Piper auritum ethanol extract is a potent antimutagen against food-borne aromatic amines. Mechanisms of action and chemical composition.

An ethanol extract of Piper auritum leaves (PAEE) inhibits the mutagenic effect of three food-borne aromatic amines (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) in the TA98 Salmonella typhimurium strain. Preincubation with MeIQx demonstrated in mutagenesis experiments that inhibition of Cytochrome P450 (CYP), as well as direct interaction between component(s) of the plant extract with mutagens, might account for the antimutagenic observed effect. Gas chromatography/mass spectrometry analysis revealed that safrole (50.7%), α-copaene (7.7%), caryophyllene (7.2%), ß-pinene (4.2%), γ-terpinene (4.1%) and pentadecane (4.1%) as the main components of PAEE. Piper extract and safrole were able to inhibit the rat liver microsomal CYP1A1 activity that participates in the amines metabolism, leading to the formation of the ultimate mutagenic/ molecules. According to this, safrole and PAEE inhibited MeIQx mutagenicity but not that of the direct mutagen 2-nitrofluorene. No mutagenicity of plant extract or safrole was detected. This study show that PAEE and its main component safrole are associate with the inhibition of heterocyclic amines activation due in part to the inhibition of CYP1A subfamily activity.

Spatial aggregation patterns in four mistletoe species: ecological and environmental determinants.

Plant spatial distribution is an important topic in ecology as it determines species coexistence and biodiversity dynamics. Usually, plants show clustered distributions in nature. Mistletoes are a good example of aggregated distributions, as they form dense aggregations due to several factors (availability of competent hosts, seed dispersal vectors, microclimate conditions). We analysed four native mistletoe species with divergent life histories and host ranges: Desmaria mutabilis and Tristerix corymbosus from the temperate rainforests of southern Chile; and Tristerix aphyllus and Tristerix verticillatus from the northern semi-desert zone. While T. corymbosus and T. verticillatus have a wide host range, T. aphyllus and D. mutabilis are specialists that can parasitize only a few plant species. We hypothesized that specialized species would be more aggregated due to ecological and environmental restrictions. We used heterogeneous Poisson models to quantify spatial aggregation. Three of the four mistletoe species were spatially clustered at both environments, with aggregation being stronger in the temperate rainforest of southern Chile and particularly in the host-specialist species. Our results suggest that environmental constraints are more important than ecological constraints (host range) in shaping mistletoe spatial structure. Mistletoe aggregated spatial distribution depends primarily on the environment that they inhabit, which conditions host spatial availability, and arrangement.

Colesteatoma del conducto auditivo externo: Experiencia de 5 años Hospital del Salvador / External ear canal cholesteatoma: 5-year experience Hospital del Salvador

Introducción: El colesteatoma del conducto auditivo externo (CCAE) es una estructura quística revestida por epitelio escamoso estratificado queratinizado que tiene la capacidad de invadir y erosionar localmente al hueso temporal. Su incidencia es de 0,19 a 0,3/100.000 habitantes siendo 60 veces menos frecuente que el de oído medio. Objetivo: Describir las características epidemiológicas, clínicas, imagenológicas y tratamiento de los pacientes diagnosticados con CCAE en el Servicio de Otorrinolaringología Hospital del Salvador. Material y Método: Se presenta una serie de ocho casos clínicos recopilados durante el período 2017 y 2021. Se realizó revisión de fichas clínicas, biopsias y tomografías computadas de oídos (TC oídos). Se describen los hallazgos y tratamiento efectuado. Resultados: El promedio de edad fue de 65,6 años, correspondiente a 5 mujeres y 3 hombres con presencia de tabaquismo y diabetes en la mitad de los casos. Los síntomas y signos más frecuentes fueron otalgia e hipoacusia seguido de otorrea. 7 pacientes se presentaron con tímpano íntegro y el compromiso de la pared inferior del conducto se evidenció en 6 de 8 pacientes. La TC oídos mostró erosión ósea del conducto, con o sin compromiso de estructuras adyacentes, en todos los casos y el diagnóstico histológico fue efectuado en el 100% de los pacientes. Se privilegió el tratamiento conservador mediante curaciones óticas periódicas asociado a ácido salicílico al 3% y/o antibióticos tópicos en 6/8 pacientes. Conclusiones: El CCAE es una entidad poco frecuente sin signos ni síntomas patognomónicos por lo que el diagnóstico histológico junto con el estudio imagenológico es perentorio. El tratamiento conservador es una alternativa terapéutica válida que ofrece buenos resultados en pacientes con adecuada adherencia al tratamiento y posibilidad de seguimiento estricto.

Introduction: External ear canal cholesteatoma (EECC) is a cystic structure lined by keratinized stratified squamous epithelium that has the ability to locally invade and erode the temporal bone. Its incidence is 0.19 to 0.3 / 100,000 habitants, being 60 times less frequent than that of the middle ear. Aim: To describe the epidemiological, clinical, imaging and treatment characteristics of patients diagnosed with EECC in the Hospital del Salvador ENT department. Material and Methods: A series of eight clinical cases collected during the period 2017 and 2021 is presented. A review of clinical records, biopsies and computed tomography of the ear (ear CT) was carried out. The findings and treatment carried out are described. Results: The average age was 65.6 years corresponding to 5 women and 3 men with the presence of smoking and diabetes in half of the cases. The most frequent symptoms and signs were earache and hearing loss followed by otorrhea. 7 patients presented with an intact eardrum and compromise of the inferior wall of the canal was evidenced in 6 of 8 patients. Ears CT showed bone erosion of the canal with or without compromise of adjacent structures in all cases and the histological diagnosis was made in 100% of the patients. Conservative treatment with periodic ear dressings associated with 3% salicylic acid and / or topical antibiotics was favored in 6/8 patients. Conclusion: EECC is a rare entity without pathognomonic signs or symptoms, therefore the histological diagnosis together with the imaging study is peremptory. Conservative treatment is a valid therapeutic alternative that offers good results in patients with adequate adherence to treatment and the possibility of strict follow-up.

Theoretical investigation of the MXene precursors MoxV4-xAlC3 (0 ≤ x ≤ 4).

By first-principles total-energy calculations, we investigated the thermodynamic stability of the MAX solid solution MoxV4-xAlC3 in the 0 ≤ x ≤ 4 range. Results evidence that lattice parameter a increases as a function of Mo content, while the c parameter reaches its maximum expansion at x = 2.5. After that, a contraction is noticed. Mo occupies VI sites randomly until the out-of-plane ordered Mo2V2AlC3 alloy is formed. We employed the Defect Formation Energy (DFE) formalism to evaluate the thermodynamic stability of the alloys. Calculations show five stable compounds. At V-rich conditions and from Mo-rich to Mo-moderated conditions, the pristine V4AlC3 MAX is stable. In the region of V-poor conditions, from Mo-rich to Mo-moderated growth conditions, the solid solutions with x = 0.5, 1, and 1.5 and the o-MAX Mo2V2AlC3 are thermodynamically stable. The line profiles of the Electron Localization Function and Bader charge analysis show that the V-C interaction is mainly ionic, while the Mo-C is covalent. Also, the exfoliation energy to obtain a MXene layer is ~ 0.4 eV/Å2. DFE also shows that MXenes exfoliated from the MAX phase with the same Mo content and atomic arrangement are thermodynamically stable. Our results get a deeper atomic scale understanding of the previously reported experimental evidence.

Variabilidad interregional en el uso de tecnologías cardiovasculares (2011-2019). Correlación con índices económicos y frecuentación y mortalidad hospitalarias / Interregional variability in the use of cardiovascular technologies (2011-2019). Correlation with economic indicators, admissions, and in-hospital mortality

Introducción y objetivos La igualdad de oportunidades para acceder a avances técnicos de reconocido valor clínico debe ser una prioridad del sistema público de salud. Se analizó la variabilidad entre todas las comunidades autónomas españolas en el uso de técnicas cardiológicas con indicación ya establecida y su relación con indicadores económicos, carga de enfermedad y mortalidad hospitalaria. Métodos Se analizaron los registros de actividad de las asociaciones de la Sociedad Española de Cardiología desde 2011 a 2019 en coronariografía, intervención coronaria percutánea (ICP) general, ICP primaria, desfibrilador automático implantable (DAI), terapia de resincronización cardiaca e implante percutáneo de válvula aórtica (TAVI). Se obtuvieron índices económicos (producto interior bruto y gasto sanitario per cápita) y datos sobre frecuentación y mortalidad hospitalarias reportados en los informes RECALCAR (Recursos y Calidad en Cardiología) de la Sociedad Española de Cardiología. Se analizó el coeficiente de variación en la actividad y la correlación de esta con los índices regionales económicos, de frecuentación y la razón de mortalidad hospitalaria estandarizada por riesgo. Resultados Existe una variación notable en el uso de las tecnologías, especialmente ICP primaria (18%), DAI (22%), terapia de resincronización cardiaca (36%) y TAVI (42%). Solo se observó cierta correlación con la frecuentación de la ICP general y el DAI. No se encontró una correlación significativa entre la penetración de las técnicas y los índices económicos de riqueza y gasto. La correlación con la mortalidad hospitalaria no mostró resultados significativos, aunque es el análisis con más limitaciones, ya que estas técnicas tienen mayor impacto en la supervivencia en el medio y largo plazo. Conclusiones Los resultados del estudio, con sus limitaciones inherentes (AU)

Introduction and objectives Equal opportunities to access technical advances with recognized clinical value should be a priority of the publicly-funded health system. We analyzed variability among all the Spanish autonomous communities in the use of cardiovascular techniques with an established indication and its relationship with economic indicators, burden of disease, and hospital mortality. Method The activity registries of various Associations of the Spanish Society of Cardiology from 2011 to 2019 were analyzed for coronary angiography, overall percutaneous coronary intervention (PCI), primary PCI, implantable cardioverter-defibrillators (ICD), cardiac resynchronization therapy, and transcatheter aortic valve replacement (TAVR). Economic indices (gross domestic product and per capita health care expenditure) were obtained from public sources and data on attendance rates and mortality from the Resources and Quality in Cardiology (RECALCAR) reports of the Spanish Society of Cardiology. We analyzed the coefficient of variation for activity and the correlation of activity with regional economic indices, attendance rates, and risk-adjusted rates of in-hospital mortality. Results We identified wide variability in the use of technologies, especially for primary PCI (18%), ICD (22%), cardiac resynchronization therapy (36%), and TAVR (42%). A certain correlation with attendance rates was seen only for overall PCI and ICD. In general, no significant correlation was found between the use of the techniques and the economic indices of wealth and expenditure. The correlation with in-hospital mortality showed no significant results, although this was the analysis with the greatest limitations because the impact of these techniques on survival is exerted more in the mid- and long-term Conclusions The results of this study, despite its inherent limitations, show marked variability between autonomous communities in the use of cardiovascular technologies (AU)

Análisis de la atención al infarto con elevación del segmento ST en España. Resultados del Registro de Código Infarto de la ACI-SEC / Analysis of the management of ST-segment elevation myocardial infarction in Spain. Results from the ACI-SEC Infarction Code Registry

Introducción y objetivos Las redes de Código Infarto deben garantizar una atención al infarto agudo de miocardio con elevación del segmento ST con buenos resultados clínicos y dentro de los parámetros de tiempo recomendados. No hay información contemporánea sobre el funcionamiento de estas redes en España. El objetivo es analizar las características clínicas de los pacientes atendidos, el tiempo hasta la reperfusión, las características de la intervención realizada y la mortalidad a 30 días. Métodos Registro prospectivo, observacional y multicéntrico de pacientes los consecutivos atendidos en 17 redes de Código Infarto en España (83 centros con Código Infarto) entre el 1 de abril y el 30 de junio de 2019. Resultados Se atendió a 5.401 pacientes (media de edad, 64±13 años; el 76,9% varones), de los que 4.366 (80,8%) sufrieron un infarto con elevación del ST. De estos, se trató al 87,5% con angioplastia primaria, al 4,4% con fibrinolisis y al 8,1% sin reperfusión. En los casos tratados con angioplastia primaria, el tiempo entre el inicio de los síntomas y la reperfusión fue 193 [135-315] min y el tiempo entre el primer contacto médico y la reperfusión, 107 [80-146] min. La mortalidad total a 30 días por infarto agudo de miocardio con elevación del ST fue del 7,9%, mientras que entre los pacientes tratados con angioplastia primaria fue del 6,8%. Conclusiones Se trató con angioplastia primaria a la inmensa mayoría de los pacientes con infarto agudo de miocardio con elevación del ST, y en más de la mitad de los casos el tiempo desde el primer contacto médico hasta la reperfusión fue <120 min. La mortalidad a 30 días fue relativamente baja (AU)

Introduction and objectives ST-segment elevation myocardial infarction (STEMI) networks should guarantee STEMI care with good clinical results and within the recommended time parameters. There is no contemporary information on the performance of these networks in Spain. The objective of this study was to analyze the clinical characteristics of patients, times to reperfusion, characteristics of the intervention performed, and 30-day mortality. Methods Prospective, observational, multicenter registry of consecutive patients treated in 17 STEMI networks in Spain (83 centers with the Infarction Code), between April 1 and June 30, 2019. Results A total of 5401 patients were attended (mean age, 64±13 years; 76.9% male), of which 4366 (80.8%) had confirmed STEMI. Of these, 87.5% were treated with primary angioplasty, 4.4% with fibrinolysis, and 8.1% did not receive reperfusion. In patients treated with primary angioplasty, the time between symptom onset and reperfusion was 193 [135-315] minutes and the time between first medical contact and reperfusion was 107 [80-146] minutes. Overall 30-day mortality due to STEMI was 7.9%, while mortality in patients treated with primary angioplasty was 6.8%. Conclusions Most patients with STEMI were treated with primary angioplasty. In more than half of the patients, the time from first medical contact to reperfusion was <120 minutes. Mortality at 30 days was relatively low (AU)

Resultados clínicos tempranos tras el implante percutáneo de válvula aórtica por acceso transaxilar comparado con el acceso transfemoral. Datos del registro español de TAVI / Early clinical outcomes after transaxillary versus transfemoral TAVI. Data from the Spanish TAVI registry

Introducción y objetivos: El acceso transaxilar (ATx) se ha convertido en el acceso alternativo al transfemoral (ATF), más utilizado en pacientes sometidos a implante percutáneo de válvula aórtica (TAVI). El objetivo principal de este estudio es comparar la mortalidad total hospitalaria y a los 30 días de los pacientes incluidos en el registro español de TAVI a los que se trató por acceso ATx frente a ATF. Métodos: Se analizó a todos los pacientes incluidos en el registro español de TAVI tratados por ATx o ATF. Los eventos hospitalarios y a los 30 días de seguimiento se definieron según las recomendaciones de la Valve Academic Research Consortium. Se evaluó el impacto de la vía de acceso mediante emparejamiento por puntuación de propensión según las características clínicas y ecográficas. Resultados: Se incluyó a 6.603 pacientes, 191 (2,9%) tratados por ATx y 6.412 con ATF. Después del ajuste (grupo de ATx, n=113; grupo de ATF, n=3.035), el éxito del dispositivo fue similar entre ambos grupos (el 94% en el grupo de ATx frente al 95% en el de ATF; p=0,95); sin embargo, se observó un incremento en la tasa de infarto agudo de miocardio (OR=5,3; IC95%, 2,0-13,8; p=0,001), complicaciones renales (OR=2,3; IC95%, 1,3-4,1; p=0,003) e implante de marcapasos (OR=1,6; IC95%, 1,01-2,6; p=0,03) en el grupo de ATx comparado con el de ATF. De mismo modo, la mortalidad hospitalaria y a los 30 días fueron superiores en el grupo de ATx (respectivamente, OR=2,2; IC95%, 1,04-4,6; p=0,039; y OR=2,3; IC95%, 1,2-4,5; p=0,01). Conclusiones: El ATx se asocia con un aumento en la mortalidad total tanto hospitalaria como a los 30 días frente al ATF. Ante estos resultados, el ATx debe considerarse solo en caso de que el ATF no sea posible (AU)

Introduction and objectives: Transaxillary access (TXA) has become the most widely used alternative to transfemoral access (TFA) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to compare total in-hospital and 30-day mortality in patients included in the Spanish TAVI registry who were treated by TXA or TFA access. Methods: We analyzed data from patients treated with TXA or TFA and who were included in the TAVI Spanish registry. In-hospital and 30-day events were defined according to the recommendations of the Valve Academic Research Consortium. The impact of the access route was evaluated by propensity score matching according to clinical and echocardiogram characteristics. Results: A total of 6603 patients were included; 191 (2.9%) were treated via TXA and 6412 via TFA access. After adjustment (n=113 TXA group and n=3035 TFA group) device success was similar between the 2 groups (94%, TXA vs 95%, TFA; P=.95). However, compared with the TFA group, the TXA group showed a higher rate of acute myocardial infarction (OR, 5.3; 95%CI, 2.0-13.8); P=.001), renal complications (OR, 2.3; 95%CI, 1.3-4.1; P=.003), and pacemaker implantation (OR, 1.6; 95%CI, 1.01-2.6; P=.03). The TXA group also had higher in-hospital and 30-day mortality rates (OR, 2.2; 95%CI, 1.04-4.6; P=.039 and OR, 2.3; 95%CI, 1.2-4.5; P=.01, respectively). Conclusions: Compared with ATF, TXA is associated with higher total mortality, both in-hospital and at 30 days. Given these results, we believe that TXA should be considered only in those patients who are not suitable candidates for TFA (AU)

Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia / Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). Aim: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. Conclusion: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

[Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile]. / Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia.

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). AIM: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. CONCLUSION: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

A new family of copper-based MXenes.

In this work, we demonstrate, through first-principles calculations, the existence of a new family of copper-based MXenes. These add up new structures to the previously reported universe and span the interest of such 2D materials for applications in heterogeneous catalysis, ion-based batteries, sensors, biomedical applications, and so on. First, we propose the MXene-like structures: Cu2N, Cu2C, and Cu2O. Phonon spectra calculations confirmed their dynamical stability by showing just positive frequencies all through the 2D Brillouin zone. The new MXenes family displays metallic characteristics, mainly induced by the Cu-3d orbitals. Bader charge analysis and charge density differences depict bonds with ionic character in which Cu is positively charged, and the non-metal atom gets an anionic character. Also, we investigate the functionalization of the proposed structures with Cl, F, O, and OH groups. Results show that the H3 site is the most favorable for functionalization. In all cases, the non-magnetic nature and metallic properties of the pristine MXenes remain. Our results lay the foundations for the experimental realization of a new MXenes family.

Neuroinflammation is able to downregulate cytochrome P450 epoxygenases 2J3 and 2C11 in the rat brain.

Cytochrome P450 (CYP) epoxygenases have been considered the main producers of epoxyeicosatrienoic acids (EETs) through the oxidation of arachidonic acid (AA). EETs display various biological properties, notably their powerful anti-inflammatory activities. In the brain, EETs have proven to be neuroprotective and to improve neuroinflammation. However, it is known that inflammation could modify CYP expression. We have previously reported that an inflammatory process in astrocytes is able to down-regulate CYP2J3 and CYP2C11 mRNA, protein levels, and activity (Navarro-Mabarak et al., 2019). In this work, we evaluated the effect of neuroinflammation in protein expression of CYP epoxygenases in the brain. Neuroinflammation was induced by the intraperitoneal administration of LPS (1 mg/kg) to male Wistar rats and was corroborated by IL-6, GFAP, and Iba-1 protein levels in the cortex over time. CYP2J3 and CYP2C11 protein levels were also evaluated in the cortex after 6, 12, 24, 48, and 72 h of LPS treatment. Our results show for the first time that neuroinflammation is able to downregulate CYP2J3 and CYP2C11 protein expression in the brain cortex.

Experiencia en estapedostomías en Hospital del Salvador entre 2012 y 2018 / Stapedotomy experience at Hospital del Salvador between 2012 and 2018

INTRODUCCIÓN: La otoesclerosis es una enfermedad de presumible origen metabólico que determina la fijación de la cadena osicular. La estapedostomía con instalación de prótesis es la cirugía de elección en la actualidad para esta patología. OBJETIVO: Describir experiencia y resultados del tratamiento quirúrgico de pacientes con otoesclerosis en el Hospital del Salvador entre los años 2012 y 2018. Material y método: Estudio descriptivo retrospectivo mediante revisión de fichas clínicas de pacientes intervenidos quirúrgicamente en nuestro servicio desde enero de 2012 hasta septiembre de 2018 con sospecha de otoesclerosis. RESULTADOS: Se realizaron en total 52 cirugías a 45 pacientes, 40 vía microscópica, 10 vía endoscópica y 2 mixtas, se utilizaron dos modelos de prótesis, Schuknecht - type piston and wire y Stapes-Prothesen. El promedio tonal puro (PTP) por vía aérea prequirúrgico fue de 65 dB, con una diferencia ósea-aérea (gap) promedio de 36 dB. El PTP promedio posquirúrgico fue de 35 dB con gap promedio de 9 dB, logrando en promedio una mejoría de 31 dB en la vía aérea y 27 dB de cierre de gap. El 92% de los pacientes intervenidos lograron mejoría con respecto al gap posoperatorio. CONCLUSIÓN: La estapedostomía es una intervención que si bien no está exenta de complicaciones, ha demostrado ser segura y tener buenos resultados auditivos en la mayoría de los pacientes.

INTRODUCTION: Otosclerosis is a presumable metabolic disease that determines ossicular chain fixation. Stapedotomy with prosthesis installation is the surgery of choice for this pathology at present. AIM: To describe the experience and results of the surgical treatment of patients with otosclerosis in the Hospital del Salvador between 2012 and 2018. MATERIAL AND METHODS: Clinical records were reviewed of patients treated surgically in our department from January 2012 to September 2018 with suspicion of otosclerosis. RESULTS: A total of 52 surgeries were performed in 45 patients, 42 via microscopy and 10 via endoscopy, two models of prostheses were used Schuknecht - type piston and wire y Stapes-Prothesen. The pure tonal average (PTP) by pre-surgical air was 65 dB, with an average air gap (gap) of 36 dB. The average post-surgical PTP was 35 dB with an average gap of 9 db, achieving on average an improvement of 31 dB in the airway and 27 dB of gap closure. 92% of the patients who underwent surgery improved with respect to the postoperative gap. CONCLUSION: The stapedotomy is an intervention that although not free of complications, has been shown to be safe and have good hearing results in most patients.

Reduction in CYP1A1 and 2B2 activity at low oxygen tension.

The Cytochrome P450 (CYP) enzyme family comprises a wide array of monooxygenases involved in the oxidation of endobiotic and xenobiotic molecules. The active site of a CYP enzyme contains an iron protoporphyrin center coordinated to a cysteine thiolate, and then, molecular oxygen is associated with the iron to be converted into dioxygen complex plus substrate. Reduction by CYP reductase expedites hydroxylation of the compound. In this oxidation reaction, insufficient oxygen molecules would affect enzyme catalysis. Nevertheless, biochemical data about CYP kinetics at low oxygen concentrations are not available. In this work, we present the results on the variation in rat liver microsomal CYP Vmax app and Km app under normal and hypoxic conditions. Using alkoxyresorufin molecules as substrates, the Vmax/Km ratios for resorufin production decreased from 426 to 393 for CYP1A1 and from 343 to 202 for CYP2B1 at a low oxygen concentration (4.1 ppm) compared to the ratios observed at a normal oxygen concentration (6.5 ppm). Additionally, the bacterial mutagenicity of 2-aminoanthracene and cyclophosphamide, decreased by 32% and 42%, respectively, at low oxygen concentrations. These results support the hypothesis that low oxygen availability is implicated in the low efficiency of substrate oxidation by CYP.

Best Practice Framework of Fracture Liaison Services in Spain and their coordination with Primary Care.

The coordination of Fracture Liaison Services (FLS) with Primary Care (PC) is necessary for the continuity of care of patients with fragility fractures. This study proposes a Best Practice Framework (BPF) and performance indicators for the implementation and follow-up of FLS-PC coordination in clinical practice in Spain. PURPOSE: To develop a BPF for the coordination of FLS with PC in Spain and to improve the continuity of care for patients with fragility fractures. METHODS: A Steering Committee selected experts from seven Spanish FLS and related PC doctors and nurses to participate in a best practice workshop. Selection criteria were an active FLS with an identified champion and prior contact with PC centres linked to the hospital. The main aim of the workshop was to review current FLS practices in Spain and their integration with PC. A BPF document with processes, tools, roles, and metrics was then generated. RESULTS: Spanish FLS consists of a multidisciplinary team of physicians/nurses but with low participation of other professionals and PC staff. Evaluation and treatment strategies are widely variable. Four desired standards were agreed upon: (1) Effective channels for FLS-PC communication; (2) minimum contents of an FLS clinical report and its delivery to PC; (3) adherence monitoring 3 months after FLS baseline visit; and (4) follow-up by PC. Proposed key performance indicators are (a) number of FLS-PC communications, including consensus protocols; (b) confirmation FLS report received by PC; (c) medical/nursing PC appointment after FLS report received; and (d) number of training sessions in PC. CONCLUSIONS: The BPF provides a comprehensive approach for FLS-PC coordination in Spain, to promote the continuity of care in patients with fragility fractures and improve secondary prevention. The implementation of BPF recommendations and performance indicator tracking will benchmark best FLS practices in the future.

Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress.

Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.

SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression.

Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty.

Timpanoplastía endoscópica: experiencia en el Hospital del Salvador / Endoscopic tympanoplasty: experience in Hospital del Salvador

RESUMEN Introducción: La técnica endoscópica para la cirugía de oído ha presentado un gran avance en los últimos años, debido al avance de las ópticas de alta resolución e instrumental quirúrgico. El uso de endoscopio en timpanoplastías facilita la visualización de zonas de difícil acceso, como es el caso de pacientes con pared anterior del conducto auditivo externo prominente y perforaciones timpánicas anteriores, además permite la revisión de la caja timpánica y de las vías de ventilación del oído medio. Objetivo: Mostrar la timpanoplastía endoscópica (TE) como alternativa en pacientes con otitis media crónica y analizar el éxito anatómico y funcional. Material y método: Revisión de fichas clínicas de pacientes sometidos a TE en el Hospital del Salvador. Resultados: Catorce pacientes fueron operados entre octubre de 2015 y agosto de 2016. La edad promedio fue de 45 años. Todos fueron sometidos a TE unilateral. Once de 14 perforaciones comprometía alguno de los cuadrantes anteriores. De éstas, en el 82% el borde anterior de la perforación no era visible con otomicroscopía. Se realizó otoendoscopía y audiometría 2 meses poscirugía, logrando un éxito anatómico de 92,8%, y mejoría en el PTP posoperatorio en todos los pacientes. Conclusión: Los resultados obtenidos son similares a los descritos utilizando microscopio. La TE permite mejor visualización convirtiendo esta técnica en una alternativa quirúrgica y de docencia atractiva. Es necesario realizar seguimiento a estos pacientes y aumentar el número de pacientes en el futuro.

ABSTRACT Introduction: The endoscopic ear surgery technique has been a great advance in the last years due to the developments in high resolution optics and surgical instruments. The use of an endoscope provides the visualization of difficult access zones in the middle ear, such as patients with prominent anterior wall of the external auditory canal and anterior tympanic perforations. Aim: To describe the endoscopic tympanoplasty (ET) as an alternative treatment for patients who suffer from chronic otitis media, and to analyze the functional and anatomic outcome. Material and method: Clinical record review of patients submitted to a ET in Hospital del Salvador. Results: 14 patients were operated during October 2015 and August 2016. The average age was 45 years. All of them where submitted to a unilateral ET. 11 of 14 perforations compromised some of the anterior quadrants. In 82% of the latter the anterior edge of the perforation was not visible with otomicroscopy. An otomicroscopy and audiometry were performed 2 months after surgery, anatomic outcome success was of 92,8%, and PTA improved after surgery in all patients. Conclusion: The obtained results are similar to those described using microscope. ET allows improved visualization making this technique an attractive surgery and teaching choice. It is necessary to evaluate these results with a higher number of patients.

Cirugía endoscópica de oído para el manejo del colesteatoma atical / Endoscopic ear surgery approach for attic cholesteatoma treatment

RESUMEN El colesteatoma es la presencia de epitelio plano queratinizado en zonas neumatizadas del hueso temporal, cuya ubicación más frecuente es el ático. En la década de los noventa, se inicia el desarrollo de la cirugía endoscópica de oído, ofreciendo una nueva perspectiva en el tratamiento del colesteatoma. Se presentan dos casos clínicos de pacientes con colesteatoma atical. Se realiza abordaje endoscópico transcanal con resección macroscópica completa del colesteatoma. Audiometría posoperatoria evidencia mejoría de hipoacusia de conducción.

ABSTRACT The cholesteatoma is the presence of keratinized squamous epithelium in pneumatized areas of the temporal bone, its most frequent location is the attic. In the 1990s the development of the ear endoscopic surgery begins, offering a new perspective for cholesteatoma treatment. Two clinical cases of patients who present attic cholestatoma are described. A transcanal endoscopic approach with complete macroscopic resection was accomplished. Post-surgical audiometry shows improvement of the conductive hearing loss.

Deprivación andrógenica en cáncer de próstata y riesgo de fractura a largo plazo / Androgen deprivation in prostate cancer and the long-term risk of fracture

Objetivos: Determinar el porcentaje de pérdida de masa ósea y el riesgo de fractura inducido por la terapia de deprivación androgénica en pacientes con cáncer de próstata. Material y métodos: Estudio prospectivo en 2 fases. En la primera se recogieron variables demográficas, FRAX(R), densidad mineral ósea y fracturas clínicas antes de iniciar la terapia y hasta un año después de finalizada. En la segunda se realizó una entrevista telefónica una media de 8,5 años después del inicio del estudio para evaluar nuevas fracturas. Resultados: Se incluyeron 150 pacientes con una edad media de 67 años y duración media de la terapia de 24 meses. Antes del inicio del tratamiento 62 pacientes (41%) presentaban osteoporosis o baja masa ósea en la densitometría. Después del primer año de tratamiento la densidad mineral ósea descendió una media de 3,7% y 2,1% en la columna lumbar y el cuello femoral, respectivamente. Al final del segundo y tercer año el porcentaje de pérdida fue menor. Durante la primera fase del estudio 4 pacientes (2,7%) sufrieron una fractura. En la entrevista telefónica a 80 pacientes (53%) solo uno había sufrido una fractura. Conclusiones: En los pacientes con cáncer de próstata y terapia de deprivación androgénica la mayor pérdida ósea se produce durante el primer año. Cuando el tratamiento no supera los 2 años el riesgo absoluto de fractura es bajo, y la fractura clínica infrecuente a corto y a largo plazo

Objectives: To determine the rate of bone mass loss and the risk of fracture induced by androgen deprivation therapy in patients with prostate cancer. Material and methods: Prospective study in 2 phases. In the first phase, demographic variables, FRAX(R), bone mineral density and clinical fractures were collected, before starting the therapy and up to 1 year after ending the therapy. In the second phase, we conducted a telephone interview a mean of 8.5 years after the start of the study to assess new fractures. Results: We included 150 patients with a mean age of 67 years and a mean therapy duration of 24 months. Before starting the treatment, 62 patients (41%) showed osteoporosis or low bone mass in the densitometry. After the first year of treatment, the bone mineral density decreased a mean of 3.7% and 2.1% in the lumbar spine and femoral neck, respectively. At the end of the second and third year, the loss rate was lower. During the first phase of the study, 4 patients (2.7%) experienced a fracture. In the telephone interviews with 80 patients (53%), only 1 had experienced a fracture. Conclusions: In the patients with prostate cancer and androgen deprivation therapy, greater bone loss occurred during the first year. When the treatment did not exceed 2 years, the absolute risk of fracture was low, and clinical fractures were uncommon in the short and long term

Androgen deprivation in prostate cancer and the long-term risk of fracture. / Deprivación andrógenica en cáncer de próstata y riesgo de fractura a largo plazo.

OBJECTIVES: To determine the rate of bone mass loss and the risk of fracture induced by androgen deprivation therapy in patients with prostate cancer. MATERIAL AND METHODS: Prospective study in 2 phases. In the first phase, demographic variables, FRAX®, bone mineral density and clinical fractures were collected, before starting the therapy and up to 1 year after ending the therapy. In the second phase, we conducted a telephone interview a mean of 8.5 years after the start of the study to assess new fractures. RESULTS: We included 150 patients with a mean age of 67 years and a mean therapy duration of 24 months. Before starting the treatment, 62 patients (41%) showed osteoporosis or low bone mass in the densitometry. After the first year of treatment, the bone mineral density decreased a mean of 3.7% and 2.1% in the lumbar spine and femoral neck, respectively. At the end of the second and third year, the loss rate was lower. During the first phase of the study, 4 patients (2.7%) experienced a fracture. In the telephone interviews with 80 patients (53%), only 1 had experienced a fracture. CONCLUSIONS: In the patients with prostate cancer and androgen deprivation therapy, greater bone loss occurred during the first year. When the treatment did not exceed 2 years, the absolute risk of fracture was low, and clinical fractures were uncommon in the short and long term.