PurposeThe coronavirus disease 2019 (COVID-19) pandemic is projected to drive 1.5 million Americans toward homelessness, adding to the 3.5 million currently affected. Homelessness poses both socioeconomic and public health challenges because housing status is a social determinant of health. Given ophthalmic health's importance in daily functioning, we characterized ophthalmic disease and vision-related quality of life (VRQOL) among a population experiencing homelessness in Baltimore, Maryland.MethodsQuestionnaires, including a Visual Function Index-14 (VF-14) for measuring VRQOL, were administered among patients seeking eye examinations at Health Care for the Homeless (HCH) from October 2018 to March 2020.ResultsOne hundred sixty-two participants were enrolled in this study. The average age was 53 years. Participants' most common vision concerns were blurry vision (70%) and desire for glasses (52%). Best corrected visual acuity (BCVA) measurements revealed significant vision loss (18%, P < 0.001). Physicians mostly diagnosed refractive error (77%), cataracts (36%), glaucoma/glaucoma suspect (25%), and dry eye (24%). Nearly half were referred to additional ophthalmic care (46%). VRQOL trends reflected functional vision categories (P = 0.042 and P = 0.021). The 1:1 VRQOL and BCVA comparison showed correlation (rho = -0.3, P < 0.001). Cronbach's alpha demonstrated VF-14 reliability (alpha = 0.92).ConclusionsWe find high ophthalmic disease prevalence within a population experiencing homelessness. Comparison to studies worldwide reveals healthcare disparities despite healthcare system differences, suggesting a need for more targeted solutions. VF-14 is valid and reliable in assessing those experiencing homelessness. Intragroup VRQOL comparisons may reveal subgroup needs. It is imperative that future studies continue monitoring those experiencing homelessness.Translational RelevanceValidation of VF-14 will allow future studies to utilize this patient-oriented metric within populations experiencing homelessness.

01 Sep 2023·Journal of Cancer Research and Clinical Oncology

Synergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells

Article

Author: Henao-Restrepo, Julián Andrés ; Beck, James F ; Proquitté, Hans ; Becker, Sabine ; Sonnemann, Jürgen ; Sturm, Max-Johann

AbstractPurposeEwing’s sarcoma is a highly malignant childhood tumour whose outcome has hardly changed over the past two decades despite numerous attempts at chemotherapy intensification. It is therefore essential to identify new treatment options. The present study was conducted to explore the effectiveness of combined inhibition of two promising targets, ATR and ribonucleotide reductase (RNR), in Ewing’s sarcoma cells.MethodsEffects of the ATR inhibitor VE821 in combination with the RNR inhibitors triapine and didox were assessed in three Ewing’s sarcoma cell lines with different TP53 status (WE-68, SK-ES-1, A673) by flow cytometric analysis of cell death, mitochondrial depolarisation and cell cycle distribution as well as by caspase 3/7 activity determination, by immunoblotting and by real-time RT-PCR. Interactions between inhibitors were evaluated by combination index analysis.ResultsSingle ATR or RNR inhibitor treatment produced small to moderate effects, while their combined treatment produced strong synergistic ones. ATR and RNR inhibitors elicited synergistic cell death and cooperated in inducing mitochondrial depolarisation, caspase 3/7 activity and DNA fragmentation, evidencing an apoptotic form of cell death. All effects were independent of functional p53. In addition, VE821 in combination with triapine increased p53 level and induced p53 target gene expression (CDKN1A, BBC3) in p53 wild-type Ewing’s sarcoma cells.ConclusionOur study reveals that combined targeting of ATR and RNR was effective against Ewing’s sarcoma in vitro and thus rationalises an in vivo exploration into the potential of combining ATR and RNR inhibitors as a new strategy for the treatment of this challenging disease.

29 Jun 2023·Pathogens (Basel, Switzerland)

Hepatitis C Virus Down-Regulates the Expression of Ribonucleotide Reductases to Promote Its Replication.

Article

Author: Chan, Yu-Ru ; Li, Hui-Chun ; Lo, Shih-Yen ; Lua, Ahai-Chang ; Wu, Cheng-Hao ; Yang, Chee-Hing

Ribonucleotide reductases (RRs or RNRs) catalyze the reduction of the OH group on the 2nd carbon of ribose, reducing four ribonucleotides (NTPs) to the corresponding deoxyribonucleotides (dNTPs) to promote DNA synthesis. Large DNA viruses, such as herpesviruses and poxviruses, could benefit their replication through increasing dNTPs via expression of viral RRs. Little is known regarding the relationship between cellular RRs and RNA viruses. Mammalian RRs contain two subunits of ribonucleotide reductase M1 polypeptide (RRM1) and two subunits of ribonucleotide reductase M2 polypeptide (RRM2). In this study, expression of cellular RRMs, including RRM1 and RRM2, is found to be down-regulated in hepatitis C virus (HCV)-infected Huh7.5 cells and Huh7 cells with HCV subgenomic RNAs (HCVr). As expected, the NTP/dNTP ratio is elevated in HCVr cells. Compared with that of the control Huh7 cells with sh-scramble, the NTP/dNTP ratio of the RRM-knockdown cells is elevated. Knockdown of RRM1 or RRM2 increases HCV replication in HCV replicon cells. Moreover, inhibitors to RRMs, including Didox, Trimidox and hydroxyurea, enhance HCV replication. Among various HCV viral proteins, the NS5A and/or NS3/4A proteins suppress the expression of RRMs. When these are taken together, the results suggest that HCV down-regulates the expression of RRMs in cultured cells to promote its replication.

100 Deals associated with Didox

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiotoxicity	Phase 1	United States	Molecules For Health, Inc.	15 Apr 2006
Cytomegalovirus Infections	Phase 1	United States	Molecules For Health, Inc.	-
Breast Cancer	Preclinical	United States	Molecules For Health, Inc.	11 Nov 1995
Anemia, Sickle Cell	Preclinical	United States	Molecules For Health, Inc.	-
HIV Infections	Preclinical	United States	Molecules For Health, Inc.	-
Psoriasis	Preclinical	United States	Molecules For Health, Inc.	-

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