Telocytes regulate macrophages in periodontal disease.

Telocytes (TCs) or interstitial cells are characterised in vivo by their long projections that contact other cell types. Although telocytes can be found in many different tissues including the heart, lung, and intestine, their tissue-specific roles are poorly understood. Here we identify a specific cell signalling role for telocytes in the periodontium whereby telocytes regulate macrophage activity. We performed scRNA-seq and lineage tracing to identify telocytes and macrophages in mouse periodontium in homeostasis and periodontitis and carried out hepatocyte growth factor (HGF) signalling inhibition experiments using tivantinib. We show that telocytes are quiescent in homeostasis; however, they proliferate and serve as a major source of HGF in periodontitis. Macrophages receive telocyte-derived HGF signals and shift from an M1 to an M1/M2 state. Our results reveal the source of HGF signals in periodontal tissue and provide new insights into the function of telocytes in regulating macrophage behaviour in periodontitis through HGF/Met cell signalling, which may provide a novel approach in periodontitis treatment.

Apendicitis aguda secundaria a ingesta de cuerpo extraño / Acute appendicitis secondary to foreign body ingestion

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Silicone oil droplets in repackaged anti-vascular endothelial growth factors for intravitreal injections: In search of the main source of contamination.

INTRODUCTION: Repackaging of anti-vascular endothelial growth factors in polypropylene syringes lubricated with silicone oil for intravitreal use is associated with the presence of intravitreal silicone oil droplets. The objective of this study is to assess how the use of silicone-free syringes (for storage and/or administration) would reduce the amount of silicone oil droplets in the product to be administered. METHODS: Two 16 mL vials of bevacizumab were repackaged at the compounding pharmacy to obtain four sets of product, each consisting of three 1.2 mL tubes of the drug repackaged in different ways. Set A was repackaged according to routine practice, that is, the drug was placed into 1 mL siliconized syringes and 60 µL aliquots were extracted with 0.5 mL insulin siliconized syringes until reaching 1.2 mL. In set B, a 1-mL silicone-free syringe was used, followed by a 0.5 mL siliconized syringe. In set C, only 0.5 mL siliconized syringes were used. In set D, only the 1-mL silicone-free syringe was used. Micro-Flow Imaging technology was used for quantifying silicone oil droplet-like particles below 25 µm. RESULTS: Silicone oil droplet-like particles were absent in set D. Set C had the highest average frequency of these particles, which was much lower in sets A and B. Set B had the lowest frequency. CONCLUSION: 0.5 mL insulin syringes with staked-in needles used for supplying the product seem to be the main source of silicone oil contamination in repackaged anti-vascular endothelial growth factors. Silicone-free insulin syringes with staked-in needles would be strongly recommended for supplying anti-vascular endothelial growth factor intravitreal injections from compounding pharmacies.

Relationship Between Dryland Strength and Swimming Performance: Pull-Up Mechanics as a Predictor of Swimming Speed.

Pérez-Olea, JI, Valenzuela, PL, Aponte, C, and Izquierdo, M. Relationship between dryland strength and swimming performance: pull-up mechanics as a predictor of swimming speed. J Strength Cond Res 32(6): 1637-1642, 2018-This study aimed to examine the validity of the countermovement jump (CMJ) and the pull-up exercise as predictors of swimming performance. Twelve young male swimmers (Mean ± SD, 19 ± 3 years; 75 ± 10 kg; 180 ± 6 cm) with a homogenous level of performance (50-m freestyle time [50F]: 26.41 ± 1.44 seconds, coefficient of variance: 5.5%) participated in this study. Subjects performed a test of a single pull-up (PU) and a test of maximum number of pull-ups until muscular failure (PUF), and the mechanics of the ascending phase were recorded using a lineal force transducer. The height reached in a single CMJ test and the mean height during 30 consecutive CMJs were also determined. The swimmers' 50-m leg-only swimming time (50L) was also registered. The 50F time was strongly correlated with different variables of the PU (r = -0.76 to -0.80; p ≤ 0.05) and PUF test (r = -0.64 to -0.88; p ≤ 0.05), but not with the number of pull-ups performed. A significant relationship between 50F and 50L was observed (r = 0.78; p ≤ 0.05), with no relationship between the CMJ tests and swimming performance. Furthermore, multiple linear regression showed that 50L and the relative loss of velocity during the PUF test accounted for 84% (p < 0.001) of the 50F performance variance. This study shows the validity of the analysis of pull-up mechanics and 50L to predict short-distance swimming performance in trained swimmers, confirming the importance of upper-limb strength and leg kick on this sport.

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

Specific association of IL17A genetic variants with panuveitis.

BACKGROUND/AIMS: A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to non-anterior uveitis and its main clinical subgroups. METHODS: Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls. RESULTS: The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis. CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology. SUBTITLE: Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.

Estimation of antioxidants dietary intake in wet age-related macular degeneration patients.

AIMS: The aim of this study was to estimate the intake of antioxidant nutrients in wet age-related macular degeneration (AMD) patients, a degenerative and progressive disorder of the macula, which is the central part of the retina, associated with central vision loss. METHODS: A sample (n = 52, 78.9 ± 6.6 years old, 40.4% females and 59.6% males) of patients diagnosed of AMD was interviewed. Anthropometric measurements, two 24- h recalls, a semi-quantitative food frequency questionnaire and a general questionnaire incorporating questions related to socio-demographic and lifestyle variables were used. RESULTS: Most of wet AMD patients showed inadequate antioxidant nutrient intake (< 2/3 of Recommended Dietary Intake, RDI), and more than 60% of patients showed serious deficient intake (< 1/3 RDI) of lutein and zeaxanthin. Most consumed antioxidant rich foods only represented low contributions to antioxidant intake. Although adiposity is a factor risk for AMD progression; the fat and saturated fatty acids (SFA) intake of study participants were higher than the recommendations; the prevalence of overweight was 61.9% men and 58.1% in women; and 83% of patients (90.5% men and 77.4% women) showed fat mass over the cut-off limits. CONCLUSIONS: The food pattern of wet AMD patients should be improved by means of an increase in the consumption of antioxidant rich foods, and a decrease in SFA rich foods.L.

Objetivos: El objetivo de este estudio fue estimar la ingesta de nutrientes antioxidantes en pacientes con degeneración macular asociada a la edad (AMD) variedad húmeda, un trastorno degenerativo y progresivo de la mácula, la parte central de la retina, asociada con la pérdida de la visión central. Métodos: En una muestra de pacientes diagnosticados de AMD (n = 52, 78,9 ± 6,6 años, 40,4% mujeres y 59,6% hombres) se registraron medidas antropométricas, dos recordatorios de 24 h, un cuestionario semicuantitativo de frecuencia de consumo de alimentos y cuestiones sociodemográficas y de estilo de vida. Resultados: La mayoría de los pacientes con AMD húmeda mostraron una ingesta inadecuada de nutrientes antioxidantes (< 2/3 de las Ingestas Dietéticas Recomendadas, RDI) y más de 60% de los pacientes mostraron un déficit grave (< 1/3 RDI) de luteína y zeaxantina. Los alimentos ricos en antioxidantes más consumidos sólo aportaron bajas contribuciones a la ingesta de antioxidantes. Aunque la adiposidad es un factor de riesgo para la progresión de la AMD, el consumo de grasas y ácidos grasos saturados (SFA) de los pacientes fueron superiores a las recomendaciones; la prevalencia de sobrepeso fue del 61,9% hombres y 58.1% en las mujeres; y el 83% de los pacientes (90,5% hombres y 77,4% mujeres) mostró una masa grasa superior a los límites. Conclusiones: El patrón alimentario de los pacientes con AMD debería mejorarse aumentando el consumo de alimentos ricos en antioxidantes y disminuyendo los alimentos ricos en SFA.

Estimation of antioxidants dietary intake in wet age-related macular degeneration patients / Estimación de la ingesta de antioxidantes en pacientes con degeneración macular asociada con la edad; variedad húmeda

Aims: The aim of this study was to estimate the intake of antioxidant nutrients in wet age-related macular degeneration (AMD) patients, a degenerative and progressive disorder of the macula, which is the central part of the retina, associated with central vision loss. Methods: A sample (n = 52, 78.9 ± 6.6 years old, 40.4% females and 59.6% males) of patients diagnosed of AMD was interviewed. Anthropometric measurements, two 24- h recalls, a semi-quantitative food frequency questionnaire and a general questionnaire incorporating questions related to socio-demographic and lifestyle variables were used. Results: Most of wet AMD patients showed inadequate antioxidant nutrient intake (< 2/3 of Recommended Dietary Intake, RDI), and more than 60% of patients showed serious deficient intake (< 1/3 RDI) of lutein and zeaxanthin. Most consumed antioxidant rich foods only represented low contributions to antioxidant intake. Although adiposity is a factor risk for AMD progression; the fat and saturated fatty acids (SFA) intake of study participants were higher than the recommendations; the prevalence of overweight was 61.9% men and 58.1% in women; and 83% of patients (90.5% men and 77.4% women) showed fat mass over the cut-off limits. Conclusions: The food pattern of wet AMD patients should be improved by means of an increase in the consumption of antioxidant rich foods, and a decrease in SFA rich foods (AU)

Objetivos: El objetivo de este estudio fue estimar la ingesta de nutrientes antioxidantes en pacientes con degeneración macular asociada a la edad (AMD) variedad hú- meda, un trastorno degenerativo y progresivo de la mácula, la parte central de la retina, asociada con la pérdida de la visión central. Métodos: En una muestra de pacientes diagnosticados de AMD (n = 52, 78,9 ± 6,6 años, 40,4% mujeres y 59,6% hombres) se registraron medidas antropométricas, dos recordatorios de 24 h, un cuestionario semicuantitativo de frecuencia de consumo de alimentos y cuestiones sociodemográficas y de estilo de vida. Resultados: La mayoría de los pacientes con AMD húmeda mostraron una ingesta inadecuada de nutrientes antioxidantes (< 2/3 de las Ingestas Dietéticas Recomendadas, RDI) y más de 60% de los pacientes mostraron un déficit grave (< 1/3 RDI) de luteína y zeaxantina. Los alimentos ricos en antioxidantes más consumidos sólo aportaron bajas contribuciones a la ingesta de antioxidantes. Aunque la adiposidad es un factor de riesgo para la progresión de la AMD, el consumo de grasas y ácidos grasos saturados (SFA) de los pacientes fueron superiores a las recomendaciones; la prevalencia de sobrepeso fue del 61,9% hombres y 58.1% en las mujeres; y el 83% de los pacientes (90,5% hombres y 77,4% mujeres) mostró una masa grasa superior a los límites. Conclusiones: El patrón alimentario de los pacientes con AMD debería mejorarse aumentando el consumo de alimentos ricos en antioxidantes y disminuyendo los alimentos ricos en SFA (AU)

Flexible single-incision surgery: a fusion technique.

INTRODUCTION: The development of natural orifice transluminal endoscopic surgery has led to other techniques, such as single-incision surgery. The use of the flexible endoscope for single-incision surgery paves the way for further refinement of both surgical methods. OBJECTIVE: To describe a new, single-incision surgical technique, namely, flexible single-incision surgery. PATIENTS AND METHODS: Assessment of the safety and effectiveness of endoscopic cholecystectomy in a series of 30 patients. This technique consists of a single umbilical incision through which a flexible endoscope is introduced and consists of 2 parallel entry ports that provide access to nonarticulated laparoscopic instruments. RESULTS: The technique was applied in all patients for whom it was prescribed. No general or surgical wound complications were noted. Surgical time was no longer than usual for single-port surgery. CONCLUSIONS: Flexible single-incision surgery is a new single-site surgical technique offering the same level of patient safety, with additional advantages for the surgeon at minimal cost.

Integración del endoscopio flexible en cirugía digestiva / Incorporation of the flexible endoscope in gastrointestinal surgery

El endoscopio flexible no ha figurado tradicionalmente entre el conjunto de dispositivos manejados por el cirujano digestivo. La endoscopia flexible intraoperatoria puede ser una de las técnicas que en un futuro no lejano estén disponibles en el quirófano de manera habitual. Al analizar el desarrollo de la cirugía mínimamente invasiva y de la endoscopia flexible, nos damos cuenta de cómo estamos convergiendo y de cómo podemos ir cediendo terreno a la endoscopia digestiva por un lado y ganándolo, con el endoscopio flexible, por otro. El desarrollo de las técnicas «híbridas» NOTES nos ha enseñado a mirar como potencialmente útiles en el quirófano equipos que no son habituales en nuestro entorno. La endoscopia flexible es probablemente la técnica que ofrece mayor rentabilidad al incorporarse al área quirúrgica. Es necesaria la colaboración estrecha con los digestólogos endoscopistas, a la vez que vamos formando a los cirujanos en este tipo de técnicas para un futuro de especialistas «híbridos» (AU)

The flexible endoscope has not traditionally figured among the tools used by the surgeon. Intra-operative flexible endoscopy may be one of the techniques available in the operating room in the near future. On analysing the development of minimally invasive surgery and flexible endoscopy, it can be seen that they are converging and losing ground to gastrointestinal endoscopy on the one hand, and gaining it with the flexible endoscope, on the other. The technical development of «hybrid» NOTES has shown how some tools not usually available in theatre may bevery useful. Flexible endoscopy is probably the technique to enter into the surgical area that offers improved performance. Surgeons need to work closely with the gastroenterologists, while they are trained in these techniques for future «hybrid» specialists (AU)

Prospective randomized clinical trial comparing laparoscopic cholecystectomy and hybrid natural orifice transluminal endoscopic surgery (NOTES) (NCT00835250).

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is a technique still in experimental development whose safety and effectiveness call for assessment through clinical trials. In this paper we present a three-arm, noninferiority, prospective randomized clinical trial of 1 year duration comparing the vaginal and transumbilical approaches for transluminal endoscopic surgery with the conventional laparoscopic approach for elective cholecystectomy. PATIENTS AND METHODS: Sixty female patients between the ages of 18 and 65 years who were eligible for elective cholecystectomy were randomized in a ratio of 1:1:1 to receive hybrid transvaginal NOTES (TV group), hybrid transumbilical NOTES (TU group) or conventional laparoscopy (CL group). The main study variable was parietal complications (wound infection, bleeding, and eventration). The analysis was by intention to treat, and losses were not replaced. RESULTS: Cholecystectomy was successfully performed on 94% of the patients. One patient in the TU group was reconverted to CL owing to difficulty in maneuvering the endoscope. After a minimum follow-up period of 1 year, no differences were noted in the rate of parietal complications. Postoperative pain, length of hospital stay, and time off from work were similar in the three groups. No patient developed dyspareunia. Surgical time was longer among cases in which a flexible endoscope was used (CL, 47.04 min; TV, 64.85 min; TU, 59.80 min). CONCLUSIONS: NOTES approaches using the flexible endoscope are not inferior in safety or effectiveness to conventional laparoscopy. The transumbilical approach with flexible endoscope is as effective and safe as the transvaginal approach and is a promising, single-incision approach.

Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients.

OBJECTIVE: To evaluate adalimumab therapy in refractory uveitis. DESIGN: Prospective case series. PARTICIPANTS: A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated. INTERVENTION: Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). MAIN OUTCOME MEASURES: Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (optical coherence tomography). RESULTS: There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçet's disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) µ at baseline versus 240 (36) µ at the 6-month visit (P < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] vs 5.40 [4.43]; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses during the 6 months of follow-up. CONCLUSIONS: Adalimumab seems to be well tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Further controlled studies of adalimumab for uveitis are warranted.

[Incorporation of the flexible endoscope in gastrointestinal surgery]. / Integración del endoscopio flexible en cirugía digestiva.

The flexible endoscope has not traditionally figured among the tools used by the surgeon. Intra-operative flexible endoscopy may be one of the techniques available in the operating room in the near future. On analysing the development of minimally invasive surgery and flexible endoscopy, it can be seen that they are converging and losing ground to gastrointestinal endoscopy on the one hand, and gaining it with the flexible endoscope, on the other. The technical development of «hybrid¼ NOTES has shown how some tools not usually available in theatre may be very useful. Flexible endoscopy is probably the technique to enter into the surgical area that offers improved performance. Surgeons need to work closely with the gastroenterologists, while they are trained in these techniques for future «hybrid¼ specialists.

Patients with neovascular age-related macular degeneration in Spain display a high cardiovascular risk.

PURPOSE: Cardiovascular disease and its risk factors may have a significant role in the development of neovascular age-related macular degeneration (NV-AMD). This study aims to assess the impact of these factors in this population and define their level of cardiovascular risk according to the Framingham model. METHODS: This was a cross-sectional, observational, multicenter study that included patients aged 50 years or older who attended ophthalmic centers for the diagnosis or follow-up of NV-AMD. Information collected included demographic and AMD data, a complete history of cardiovascular disease and its risk factors, lipid profile, blood pressure, and treatment history. RESULTS: The study population consisted of 901 patients, predominantly Caucasian, with a mean age of 75.7 years, receiving anti-vascular endothelial growth factor therapy for their NV-AMD in 77.7% of the cases. Blood pressure measurement during the study visit and lipid analyses revealed poor control in 67.7% and 93.3% of the patients, respectively. Hypertension was the most prevalent cardiovascular risk factor (77.7%), followed by a history of cardiac disease or other forms of atherosclerotic disease (53.8%). Diabetes was present in 28% of the subjects. The study population was considered a high-risk population according to the National Cholesterol Education Program Expert Panel Clinical Guidelines (NCEP ATP III), with a probability of a cardiovascular event in 10 years of 19.3% according to the Framingham model. CONCLUSIONS: This NV-AMD population is associated with a significant cardiovascular risk, and the Framingham model can help us identify those subjects with higher risk levels in order to improve their overall management.

Two novel disease-causing mutations in the CLRN1 gene in patients with Usher syndrome type 3.

PURPOSE: To identify the genetic defect in Spanish families with Usher syndrome (USH) and probable involvement of the CLRN1 gene. METHODS: DNA samples of the affected members of our cohort of USH families were tested using an USH genotyping array, and/or genotyped with polymorphic markers specific for the USH3A locus. Based on these previous analyses and clinical findings, CLRN1 was directly sequenced in 17 patients susceptible to carrying mutations in this gene. RESULTS: Microarray analysis revealed the previously reported mutation p.Y63X in two unrelated patients, one of them homozygous for the mutation. After CLRN1 sequencing, we found two novel mutations, p.R207X and p.I168N. Both novel mutations segregated with the phenotype. CONCLUSIONS: To date, 18 mutations in CLRN1 have been reported. In this work, we report two novel mutations and a third one previously identified in the Spanish USH sample. The prevalence of CLRN1 among our patients with USH is low.