Dermo-epidermal organotypic cultures for in vitro evaluation of skin irritation and corrosion.

In recent years, in-vitro skin models for chemical hazard identification have been developed. Most of them consist only of human keratinocytes, neglecting the contribution of other skin constituents. Cultures containing the dermal and epidermal component provide an attractive system to investigate, in a more realistic model, toxicological responses, which represents a distinct advantage over keratinocytes-based models that do not mimic faithfully the in vivo environment. This study aimed to validate dermo-epidermal organotypic cultures (ORGs) as a platform to perform irritation and corrosion tests. Skin models were constructed by seeding keratinocytes on fibroblast-containing fibrin gels. After 21 days, the ORGs were evaluated histologically, and the irritant and corrosion potential was determined by means of viability measurements (MTT assay) and cytokine release, according to 431 and 439 OECD tests guidelines. Skin models showed similar histological characteristics to native skin and were able to classify different substances with high accuracy, showing their applicability to skin irritation and corrosion tests. Although cytokines release seems to be chemical-dependent, a tendency was observed, leading to the improvement of the prediction capacity. Nevertheless, further studies should be done to reduce variability in order to increase prediction capacity.

Eficacia y seguridad de la ciclofotocoagulación transescleral con micropulsos en el tratamiento del glaucoma / Efficacy and Safety of Micropulse(R) Transscleral Cyclophotocoagulation in Glaucoma

PROPÓSITO: Comunicar nuestros resultados con la ciclofotocoagulación transescleral con el láser diodo Micropulse(R) (Iridex) en el tratamiento del glaucoma. MÉTODOS: Estudio retrospectivo en pacientes adultos con glaucoma con al menos 6 meses de seguimiento y solo una sesión de Micropulse(R). Se utilizó la misma técnica quirúrgica, el único parámetro de láser que podía variar fue el tiempo total de tratamiento (en segundos). Los parámetros restantes se mantuvieron fijos en 2 W de potencia y 0,5 ms (31,3%) de ciclo activo. RESULTADOS: Se obtuvo un total de 22 ojos de 17 pacientes con glaucoma de diversos tipos y estadios (en su mayoría congénitos y pseudoexfoliativos). El tiempo medio de seguimiento fue 7,9 meses. La duración total del tratamiento varió de 100 a 180 segundos. Definición de éxito: 5 mmHg < presión intraocular (PIO) < 21 mmHg, y una reducción ≥ 20% del valor basal y no adición de inhibidores orales de la anhidrasa carbónica y no reoperación. La tasa de éxito global fue del 72,7% en el primer mes, del 54% a los 4 meses, del 41% a los 6 meses y del 27,3% en el seguimiento final. Los pacientes tratados con duraciones de tratamiento más prolongadas (180 s) lograron mejores resultados. La reducción promedio de la PIO en ojos exitosos fue del 36% (de 26,3 a 16,7 mmHg, DE: 4,58, p = 0,028). No se informaron complicaciones. CONCLUSIONES: En una población heterogénea de glaucoma (principalmente de tipo congénito y pseudoexfoliativo) obtuvimos una baja tasa de éxito (27,3%) en el mediano plazo con una sola sesión de Micropulse(R)

OBJECTIVE: To report the results using Micropulse(R) transscleral cyclophotocoagulation (Iridex) in the treatment of glaucoma. METHODS: Retrospective study in adult patients with glaucoma with at least 6 months of follow-up, and only one session of Micropulse (R). The same surgical technique was used in all cases. The only laser parameter that could vary was the total treatment duration (in seconds). The remaining parameters were fixed at 2 Watts of power and 0.5 ms (31.3%) of active cycle. RESULTS: A total of 22 eyes of 17 patients with glaucoma of various types and stages were included (mainly congenital and pseudoexfoliation). The mean follow-up time was 7.9 months. The total treatment duration varied from 100 to 180 seconds. Definition of success: 5 mmHg < Intraocular pressure (IOP) < 21mmHg and a reduction of ≥ 20% of the baseline value and no addition of oral carbonic anhydrase inhibitors, and no re-operation. The overall success rate was 72.7% in the first month, 54% at 4 months, 41% at 6 months, and 27.3% at final follow-up. Patients with longer treatment durations (180 s) achieved better results. The mean reduction in IOP in successful eyes was 36% (from 26.3 to 16.7 mmHg, SD 4.58, P = .028). No complications were reported. CONCLUSIONS: In a heterogeneous population of glaucoma (mostly congenital and pseudoexfoliation types), a low success rate (27.3%) was obtained in the medium-term with a single session of Micropulse(R)

Efficacy and Safety of Micropulse® Transscleral Cyclophotocoagulation in Glaucoma. / Eficacia y seguridad de la ciclofotocoagulación transescleral con micropulsos en el tratamiento del glaucoma.

OBJECTIVE: To report the results using Micropulse® transscleral cyclophotocoagulation (Iridex) in the treatment of glaucoma. METHODS: Retrospective study in adult patients with glaucoma with at least 6 months of follow-up, and only one session of Micropulse®. The same surgical technique was used in all cases. The only laser parameter that could vary was the total treatment duration (in seconds). The remaining parameters were fixed at 2 Watts of power and 0.5ms (31.3%) of active cycle. RESULTS: A total of 22 eyes of 17 patients with glaucoma of various types and stages were included (mainly congenital and pseudoexfoliation). The mean follow-up time was 7.9 months. The total treatment duration varied from 100 to 180seconds. Definition of success: 5mmHg

Trastornos temporomandibulares en la infancia: bruxismo de sueño y compromiso de atm en artritis idiopática juvenil / Temporomandibular disorders in childhood: sleep bruxism and temporomandibular joint involvement in juvenile idiopathic arthritis

Los trastornos temporomandibulares (TTM) corresponden a un grupo de condiciones musculoesqueletales y neruromusculares que involucran las articulaciones temporomandibulares (ATM), los músculos masticatorios y todos los tejidos asociados. La etiología de los TTM es considerada multifactorial, siendo el bruxismo de sueño (BS) uno de muchos factores asociados con TTM dolorosos. Tanto los TTM como el BS se presentan en adultos y niños y actualmente es sabido que la etiopatogenia de ambos no difiere de acuerdo a la edad. Las ATM son articulaciones sinoviales que pueden verse afectadas por diversos TTM o por condiciones sistémicas como la artritis idiopática juvenil (AIJ). La ATM está involucrada en un 40% de los pacientes con AIJ, siendo subestimada debido a que clínica-mente se manifiesta con poco dolor. En el presente artículo se revisarán los conceptos de TTM y BS en niños, así como también la manifestación de la AIJ en el territorio orofacial, entregando una aproximación de su etiopatogenia, identificación y manejo.

Temporomandibular disorders (TMD) encompass a group of musculoskeletal and neuromuscular conditions that involve the temporomandibular joints (TMJ), the masticatory muscles, and all associated tissues. TMD's etiology is considered to be mul-tifactorial, were sleep bruxism (SB) is one of many causes of painful TMD. TMD and SB can present in adults and children and the etiology does not differ regarding age.TMJ are synovial joints that can be affected by many TMD as well as systemic conditions such as juvenile idiopathic arthritis (JIA). TMJ are involved in 40% of patients with JIA, which is usually underestimated because of its painless presentation.This article will review the concepts of TMD and SB in children, as well as JIA presentation in the orofacial region.

A report on the outbreak of Zika virus on Easter Island, South Pacific, 2014.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus circulating in Asia and Africa. In 2013, a large outbreak was reported on the archipelago of French Polynesia. In this study, we report the detection and molecular characterization of Zika virus for the first time in Chile from an outbreak among the inhabitants of Easter Island. A total of 89 samples from patients suspected of having ZIKV infection were collected between the period from January to May, 2014. Molecular diagnosis of the virus was performed by RT-PCR followed by the sequencing of the region containing the NS5 gene. A comparison of the viral nucleic acid sequence with those of other strains of ZIKA virus was performed using the MEGA software. Fifty-one samples were found positive for ZIKV by RT-PCR analysis. Further analysis of the NS5 gene revealed that the ZIKV strains identified in Easter Island were most closely related to those found in French Polynesia (99.8 to 99.9% nt and 100% aa sequence identity). These results strongly suggest that the transmission pathway leading to the introduction of Zika virus on Easter Island has its origin in French Polynesia.

Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors.

Factor replacement therapy for the treatment of moderate to severe haemophilia A and B can be complicated by the production of inhibitory alloantibodies to factor VIII (FVIII) or factor IX. Treatment with the nanofiltered anti-inhibitor coagulant complex, Factor Eight Inhibitor Bypassing Activity (FEIBA NF), is a key therapeutic option for controlling acute haemorrhages in patients with high-titre inhibitors or low-titre inhibitors refractory to replacement therapy. Given the high risk for morbidity and mortality in haemophilia patients with inhibitors to FVIII or FIX, we conducted this Phase 3 prospective study to evaluate whether prophylaxis with FEIBA NF is a safe and effective treatment option. Over a 1-year period, 17 subjects were treated prophylactically (85 ± 15 U kg(-1) every other day) while 19 subjects were treated on demand. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 7.9 (8.1), compared to 28.7 (32.3) during on-demand treatment, which amounts to a 72.5% reduction and a statistically significant difference in ABRs between arms (P = 0.0003). Three (17.6%) subjects (ITT) on prophylaxis experienced no bleeding episodes, whereas none treated on demand were bleeding episode-free. Total utilization of FEIBA NF for the treatment of bleeding episodes was significantly higher during on-demand therapy than prophylaxis (P = 0.0067). There were no differences in the rates of related adverse events between arms. This study demonstrates that FEIBA prophylaxis significantly reduces all types of bleeding compared with on-demand treatment, and the safety of prophylaxis is comparable to that of on-demand treatment.

Oclusión terapéutica: desde las escuelas de oclusión a la odontología basada en evidencia / Therapeutic occlusion: from occlusal schools of thought to evidence-based dentistry

Tanto en la práctica clínica como en la academia, siempre está presente la interrogante de cuál es la mejor posición mandibular para organizar una oclusión terapéutica y satisfacer los requerimientos estéticos y funcionales de los pacientes. Esta pregunta se podría responder desde la perspectiva de las diferentes escuelas de oclusión, siguiendo sus técnicas y utilizando su aparatología. Sin embargo, debido a que no existe suficiente evidencia científica que sustente la superioridad de una escuela sobre la otra, es preciso hacer una revisión donde se expongan los principios en que se basan las distintas filosofías oclusales, los autores que les dieron origen, la época en que surgieron y la terminología que usaron -desde el siglo pasado hasta nuestros días-, contrastándolas con la literatura científica actual. Esta no es una tarea fácil, ya que los estudios disponibles acerca de oclusión presentan gran variabilidad en la definición operacional de los términos, haciendo difícil su comparación. Se sugiere para el futuro buscar una estandarización de las definiciones y técnicas de registro, con el objeto de generar evidencia científica confiable, conducente a la creación de protocolos de recomendación para la toma de decisiones clínicas predecibles desde el punto de vista oclusal.

Both in clinical practice and academia, there is always the question about what is the best mandibular position to organize a therapeutic occlusion that satisfies functional and aesthetic requirements from patients. This question could be answered from the point of view of different occlusion schools of thought, following their techniques and using their apparatuses. However, due to the lack of scientific evidence to support the pre-eminence of a particular school over the rest, it is necessary to go through the princip les that provide the foundations for the different occlusal philosophies: the authors who gave birth to each school of thought, the time in which they were formed and the terminology they used, from the early 20th century to present times and making a comparison with current scientific literature. This is not an easy task, given that available studies about occlusion feature a great variability in the operational definition of terms, making comparison difficult. The article suggests that it would be necessary for the future to look for a standardization of recording definitions and techniques. The aim is to generate reliable scientific evidence for the creation of protocols of recommendation for predictable decision-making from an occlusal point of view.

High-throughput measurement of ionic conductivity in composition-spread thin films.

This paper demonstrates the feasibility of high-throughput investigation of ionic conductivity in oxygen-ion conductors. Yttria stabilized zirconia (YSZ) composition-spread thin films with nanometer-size grains were prepared by 90° off-axis reactive RF cosputtering. We compare results for two electrode configurations, namely, out-of-plane (parallel plate) and in-plane (planar interdigitated electrode) and find that the contribution from the intragrain conductivity in YSZ thin films (150 nm) is more explicit in the latter configuration because it greatly diminishes electrode effects. The intragrain oxygen ion conductivity of thin film YSZ was systematically measured as a function of yttria concentration over the range 2 mol % to 12 mol %. The results show that the measured conductivity of the YSZ thin films is close to that of corresponding bulk materials with a peak value around 3 × 10⁻4 S cm⁻¹ at 440 °C at the optimum Y2O3 concentration of 8 mol %. Validation of this technique means that it can be applied to novel chemical systems for which systematic bulk measurements have not been attempted.

The Innovative Socio-economic Interventions Against Tuberculosis (ISIAT) project: an operational assessment.

SETTING: Tuberculosis (TB) affected households in impoverished shantytowns, Lima, Peru. OBJECTIVE: To evaluate socio-economic interventions for strengthening TB control by improving uptake of TB care and prevention services. DESIGN: Barriers to TB control were characterised by interviews with TB-affected families. To reduce these barriers, a multidisciplinary team offered integrated community and household socio-economic interventions aiming to: 1) enhance uptake of TB care by education, community mobilisation and psychosocial support; and 2) reduce poverty through food and cash transfers, microcredit, microenterprise and vocational training. An interim analysis was performed after the socio-economic interventions had been provided for 2078 people in 311 households of newly diagnosed TB patients for up to 34 months. RESULTS: Poverty (46% earned

Associations of self-reported oral health with physical and mental health in a nationally representative sample of HIV persons receiving medical care.

BACKGROUND: The impact of oral health on HIV patients has not been sufficiently documented. OBJECTIVE: To estimate the associations between measures of oral and generic health-related quality of life in persons receiving medical care for HIV. DESIGN: This is a longitudinal study of interview data collected in a probability sample of adults with HIV receiving health care in the US. The data were collected at three points in time. PATIENTS: Two thousand eight hundred and sixty-four HIV-infected adults using medical care. MEASUREMENTS: Physical and mental health were assessed using 28 items and oral health was assessed using seven items on oral-related pain and discomfort, worry, appearance, and function. Clinical measures included CD4 count, oral symptoms, physical symptoms, and stage of HIV. Physical functioning and emotional well-being were measured on a 0-100 scale with higher scores indicating better health. Oral health was measured using seven items with a five point scale. RESULTS: In multivariate analyses, oral symptoms had the strongest association with oral health-related quality of life. Each additional oral symptom was associated with an average decrease in oral health (0-100 possible range) of 3.97 points (p = 0.000). In addition, oral health was significantly associated with both physical and mental health. A one-point increase in oral health was associated with a 0.05 (p = 0.000) increase in mental health and 0.02 increase in physical health (p = 0.031). CONCLUSIONS: Oral health is strongly associated with physical and mental health but provides noteworthy unique information in persons with HIV infection. Thus, physical and mental health measures of HIV patients should incorporate indicators of oral functioning and well-being.

The foot-and-mouth disease RNA virus as a model in experimental phylogenetics.

Phylogenetic reconstruction methods are subject to two types of limitations: our knowledge about the true history of organisms and the gross simplification implied in the numerical simulation models of the relationships between them. In such a situation, experimental phylogenetics provides a way to assess the accuracy of the phylogenetic reconstruction methods. Nonetheless, this capacity is only feasible for organisms in which replication and mutation rates are high enough to provide valuable data. On the other hand, experimental phylogenetics also provides insights on the main evolutionary processes acting on viral variability under different population dynamics. Our study with the foot-and-mouth disease virus (FMDV) strongly suggests that the phylogenetic reconstruction methods can infer erroneous phylogenies due to nucleotide convergences between isolates belonging to different experimental lineages. We also point out that the diverse evolutionary mechanisms acting in different experimental dynamics generate alterations and change the frequencies of genetic variants, which can lead to the misinterpretation of the real evolutionary history.

Glutamic acid decarboxylase in rat olfactory bulb: effect of ovarian steroids or male pheromones.

The effect of ovarian steroids and pheromones on the activity of glutamic acid decarboxylase, the enzyme that synthesizes gamma-aminobutyric acid (GABA), was studied in the rat olfactory bulbs. The enzyme activity was measured in the main and accessory olfactory bulbs at 11:00 h and 17:00 h in ovariectomized rats, and in rats treated with ovarian steroids or exposed to male pheromones. The enzyme activity in both bulbs showed a diurnal fluctuation that was not affected in the accessory bulbs by the exposure to pheromones while the rhythm disappeared in the main bulbs. Estrogen and estrogen-progesterone treatments decreased the enzyme activity in both bulbs either in the morning or in the afternoon. The exposure of ovariectomized estrogen-primed rats to male pheromones reversed the effect of estrogen on the enzyme activity in the morning but not in the afternoon. Ovarian hormones plus pheromones prevented the steroid effect only in the morning. These results support the view that in olfactory bulbs, the GABAergic system can be modulated by endocrine and pheromonal factors.

Glutamic acid decarboxylase activity of the olfactory bulb in male rats is influenced by olfactory stimuli and hormonal status.

Changes is glutamate decarboxylase activity (GAD) in the main (MOB) and accessory (AOB) olfactory bulbs were determined at 11:00 hr and 17:00 hr in intact odor deprived (IOD) male rats exposed to female olfactory stimuli, and in castrated odor deprived males (COD) either injected with testosterone (T), exposed to female pheromone or injected with T and exposed to pheromone. Grouping IOD males by female olfactory stimulus and time of the day. MOB and AOB-GAD activity changed in the morning and not in the afternoon. In COD males, T injection induced an increased response in MOB-GAD activity 24 hr later either in the morning or in the afternoon, while no changes were seen at 11:00 or 17:00 hr exposure to female odor. In the AOB of COD males, both T administration or exposure to female pheromone, only induced an increase of enzyme activity in the morning. The association of T and female pheromone, decreased morning GAD activity both in the MOB and in the AOB compared with the values of COD males treated with T. In the afternoon this association had no effect compared with MOB, AOB-GAD activity of COD males injected with testosterone. These results indicate that hormonal and olfactory inputs in IOD and COD males are effective in changing olfactory bulb-GAD activity mainly in the morning.

gamma-Aminobutyric acid activity in the olfactory bulb of the rat during the sexual cycle and response to olfactory stimuli.

Glutamic acid decarboxylase activity in the main and accessory olfactory bulbs throughout the sexual cycle of the rat was studied. The effect of male pheromonal secretion on enzyme activity during proestrus and estrus day was also tested. The enzyme activity showed circadian rhythm during the estrous cycle. This rhythm was disrupted during diestrus-2 afternoon in the main bulb and came back during proestrus afternoon. A different pattern of enzyme activity was present in the accessory bulb, since the circadian rhythm was altered during proestrus morning, returning during estrus afternoon. Male odor exposition did not change enzyme profile activity during proestrus day and during estrus morning in the main bulb. In contrast, in the accessory bulb the olfactory stimuli induced opposite changes to that found in rats from the vivarium during proestrus. Comparison of enzyme activity in olfactory stimuli-deprived rats with that of pheromone-stimulated rats during proestrus showed that male odor exposure specifically affects accessory bulb enzyme activity. It is concluded that the changes of the olfactory bulb GABAergic system during proestrus and estrus day, or that evoked by odor stimuli, demonstrate the discriminative response of this system between the accessory olfactory bulb and the main olfactory bulb.