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INTRODUCTION: Pain catastrophizing is an exaggerated negative orientation to painful stimuli which in obstetric patients is associated with fear of overwhelming labor pain and negative pain-related outcomes. This study aimed to quantitatively examine the association of pain catastrophizing with maternal labor pain outcomes. METHODS: We conducted a prospective observational study of women admitted for a vaginal trial of labor. Subjects completed the 13-item Pain Catastrophizing scale (PCS) questionnaire (scored 0 to 52, higher scores representing greater catastrophizing). Pain was assessed at baseline and at request for neuraxial labor analgesia. Labor and postpartum pain intensity was assessed as the average area under the pain intensity by time curve. Pain at request for analgesia, labor pain, postpartum pain, analgesic consumption, and quality of recovery was compared between high (PCSâ¯≥â¯17) and low catastrophizing groups. RESULTS: Data from 138/157 (88%) subjects were included in the analysis. Median (IQR) pain scores at request for analgesia were 9 (8,10) and 8 (6,9), a difference of 1 (95% CI 0 to 2.5, Pâ¯=â¯0.008) in high-catastrophizing and in low-catastrophizing groups, respectively. Adjusted pain during labor, postpartum pain and opioid analgesic use were not significantly different. High-catastrophizers reported less comfort, ability to mobilize and less control during hospitalization. Post-discharge there were no differences in pain or analgesic use. CONCLUSION: We did not observe greater labor or post-delivery pain or increased analgesic use in high-catastrophizing parturients. High catastrophizers reported greater pain when requesting analgesia, which is consistent with the role of catastrophizing in intensifying the experience of pain.
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Analgesia Epidural , Analgesia Obstétrica , Dolor de Parto , Trabajo de Parto , Embarazo , Humanos , Femenino , Dolor de Parto/tratamiento farmacológico , Cuidados Posteriores , Alta del Paciente , Catastrofización , AnalgésicosRESUMEN
INTRODUCTION: Subspecialty training in obstetric anesthesiology is associated with improved patient outcomes and reduced anesthesia-related morbidity and mortality. Despite this, the demand for fellowship-trained obstetric anesthesiologists far exceeds the supply. This survey study aimed to evaluate the perceived value of obstetric anesthesiology subspecialty training on career trajectory, job satisfaction, quality of life, and job autonomy. METHODS: After Institutional Review Board approval, we conducted a cross-sectional study of fellowship-trained obstetric anesthesiologists in the United States of America. In March and April 2022, program directors of obstetric anesthesiology fellowships distributed an electronic survey link containing 29 multiple-choice questions to their program alumni. Survey content included respondent demographic characteristics, practice models, career information, and perceived value of an obstetric anesthesiology fellowship. RESULTS: We surveyed 217/502 (43%) fellowship-trained obstetric anesthesiologists with a response rate of 158/217 (73%). Most worked in urban, academic, and level IV perinatal health centers. The majority believed an obstetric anesthesiology fellowship was "extremely beneficial" (77%), enhanced quality of life (84%), improved the quality of patient care (99%), and was influential in helping obtain their first post-training job (86%). The perceived value of the fellowship included an enhanced career trajectory, a sense of purpose, improved job satisfaction, a sense of work community, lower burnout, involvement in maternal health initiatives, increased mentorship, and departmental leadership. CONCLUSION: In this survey study, fellowship-trained obstetric anesthesiologists perceived a positive impact of fellowship training on career trajectory, job protection and autonomy, quality of life, and job satisfaction. This information may be meaningful to trainees considering pursuing a fellowship and a career in obstetric anesthesiology.
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Anestesiología , Internado y Residencia , Femenino , Embarazo , Humanos , Estados Unidos , Anestesiología/educación , Anestesiólogos , Becas , Estudios Transversales , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: It has been proposed that regular emollient application in early life could enhance skin barrier function and prevent atopic dermatitis (AD) especially in predisposed infants. This hypothesis was supported by evidence from exploratory and pilot trials showing protective effects in terms of reduced cumulative atopic dermatitis incidence with the use of daily emollient therapy starting immediately after birth. OBJECTIVES: To investigate the effectiveness of a standardized skin care regimen for infants on the development of AD compared to not structured skin care regimen in infants with atopic predisposition. METHODS: Prospective, parallel group, randomized, pragmatic, investigator-blinded intervention trial including 160 infants with 52 weeks intervention and 52 weeks follow up phase up to the age of two years. Infants were randomly assigned to receive a standardized skin care regimen including once daily leave-on product application (lipid content 21%) or skin care as preferred by the parents. RESULTS: Using the intention to treat approach, the cumulative AD incidence was 10.6% after one year, and 19.5% after two years in the total sample. There were no statistical significant differences between intervention and control groups. Skin barrier parameters between the intervention and control groups were comparable. AD severity was higher and quality of life was more affected in the control group. CONCLUSIONS: Regular emollient application during the first year of life does not prevent the development of atopic dermatitis. A standardized skin care regimen does not delay skin barrier development or causes side effects.
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PURPOSE: To investigate retinal microstructure differences in central retinal artery occlusion (CRAO) patients with and without visible retinal diffusion restriction (RDR) on diffusion-weighted magnetic resonance imaging (DWI). METHODS: Consecutive CRAO patients with available optical coherence tomography (OCT) and DWI, both performed within 7 days after symptom onset, were included in a retrospective cohort study. The OCT scans were reviewed to assess retinal layer thickness, optical intensity and structural integrity. The OCT findings were compared between patients with and without visible RDR on DWI using Mann-Whitney U or Pearson's Χ2 test. RESULTS: A total of 56 patients (mean age 70.8 ± 12.8 years) were included. RDR was observed in 38 subjects (67.9%) with visually correlating low ADC map in 26 of 38 cases (68.4%). Superior and inferior parafoveal macular thickness measurements (SMT, IMT) of RDR negative patients were significantly lower when compared to RDR+ patients (370.5 ± 43.8⯵m vs. 418.2 ± 76.0⯵m, pâ¯=â¯0.016; 374.4 ± 42.9⯵m vs. 428.8 ± 63.2⯵m, pâ¯=â¯0.004) due to differences in inner retinal layer thickness (IRLT, 188.8 ± 34.4⯵m vs. 234.7 ± 49.0⯵m, pâ¯=â¯0.002). IRLT values of RDR negative patients were higher in 1.5T compared to 3T the DWI (205.0 ± 26.0⯵m vs. 168.6 ± 32.8⯵m, pâ¯=â¯0.026). CONCLUSIONS: Detectability of RDR is likely contingent upon the degree of ischemic retinal swelling in CRAO. Technical adjustments to the DWI protocol, such as increased field strength, may improve visibility of RDR.
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Papiledema , Oclusión de la Arteria Retiniana , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Retina/diagnóstico por imagen , Retina/patología , Oclusión de la Arteria Retiniana/diagnóstico por imagen , Oclusión de la Arteria Retiniana/patología , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. OBJECTIVES: This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. CONCLUSION: As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.
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Audiología/métodos , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/prevención & control , Otolaringología/métodos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Audiología/normas , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/cirugía , Trastornos de Deglución/virología , Europa (Continente)/epidemiología , Humanos , Exámenes Obligatorios/normas , Otolaringología/normas , Pediatría/normas , Equipo de Protección Personal/normas , Equipo de Protección Personal/provisión & distribución , Neumonía Viral/epidemiología , Neumonía Viral/virología , Guías de Práctica Clínica como Asunto , SARS-CoV-2 , Sociedades Médicas/organización & administración , Trastornos de la Voz/diagnóstico , Trastornos de la Voz/cirugía , Trastornos de la Voz/virologíaRESUMEN
OBJECTIVE: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36-40 years of age? DESIGN: Decision tree model. POPULATION: A randomised clinical trial on PGT-A (ESTEEM study). METHODS: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A. Costs and effects were analysed with this model for four different cost scenarios: high-, higher medium, lower medium and low-cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost-effectiveness implications of PGT-A. RESULTS: PGT-A increased the cost per live birth by approximately 15% in the high-cost scenario to approximately 285% in the low-cost scenario. Threshold analysis revealed that PGT-A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high-cost scenario) to US$4,888 (low-cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT-A using the base case assumptions was calculated to be US$34,427 (high-cost scenario) to US$51,146 (low-cost scenario). A probabilistic sensitivity analysis showed cost-effectiveness for PGT-A from 1.9% (high-cost scenario) to 0.0% (low-cost scenario) of calculated samples. CONCLUSIONS: While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high-cost implications of applying PGT-A using aCGH on polar bodies. TWEETABLE ABSTRACT: PGT-A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.
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Aborto Espontáneo/genética , Aneuploidia , Pruebas Genéticas/economía , Edad Materna , Diagnóstico Preimplantación/economía , Aborto Espontáneo/prevención & control , Adulto , Análisis Costo-Beneficio , Femenino , Humanos , Cuerpos Polares/trasplante , EmbarazoRESUMEN
BACKGROUND: Metabolic syndrome (MS) and sleep-disordered breathing (SDB) are highly prevalent in patients with diabetes mellitus type 2 (DM2). The present study examined whether there is an independent association between SDB and MS in a sample of outpatients with DM2. METHODS: MS was determined in 679 patients of the DIACORE-SDB substudy, a study of outpatients with DM2. According to the National Cholesterol Education Program (NCEP) criteria, MS is defined by at least three of the following five criteria: waist circumference of >102 cm (men)/>88 cm (women), blood pressure of ≥130/85 mmHg, a fasting triglyceride level of >150 mg/dl, high-density lipoprotein (HDL) of <40 mg/dl (men)/<50 mg/dl (women), and a fasting glucose level of ≥110 mg/dl. The apnea-hypopnea index (AHI) was assessed with a 2-channel ambulatory monitoring device and used to define the severity of SDB (AHI < 15.0: no/mild SDB; AHI 15.0-29.9: moderate SDB; AHI ≥ 30.0: severe SDB). RESULTS: 228 (34%) of the 679 participants (mean age 66 years, mean body mass index (BMI) 31.2 kg/m2, and mean AHI 14/hour) had SDB. MS was significantly more frequent in patients with more severe SDB (no/mild SDB vs. moderate SDB vs. severe SDB: 72% vs. 79% vs. 85%, respectively, p = 0.038). Logistic regression analysis adjusted for sex, age, obesity (BMI ≥ 30 kg/m2), and the HOMA index showed a significant association between the AHI and the presence of MS (OR (95%CI) = 1.039 (1.011; 1.068); p = 0.007). Further, male sex, obesity, and the HOMA index were significantly associated with MS. CONCLUSION: SDB is significantly and independently associated with MS in outpatients with DM2.
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Diabetes Mellitus Tipo 2/fisiopatología , Síndrome Metabólico/fisiopatología , Síndromes de la Apnea del Sueño/fisiopatología , Anciano , Apnea , Glucemia/análisis , Presión Sanguínea , Índice de Masa Corporal , Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hipoxia , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Obesidad/complicaciones , Pacientes Ambulatorios , Prevalencia , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Síndromes de la Apnea del Sueño/complicaciones , Triglicéridos/sangreRESUMEN
Persistent speech fluency disorders, mostly stuttering and less frequently cluttering, occur in approximately 1% of children and adolescents. They considerably impair the social participation and quality of life of those affected. The German interdisciplinary evidence-based S3 guidelines provide information about the pathogenesis, diagnostics and treatment of speech fluency disorders and contain a systematic review on the efficacy of stuttering treatment. For preschool children the Lidcombe therapy shows the best evidence of efficacy. Strong evidence also exists for an indirect approach. For adolescents and recently for children aged 612 years old there is a high level of evidence for speech restructuring methods, such as fluency shaping. There is weak evidence for stuttering modification procedures and for combined speech restructuring and stuttering modification approaches. Negative evidence exists for the eclectic, unspecified stuttering therapies, breathing regulation, and hypnosis, which are frequently applied in Germany. An early start of treatment is decisive.
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Trastornos del Habla , Habla , Tartamudeo , Adolescente , Anciano , Niño , Preescolar , Alemania , Humanos , Calidad de Vida , Trastornos del Habla/terapia , Logopedia , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Digitalization is significantly changing the entire healthcare sector. Hospitals must act now in order to remain competitive. OBJECTIVE: To assess which approaches exist for digitalization along the treatment chain and how digitalization can be strategically implemented. MATERIALS AND METHODS: An analysis of relevant examples from consulting work and success stories from the specialist press is presented, as is a discussion of expert recommendations. RESULTS: More than 90% of German hospitals are currently investing in digitalization. However, they often fail to understand that first and foremost, digitalization offers them the chance to successfully innovate their entire business model. Digital solutions can enhance quality of care, boost efficiency, and greatly improve attractiveness for the employees entrusted with these processes. CONCLUSION: German hospitals should be doing much more to exploit the many digital opportunities that exist. They can do so by deciding where to act first in the treatment chain, prioritizing the underlying actions, and making the necessary funds available. Other key success factors include forming strategic partnerships with startups and "medtech" companies, and introducing an agile corporate culture.
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Toma de Decisiones Asistida por Computador , Atención a la Salud , Eficiencia Organizacional , Hospitales , Comunicación , Atención a la Salud/métodos , Predicción , Humanos , Técnicas de PlanificaciónRESUMEN
BACKGROUND: To give an overview on implant survival rates in patients with oral manifestations of systemic autoimmune (oral Lichen planus (oLp), Pemphigus (Pe)), muco-cutaneous (Epidermolysis bullosa (EB)), autoimmune multisystemic rheumatic diseases (Sjögren's syndrome (SjS), systemic Lupus erythematosus (sLE), or systemic Sclerosis (sSc)). MATERIAL AND METHODS: Systematic literature review (PubMed/Medline, Embase) using MESH and search term combinations, published between 1980 and August 2018 in English language reporting on dental implant-prosthetic rehabilitation of patients with oLp, Pe, EB, SjS, sLE, sSc, study design, age, gender, follow-up period (≥ 12 months), implant survival rate. Implant-related weighed mean values of implant survival rate (wmSR) were calculated. RESULTS: After a mean follow-up period (mfp) of 44.6 months, a wmSR of 98.3 % was calculated from data published for patients with oLp (100 patients with 302 implants). Data of 27 patients (152 implants) with EB revealed wmSR of 98.7 % following mfp of 32.6 months. For 71 patients (272 implants) with SjS, wmSR was 94.2 % following a mfp of 45.2 months, and for 6 patients (44 implants) with sSc, wmSR was 97.7 % after mfp of 37.5 months. One case report on one patient each with Pe (two implants) as well as sLE (6 implants) showed 100 % SR following at least 24 months. CONCLUSIONS: Guidelines regarding implant treatment of patients with oLp, Pe, EB, SjS, sLE or sSc do not exist nor are contraindicating conditions defined. Implant survival rates of patients affected are comparable to those of healthy patients. For implant-prosthetic rehabilitation of patients with Pe and sLE no conclusions can be drawn due to lack of sufficient clinical data. Implant-prosthetic treatment guidelines regarding healthy patients should be strictly followed, but frequent recall is recommended in patients affected with oLp, SjS, EB, SSc, Pe or sLE.
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Implantes Dentales , Epidermólisis Ampollosa/complicaciones , Liquen Plano Oral/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Pénfigo/complicaciones , Esclerodermia Sistémica/complicaciones , Síndrome de Sjögren/complicaciones , Bases de Datos Factuales , Prótesis Dental de Soporte Implantado , Fracaso de la Restauración Dental , Humanos , Enfermedades de la Boca , Resultado del TratamientoRESUMEN
The taxonomy of the genus Cricetulus has been controversial. The phylogenetic relationships both within the genus and among Cricetulus lineages and other genera were examined using a set of five nuclear and two mitochondrial genes. The results demonstrate that Cricetulus in its current treatment is a polyphyletic assemblage because the subgenus Urocricetus is phylogenetically unrelated to all other Cricetulus and is a distant sister group to Phodopus. The grey hamster (C. migratorius) proved to be closer to Cricetus and Allocricetulus than to Cricetulus proper, which includes C. barabensis C. sokolovi and C. longicaudatus. Based on these results Urocricetus is elevated to the rank of a full genus and a new genus Nothocricetulus gen.nov. is described for the grey hamster.
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Cricetulus , Animales , Arvicolinae , Cricetinae , Filogenia , RoedoresRESUMEN
OBJECTIVES: The aim of the study was to investigate the effects of various self-adhesive resin cements on the push-out bond strengths and nanoleakage expression at the luting interfaces of fiber posts immediately and after one year of aging. METHODS AND MATERIALS: One hundred forty-four extracted human anterior teeth were endodontically treated. After post space preparation, fiber posts were luted using five commercially available self-adhesive resin (SAR) cements and a core build-up material applied with a self-etch adhesive (BF: Bifix SE/Rebilda Post, VOCO; CSA: Clearfil SA Cement/Rely X Fiber Post, 3M ESPE; RX: RelyX Unicem 2/Rely X Fiber Post, 3M ESPE; SPC: Speed Cem/FRC Postec, Ivoclar Vivadent; SMC: Smart Cem/X Post, Dentsply; RB: Rebilda DC-Futurabond/Rebilda Post; n=22). For each group, half of the specimens were subjected to thermocycling (TC) (5°C-55°C, 10,000 cycles) and stored humid for one year at 37°C. Push-out bond strength data of six slices (thickness 1 mm) per root and nanoleakage expression of representative specimens were evaluated after 24 hours (baseline) and after TC and storage for one year (aging), respectively. RESULTS: Bond strength differed significantly among resin cements (p<0.0005) and the location inside the root canal (p<0.0005), but not by aging (p=0.390; repeated-measures analysis of variance). SMC (14.6±5.8 MPa) and RX (14.1±6.8 MPa) revealed significantly higher bond strength compared to BF (10.6±5.4 MPa) and RB (10.0±4.6 MPa) but differed not significantly from SPC (12.8±4.8) MPa; CSA (6.1±4.6 MPa) revealed significantly lower bond strength compared to all other investigated materials (p<0.05; Tukey Honestly Significantly Different). Qualitative nanoleakage analysis revealed more silver deposits at the interface in all groups after aging. For CSA, a large amount of silver deposits inside the cement was also observed at baseline and after aging. CONCLUSIONS: Fiber post luting using SAR cements demonstrated reliable bond strengths. Product-specific differences and initial degradation effects could be demonstrated.
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Técnica de Perno Muñón , Cementos de Resina/uso terapéutico , Tratamiento del Conducto Radicular/métodos , Auto-Curación de Resinas Dentales/métodos , Análisis del Estrés Dental , HumanosRESUMEN
INTRODUCTION: To test for colposcopic differences between CIN2+ and non CIN2+ lesions of the "major changes" of the RIO 2011 nomenclature of the International Federation of Cervical Pathology (IFCPC). MATERIAL AND METHODS: Retrospective cohort analysis of colposcopic examinations of patients with histologically confirmed CIN2+ (n=99) and non CIN2+ (n=102) lesions during a four years period. MAIN OUTCOME MEASURES: leukoplakia, coarse mosaic and punctuation, dense acetowhitening, sharp boarders, ridge sign, atypical vessels. RESULTS: Only coarse punctuation (P≤0.001; OR 9.64; 95% CI 2.15-43.13), coarse mosaic (P≤0.001; OR 4.00; 95% CI 1.83-8.73) and dense acetowhitening (P≤0.05; OR 1.86; 95% CI 1.06-3.26) occurred more frequently in CIN2+ lesions which were confirmed as predictors by a regression analysis. CONCLUSIONS: Only coarse punctuation and coarse mosaic followed by dense acetowhitening as part of the "major changes" of the IFCPC Rio 2011 nomenclature achieve predictive values for CIN2+ lesions and should be therefore emphasized in colposcopy.
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Colposcopía , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Estudios de Cohortes , Femenino , Humanos , Leucoplasia/patología , Análisis de Regresión , Estudios Retrospectivos , Terminología como AsuntoRESUMEN
PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. RESULTS: The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. CONCLUSION: Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.
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Neoplasias de las Glándulas Suprarrenales/radioterapia , Braquiterapia/mortalidad , Carcinoma/prevención & control , Carcinoma/secundario , Fraccionamiento de la Dosis de Radiación , Recurrencia Local de Neoplasia/mortalidad , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Prevalencia , Dosificación Radioterapéutica , Radioterapia Guiada por Imagen , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Super-resolution (SR) is a technique used in digital image processing to overcome the resolution limitation of imaging systems. In this process, a single high resolution image is reconstructed from multiple low resolution images. SR is commonly used for CCD and CMOS (Complementary Metal-Oxide-Semiconductor) sensor images, as well as for medical applications, e.g., magnetic resonance imaging. Here, we demonstrate that super-resolution can be applied with scanning light stimulation (LS) systems, which are common to obtain space-resolved electro-optical parameters of a sample. For our purposes, the Projection Onto Convex Sets (POCS) was chosen and modified to suit the needs of LS systems. To demonstrate the SR adaption, an Optical Beam Induced Current (OBIC) LS system was used. The POCS algorithm was optimized by means of OBIC short circuit current measurements on a multicrystalline solar cell, resulting in a mean square error reduction of up to 61% and improved image quality.
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BACKGROUND: Despite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment. PATIENTS AND METHODS: Tumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome. RESULTS: Mutational profiles and HPV status were successfully established for 179 cases. HPV- tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV- cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV- carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5-12.1, P=0.006) and death (HR 2.2, 95% CI 1.1-4.4, P=0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7-21.1, P=0.11). CONCLUSIONS: Distinct mutation profiles in HPV- and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation.
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Carcinoma de Células Escamosas/genética , Neoplasias de Cabeza y Cuello/genética , Mutación/genética , Análisis de Secuencia de ADN/métodos , Adulto , Anciano , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante/métodos , Fosfatidilinositol 3-Quinasa Clase I , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Genotipo , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Fosfatidilinositol 3-Quinasa/genética , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteína p53 Supresora de Tumor/genética , Infecciones Tumorales por Virus/genéticaRESUMEN
A hyperpolarization technique using carbonate precursors of biocompatible molecules was found to yield high concentrations of hyperpolarized (13)C bicarbonate in solution. This approach enabled large signal gains for low-toxicity hyperpolarized (13)C pH imaging in a phantom and in vivo in a murine model of prostate cancer.
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Materiales Biocompatibles , Isótopos de Carbono/química , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética con Carbono-13RESUMEN
The aim of the study was to identify the effect of high dietary zinc oxide (ZnO) levels on the histamine-induced secretory-type response and histamine metabolism in the porcine proximal colon. After weaning at d 26, 3 diets with low (LZn), normal (NZn), and high (HZn) concentrations of zinc (57, 164, or 2,425 mg/kg) were fed to a total of 120 piglets. Digesta and tissue samples were taken from the ascending colon after 7 ± 1, 14 ± 1, 21 ± 1, and 28 ± 1 d. Partially stripped tissue was mounted in Ussing chambers, and histamine was applied either to the serosal or mucosal compartments. Tissue was pretreated with or without aminoguanidine and amodiaquine to block the histamine-degrading enzymes diamine oxidase (DAO) and histamine -methyltransferase (HMT), respectively. Gene expression and catalytic activity of DAO and HMT in the tissue were analyzed. The numbers of mast cells were determined in tissue samples, and histamine concentration was measured in the colon digesta. Colon tissue from another 12 piglets was used for functional studies on histamine H and H receptors by using the neuronal conduction blocker tetrodotoxin (TTX) and the H and H receptor blocker chloropyramine and famotidine, respectively. After serosal histamine application to colonic tissue in Ussing chambers, the change of short-circuit current (Δ) was not affected by pretreatment and was not different between Zn feeding groups. The Δ after mucosal histamine application was numerically lower ( = 0.168) in HZn compared to LZn and NZn pigs. Mast cell numbers increased from 32 to 46 d of life ( < 0.05). Further studies elucidated that the serosal histamine response was partly inhibited by chloropyramine or famotidine ( < 0.01). The response to mucosal histamine tended to be decreased when chloropyramine but not famotidine was applied from either the serosal or the mucosal side ( = 0.055). Tetrodotoxin alone or in combination with chloropyramine resulted in a similar reduction in the mucosal histamine response ( < 0.01). In conclusion, the present study could not identify marked changes in colonic histamine metabolism on dietary ZnO oversupplementation. For the first time, however, H receptors were functionally identified in the pig colon that are localized either on neurons or on cells that activate secretion via neurons. Luminal histamine can elicit a secretory-type response via these receptors.
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Colon/metabolismo , Histamina/metabolismo , Receptores Histamínicos/metabolismo , Porcinos/fisiología , Óxido de Zinc/administración & dosificación , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Dieta , Histamina N-Metiltransferasa/metabolismo , Mucosa Intestinal/metabolismo , Mastocitos , Óxidos , Sus scrofa/metabolismo , Destete , Zinc/administración & dosificación , Zinc/metabolismo , Óxido de Zinc/metabolismoRESUMEN
Salmonellae are among the most widespread sources of foodborne infections and Salmonella Typhimurium, in particular, is correlated with human disease caused by the consumption of contaminated pork. Intraepithelial lymphocytes (IEL) have early contact with intestinal antigens and play an important role in the detection of pathogenic bacteria. The objective of this study was to determine whether a presumed probiotic Enterococcus faecium strain could improve histomorphological and immune system-related parameters of gut function after a Salmonella challenge in weaned pigs. In particular the morphological parameters villus length and width, crypt depth and width as well as the actual enlargement of the intestinal epithelial surface were calculated and the number of IEL was evaluated in sections of the porcine gut. Weaned piglets were challenged with Salmonella enterica serovar Typhimurium DT 104, and half of them also received Enterococcus faecium NCIMB 10415 in the diet. Animals were sacrificed at days post infection (DPI) 2 and 28. The effect of the factors "time post-infection/age" and "probiotic treatment" on jejunal morphology and IEL numbers and distribution was evaluated by light microscopy. The time post-infection had significant effects in both feeding groups. Animals sacrificed at DPI 28 had longer and wider villi, deeper and wider crypts, a higher villus enlargement factor, a higher ratio between villus and crypt enlargement factors as well as more IEL. Probiotic treatment resulted in longer villi, a higher ratio of villus surface/crypt circumference enlargement factors and significantly more IEL. The larger total number of IEL displayed by the probiotic group resulted from significantly higher numbers of IEL at the nuclear and apical levels of the intraepithelial compartment but not from the number of IEL situated at the basement membrane. The probiotic effects were only measurable 28 DPI. It is proposed that Enterococcus faecium NCIMB 10415 exerts an immune modulatory effect by increasing the numbers of intraepithelial lymphocytes.