Lymphedema after pelvic and para-aortic lymphadenectomy—results of a systematic evaluation in patients with cervical and endometrial carcinoma

Background Lymphedema is a frequent complication after surgical treatment in gynecological oncology with substantial impact on patients ' Quality of Life (QoL). Little is known about screening instruments and prevention. Primary objective was to develop and validate the German version of a 13 items screening questionnaire (SQ) developed by Yost et al. to provide a valid instrument for early diagnosis of lower extremity lymphedema (LEL). Methods After translation the SQ was used in pt. with cervical or endometrial cancer who underwent pelvic/paraaortic Lymphadenectomy. Sensitivity and specifity were analysed regarding possible prediction and influencing factors of LEL. Results 67 pt. had LEL (N = 128). Nearly 50% of women in each group (38 in LEL + e 30 in LEL - ) had a body mass index (BMI) > 30 kg/m(2). Number of removed lymphnodes, radiotherapy and were significantly associated with development of LEL. Translated Mayo Clinic questionnaire can be used with reliable specifity and sensitivity. Four additional questions improved the diagnostic accuracy of the SQ. Conclusions The translated SQ is a valuable and predictive tool for screening and early detection of LEL in Gynecological cancer surgery and can even improved by adding simple questions

Reduced Anxiety and Depression-Like Behaviours in the Circadian Period Mutant Mouse Afterhours

Disruption of the circadian rhythm is a key feature of bipolar disorder. Variation in genes encoding components of the molecular circadian clock has been associated with increased risk of the disorder in clinical populations. Similarly in animal models, disruption of the circadian clock can result in altered mood and anxiety which resemble features of human mania; including hyperactivity, reduced anxiety and reduced depression-like behaviour. One such mutant, after hours (Afh), an ENU-derived mutant with a mutation in a recently identified circadian clock gene Fbxl3, results in a disturbed (long) circadian rhythm of approximately 27 hours.Anxiety, exploratory and depression-like behaviours were evaluated in Afh mice using the open-field, elevated plus maze, light-dark box, holeboard and forced swim test. To further validate findings for human mania, polymorphisms in the human homologue of FBXL3, genotyped by three genome wide case control studies, were tested for association with bipolar disorder.Afh mice showed reduced anxiety- and depression-like behaviour in all of the behavioural tests employed, and some evidence of increased locomotor activity in some tests. An analysis of three separate human data sets revealed a gene wide association between variation in FBXL3 and bipolar disorder (P = 0.009).Our results are consistent with previous studies of mutants with extended circadian periods and suggest that disruption of FBXL3 is associated with mania-like behaviours in both mice and humans

Inductive localization accuracy of a passive 3-D coil in an Industry 4.0 environment

In this paper a localization system of a passive 3-D coil is proposed and signal uncertainties due to the 3-D coil's arbitrary orientation are analyzed. The 3-D coil is excited by an alternating primary magnetic field. Geometrically distributed pick-up coils measure the 3-D coil's secondary field. By means of a simulated look-up table that assigns expected voltages from the pick-up coils to the positions of the 3-D coil, the position of the 3-D coil is deduced by a least-squares approach. A basic assumption is that the secondary field is invariant to the orientation of the 3-D coil. This allows a reduction of the computational effort for the look-up table generation and the table search during the localization phase since for each position the field distribution for only one orientation has to be calculated. However, the assumption of invariance to rotation is only valid for a dipole model. In this paper we investigate the localization error introduced by this assumption when using 3-D coils with a geometric extent in an inhomogeneous primary field. Optimized localization methods that decrease the statistical error are proposed. The theoretical results are verified with measurements conducted on a laboratory system.</p

A Gene for Universal Congenital Alopecia Maps to Chromosome 8p21-22

SummaryComplete or partial congenital absence of hair (congenital alopecia) may occur either in isolation or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal-recessive mode of inheritance (MIM 203655). As yet, no gene has been linked to isolated congenital alopecia, nor has linkage been established to a specific region of the genome. In an attempt to map the gene for the autosomal recessive form of the disorder, we have performed genetic linkage analysis on a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia). We have analyzed individuals of this family, using >175 microsatellite polymorphic markers of the human genome. A maximum LOD score of 7.90 at a recombination fraction of 0 has been obtained with locus D8S258. Haplotype analysis of recombination events localized the disease to a 15-cM region between marker loci D8S261 and D8S1771. We have thus mapped the gene for this hereditary form of isolated congenital alopecia to a locus on chromosome 8p21-22 (ALUNC [alopecia universalis congenitalis]). This will aid future identification of the responsible gene, which will be extremely useful for the understanding of the biochemistry of hair development

Immunoisolating poly(ethylene glycol) based capsules support ovarian tissue survival to restore endocrine function

A common irreversible adverse effect of life‐saving anticancer treatments is loss of gonadal endocrine function and fertility, calling for a need to focus on post‐treatment quality of life. Here, we investigated the use of poly(ethylene glycol)‐vinyl sulfone (PEG‐VS) based capsules to support syngeneic donor ovarian tissue for restoration of endocrine function in mice. We designed a dual immunoisolating capsule (PEG‐Dual) by tuning the physical properties of the PEG hydrogels and combining proteolytically degradable and nondegradable layers to meet the numerous requirements for encapsulation and immunoisolation of ovarian tissue, such as nutrient diffusion and tissue expansion. Tuning the components of the PEG‐Dual capsule to have similar physical properties allowed for concentric encapsulation. Upon implantation, the PEG‐based capsules supported ovarian tissue survival and led to a significant decrease in follicle stimulating hormone levels 60 days postimplantation. Mice that received the implants resumed regular estrous cycle activity and follicle development in the implanted grafts. The PEG‐Dual capsule provided an environment conducive for tissue survival, while providing a barrier to the host environment. This study demonstrated for the first time that immunoisolating PEG‐VS capsules can support ovarian follicular development resulting in the restoration of ovarian endocrine function and can be applied to future allogeneic studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1381–1389, 2018.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142967/1/jbma36338_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142967/2/jbma36338.pd

Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine.

In a wide range of neuroblastoma-derived lines oxovanadium compounds such as bis(maltolato)oxovanadium(IV) (BMOV) are cytotoxic. This is not explained by oxidative stress or inhibition of ion channels. Genotoxicity is unlikely given that a p53 response is absent and p53-mutant lines are also sensitive. Cytotoxicity is inhibited by N-acetyl cysteine and glutathione ester, indicating that BMOV action is sensitive to cytoplasmic redox and thiol status. Significantly, combining BMOV with glutathione synthesis inhibition greatly enhances BMOV-induced cell death. This combination treatment triggers high AKT pathway activation, highlighting the potential functional importance of PTP inhibition by BMOV. AKT activation itself, however, is not required for cytotoxicity. Oxovanadium compounds may thus represent novel leads as p53-independent therapeutics for neuroblastoma

Physicochemical and Biological Characterisation of Diclofenac Oligomeric Poly(3-hydroxyoctanoate) Hybrids as β-TCP Ceramics Modifiers for Bone Tissue Regeneration

Nowadays, regenerative medicine faces a major challenge in providing new, functional materials that will meet the characteristics desired to replenish and grow new tissue. Therefore, this study presents new ceramic-polymer composites in which the matrix consists of tricalcium phosphates covered with blends containing a chemically bounded diclofenac with the biocompatible polymer-poly(3-hydroxyoctanoate), P(3HO). Modification of P(3HO) oligomers was confirmed by NMR, IR and XPS. Moreover, obtained oligomers and their blends were subjected to an in-depth characterisation using GPC, TGA, DSC and AFM. Furthermore, we demonstrate that the hydrophobicity and surface free energy values of blends decreased with the amount of diclofenac modified oligomers. Subsequently, the designed composites were used as a substrate for growth of the pre-osteoblast cell line (MC3T3-E1). An in vitro biocompatibility study showed that the composite with the lowest concentration of the proposed drug is within the range assumed to be non-toxic (viability above 70%). Cell proliferation was visualised using the SEM method, whereas the observation of cell penetration into the scaffold was carried out by confocal microscopy. Thus, it can be an ideal new functional bone tissue substitute, allowing not only the regeneration and restoration of the defect but also inhibiting the development of chronic inflammation