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1.
Int J Legal Med ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822837

RESUMO

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.

2.
Nature ; 523(7560): 352-6, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-26009011

RESUMO

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.


Assuntos
Linfoma/tratamento farmacológico , Linfoma/metabolismo , Terapia de Alvo Molecular/métodos , Proteínas Mutantes/antagonistas & inibidores , Estabilidade Proteica , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Alelos , Aloenxertos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Desacetilase 6 de Histona , Histona Desacetilases/metabolismo , Humanos , Linfoma/genética , Linfoma/patologia , Masculino , Camundongos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Transplante de Neoplasias , Estabilidade Proteica/efeitos dos fármacos , Taxa de Sobrevida , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Triazóis/farmacologia , Triazóis/uso terapêutico , Proteína Supressora de Tumor p53/genética
3.
Ecotoxicol Environ Saf ; 209: 111848, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421672

RESUMO

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.


Assuntos
Anfípodes/fisiologia , Fungicidas Industriais/toxicidade , Estrobilurinas/toxicidade , Poluentes Químicos da Água/toxicidade , Anfípodes/efeitos dos fármacos , Animais , Dieta , Ecossistema , Folhas de Planta/metabolismo , Pirimidinas , Rios , Testes de Toxicidade Crônica
4.
Int J Legal Med ; 134(2): 745-751, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31907616

RESUMO

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.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Determinação da Idade pelo Esqueleto/estatística & dados numéricos , Clavícula/diagnóstico por imagem , Medicina Legal , Ossos da Mão/diagnóstico por imagem , Menores de Idade/legislação & jurisprudência , Adolescente , Determinação da Idade pelos Dentes , Feminino , Alemanha , Humanos , Masculino , Exame Físico , Radiografia Panorâmica , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
Aging Clin Exp Res ; 31(12): 1839-1842, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30623316

RESUMO

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.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Masculino , Estudos Retrospectivos , Medição de Risco/métodos
6.
Eur Cell Mater ; 35: 225-241, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29683471

RESUMO

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.


Assuntos
Corantes Azur/metabolismo , Condrócitos/metabolismo , Bandeamento Cromossômico , Loci Gênicos , Genômica/métodos , Hibridização in Situ Fluorescente , Polimorfismo de Nucleotídeo Único/genética , Cariotipagem Espectral , Idoso , Biópsia , Células Cultivadas , Aberrações Cromossômicas , Cromossomos Humanos/genética , Variações do Número de Cópias de DNA/genética , Endorreduplicação/genética , Feminino , Humanos , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Poliploidia , Esferoides Celulares/citologia
7.
J Chem Phys ; 149(24): 244504, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30599706

RESUMO

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.

8.
Z Gerontol Geriatr ; 51(2): 231-236, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28660533

RESUMO

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.


Assuntos
Anemia/epidemiologia , Leucopenia/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Trombocitopenia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Estudos de Coortes , Estudos Transversais , Contagem de Eritrócitos , Índices de Eritrócitos/efeitos dos fármacos , Feminino , Hemoglobinometria , Hospitais Urbanos , Humanos , Contagem de Leucócitos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/induzido quimicamente
9.
BMC Genomics ; 18(1): 801, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-29047327

RESUMO

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.


Assuntos
Perfilação da Expressão Gênica , MicroRNAs/genética , Puberdade/genética , Salmo salar/genética , Salmo salar/fisiologia , Testículo/metabolismo , Animais , Masculino , RNA Mensageiro/genética
10.
Int J Legal Med ; 131(6): 1665-1673, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28889331

RESUMO

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.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Clavícula/crescimento & desenvolvimento , Epífises/crescimento & desenvolvimento , Imageamento por Ressonância Magnética , Osteogênese , Adolescente , Criança , Clavícula/diagnóstico por imagem , Epífises/diagnóstico por imagem , Feminino , Antropologia Forense , Alemanha , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
11.
Int J Legal Med ; 131(2): 579-584, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27924404

RESUMO

To improve the accuracy of forensic age estimation where there is no legal basis for carrying out x-ray examinations, it would be useful to establish non-x-ray imaging techniques. The objective of this study was to provide reference data for the magnetic resonance imaging-based evaluation of the ossification stage of the distal radius. Furthermore, we tested a new criterion of the maturity of the distal radial epiphysis for determining whether an individual has completed the age of 18. We investigated 668 MRI scans of the distal radial epiphysis from 333 female and 335 male subjects ranging in age from 12 to 24. To determine the ossification stage, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IV as described by Schmeling et al. was divided into two sub-stages, IVa and IVb, depending on whether or not it was possible to identify a triple-banded meta-epiphyseal zone of calcification. All study subjects were able to be assigned to an ossification stage without ambiguity. We present statistics relating to the distribution of ossification stages divided by sex. The age of the youngest female subject assessed as ossification stage IVb was 16.8, the age of the youngest male subject 18.6. The youngest age at which female subjects were assessed as ossification stage V was 22.3; for male subjects it was 23.1. Further independent studies should be carried out to determine whether ossification stage IVb can indeed be used to reliably determine whether a male subject has completed the age of 18.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Epífises/crescimento & desenvolvimento , Osteogênese , Rádio (Anatomia)/crescimento & desenvolvimento , Adolescente , Criança , Epífises/diagnóstico por imagem , Feminino , Antropologia Forense , Humanos , Imageamento por Ressonância Magnética , Masculino , Rádio (Anatomia)/diagnóstico por imagem , Adulto Jovem
12.
Gesundheitswesen ; 79(6): 514-520, 2017 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-27171732

RESUMO

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.


Assuntos
Censos , Coleta de Dados/estatística & dados numéricos , Atenção à Saúde/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde/estatística & dados numéricos , Indicadores Básicos de Saúde , Programas Nacionais de Saúde/organização & administração , Diabetes Mellitus/epidemiologia , Alemanha , Humanos , Renda/estatística & dados numéricos , Cobertura do Seguro/estatística & dados numéricos , Modelos Lineares , Métodos de Controle de Pagamentos/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Análise de Pequenas Áreas , Revisão da Utilização de Recursos de Saúde/estatística & dados numéricos
13.
J Fish Biol ; 90(4): 1597-1608, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28097662

RESUMO

Thermal requirements of larval weatherfish Misgurnus fossilis were investigated in terms of growth, survival and aerobic performance. Growth and survival of M. fossilis larvae acclimated to five temperatures (11, 15, 19, 23 and 27° C) were measured over 25 days. In the upper temperature treatments (19, 23 and 27° C), survival of larvae was stable throughout the entire rearing period (>75%), whereas 11 and 15° C resulted in severe declines in survival (to <10%). Growth of larvae (expressed as dry mass and total length) was highest at 19 and 23° C, but significantly decreased at 27° C. Routine metabolic rate of 3 days post-hatch larvae was estimated as oxygen consumption rate (MO2 ) during acute exposure (30 min to 1 h) to seven temperatures (11, 15, 19, 23, 27, 31 and 35° C). Larval oxygen uptake increased with each consecutive temperature step from 11 to 27° C, until a plateau was reached at temperatures >27° C. All larvae of the 35° C regime, however, died within the MO2 measurement period. M. fossilis larvae show greater than expected tolerance of high temperatures. On the other hand, low temperatures that are within the range of likely habitat conditions are critical because they might lead to high mortality rates when larvae are exposed over periods >10 days. These findings help to improve rearing conditions and to identify suitable waters for stocking and thus support the management of re-introduction activities for endangered M. fossilis.


Assuntos
Cipriniformes/crescimento & desenvolvimento , Consumo de Oxigênio , Temperatura , Animais , Cipriniformes/fisiologia , Larva/crescimento & desenvolvimento
14.
Cell Tissue Res ; 363(2): 579-88, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26077926

RESUMO

INSL3 (insulin-like peptide 3) is a relaxin peptide family member expressed by Leydig cells in the vertebrate testis. In mammals, INSL3 mediates testicular descent during embryogenesis but information on its function in adults is limited. In fish, the testes remain in the body cavity, although the insl3 gene is still expressed, suggesting yet undiscovered, evolutionary older functions. Anti-Müllerian hormone (Amh), in addition to inhibiting spermatogonial differentiation and androgen release, inhibits the Fsh (follicle-stimulating hormone)-induced increase in insl3 transcript levels in zebrafish testis. Therefore, the two growth factors might have antagonistic effects. We examine human INSL3 (hINSL3) effects on zebrafish germ cell proliferation/differentiation and androgen release by using a testis tissue culture system. hINSL3 increases the proliferation of type A undifferentiated (Aund) but not of type A differentiating (Adiff) spermatogonia, while reducing the proliferation of Sertoli cells associated with proliferating Aund. Since the area occupied by Aund decreases and that of Adiff increases, we conclude that hINSL3 recruits Aund into differentiation; this is supported by the hINSL3-induced down-regulation of nanos2 transcript levels, a marker of single Aund spermatogonia in zebrafish and other vertebrates. Pulse-chase experiments with a mitosis marker also indicate that hINSL3 promotes spermatogonial differentiation. However, hINSL3 does not modulate basal or Fsh-stimulated androgen release or growth factor transcript levels, including those of amh. Thus, hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis.


Assuntos
Envelhecimento/fisiologia , Diferenciação Celular/efeitos dos fármacos , Insulina/farmacologia , Proteínas/farmacologia , Espermatogônias/citologia , Peixe-Zebra/crescimento & desenvolvimento , Envelhecimento/efeitos dos fármacos , Androgênios/metabolismo , Animais , Bromodesoxiuridina/metabolismo , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Masculino , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Testículo , Peixe-Zebra/genética
15.
Eur Cell Mater ; 31: 119-35, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26853622

RESUMO

Objective and sensitive assessment of cartilage repair outcomes lacks suitable methods. This study investigated the feasibility of 3D ultrasound biomicroscopy (UBM) to quantify cartilage repair outcomes volumetrically and their correlation with established classification systems. 32 sheep underwent bilateral treatment of a focal cartilage defect. One or two years post-operatively the repair outcomes were assessed and scored macroscopically (Outerbridge, ICRS-CRA), by magnetic resonance imaging (MRI, MOCART), and histopathology (O'Driscoll, ICRS-I and ICRS-II). The UBM data were acquired after MRI and used to reconstruct the shape of the initial cartilage layer, enabling the estimation of the initial cartilage thickness and defect volume as well as volumetric parameters for defect filling, repair tissue, bone loss and bone overgrowth. The quantification of the repair outcomes revealed high variations in the initial thickness of the cartilage layer, indicating the need for cartilage thickness estimation before creating a defect. Furthermore, highly significant correlations were found for the defect filling estimated from UBM to the established classification systems. 3D visualisation of the repair regions showed highly variable morphology within single samples. This raises the question as to whether macroscopic, MRI and histopathological scoring provide sufficient reliability. The biases of the individual methods will be discussed within this context. UBM was shown to be a feasible tool to evaluate cartilage repair outcomes, whereby the most important objective parameter is the defect filling. Translation of UBM into arthroscopic or transcutaneous ultrasound examinations would allow non-destructive and objective follow-up of individual patients and better comparison between the results of clinical trials.


Assuntos
Osso e Ossos/diagnóstico por imagem , Cartilagem Articular , Microscopia Acústica/métodos , Animais , Desenvolvimento Ósseo/fisiologia , Osso e Ossos/citologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Cartilagem Articular/cirurgia , Método Duplo-Cego , Feminino , Estudos Prospectivos , Distribuição Aleatória , Reprodutibilidade dos Testes , Ovinos , Cicatrização/fisiologia
16.
Mol Psychiatry ; 20(3): 353-60, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24798585

RESUMO

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.


Assuntos
Doença de Alzheimer/terapia , Núcleo Basal de Meynert/fisiologia , Estimulação Encefálica Profunda/métodos , Resultado do Tratamento , Idoso , Doença de Alzheimer/diagnóstico , Eletroencefalografia , Feminino , Fluordesoxiglucose F18/farmacocinética , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Escalas de Graduação Psiquiátrica , Qualidade de Vida
17.
Int J Legal Med ; 130(6): 1615-1621, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27631994

RESUMO

Evaluation of the ossification of the medial clavicular epiphysis plays a key role in forensic age estimation, particularly in determining whether the age of 18 has been attained. A key research objective in the forensic age estimation field at present is to establish non-X-ray methods for investigating the clavicle. This paper looks at the use of magnetic resonance imaging for evaluating the developmental state of the medial clavicular epiphysis. Clavicle specimens obtained from autopsies of 125 female and 270 male subjects aged from 10 to 30 were examined using a 3-T magnetic resonance scanner. One FFE-3D-T1 gradient echo sequence and one 2D-T2 turbo spin echo sequence were acquired. In each case, two investigators undertook a consensual determination of the ossification stage of the medial clavicular epiphysis using recognised classification systems. To determine intra-observer and inter-observer agreement, 80 clavicle specimens were subjected to repeat evaluation. We present statistics relating to the ossification stages. The inclusion of established sub-stages of clavicular ossification offers an additional option for determining whether a subject has attained the age of 18 which is applicable in both sexes. For both sexes, the minimum ages for ossification stages 4 and 5 allow conclusions to be drawn about a subject's age at a point in time lying several years in the past. Magnetic resonance imaging is a valid investigatory procedure for determining the ossification stage of the medial clavicular epiphysis. This paper makes a contribution to expanding the range of methods available for forensic age estimation.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Clavícula/diagnóstico por imagem , Epífises/diagnóstico por imagem , Osteogênese , Adolescente , Adulto , Criança , Clavícula/anatomia & histologia , Epífises/anatomia & histologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
19.
J Appl Clin Med Phys ; 22(1): 350, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33395502
20.
Z Gerontol Geriatr ; 49(3): 227-31, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26062963

RESUMO

BACKGROUND: The implementation of a computerized physician order entry (CPOE) can help reduce prescription errors in clinical practice. OBJECTIVE: The aim of this study was to evaluate the effects of a CPOE for geriatric patients with the two most common conditions for drug-induced iatrogenic diseases, dysphagia and renal failure. SUBJECTS AND METHODS: A retrospective analysis of actual drug prescriptions versus CPOE recommendations in the geriatric department of the St. Marien Hospital in Cologne, Germany was carried out. Actual drug prescriptions were collected for 26 patients with dysphagia (15 female, 11 male, average age 82.3 ± 8.0 years) and 35 patients with renal failure (23 female, 12 male, average age 80.5 ± 6.7 years) which were compared with recommended prescriptions by means of a CPOE and discrepancies were statistically analyzed. RESULTS: Prescription errors for at least 1 drug were detected in 46 % of patients with renal failure and the administration of at least 1 drug with inadequate crushing was observed in 77 % of dysphagia patients. CONCLUSION: Prescription errors appear to be frequent to highly frequent in the medical routine even in a highly specialized geriatric setting. Inaccuracies might be reduced by the implementation of a CPOE and even more if coupled to a decision support system. Drug-drug or drug-disease interactions, which are particularly high risks in patients with multimorbidities, multidrug therapy, renal failure or malnutrition, might be kept under control through careful verification of medication indications, organ function status as well as drug administration and preparation in cases of tube feeding.


Assuntos
Transtornos de Deglutição/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Sistemas de Registro de Ordens Médicas/estatística & dados numéricos , Erros de Medicação/prevenção & controle , Erros de Medicação/estatística & dados numéricos , Insuficiência Renal/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/epidemiologia , Alemanha/epidemiologia , Humanos , Masculino , Insuficiência Renal/epidemiologia , Estudos Retrospectivos
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