCLUSION: Hospitalized COVID-19 survivors showed a considerable prevalence of neurocognitive impairment, psychiatric morbidity and poor QoL in the short term. It is uncertain if these impacts persist over the long term.

[Quantitative electroencephalogram for prediction of delayed ischemia in subarachnoid haemorrhage. Report of one case]. / Electroencefalograma cuantitativo en la predicción precoz de la isquemia cerebral tardía en hemorragia subaracnoidea aneurismática.Reporte de un caso.

Subarachnoid hemorrhage (SAH) is a devastating disease, with a mortality rate of 35%. Among patients who survive the initial bleeding, the leading cause of morbidity and mortality is delayed cerebral ischemia (DCI). Electroencephalography (EEG) can detect cerebral ischemia in the early stages. We report a 66-year-old female patient who consulted for ictal headache and impaired consciousness. On admission, she was confused, dysarthric, and with meningeal signs. Brain angio-CT showed SAH FISHER IV and an aneurysm of the left posterior cerebral artery. After excluding the aneurysm (by coiling), the patient recovered the altered consciousness. Continuous EEG monitoring was initiated. On the sixth day of follow up, she had a transient headache and apathy. The brain MRI showed low cerebral blood flow in the left frontotemporal area, without ischemic lesions. On the seventh day, she presented expression aphasia and right facial-brachial paresis. Angiography confirmed severe vasospasm in M1 and M2 segments bilaterally. Pharmacological angioplasty with nimodipine was performed, with an excellent radiological response, although not clinical. A second MRI was carried out on the eighth day, which showed a left insular infarction and generalized vasospasm. A second therapeutic angiography was performed; the patient persisted with aphasia and left central facial paresis. The quantitative EEG analysis performed retrospectively showed a generalized reduction in the spectral edge frequency 95 (SEF95; meaning slowing in the EEG signal) at the fourth day of follow up, three days earlier than the clinical and imaging diagnosis of DCI was established.

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.

Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.

IMMUNEPOTENT CRP induces DAMPS release and ROS-dependent autophagosome formation in HeLa and MCF-7 cells.

BACKGROUND: IMMUNEPOTENT CRP (ICRP) can be cytotoxic to cancer cell lines. However, its widespread use in cancer patients has been limited by the absence of conclusive data on the molecular mechanism of its action. Here, we evaluated the mechanism of cell death induced by ICRP in HeLa and MCF-7 cells. METHODS: Cell death, cell cycle, mitochondrial membrane potential and ROS production were evaluated in HeLa and MCF-7 cell lines after ICRP treatment. Caspase-dependence and ROS-dependence were evaluated using QVD.oph and NAC pre-treatment in cell death analysis. DAMPs release, ER stress (eIF2-α phosphorylation) and autophagosome formation were analyzed as well. Additionally, the role of autophagosomes in cell death induced by ICRP was evaluated using SP-1 pre-treatment in cell death in HeLa and MCF-7 cells. RESULTS: ICRP induces cell death, reaching CC50 at 1.25 U/mL and 1.5 U/mL in HeLa and MCF-7 cells, respectively. Loss of mitochondrial membrane potential, ROS production and cell cycle arrest were observed after ICRP CC50 treatment in both cell lines, inducing the same mechanism, a type of cell death independent of caspases, relying on ROS production. Additionally, ICRP-induced cell death involves features of immunogenic cell death such as P-eIF2α and CRT exposure, as well as, ATP and HMGB1 release. Furthermore, ICRP induces ROS-dependent autophagosome formation that acts as a pro-survival mechanism. CONCLUSIONS: ICRP induces a non-apoptotic cell death that requires an oxidative stress to take place, involving mitochondrial damage, ROS-dependent autophagosome formation, ER stress and DAMPs' release. These data indicate that ICRP could work together with classic apoptotic inductors to attack cancer cells from different mechanisms, and that ICRP-induced cell death might activate an immune response against cancer cells.

Prevalence of ankylosing spondylitis in Spain: EPISER2016 Study.

Objective: The aim of this study was to estimate the prevalence of ankylosing spondylitis (AS) in Spain.Method: This is a cross-sectional, population-based study of people aged 20 years or older in Spain. Randomly selected individuals were contacted by telephone and rheumatic disease screening was performed. If the first screening was positive, medical records were then reviewed and/or a telephone questionnaire was conducted by a rheumatologist, followed by an appointment if necessary. Cases had to fulfil the modified New York (mNY) criteria.Results: In total, 4916 individuals were included, of whom 355 had a positive screening result for AS. Of these, 11 were classified as AS. An additional individual who reported a prior diagnosis of rheumatoid arthritis had a diagnosis of AS confirmed on review of the medical records. Estimated prevalence was 0.26% (95% CI 0.14-0.49).Conclusion: EPISER2016 is the first population-based study to estimate the prevalence of AS in Spain, which has been estimated as being similar to that in other European countries.

Physical inactivity and excessive sucrose consumption are associated with higher serum lipids in subjects with Taq1B CETP polymorphism.

BACKGROUND: Dyslipidaemias result from the interaction between genetic and environmental factors, including diet disequilibrium and physical inactivity. Among the genetic factors associated with serum lipids, the Taq1B CETP polymorphism has been investigated. The B1 allele has been considered as a risk factor for dyslipidaemia because of its association with greater CETP levels and higher serum triglycerides. The present study aimed to determine the role of the Taq1B polymorphism with lipid and anthropometric variables and its interaction with diet and physical activity. METHODS: In total, 215 subjects were enrolled in this cross-sectional study. Diet intake was evaluated using a 3-day food consumption record and physical activity was determined in accordance with World Health Organization recommendations. The Taq1B CETP polymorphism was determined by allelic discrimination. RESULTS: Subjects with the B1B2/B2B2 genotype, who had a sucrose consumption ≥5% of the total kcal day-1 , had higher levels of total cholesterol (TC) [165.55 (142.21-188.89) mg dL-1 versus 200.19 (184.79-215.60) mg dL-1 ; P for interaction = 0.034] and low-density lipoprotein [99.29 (75.52-123.05) mg dL-1 versus 128.64 (113.59-143.69) mg dL-1 ; P for interaction = 0.037] than subjects with the B1B1 genotype. Subjects who did not perform physical activity and had the B1B2/B2B2 genotype showed significantly higher levels of TC [177.48 (161.36-193.60) mg dL-1 versus 194.49 (185.43-203.56) mg mL-1 ; P for interaction = 0.033] than subjects with the B1B1 genotype. CONCLUSIONS: We provide evidence that subjects with inadequate environmental factors carriers of the polymorphic genotype had higher serum lipid levels than subjects with the B1B1 genotype.

[Primary lymphocytic hypophysitis. Report of one case]. / Hipofisitis linfocitaria primaria. Caso clínico.

Primary lymphocytic hypophysitis is an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland, with a higher incidence during late pregnancy and the postpartum period. It causes glandular destruction, mass effect and symptoms such headache, visual field defects, ophthalmoplegia and symptoms of hypopituitarism. We report a 38-year-old postpartum woman who, after giving birth presented decreased left visual acuity associated with a non ictal headache. Magnetic resonance imaging demonstrated a sellar mass associated with decreased free thyroxine and cortisol levels. Suspecting a primary lymphocytic hypophysitis, she was treated with prednisone 60 mg/day and hormonal replacement therapy. One month later, size of the pituitary gland decreased, and the visual field defect improved. Steroidal treatment was maintained for 36 months and progressively tapered. After two years of follow-up, the imaging studies show a normal sized pituitary gland.

[Emergency endovascular management of ischemic stroke. Experience in 104 patients]. / Experiencia en el tratamiento endovascular del accidente cerebrovascular isquémico agudo en un centro chileno.

BACKGROUND: Recently, five randomized controlled trials confirmed the efficacy and safety of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. AIM: To report patients with ischemic stroke treated with endovascular methods. MATERIAL AND METHODS: Retrospective analysis of 104 patients aged 61 ± 15 years (54% males) with ischemic stroke who received endovascular treatment at a single medical center between 2009 and 2017. RESULTS: Sixty one percent were treated with intravenous thrombolysis plus endovascular procedures and 39% with endovascular procedures alone. The median door-to needle time was 61 minutes and door-to femoral puncture was 135 minutes. The median National Institute of Health Stroke Scale (NIHSS) scores on admission, 24 hours later and at discharge were 12,4 and 1 points, respectively. Middle cerebral artery was occluded in 60% of cases. Other frequent localizations where distal carotid artery in 17% and vertebro-basilar artery in 14%. Thrombolysis in cerebral infarction (TICI) scale flow score after the procedure was 3 or 2b in 58% of cases and significantly correlated with NIHSS scores at 24 hours and discharge. Fifty percent of patients had a mRankin score < = 1 and ten patients died (9.6%). Eight percent had a symptomatic intracerebral hemorrhage. CONCLUSIONS: The clinical improvement of these patients 24 hours after the procedure and at discharge demonstrate the effectiveness of endovascular treatment in ischemic stroke. The presence neurologists able to interpret multimodal images at the emergency room, the use of local guidelines, the availability of an experienced neuro-interventional team engaged with the workflow and the use of stent retrievers are strongly associated with good outcomes.

Easy Handling of Sensors and Actuators over TCP/IP Networks by Open Source Hardware/Software.

There are several specific solutions for accessing sensors and actuators present in any process or system through a TCP/IP network, either local or a wide area type like the Internet. The usage of sensors and actuators of different nature and diverse interfaces (SPI, I2C, analogue, etc.) makes access to them from a network in a homogeneous and secure way more complex. A framework, including both software and hardware resources, is necessary to simplify and unify networked access to these devices. In this paper, a set of open-source software tools, specifically designed to cover the different issues concerning the access to sensors and actuators, and two proposed low-cost hardware architectures to operate with the abovementioned software tools are presented. They allow integrated and easy access to local or remote sensors and actuators. The software tools, integrated in the free authoring tool Easy Java and Javascript Simulations (EJS) solve the interaction issues between the subsystem that integrates sensors and actuators into the network, called convergence subsystem in this paper, and the Human Machine Interface (HMI)-this one designed using the intuitive graphical system of EJS-located on the user's computer. The proposed hardware architectures and software tools are described and experimental implementations with the proposed tools are presented.

A Controlled Randomized Preliminary Trial of a Modified Dissonance-Based Eating Disorder Intervention Program.

OBJECTIVE: We conducted a controlled randomized preliminary trial of a modified dissonance-based eating disorder program (n = 24) compared to an assessment-only control condition (n = 23) via a longitudinal design (baseline, postintervention, 2-month follow-up) in a community sample of women (N = 47) with clinical (n = 22) and subclinical (n = 25) eating disorder symptoms. METHOD: The traditional content of the Body Project, a dissonance-based eating disorder prevention program, was modified to include verbal, written, and behavioral exercises designed to dissuade self-objectification and maladaptive social comparison. Women with clinical and subclinical symptoms were included in the target audience to investigate both the treatment and the indicated prevention utility of the modified dissonance program. Body dissatisfaction, self-esteem, self-objectification, thin-ideal internalization, maladaptive social comparison, trait anxiety, and eating disorder symptoms were evaluated in the control and the modified dissonance condition at baseline, postintervention, and 2-month follow-up. RESULTS: We predicted a statistically significant 2 (condition: control, modified dissonance) x 3 (time: baseline, postintervention, 2-month follow-up) interaction in the mixed factorial multivariate analyses of variance results. Results confirmed this hypothesis. Eating disorder risk factors and symptoms decreased significantly among participants in the modified dissonance condition at postintervention and 2-month follow-up compared to baseline; symptom improvement was greater among participants in the modified compared to the control condition. A secondary analysis indicated symptom improvement did not vary as a function of symptom status (clinical, subclinical), suggesting the program is efficacious in both indicated prevention and treatment applications. CONCLUSION: Results provide preliminary support for the modified dissonance program.

Inhibitory control in otherwise healthy overweight 10-year-old children.

BACKGROUND: Preventing obesity is a worldwide public health priority. In vulnerable children living in obesogenic environments, with easy access to high-caloric food, alterations in inhibitory control functions might favor excessive food intake and affect energy regulation. We hypothesized that overweight/obese children would present lower inhibitory control in comparison to normal weight children. METHODS: We measured inhibitory control functions in 93 otherwise healthy overweight/obese and 92 normal weight 10-year-old children using the Stroop test and the Go/No-Go task. Event-related potentials were recorded during the Go/No-Go task. RESULTS: Overweight/obese children showed slower reaction times (1248.6 ms (95% confidence interval (CI): 1182.9-1314.3) vs 1149.0 ms (95% CI: 1083.0-1215.1)) on the Stroop test, higher reaction time variability (0.25 (95% CI: 0.22-0.27) vs 0.21 (95% CI: 0.19-0.24)) on the Go/No-Go task and decreased P300 amplitude (4.1 µV (95% CI: 3.0-5.2) vs 6.4 µV (95% CI: 5.2-7.6)) on event-related potentials compared with normal weight children. CONCLUSIONS: Our results indicate altered inhibitory control functions in otherwise healthy overweight/obese children, which might contribute to their excessive food consumption.

[Natural history of mucopolysaccharidosis type III in a series of Colombian patients]. / Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.

INTRODUCTION: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. CASE REPORTS: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. CONCLUSIONS: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.

TITLE: Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.Introducción. La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos. Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones. La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.

Hyaluronic acid-silica nanohybrid gels.

Excessive water sorption and low mechanical properties are a severe drawback in some biomedical applications of hyaluronic acid (HA). A way to improve these properties is here explored through the novel concept of nanohybrid hydrogels consisting of a HA matrix including different amounts of silica-derived species. This inorganic filler phase controls the mechanical and swelling properties of HA cross-linked matrices. Below a 2 wt % of silica in the systems, nanoparticle aggregates of tens of nanometers and silica oligomers are distributed more or less homogeneously throughout the organic matrix, without percolating. This morphology of the silica phase is accompanied by an increased swelling degree of the composite when compared with pure HA. For higher silica mass ratios in the composites the inorganic counterpart coalesces, leading to a continuous inorganic silica network interpenetrated with the organic HA network, which coexists with a dispersed phase of silica-nanoparticle aggregates. Silica oligomers originating in the exposition of the nanoparticles to reactives during the composite preparation procedure contribute to the continuity of the silica network. For these compositions, swelling is reduced three times when compared with pure HA, and a significant improvement of the mechanical properties occurs. Water-containing samples of these materials exhibited a glass transition, which pure dry HA does not. None of the compositions studied showed any cytotoxicity. Thus, the materials could be of use in tissue engineering applications where these properties of HA need to be modulated.