Silver-catalyzed regioselective synthesis of pyrano heterocycles: a versatile route to samoquasine A derivatives.

This study introduces a silver-catalyzed method for the efficient and regioselective synthesis of pyrano heterocycles, utilizing readily available alcohols and water as nucleophiles. The method demonstrates high efficiency, delivering excellent yields and selectivity, and is scalable to gram quantities while maintaining broad functional group tolerance. Notably, the synthesized pyrano[3,4-]quinolines were successfully transformed into diverse samoquasine A derivatives, underscoring the method's applicability in natural product synthesis.

Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets.

Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients.

Tribological Performance Evaluation of Greases on a Four-Ball Tester with Graphene Oxide Nanoparticles.

Conventional greases have an exceptional place in the field of lubrication. They are unique in the sense of their areas of application and are very difficult to replace with other lubricating substances for the same reason. The advancements in the field of nanoparticles and the results they provide as an additive in greases have great scientific interest as they improve the tribological properties of greases to a great extent.

Hyperglycaemia following immune checkpoint inhibitor therapy-Incidence, aetiology and assessment.

Aims: We systematically studied the presence of hyperglycaemia during treatment with Immune Checkpoint Inhibitors (ICPI) for cancer, in those with and without diabetes at baseline, and determined the cause of new-onset hyperglycaemia, METHODS: Retrospective review of electronic records of those receiving an ICPI for melanoma, lung or renal cancer.

Results: Overall, 959 participants were included. In this study, 103 had diabetes at baseline (10.

Establishing a colorectal cancer research database from routinely collected health data: the process and potential from a pilot study.

Objective: Colorectal cancer is a common cause of death and morbidity. A significant amount of data are routinely collected during patient treatment, but they are not generally available for research. The National Institute for Health Research Health Informatics Collaborative in the UK is developing infrastructure to enable routinely collected data to be used for collaborative, cross-centre research.

Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease.

Background: Instances of resistant fungal infection are rising in pulmonary disease, with limited therapeutic options. Therapeutic drug monitoring of azole antifungals has been necessary to ensure safety and efficacy but is considered unnecessary for the newest triazole isavuconazole. Aims: To characterise the prevalence of isavuconazole resistance and use in a tertiary respiratory centre.

Development of a Structured Query Language and Natural Language Processing Algorithm to Identify Lung Nodules in a Cancer Centre.

The stratification of indeterminate lung nodules is a growing problem, but the burden of lung nodules on healthcare services is not well-described. Manual service evaluation and research cohort curation can be time-consuming and potentially improved by automation. To automate lung nodule identification in a tertiary cancer centre.

Lyme Disease: What the Neuroradiologist Needs to Know.

Lyme disease is the most common tick-borne disease in Canada and the United States, caused by , which affects multiple organ systems. Epidemiology, clinical presentation, and neuroimaging findings are reviewed.

A new in vitro model for the study of microbial microleakage around dental restorations: a preliminary qualitative evaluation.

Aim: The aim of this study was to develop an in vitro model to replicate microbial microleakage at a tooth/ restoration interface using a constant depth film fermentor (CDFF).

Methodology: Amalgam restorations were placed in machined bovine dentine cylinders and sealed externally with varnish, leaving a 1-mm perimeter exposed around the tooth/restoration interface. The dentine cylinders were housed in a CDFF and 300-microm thick microcosm dental plaques were grown over their exposed surfaces.

Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] propenamide and related compounds.

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized.

(Imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics.

Several series of heterocyclic carboxylic esters were found to be active in the benzodiazepine receptor binding assay, a typical example being ethyl 7-ethyl-5-methoxyimidazo[1,2-a]quinoline-2-carboxylate (4b) with an IC50 of 150 nM. The corresponding phenylmethanone 5d was more potent with an IC50 of 14 nM and was orally active in animal models thought to predict anxiolytic effects. The synthesis of a large number of compounds resulted in the optimization of this activity in a series of (imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones of which compounds 7e, 8b, 8h, 8j, and 8k were equipotent with chlordiazepoxide while exhibiting reduced anticonvulsant activity, little or no muscle relaxation, and negligible sedative effects.

Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles.

4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured.

Presentation of cancer to hospital as 'acute abdominal pain'.

In a survey of 5675 patients presenting to five hospitals in England, Scotland and Denmark with acute undiagnosed abdominal pain, 106 patients later proved to have intraabdominal cancer. The risk of cancer was age-dependent: amongst patients over 50 years with 'non-specific' pain the risk of cancer was 10 per cent. The commonest primary cancer site (in 57 cases, 53.

Pharmacologically active sulfoximides: 5-hexyl-7-)S-methylsulfonimidoly) xanthone-2-carboxylic acid, a potent antiallergic agent.

The antiallergic activity of some xanthone derivatives containing a sulfoximide substitutent has been investigated. While 2-(S-methylsulfonimidoyl)xanthone itself was found to be inactive, a series of 7-(S-methylsulfonimidoly)-xanthone-2-carboxylic acids showed good levels of activity in the passive cutaneous anaphylaxis screen. N-Substituted sulfoximide derivatives were, without exception, less active than the corresponding unsubstituted compounds.

The penetrability of cephazolin into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease.

Seventeen patients with atherosclerotic disease, who were undergoing arterial reconstruction or amputation of the lower limb, had 2 g cephazolin injected per-operatively in two equal doses by intramuscular and intravenous routes. Samples of subcutaneous fat and skeletal muscle from the ischaemic leg, and serum were collected during the operation for assay of cephazolin content. The mean cephazolin levels in the serum, skeletal muscle and subcutaneous fat were found to be well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens.

Sampling gastro-enterologists' opinions--an OMGE study.

This study describes a pilot project to sample gastroenterologists' opinions on a variety of interesting and controversial topics. At the Madrid World Congress, a sample of delegates were asked to respond to a questionnaire distributed at the meeting itself. A total of 224, representative of those attending by discipline and by geographical area, did so.

A study on tissue concentrations of cephradine achieved in patients with peripheral vascular disease.

The levels of cephradine were measured in serum, voluntary muscle and subcutaneous fat samples collected from 30 patients during surgical operations for peripheral vascular disease. Cephradine 2 g was administered in two equal doses by intramuscular and intravenous routes before each operation. The mean levels found in the serum and muscle were well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens, in contrast to the relatively low mean level found in subcutaneous fat.

Synthesis and antitussive activity of aminotetra- (and -hexa-) hydrodibenzofurans.

The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with that of codeine, was found in the 4alpha-amino series.

New hepato-protective agents. II. Maleopimaridyl morpholides.

A further series of derivatives of maleopimaric acid, the maleopimaridyl morpholides, has been prepared and results on their protection against galactosamine-inducted liver damage in the rat are described. The compounds (3, 4, 8 and 10) were found to display the highest levels of hepato-protective activity in the series. Compound 8 (LD50 greater than 10 g/kg) which exhibited significant, dose-related protection at a daily dose in the range of 50-400 mg/kg, was selected for detailed investigation.