Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial.

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.

AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.

Single domain antibodies (VHHs) are potentially disruptive therapeutics, with important biological value for treatment of several diseases, including neurological disorders. However, VHHs have not been widely used in the central nervous system (CNS), largely because of their restricted blood-brain barrier (BBB) penetration. Here, we propose a gene transfer strategy based on BBB-crossing adeno-associated virus (AAV)-based vectors to deliver VHH directly into the CNS. As a proof-of-concept, we explored the potential of AAV-delivered VHH to inhibit BACE1, a well-characterized target in Alzheimer's disease. First, we generated a panel of VHHs targeting BACE1, one of which, VHH-B9, shows high selectivity for BACE1 and efficacy in lowering BACE1 activity in vitro. We further demonstrate that a single systemic dose of AAV-VHH-B9 produces positive long-term (12 months plus) effects on amyloid load, neuroinflammation, synaptic function, and cognitive performance, in the AppNL-G-F Alzheimer's mouse model. These results constitute a novel therapeutic approach for neurodegenerative diseases, which is applicable to a range of CNS disease targets.

Esfuerzos generados en la ATM en maloclusión clase II, tratada con exodoncias de premolares y ortodoncia: análisis mediante el método de elementos finitos / Strain generated in the TMJ with class II malocclusions, treated with extraction of premolars and orthodontics: analysis with the finite element method

RESUMEN Introducción: la exodoncia de premolares es una alternativa para el tratamiento de la maloclusión clase II. Un cambio en la biomecánica puede generar alteraciones en la Articulación Temporomandibular (ATM) lo que produce mayor desgaste dental y aparición de patologías articulares. El objetivo fue analizar mediante el método de elementos finitos la concentración de esfuerzos en la ATM, en maloclusión clase II, tratados con exodoncia de premolares y Ortodoncia. Métodos: dos modelos de simulación en 3D cada uno con estructuras óseas de los 2 maxilares, dentición completa y disco en la ATM. Uno corresponde al paciente sin recidiva (SR) tratado con exodoncia de primeros premolares y ortodoncia, donde se mantiene la estabilidad dental clase I. El otro modelo con recidiva (CR) tratada con exodoncia de primeros premolares y ortodoncia, aumento de overjet y overbite y clase II canina; la carga se aplicó sobre la rama mandibular. Resultados: con una carga de 900N los esfuerzos se triplicaron en todas las estructuras de los dos modelos al ser comparados con una carga de 300N; sin embargo, se dieron diferencias considerables en el modelo CR entre las cavidades glenoideas, a 300N de 19.9 MPa y a 900N de 59.3 MPa. La mayor concentración del disco se da en la parte lateral. Conclusiones: dada la asimetría en las estructuras de la ATM, los esfuerzos y la concentración de tensiones difieren entre el lado derecho e izquierdo en los dos modelos.

Abstract Introduction: premolar extraction is an alternative for the treatment of class II malocclusion. A change in biomechanics can generate alterations in the Temporomandibular Joint (TMJ), which produces greater dental wear and the appearance of joint dysfunctions. The objective was to assess the effort concentration in the TMJ by means of finite element analysis in class II malocclusions treated with premolar extraction and orthodontics. Method: two 3D simulation models each with bone structures of the 2 jaws, complete dentition and disc in the TMJ. One corresponds to the patient without recurrence (WR) treated with extraction of first premolars and orthodontics, where class I dental stability is maintained. The other model with recurrence (R) treated with extraction of first premolars and orthodontics, increased overjet and overbite and canine class II; the load was applied to the mandibular ramus. Results: loads of 900N triplicated on all structures compared to 300N in both models. However, there were considerable differences between the left and right glenoid cavities in the WR model, at 300N of 19.9 MPa and 900N at 59.3 MPa. Most tensions of the disc occur in the lateral part. Conclusions: due to the asymmetry in the TMJ structures, the stresses and stress concentration differ between the right and left sides in the two models.

AAV9-mediated gene delivery of MCT1 to oligodendrocytes does not provide a therapeutic benefit in a mouse model of ALS.

Oligodendrocyte dysfunction has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by progressive motor neuron loss. The failure of trophic support provided by oligodendrocytes is associated with a concomitant reduction in oligodendroglial monocarboxylate transporter 1 (MCT1) expression and is detrimental for the long-term survival of motor neuron axons. Therefore, we established an adeno-associated virus 9 (AAV9)-based platform by which MCT1 was targeted mostly to white matter oligodendrocytes to investigate whether this approach could provide a therapeutic benefit in the SOD1G93A mouse model of ALS. Despite good oligodendrocyte transduction and AAV-mediated MCT1 transgene expression, the disease outcome of SOD1G93A mice was not altered. Our study further increases our current understanding about the complex nature of oligodendrocyte pathology in ALS and provides valuable insights into the future development of therapeutic strategies to efficiently modulate these cells.

Orthodontic treatment stability and periodontal condition with circumferential supracrestal fiberotomy: a systematic review / Estabilidad del tratamiento de ortodoncia y de la condición periodontal con la fibrotomía supracrestal circunferencial: revisión sistemática

ABSTRACT Introduction: stability is one of the main goals of orthodontic treatment, and circumferential supracrestal fiberotomy is an alternative to prevent relapse in cases of tooth rotation, crowding and inclined teeth. However, there are no studies demonstrating the effectiveness of this treatment and its effects on the periodontal condition. The aim of this systematic review (SR) was to evaluate the effectiveness of circumferential supracrestal fiberotomy (CSF) as an adjuvant in the stability of orthodontic treatment during retention and its effects on the periodontal condition once it has been performed. Methods: the search for topic-related studies was conducted on the PubMed and EMBASE databases until October 2018. The studies were considered eligible if they covered the use of CSF during the retention period and reported the periodontal condition in a follow-up period longer than or equal to 1 year. For bias-risk assessment in the chosen studies, the Newcastle-Ottawa Scale was applied to observational studies, and the Cochrane Collaboration tool for Randomized Clinical Trials (RCTs) and Controlled Clinical Trials (CCTs). Results: the search strategy yielded 85 potential eligible articles, of which 5 were included in the SR. Four of the five studies reported a lower irregularity rate in patients who had CSF when compared to a control group. No changes in plaque index, gingival index, insertion levels, probe depth and keratinized gingiva amount were reported. Conclusions: fiberotomy is an effective method to prevent relapse of previously rotated teeth and does not cause periodontal alterations. However, it is important to note that the studies' methodological quality was low.

RESUMEN Introducción: la estabilidad es uno de los principales objetivos del tratamiento de ortodoncia, y la fibrotomía supracrestal circunferencial es una de las alternativas para prevenir la recidiva en casos de rotaciones dentales, apiñamiento y dientes con inclinación; sin embargo, no se tienen estudios que demuestren la efectividad de este tratamiento, así como sus efectos en la condición periodontal. El objetivo de esta revisión sistemática (RS) consistió en evaluar la efectividad de la fibrotomía supracrestal circunferencial (FSC) como procedimiento coadyuvante en la estabilidad del tratamiento de ortodoncia durante la retención, así como los efectos en la condición periodontal posterior a su realización. Métodos: la búsqueda de estudios relacionados con el tema se realizó mediante las bases de datos PubMed y EMBASE hasta octubre de 2018. Los estudios fueron considerados elegibles si abarcaban el uso de la FSC durante el periodo de retención y si reportaban la condición periodontal con un tiempo de seguimiento mayor o igual a un año. Para la evaluación del riesgo de sesgos en los estudios elegidos, se aplicó la escala Newcastle-Ottawa en los estudios observacionales y la herramienta de colaboración Cochrane para los ensayos clínicos aleatorizados (ECA) y ensayos clínicos controlados (ECC). Resultados: la estrategia de búsqueda arrojó 85 posibles artículos elegibles, de los cuales 5 fueron incluidos en la RS. Cuatro de los cinco estudios reportaron un índice de irregularidad menor en los pacientes que tuvieron FSC cuando se compararon con un grupo control. Con respecto a la condición periodontal, no se reportaron cambios en índice de placa, índice gingival, niveles de inserción, profundidad al sondaje y cantidad de encía queratinizada. Conclusiones: la fibrotomía es un método eficaz para evitar la recidiva de dientes previamente rotados y no genera alteraciones a nivel periodontal. Sin embargo, es importante tener en cuenta que la calidad metodológica de los estudios no fue alta.

Widespread transduction of astrocytes and neurons in the mouse central nervous system after systemic delivery of a self-complementary AAV-PHP.B vector.

Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher efficiency. We investigated how much we could boost CNS transgene expression by using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or scAAV2/PHP.B-GFP at equivalent doses. Three weeks postinjection, transgene expression was assessed in brain and spinal cord. We consistently observed more widespread CNS transduction and higher levels of transgene expression when using the scAAV2/PHP.B-GFP vector. In particular, we observed an unprecedented level of astrocyte transduction in the cortex, when using a ubiquitous CBA promoter. In comparison, neuronal transduction was much lower than previously reported. However, strong neuronal expression (including spinal motor neurons) was observed when the human synapsin promoter was used. These findings constitute the first reported use of an AAV-PHP.B capsid, encapsulating a scAAV genome, for gene transfer in adult mice. Our results underscore the potential of this AAV construct as a platform for safer and more efficacious gene therapy vectors for the CNS.

An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody.

Astrocytes are a major cell type in the mammalian CNS. Astrocytes are now known to play a number of essential roles in processes including synapse formation and function, as well as blood-brain barrier formation and control of cerebral blood flow. However, our understanding of the molecular mechanisms underlying astrocyte development and function is still rudimentary. This lack of knowledge is at least partly due to the lack of tools currently available for astrocyte biology. ACSA-2 is a commercially available antibody originally developed for the isolation of astrocytes from young postnatal mouse brain, using magnetic cell-sorting methods, but its utility in isolating cells from adult tissue has not yet been published. Using a modified protocol, we now show that this tool can also be used to isolate ultrapure astrocytes from the adult brain. Furthermore, using a variety of techniques (including single-cell sequencing, overexpression and knockdown assays, immunoblotting, and immunohistochemistry), we identify the ACSA-2 epitope for the first time as ATP1B2 and characterize its distribution in the CNS. Finally, we show that ATP1B2 is stably expressed in multiple models of CNS injury and disease. Hence, we show that the ACSA-2 antibody possesses the potential to be an extremely valuable tool for astrocyte research, allowing the purification and characterization of astrocytes (potentially including injury and disease models) without the need for any specialized and expensive equipment. In fact, our results suggest that ACSA-2 should be a first-choice method for astrocyte isolation and characterization.

A large animal model of spinal muscular atrophy and correction of phenotype.

OBJECTIVES: Spinal muscular atrophy (SMA) is caused by reduced levels of survival motor neuron (SMN) protein, which results in motoneuron loss. Therapeutic strategies to increase SMN levels including drug compounds, antisense oligonucleotides, and scAAV9 gene therapy have proved effective in mice. We wished to determine whether reduction of SMN in postnatal motoneurons resulted in SMA in a large animal model, whether SMA could be corrected after development of muscle weakness, and the response of clinically relevant biomarkers. METHODS: Using intrathecal delivery of scAAV9 expressing an shRNA targeting pig SMN1, SMN was knocked down in motoneurons postnatally to SMA levels. This resulted in an SMA phenotype representing the first large animal model of SMA. Restoration of SMN was performed at different time points with scAAV9 expressing human SMN (scAAV9-SMN), and electrophysiology measurements and pathology were performed. RESULTS: Knockdown of SMN in postnatal motoneurons results in overt proximal weakness, fibrillations on electromyography indicating active denervation, and reduced compound muscle action potential (CMAP) and motor unit number estimation (MUNE), as in human SMA. Neuropathology showed loss of motoneurons and motor axons. Presymptomatic delivery of scAAV9-SMN prevented SMA symptoms, indicating that all changes are SMN dependent. Delivery of scAAV9-SMN after symptom onset had a marked impact on phenotype, electrophysiological measures, and pathology. INTERPRETATION: High SMN levels are critical in postnatal motoneurons, and reduction of SMN results in an SMA phenotype that is SMN dependent. Importantly, clinically relevant biomarkers including CMAP and MUNE are responsive to SMN restoration, and abrogation of phenotype can be achieved even after symptom onset.

scAAV9 intracisternal delivery results in efficient gene transfer to the central nervous system of a feline model of motor neuron disease.

On the basis of previous studies suggesting that vascular endothelial growth factor (VEGF) could protect motor neurons from degeneration, adeno-associated virus vectors (serotypes 1 and 9) encoding VEGF (AAV.vegf) were administered in a limb-expression 1 (LIX1)-deficient cat-a large animal model of lower motor neuron disease-using three different delivery routes to the central nervous system. AAV.vegf vectors were injected into the motor cortex via intracerebral administration, into the cisterna magna, or intravenously in young adult cats. Intracerebral injections resulted in detectable transgene DNA and transcripts throughout the spinal cord, confirming anterograde transport of AAV via the corticospinal pathway. However, such strategy led to low levels of VEGF expression in the spinal cord. Similar AAV doses injected intravenously resulted also in poor spinal cord transduction. In contrast, intracisternal delivery of AAV exhibited long-term transduction and high levels of VEGF expression in the entire spinal cord, yet with no detectable therapeutic clinical benefit in LIX1-deficient animals. Altogether, we demonstrate (i) that intracisternal delivery is an effective AAV delivery route resulting in high transduction of the entire spinal cord, associated with little to no off-target gene expression, and (ii) that in a LIX1-deficient cat model, however, VEGF expressed at high levels in the spinal cord has no beneficial impact on the disease course.

A single intravenous AAV9 injection mediates bilateral gene transfer to the adult mouse retina.

Widespread gene delivery to the retina is an important challenge for the treatment of retinal diseases, such as retinal dystrophies. We and others have recently shown that the intravenous injection of a self-complementary (sc) AAV9 vector can direct efficient cell transduction in the central nervous system, in both neonatal and adult animals. We show here that the intravenous injection of scAAV9 encoding green fluorescent protein (GFP) resulted in gene transfer to all layers of the retina in adult mice, despite the presence of a mature blood-eye barrier. Cell morphology studies and double-labeling with retinal cell-specific markers showed that GFP was expressed in retinal pigment epithelium cells, photoreceptors, bipolar cells, Müller cells and retinal ganglion cells. The cells on the inner side of the retina, including retinal ganglion cells in particular, were transduced with the highest efficiency. Quantification of the cell population co-expressing GFP and Brn-3a showed that 45% of the retinal ganglion cells were efficiently transduced after intravenous scAAV9-GFP injection in adult mice. This study provides the first demonstration that a single intravenous scAAV9 injection can deliver transgenes to the retinas of both eyes in adult mice, suggesting that this vector serotype is able to cross mature blood-eye barriers. This intravascular gene transfer approach, by eliminating the potential invasiveness of ocular surgery, could constitute an alternative when fragility of the retina precludes subretinal or intravitreal injections of viral vectors, opening up new possibilities for gene therapy for retinal diseases.

Intramuscular scAAV9-SMN injection mediates widespread gene delivery to the spinal cord and decreases disease severity in SMA mice.

We have recently demonstrated the remarkable efficiency of self-complementary (sc) AAV9 vectors for central nervous system (CNS) gene transfer following intravenous delivery in mice and larger animals. Here, we investigated whether gene delivery to motor neurons (MNs) could also be achieved via intramuscular (i.m.) scAAV9 injection and subsequent retrograde transport along the MNs axons. Unexpectedly, we found that a single injection of scAAV9 into the adult mouse gastrocnemius (GA) mediated widespread MN transduction along the whole spinal cord, without limitation to the MNs connected to the injected muscle. Spinal cord astrocytes and peripheral organs were also transduced, indicating vector spread from the injected muscle to both the CNS and the periphery through release into the blood circulation. Moreover, we showed that i.m. injection of scAAV9 vectors expressing "survival of motor neuron" (Smn) in spinal muscular atrophy (SMA) mice mediated high survival motor neuron (SMN) expression levels at both the CNS and the periphery, and increased the median lifespan from 12 days to 163 days. These findings represent to date the longest extent in survival obtained in SMA mice following i.m. viral vector gene delivery, and might generate a renewed interest in the use of i.m. adeno-associated viruses (AAV) delivery for the development of gene therapy strategies for MN diseases.

Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders.

Adeno-associated virus type 9 (AAV9) is a powerful tool for delivering genes throughout the central nervous system (CNS) following intravenous injection. Preclinical results in pediatric models of spinal muscular atrophy (SMA) and lysosomal storage disorders provide a compelling case for advancing AAV9 to the clinic. An important translational step is to demonstrate efficient CNS targeting in large animals at various ages. In the present study, we tested systemically injected AAV9 in cynomolgus macaques, administered at birth through 3 years of age for targeting CNS and peripheral tissues. We show that AAV9 was efficient at crossing the blood-brain barrier (BBB) at all time points investigated. Transgene expression was detected primarily in glial cells throughout the brain, dorsal root ganglia neurons and motor neurons within the spinal cord, providing confidence for translation to SMA patients. Systemic injection also efficiently targeted skeletal muscle and peripheral organs. To specifically target the CNS, we explored AAV9 delivery to cerebrospinal fluid (CSF). CSF injection efficiently targeted motor neurons, and restricted gene expression to the CNS, providing an alternate delivery route and potentially lower manufacturing requirements for older, larger patients. Our findings support the use of AAV9 for gene transfer to the CNS for disorders in pediatric populations.

Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice.

Spinal muscular atrophy (SMA) is the most common genetic disease leading to infant mortality. This neuromuscular disorder is caused by the loss or mutation of the telomeric copy of the 'survival of motor neuron' (Smn) gene, termed SMN1. Loss of SMN1 leads to reduced SMN protein levels, inducing degeneration of motor neurons (MN) and progressive muscle weakness and atrophy. To date, SMA remains incurable due to the lack of a method to deliver therapeutically active molecules to the spinal cord. Gene therapy, consisting of reintroducing SMN1 in MNs, is an attractive approach for SMA. Here we used postnatal day 1 systemic injection of self-complementary adeno-associated virus (scAAV9) vectors carrying a codon-optimized SMN1 sequence and a chimeric intron placed downstream of the strong phosphoglycerate kinase (PGK) promoter (SMNopti) to overexpress the human SMN protein in a mouse model of severe SMA. Survival analysis showed that this treatment rescued 100% of the mice, increasing life expectancy from 27 to over 340 days (median survival of 199 days) in mice that normally survive about 13 days. The systemic scAAV9 therapy mediated complete correction of motor function, prevented MN death and rescued the weight loss phenotype close to normal. This study reports the most efficient rescue of SMA mice to date after a single intravenous injection of an optimized SMN-encoding scAAV9, highlighting the considerable potential of this method for the treatment of human SMA.

La pensión de vejez por deficiencia en la legislación colombiana: restricciones de acceso desde su instrumento evaluador / The old age pension based in deficiency in Colombian legislation and the restrictions to access to it due to its assessment tool

En el sistema de pensiones, a través de la Ley 797 del 2003, se consagró la pensión especial de vejez con el propósito de proteger personas con 50% o más de deficiencia física, psíquica o sensorial, a partir de los 55 años de edad y que acrediten 1.000 semanas cotizadas en cualquier tiempo. Aunque la norma está vigente, su consagración no es muy difundida, y se asimila a una pensión de invalidez que, además de comprender la deficiencia, reúne la discapacidad y la minusvalía, es decir, que se equipara en la práctica a los conceptos de deficiencia e invalidez. Las barreras en la aplicación de la norma se focalizan desde el instrumento para evaluar estos criterios, denominado Manual único de calificación, el cual no está acorde con la actualización de los parámetros internacionales que sirvieron de base para su elaboración; es decir, los indicados por la Organización Mundial de la Salud, lo que dificulta la evaluación de la deficiencia como criterio autónomo para una prestación económica de vejez. La controversia abarca tanto a médicos como abogados y afiliados al régimen, ya que hace necesario incentivar una reforma o proponer un nuevo instrumento de calificación en el Sistema General de Seguridad Social en Colombia.

In the pension system, through Act 797 of 2003, it devoted special old-age pension for the purpose of protecting people with 50% or more of physical, mental or sensory impairment, from 55 years of age 1000 weeks and prove listed at any time. Although the standard was in place, its consecration is not wi¬despread and is treated as a disability pension in addition to un¬derstanding the gap, meets the disability and handicap, that is equated in practice the concepts of impairment and disability. The barriers in the application of the rule, focus from the instru¬ment to assess these criteria, called the Unified Rating Manual, which is not according to the updating of international standards which were the basis for elaboration, ie, those specified by the International Health Organization, making more difficult the as-sessment of the deficiency as an independent criterion for eco¬nomic provision of old age controversy involving both doctors, lawyers and members of the regime as necessary to encourage reform or propose a new instrument qualification in the Social Security System of Colombia.

Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons.

Therapeutic gene delivery to the whole spinal cord is a major challenge for the treatment of motor neuron (MN) diseases. Systemic administration of viral gene vectors would provide an optimal means for the long-term delivery of therapeutic molecules from blood to the spinal cord but this approach is hindered by the presence of the blood-brain barrier (BBB). Here, we describe the first successful study of MN transduction in adult animals following intravenous (i.v.) delivery of self-complementary (sc) AAV9 vectors (up to 28% in mice). Intravenous MN transduction was achieved in adults without pharmacological disruption of the BBB and transgene expression lasted at least 5 months. Importantly, this finding was successfully translated to large animals, with the demonstration of an efficient systemic scAAV9 gene delivery to the neonate and adult cat spinal cord. This new and noninvasive procedure raises the hope of whole spinal cord correction of MN diseases and may lead to the development of new gene therapy protocols in patients.

Delamination of cells from neurogenic placodes does not involve an epithelial-to-mesenchymal transition.

Neurogenic placodes are specialized regions of embryonic ectoderm that generate the majority of the neurons of the cranial sensory ganglia. Here we examine in chick the mechanism underlying the delamination of cells from the epibranchial placodal ectoderm. We show that the placodal epithelium has a distinctive morphology, reflecting a change in cell shape, and is associated with a breach in the underlying basal lamina. Placodal cell delamination is distinct from neural crest cell delamination. In particular, exit of neuroblasts from the epithelium is not associated with the expression of Snail/Snail2 or of the Rho family GTPases required for the epithelial-to-mesenchymal transition seen in neural crest cell delamination. Indeed, cells leaving the placodes do not assume a mesenchymal morphology but migrate from the epithelium as neuronal cells. We further show that the placodal epithelium has a pseudostratified appearance. Examination of proliferation shows that the placodal epithelium is mitotically quiescent, with few phosphohistone H3-positive cells being identified. Where division does occur within the epithelium it is restricted to the apical surface. The neurogenic placodes thus represent specialized ectodermal niches that generate neuroblasts over a protracted period.

Despistaje de infecciones vaginales a través de citología en la población de Bramón 2001 / Screening for vaginal infections through cytology in population Bramón 2001

Las infecciones vaginales constituyen la razón más frecuente de consulta ginecológica, ya sea por vaginitis, vaginosis, enfermedades de transmisión sexual. Nuestro objetivo es determinar la prevalencia de infecciones vaginales, a través de citología relacionándola con sus principales factores de riesgo. Se estudiaron 108 pacientes entre 16 y 82 años, se les tomó citología exo cervical, siendo agrupados y analizados los datos bajo método estadístico porcentual simple. El 43,52 por ciento presentó algún tipo de infección, siendo el VPH la de mayor incidencia, seguida de Gardnerella vaginalis y Moniliasis. Con inicio de actividad sexual en la adolescencia, más de dos parejas sexuales y consumo de cigarrillos. Sugerimos realizar estudios de mayor tamaño, a fin de tener estadísticas propias para fortralecer los programas de prevención primaria.