Aspectos clínicos, epidemiológicos e histopatológicos de pacientes con lesiones en la mucosa bucal / Clinical, epidemiological, histological and pathological aspects of patients with lesions in the oral mucosa i: en

Introducción: Las lesiones en la mucosa bucal constituyen un grupo heterogéneo de alteraciones, de cuyo diagnóstico temprano depende el pronóstico y el tratamiento. Objetivo: Caracterizar a pacientes con lesiones en la mucosa bucal según variables clínicas, epidemiológicas e histopatológicas. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo de 23 pacientes con lesiones en la mucosa bucal pertenecientes a los consultorios médicos de la familia del reparto Vista Alegre, quienes fueron asistidos en la consulta de estomatología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba desde septiembre del 2021 hasta junio del 2022. Resultados: En la serie predominaron el sexo femenino, el grupo etario de 60 y más años, la estomatitis subprótesis como lesión más frecuente (39,1 %) y los traumatismos crónicos como factores de riesgo (65,2 %); asimismo, en los pacientes remitidos al nivel secundario de atención hubo coincidencia entre los diagnósticos clínico e histopatológico (76,9 % ). Conclusiones: De la valoración clínica, epidemiológica e histopatológica de estas lesiones y de la preparación de los especialistas sobre el tema dependerá el diagnóstico definitivo.

Introduction: Lesions in the oral mucosa constitute a heterogeneous group of disorders which prognosis and treatment depend on the early diagnosis. Objective: To characterize patients with lesions in the oral mucosa according to clinical, epidemiological, histological and pathological variables. Methods: A descriptive, longitudinal and prospective study of 23 patients with lesions in the oral mucosa was carried out. They belonged to the family doctor offices from Vista Alegre neighborhood and were assisted in the Stomatology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba from September, 2021 to June, 2022. Results: In the series there was a prevalence of the female sex, the 60 years and over age group, subprosthesis stomatitis as more frequent lesion (39.1%) and chronic traumatisms as risk factors (65.2%); also, in patients referred to the secondary care level there was coincidence between the clinical, histological and pathological diagnoses (76.9%). Conclusions: The final diagnosis will depend on the clinical, epidemiological, histological and pathological valuation of these lesions and on the preparation of the specialists on the topic.

Cortical Lewy body injections induce long-distance pathogenic alterations in the non-human primate brain.

Aggregation of α-synuclein (α-syn) is the cornerstone of neurodegenerative diseases termed synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). These synucleinopathies are characterized by the deposit of aggregated α-syn in intracellular inclusions observable in neurons and glial cells. In PD and DLB, these aggregates, predominantly located in neurons, are called Lewy Bodies (LBs). These LBs are one of the pathological hallmarks of PD and DLB, alongside dopaminergic neuron loss in the substantia nigra. Previous studies have demonstrated the ability of PD patient-derived LB fractions to induce nigrostriatal neurodegeneration and α-syn pathology when injected into the striatum or the enteric nervous system of non-human primates. Here, we report the pathological consequences of injecting these LB fractions into the cortex of non-human primates. To this end, we inoculated mesencephalic PD patient-derived LB fractions into the prefrontal cortex of baboon monkeys terminated one year later. Extensive analyses were performed to evaluate pathological markers known to be affected in LB pathologies. We first assessed the hypothesized presence of phosphorylated α-syn at S129 (pSyn) in the prefrontal cortices. Second, we quantified the neuronal, microglial, and astrocytic cell survival in the same cortices. Third, we characterized these cortical LB injections' putative impact on the integrity of the nigrostriatal system. Overall, we observed pSyn accumulation around the injection site in the dorsal prefrontal cortex, in connected cortical regions, and further towards the striatum, suggesting α-syn pathological propagation. The pathology was also accompanied by neuronal loss in these prefrontal cortical regions and the caudate nucleus, without, however, loss of nigral dopamine neurons. In conclusion, this pilot study provides novel data demonstrating the toxicity of patient-derived extracts, their potential to propagate from the cortex to the striatum in non-human primates, and a possible primate model of DLB.

Brain injections of glial cytoplasmic inclusions induce a multiple system atrophy-like pathology.

Synucleinopathies encompass several neurodegenerative diseases, which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit of α-synuclein aggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson's disease and dementia with Lewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated with α-synuclein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark of multiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neurodegeneration. To evaluate the possible pathogenic role of glial cytoplasmic inclusions, we inoculated glial cytoplasmic inclusion-containing brain fractions obtained from multiple system atrophy patients into the striatum of non-human primates. After a 2-year in vivo phase, extensive histochemical and biochemical analyses were performed on the whole brain. We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendrocytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neuroinflammation and α-synuclein pathology were also observed. These results show that the α-synuclein species in multiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human primates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy and gliosis. The present data pave the way for using this experimental model for MSA research and therapeutic development.

Efectividad de la terapia láser combinada con la técnica convencional en pacientes con discromías dentales / Effectiveness of laser therapy combined with the conventional technique in patients with dental dischromya

Introducción: La discromía dental es una afectación estética, de causa multifactorial, caracterizada por el cambio de coloración de uno o varios dientes. Objetivo: Evaluar la efectividad de la terapia láser como fuente de luz y calor en pacientes con discromías dentales. Método: Se realizó un estudio cuasi experimental, de intervención terapéutica, en 24 pacientes con discromías dentales atendidos en la Clínica Estomatológica Provincial DocenteMártires del Moncada de Santiago de Cuba, desde julio de 2017 hasta julio de 2018. Los integrantes del estudio se asignaron de forma aleatoria a 2 grupos de tratamiento:a los pares (grupo de estudio) se les aplicó láser combinado con la técnica convencional de peróxido de hidrógeno;a los impares (grupo control), tratamiento convencional solamente.Se utilizaron las frecuencias absoluta y relativa como medidas de resumen, así como la prueba de X 2 de homogeneidad para la validación estadística, con un nivel de significación de 0,05. Resultados: Para los pacientes del grupo de estudio, la segunda y tercera sesiones fueron más efectivas. Al culminar el tratamiento, ambos resultaron efectivos, pero los que recibieron láser evolucionaron más rápidamente que los tratados solo con peróxido de hidrógeno. Conclusiones: El uso de la terapia láser y peróxido de hidrógeno fue efectivo en pacientes con discromías dentales y demostró que no provoca efectos adversos en los dientes tratados.

Introduction: The dental dischromya is an esthetic disorder, of multifactorial cause, characterized by the change of coloration of one or several teeth. Objective: To evaluate the effectiveness of laser therapy as a source of light and heat in patients with dental dischromya. Method: A quasi-experiment, of therapeutic intervention study, was carried out in 24 patients with dental dischromya assisted in Mártires del Moncada Teaching Provincial Stomatological Clinic in Santiago de Cuba, from July, 2017 to March, 2018. The members of the study were assigned at random with 2 treatment groups: a study group (pairs) to whom laser combined with the conventional technique of peroxide of hydrogen was applied; to odd number patients (control group), conventional treatment only. The absolute and relative frequencies were used as summary measures, as well as the chi-square test of homogeneity for the statistical validation, with a level of significance of 0.05. Results: For the patients of the study group, the second and third sessions were more effective. When culminating the treatment, both were effective, but those that received laser evolved more quickly than those treated with peroxide of hydrogen. Conclusions: The use of the laser therapy and peroxide of hydrogen was effective in patients with dental dischromya and it was demonstrated that doesn't cause adverse effects in the treated teeth.

Inhibition of melanin production and tyrosinase activity by flavonoids isolated from Loranthus acutifolius.

Activity-guided fractionations of leaves and stems from Loranthus acutifolius led to the isolation of 2',4',6-trimethoxyflavone (1), 3',4',5-trihydroxy-6,7,8-trimethoxyflavone (2), 2'4'-dihydroxy-6'-methoxy-chalcone (3) and 4',5-dihydroxy-6,7,8-trimethoxyflavone (4). The potential for inhibition against melanin production and tyrosinase activity of these 4 compounds was tested in B16-F10 cells. 2',4',6-trimethoxyflavone, 3',4',5-trihydroxy-6,7,8-trimethoxyflavone, 2'4'-dihydroxy-6'-methoxy-chalcone and 4',5-dihydroxy-6,7,8-trimethoxyflavone showed an inhibitory activity of melanin production with IC50 of 3.6 ± 0.05 µM, 8.1 ± 0.05 µM, 1.6 ± 0.03 µM and 6.5 ± 0.05 µM, respectively. In addition, 2',4',6-trimethoxyflavone, 3',4',5-trihydroxy-6,7,8-trimethoxyflavone, 2'4'-dihydroxy-6'-methoxy-chalcone and 4',5-dihydroxy-6,7,8-trimethoxyflavone were able to inhibit tyrosinase activity with IC50 of 4.0 ± 0.03 µM, 11.3 ± 0.05 µM, 5.7 ± 0.02 µM and 8.6 ± 0.04 µM, respectively. This is the first time that these compounds are reported in the L. acutifolius species showing anti-melanogenic activities.

Identification of TRPV1 Ion Channels Agonists of Tropaeolum tuberosum in Human Skin Keratinocytes.

Tropaeolum tuberosum, commonly known as Mashua, is an herbal remedy used in traditional Andean medicine for the relief of kidney and bladder pain, as well as contusions. This study aimed to evaluate the fractions and isolated compounds from T. tuberosum with analgesic activity mediated by the transient receptor potential vanilloid-1 receptor. A bioguided phytochemical analysis based on NMR/MS was performed to identify the compounds of the n-heptane fractions from samples of purple tubers of T. tuberosum. The transient receptor potential vanilloid-1 agonist and antagonist activity were assessed through the measurement of intracellular Ca2+ in HEK001 cells. The chemical structure determination led to the identification of two alkamides: N-(2-hydroxyethyl)-7Z,10Z,13Z,16Z-docosatetraenamide (1: ) and N-oleoyldopamine (2: ). Both compounds induced increased intracellular calcium flow with IC50 values of 3.2 nM and 7.9 nM, respectively, thus activating the transient receptor potential vanilloid-1 receptor. Our research is the first report to show that these two compounds isolated from T. tuberosum can act as agonists of the transient receptor potential vanilloid-1 receptor, providing scientific evidence for the traditional use of this species in pain relief.

Evaluación económica de las alternativas terapéuticas en pacientes con hiperestesia dentinaria / Economic evaluation of the therapeutic alternatives in patients with dentin hyperesthesia

Introducción: La hiperestesia dentinaria es una sensación dolorosa de intensidad variable, que va de leve a moderada y, al encontrarse la dentina expuesta, puede convertirse en una molestia constante. Objetivo: Determinar la alternativa menos costosa en el tratamiento de pacientes con hiperestesia dentinaria. Método: Se realizó una evaluación económica completa del tipo minimización de costo, en la Clínica Estomatológica Provincial Docente Mártires del Moncada de Santiago de Cuba, desde enero hasta mayo de 2019. Se revisaron 40 historias clínicas, escogidas a conveniencia, ya que contaban con los datos necesarios para la investigación. Se crearon 2 grupos de estudios, cuyos integrantes fueron tratados con laca flúor y láser, respectivamente. Se analizaron las variables de edad, sexo, efectividad de los tratamientos, costo directo e indirecto y costo unitario. Resultados: En la serie predominaron el grupo etario de 15-24 años (30,0 %), seguido por el de 25- 34 (25,0 %), así como el sexo femenino (70,0 %). El costo unitario del tratamiento con laca flúor fue de $7,77 y con láser de $5,74, para una diferencia de $2,03. Conclusión: La alternativa menos costosa en el tratamiento de pacientes con hiperestesia dentinaria resultó ser la aplicación de láser; mientras que la evaluación económica realizada demostró ser apropiada en materia de eficiencia económica.

Introduction: Dentin hyperesthesia is a painful sensation of variable intensity that goes from light to moderate and, as dentin is exposed, it can become a constant discomfort. Objective: To determine the less expensive alternative in the treatment of patients with dentin hyperesthesia. Method: A complete economic evaluation of the cost minimization type was carried out in Martires del Moncada Teaching Provincial Stomatological Clinic in Santiago de Cuba, from January to May, 2019. Forty medical records were reviewed, chosen of convenience, since they had the necessary data for the investigation. Two groups of studies were created whose members were treated with lacquer fluorine and laser, respectively. The age, sex, effectiveness of the treatments, direct and indirect cost and unitary cost variables were analyzed. Results: In the series there was a prevalence of the 15-24 age group (30.0 %), followed by that of 25-34 (25.0 %), as well as the female sex (70.0 %). The unitary cost of the treatment with lacquer fluorine was of $7.77 and with laser of $5.74, for a difference of $2.03. Conclusion: The less expensive alternative in the treatment of patients with dentin hyperesthesia was the laser application; while the economic evaluation carried out demonstrated to be appropriate as regards economic efficiency.

Impact of clinical guidance and rapid molecular pathogen detection on evaluation and outcomes of febrile or hypothermic infants.

OBJECTIVE: To quantify the impact of clinical guidance and rapid respiratory and meningitis/encephalitis multiplex polymerase chain reaction (mPCR) testing on the management of infants. DESIGN: Before-and-after intervention study. SETTING: Tertiary-care children's hospital. PATIENTS: Infants ≤90 days old presenting with fever or hypothermia to the emergency department (ED). METHODS: The study spanned 3 periods: period 1, January 1, 2011, through December 31, 2014; period 2, January 1, 2015, through April 30, 2018; and period 3, May 1, 2018, through June 15, 2019. During period 1, no standardized clinical guideline had been established and no rapid pathogen testing was available. During period 2, a clinical guideline was implemented, but no rapid testing was available. During period 3, a guideline was in effect, plus mPCR testing using the BioFire FilmArray respiratory panel 2 (RP 2) and the meningitis encephalitis panel (MEP). Outcomes included antimicrobial and ancillary test utilization, length of stay (LOS), admission rate, 30-day mortality. Outcomes were compared across periods using Kruskal-Wallis and Pearson tests and interrupted time series analysis. RESULTS: Overall 5,317 patients were included: 2,514 in period 1, 2,082 in period 2, and 721 in period 3. Over the entire study period, we detected reductions in the use of chest radiographs, lumbar punctures, LOS, and median antibiotic duration. After adjusting for temporal trends, we observed that the introduction of the guideline was associated with reductions in ancillary tests and lumbar punctures. Use of mPCR testing with the febrile infant clinical guideline was associated with additional reductions in ancillary testing for all patients and a higher proportion of infants 29-60 days old being managed without antibiotics. CONCLUSIONS: Use of mPCR testing plus a guideline for young infant evaluation in the emergency department was associated with less antimicrobial and ancillary test utilization compared to the use of a guideline alone.

Factors Associated With Physician Empowerment and Well-being at an Academic Medical Center.

OBJECTIVE: This study reports an institutional approach to rapidly measure burnout and gather physicians' opinions on workplace factors that empower well-being. METHODS: In July 2017, physicians at Vanderbilt University Medical Center were invited to participate in a two-question survey measuring self-reported burnout and providing an opportunity to describe structures that empower well-being. Free-text responses were analyzed and a linear regression model assessed factors associated with well-being. RESULTS: A total of 1135 physicians responded (43.3% response rate) with a mean well-being score of 56 (scale 0 to 100). Higher scores were associated with clinical fellow status (P = 0.002), male sex (P = 0.008), less allocation of time to clinical care (P < 0.001), and not commenting on "leadership" and "autonomy" in the free-text response. CONCLUSIONS: Brief surveys collecting perspectives on well-being can help employers identify high-risk groups and provide a roadmap for institutional change.

Morbilidad en ancianos con pérdida dentaria / Morbidity in elderly with dental loss

Introducción: La pérdida dentaria tiene consecuencias en la apariencia y en la función fisiológica general del adulto mayor, lo cual constituye un problema aún no resuelto en la República Bolivariana de Venezuela. Objetivo: Describir la morbilidad en adultos mayores con pérdida de dientes permanentes. Método: Se realizó un estudio descriptivo, observacional y de corte transversal en la Clínica Simón Bolívar del municipio de Diego Ibarra, perteneciente al estado venezolano de Carabobo, desde enero hasta junio del 2016. El universo estuvo constituido por 100 adultos mayores de 60 años y más, ambos sexos y desdentados parciales o totales. Las variables analizadas fueron edad, sexo, higiene bucal, número de dientes permanentes perdidos, así como el tipo de aparatología protésica requerida. Se emplearon las frecuencias relativa y absoluta como medidas de resumen. Resultados: Se encontró que 73,0 % de los ancianos perdieron sus dientes por caries dental, siendo las féminas y el grupo de 60-64 años de edad el más afectado. Asimismo, predominaron la higiene bucal deficiente y la necesidad de prótesis parcial. Conclusiones: Existió una elevada morbilidad en los adultos mayores con pérdida dentaria, lo cual afectó su funcionalidad, estética y autoestima, que de no ser corregida pudiera provocar consecuencias importantes en la cavidad bucal y en el resto del cuerpo, sin olvidar la prevención o detección precoz de cualquier otra enfermedad bucal que la genere.

Introduction: Dental loss has consequences in the elderly general physiologic function and appearance, that constitutes an unsolved problem in the Bolivian Republic of Venezuela. Objective: To describe the morbidity in elderly with loss of permanent teeth. Method: A descriptive, observational and cross-sectional study was carried out in Simón Bolívar Clinic from Diego Ibarra municipality, belonging to Carabobo in Venezuela, from January to June, 2016. The universe was constituted by 100 elderly of 60 years and more from both sexes and partially or totally toothless. The analyzed variables were age, sex, oral hygiene, number of lost permanent teeth, as well as the type of prosthesis required. The relative and absolute frequencies were used as summary measures. Results: It was found that 73.0 % of the elderly lost their teeth due to dental decay, being women and the 60-64 age group the most affected one. Also, the poor oral hygiene and the necessity of partial prosthesis prevailed. Conclusions: A high morbidity existed in elderly with dental loss, which affected their functionality, aesthetics and self-esteem that could cause important consequences in the oral cavity and in the rest of the body if it is not corrected, without forgetting the prevention or early detection of any other oral disease that generates it.

Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates.

In Parkinson's disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of α-synuclein-containing Lewy body extracts from patients with Parkinson's disease. This study shows that patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of α-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that α-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of α-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous α-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson's disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson's disease.

Cardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys.

BACKGROUND: Autonomic dysfunction is a well-known dominant symptom in the advanced stages of Parkinson's disease. However, the role of cardiac sympathetic nerves still needs to be elucidated. OBJECTIVES: To evaluate cardiac sympathetic response in Parkinsonian and dyskinetic monkeys. METHODS: Adult male monkeys were divided into 1 of the following 3 groups: controls, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine+levodopa-treated animals. Noradrenaline, its metabolite normetanephrine, and phospho-Heat shock proten 27 (p-Hsp27) at serine 82 levels were analyzed in the left and right ventricles of the heart. Tyrosine hydroxylase immunohistochemistry was performed in the ventral mesencephalon. RESULTS: The results were the following: (1) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication significantly increased normetanephrine levels and decreased noradrenaline turnover in the right ventricle without changes in the left ventricle; however, (2) levodopa treatment decreased noradrenaline levels and enhanced the normetanephrine/noradrenaline ratio in parallel with a very significant increase of Hsp27 activity in both ventricles. CONCLUSIONS: Levodopa treatment could induce protective cardiac effects through the increased Hsp27 activity. © 2019 International Parkinson and Movement Disorder Society.

Voluntary exercise reduces plasma cortisol levels and improves transitory memory impairment in young and aged Octodon degus.

Sleep deprivation (SD) has been reported to induce transient cognitive impairment in functional domains commonly affected in dementia, including memory. Indeed, sleep disturbance has been proposed as an early marker for Alzheimer's disease (AD). SD emulates many aging-related modifications, including important memory dysfunctions possibly caused by triggers of stress such as cortisol. Although exercise is widely assumed to be beneficial for overall health, only recently has the research community focused its attention on its possible effects on brain functions such as cognition. Octodon degus (O. degus) is a recent rodent model considered suitable for the study of neurodegenerative diseases, since it spontaneously develops several histopathological hallmarks observed in AD. We aimed to uncover the interaction between stress, exercise, age and transient memory impairments after SD insult. In this study, animals had free individual access to wheels to practice voluntary exercise. The Barnes Maze (BM) task was conducted with young and aged O. degus animals after combining voluntary exercise and either normal sleep or SD. Plasma cortisol levels were measured after each condition. SD impaired hippocampus-dependent memory in both young and old animals, while cortisol levels did not significantly differ between non-SD and SD animals. However, voluntary exercise for 45 days improved the cognitive impairment caused by SD compared with the control condition. Moreover, voluntary exercise decreased plasma cortisol levels in both conditions, independently of the age.

Local Gastrointestinal Injury Exacerbates Inflammation and Dopaminergic Cell Death in Parkinsonian Mice.

The cause of progressive degeneration in Parkinson's disease is not clear, although, in the last years, different studies have suggested that both brain and peripheral inflammation could play a key role in the progression of this disorder. In our study, we aimed to analyze the effect of an acute inflammation confined to the colon on dopaminergic neuronal death and glial response in mice intoxicated with MPTP. The results obtained show a very significant decrease of dopaminergic neurons in the SNpc as well as a significant decrease of dopaminergic fibers in the striatum of the MPTP+DSS-treated group compared with the control animals. In addition, there was a significant exacerbation of microglial and astrocytes activation in MPTP+DSS animals compared with the control group. This data suggests that a specific gastrointestinal injury, which induces a systemic inflammatory response, is able to exacerbate cell death mechanisms of the remaining dopaminergic neurons and then contributes to the persistent progression of the disease. These results leave open new lines of research on the role of exclusive colonic inflammation and the progression of nigrostriatal dopaminergic degeneration.

Unexpected Exacerbation of Neuroinflammatory Response After a Combined Therapy in Old Parkinsonian Mice.

The design of therapeutic strategies that focus on the repositioning of anti-inflammatory and antioxidant drugs are a great bet to slow down the progression of neurodegenerative disorders. Despite the fact that Parkinson's disease (PD) is an age-related pathology, almost all experimental studies are carried out in young animals. Here, we evaluated the possible neuroprotective effect of the combination of the antioxidant N-acetylcysteine (NAC) and the anti-inflammatory HA-1077 in aged 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (C57BL/6 mice, 20 months old), whose individual treatment has been shown to have neuroprotective effects in this Parkinsonism model. Interestingly, NAC+HA-1077-based treatment produced a significant increase in dopaminergic neuronal death accompanied by an increase in microglial and astroglial activation in the Substantia Nigra pars compacta (SNpc) and striatum of old-Parkinsonian mice compared to their control group. The astroglial response was also explored by co-immunostaining for GFAP and S100b together with p-JNK and it was found to be particularly exacerbated in the MPTP+NAC+HA-1077 group. The unexpected toxic effects found in the combined use of NAC and HA-1077 in old-Parkinsonian mice highlight the importance of taking into account that in elderly Parkinsonian patients the combination of some drugs (most of them used for other different age-related alterations) can have side effects that may result in the exacerbation of the neurodegenerative process.

Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?

BACKGROUND: Neuroprotective strategies are becoming relevant to slow down dopaminergic cell death and inflammatory processes related to the progressive neurodegeneration in Parkinson's disease (PD). Interestingly, among others, physical activity (PA) or anti-oxidant agents (such as N-acetyl-L-cysteine, NAC) are common therapeutic strategies. Therefore, this study aims to analyze if there is a synergistic effect of physical activity along with NAC treatment on dopaminergic degeneration and neuroinflammatory response in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism model after subchronic intoxication. METHODS: To ascertain this possibility, 48 8-week-old male mice (C57BL/6 strain) were used. Twenty four of them were placed individually in cages where voluntary physical activity was automatically monitored during 30 days and were divided into groups: (i) control; (ii) NAC; (iii) MPTP, and (iv) MPTP+NAC. The other 24 mice were divided into the same four groups but without physical activity. RESULTS: The data collected during the treatment period showed that there was an overall increase in the total running distance in all groups under physical activity, including Parkinsonian animals. However, the monitoring data per day showed that the activity routine by MPTP and MPTP+NAC groups was disrupted by alterations in the circardian rhythm because of MPTP intoxication. Results from post-mortem studies in the substantia nigra pars compacta (SNpc) showed significant decrease in the number of TH+ cells in all MPTP groups. Moreover, TH+ expression in the striatum was significantly decreased in all MPTP groups. Thus, PA + NAC treatment do not protect dopaminergic neurons against a subchronic intoxication of MPTP. Regarding glial response, the results obtained from microglial analysis do not show significant increase in the number of Iba-1+ cell in MPTP+NAC and MPTP+PA + NAC. In the striatum, a significant decrease is observed only in the MPTP+NAC group compared with that of the MPTP group. The microglial results are reinforced by those obtained from the analysis of astroglial response, in which a decrease in the expression of GFAP+ cells are observed in MPTP+NAC and MPTP+PA + NAC compared with MPTP groups both in the SNpc and in the striatum. Finally, from the study of the astroglial response by the co-localization of GFAP/S100b, we described some expression patterns observed based on the severity of the damage produced by the MPTP intoxication in the different treated groups. CONCLUSIONS: These results suggest that the combination of physical activity with an anti-oxidant agent does not have a synergistic neuroprotective effect in the nigrostriatal pathway. Our results show a potential positive effect, only due to NAC treatment, on the neuroinflammatory response after subchronic MPTP intoxication. Thus, physical activity is not essential, under these conditions. However, we believe that physical activity, used for therapeutic purposes, has a beneficial long-term effect. In this line, these results open the door to design longer studies to demonstrate its promising effect as neuroprotective strategy.

Fractures in the Pediatric Emergency Department: Are We Considering Abuse?

Approximately one fourths of infant fractures are due to abuse. Recognition of abuse is important to avoid further morbidity/mortality. There is limited knowledge regarding how frequently pediatric emergency department clinicians consider abuse in infants with fractures. Our primary objective was to estimate the percentage of infants with fractures for whom abuse was considered, and to examine characteristics associated with abuse consideration. We performed a retrospective review of infants <1 year of age presenting to a pediatric emergency department. Our primary outcome variable was consideration of abuse. Our secondary outcome measures were identification of predictor variables associated with consideration of abuse. We identified 509 infants meeting study criteria. Pediatric emergency physicians considered abuse in approximately two thirds of infants with fractures. Consideration was more likely to occur in younger infants, in the presence of no history or unwitnessed injury mechanism, when evaluated by male physicians, and emergency department encounters from 12 am to 6 am.

Efectividad del Oleozón® en el tratamiento de pacientes con discromía dental / Effectiveness of Oleozon® in the treatment of patients with dental dischromya

Se realizó un estudio cuasiexperimental, de intervención terapéutica, para evaluar la efectividad del Oleozón® tópico y la luz halógena como fuente de luz azul y calor en el tratamiento de 52 pacientes con discromías dentales, atendidos en el Policlínico Docente Ramón López Peña del municipio de Santiago de Cuba, desde junio del 2015 hasta marzo del 2016. Se conformaron 2 grupos: de estudio (pares), a los cuales se les aplicó Oleozón® tópico; de control (impares), quienes recibieron tratamiento convencional con peróxido de hidrógeno. Al culminar las sesiones, ambos medicamentos resultaron efectivos en 100 por ciento de los afectados, aunque los del segundo grupo evolucionaron más rápidamente que los del primero. Se demostró que el Oleozón® tópico y la luz halógena son efectivos en el tratamiento de pacientes con discromías dentales y no provocan efectos adversos en los dientes tratados(AU)

A quasi-experiment, of therapeutic intervention study was carried out, to evaluate the effectiveness of the topic Oleozon® and the halogen light as source of blue light and heat in the treatment of 52 patients with dental dischromyas, assisted in Ramón López Peña Teaching Polyclinic in Santiago de Cuba from June, 2015 to March, 2016. Two groups were conformed: a study group (pairs), to whom topic Oleozon® was applied; a control group (odd numbers) who received conventional treatment with peroxide of hydrogen. When culminating the sessions, both medications were effective in 100 percent of the affected patients, although those of the second group evolved more quickly than those of the first one. It was demonstrated that topic Oleozon® and halogen light are effective in the treatment of patients with dental dischromyas and they cause no adverse effects in the treated teeth(AU)

Efectividad del Oleozón® en el tratamiento de pacientes con discromía dental / Effectiveness of Oleozon® in the treatment of patients with dental dischromya

Se realizó un estudio cuasiexperimental, de intervención terapéutica, para evaluar la efectividad del Oleozón® tópico y la luz halógena como fuente de luz azul y calor en el tratamiento de 52 pacientes con discromías dentales, atendidos en el Policlínico Docente Ramón López Peña del municipio de Santiago de Cuba, desde junio del 2015 hasta marzo del 2016. Se conformaron 2 grupos: de estudio (pares), a los cuales se les aplicó Oleozón® tópico; de control (impares), quienes recibieron tratamiento convencional con peróxido de hidrógeno. Al culminar las sesiones, ambos medicamentos resultaron efectivos en 100 por ciento de los afectados, aunque los del segundo grupo evolucionaron más rápidamente que los del primero. Se demostró que el Oleozón® tópico y la luz halógena son efectivos en el tratamiento de pacientes con discromías dentales y no provocan efectos adversos en los dientes tratados

A quasi-experiment, of therapeutic intervention study was carried out, to evaluate the effectiveness of the topic Oleozon® and the halogen light as source of blue light and heat in the treatment of 52 patients with dental dischromyas, assisted in Ramón López Peña Teaching Polyclinic in Santiago de Cuba from June, 2015 to March, 2016. Two groups were conformed: a study group (pairs), to whom topic Oleozon® was applied; a control group (odd numbers) who received conventional treatment with peroxide of hydrogen. When culminating the sessions, both medications were effective in 100 percent of the affected patients, although those of the second group evolved more quickly than those of the first one. It was demonstrated that topic Oleozon® and halogen light are effective in the treatment of patients with dental dischromyas and they cause no adverse effects in the treated teeth

A multiyear assessment of a hospital-school program to promote teen motor vehicle safety.

BACKGROUND: Motor vehicle crashes are the leading cause of death among teen drivers. The main goal of this program was to reduce texting while driving among high school teens through a unique peer-generated anti-texting campaign. METHODS: The program consisted of two phases. In phase 1, student leaders participated in a half-day, hospital-based experiential program that emphasized safe teen driving. In phase 2, these students conceptualized and implemented an anti-texting while driving campaign during the school year. The program enrolled 32 schools with 137 student participants in phase 1. This study uses a prospective quasi-experimental pre-post design. A presurvey and a follow-up online survey were used. Response rate was 81%. In phase 2, two rounds of observations of drivers were made near the participating schools at the beginning and end of the phase 2 campaign. The results were analyzed using proportion tests. RESULTS: There was a strong belief (6.49 on a seven-point scale) that texting while driving could result in a crash. About 58% had texted while driving in the previous 7 days in the pre-survey. This proportion decreased significantly to 44% in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing laws and feeling of empowerment to take action with a teen driver who was texting improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens) were observed in the first round, and 13,153 were observed in the second round of observations. Significant reduction in the proportion of drivers texting while driving (from 13% to 9%; p < 0.0001) was observed. CONCLUSION: Results of driver observations support the effectiveness of this program in meeting the key objective of reducing texting while driving. The program also influenced teenagers' willingness to take positive steps when faced with a driver who was texting. Future efforts should aim to influence social and peer norms. LEVEL OF EVIDENCE: Therapeutic study, level IV.