Balloon-Expandable Pulmonary Valves for Patched or Native Right Ventricular Outflow Tracts.

The implantation of percutaneous balloon expandable valves in native or patched right ventricular outflow tracts (nRVOT) is a challenging technique due to the diversity of anatomies and shapes, the large sizes, and the distensibility of the nRVOT, for which specific techniques have been developed. We present a single center experience with balloon expandable percutaneous pulmonary valves in nRVOT, describing the techniques used, complications observed, and a short-mid term follow-up.. This is a single center descriptive study of patients who underwent a percutaneous pulmonary valve implantation in a nRVOT with a balloon expandable pulmonary valve in our center between September 2012 and June 2022.. We implanted successfully 45 valves in 46 patients (20 Sapien and 25 Melody). Tetralogy of Fallot or pulmonary atresia with VSD were the main congenital heart disease (n = 32). All were pre-stented, 18 in a one step procedure. We used a Dryseal sheath in 13/21 Sapien. In 6 patients we used the anchoring technique, 5 with a very large nRVOT and one pyramidal nRVOT. In the 3.5 year follow-up 7 patients developed endocarditis and 3 required a valve redilation, no fractures were observed. PPVI of native RVOT with balloon expandable valves is feasible in a number of selected anatomies, including large or pyramidal nRVOT, using specific techniques, (presenting, LPA anchoring).

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

Epidermólisis bullosa en España: Estudio observacional de una cohorte de pacientes atendidos en un centro de referencia nacional / Epidermolysis Bullosa in Spain: Observational Study of a Cohort of Patients Treated in a National Referral Center

Antecedentes y objetivo La epidermólisis bullosa (EB) es un grupo heterogéneo de trastornos hereditarios caracterizado por un aumento de la fragilidad mucocutánea. El objetivo del presente estudio es describir las características clínicas y epidemiológicas de los pacientes con EB atendidos en el Hospital Universitario La Paz, centro de referencia nacional para EB hereditaria. Material y método Estudio observacional, retrospectivo y unicéntrico. Se incluyeron todos los pacientes con diagnóstico clínico y molecular de EB atendidos en el Servicio de Dermatología del Hospital Universitario La Paz desde el 1 de enero de 2000 hasta el 28 de febrero de 2021. Resultados Se registraron 214 pacientes, con una edad mediana de 17 años (RIQ: 8-32); el 54,2% fueron mujeres. Las formas clínicas correspondieron a EB distrófica con 135 (63,1%) casos, EB simple con 67 (31,3%) casos, EB juntural con ocho (3,7%), EB Kindler con tres (1,4%) casos y EB adquirida con un (0,5%) caso. El 35,5% de los pacientes procedían de Madrid. Las complicaciones clínicas más frecuentes en nuestra serie fueron el prurito (63,1%), las infecciones locales (56,5%) y el dolor (54,7%). Las complicaciones más graves fueron las cardíacas (5,6%) y la aparición de CCE (10,3%). Fallecieron 22 pacientes (10,3%). Conclusiones La forma clínica predominante fue la EBDR. Las complicaciones más prevalentes fueron el prurito, el dolor y las infecciones, y las más graves, la miocardiopatía y el CCE. Es un estudio pionero realizado en nuestro país que permitirá implementar estrategias para mejorar la situación sociosanitaria de los pacientes con EB (AU)

Background and objective Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by a high degree of mucocutaneous fragility. This study aimed to describe the clinical and epidemiologic characteristics of patients with EB treated in Hospital Universitario La Paz, a national referral center for inherited EB. Material and methods Observational, retrospective, single-center study. We included all cases with a clinical and molecular diagnosis of EB managed in the hospital's dermatology department from January 2, 2000, to February 28, 2021. Results A total of 214 cases were studied. The median (interquartile range) age was 17 (8–32) years; 54.2% were women. One hundred thirty-five (63.1%) patients had dystrophic EB, 67 (31.3%) had EB simplex, 8 (3.7%) had junctional EB, and 3 (1.4%) had Kindler syndrome. One (0.5%) had EB acquisita. Over a third (35.5%) of the patients resided in Madrid. The most common clinical complications were pruritus (63.1%), local infections (56.5%), and pain (54.7%). The most serious ones were cardiomyopathy (in 5.6%) and squamous cell carcinoma (10.3%). Twenty-two patients (10.3%) died. Conclusions Dystrophic EB was the most prevalent clinical form. The most prevalent complications were pruritus, pain, and infections. The most serious ones were cardiomyopathy and squamous cell carcinoma. This study is the first in Spain that explores strategies for improving the health status and quality of life of patients with EB (AU)

Epidermolysis Bullosa in Spain: Observational Study of a Cohort of Patients Treated in a National Referral Center. / Epidermólisis bullosa en España: Estudio observacional de una cohorte de pacientes atendidos en un centro de referencia nacional.

BACKGROUND AND OBJECTIVE: Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by a high degree of mucocutaneous fragility. This study aimed to describe the clinical and epidemiologic characteristics of patients with EB treated in Hospital Universitario La Paz, a national referral center for inherited EB. MATERIAL AND METHODS: Observational, retrospective, single-center study. We included all cases with a clinical and molecular diagnosis of EB managed in the hospital's dermatology department from January 2, 2000, to February 28, 2021. RESULTS: A total of 214 cases were studied. The median (interquartile range) age was 17 (8-32) years; 54.2% were women. One hundred thirty-five (63.1%) patients had dystrophic EB, 67 (31.3%) had EB simplex, 8 (3.7%) had junctional EB, and 3 (1.4%) had Kindler syndrome. One (0.5%) had EB acquisita. Over a third (35.5%) of the patients resided in Madrid. The most common clinical complications were pruritus (63.1%), local infections (56.5%), and pain (54.7%). The most serious ones were cardiomyopathy (in 5.6%) and squamous cell carcinoma (10.3%). Twenty-two patients (10.3%) died. CONCLUSIONS: Dystrophic EB was the most prevalent clinical form. The most prevalent complications were pruritus, pain, and infections. The most serious ones were cardiomyopathy and squamous cell carcinoma. This study is the first in Spain that explores strategies for improving the health status and quality of life of patients with EB.

Doxycycline-functionalized polymeric nanoparticles inhibit Enterococcus faecalis biofilm formation on dentine.

AIM: To evaluate in a laboratory setting the antimicrobial properties and the potential to inhibit biofilm formation of novel remineralizing polymeric nanoparticles (NPs) when applied to dentine surfaces and to ascertain the effect of the functionalization of these NPs with zinc, calcium or doxycycline. METHODOLOGY: The antimicrobial activity and inhibition of biofilm formation of polymeric NPs were analysed on human dentine blocks that were infected with Enterococcus faecalis before or after application of NPs. LIVE/DEAD ® testing under Confocal Laser Scanning Microscopy and bacterial culturing were employed to analyse biofilm biovolume and bacterial viability. Field Emission Scanning Electron Microscopy was also employed to assess biofilm morphology. One-way anova with Welch's correction and post hoc comparison by the Games-Howell test were performed for comparisons between groups. RESULTS: The un-functionalized NPs displayed the greatest antimicrobial activity against E. faecalis biofilms as they provided the lowest biovolume (3865.7 ± 2926.97 µm3 ; P < 0.001) and the highest dead/injured cells percentage (79.93 ± 18.40%; P < 0.001), followed by Dox-NPs (biovolume: 19,041.55 ± 17,638.23 µm3 , dead/injured cells: 45.53 ± 26.50%; P < 0.001). Doxycycline-loaded NPs had the largest values of inhibition of biofilm formation with the lowest biofilm biovolume (8517.65 ± 7055.81 µm3 ; P < 0.001) and a high dead/injured bacterial percentage (68.68 ± 12.50%; P < 0.001). Un-functionalized NPs did not reduce biomass growth (P > 0.05), but attained the largest percentage of compromised cells (93 ± 8.23%; P < 0.001), being able to disrupt biofilm formation. It also produced occlusion of dentinal tubules, potentially interfering with bacterial tubule penetration. CONCLUSIONS: A new generation of bioactive nano-fillers (doxycycline-functionalized polymeric NPs) had antibacterial activity and occluded dentinal tubules. Incorporating these NPs into endodontic sealers may have the potential to enhance the outcome of root canal treatment.

Antimicrobial effect of nanostructured membranes for guided tissue regeneration: an in vitro study.

OBJECTIVE: The purpose of this in vitro study was to evaluate the antibacterial effect of a novel non-resorbable, bioactive polymeric nanostructured membrane (NMs), when doped with zinc, calcium and doxycycline. METHODS: A validated in vitro subgingival biofilm model with six bacterial species (Streptococcus oralis, Actinomyces naeslundii, Veillonela parvula, Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans) was used. The experimental NMs, with and without being doped with doxycycline, calcium and zinc, were placed on hydroxyapatite (HA) discs. As positive control membranes, commercially available dense polytetrafluoroethylene (d-PTFE) membranes were used and, as negative controls, the HA discs without any membrane. The experimental, positive and negative control discs were exposed to a mixed bacterial suspension, at 37 °C under anaerobic conditions, during 12, 24, 48 and 72 h. The resulting biofilms were analyzed through scanning electron microscopy (SEM), to study their structure, and by quantitative polymerase chain reaction (qPCR), to assess the bacterial load, expressed as colony forming units (CFU) per mL. Differences between experimental and control groups were evaluated with the general linear model and the Bonferroni adjustment. RESULTS: As shown by SEM, all membrane groups, except the NMs with doxycycline, resulted in structured biofilms from 12-72 hours. Similarly, only the membranes loaded with doxycycline demonstrated a significant reduction in bacterial load during biofilm development, when compared with the control groups (p < 0.001). SIGNIFICANCE: Doxycycline-doped nanostructured membranes have an impact on biofilm growth dynamics by significant reducing the bacterial load.

Small-area methods for investigation of environment and health.

Small-area studies offer a powerful epidemiological approach to study disease patterns at the population level and assess health risks posed by environmental pollutants. They involve a public health investigation on a geographical scale (e.g. neighbourhood) with overlay of health, environmental, demographic and potential confounder data. Recent methodological advances, including Bayesian approaches, combined with fast-growing computational capabilities, permit more informative analyses than previously possible, including the incorporation of data at different scales, from satellites to individual-level survey information. Better data availability has widened the scope and utility of small-area studies, but has also led to greater complexity, including choice of optimal study area size and extent, duration of study periods, range of covariates and confounders to be considered and dealing with uncertainty. The availability of data from large, well-phenotyped cohorts such as UK Biobank enables the use of mixed-level study designs and the triangulation of evidence on environmental risks from small-area and individual-level studies, therefore improving causal inference, including use of linked biomarker and -omics data. As a result, there are now improved opportunities to investigate the impacts of environmental risk factors on human health, particularly for the surveillance and prevention of non-communicable diseases.

Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort.

AIM: The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. RESULTS: Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20-37) years and 47.8 (17.9-68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48-0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69-10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35-16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10-2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01-1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11-1.34; p < 0.0001) were predictive factors of serious infections. CONCLUSIONS: Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

Bayesian spatial modelling for quasi-experimental designs: An interrupted time series study of the opening of Municipal Waste Incinerators in relation to infant mortality and sex ratio.

BACKGROUND: There is limited evidence on potential health risks from Municipal Waste Incinerators (MWIs), and previous studies on birth outcomes show inconsistent results. Here, we evaluate whether the opening of MWIs is associated with infant mortality and sex ratio in the surrounding areas, extending the Interrupted Time Series (ITS) methodological approach to account for spatial dependencies at the small area level. METHODS: We specified a Bayesian hierarchical model to investigate the annual risks of infant mortality and sex-ratio (female relative to male) within 10 km of eight MWIs in England and Wales, during the period 1996-2012. We included comparative areas matched one-to-one of similar size and area characteristics. RESULTS: During the study period, infant mortality rates decreased overall by 2.5% per year in England. The opening of an incinerator in the MWI area was associated with -8 deaths per 100,000 infants (95% CI -62, 40) and with a difference in sex ratio of -0.004 (95% CI -0.02, 0.01), comparing the period after opening with that before, corrected for before-after trends in the comparator areas. CONCLUSION: Our method is suitable for the analysis of quasi-experimental time series studies in the presence of spatial structure and when there are global time trends in the outcome variable. Based on our approach, we do not find evidence of an association of MWI opening with changes in risks of infant mortality or sex ratio in comparison with control areas.

Correction to: PANLAR consensus statement on biosimilars.

The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".

The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study.

OBJECTIVE: Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease. METHODS: A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008-2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression. RESULTS: Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008-2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5-53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis. CONCLUSIONS: This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival.

PANLAR consensus statement on biosimilars.

INTRODUCTION: Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. OBJECTIVE: The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). METHODS: Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. RESULTS: Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. CONCLUSION: The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. KEY POINTS: • Biologics have improved the treatment of rheumatic diseases. • Their high cost limits access for many patients in both North America and Latin America. • Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. • PANLAR presents its consensus on biosimilars in rheumatology.

Silver-loaded nanoparticles affect ex-vivo mechanical behavior and mineralization of dentin.

BACKGROUND: The aim was to evaluate the effect of silver loaded nanoparticles (NPs) application on the triboscopic, crystallographic and viscoelastic properties of demineralized dentin. Polymethylmetacrylate-based NPs and Ag loaded NPs were applied on demineralized dentin. MATERIAL AND METHODS: Treated and untreated surfaces were probed by a nanoindenter to test viscoelasticity, and by atomic force microscopy to test nanoroughness and collagen fibril diameter. X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging were also used. RESULTS: Dentin treated with Ag-NPs attained the lowest complex modulus, and the highest tan delta values after 7 days of storage. Dentin treated with undoped-NPs achieved the lowest nanoroughness and the greatest collagen bandwidths among groups. Crystals were identified as hydroxyapatite with the highest crystallographic maturity and crystallite size in dentin treated with undoped-NPs. Texture increased in all samples from 24 h to 7 d, except in dentin surfaces treated with Ag-NPs at 310 plane. Polyhedral, block-like, hexagonal or plate-like shaped apatite crystals constituted the bulk of minerals in dentin treated with Ag-NPs, after 7 d. Polyhedral or rounded/drop-like, and polymorphic in strata crystal apatite characterized the minerals when undoped-NPs were used, with more crystalline characteristics after 7 d than that found when Ag-NPs were applied. Ag-NPs application did not improve the mechanical performance of dentin and did not produce dentin remineralization. However, energy was dissipated through the dentin without showing stress concentration; contrary was occurring at dentin treated with undoped-NPs, that provoked bridge-like mineral deposits at the dentin surface. CONCLUSIONS: Ag-NPs application did not enhance the mechanical properties of cervical dentin, though the energy dissipation did not damage the dentin structure. Remineralization at dentin was not produced after Ag-NPs application, though improved crystallinity may lead to increase stability of the apatite that was generated at the dentin surface.

Outcomes of laparoscopic management of multicompartmental pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) is an increasing medical problem with complex diagnostics and controversial surgical management. It causes a series of dysfunctions in the gynecological, urinary, and anorectal organs. Numerous procedures have been proposed to treat these conditions, but in recent years, ventral mesh rectocolposacropexy (VMRCS) has emerged as the procedure of choice for the surgical treatment of POP, especially by a laparoscopic approach. This surgical technique limits the risk of autonomic nerve damage, and the colpopexy allows the correction of concomitant prolapse of the middle compartment. However, symptoms derived from anterior compartment prolapse remain a major morbidity and sometimes require an additional procedure. The aim of this study is to evaluate the results of laparoscopic prosthetic rectocolposacropexy (LRCS) and colposacropexy (LCS) procedures performed to manage combined multicompartmental POP. METHODS: Between November 2008 and December 2017, 38 patients with symptomatic POP underwent rectocolposacropexy (RCS) or colposacropexy (CS) by a laparoscopic approach. Demographics, mortality, morbidity, hospital stay, and functional outcomes were retrospectively analyzed. RESULTS: The median operating time was 200 min (IQR 160-220). Additional simultaneous surgery for POP was performed in nine cases: five suburethral slings and four hysterectomies were performed. No mortality was recorded. The conversion rate was 7.89%. There were two intraoperative complications (5.26%): one enterotomy and one urinary bladder tear. Late complications occurred in 5.26% of cases. After a mean follow-up of 20 months, constipation was completely resolved or improved in 83.33% of patients, urinary stress incontinence was resolved or improved in 52.94%, and gynecological symptomatology was resolved or improved in 93.75%. The recurrence rate was 5.26%. CONCLUSIONS: Laparoscopic mesh rectocolposacropexy and colposacropexy are safe and effective techniques associated with very low morbidity. In the medium term, they provide good results for POP and associated symptoms, but urinary symptomology has a worse outcome.

Antibacterial effects of polymeric PolymP-n Active nanoparticles. An in vitro biofilm study.

OBJECTIVE: to study the antibacterial effect of polymeric PolymP-n Active nanoparticles using an in vitro subgingival biofilm model. METHODS: Hydroxyapatite discs coated with five modalities of nanoparticles (NPs): NPs, NPs doped with zinc, calcium, silver and doxycycline, PBS as control, and Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were studied in a static in vitro biofilm model (12, 24, 48, and 72h). Nano-roughness of the different disc surfaces (SRa, in nm) and morphological characteristic of the biofilms (thickness (µm) and bacterial viability) were studied by different microscopy modalities. Quantitative Polymerase Chain Reaction was used to assess the effect of the nanoparticles on the bacterial load (colony forming unit per milliliter) (CFUmL-1). Analysis of variance and post-hoc testing with T3 Dunnett́s, and Student Newman Keuls correction was used. Results were considered statistically significant at p<0.05. RESULTS: Surfaces containing the different nanoparticles showed significant increments in roughness when compared to controls (p<0.05). A similar biofilm formation and dynamics was observed, although reductions in bacterial viability were detected in biofilms in contact with the different nanoparticles, more pronounced with silver and doxycycline NPs. Doxycycline-NPs biofilms resulted in unstructured biofilm formation and significantly lower number of the six species when compared with the other nanoparticles specimens and controls (p<0.001 in all cases). SIGNIFICANCE: Polymeric PolymP-n Active nanoparticles when combined with silver and doxycycline showed a significant antibacterial effect when tested in an in vitro subgingival biofilm model.

Apendicitis aguda complicada en el anciano. factores predisponentes. Utilidad de las escalas de probabilidad diagnóstica y tratamiento más adecuado / Complicated acute appendicitis in the elderly. predisposing factors. utility of the diagnostic probability scales and the most adequate treatment

Introducción. La apendicitis aguda (AA) tradicionalmente se ha considerado una patología de gente joven. Con el envejecimiento progresivo de la población, aparece más frecuentemente a partir de los 65 años. El diagnóstico precoz y el tratamiento mínimamente invasivo evitarían una elevada morbi-mortalidad en estos pacientes. Material y métodos. Se realizó un estudio retrospectivo de las apendicectomías realizadas en un Hospital de Nivel 1 durante 2010-2016. Se seleccionaron los pacientes con edad mayor o igual a 65 años. Se efectuó un análisis descriptivo de la cohorte y después un análisis univariante, comparando AA complicada (plastrón, gangrenosa, perforada) frente a AA no complicada. Con las variables estadísticamente significativas (p<0,050) de éste, se realizó un análisis multivariante (método de Wald), para hallar factores predictores independientes para AA complicada. Resultados. De los 458 pacientes, 51 tenían edad ≥65 años. El 47,06% (24) tuvieron AA complicada. La mediana de edad fue 77 años [70,8-79,0]. El 70,8% eran varones. Edad, sexo, cirugía laparoscópica, evolución del dolor en horas, PCR mayor a 18 mg/ml y leucocitos mayor a 10.000/mL, fueron factores estadísticamente significativos en el análisis univariante. En el análisis multivariante, resultaron estadísticamente significativas: PCR>18mg/ml [OR=14,35(1,49-141,52)] y Leucocitos>10.000/mL [OR=11,70(1,15-119,26)]. Conclusiones. La apendicitis aguda es una entidad cada vez más frecuente en ancianos. Las escalas de probabilidad diagnóstica no son buenos predictores en ancianos. La PCR>18 mg/ml y los Leucocitos>10.000/mL demostraron ser factores predictores independientes para AA complicada. La apendicetomía laparoscópica se consolida como un tratamiento idóneo, seguro y con buenos resultados también en ancianos

Introduction. Acute appendicitis (AA) has traditionally been considered a pathology of young people. With the progressive aging of the population, it appears more frequently after 65 years of age. Early diagnosis and minimally invasive treatment would avoid a high morbidity and mortality in these patients. Material and methods. A retrospective study of appendectomies performed in a Level 1 Hospital during 2010-2016 was conducted. Patients older than or equal to 65 years were selected. A descriptive analysis of the cohort was made and then a univariate analysis, comparing complicated AA (plastron, gangrenous, perforated) versus uncomplicated AA. With the statistically significant variables (p <0.050) of this, a multivariate analysis (Wald’s method) was performed to find independent predictors for complicated AA. Results. Of the 458 patients, 51 were aged to 65 years. 47.06% (24) had complicated AA. The median age was 77 years [70.8-79.0]. 70.8% were males. Age, sex, laparoscopic surgery, pain evolution in hours, CRP greater than 18 mg / ml and leukocytes greater than 10,000 / mL were statistically significant factors in the univariate analysis. In the multivariate analysis, they were statistically significant: CRP> 18mg / ml [OR = 14.35 (1.49-141.52)] and Leukocytes > 10,000 / (L [OR = 11.70 (1.15-119, 26)]. Conclusions. Acute appendicitis is an increasingly common entity in the elderly. Diagnostic probability scales are not good predictors in the elderly. CRP> 18 mg / ml and Leukocytes> 10,000 / μL proved to be independent predictors for complicated AA. Laparoscopic appendectomy is consolidated as a suitable, safe treatment with good results also in the elderly

A zinc-doped endodontic cement facilitates functional mineralization and stress dissipation at the dentin surface.

BACKGROUND: The purpose of this study was to evaluate nanohardness and viscoelastic behavior of dentin surfaces treated with two canal sealer cements for dentin remineralization. MATERIAL AND METHODS: Dentin surfaces were subjected to: i) 37% phosphoric acid (PA) or ii) 0.5 M ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite), respectively. Samples were stored in simulated body fluid during 24 h or 21 d. The intertubular and peritubular dentin were evaluated using a nanoindenter to assess nanohardness (Hi). The load/displacement responses were used for the nano-dynamic mechanical analysis to estimate complex modulus (E*) and tan delta (δ). The modulus mapping was obtained by imposing a quasistatic force setpoint to which a sinusoidal force was superimposed. AFM imaging and FESEM analysis were performed. RESULTS: After 21 d of storage, dentin surfaces treated with EDTA+calcypatite, PA+calcypatite and EDTA+oxipatite showed viscoelastic discrepancies between peritubular and intertubular dentin, meaning a risk for cracking and breakdown of the surface. At both 24 h and 21 d, tan δ values at intertubular dentin treated with the four treatments performed similar. At 21 d time point, intertubular dentin treated with PA+oxipatite achieved the highest complex modulus and nanohardness, i.e., highest resistance to deformation and functional mineralization, among groups. CONCLUSIONS: Intertubular and peritubular dentin treated with PA+oxipatite showed similar values of tan δ after 21 d of storage. This produced a favorable dissipation of energy with minimal energy concentration, preserving the structural integrity at the dentin surface.

Sulindac induces differentiation of glioblastoma stem cells making them more sensitive to oxidative stress.

Glioblastoma tumors (GBM) are very heterogeneous, being comprised of several cell subtypes, including glioblastoma stem cells (GSC). These tumors have a high rate of recurrence after initial treatment and one of the most prevalent theories to explain this is the cancer stem cell theory, which proposes that glioblastomas arise from mutations that transform normal neural stem cells (NSC) into GSC, which are highly resistant to oxidative stress and anti-cancer therapies. Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has been shown to protect the normal cells against oxidative damage by initiating a preconditioning response, but selectively sensitizes several cancer cell lines to agents that affect mitochondrial respiration, resulting in enhanced killing of the cancer cells. These effects of sulindac are independent of its NSAID activity. There is little information on the effect of sulindac on normal and cancer stem cells. To study the effect of sulindac on both normal and cancer stem cells, we have isolated normal neural stem cells (NSC), from mice hippocampi and glioblastoma stem cells (GSC) from a glioma cell line, U87. As expected from previous studies sulindac can protect normal astrocytes against oxidative stress. Sulindac induces differentiation of both NSC and GSC cells and sulindac upregulates neurogenesis in NSC. The differentiated NSC are also protected from oxidative stress damage, whereas the differentiation of GSC by sulindac increases the sensitivity of these cells to agents that cause oxidative stress. The S epimer of sulindac is more effective than the R epimer in inducing neuronal differentiation in both NSC and GSC. These results indicate that the ability of sulindac to induce GSC differentiation may have therapeutic value in preventing tumour recurrence.

Ion-modified nanoparticles induce different apatite formation in cervical dentine.

AIM: To investigate if crystallinity and ultrastructure are modified when cervical dentine is treated with four different nanogels-based solutions for remineralizing purposes. METHODOLOGY: Experimental nanogels based on polymeric nanoparticles (NPs) and zinc, calcium or doxycycline-loaded NPs were applied to citric acid etched dentine to facilitate the occlusion of tubules and the mineralization of the dentine surface. Dentine surfaces were studied by X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging. RESULTS: Crystals at the dentine surface were identified as hydroxyapatite with the highest crystallographic maturity and crystallite size in dentine treated with Zn-NPs-based gel. Texture increased in all samples from 24 h to 7 days, except in dentine surfaces treated with Zn-NPs gel. Polyhedral, plate-like and drop-like shaped apatite crystals constituted the bulk of minerals in dentine treated with Zn-NPs gel, after 7 days. Polymorphic, cubic and needle-like shaped crystals distinguished minerals, with more amorphous characteristics in dentine treated with Ca-NPs gel after 7 days than that found when Zn-NPs were applied. Doxycycline-NPs produced the smallest crystallites with poor crystallinity, maturity and chemical stability. CONCLUSIONS: Crystalline and amorphous phases of newly formed hydroxyapatite were described in both types of dentine treated with Zn-NPs as well as Ca-NPs gels with multiple shapes of crystallites. Crystal shapes ranged from rounded/drop-like or plate-like crystals to needle-like or polyhedral and cubic apatite appearance.