Selective loss of CD107a TIGIT+ memory HIV-1-specific CD8+ T cells in PLWH over a decade of ART.

The co-expression of inhibitory receptors (IRs) is a hallmark of CD8+ T-cell exhaustion (Tex) in people living with HIV-1 (PLWH). Understanding alterations of IRs expression in PLWH on long-term antiretroviral treatment (ART) remains elusive but is critical to overcoming CD8+ Tex and designing novel HIV-1 cure immunotherapies. To address this, we combine high-dimensional supervised and unsupervised analysis of IRs concomitant with functional markers across the CD8+ T-cell landscape on 24 PLWH over a decade on ART. We define irreversible alterations of IRs co-expression patterns in CD8+ T cells not mitigated by ART and identify negative associations between the frequency of TIGIT+ and TIGIT+ TIM-3+ and CD4+ T-cell levels. Moreover, changes in total, SEB-activated, and HIV-1-specific CD8+ T cells delineate a complex reshaping of memory and effector-like cellular clusters on ART. Indeed, we identify a selective reduction of HIV-1 specific-CD8+ T-cell memory-like clusters sharing TIGIT expression and low CD107a that can be recovered by mAb TIGIT blockade independently of IFNγ and IL-2. Collectively, these data characterize with unprecedented detail the patterns of IRs expression and functions across the CD8+ T-cell landscape and indicate the potential of TIGIT as a target for Tex precision immunotherapies in PLWH at all ART stages.

Different Brain Phenotypes in Magnetic Resonance Imaging of Healthy Children after Prenatal Insults.

In this study, we used magnetic resonance imaging (MRI) to identify the different brain phenotypes within apparently healthy children and to evaluate whether these phenotypes had different prenatal characteristics. We included 65 healthy children (mean age, 10 years old) with normal neurological examinations and without structural abnormalities. We performed cluster analyses to identify the different brain phenotypes in the brain MRI images. We performed descriptive analyses, including demographic and perinatal characteristics, to assess the differences between the clusters. We identified two clusters: Cluster 1, or the "small brain phenotype" (n = 44), which was characterized by a global reduction in the brain volumes, with smaller total intracranial volumes (1044.53 ± 68.37 vs. 1200.87 ± 65.92 cm3 (p < 0.001)), total grey-matter volumes (644.65 ± 38.85 vs. 746.79 ± 39.37 cm3 (p < 0.001)), and total white-matter volumes (383.68 ± 40.17 vs. 443.55 ± 36.27 cm3 (p < 0.001)), compared with Cluster 2, or the "normal brain phenotype" (n = 21). Moreover, almost all the brain areas had decreased volumes, except for the ventricles, caudate nuclei, and pallidum areas. The risk of belonging to "the small phenotype" was 82% if the child was preterm, 76% if he/she was born small for his/her gestational age and up to 80% if the mother smoked during the pregnancy. However, preterm birth appears to be the only substantially significant risk factor associated with decreased brain volumes.

Development and validation of a questionnaire to evaluate satisfaction of the patient with diabetes at the primary care level.

Aims: To develop and validate a new instrument to measure satisfaction with integral care (doctor-nurse) of the patient with type 2 diabetes mellitus, considering expectations-experiences together for the primary level of care. Methods: The instrument was constructed with questions regarding integral care to measure the satisfaction of the diabetes patient and was classified into four domains. The validity of the content was done through a panel of experts, apparent validity through a focus group, the validity of the construct through analysis of the main components and confirmatory factorial analysis, instrument reliability with internal consistency, determined by Cronbach alpha and temporal stability (test-retest). Results: The reliability of the questionnaire was 0.942. The intraclass correlation coefficient was 0.849. Validity of the construct showed acceptable goodness-of-fit and factorial structure with four factors: communication, empathy, technical care, care continuity, and 24 items for each domain, giving a Kayser-Meyer-Olkin index above 0.80 and a total variance above 73. Conclusions: The instrument is reliable and is also valid in terms of up into construct and content to evaluate satisfaction. Practice Implications: In addition, these results allow to have elements for the design of strategies aimed at improving the relationship of health personnel with the patient.

¿Cómo afectará a la expansión de la pandemia del coronavirus SARS CoV-2 el verano boreal? / How will the SARS CoV-2 coronavirus pandemic affect the boreal summer?

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Duration of immunity to measles, rubella and mumps during the first year of life.

INTRODUCTION AND OBJECTIVES: The MMR vaccine was included in the official vaccination schedule in Spain in 1981. Currently, most women of childbearing age are vaccinated and have not been naturally infected. Several studies have shown that vaccinated women have a lower antibody concentration than that achieved after natural infection, and a shorter duration of transplacentally acquired antibodies in their children. The objective of this study was to determine the antibody titer in mothers and their infants at birth and throughout the first year of life under current epidemiological circumstances. MATERIAL AND METHODS: Single-center, observational, descriptive and prospective study conducted between October 2013 and December 2014. One sample of serum and another of a dried blood spot on filter paper were taken from each mother. Dried blood spot samples on filter paper were taken from the children at birth, and at 3, 6, 9 and 12 months. In all the samples, levels of antibodies to the measles, rubella and mumps viruses were measured using standardized quantitative assays. RESULTS: 146 mother-child pairs were included. 78.4%, 86.9% and 67.1% of mothers had antibodies to measles, rubella and mumps, respectively. A decrease in the antibody titer in children was observed after 3 months, and no antibodies against the three diseases were detected by the age of 6 months. Comparisons revealed no statistically significant differences between the antibody titers of children of mothers born before or after 1981 during the first year of their life. DISCUSSION: The rapid loss of transplacentally acquired antibodies against measles, rubella and mumps, under current epidemiological conditions, suggests that bringing the MMR vaccination forward to 9 months might be justified. Larger population studies are needed to confirm these results.

Bioselection Reveals miR-99b and miR-485 as Enhancers of Adenoviral Oncolysis in Pancreatic Cancer.

Oncolytic viruses are designed for cancer treatment. Cell-virus interactions are key determinants for successful viral replication. Therefore, the extensive reprogramming of gene expression that occurs in tumor cells might create a hurdle for viral propagation. We used a replication-based approach of a microRNA (miRNA) adenoviral library encoding up to 243 human miRNAs as a bioselection strategy to identify miRNAs that facilitate adenoviral oncolytic activity in pancreatic ductal adenocarcinoma. We identify two miRNAs, miR-99b and miR-485, that function as enhancers of adenoviral oncolysis by improving the intra- and extracellular yield of mature virions. An increased adenoviral activity is the consequence of enhanced E1A and late viral protein expression, which is probably mediated by the downregulation of the transcriptional repressors ELF4, MDM2, and KLF8, which we identify as miR-99b or miR-485 target genes. Arming the oncolytic adenovirus ICOVIR15 with miR-99b or miR-485 enhances its fitness and its antitumoral activity. Our results demonstrate the potential of this strategy to improve oncolytic adenovirus potency, and they highlight miR-99b and miR-485 as sensitizers of adenoviral replication.

Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a disease with a high prevalence in the adult population. Nonsteroidal anti-inflammatory drugs (NSAID) or intra-articular injections [hyaluronic acid (HA) or platelet-rich plasma (PRP)] can provide clinical benefit. Magnetic resonance imaging (MRI) has proven to be useful for the evaluation of cartilage volume and thickness in knee osteoarthritis. The purpose of this study was to evaluate the benefit provided by PRP injection in comparison with hyaluronic acid and NSAID in knee OA patients and to compare the radiographic evolution at the 52-week follow-up. METHODS: One hundred and six patients were enrolled and randomized according to the Spanish Rheumatology Society knee osteoarthritis diagnosis criteria. Ninety-eight patients completed the study (33 received NSAID treatment, 32 a single hyaluronic acid injection and 33 a single PRP injection). Patients were prospectively evaluated at baseline, 26 and 52 weeks using the Western Ontario McMaster Universities osteoarthritis index (WOMAC) and the visual analogue scale (VAS), and at baseline and 52 weeks with X-ray and MRI. RESULTS: A 20% decrease in WOMAC pain and increase in physical function was found in 30 and 24%, respectively, of those patients who received PRP treatment, at the 52-week follow-up. WOMAC pain and VAS improved in the hyaluronic acid and NSAID groups. However, better results were obtained in the PRP group compared to hyaluronic acid and NSAIDs (P < 0.05). No differences in Kellgren-Lawrence or cartilage thickness progression were found. CONCLUSIONS: Leukocyte-poor platelet-rich plasma (LP-PRP) injections are better in terms of clinical improvement with respect to HA injections or oral NSAID treatment in knee osteoarthritis patients at the 52-week follow-up. Moreover, a single LP-PRP injection is effective. However, LP-PRP has no influence on cartilage progression. LEVEL OF EVIDENCE: Level II.

Retinal structure assessed by OCT as a biomarker of brain development in children born small for gestational age.

PURPOSE: To identify differences in neuronal tissue from retinal and brain structures in children born small for gestational age (SGA) with no abnormality in neonatal brain ultrasonography and no previous neurological impairment, and to evaluate the relationship between retinal structure and brain changes in school-age children born SGA. METHODS: Two cohorts of children were recruited: 25 children born SGA and 25 children born with an appropriate birth weight according to gestational age. All the children underwent an ophthalmic examination, which included retinal imaging using spectral-domain optical coherence tomography, and a brain MRI. MRI images were automatically segmented and global and regional brain volumes were obtained. RESULTS: Although visual function did not differ between both groups, the complex ganglion cell and inner plexiform layers (GCL-IPL) was thinner in SGA children. Total intracranial volume, and global grey and white matter volumes in brain and cerebellum were correlated with birthweight centile, as were certain regional volumes (temporal and parietal lobes, hippocampus and putamen). Abnormal GCL-IPL measurements accurately identified SGA children with the most severe grey and white matter changes in the brain. CONCLUSIONS: SGA children, both preterm and term born, showed evidence of structural abnormalities in the retina, which may be an accurate and non-invasive biomarker of neuronal damage in brain tissue.

Determination of mutagenic amines in water and food samples by high pressure liquid chromatography with amperometric detection using a multiwall carbon nanotubes-glassy carbon electrode.

A chromatographic method, using amperometric detection, for the sensitive determination of six representative mutagenic amines was developed. A glassy carbon electrode (GCE), modified with multiwall carbon nanotubes (GCE-CNTs), was prepared and its response compared to a conventional glassy carbon electrode. The chromatographic method (HPLC-GCE-CNTs) allowed the separation and the determination of heterocyclic aromatic amines (HAAs) classified as mutagenic amines by the International Agency for Research of Cancer. The new electrode was systematically studied in terms of stability, sensitivity, and reproducibility. Statistical analysis of the obtained data demonstrated that the modified electrode provided better sensitivity than the conventional unmodified ones. Detection limits were in the 3.0 and 7.5 ng/mL range, whereas quantification limits ranged between 9.5 and 25.0 ng/mL were obtained. The applicability of the method was demonstrated by the determination of the amines in several types of samples (water and food samples). Recoveries indicate very good agreement between amounts added and those found for all HAAs (recoveries in the 92% and 105% range).

Primary intracranial mucosa-associated lymphoid tissue lymphoma. A report of two cases and literature review.

Low-grade B cell non-Hodgkin lymphomas typically arise from the marginal zone of the secondary lymphatic follicles. Their intracranial expression is very rare, most frequently affecting the dura mater and the choroid plexus glomi in the lateral ventricles. Their initial evaluation requires the exclusion of more common extra-axial lesions, such as meningiomas, dural metastasis, granulomatous lesions or secondary lymphoproliferative dural extension from body lymphomas. Whenever a ventricular lesion is present, the patient's age and lesion location help narrow the differential diagnosis. Dural-based lymphomas and ventricular/choroid plexus lymphomas are slow-growing lesions with imaging features similar to meningiomas, which is typically their main differential consideration. Diffusion-weighted images frequently show restricted diffusion behaviour on lymphomas, helping to differentiate them from the typical meningiomas.

Sistema de teleconsulta médica / Medical tele consults system

En Cuba, los profesionales de la salud se comunican a través del intercambio persona-persona, y a través de vías como teléfono, correo electrónico y en ocasiones mediante la clínica virtual cubana. Todo esto hace más compleja la evaluación y diagnóstico temprano de los profesionales médicos. El presente trabajo se centra en el producto Sistema de Teleconsulta, del proyecto Teleconsulta, del Departamento de Sistemas Especializados de la Facultad 7, UCI (Universidad de las Ciencias Informáticas). Este tiene como objetivo intercambiar información online, que servirá para realizar diagnósticos certeros y rápidos de los pacientes. Para darle cumplimiento al objetivo, se realizó un estudio de las herramientas y tecnologías necesarias para su desarrollo, entre ellas, Java como lenguaje de programación, Eclipse como entorno de desarrollo, Base de Datos PostgreSQL y Servidor de Streamin Red5(AU)

In Cuba, health professionals communicate by person-person exchanging, and through means such as telephone, email and sometimes through the virtual clinic in Cuba. All this complicates the assessment and early diagnosis of medical professionals. This work focuses on the product Teleconsulta System, Teleconsulta project, Specialized Systems Department, Faculty 7, UCI (University of Information Sciences). This aims to exchange information online, that will assist in accurate and rapid diagnosis of patients. To accomplish the objective, this paper includes a study of the tools and technologies needed for development, including Java programming language, Eclipse as a development environment, and PostgreSQL Database Server Streamin Red5(AU)

Sistema automatizado para la gestión del programa de control sanitario internacional de Cuba / Automated system for management of the international health control program in Cuba

El programa de Control Sanitario Internacional propuesto en Cuba permite el control y seguimiento de la importación de productos, enfermedades endémicas de otros países y las transmisibles por vectores. Todo esto es realizado en formato duro, de forma manual, por teléfono, correo y Excel. Existen algunos sistemas desarrollados que no presentan todas las funcionalidades necesarias para el manejo de la información requerida. En la Universidad de las Ciencias Informáticas (UCI), se desarrolló el sistema Control Sanitario Internacional (CSI) y su objetivo fundamental es automatizar todos los procesos relacionados a la vigilancia, seguimiento de la higiene de los productos, control de foco y la detección de enfermedades. Para la implementación se utilizó Apache, base de datos MySQL 5, PHP 5 y el framework CodeIgniter v1.6. Con la implantación del sistema se espera centralizar la gestión de la información, otorgando rapidez, calidad y seguridad en la información(AU)

The International Health Control Program proposed in Cuba allows the control and monitoring of the import of products, endemic and vector borne diseases from other countries. All this is done in hard format, manually, by phone, mail and Excel. There are some systems that doesn't have developed all the necessary features for managing the information required. At the University of Informatics Sciences (UCI), we developed the system International Health Control (CSI). Its main objective is to automate all the processes related to surveillance, monitoring of hygiene, control of focus and the disease detection. For the implementation we used Apache, MySQL 5 database, PHP 5 and CodeIgniter 1.6 framework. With the implementation of the system is expected to centralize information management, providing speed, quality and information security(AU)

New findings in the ataxia of Charlevoix-Saguenay.

The aim of the study was to enhance our understanding of the pathogenesis of the ataxia of Charlevoix-Saguenay, based on the findings presented herein. Five patients with a molecular diagnosis of this disease underwent clinical, radiological, ophthalmologic and electrophysiological examinations. Five novel mutations, which included nonsense and missense variants, were identified, with these resulting in milder phenotypes. In addition to the usual manifestations, a straight dorsal spine was found in every case, and imaging techniques showed loss of the dorsal kyphosis. Cranial MRI demonstrated hypointense linear striations at the pons. Tensor diffusion MRI sequences revealed that these striations corresponded with hyperplastic pontocerebellar fibres, and tractographic sequences showed interrupted pyramidal tracts at the pons. Ocular coherence tomography demonstrated abnormal thickness of the nerve fibre layer. Electrophysiological studies showed nerve conduction abnormalities compatible with a dysmyelinating neuropathy, with signs of chronic denervation in distal muscles. The authors suggest that the hyperplastic pontocerebellar fibres compress the pyramidal tracts at the pons, and that the amount of retinal fibres traversing the optic discs is enlarged. These facts point to the contribution of an abnormal developmental mechanism in the ataxia of Charlevoix-Saguenay. Accordingly, spasticity would be mediated by compression of the pyramidal tracts, neuromuscular symptoms by secondary axonal degeneration superimposed on the peripheral myelinopathy, while the cause of the progressive ataxia remains speculative. The distinctive aspect of the dorsal spine could be of help in the clinical diagnosis.

Is the ataxia of Charlevoix-Saguenay a developmental disease?

The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is considered a neurodegenerative disease caused by mutations in the SACS gene, located on chromosome 13q12.12. It is a syndrome that comprises skeletal, retinal and neurological manifestations, among which feature spasticity, cerebellar ataxia and peripheral neuropathy. Five patients with a molecular diagnosis of ARSACS underwent clinical, radiological, and ophthalmologic examinations. Every one of the identified causal mutations was novel. Spastic ataxia, peripheral neuropathy, pes cavus, and hammertoes were found in every case. T2 and T2-fluid attenuation inversion recovery-weighted MRI sequences demonstrated cerebellar atrophy and a hypointense linear striation at the pons. Tensor diffusion sequences revealed that the hypointense striation corresponded with hyperplasia of the pontocerebellar fibres, which gave place to abnormally thick middle cerebellar peduncles. Stereophotographs of the optic discs showed an increased number of retinal fibres, and ocular coherence tomography, increased thickness of the retinal nerve fibre layer. The authors suggest that the hyperplasic pontocerebellar fibres compress the pyramidal tracts at the pons since a very early stage of central nervous system development, causing spasticity, and may also cause cerebellar atrophy by means of glutamate-induced excitotoxicity. The abnormal amount of retinal fibres traversing the optic discs could have caused the detected mild peripheral visual field defects. Taken together, these facts point to a developmental cause in ARSACS, as it does not exhibit the tissue atrophy characteristic of degenerative diseases. Clinical deterioration in ARSACS seems to be mediated by phenomena (compression of the pyramidal tracts and cerebellar glutamate-mediated excitotoxicity) derived from the developmental anomalies referred to, while the neuromuscular symptoms are caused by a peripheral neuropathy with pathologic features suggestive of a similar origin. These observations should be taken into account when research about the origin of ARSACS is undertaken.

Outpatient treatment with corticosteroids and antibiotics for acalculous cholecystitis in chronic granulomatous disease.

UNLABELLED: We report the outpatient management of acalculous colecistitis in an 18-y-old male with X-linked chronic granulomatous disease. The patient complained of abdominal pain and the initial ultrasound showed a gallbladder with a thickened wall. CONCLUSION: In chronic granulomatous disease, pain from a thickened gallbladder disappears after oral treatment with glucocorticoids and antibiotics.

Creencias sobre infecciones respiratorias aguda en niños menores de cinco años: estudio etnográfico en dos comunidades indígenas del estado de Oaxaca / Beliefs on acute respiratory infection in children younger than five years old: ethnographic study in two indigenous communities of the State of Oaxaca

Introducción. En México se ha logrado disminuir la mortalidad por infecciones respiratorias agudas, en un 41.5 por ciento de 1990 a 1997. El descenso no ha sido mayor, porque los grupos indígenas y marginados siguen manteniendo altas tasas de mortalidad. Material y métodos. Estudio etnográfico, realizado en dos comunidades indígenas una mixteca y otra zapoteca de diferentes regiones del estado de Oaxaca. Población de estudio: 24 madres mixtecas y 15 zapotecas entre 15 y 65 años, con uno o más niños menores de cinco años. Se les aplicaron dos cuestionarios: uno, semi-abierto y otro socioeconómico, traducidos oralmente por personas de las comunidades. Objetivo. Conocer ¿cómo las madres de dos comunidades indígenas de diferentes regiones del estado de Oaxaca perciben e identifican a las infecciones respiratorias agudas y a qué prácticas médicas recurren? Resultados. En la comunidad mixteca, ninguna madre reconoció la neumonía, y en la zapoteca sólo un tercio. De las infecciones respiratorias agudas superiores, la mayoría de ambas comunidades, reconoce principalmente al resfriado común. Para la atención de las enfermedades, recurren a tres acciones: tradicional, doméstica y automedicación. Ninguna madre mencionó el uso de antibióticos. Sólo cuando sus hijos tienen una infección respiratoria aguda grave, acuden a la clínica oficial. Conclusión. El desconocimiento de las percepciones maternas del proceso salud-enfermedad-atención de las infecciones respiratorias agudas, puede hacer que las actividades de capacitación, para su prevención y control, planeadas bajo la concepción occidental del modelo biomédico les resulten ajenas, contribuyendo a mantener la morbilidad y mortalidad en sus comunidades