Broad-Spectrum Antiviral Activities of Neplanocin A, 3-Deazaneplanocin A, and Their 5'-Nor Derivatives

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were studied for their broad-spectrum antiviral potential. 3-Deazaneplanocin A, DHCA, and DHCDA proved specifically effective against vesicular stomatitis virus, vaccinia virus, parainfluenza virus, reovirus, and rotavirus. Their selectivity was greater than that of neplanocin A, particularly against vesicular stomatitis virus and rotavirus. As could be expected from adenosine analogs that are directly targeted at AdoHcy hydrolase, 3-deazaneplanocin A, DHCA, and DHCDA were fully active in adenosine kinase-deficient cells, implying that their activity did not depend on phosphorylation by adenosine kinase. None of the AdoHcy hydrolase inhibitors showed selective activity against human immunodeficiency virus (type 1). 3-Deazaneplanocin A at a dose of 0.5 mg/kg per day conferred marked protection against a lethal infection of newborn mice with vesicular stomatitis virus.This work was supported by the Belgian Fonds voor Geneeskundig Wetenschappelijk Onderzoek (project no. 3.0040.83) and the Belgian Geconcerteerde Onderzoeksacties (project no. 85/90-79). We thank Anita Van Lierde, Frieda De Meyer, Ria Van Berwaer, Ann Absillis, Etsuko Nitanai, and Willy Zeegers for excellent technical assistance and Christiane Callebaut for fine editorial help

Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation

Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of a parts per thousand yen1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with a parts per thousand yen3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored. More patients had an increase from baseline of a parts per thousand yen1 SCBM per week (weeks 1-4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1-4, more patients in the prucalopride groups achieved an average of a parts per thousand yen3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters. In this population with OIC, prucalopride improved bowel function and was safe and well tolerated

SARS-CoV-2 seroprevalence among vaccinated nursing home residents and staff in Belgium in August 2021

The SCOPE study assesses the prevalence of anti-SARS-CoV-2 antibodies among a representative sample of residents and staff in Belgian NH (nursing homes). Starting from February 1st 2021, a cohort of 1,640 residents and 1.368 staff members in 69 Belgian NHs are being tested every two months on the presence of anti-SARS-CoV-2 antibodies. This brief communication reports on the prevalence of anti-SARS-CoV-2 antibodies among vaccinated nursing home residents and staff. At the end of April 2021, the large scale vaccination campaign in Belgian nursing homes, which took place between January 5th and March 24th 2021, resulted in a vaccination coverage of 97% in NH residents and 84% in staff members. For these vaccinated groups, we describe the prevalence of anti-SARS-CoV-2 antibodies immediately following the vaccination campaign (April, 2021) and the seroprevalence evolution over the two following testing periods (in June and August 2021). Data collection of the August 2021 testing period was not finished at the time of compiling this brief communication. The August 2021 testing period comprises the data from 65 out of the 69 nursing homes. Additionally, some antibody test results are expected the coming weeks in case of self-sampling (for staff in particular). Results given here are preliminary. Small adaptations in some data might occur in future reports.SCOP

Prevalence of SARS-CoV-2 antibodies among Belgian nursing home residents and staff during the primary COVID-19 vaccination campaign.

peer reviewed[en] BACKGROUND: Nursing home residents (NHR) and staff have been disproportionally affected by the COVID-19 pandemic and were therefore prioritised in the COVID-19 vaccination strategy. However, frail older adults, like NHR, are known to have decreased antibody responses upon vaccination targeting other viral antigens. OBJECTIVES: As real-world data on vaccine responsiveness, we assessed the prevalence of SARS-CoV-2 antibodies among Belgian NHR and staff during the primary COVID-19 vaccination campaign. METHODS: In total, we tested 1629 NHR and 1356 staff across 69 Belgian NHs for the presence of SARS-CoV-2 IgM/IgG antibodies using rapid tests. We collected socio-demographic and COVID-19-related medical data through questionnaires. Sampling occurred between 1 February and 24 March 2021, in a randomly sampled population that received none, one or two BNT162b2 vaccine doses. RESULTS: We found that during the primary vaccination campaign with 59% of the study population fully vaccinated, 74% had SARS-CoV-2 antibodies. Among fully vaccinated individuals only, fewer residents tested positive for SARS-CoV-2 antibodies (77%) than staff (98%), suggesting an impaired vaccine-induced antibody response in the elderly, with lowest seroprevalences observed among infection naïve residents. COVID-19 vaccination status and previous SARS-CoV-2 infection were predictors for SARS-CoV-2 seropositivity. Alternatively, age ≥ 80 years old, the presence of comorbidities and high care dependency predicted SARS-CoV-2 seronegativity in NHR. CONCLUSION: These findings highlight the need for further monitoring of SARS-CoV-2 immunity upon vaccination in the elderly population, as their impaired humoral responses could imply insufficient protection against COVID-19. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov (NCT04738695)

Developing language and professional skills through translation-reviewing/editing projects [TAPP-Virtual exchange]

This paper focuses on a series of telecollaborative translation-reviewing/editing projects, conducted within the framework of the Trans-Atlantic and Pacific Project (TAPP), an academic network linking university classes in workplace-like projects. The projects aim to finetune the language and professional skills and, also, to enhance the trans-cultural awareness of four classes of students in Italy, Greece and the USA. The tasks include translation of published materials by students in Italy and Greece, followed by review and editing of the translations by students in the USA. The materials comprise articles on science and technology from magazines and on international or Italian/Greek current affairs from the local press, with the aim of translating them accurately and appropriately for a readership of American English speakers. The collaborative projects lead students to various linguistic and intercultural gains and can be used as a tool to promote realistic international professional communication by effectively preparing students for workplace collaborations of this type

[1,4]-Benzodiazepines as Vasopressin V2 Receptor Antagonists -...

The invention relates to a novel class of [1,4]-benzodiazepine derivatives, processes for their preparation, intermediates usable in these processes, and pharmaceutical compositions containing the compounds. Other aspects of the invention are directed to the use of said [1,4]-benzodiazepine derivatives in therapy based on the capability of said compounds to interfere with the binding of the peptide hormone, vasopressin, to its receptors. In particular as vasopressin V2 receptor antagonists and therefore useful for treating involving increased vascular resistance, cardiac insufficiency, and water retention

[1,4]-Benzodiazepines as Vasopressin V2 Receptor Antagonists -...

The invention relates to a novel class of [1,4]-benzodiazepine derivatives, processes for their preparation, intermediates usable in these processes, and pharmaceutical compositions containing the compounds. Other aspects of the invention are directed to the use of said [1,4]-benzodiazepine derivatives in therapy based on the capability of said compounds to interfere with the binding of the peptide hormone, vasopressin, to its receptors. In particular as vasopressin V2 receptor antagonists and therefore useful for treating involving increased vascular resistance, cardiac insufficiency, and water retention