Mn-labelled Beta-cyclodextrin for Melanoma Imaging: A Proof-of-concept Preclinical Study.

Background/aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled (Mn) randomly methylated beta-cyclodextrin ([Mn]Mn-DOTAGA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [Ga]Ga-DOTA-NAPamide and PGE2 selective [Ga]Ga-DOTAGA-RAMEB cyclodextrin.

Materials And Methods: Post-injection of [Ga]Ga-DOTA-NAPamide, [Ga]Ga-DOTAGA-RAMEB, and [Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter.

The DNA damage response of , revisited: Differential gene expression after replication inhibition.

In 1967, in this journal, Evelyn Witkin proposed the existence of a coordinated DNA damage response in , which later came to be called the "SOS response." We revisited this response using the replication inhibitor azidothymidine (AZT) and RNA-Seq analysis and identified several features. We confirm the induction of classic Save our ship (SOS) loci and identify several genes, including many of the pyrimidine pathway, that have not been previously demonstrated to be DNA damage-inducible.

Acute Myelomonoblastic Leukemia (My1/De): A Preclinical Rat Model.

Background/aim: Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and whole-body autoradiography.

Materials And Methods: In vitro [F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions.

Concomitant [F]F-FAZA and [F]F-FDG Imaging of Gynecological Cancer Xenografts: Insight into Tumor Hypoxia.

Background/aim: Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [F]F-FAZA and [F]F-FDG in bypassing the limitations derived from the non-specific findings of [F]F-FDG PET imaging of tumor-related hypoxia.

Materials And Methods: CoCl-generated hypoxia was induced in multidrug resistant (Pgp+) or sensitive (Pgp-) human ovarian (Pgp- A2780, Pgp+ A2780AD), and cervix carcinoma (Pgp- KB-3-1, Pgp+ KB-V-1) cell lines to establish corresponding tumor-bearing mouse models. Prior to [F]F-FDG/[F]F-FAZA-based MiniPET imaging, in vitro [F]F-FDG uptake measurements and western blotting were used to verify the presence of hypoxia.

Optimization of RNA Extraction from Dry Blood Spots for Nanostring Analysis.

Dry blood spot (DBS) technology has been widely used since the 1960's for the detection of protein biomarkers associated with various disease states. In this manuscript we report a revised approach using DBS samples to extract total RNA for use in downstream multiplex RNA detection methodology (Nanostring). To accomplish this objective, we have used commercially available supplies, kits, and equipment to ensure that the procedure described in this report can be adopted by any laboratory.

Magnetic Isolation, RNA Extraction, and Nanostring Analysis of Human Peripheral Blood Leukocytes Subsets.

Advancements in multiplexed molecular biology techniques have allowed for blood samples and specific circulating blood leukocytes to be a useful sample source when examining systemic changes associated with changes in body weight, muscle injury, disease onset/progression, and other common conditions. One gap in the current scientific knowledge relates to the impact of changes in individual leukocyte subsets on the overall systemic response. While many studies have published data related to changes observed in a mixed population of circulating leukocytes (i.

An Exploratory Study Provides Insights into MMP9 and Aβ Levels in the Vitreous and Blood across Different Ages and in a Subset of AMD Patients.

Matrix metalloproteinase-9 (MMP9) and total amyloid-beta (Aβ) are prospective biomarkers of ocular ageing and retinopathy. These were quantified by ELISA in the vitreous and blood from controls ( = 55) and in a subset of age-related macular degeneration (AMD) patients ( = 12) for insights and possible additional links between the ocular and systemic compartments. Vitreous MMP9 levels in control and AMD groups were 932.

DnaA and SspA regulation of the iraD gene of Escherichia coli: an alternative DNA damage response independent of LexA/RecA.

The transcription factor RpoS of Escherichia coli controls many genes important for tolerance of a variety of stress conditions. IraD promotes the post-translation stability of RpoS by inhibition of RssB, an adaptor protein for ClpXP degradation. We have previously documented DNA damage induction of iraD expression, independent of the SOS response.

[Augmentation of the vertical bone defects of the mandible and maxilla with autogenous bone block].

Introduction: Vertical augmentation of the alveolar process for dental implantation is a well-established approach. The literature suggests that vertical ridge augmentation is associated with an elevated risk of complications and bone resorption compared to lateral bone augmentation or sinus elevation. Objective: We sought to retrospectively analyze the long-term success of vertical augmentation in terms of bone stability and complications.

Esthetic and functional reconstruction of large mandibular defects using free fibula flap and implant-retained prosthetics - a case series with long-term follow-up.

Background: The reconstructive and rehabilitative management of large mandibular defects with basal continuity is challenging in many respects, especially in the vertical dimension. The free fibula flap is an under-utilised but efficient approach in this indication. The aim of this case series is to demonstrate its use and long-term success.

Vertical mandibular bone augmentation by the osteodistraction of the transplanted fibula free flap: A case series with long-term follow-up.

Vertical augmentation of the mandible to prepare dental implant therapy is still a challenge, especially with large mandible defects. Reconstruction with fibula free flap is a regularly applied approach in such cases, but it does not always yield optimal results: the resulting crestal height might differ significantly from the crestal height of the patient's intact bone, which makes esthetic and functional rehabilitation difficult. Osteodistraction of the integrated flap is a known but rarely discussed approach where the already integrated flap undergoes additional distraction.

High-Throughput Method for Measuring Alcohol Sedation Time of Individual Drosophila melanogaster.

Drosophila melanogaster provides an excellent model to study the genetic underpinnings of alcohol sensitivity. In contrast to studies in human populations, the Drosophila model allows strict control over genetic background, and virtually unlimited numbers of individuals of the same genotype can be reared rapidly under well-controlled environmental conditions without regulatory restrictions and at relatively low cost. Flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance.

Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive disease occurring during childhood. The gene responsible for disease development is a ubiquitously expressed protein, IGHMBP2. Mutations in IGHMBP2 result in the loss of α-motor neurons leading to muscle atrophy in the distal limbs accompanied by respiratory complications.

A longitudinal study on bone mineral density until adulthood in girls with Turner's syndrome participating in a growth hormone injection frequency-response trial.

Objective: The aim of this study was to assess the volumetric bone mineral density (BMD) in girls with Turner's syndrome (TS) before and during growth hormone (GH) treatment in combination with low dose oestrogens as well as three years after discontinuation of GH treatment.

Design: In a prospective, randomized injection frequency-response study, the effect of GH treatment in combination with low dose ethinyl oestradiol (starting with 0.05 microgram/kg/day), on BMD was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 IU/m2/day until adult height was reached.

Physician ownership of ancillary services: indirect demand inducement or quality assurance?

This paper analyzes two competing explanations for the ownership of ancillary facilities by referring physicians: indirect demand inducement and quality assurance. Consistent with the demand-inducement explanation we find physician-owned clinics treat patients for 50 percent more visits than do independent clinics and the differential is directly related to factors facilitating demand inducement. We find no difference in quality of care across ownership structures, however.