Reference equations using segmented regressions for impulse oscillometry in healthy subjects aged 2.7-90 years.

Background: Published reference equations for impulse oscillometry (IOS) usually encompass a specific age group but not the entire lifespan. This may lead to discordant predicted values when two or more non-coincident equations can be applied to the same person, or when a person moves from one equation to the next non-convergent equation as he or she gets older. Thus, our aim was to provide a single reference equation for each IOS variable that could be applied from infancy to old age. Methods: This was an ambispective cross-sectional study in healthy nonsmokers, most of whom lived in Mexico City, who underwent IOS according to international standards. A multivariate piecewise linear regression, also known as segmented regression, was used to obtain reference equations for each IOS variable. Results: In a population of 830 subjects (54.0% female) aged 2.7 to 90 years (54.8% children ≤12 years), segmented regression estimated two breakpoints for age in almost all IOS variables, except for R5-R20 in which only one breakpoint was detected. With this approach, multivariate regressions including sex, age, height and body mass index as independent variables were constructed, and coefficients for calculating predicted value, lower and upper limits of normal, percentage of predicted and z-score were obtained. Conclusions: Our study provides IOS reference equations that include the major determinants of lung function, i.e. sex, age, height and body mass index, that can be easily implemented for subjects of almost any age.

Córnea plana congénita y error innato del metabolismo en un niño

Introducción: La córnea plana congénita es una rara anomalía de herencia autosómica dominante o recesiva. Los defectos del ciclo de la urea son errores innatos del metabolismo que puede producir encefalopatía progresiva. Objetivo: Describir las características clínicas de un paciente con diagnósticos de córnea plana congénita y error innato del metabolismo. Presentación del caso: Paciente masculino de 7 años de edad, miembro de la cuarta generación de una familia con diagnóstico de córnea plana congénita. Al examen oftalmológico se observó en ambos ojos esclerización superior del limbo, aplanamiento corneal generalizado y cámaras anteriores estrechas. La topografía corneal mostró patrones esféricos y aplanamiento corneal más prominente en la media y extrema periferia. A la edad de 5 años comenzó a presentar ataxia recurrente, crisis epilépticas de inicio focal motoras clónicas en el hemicuerpo derecho y vómitos. Ingresó en estado de coma en la unidad de cuidados intensivos pediátricos del Hospital Pediátrico Universitario "William Soler". Se planteó encefalopatía progresiva por trastorno en el ciclo de la urea luego de constatarse hiperamonemia (error congénito del metabolismo), sin acidosis metabólica. Conclusiones: La córnea plana congénita es una enfermedad caracterizada por aplanamiento corneal generalizado con repercusión en la calidad visual. Los errores innatos del metabolismo debidos a trastornos en el ciclo de la urea se caracterizan por manifestaciones neurológicas graves con peligro potencial para la vida. Resulta novedosa la presentación de estas dos enfermedades infrecuentes en un mismo paciente, asociación que no aparece publicada con anterioridad.

Introduction: Congenital flat cornea is a rare anomaly of dominant or recessive autosomal inheritance. Urea cycle defects are inborn errors of metabolism that can lead to progressive encephalopathy. Objective: To describe the clinical characteristics of a patient with diagnoses of congenital flat cornea and inborn error of metabolism. Case Presentation: A 7-year-old male patient, member of the fourth generation of a family diagnosed with congenital flat cornea. Ophthalmological examination showed upper limbal sclerization, generalized corneal flattening and narrow anterior chambers in both eyes. Corneal topography showed more prominent spherical patterns and corneal flattening in the middle and extreme periphery. At the age of 5 years, he began to present recurrent ataxia, focal onset epileptic seizures of clonic motor in the right hemibody and vomiting. He was admitted in a coma in the pediatric intensive care unit of "William Soler" University Pediatric Hospital. Progressive encephalopathy was stated due to disorder in the urea cycle after hyperammonemia (congenital error of metabolism) was observed, without metabolic acidosis. Conclusions: Congenital flat cornea is a disease characterized by generalized corneal flattening with an impact on visual quality. Inborn errors of metabolism due to disorders in the urea cycle are characterized by severe neurological manifestations with potential danger to life. The presentation of these two rare diseases in the same patient is novel; an association that has not been published previously.

Renal TLR-7/TNF-α pathway as a potential female-specific mechanism in the pathogenesis of autoimmune-induced hypertension.

Hypertension is prevalent in patients with systemic lupus erythematosus (SLE). The goal of the current study is to track the pathogenesis of hypertension and renal injury in SLE, identify contributory mechanisms, and highlight differences in disease development among sexes. Mean arterial pressure was measured in conscious male and female SLE (NZBWF1) and control (NZW) mice at 34-35 wk of age using indwelling arterial catheters. Measures of renal injury, renal inflammation, and renal hemodynamics were used to monitor the potential contributors to latent sex differences. Both male and female SLE mice were hypertensive at 35 wk of age, and the hypertension was linked to renal injury in females, but not in males. A known contributor of renal pathology in SLE, Toll-like receptor (TLR)-7, and its downstream effector, the proinflammatory cytokine tumor necrosis factor (TNF)-α, were lower in male SLE mice than in females. Male SLE mice also had higher glomerular filtration rate (GFR) and lower renal vascular resistance (RVR) than females. Our data suggest that although hypertension in female SLE mice is associated with renal mechanisms, hypertension in male SLE mice may develop independent of renal changes. Future studies will continue to dissect sex-specific factors that should be considered when treating patients with hypertension with underlying chronic inflammation and/or autoimmunity.NEW & NOTEWORTHY There is a high prevalence of hypertension in male and female SLE; however, male SLE mice are hypertensive without renal involvement. The development of hypertension in female SLE mice is renocentric and strongly associated with injurious renal mechanisms like the TLR-7→TNF-α pathway. This clear difference in the pathogenesis among the sexes could have a significant impact on how we treat patients with hypertension with underlying chronic autoimmune/inflammatory diseases.

Study protocol for monitoring SARS-CoV-2 infection and its determinants in Catalonia (Spain): an observational and participatory research approach in a Sentinel Network of Schools.

INTRODUCTION: Since the SARS-CoV-2 became of concern in January 2020, many preventive measures have been adopted in educational settings to ensure the control of COVID-19 pandemic among children and staff in schools. This study aims to set up a school sentinel surveillance network with the purpose of monitoring SARS-CoV-2 infection, seroprevalence as well as to analyse the impact of preventive interventions of SARS-CoV-2 in school settings. Additionally, we will assess diverse screening strategies in a cohort of students and school staff to monitor the screening acceptance and its potential impact. Altogether, we hope this study will enable the design of more effective strategies for the prevention of COVID-19 spread. METHODS AND ANALYSIS: The sentinel schools' study is a cross-sectional, school-based project including 26 participating sentinel schools in Catalonia (Spain). Children, adolescents and staff at the schools will be invited to participate. This project will be carried out from January 2021 to June 2022 as follows: (1) twice yearly serological testing and molecular SARS-CoV-2 detection and questionnaires covering SARS-CoV-2 symptoms, tests, health, knowledge, attitudes and behaviours; (2) an environmental evaluation carried out in different classrooms; (3) SARS-CoV-2 transmission dynamics and the impact of different variants among confirmed cases and classmates; (4) a participatory process by which the participants are invited to act as coinvestigators to evaluate prevention strategies and provide recommendations to improve COVID-19 prevention in schools. Descriptive analysis will be performed for the main variables collected. The incidence and seroprevalence will be calculated and the association with sociodemographic factors and school characteristics will be determined using multivariate logistic regression. ETHICS AND DISSEMINATION: Ethical approval was obtained from the IDIAPJGol and the Hospital Universitari Vall d'Hebron ethics committees. A report will be generated quarterly. Findings will be disseminated at national and international conferences and published in peer-reviewed journals.

Chitosan coatings with distinct innate immune bioactivities differentially stimulate angiogenesis, osteogenesis and chondrogenesis in poly-caprolactone scaffolds with controlled interconnecting pore size.

This study tested whether osseous integration into poly (ε-caprolactone) (PCL) bioplastic scaffolds with fully-interconnecting 155 ± 8 µm pores is enhanced by an adhesive, non-inflammatory 99% degree of deacetylation (DDA) chitosan coating (99-PCL), or further incorporation of pro-inflammatory 83% DDA chitosan microparticles (83-99-PCL) to accelerate angiogenesis. New Zealand White rabbit osteochondral knee defects were press-fit with PCL, 99-PCL, 83-99-PCL, or allowed to bleed (drill-only). Between day 1 and 6 weeks of repair, drill-only defects repaired by endochondral ossification, with an 8-fold higher bone volume fraction (BVF) versus initial defects, compared to a 2-fold (99-PCL), 1.1-fold (PCL), or 0.4-fold (83-99-PCL) change in BVF. Hematoma innate immune cells swarmed to 83-99-PCL, elicited angiogenesis throughout the pores and induced slight bone resorption. PCL and 99-PCL pores were variably filled with cartilage or avascular mesenchyme near the bone plate, or angiogenic mesenchyme into which repairing trabecular bone infiltrated up to 1 mm deep. More repair cartilage covered the 99-PCL scaffold (65%) than PCL (18%) or 83-99-PCL (0%) (p < 0.005). We report the novel finding that non-inflammatory chitosan coatings promoted cartilage infiltration into and over a bioplastic scaffold, and were compatible with trabecular bone integration. This study also revealed that in vitro osteogenesis assays have limited ability to predict osseous integration into porous scaffolds, because (1) in vivo, woven bone integrates from the leading edge of regenerating trabecular bone and not from mesenchymal cells adhering to scaffold surfaces, and (2) bioactive coatings that attract inflammatory cells induce bone resorption.

Increasing URiM Family Medicine Residents at University of Utah Health.

INTRODUCTION: The Department of Family and Preventive Medicine is home for the University of Utah's Family Medicine Residency program. Although Utah's diversity is steadily increasing, the race/ethnic diversity of the program's family medicine residency does not reflect the state's general population. METHODS: From 2017 to 2021, the residency instituted several adjustments to recruitment processes, including modification of an existing screening system to better highlight resiliency in overcoming challenging life experiences; promotion of commitment to diversity during interview days; incorporation of increased participation from diverse faculty and residents on interview days; and addition of outreach from the Office of Health, Equity, Diversity, and Inclusion. Underrepresented in medicine (URiM) applicants were the first to be offered interviews in an identical screening score cohort, and were ranked highest in rank lists in cohorts with identical final rank scores. RESULTS: Over the past five match cycles, Latinx residents have increased from zero to six, and underrepresented Asian residents from zero to two. In the 2021 match cycle, five of 10 incoming residents (50%) are URiM. Overall, URiM residents are now 30%, and residents of color 36%, of a total of 30 residents across all 3 training years. We found that eight URiM interviews were needed for every one URiM match. CONCLUSION: Intentional resident recruitment initiatives can transform racial/ethnic diversity in a family medicine residency program in a short amount of time.

Systemic Administration of α7-Nicotinic Acetylcholine Receptor Ligands Does Not Improve Renal Injury or Behavior in Mice With Advanced Systemic Lupus Erythematosus.

There is a critical need for safe treatment options to control inflammation in patients with systemic lupus erythematosus (SLE) since the inflammation contributes to morbidity and mortality in advanced disease. Endogenous neuroimmune mechanisms like the cholinergic anti-inflammatory pathway can be targeted to modulate inflammation, but the ability to manipulate such pathways and reduce inflammation and end organ damage has not been fully explored in SLE. Positive allosteric modulators (PAM) are pharmacological agents that inhibit desensitization of the nicotinic acetylcholine receptor (α7-nAChR), the main anti-inflammatory feature within the cholinergic anti-inflammatory pathway, and may augment α7-dependent cholinergic tone to generate therapeutic benefits in SLE. In the current study, we hypothesize that activating the cholinergic anti-inflammatory pathway at the level of the α7-nAChR with systemic administration of a partial agonist, GTS-21, and a PAM, PNU-120596, would reduce inflammation, eliminating the associated end organ damage in a mouse model of SLE with advanced disease. Further, we hypothesize that systemic α7 ligands will have central effects and improve behavioral deficits in SLE mice. Female control (NZW) and SLE mice (NZBWF1) were administered GTS-21 or PNU-120596 subcutaneously via minipumps for 2 weeks. We found that the increased plasma dsDNA autoantibodies, splenic and renal inflammation, renal injury and hypertension usually observed in SLE mice with advanced disease at 35 weeks of age were not altered by GTS-21 or PNU-120596. The anxiety-like behavior presented in SLE mice was also not improved by GTS-21 or PNU-120596. Although no significant beneficial effects of α7 ligands were observed in SLE mice at this advanced stage, we predict that targeting this receptor earlier in the pathogenesis of the disease may prove to be efficacious and should be addressed in future studies.

Tolerance and effectiveness of eccentric vs. concentric muscle strengthening in rotator cuff partial tears and moderate to severe shoulder pain. A randomized pilot study.

INTRODUCTION: Rotator cuff tears are the main cause of shoulder pain and disability. First line of treatment is conservative; there is evidence regarding the advantage of using eccentric over concentric exercises in tendinopathies, but there are no evidence-based recommendations on starting strengthening exercise during painful phases nor on the effectiveness and advantages of eccentric vs. concentric exercise in rotator cuff tears. OBJECTIVE: To evaluate the tolerance of a resistance strengthening program and to compare eccentric vs. concentric programs. DESIGN: A pilot, experimental, randomized controlled study. SETTING: Outpatient Rehabilitation Center. PATIENTS: Twenty-six patients with a diagnosis of partial rotator cuff tear were randomly assigned to: the experimental group (eccentric, n = 12) and the control (concentric, n = 14). INTERVENTION: The experimental group performed muscle strengthening with eccentric technique directed to shoulder and scapular girdle muscles, while the control group performed the concentric technique. MAIN OUTCOME MEASURES: Visual Analogue Scale (VAS), Constant Scale, Strength, Structure (Ultrasound report). RESULTS: The tolerance rate was 96% in both groups. Median age (experimental vs. control) was 54.5 vs. 54 years (p = 0.69). Results at baseline, and at months 1, 3, and 12 (median) were as follows: for VAS (mm), experimental: 55, 30, 30, and 10, p < 0.001 (intra-group); control: 50, 30, 30, and 5, p = 0.01; Constant scale (points): experimental 58.5, 88, 93, and 85, p < 0.001; control 50.62, 80, and 91.5, p = 0.038; normalized strength (Kg); experimental: 0.23, 0.29, 0.73, and 0.72, p = 0.001, and control: 0.24, 0.21, 0.54, and 0.66, p = 0.01. We found inter-group differences in the Constant scale at 1 and 3 months (p < 0.05), and in strength at months 1 and 3 (p < 0.05). We observed structural differences in tendon (healing) between groups at 3 and 12 months. CONCLUSIONS: Eccentric and concentric strengthening were well tolerated; both show early improvement in pain, functionality and tendon structure. Eccentric training appears to be more effective than concentric in the early improvement of functionality, strength and tendon healing.

Alteraciones anatomopatológicas en la escleritis anterior nodular necrotizante / Pathological alterations in necrotizing nodular anterior scleritis

RESUMEN La presencia de la escleritis necrotizante es rara; necesita de un diagnóstico y de un tratamiento oportuno, ya que su curso es rápido, severo y destructivo de la integridad del globo ocular. Se presenta una paciente de 43 años de edad, quien requirió atención oftalmológica al presentar el ojo derecho rojo con intenso dolor. Se le encontraron 3 nódulos en la región antero-inferior escleral. Se le realizó punción-aspiración con aguja fina en los nódulos esclerales y se obtuvo un fragmento de uno de ellos para el corte histológico. En ambas muestras se observó infiltrado inflamatorio de linfocitos y neutrófilos con algunas células plasmáticas. Se le impuso tratamiento con prednisona oral (0,5 mg/kg/día), prednisolona colirio y azatioprina a dosis de 1,5 mg/kg/día. La evolución al mes fue satisfactoria con mejoría gradual de las lesiones. El tratamiento se mantuvo por 3 meses con chequeos hematológicos reiterados. Se disminuyeron posteriormente las dosis medicamentosas hasta su eliminación a los 6 meses. La curación de las lesiones fue total. No se encontró enfermedad sistémica en el chequeo clínico efectuado(AU)

ABSTRACT The presence of necrotizing scleritis is rare; it needs a diagnosis and an opportune treatment, since its course is fast, severe and destructive of the integrity of the eyeball. We present a 43-year-old patient who required ophthalmological attention when presenting the red right eye with intense pain. Three nodules were found in the antero-inferior scleral region. Fine needle aspiration was performed on the scleral nodules and a fragment of one of them was obtained for the histological section. In both samples, inflammatory infiltrate of lymphocytes and neutrophils with some plasma cells was observed. He was prescribed treatment with oral prednisone (0.5 mg /kg/day), prednisolone eye drops and azathioprine at a dose of 1.5 mg/kg/day. The evolution to the month was satisfactory with gradual improvement of the lesions. The treatment was maintained for 3 months with repeated blood tests. Drug doses were subsequently reduced until their elimination at 6 months. The healing of the injuries was total. No systemic disease was found during the clinical check-up(AU)

Estandarización de la oscilometría de impulso y generación de ecuaciones piloto para generar valores de referencia en el Hospital Central Militar / Standardization of impulse oscillometry and the generation of pilot equations to generate reference values in the Central Military Hospital

Resumen Introducción La oscilometría de impulso es una prueba que evalúa la mecánica respiratoria a través de la aplicación de pequeños pulsos de presión que producen oscilaciones de flujo a una frecuencia determinada. Su aplicación relevante es en el estudio de las enfermedades de la vía aérea pequeña. El software integrado al equipo que ejecuta esta prueba genera cálculos de valores predictivos para cada uno de los parámetros oscilométricos, los cuales se basan en datos de población alemana. Objetivo Estandarizar la prueba de oscilometría de impulso y obtener ecuaciones piloto para valores de referencia. Material y métodos Se realizó un estudio experimental, analítico, prospectivo y longitudinal con sujetos voluntarios sanos. Se llevaron a cabo pruebas de espirometría y oscilometría de impulso basales y, tras broncodilatador, se registraron las impedancias, resistencias y reactancias del sistema respiratorio a 5, 10, 15 y 20 Hz. Los resultados se analizaron por sexo, edad, talla y peso. Se de 127 participantes sanos ingresaron al estudio, 51.5% del sexo efectuó un modelo de regresión lineal múltiple. Resultados Un total masculino (68) y 48.5% (64) del femenino, con edad promedio de 39.65 ± 15.26 años; la talla tuvo un promedio de 1.63 ± 0.09 m. Se demostró que el sexo influye en los valores de la oscilometría en el volumen corriente (VT), la impedancia, las resistencias y el área de reactancia (p < 0.05), y no afecta las reactancias (XRs) (p > 0.05); este parámetro está mayormente asociado a la talla (r = 0.727, r2 = 0.528). La edad incide en los valores de la oscilometría, ya que las resistencias (Rrs) son menores en los grupos más jóvenes; el IMC y el peso no comprometieron los valores de IOS. Conclusiones Este estudio proporciona ecuaciones piloto de referencia para los índices comunes de oscilometría de impulso en sujetos mexicanos. Así, integra una prueba de función pulmonar para facilitar la detección de alteraciones funcionales en vía aérea pequeña. Sugerimos realizar más trabajos en población mexicana, sobre todo de edad avanzada, para confirmar nuestros resultados y proporcionar una base más sólida a las ecuaciones de referencia para IOS, con un fin clínico y epidemiológico.

Abstract Introduction Impulse oscillometry is a test that evaluates the respiratory mechanics by the application of small pulses of pressure, which produce flow oscillations to a certain frequency. Its main application is in the study of the illnesses of the small airline. The integrated software of the test equipment generates predictive values for each of the oscillometric parameters, based on German population data. Objective To standardize the impulse oscillometry test in order to design pilot equations for reference values in our population. Material and methods We performed a pilot, experimental, analytical, longitudinal study with healthy volunteer subjects. Spirometry and impulse oscillometry tests were performed, both basal impedances, resistances, and reactances of the respiratory system to and after bronchodilator application; we measured and registered the 5, 10, 15, and 20 Hz. The results were analyzed by sex, age, height, and weight. The analysis was performed using a model of multiple linear retrogression. Results A total of 127 healthy participants were recruited, 51.5% men (68) and 48.5% (64) women, with an average age of 39.65 ± 15.26 years; their height was an average of 1.63 ± 0.09 m. It was proved that the gender influences the oscillometry values of tidal volume (VT), the impedance, the resistances and reactance area (p < 0.05), but not the reactances (XRs) (p > 0.05); this parameter is mainly associated with the size (r = 0.727, r2 = 0.528). The age influences the oscillometry values since the resistances (Rrs) are lower in the youngest groups; the BMI and the weight had no influence on the values of IOS. Conclusions This study provides pilot reference equations for the common indexes of impulse oscillometry in Mexican subjects, in order to integrate this test of pulmonary function to facilitate the detection of functional alterations in the small airline. We suggest more studies should be done on Mexican population, and especially on people of advanced age, to confirm our results and to provide a more solid base for the equations of reference to IOS, with clinical and epidemiologic purposes.

Caracterización morfológica de la dentición permanente de un grupo de afrodescendientes de Istmina (Chocó, Colombia) / Morphological characterization of permanent dentition of a group of Afrodescendants at Istmina (Chocó, Colombia)

Objetivo: Caracterizar la morfología de la dentición permanente de un grupo de afrodescendientes de Istmina (Chocó, Colombia) Materiales y métodos: Estudio descriptivo transversal cuantitativo que determinó la frecuencia y variabilidad de 35 rasgos morfológicos dentales coronales (RMDC) de incisivos, caninos, premolares y molares mediante la metodología de la Arizona State University Dental Anthropology System en 100 individuos autoreconocidos como afrodescendientes (50 femeninos y 50 masculinos), con edades comprendidas entre los 5 y los 18 años. Resultados: Se identificaron frecuencias significativas de winging (99%), forma de doble pala de los incisivos centrales (86%), convexidad labial (41%), cresta msial (35%), cresta distal (entre 39% y 45%) surco vestibular (entre 95% y 98%), la cresta central (82% y 80%), surco mesolingual (79%), surco distolingual (81%), reducción del hipocono (86%), cúspide de Carabelli (33%) y cúspide 7 (64%). No se encontró dimorfismo sexual y asimetría bilateral en los RMDC estudiados. Conclusiones: La frecuencia y variabilidad de los RMDC incluidos en el dendograma, demostraron que el grupo de Istmina presentó una morfología dental típica de las poblaciones afrodescendientes que se distribuyen en el litoral pacífico colombiano, las cuales derivaron de grupos de la costa occidental africana incluidos en el complejo dental de África Sahariana. De igual forma, fue posible detectar la influencia de poblaciones mestizas e indígenas que ocupan el mismo espacio geopolítico.

Aim: Characterize the permanent dentition morphology of a group of Afrodescendants of Istmina (Chocó, Colombia) Materials y methods: This quantitative cross-sectional study determined the frequency and variability of 35 incisor, canine, premolar and molar morphological features of the Arizona State University Dental Anthropology System in 100 self-described individuals as Afrodescendants (50 Female and 50 male), aged between 5 and 18 years. Results: Significant frequencies of winging (99%), double blade of the central incisors (86%), convexity of the lips (41%), crest of the shoulder (35%), and distal crest (39% to 45%) were identified (95% to 98%), central ridge (82% and 80%), mesolingual groove (79%), distolingual groove (81%), hippocampus reduction (86%), Carabelli cusp ) And cusp 7 (64%). No sexual dimorphism and bilateral asymmetry were found in the MCDS studied. Conclusions: The frequency and variability of the MCDD included in the dendrogram showed that the Isthmian group had a typical dental morphology of the Afrodescendant populations distributed on the Colombian Pacific coast, which were derived from groups of the West African coast included in The dental complex of Saharan Africa. Likewise, it was possible to detect the influence of mestizo and indigenous populations occupying the same geopolitical space.

Novel mutation of FKBP10 in a pediatric patient with osteogenesis imperfecta type XI identified by clinical exome sequencing.

Osteogenesis imperfecta (OI) is a hereditary disease characterized by bone fragility caused by mutations in the proteins that support the formation of the extracellular matrix in the bone. The diagnosis of OI begins with clinical suspicion, from phenotypic findings at birth, low-impact fractures during childhood or family history that may lead to it. However, the variability in the semiology of the disease does not allow establishing an early diagnosis in all cases, and unfortunately, specific clinical data provided by the literature only report 28 patients with OI type XI. This information is limited and heterogeneous, and therefore, detailed information on the natural history of this disease is not yet available. This paper reports the case of a male patient who, despite undergoing multidisciplinary management, did not have a diagnosis for a long period of time, and could only be given one with the use of whole-exome sequencing. The use of the next-generation sequencing in patients with ultrarare genetic diseases, including skeletal dysplasias, should be justified when clear clinical criteria and an improvement in the quality of life of the patients and their families are intended while reducing economic and time costs. Thus, this case report corresponds to the 29th patient affected with OI type XI, and the 18th mutation in FKBP10, causative of this pathology.

Cationic osteogenic peptide P15-CSP coatings promote 3-D osteogenesis in poly(epsilon-caprolactone) scaffolds of distinct pore size.

P15-CSP is a biomimetic cationic fusion peptide that stimulates osteogenesis and inhibits bacterial biofilm formation when coated on 2-D surfaces. This study tested the hypothesis that P15-CSP coatings enhance 3-D osteogenesis in a porous but otherwise hydrophobic poly-(ɛ-caprolactone) (PCL) scaffold. Scaffolds of 84 µm and 141 µm average pore size were coated or not with Layer-by-Layer polyelectrolytes followed by P15-CSP, seeded with adult primary human mesenchymal stem cells (MSCs), and cultured 10 days in proliferation medium, then 21 days in osteogenic medium. Atomic analyses showed that P15-CSP was successfully captured by LbL. After 2 days of culture, MSCs adhered and spread more on P15-CSP coated pores than PCL-only. At day 10, all constructs contained nonmineralized tissue. At day 31, all constructs became enveloped in a "skin" of tissue that, like 2-D cultures, underwent sporadic mineralization in areas of high cell density that extended into some 141 µm edge pores. By quantitative histomorphometry, 2.5-fold more tissue and biomineral accumulated in edge pores versus inner pores. P15-CSP specifically promoted tissue-scaffold integration, fourfold higher overall biomineralization, and more mineral deposits in the outer 84 µm and inner 141 µm pores than PCL-only (p < 0.05). 3-D Micro-CT revealed asymmetric mineral deposition consistent with histological calcium staining. This study provides proof-of-concept that P15-CSP coatings are osteoconductive in PCL pore surfaces with 3-D topography. Biomineralization deeper than 150 µm from the scaffold edge was optimally attained with the larger 141 µm peptide-coated pores. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2171-2181, 2017.

Resultados de la queratoplastia penetrante óptica en el Centro Oftalmológico de Ciego de Ávila / Results of the optical penetrating keratoplasty in the Ciego de Avila Ophthalmic Center

Introducción: la queratoplastia penetrante óptica es la sustitución de todo el espesor de la córnea por la procedente de un donante con la finalidad de devolver la transparencia corneal y mejorar la agudeza visual. El Centro Oftalmológico de Ciego de Ávila está adscrito al Programa Nacional de Donación de Órganos y Tejidos y en él se realizan cirugías de queratoplastias penetrantes desde el año 2011; hasta el presente se han operado 6 pacientes de trasplante corneal óptico. Objetivo: describir algunos aspectos generales relacionados con los pacientes sometidos a este proceder en el Servicio de Córnea del Centro Oftalmológico de Ciego de Ávila. Método: la muestra estuvo constituida por 6 pacientes, del sexo masculino 4 y dos del femenino, con edades comprendidas entre 43 y 76 años. Resultados y Discusión: las afecciones corneales por las cuales se indicó el proceder quirúrgico: queratopatía bullosa pseudofáquica, leucoma corneal, distrofia corneal gelatinosa en gota y rechazo al injerto; todos tenían una deteriorada agudeza visual mejor corregida preoperatoria en rangos de movimientos de la mano a 0.05 la cual mejoró tres meses después de operados entre 0.2 y 0.5, igualmente los componentes esféricos y cilíndricos de la refracción. Conclusiones: la queratoplastia penetrante óptica significó una excelente opción terapéutica en los pacientes investigados. En todos se constató una recuperación de los componentes esférico y cilíndrico en la refracción posoperatoria(AU)

Introduction: optical penetrating keratoplasty is the replacement of all corneal thickness from a donor with the purpose of returning the corneal transparency and improve visual acuity. The Ophthalmological Center of Ciego de Avila is attached to the National Program of Organ and Tissue Donation and penetrating keratoplasty surgery from 2011; 6 patients of optical corneal transplant have been operated up to the present. Objective: to describe some general aspects of patients undergoing this procedure in the corneal service of the Ophtalmological Center of Ciego de Avila. Method: the sample consisted of 6 patients, 4 male and two female, aged between 43 and 76 years. Results and Discussion: corneal conditions under which the surgical procedure is indicated: pseudophakic bullous keratopathy, corneal leukoma, corneal dystrophy gelatinous drop and graft rejection; all of them had impaired preoperative best corrected visual acuity in ranges of hand movements to 0.05 which improved three months after surgery between 0.2 and 0.5, also spherical and cylindrical components of refraction. Conclusions: optical penetrating keratoplasty meant an excellent treatment option for the investigated patients. It was found a recovery of spherical and cylindrical components in the postoperative refraction(AU)

Replication study of previous migraine genome-wide association study findings in a Spanish sample of migraine with aura.

BACKGROUND: Migraine is a common disabling condition that affects approximately 15% of the population. Several genome-wide association studies have attempted to identify susceptibility variants involved in migraine, reporting several candidate loci for the disorder. METHODS: In order to replicate findings from previous genome-wide association studies, a case-control association study was performed. Twelve single nucleotide polymorphisms were genotyped in a Spanish sample of 512 migraine with aura patients and 535 migraine-free controls. RESULTS: Nominal associations were found for single nucleotide polymorphisms rs2651899 (within the PRDM16 gene), rs10166942 (near TRPM8), rs12134493 (close to TSPAN2) and rs10504861 (near MMP16) in our migraine with aura sample. CONCLUSIONS: Our study provides suggestive replication, in a Spanish migraine with aura sample, of four genome-wide association study findings previously reported in common migraine. However, larger sample sets should be explored to confirm our results.

ACCIÓN COMBINADA DE FEROMONA SEXUAL Y DE AVISPAS Apanteles gelechiidivoris PARA EL CONTROL DE Tuta absoluta EN CULTIVOS DE TOMATE BAJO INVERNADERO / Combined Action of Sex Pheromone and Wasp Apanteles gelechiidivoris in Greenhouse Tomato Crops

El cogollero del tomate, Tuta absoluta, es considerado plaga principal del cultivo de tomate. Su control se realiza con químicos, aunque existen otros tipos de control como el biológico y etológico. En Colombia no existe ningún precedente que involucre la acción combinada de estrategias de control etológico incluyendo feromona sexual y biológico con Apanteles gelechiidivoris para el control de la plaga en cultivos de tomate. En este trabajo, se evaluaron cuatro tratamientos bajo condiciones de invernadero que incluyen control biológico con A. gelechiidivoris, etológico con trampas de feromona sexual, acción combinada de ambos controles y convencional (químico), con el objetivo de desarrollar una estrategia de control de T. absoluta a través de la acción combinada de control etológico con feromona sexual y biológico. Se realizó un muestreo sistemático, tomando una planta cada 2 m. En cada planta se tomó una hoja por estrato, semanalmente se registró el número de larvas totales, de tercer instar y parasitadas, y número de adultos capturados por trampa. El máximo parasitismo en la población de larvas susceptibles fue del 86,38 % y de la población de larvas totales 68,75 %. Se encontró que la acción combinada presenta una mayor efectividad y permanencia a través del tiempo para el control de larvas de T. absoluta.

The tomato budworm, Tuta absoluta, is considered main pest of tomato crops. Control of this pest is performed with hemicals, although, there are other strategies such as biological and ethological control. In Colombia there is not precedent that combines both strategies: ethological control with sexual pheromone and biological control with Apanteles gelechiidivoris, for the control of this pest in tomato crops. In this work four different treatments under greenhouse conditions were evaluated including biological control with A. gelechiidivoris, ethological control with sexual pheromone traps, combined action of both controls and traditional control (Chemicals). The experiments aimed to developing a control strategy to reduce populations of T. absoluta. This was done sampling a plant every to 2 meters. From each plant a sample composed by one leaf by stratum was taken and the variables number of total larvae of third instar and parasited and number of captured adults for trap. The maximum parasitism in the population of susceptible larvae was 86.38 % and for total population of larvae was 68.75 %. The combined action of pheromone traps and A. gelechiidivoris presented a greater efficiency and permanence on the control of larvae of T. absoluta.

The addition of a pregnenolone pendant group enhances the anticancer properties of titanocene dichloride in a mcf-7 xenograft model.

BACKGROUND/AIM: Titanocene dichloride held great promise as a chemotherapeutic compound in pre-clinical studies. However, subsequent clinical trials revealed hepatoxicity and nephrotoxicity, which limited its use in clinical applications. Therefore, we used steroid pendant groups to improve the targeting of titanocene in MCF-7 breast cancer cells, and demonstrated a 10-fold lower effective dose compared to titanocene in in vitro assays. The aim of the present study was to test the efficacy of a titanocene functionalized with pregnenolone (Ti-Preg) in an in vivo breast cancer model. MATERIALS AND METHODS: Xenografts from the MCF7 breast cancer cell line were implanted into athymic nu/nu mice to evaluate the potential of Ti-Preg as an anti-breast cancer agent. RESULTS: Ti-Preg demonstrated significant inhibition of MCF-7 tumor growth when compared to vehicle and to titanocene controls. CONCLUSION: Our findings demonstrate the potential of steroid pendent groups for targeting chemotherapeutics to steroid hormone-dependent cancer.

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis.

Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1ß, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3-dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor-null (Prlr(-/-)) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.

Genes involved in hemorrhagic transformations that follow recombinant t-PA treatment in stroke patients.

AIM: Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients. METHODS: We studied by microarrays 11 blood samples from patients with stroke that had received rt-PA of whom six of them had suffered a HT. For replication step RNA was collected from 14 new subjects (seven with HT, seven without) and then analyzed by real-time PCR. Four proteins were measured by ELISA in 72 new subjects to analyze their role as potential protein biomarkers. RESULTS: The microarray analysis revealed that 14 genes were altered among the HT patients. The replication study confirmed these results for six genes. Two of them (BCL2 and OLFM4) are associated with apoptosis, whereas the other four (LTF, LCN2 [also known as NGAL], CEACAM8 and CRISP3) are involved in the regulation of neutrophil processes. CONCLUSION: Our data revealed that genes related to apoptosis and neutrophil regulation pathways could be associated with HTs after rt-PA.

Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition.

BACKGROUND: In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. METHODS: Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with tissue factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received tissue factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. RESULTS: All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. CONCLUSIONS: Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair.