159 research outputs found

    Eye enucleation and exenteration in -cattle: a retrospective study of 38 cases (2013-2020).

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    INTRODUCTION The study aimed to describe clinical indications for eye enucleation and exenteration, the occurrence of complications and long-term outcome in cattle, and examine owners' attitude towards enucleation and exenteration and their satisfaction with the surgical outcome. Medical records from the two veterinary teaching hospitals in Switzerland were reviewed to identify cattle that underwent unilateral enucleation or exenteration between January 2013 and December 2020. Data extracted included medical history, ocular examination, clinical diagnosis, surgical procedure including anesthesia, suture material and pattern used, complications, and treatment thereof. Long-term follow-up was evaluated via national animal database inquiries to determine survival time and via owners' interviews with the use of a standardized questionnaire that included questions regarding the occurrence of complications and reason for culling, production performances and perceived quality of life after surgery, concerns, factors affecting the decision to proceed with surgery, and general satisfaction with the outcome. Descriptive statistics, Fisher's exact tests and unpaired t-test were used to summarize the data and assess association between variables. Association was considered significant if p < 0,05. Thirty-eight cases were identified, with a median age of 5 years. More than half of the cases (55,3 %) were diagnosed with non-neoplastic ocular lesions represented by severe trauma with loss of globe content, globe rupture with history of infectious keratoconjunctivitis or hypopyon, or congenital malformations. The remaining cases were diagnosed with neoplastic lesions, including ocular squamous cell carcinoma (OSCC), melanoma, or sarcoma. Complications following surgery were reported in 29 % of cases and included postoperative infection and recurrence of OSCC. There was no significant association between ocular diagnosis and the occurrence of postoperative complications or survival time. Surgery did not seem to influence the animals' postoperative production performance or the perceived quality of life. Most owners (92 %) were satisfied with the surgical outcome. The occurrence of postoperative complications leading to increased overall costs and culling was the main reason for lower owner satisfaction

    CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II

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    Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m−2) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN+). Median age was 60 years (range 43–75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2–15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48–0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population

    Tight-binding parameters for charge transfer along DNA

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    We systematically examine all the tight-binding parameters pertinent to charge transfer along DNA. The π\pi molecular structure of the four DNA bases (adenine, thymine, cytosine, and guanine) is investigated by using the linear combination of atomic orbitals method with a recently introduced parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are discussed and then used for calculating the corresponding wavefunctions of the two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases are in good agreement with available experimental values. Our results are then used for estimating the complete set of charge transfer parameters between neighboring bases and also between successive base-pairs, considering all possible combinations between them, for both electrons and holes. The calculated microscopic quantities can be used in mesoscopic theoretical models of electron or hole transfer along the DNA double helix, as they provide the necessary parameters for a tight-binding phenomenological description based on the π\pi molecular overlap. We find that usually the hopping parameters for holes are higher in magnitude compared to the ones for electrons, which probably indicates that hole transport along DNA is more favorable than electron transport. Our findings are also compared with existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table

    Epigenetics and the power of art

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    This review presents an epigenetic view on complex factors leading to development and perception of “genius.” There is increasing evidence which indicates that artistic creativity is influenced by epigenetic processes that act both as targets and mediators of neurotransmitters as well as steroid hormones. Thus, perception and production of art appear to be closely associated with epigenetic contributions to physical and mental health

    Cytotoxic T-cell precursor frequencies to HER-2 (369 – 377) in patients with HER-2/neu-positive epithelial tumours

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    HER-2/neu oncoprotein contains several major histocompatibility complex class I-restricted epitopes, which are recognised by cytotoxic T lymphocyte (CTL) on autologous tumours and therefore can be used in immune-based cancer therapies. Of these, the most extensively studied is HER-2(9(369)). In the present report, we used dendritic cells pulsed with HER-2(9(369)) to stimulate, in the presence of IL-7 and IL-12, the production of IFN-gamma by patients' CTL detected by the enzyme-linked immunosorbent spot-assay. Frequencies of peptide-specific precursors were estimated in HLA-A2, HLA-A3 and HLA-A26 patients with HER-2/neu-positive (+) breast, ovarian, lung, colorectal and prostate cancers and healthy individuals. We found increased percentages of such precursors in HLA-A2 (25%) and HLA-A26 (30%) patients, which were significantly higher (60%) in HLA-A3 patients. Our results demonstrate for the first time that pre-existing immunity to HER-2(9(369)) occurs in patients with colorectal, lung and prostate cancer. They also suggest that HER-2(9(369)) can be recognised by CTL, besides HLA-A2, also in the context of HLA-A3 and HLA-A26, thus increasing the applicability of HER-2(9(369))-based vaccinations in a considerably broader patients' population.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

    Impact of vitamin D metabolism on clinical epigenetics

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    The bioactive vitamin D (VD) metabolite, 1,25-dihydroxyvitamin D3 regulates essential pathways of cellular metabolism and differentiation via its nuclear receptor (VDR). Molecular mechanisms which are known to play key roles in aging and cancer are mediated by complex processes involving epigenetic mechanisms contributing to efficiency of VD-activating CYP27A1 and CYP27B1 or inactivating CYP24 enzymes as well as VDR which binds to specific genomic sequences (VD response elements or VDREs). Activity of VDR can be modulated epigenetically by histone acetylation. It co-operates with other nuclear receptors which are influenced by histone acetyl transferases (HATs) as well as several types of histone deacetylases (HDACs). HDAC inhibitors (HDACi) and/or demethylating drugs may contribute to normalization of VD metabolism. Studies link VD signaling through the VDR directly to distinct molecular mechanisms of both HAT activity and the sirtuin class of HDACs (SIRT1) as well as the forkhead transcription factors thus contributing to elucidate complex epigenetic mechanisms for cancer preventive actions of VD

    German S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" – long version of the update 2023

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    Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC

    Estrogen and Progestogen Correlates of the Structure of Female Copulation Calls in Semi-Free-Ranging Barbary Macaques (Macaca sylvanus)

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    Females of many Old World primates produce conspicuous vocalizations in combination with copulations. Indirect evidence exists that in Barbary macaques (Macaca sylvanus), the structure of these copulation calls is related to changes in reproductive hormone levels. However, the structure of these calls does not vary significantly around the timing of ovulation when estrogen and progestogen levels show marked changes. We here aimed to clarify this paradox by investigating how the steroid hormones estrogen and progesterone are related to changes in the acoustic structure of copulation calls. We collected data on semi-free-ranging Barbary macaques in Gibraltar and at La Forêt des Singes in Rocamadour, France. We determined estrogen and progestogen concentrations from fecal samples and combined them with a fine-grained structural analysis of female copulation calls (N = 775 calls of 11 females). Our analysis indicates a time lag of 3 d between changes in fecal hormone levels, adjusted for the excretion lag time, and in the acoustic structure of copulation calls. Specifically, we found that estrogen increased the duration and frequency of the calls, whereas progestogen had an antagonistic effect. Importantly, however, variation in acoustic variables did not track short-term changes such as the peak in estrogen occurring around the timing of ovulation. Taken together, our results help to explain why female Barbary macaque copulation calls are related to changes in hormone levels but fail to indicate the fertile phase

    SOLID-PHASE SYNTHESIS OF A SOMATOSTATIN AMIDE ANALOG USING ACID LABILE TERT-BUMEOC PROTECTION AND AN ACID LABILE ANCHOR GROUP

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    The solid phase synthesis of an amidated somatostatin analogue based on the principle of differentiated acidolysis is described. The acid labile and smoothly cleavable t-Bumeoc moiety (1% TFA/DCM) is used for temporary N(alpha)-protection of D- and L-amino acids and [4-[[[9H-fluoren-9-yl-methoxycarbonyl]amino](4-methoxyphenyl)met hyl]-2-methylphenoxy]acetic acid, attached to an aminomethylated polystyrene resin is used as acid sensitive linker of the solid carrier which releases the peptide in its amide form by treatment with TFA. Its preparation is described in detail
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