A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 760 million cases and over 6.8 million deaths as of March 2023. Vaccination has been the main strategy used to contain the spread of the virus and to prevent hospitalizations and deaths.

A linear DNA encoding the SARS-CoV-2 receptor binding domain elicits potent immune response and neutralizing antibodies in domestic cats.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, has been shown to infect a wide range of animal species, especially mammals, and besides human-to-human transmission, human-to-animal transmission has also been observed in some wild animals and pets, especially in cats. It has been demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species.

From Volumes to Valued Experiences: Measurement and the Challenge before Us.

We are grateful for the thoughtful discussion and ideas put forth in this issue on the measurement of healthcare experiences. Our colleagues, who span multiple jurisdictions across Canada and internationally, agree that we need to do a better job at engaging patients and families in their care and measuring their experiences across health services and sectors. In this response paper, we reflect on three core content areas that were identified across the eight papers in this issue: the role of context and engagement-capable environments; approaches to improve the measurement of experience and acting on results; and challenges that must be attended to in our quest to make our healthcare systems work better.

Experience of Care as a Critical Component of Health System Performance Measurement: Recommendations for Moving Forward.

People's experiences can provide critical guidance on how to better meet their quality of life and care needs and deploy resources more appropriately. To maximize the utility of experience data and to advance the current debate, we present four recommendations: (1) measuring experiences outside the healthcare system can provide insight into what needs to change within the healthcare system; (2) focusing on patient experience is necessary but insufficient, (family) caregiver insights and experiences require attention and can provide insight into the needs of the patient; (3) moving from "one time/single sector" measurement of experience to iterative, ongoing measurement across sectors better reflects the true lived experience of patients (especially those with complex care needs) and their caregivers; and (4) embedding measurement within engagement-capable environments that adequately resource patients, caregivers, and providers to work together is required to move from collection to meaningful change. Applying these recommendations requires a longer-term vision, shifting from provider-centred to person-centred models of care, and a deep understanding of the structural, cultural, and normative barriers to measuring care experiences.

A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor.

Purpose: To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of the virus, look for evidence of biological activity, and identify a dosing schedule for later studies.

Experimental Design: The virus was administered by intratumoral injection in patients with cutaneous or s.c.

[Au(CN)4]- as both an intramolecular and intermolecular bidentate ligand with [(tmeda)Cu(mu-OH)] dimers: from antiferro- to ferromagnetic coupling in polymorphs.

Two polymorphic products, [[Cu(tmeda)(mu-OH)}2Au(CN)4][Au(CN)4] (1) and [Cu(tmeda)(mu-OH)Au(CN)4]2 (2), were synthesized from {Cu(tmeda)(mu-OH)}(2)X(2) (tmeda = N,N,N',N'-tetramethylethylenediamine, X = ClO4-, BF4-) and 2 equiv of K[Au(CN)4], and their X-ray structures were determined. Both compounds have [Cu(tmeda)(mu-OH)}2(2+) dimers with [Au(CN)4]- units bound in the axial positions. However, in 1, two trans N-donor cyanides of each [Au(CN)4]- unit bind to adjacent copper(II) dimers, forming a 1-D chain, whereas complex 2 is molecular, with two mono-coordinated [Au(CN)4]- units.

Are metal stents effective for palliation of malignant dysphagia and fistulas?

Background: One of the available treatments for unresectable oesophagogastric malignancies is the insertion of metal stents.

Aims: We evaluated prospectively 147 patients suffering from malignant dysphagia and/or fistula, after inserting a self-expandable metal stent.

Patients And Methods: The study included 147 patients (87 males, mean age 73 years).

[Au(CN)4]- as a supramolecular building block for heterobimetallic coordination polymers.

A series of the first coordination polymers using the [Au(CN)(4)](-) anion as a building block has been prepared. The planar tetracyanoaurate anion uses one, two, or four cyano groups to bridge to Ni(II) or Cu(II) centers and exhibits weak Au(III)-N(cyano) interactions between anions. Ni(en)(2)[Au(CN)(4)](2).

Heterobimetallic coordination polymers incorporating [M(CN)(2)](-) (M = Cu, Ag) and [Ag(2)(CN)(3)](-) units: increasing structural dimensionality via M-M' and M...NC interactions.

A series of new heterometallic coordination polymers has been prepared from the reaction of metal-ligand cations and KAg(CN)(2) units. Many of these contain silver-silver (argentophilic) interactions, analogous to gold-gold interactions, which serve to increase supramolecular structural dimensionality. Compared to [Au(CN)(2)](-) analogues, these polymers display new trends specific to [Ag(CN)(2)](-), including the formation of [Ag(2)(CN)(3)](-) and the presence of Ag.

Analysis of the conversion of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate by active-site mutants of Aspergillus nidulans isopenicillin N synthase.

Background: Penicillins and cephalosporins constitute a major class of clinically useful antibiotics. A key step in their biosynthesis involves the oxidative cyclisation of delta-(Lalpha-aminoadipoyl)-L-cysteinyl-D-valine to isopenicillin N by isopenicillin N synthase (IPNS). This chemically remarkable transformation has been extensively studied using substrate analogues.

RT-PCR based diagnosis and molecular characterisation of mumps viruses derived from clinical specimens collected during the 1996 mumps outbreak in Portugal.

Clinical specimens collected during an outbreak of mumps were characterised by RT-PCR, nested PCR, and nucleotide sequencing. Mumps virus was positively identified in 12/21(57%) saliva, 9/21(43%), throat and 1/33(3%) urine specimens and further sequence comparison revealed that at least six strains of viruses, which differed from 0-9.43% at the nucleotide levels, were cocirculating during the epidemic.

Risks of gastrointestinal bleeding during secondary prevention of vascular events with aspirin--analysis of gastrointestinal bleeding during the UK-TIA trial.

From 1979 to 1985 2435 patients having had transient ischaemic attacks (TIAs) or minor ischaemic strokes, were enrolled in the UK TIA trial and were randomised to receive either aspirin 300 mg, daily or aspirin 1200 mg or placebo. Analysis of reported upper gastrointestinal bleeding events (defined as haematemesis or melaena, or both) showed a risk of bleeding in a dose dependent manner, odds ratios (95% CI) for 300 mg of aspirin = 3.3 (1.

Outbreaks of gastroenteritis due to Norwalk-like virus in two long-term care facilities for the elderly.

In February 1993, outbreaks of gastroenteritis due to Norwalk-like viruses occurred simultaneously among the elderly residents of two long-term care facilities. Facility A instituted infection control measures that included increased surveillance, reinforcement of handwashing, keeping symptomatic residents in their rooms and relieving symptomatic staff of their work duties until 48 h after resolution of their symptoms. Facility B instituted a more stringent set of control measures that included all those implemented by facility A plus the following: staff from affected units were not permitted to work on other units, affected units were closed to new admissions, enteric precautions were instituted for ill residents, residents were restricted to their own units and education was provided to staff and residents about gastroenteritis.

Nonsteroidal anti-inflammatory drug-induced gastric damage: epidemiology.

Although figures vary considerably, the ingestion of aspirin or other non-aspirin non-steroidal anti-inflammatory drugs is associated with an increased risk of gastric ulceration, ulcer bleeding, ulcer complications and of death by a factor of around 3. Evidence for duodenal ulcer (DU) disease is less convincing, but the risk of complications of DU disease, bleeding and perforation, are increased to much the same extent as for gastric ulcer. Whether this increase in complications for DU represents exacerbation of an existing DU diathesis remains unresolved.

The use of proprietary medicines by patients presenting with peptic ulcer haemorrhage.

1. Medication, social and symptom histories were compared in patients with severe haemorrhage from a peptic ulcer (n = 71) and matched control subjects. Self-medication with proprietary agents was catalogued in addition to therapy prescribed by general medical practitioners.

Mucosal adaptation to indomethacin induced gastric damage in man--studies on morphology, blood flow, and prostaglandin E2 metabolism.

The effect of 28 days' continuous administration of oral indomethacin on gastroduodenal morphology, gastric mucosal blood flow, and gastric mucosal prostaglandin E2 (PGE2) metabolism in man was studied to define further the mechanisms of mucosal injury induced by indomethacin. Indomethacin caused acute gastroduodenal damage in all cases, which was maximal at 24 hours of administration. With continued intake, mucosal adaptation occurs resulting in resolution of endoscopic mucosal damage.

The effects of indomethacin on gastroduodenal morphology and mucosal pH gradient in the healthy human stomach.

To define further the injury and the mechanisms of mucosal injury induced by indomethacin, the effect of 28-day continuous administration of oral indomethacin on gastroduodenal morphology, gastric histology, and the protective mucus-bicarbonate barrier overlying gastroduodenal mucosa in humans was studied. In the studies, indomethacin caused acute gastroduodenal damage in 100% of cases, with maximal damage at 24 hours of administration. With continued intake this damage resolves, although a minority (two study subjects) progressed to discrete ulceration.

Effect of bismuth subcitrate and sucralfate on rat duodenal and human gastric bicarbonate secretion in vivo.

Acid and alkali secretion have been examined together with prostaglandin E2 production in response to two mucosal protective drugs, colloidal bismuth subcitrate and sucralfate. Doses of colloidal bismuth subcitrate in the therapeutic range (120 and 1200 mg) had no effect on alkali secretion or luminal PGE2 output when perfused into the stomach of human volunteers. Similarly, in the anaesthetised rat, neither gastric acid nor duodenal alkali secretions were influenced by iv (12 mg/kg) or topical (120 mg/ml) administration of colloidal bismuth subcitrate.