Short fractionation radiotherapy for early prostate cancer in the time of COVID-19: long-term excellent outcomes from a multicenter Italian trial suggest a larger adoption in clinical practice

Abstract Introduction: To evaluate stereotactic body radiotherapy (SBRT) in low-risk Prostate Cancer patients as preferred treatment option in emergency health conditions. Materials and methods: From April 2013 to September 2015, 28 patients with low-risk prostate cancer were prospectively enrolled. The SBRT prescribed dose was 36.25 Gy in 5 fractions, twice a week. Primary endpoints were acute and late toxicity. Secondary endpoints were biochemical recurrence free survival (bRFS) and overall survival. Results: Median follow-up was 65.5 months (range 52-81). No acute G3 or G4 toxicity was recorded. Acute G1 or G2 genitourinary (GU) toxicity occurred in 43% and acute G1-G2 gastrointestinal (GI) toxicity in 14%. Late G1 and G3 GU toxicity in 18% and 3.5%, respectively. The G3 toxicity was not directly attributable to radiotherapy. Late G1 GI toxicity occurred in 18%. 5yy bRFS was 96.5% (95% CI 82.3-99.4%). Conclusions: Stereotactic body radiotherapy for early prostate cancer reported safe toxicity profile and a good clinical outcome at the median follow-up of 5 years. It may be an useful option if radiotherapy is required in emergency medical conditions

Nitric Oxide (NO): An Emerging Target for the Treatment of Glaucoma

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Repeated dosing with NCX1404, a nitric oxide-donating pregabalin, re-establishes normal nociceptive responses in mice with streptozotocin-induced painful diabetic neuropathy

NCX1404 [(3S)-5-methyl-3-(((1-(4-(nitrooxy)butanoyloxy)ethoxy) carbonylamino) methyl)hexanoic acid] is a novel nitric oxide (NO)-donating pregabalin that is readily absorbed and processed in vivo to pregabalin and NO. We determined the antiallodynic response of NCX1404 after acute or after 7, 14, and 21 days of repeated daily oral dosing in mice with streptozotocin (STZ)-induced painful diabetic neuropathy (PDN). Pregabalin and its combination with the NO donor isosorbide mononitrate (ISMN) were used for comparison. The blood levels of pregabalin and nitrites, used as surrogate marker of NO release, after NCX1404 or pregabalin dosing were monitored in parallel experiments using liquid chromatography with tandem mass spectrometry (LC-MS/MS). NCX1404 and pregabalin resulted in similar pregabalin levels as it was their antiallodynic activity after acute dosing in STZ mice. However, NCX1404 resulted in disease-modifying properties when administered daily for 21 days, as indicated by the time- and dose-dependent reversal of STZ-induced mechanical allodynia (paw withdrawal threshold [PWT]Veh-21d = 1.3 v 0.15 g for vehicle; PWTNCX1404-21d = 1.4 ± 0.5 g, 2.9 ± 0.2 g∗ and 4.1 ± 0.2 g∗, respectively for 19, 63, and 190 μmol/kg, oral gavage [PO] of NCX1404; ∗P, 0.05 versus vehicle). This effect was not shared by pregabalin at equimolar doses (190 μmol/kg, PO, PWTPregab-21d = 1.4 ± 0.1 g∗, ∗P < 0.05 versus equimolar NCX1404). In addition, the NO donor ISMN (52.3 μmol/kg, PO) alone or combined with pregabalin (63 μmol/kg) was active at 7 days (PWTVeh-7d= 1.7 ± 0.16 g; PWTISMN-7d = 3.9 ± 0.34 g∗; PWTPregab-7d = 1.3 ± 0.07 g; PWTISMN+pregab-7d = 3.8 ± 0.29 g∗; ∗P, 0.05) but not at later time points. The long-term effect of NCX1404 was independent of residual drug exposure and lasted for several days after the treatment was stopped. In summary, like pregabalin, NCX1404 is an effective antiallodynic agent. Differently from pregabalin, repeated dosing of NCX1404 re-established normal nociceptive responses in STZ-induced PDN in mice

dHPLC efficiency for semi-automated cDNA-AFLP analyses and fragment collection in the apple scab-resistance gene model

01 Cover Photo by D. W. Hildie 02 Concerning Prayer by General Superintendent Charles H. Strickland 03 The Axe Is Laid At the Root of the Tree by Harold DeMott 04 The Upsetting Sin by Morris Chalfant 05 The Invitation by Frances Simpson 06 The Lord Is My Sheepherder by D. W. Hildie 07 Making Memories by James Hamilton 08 A Decorating—Or A Working Model? By Carl N. Hall 09 Peter, the Rock-Man—Reviewed by Don Hughes 10 Jesus Draws Men by George Privett 11 “I Will Praise Thee…” by M. A. (Bud) Lunn 12 A Daily Appointment with God by Lyle K. Potter 13 The Forever Christ by Charles Hastings Smith 14 Suffering and Darkness at Passiontide by Ruth A. Cameron 15 When I Can’t Sleep by Alice Hansche Mortenson 16 Editorials by W. E. McCumber 18 God’s World Insists on Responsibility by Theodore P. Esselstyn 30 News of Religion 31 Answer Corner 34 By All Means by Ronald M. Adamshttps://digitalcommons.olivet.edu/cotn_hoh/2213/thumbnail.jp

Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes

The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity

Envisioning the Future of European Food Systems: Approaches and Research Priorities After COVID-19

The COVID-19 pandemic unveiled the fragility of food sovereignty in cities and confirmed the close connection urban dwellers have with food. Although the pandemic was not responsible for a systemic failure, it suggested how citizens would accept and indeed support a transition toward more localized food production systems. As this attitudinal shift is aligned with the sustainability literature, this work aims to explore the tools and actions needed for a policy framework transformation that recognizes the multiple benefits of food systems, while considering local needs and circumstances. This perspective paper reviews the trends in production and consumption, and systematizes several impacts emerged across European food systems in response to the first wave of pandemic emergency, with the final aim of identifying challenges and future strategies for research and innovation toward the creation of resilient and sustainable city/region food systems. The proposal does not support a return to traditional small-scale economies that might not cope with the growing global population. It instead stands to reconstruct and upscale such connections using a “think globally act locally” mind-set, engaging local communities, and making existing and future citizen-led food system initiatives more sustainable. The work outlines a set of recommended actions for policy-makers: support innovative and localized food production, training and use of information and communication technology for food production and distribution; promote cross-pollination among city/region food systems; empower schools as agents of change in food provision and education about food systems; and support the development of assessment methodologies and the application of policy tools to ensure that the different sustainability dimensions of the food chain are considered