Atypical localized Mongolian spots in dark pigmented skin - a challenge for forensic medical examination.

The assessment of skin changes in the context of possible child abuse is an important task in forensic medicine. This requires knowledge of pigmentation variants and pigmentation disorders such as congenital dermal melanocytosis, which includes Mongolian spots. Particularly in the case of atypical localization and dark pigmented skin, the differentiation from hematomas can be challenging. A case of two Nigerian siblings with extensive and atypically localized Mongolian spots is reported. The 1.5-year-old girl showed Mongolian spots on her back and the right side of her trunk. The 8-year-old boy showed Mongolian spots only on the back of his thighs. The authors are not aware of any case in which so called Mongolian spots were present exclusively on the back of the thighs and this case is all the more noteworthy as the back of the thigh is a common localization of blunt force trauma.

Long-term functional success and patient-reported outcomes after female one-stage buccal mucosal graft urethroplasty.

INTRODUCTION AND OBJECTIVES: Female urethral strictures are a rare condition that significantly impacts patients' quality of life. Patient-reported outcomes are crucial, yet data regarding sexual function and treatment satisfaction are scarce. We aimed to provide insights from a reconstructive referral center. PATIENTS AND METHODS: We conducted a retrospective analysis of women treated with ventral onlay one-stage buccal mucosa graft urethroplasty for urethral strictures between 2009-2023. We assessed objective (retreatment-free survival, ΔQmax) and subjective outcomes (validated patient-reported outcomes). RESULTS: Of 12 women, 83% and 17% had iatrogenic and idiopathic strictures, respectively. Median number of prior interventions was 6. Strictures were located meatal and mid-urethral in 25% and 75%, respectively, 22% had the bladder neck involved. Median graft length was 2 cm. At median follow-up of 66 months, 33% of patients underwent stricture retreatment, but only one case occurred within the first 2 years postoperatively. The median improvement in maximum flow rate (ΔQmax) was 10 ml/s. Median International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS) scores were 8 for filling symptoms, 6 for voiding symptoms, and 3 for incontinence symptoms. Median ICIQ-FLUTSsex score was 4. Higher scores indicate a higher symptom burden. Median ICIQ-Satisfaction outcome and satisfaction scores were 18 and 7, respectively, reflecting high treatment satisfaction. CONCLUSIONS: Buccal mucosal graft urethroplasty by ventral onlay for female urethral strictures yields effective, durable, and positively received outcomes. However, larger studies across multiple institutions are necessary to further assess its efficacy, especially regarding patient-reported experiences and sexual function.

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.

Chronic effects of the strobilurin fungicide azoxystrobin in the leaf shredder Gammarus fossarum (Crustacea; Amphipoda) via two effect pathways.

Fungicides pose a risk for crustacean leaf shredders serving as key-stone species for leaf litter breakdown in detritus-based stream ecosystems. However, little is known about the impact of strobilurin fungicides on shredders, even though they are presumed to be the most hazardous fungicide class for aquafauna. Therefore, we assessed the impact of the strobilurin azoxystrobin (AZO) on the survival, energy processing (leaf consumption and feces production), somatic growth (growth rate and molting activity), and energy reserves (neutral lipid fatty and amino acids) of the amphipod crustacean Gammarus fossarum via waterborne exposure and food quality-mediated (through the impact of leaf colonizing aquatic microorganisms) and thus indirect effects using 2 × 2-factorial experiments over 24 days. In a first bioassay with 30 µg AZO/L, waterborne exposure substantially reduced survival, energy processing and affected molting activity of gammarids, while no effects were observed via the dietary pathway. Furthermore, a negative growth rate (indicating a body mass loss in gammarids) was induced by waterborne exposure, which cannot be explained by a loss in neutral lipid fatty and amino acids. These energy reserves were increased indicating a disruption of the energy metabolism in G. fossarum caused by AZO. Contrary to the first bioassay, no waterborne AZO effects were observed during a second experiment with 15 µg AZO/L. However, an altered energy processing was determined in gammarids fed with leaves microbially colonized in the presence of AZO, which was probably caused by fungicide-induced effects on the microbial decomposition efficiency ultimately resulting in a lower food quality. The results of the present study show that diet-related strobilurin effects can occur at concentrations below those inducing waterborne toxicity. However, the latter seems to be more relevant at higher fungicide concentrations.

Stranded cetaceans warn of high perfluoroalkyl substance pollution in the western Mediterranean Sea.

Perfluoroalkyl substances (PFASs) are a class of organohalogenated compounds of environmental concern due to similar characteristics as the well-studied legacy persistent organic pollutants (POPs) that typically show environmental persistence, biomagnification and toxicity. Nevertheless, PFAS are still poorly regulated internationally and in many aspects poorly understood. Here, we studied liver and muscle concentrations in five cetacean species stranded at the southeastern coast of Spain during 2009-2018. Twelve of the fifteen targeted compounds were detected in >50% of the liver samples. Hepatic concentrations were significantly higher than those in muscle reflecting the particular toxicokinetics of these compounds. Bottlenose dolphins Tursiops truncatus showed the highest hepatic ΣPFAS (n = 5; 796.8 ± 709.0 ng g-1 ww) concentrations, followed by striped dolphin Stenella coeruleoalba (n = 29; 259.5 ± 136.2 ng g-1 ww), sperm whale Physeter macrocephalus (n = 1; 252.8 ng g-1 ww), short-beaked common dolphin Delphinus delphis (n = 2; 240.3 ± 218.6 ng g-1 ww) and Risso's dolphin Grampus griseus (n = 1; 78.7 ng g-1 ww). These interspecies differences could be partially explained by habitat preferences, although they could generally not be related to trophic position or food chain proxied by stable N (δ15N) and C (δ13C) isotope values, respectively. PFAS profiles in all species showed a similar pattern of concentration prevalence in the order PFOS>PFOSA>PFNA≈PFFUnA>PFDA. The higher number of samples available for striped dolphin allowed for evaluating their PFAS burden and profile in relation to the stranding year, stable isotope values, and biological variables including sex and length. However, we could only find links between δ15N and PFAS burdens in muscle tissue, and between stranding year and PFAS profile composition. Despite reductions in the manufacturing industry, these compounds still appear in high concentrations compared to more than two decades ago in the Mediterranean Sea and PFOS remains the dominating compound.

Forensic age assessment of living adolescents and young adults at the Institute of Legal Medicine, Münster, from 2009 to 2018.

Due to high migration inflows to Europe, forensic age assessment of living persons has clearly gained importance. If there is a legal justification for X-ray examinations without a medical indication, the Study Group on Forensic Age Diagnostics (AGFAD) recommends the combination of a physical examination with anamnesis, an X-ray examination of the hand and a dental examination with evaluation of an orthopantomogram for age assessments of adolescents and young adults. If the development of the hand skeleton has been completed, an additional CT examination of the clavicles is to be performed. To demonstrate the outcome of forensic age assessments according to AGFAD recommendations with regard to migrants of doubtful minority declaration, this study analyzes the expert reports carried out at the Institute of Legal Medicine, Münster, from 2009 to 2018. A total of 597 age assessments were performed during the study period. A total of 227 age assessments were issued on behalf of youth welfare offices in the legal area of social law, 282 in family law proceedings, 76 in criminal proceedings, and 12 age assessments in immigration law proceedings. In 211 out of 597 cases, the stated age was compatible with the findings of the age assessment. In the remaining 386 cases, the average difference between the stated age and the minimum age was 1.9 years. The average difference between stated age and most probable age was 5.1 years. Of the 521 age assessments carried out outside criminal proceedings, 197 unaccompanied minors with questionable age minority (37.8%) have reached the age of majority beyond doubt. A total of 388 unaccompanied minors (74.5%) have most probably reached the age of majority. Forensic age assessments with the AGFAD methodology make an important contribution to legal certainty, the welfare of the child, and the fair distribution of resources.

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.

Does the identification of seniors at risk (ISAR) score effectively select geriatric patients on emergency admission?

The number of older patients admitted to emergency departments (ED) increases continuously. The Identification of Seniors at Risk (ISAR) score is currently recommended to screen patients in German ED, but its appropriateness is being criticized. ISAR scores and clinical characteristics from 98 emergency admissions (EA), 80 from acute geriatrics (AG) and 89 from a geriatric rehabilitation (GR) unit were compared retrospectively. No significant differences were found between groups, being the ISAR score positive in 87.7% of EA, 94.9% of AG and 94.4% of GR cases. None of positively identified geriatric patients in the EA was transferred to the geriatric ward of competence. EA patients showed significantly higher number of functional impairments (p = 0.001) and higher BI score (p < 0.0001) compared to AG and GR groups. A higher ISAR score threshold and additional functional information might be needed to better select patients in need of prompt treatment by a geriatric team.

Waterborne and diet-related effects of inorganic and organic fungicides on the insect leaf shredder Chaetopteryx villosa (Trichoptera).

It is well-documented that fungicides can affect crustacean leaf shredders via two effect pathways, namely waterborne exposure and their diet (i.e., via dietary uptake of fungicides adsorbed to leaf material and an altered microorganism-mediated food quality). As a consequence of different life history strategies, the relevance of these effect pathways for aquatic shredders belonging to other taxonomic classes, for instance insects, remains unclear. Therefore, we investigated waterborne and diet-related effects in larvae of the caddisfly leaf shredder Chaetopteryx villosa (Insecta: Trichoptera) and compared our observations to previous reports on effects in adults of the crustacean leaf shredder Gammarus fossarum (Malacostraca: Amphipoda). We assessed acute waterborne effects of an organic fungicide mixture (OFM) and the inorganic fungicide copper (Cu) on the leaf consumption (n = 30) of the fourth-/fifth-instar larvae of C. villosa and their food choice (n = 49) when offered leaf material, which was either conditioned in presence or in absence of the respective fungicide(s). Moreover, the larval leaf consumption (n = 50) and physiological fitness (i.e., growth as well as lipid and protein content) were examined after subjecting C. villosa for 24 days towards the combination of both effect pathways at environmentally relevant concentrations. G. fossarum and C. villosa exhibited similar sensitivities and the same effect direction when exposed to the OFM (either waterborne or dietary pathways). Both shredders also showed the same effect direction when exposed to dietary Cu, while with regards to mortality and leaf consumption C. villosa was less sensitive to waterborne Cu than G. fossarum. Finally, as observed for G. fossarum, the combined exposure to OFM over 24 days negatively affected leaf consumption and the physiology (i.e., growth and lipid reserves) of C. villosa. While no combined Cu effects were observed for larval leaf consumption, contrasting to the observations for G. fossarum, the physiology of both shredders was negatively affected, despite partly differing effect sizes and directions. Our results suggest that C. villosa and G. fossarum are of comparable sensitivity towards waterborne and diet-related organic fungicide exposure, whereas the trichopteran is less sensitive to Cu-based waterborne fungicide exposure. However, when both pathways act jointly, organic and inorganic fungicides can affect the physiology of shredder species with completely different life history strategies. As caddisflies represent a subsidy for terrestrial consumers, these observations indicate that fungicide exposure might not only affect aquatic ecosystem functioning but also the flux of energy across ecosystem boundaries.

Parietofrontal network upregulation after motor stroke.

Objective: Motor recovery after stroke shows a high inter-subject variability. The brain's potential to form new connections determines individual levels of recovery of motor function. Most of our daily activities require visuomotor integration, which engages parietal areas. Compared to the frontal motor system, less is known about the parietal motor system's reconfiguration related to stroke recovery. Here, we tested if functional connectivity among parietal and frontal motor areas undergoes plastic changes after stroke and assessed the behavioral relevance for motor function after stroke. Methods: We investigated stroke lesion-induced changes in functional connectivity by measuring high-density electroencephalography (EEG) and assessing task-related changes in coherence during a visually guided grip task with the paretic hand in 30 chronic stroke patients with variable motor deficits and 19 healthy control subjects. Quantitative changes in task-related coherence in sensorimotor rhythms were compared to the residual motor deficit. Results: Parietofrontal coupling was significantly stronger in patients compared to controls. Whereas motor network coupling generally increased during the task in both groups, the task-related coherence between the parietal and primary motor cortex in the stroke lesioned hemisphere showed increased connectivity across a broad range of sensorimotor rhythms. Particularly the parietofrontal task-induced coupling pattern was significantly and positively related to residual impairment in the Nine-Hole Peg Test performance and grip force. Interpretation: These results demonstrate that parietofrontal motor system integration during visually guided movements is stronger in the stroke-lesioned brain. The correlation with the residual motor deficit could either indicate an unspecific marker of motor network damage or it might indicate that upregulated parietofrontal connectivity has some impact on post-stroke motor function.

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.

Collective hydrogen-bond rearrangement dynamics in liquid water.

We investigate barrier-crossing processes corresponding to collective hydrogen-bond rearrangements in liquid water using Markov state modeling techniques. The analysis is based on trajectories from classical molecular dynamics simulations and accounts for the full dynamics of relative angular and separation coordinates of water clusters and requires no predefined hydrogen bond criterium. We account for the complete 12-dimensional conformational subspace of three water molecules and distinguish five well-separated slow dynamic processes with relaxation times in the picosecond range, followed by a quasi-continuum spectrum of faster modes. By analysis of the Markov eigenstates, these processes are shown to correspond to different collective interchanges of hydrogen-bond donors and acceptors. Using a projection onto hydrogen-bond states, we also analyze the switching of one hydrogen bond between two acceptor water molecules and derive the complete transition network. The most probable pathway corresponds to a direct switch without an intermediate, in agreement with previous studies. However, a considerable fraction of paths proceeds along alternative routes that involve different intermediate states with short-lived alternative hydrogen bonds or weakly bound states.

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.

Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon.

BACKGROUND: Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. RESULTS: Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b, miR-222a/b, miR-190a) or have now been found connected (miR-2188, miR-144, miR-731, miR-8157 and the novel n2) to the initiation of puberty. CONCLUSIONS: This study has - for the first time - linked testis maturation to specific miRNAs and their inversely correlated expressed targets in Atlantic salmon. The study indicates a broad functional conservation of already known miRNAs and associated pathways involved in the transition into puberty in vertebrates. The analysis also reveals miRNAs not previously associated with testis tissue or its maturation, which calls for further functional studies in the testis.

Magnetic resonance imaging-based evaluation of ossification of the medial clavicular epiphysis in forensic age assessment.

Evaluation of the degree of ossification of the medial clavicular epiphysis plays a crucial role in determining with an adequate degree of probability whether legally relevant age boundaries after the age of 17 have been crossed. In view of the need to avoid unnecessary radiation exposure, establishing non-X-ray methods for investigating the clavicle has long been a key objective in forensic age assessment research. Based on magnetic resonance imaging examinations in a large sample of healthy subjects, the current study for the first time presents statistical measures which allow inferences to be drawn for forensic age assessment in both sexes. We undertook a prospective study of a reference sample of 334 female and 335 male German volunteers aged from 12 to 24 using a 3-T MRI scanner. A 3D FFE (fast field echo) T1-weighted sequence with fat saturation was acquired. To stage ossification of the medial clavicular epiphysis, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IIIc offers a means in both sexes of demonstrating that the age of 18 has been attained prior to complete ossification of the epiphyseal plate. In both sexes, if a subject has reached ossification stage IV, it can be stated that he or she has attained the age of 21. Magnetic resonance imaging is a valid diagnostic procedure for determining the ossification stage of the medial clavicular epiphysis.