Effect of chronic intermittent hypoxia (CIH) on neuromuscular junctions and mitochondria in slow- and fast-twitch skeletal muscles of mice-the role of iNOS.

BACKGROUND: Obstructive sleep apnea (OSA) imposes vascular and metabolic risks through chronic intermittent hypoxia (CIH) and impairs skeletal muscle performance. As studies addressing limb muscles are rare, the reasons for the lower exercise capacity are unknown. We hypothesize that CIH-related morphological alterations in neuromuscular junctions (NMJ) and mitochondrial integrity might be the cause of functional disorders in skeletal muscles. METHODS: Mice were kept under 6 weeks of CIH (alternating 7% and 21% O2 fractions every 30 s, 8 h/day, 5 days/week) compared to normoxia (NOX). Analyses included neuromuscular junctions (NMJ) postsynaptic morphology and integrity, fiber cross-sectional area (CSA) and composition (ATPase), mitochondrial ultrastructure (transmission-electron-microscopy), and relevant transcripts (RT-qPCR). Besides wildtype (WT), we included inducible nitric oxide synthase knockout mice (iNOS-/-) to evaluate whether iNOS is protective or risk-mediating. RESULTS: In WT soleus muscle, CIH vs. NOX reduced NMJ size (- 37.0%, p < 0.001) and length (- 25.0%, p < 0.05) together with fiber CSA of type IIa fibers (- 14%, p < 0.05) and increased centronucleated fiber fraction (p < 0.001). Moreover, CIH vs. NOX increased the fraction of damaged mitochondria (1.8-fold, p < 0.001). Compared to WT, iNOS-/- similarly decreased NMJ area and length with NOX (- 55%, p < 0.001 and - 33%, p < 0.05, respectively) or with CIH (- 37%, p < 0.05 and - 29%, p < 0.05), however, prompted no fiber atrophy. Moreover, increased fractions of damaged (2.1-fold, p < 0.001) or swollen (> 6-fold, p < 0.001) mitochondria were observed with iNOS-/- vs. WT under NOX and similarly under CIH. Both, CIH- and iNOS-/- massively upregulated suppressor-of-cytokine-signaling-3 (SOCS3) > 10-fold without changes in IL6 mRNA expression. Furthermore, inflammatory markers like CD68 (macrophages) and IL1ß were significantly lower in CIH vs. NOX. None of these morphological alterations with CIH- or iNOS-/- were detected in the gastrocnemius muscle. Notably, iNOS expression was undetectable in WT muscle, unlike the liver, where it was massively decreased with CIH. CONCLUSION: CIH leads to NMJ and mitochondrial damage associated with fiber atrophy/centronucleation selectively in slow-twitch muscle of WT. This effect is largely mimicked by iNOS-/- at NOX (except for atrophy). Both conditions involve massive SOCS3 upregulation likely through denervation without Il6 upregulation but accompanied by a decrease of macrophage density especially next to denervated endplates. In the absence of muscular iNOS expression in WT, this damage may arise from extramuscular, e.g., motoneuronal iNOS deficiency (through CIH or knockout) awaiting functional evaluation.

Evolución hacia la era digital de la cirugía ortognática: experiencia en un centro universitario / Evolution towards the digital era of orthognatic surgery: experience in a university center

Resumen Introducción: La incorporación de tecnologías en la práctica quirúrgica, ha cambiado la forma de enfrentar el proceso quirúrgico. Objetivo: Describir la experiencia de los últimos 9 años, en cirugía ortognática, con la incorporación de la cefalometría 3D. Materiales y Método: Se realizó una revisión retrospectiva de pacientes operados de cirugía ortognática durante el período enero de 2011 a agosto de 2018. Se registraron datos demográficos, quirúrgicos, tipo de planificación quirúrgica, complicaciones y resultados a largo plazo. Resultados: 21 pacientes requirieron cirugías ortognáticas. Se realizaron 16 cirugías bimaxilares (76%), 3 cirugías de avance maxilar superior (14%) y 2 cirugías de osteotomía sagital de rama (10%). Las principales etiologías fueron: 67% maloclusión clase III (n = 14), 28% maloclusión clase II (n = 6) y 5% desviación mandibular (n = 1). La planificación prequirúrgica virtual fue utilizada en 11 pacientes (52%). La tasa de complicaciones Clavien-Dindo > III fue 4,8% (n = 1). Conclusiones: En nuestra experiencia, las técnicas de cirugía ortognática son seguras. Las complicaciones de la serie fueron escasas y bien toleradas por los pacientes. Durante los últimos años y, de acuerdo a los avances tecnológicos, la incorporación de la planificación quirúrgica virtual 3D favoreció el desarrollo de la cirugía ortognática en nuestro centro.

Introduction: Technological advances have been incorporated into cranio-maxillo-facial surgery changing the clinical practice of surgeons. Aim: The aim of this article is to describe our experience in orthognatic surgery in the last 9-years, with the incorporation of 3D cephalometry. Materials and Method: A retrospective chart review was performed from January 2011 to August 2018 on patients undergoing Orthognatic Surgery. Demographic and surgical data, type of surgical planning, complications and long-term results were recorded. Results: A total of 21 patients underwent orthognatic surgery. Average age was 28 years (DE 8.1), 11 men (52.3%) and 10 women (47.61%). The principal surgeries performed were: 16 (76%) bimaxillary, 3 maxillary advancement surgery 3 (14%) and bilateral sagital split osteotomy 2 (10%). Ethiologies were: 14 patients (this 67%) with malocclusion class III, 6 patients (28%) with malocussion class II, and 1 patient (5%) with mandibular deviation. Virtual 3D presurgical planning was used in 11 patients (52%). The total of complications Clavien-Dindo > III was 4.8% (n = 1). None patient required reoperation. Satisfaction rate with the procedure was high. Conclusions: Based on our experience, orthognatic surgery techniques are safe. The complication rate was lower and well tolerated by patients. The introduction of virtual planning provided a better scenario to develop maxillo-facial surgery.

Análisis del programa de formación de Cirugía Plástica y Reparadora de la Universidad de Chile: encuesta a egresados 2011-2017 / Analysis of the training program of Plastic and Reconstructive Surgery of the University of Chile: survey of graduates 2011-2017

INTRODUCCIÓN: La formación de cirujanos plásticos de calidad exige una constante revisión y evaluación del programa aplicado. Han transcurrido 8 años desde que se evaluó la opinión de los egresados del Programa de Cirugía Plástica de la Universidad de Chile por primera vez. OBJETIVO: Recoger la opinión de los egresados del mismo programa entre los años 2011-2017, con el fin de cotejar los resultados con generaciones anteriores. MATERIALES Y MÉTODO: Se realizó una encuesta de 28 preguntas, las cuales evalúan aspectos generales de la residencia, rotaciones específicas del residente, actividades prácticas, actividades teóricas y aspectos económicos y de investigación. RESULTADOS: De un total de 21 egresados en el período comprendido 2011-2017 se obtuvo respuesta de la encuesta en 16 de ellos, el 100% de los encuestados aprueba el programa de formación, el 63% de los encuestados considera que la duración del programa es insuficiente. La rotación mejor evaluada del programa fue el Hospital Clínico de la Universidad de Chile según un 56% de los egresados. Las áreas de mejor percepción de formación fueron cirugía de contorno corporal y cirugía estética mamaria respectivamente. CONCLUSIÓN: La aprobación del programa de formación de la especialidad sigue siendo alta en los egresados, sin embargo, se mantiene la opinión de la necesidad de un programa más extenso. El análisis recogido de esta encuesta es una buena herramienta para identificar aspectos del programa que se pueden mejorar.

BACKGROUND: The adequate plastic surgeons training demand a constant review and assessment of the training programs of residents. It has been 8 years since the first survey made to Plastic Surgery graduates of the University of Chile about the program training. AIM: Collect the opinion of Plastic Surgery graduates of the University of Chile between the years 2011-2017, in order to compare the results with previous generations. MATERIAL AND METHOD: A survey of 28 questions was conducted which evaluated general aspects of the residence, specific rotations of the resident, practical activities, theoretical activities and economic and research aspects. RESULTS: There has been 21 graduates between 2011-2017, a survey response was obtained in 16 of them, 100% of the respondents approved the training program, 63% of respondents consider the duration of the program is insufficient. The best-evaluated rotation of the program was HCUCH according to 56% of graduates. The areas of best training perceived were body contour surgery and breast aesthetic surgery, respectively. CONCLUSION: Plastic surgery training program approval is still high in graduates; nevertheless the opinion about the needing for a more extensive program is kept. The analysis collected from this survey is an excellent tool to identify aspects of the training program can be improved.

Very long-term outcome in resected and non-resected patients with temporal lobe epilepsy with medial temporal lobe sclerosis: A multiple case-study.

PURPOSE: To investigate the very long-term (i.e., ≥15 years) seizure, cognitive and psycho-social outcomes in resected patients (RP) with TLE compared to control patients not having undergone epilepsy surgery. METHODS: We applied a multiple case-study design including three non-resected patients (NRP) who were compared to a group of six RP. The latter were matched to the NRP according to clinical-demographic data. Outcome measures were various seizure, cognitive, and psycho-social variables. RESULTS: Patients were 56-72 years old. Seizure and AED outcome was more favourable among RP. RP reported better self-perceived overall health but higher subjective memory complaints. Upon formal neuropsychological testing, RP presented with lower verbal memory scores. Very long-term memory decline was evident in left-sided RP with good baseline memory scores, while RP with lower baseline performance, right-sided RP and NRP remained stable. Seizure-freedom had remarkable effects on the relationship between objective and subjective outcome: seizure-free patients, in general, subjectively reported the best psychosocial and cognitive outcome - irrespective of neuropsychological test results. CONCLUSION: Our study suggests positive effects of TLE surgery in the very long-term course of ≥15 years postoperatively. Long-term seizure-freedom appears to have the strongest impact on patients' subjectively perceived psycho-social and cognitive outcome and may even outweigh actual memory disturbances and/or decline. Overall, our data do not support the assumption of a generally accelerated cognitive decline in patients with TLE.

Gluteoplastía de aumento con implantes de silicona con técnica XYZ: serie de casos / Augmentation gluteoplasty with silicone implants with XYZ technique

Resumen Objetivo: Describir las características clínicas, demográficas, resultados y complicaciones de una serie de pacientes operados de aumento de glúteo con implantes de silicona por medio de la técnica XYZ. Materiales y Método: Serie de casos retrospectiva de pacientes sometidos a gluteoplastía de aumento con implantes de silicona por medio de técnica intramuscular. Se describe la técnica quirúrgica, datos demográficos, antecedentes médico quirúrgicos y complicaciones posoperatorias. Resultados: Entre diciembre de 2014 y junio de 2017 se operaron 19 pacientes. La complicación más frecuente fue dehiscencia de herida operatoria, presentándose en 5 pacientes. Un paciente tuvo hematoma posoperatorio. Dos pacientes tuvieron seroma posoperatorio. Una paciente presentó rotación de un implante. Una paciente se perdió de seguimiento luego del control de retiro de puntos a la 6a semana. Una paciente necesitó reinternación para manejo del dolor. Ningún paciente necesitó reoperación. Ningún paciente presentó infección de herida operatoria. Ningún paciente presentó extrusión ni pérdida de implantes. Discusión: La técnica XYZ es un método efectivo para el tratamiento estético y reconstructivo de la región glútea especialmente en pacientes que no presentan zona dadora suficiente para injerto graso. Las complicaciones descritas son acordes a la literatura, por lo que se recomienda la técnica de gluteoplastía de aumento con prótesis de silicona intramuscular como una técnica reproducible y segura.

Objective: Describing the clinical features, demographics features, outcomes and complications from a serie of patients underwent buttock augmentation with silicone implants with XYZ technique. Material and Methods: Retrospective case series of patients underwent buttock augmentation with intramuscular technique. It Is described the surgical technique, demographics data, comorbidities and post operative complications. Results: Since December 2014 to June 2017 were operated 19 patients. The most frecuent complication was wound dehiscence, it was present in 5 patients. One patient had a postoperative hematoma. Two patients presented seroma. One patient presented implant rotation. One patient left controls after removal the suture in the sixth week. None of patients needed revisional procedures. None of patients presented wound infection. None of patients presented extrusión or implant removal. Discussion: The XYZ technique is a efective method to aesthetic and reconstructive treatment of buttock area, especially in patientes without a suficient donor area to fat graft. The complications described are accord with literatura, that is why buttock augmentation with intramuscular silicone implant is recomended as a reproducible and safe technique.

Comprehensive high-resolution genomic profiling and cytogenetics of human chondrocyte cultures by GTG-banding, locus-specific FISH, SKY and SNP array.

In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: "In conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies". 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies. Single nucleotide polymorphism (SNP) array analysis was performed on chondrocyte spheroids from five of the six donors. Applying this combination of techniques, the genetic analyses performed revealed no significant genetic instability until passage 3 in monolayer cells and interphase cells from spheroid cultures at different time points. Clonal occurrence of polyploid metaphases and endoreduplications were identified associated with prolonged cultivation time. Also, gonosomal losses were observed in chondrocyte spheroids, with increasing passage and duration of the differentiation phase. Interestingly, in one of the donors, chromosomal aberrations that are also described in extraskeletal myxoid chondrosarcoma were identified. The SNP array analysis exhibited chromosomal aberrations in two donors and copy neutral losses of heterozygosity regions in four donors. This study showed the necessity of combined genetic analyses at defined cultivation time points in quality studies within the field of cell therapy.

Analysis of cytopenia in geriatric inpatients.

BACKGROUND: Peripheral blood dyscrasias in older patients are repeatedly seen in geriatric clinical practice; however, there is substantial lack of data about the epidemiology, possible causes and treatment options in this patient group. Proton pump inhibitors (PPI) are extensively used in older patients and associated with leukopenia. The primary objective of this study was the assessment of encoded cytopenia prevalence in a geriatric patient cohort and the secondary objective was the assessment of putative causes and the analysis of PPI administration in patients with cytopenia. METHODS: Retrospective evaluation of patients admitted to the geriatric department of a German urban hospital between 2010 and 2012. Electronic patient data were screened for encoded diagnosis of cytopenia according to the International Classification of Diseases (ICD) 10. Inclusion criteria were ICD code D69.0-9 and/or D70.0-7, age ≥60 years and exclusion criteria were no ICD code D69.0-9 and/or D70.0-7 and age <60 years. Out of 9328 screened inpatients 54 patients remained for analysis. Study parameters included hemoglobin (Hb), red blood cell count (RBC), leucocytes, platelets, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), presence of leukopenia (<4000/µl), presence of thrombocytopenia (<140,000/µl) and presence of anemia according to the World Health Organization (WHO). Substitution of blood products, medication with PPI and potential causes for dyscrasias were evaluated based on electronic patient records. RESULTS: The mean age was 78.3 ± 6.5 years (27 females, 27 males), anemia was seen in 78%, leukopenia was encoded in13% and thrombocytopenia in 44.4%. In most of the patients no substitution of blood products was documented. In most of the patients (20.4%) cytopenia was attributed to either heparin-induced thrombocytopenia (HIT) or hemato-oncologic (20.4%) diseases, followed by drug association in 18.5%. In 70.8% of the study patients PPIs were administered but the indication for PPI administration remained unclear in 20.4%. CONCLUSION: The results encourage accurate assessment of blood dyscrasias and appropriate documentation as well as indication check for PPI treatment in geriatric inpatients.

Ultrasound palpation for fast in-situ quantification of articular cartilage stiffness, thickness and relaxation capacity.

Most current cartilage testing devices require the preparation of excised samples and therefore do not allow intra-operative application for diagnostic purposes. The gold standard during open or arthroscopic surgery is still the subjective perception of manual palpation. This work presents a new diagnostic method of ultrasound palpation (USP) to acquire applied stress and strain data during manual palpation of articular cartilage. With the proposed method, we obtain cartilage thickness and stiffness. Moreover, repeated palpations allow the quantification of relaxation effects. USP measurements on elastomer phantoms demonstrated very good repeatability for both, stage-guided (97.2%) and handheld (96.0%) applications. The USP measurements were compared with conventional indentation experiments and revealed very good agreement on elastomer phantoms ([Formula: see text]) and good agreement on porcine cartilage samples ([Formula: see text]). Artificially degenerated cartilage samples showed reduced stiffness, weak capacity to relax after palpation and an increase of stiffness of approximately 50% with each single palpation. Intact cartilage was measured by USP directly at the patella (in situ) and after excision and removal of the subchondral bone (ex situ), leading to stiffness values of [Formula: see text] and [Formula: see text] ([Formula: see text]), respectively. The results demonstrate the potential of the USP system for cartilage testing, its sensitivity to degenerative changes and as a method for quantifying relaxation processes by means of repeated palpations. Furthermore, the differences in the results of in-situ and ex-situ measurements are of general interest, since such comparison has not been reported previously. We point out the limited comparability of ex-situ cartilage with its in-situ biomechanical behavior.

[Calculating Ratios Based on Statutory Health Care Data at the District Level - An Empirical Estimation Based on the Microcensus]. / Ratenbildung bei KV-Daten mit GKV-Versicherten auf Kreisebene ­ ein empirisches Schätzmodell auf der Basis des Mikrozensus.

Background: In Germany, data of the statutory health insurance system are used, amongst others, in health monitoring and health care research at the district level. For the calculation of exact ratios, the number of those covered by statutory health insurance is needed as denominator. For some federal states, however, this number is not available on a district level. Therefore, ratios based on statutory health care data are calculated using a surrogate defined in terms of visits to the doctor. This leads to uncertainties that limit small area comparisons. Therefore, the aim of the present study was to develop a superior estimation model for the number of those covered by statutory health insurance on a district level. Methods: The proportion of those covered by statutory health insurance in the Bavarian districts is estimated by a multiple linear regression model. The model relates data on determinants of the insurance status (income, proportions of civil servants and of self-employed persons) available on district level to data on the number of those covered by statutory health insurance obtained from microcensus on a regional level. The proportion of those covered by statutory health insurance estimated by this model is compared to the surrogate. As an example for practical application, small area estimations for diabetes prevalence are compared to data provided by the Bavarian Association of Statutory Health Insurance Physicians. Results: The proportion of those covered by the statutory health insurance in the Bavarian districts as estimated by the regression model varies between 74.7 and 91.6%. The difference to the currently used surrogate reaches up to 18.6 percentage points. This is also reflected in treatment prevalence, shown here using the example of diabetes mellitus. Conclusion: The present analysis shows the uncertainties of ratios and consequences for small area comparisons based on statutory healthcare data. Providing valid data for the denominator in accordance with the data transparency regulation in the Social Insurance Code (SGB) V should be attempted.

Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse.

To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.

Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment.

Missense mutations in p53 generate aberrant proteins with abrogated tumour suppressor functions that can also acquire oncogenic gain-of-function activities that promote malignant progression, invasion, metastasis and chemoresistance. Mutant p53 (mutp53) proteins undergo massive constitutive stabilization specifically in tumours, which is the key requisite for the acquisition of gain-of-functions activities. Although currently 11 million patients worldwide live with tumours expressing highly stabilized mutp53, it is unknown whether mutp53 is a therapeutic target in vivo. Here we use a novel mutp53 mouse model expressing an inactivatable R248Q hotspot mutation (floxQ) to show that tumours depend on sustained mutp53 expression. Upon tamoxifen-induced mutp53 ablation, allotransplanted and autochthonous tumours curb their growth, thus extending animal survival by 37%, and advanced tumours undergo apoptosis and tumour regression or stagnation. The HSP90/HDAC6 chaperone machinery, which is significantly upregulated in cancer compared with normal tissues, is a major determinant of mutp53 stabilization. We show that long-term HSP90 inhibition significantly extends the survival of mutp53 Q/- (R248Q allele) and H/H (R172H allele) mice by 59% and 48%, respectively, but not their corresponding p53(-/-) littermates. This mutp53-dependent drug effect occurs in H/H mice treated with 17DMAG+SAHA and in H/H and Q/- mice treated with the potent Hsp90 inhibitor ganetespib. Notably, drug activity correlates with induction of mutp53 degradation, tumour apoptosis and prevention of T-cell lymphomagenesis. These proof-of-principle data identify mutp53 as an actionable cancer-specific drug target.

Hiperplasia de cóndilo mandibular: reporte de doce casos / Hyperplasia of the mandibular condyle: considerations in a series of 12 patients

Introducción: La hiperplasia condilar (HC) se define como un crecimiento patológico no neoplásico que afecta tanto al tamaño como a la morfología del cóndilo mandibular. Objetivo: Evaluar la eficacia y riesgos del tratamiento quirúrgico de la HC. Material y método: Estudio descriptivo, serie de casos. Se incluyó a todos los pacientes con diagnóstico de HC tratados en el Hospital Clínico de la Pontificia Universidad Católica de Chile entre enero de 2010 y febrero de 2014. Resultados: Doce pacientes fueron operados en nuestra institución por HC. El promedio de edad fue 19,3 ± 3,4 años. La forma de presentación más frecuente fue presencia de asimetría facial. Todos los pacientes fueron estudiados con SPECT que evidenció diferencia de captación mayor a 50% ± 3,1% entre ambos cóndilos. Todos los pacientes fueron tratados con condilectomía mandibular alta del lado afectado y en 3 casos, se realizó además cirugía ortognática en el mismo tiempo para corrección de maloclusión dental. La mediana de seguimiento fue de meses 16 (5 a 54 meses). En todos los pacientes se evidenció una mejora en la oclusión dental y simetría facial, con desaparición de la disfunción articular previa. Conclusiones: La HC es una entidad de poca frecuencia. La cirugía es eficaz y segura para el tratamiento de la HC.

Introduction: Condylar hiperplasia is defined as a pathological non neoplastic growth which compromises both size and shape of the mandibular condyle and is characterized by progressive facial asymmetry. Aim: To evaluate the efficacy and risks of surgical treatment of HC. Material and method: Descriptive study, cohort of cases. All patients between 2010 and February 2014 with diagnosis of condylar hyperplasia at Hospital Clínico P. Universidad Católica de Chile were included. Results: Twelve patients were operated at our institution because of condylar hyperplasia. Age average was 19.3 ± 3.4 years. The most frequent presentation was facial asymmetry. All patients were studied with single photon emission computed tomography (SPECT) with differential intake more than 50 ± 3.1% between both condyles. All patients were treated with mandibular condylectomy of the affected site and in 3 cases orthognatic surgery was performed at the same time of the condylectomy to correct dental malocclusion. Average follow up was 16 months (5 to 54 months). All patients recovered facial symmetry and occlusion with absence of the previous joint dysfunction. Conclusions: Condylar hyperplasia is an unfrequent condition and surgery is efficient and safe for the treatment of the deformity.

Genome-wide methylation analysis in Silver-Russell syndrome patients.

Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and several additional minor malformations. The aetiology of SRS is complex and current evidence strongly implicates imprinted genes. Approximately, half of all patients exhibit DNA hypomethylation at the H19/IGF2 imprinted domain, and around 10% have maternal uniparental disomy of chromosome 7. We measured DNA methylation in 18 SRS patients at >485,000 CpG sites using DNA methylation microarrays. Using a novel bioinformatics methodology specifically designed to identify subsets of patients with a shared epimutation, we analysed methylation changes genome-wide as well as at known imprinted regions to identify SRS-associated epimutations. Our analysis identifies epimutations at the previously characterised domains of H19/IGF2 and at imprinted regions on chromosome 7, providing proof of principle that our methodology can detect DNA methylation changes at imprinted loci. In addition, we discovered two novel epimutations associated with SRS and located at imprinted loci previously linked to relevant mouse and human phenotypes. We identify RB1 as an additional imprinted locus associated with SRS, with a region near the RB1 differentially methylated region hypermethylated in 13/18 (~70%) patients. We also report 6/18 (~33%) patients were hypermethylated at a CpG island near the ANKRD11 gene. We do not observe consistent co-occurrence of epimutations at multiple imprinted loci in single SRS individuals. SRS is clinically heterogeneous and the absence of multiple imprinted loci epimutations reflects the heterogeneity at the molecular level. Further stratification of SRS patients by molecular phenotypes might aid the identification of disease causes.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

[Geriatric trauma centers - requirements catalog. An initiative to promote and guarantee the quality of care of elderly trauma patients receiving inpatient care]. / Alterstraumatologisches Zentrum - Anforderungskatalog. Eine Initiative zur Förderung und Sicherung der Qualität der Versorgung alterstraumatologischer Patienten in Deutschland im Bereich der stationären Versorgung.

For the care of the elderly, specific geriatric care facilities in hospitals and specialized rehabilitation centers have been established in the last 20 years throughout Germany. In addition, trauma surgery departments in hospitals and clinics also provide comprehensive care for trauma patients. The present requirements catalog was developed with the aim to ensure the standardization and quality assurance of these care facilities. Thus, the structural basics and, in particular, the structured cooperation between geriatrics and trauma surgery are described and defined in terms of structure, process, and outcome quality. The Bundesverband Geriatrie, the Deutsche Gesellschaft für Geriatrie, and the Deutsche Gesellschaft für Gerontologie und Geriatrie offer documentation for external and internal use and evaluation of the structures and processes for certification of geriatric trauma centers. Prerequisite for certification is to meet the technical requirements defined in the requirements catalogue or documents derived from it, and proof of a quality management system according to ISO 9001.

Influencia de la apariencia de las mamas en la calidad de vida: diferencias entre población preoperatoria de mamoplastía de reducción y población control / Criterion validity of a questionnaire to assess quality of life associated to the appearance of breasts in women

Objetivo: El Breast Q Reduction and Mastopexy Module es un instrumento específico para la evaluación de calidad de vida asociado a mamas desde la perspectiva del paciente, recientemente validado para uso en español en Chile. Cuenta con evaluación pre y postoperatoria. El objetivo del presente estudio es conocer la validez de criterio al comparar las distribuciones en distintas poblaciones de individuos así como la diferencia del puntaje entre el pre y postoperatorio. Materiales y Métodos: El instrumento validado en español Breast Q Reduction-Mastopexy Module fue sometido a prueba para evaluar su validez de criterio comparando los resultados de la escala en pacientes que deseaban someterse a cirugía versus 2 grupos control, uno de pacientes hospitalizados por otra causa y otro de estudiantes de medicina. Resultados: Se aplicó la encuesta a 46 mujeres, 6 pacientes preoperatorios de mamoplastía de reducción, 20 alumnas de medicina y 20 pacientes hospitalizadas por otra causa. Hubo diferencias estadísticamente significativas entre las pacientes y los grupos control en los dominios autoimagen corporal (p = 0,0001), desempeño social (p = 0,0035) y síntomas físicos (p = 0,0058), no se observaron diferencias en el dominio de sexualidad (p = 0,1432), sin embargo, sólo 4/6 pacientes contestaron la encuesta ya que las otras 2 declararon no tener vida sexual. Conclusiones: Estos resultados preliminares sugieren que la versión en español del Breast Q Reduction-Mastopexy Module es un instrumento útil para evaluar calidad de vida asociada a las mamas en mujeres chilenas.

Background: The Breast QoL Reduction and Mastopexy Module assesses quality of life associated to breast appearance from the point of view of the patient. Its Spanish version was recently validated in Chile. Aim: To assess the criterion validity of the instrument applying it in different populations of women and in the pre and post-operative periods. Material and Methods: The questionnaire was applied to six women subjected to reduction mammoplasty in the pre and post-operative period. It was also applied to 20 women hospitalized for other causes and 20 female medical students. Results: There were significant differences between operated women and their non-operated counterparts in the domains body self-image, social performance and physical symptoms. No differences in sexuality were found. However this last question was answered only by four operated patients, since two declared not to have sex life. Conclusions: The questionnaire is useful to assess quality of life associated to the appearance of breasts.

[Perioperative nutritional therapy]. / Perioperative Ernährungstherapie.

BACKGROUND: There is no difference in medical and nutritional therapy between elderly and young surgical patients. However, based on the high prevalence of malnutrition or a risk for malnutrition and the associated risk for complications, elderly surgical patients should receive special attention. AIM: This article addresses the options in perioperative nutritional therapy and gives an overview on current guidelines and study results. MATERIALS AND METHODS: The article includes a literature review of current national and international guidelines in the field of surgery and geriatrics. Cochrane reviews, systematic reviews, meta-analyses, and significant single studies are also included. RESULTS: Contrary to former approaches, national and international organizations recommend to keep the duration of pre- and postoperative fasting as short as possible. The benefits of nutritional therapy in stabilization and improvement of the nutritional status of surgical patients has already been shown in several patient groups like patients undergoing major abdominal surgeries. For other patients groups, like patients with sepsis, further studies are needed to evaluate the benefit of a perioperative nutritional intervention.