6-(4-Fluorophenyl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6-5] fused-ring system

The title compound, C₁₈H₁₃FN₂OS, is the first structural example of a [6-5] fused ring incorporating the 2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one molecular scaffold. The six-membered 2,3-dihydro-1,3-thiazin-4-one ring adopts an envelope conformation, with the S-CH₂ C atom displaced by 0.761 (2) Å from the five-atom plane (all within 0.05 Å of the mean plane). The imidazole ring is planar. The phenyl ring is twisted from coplanarity with the imidazole ring by 23.84 (5)° and the 4-fluorophenyl ring is twisted by 53.36 (6)°, due to a close C(aryl)-H...O=C contact with the thiazin-4-one carbonyl O atom. The primary intermolecular interaction involves a CH₂ group with the F atom [C...F = 3.256 (2) Å and C-H...F = 137°]

An exploration of educational psychologists' use of consultation using socio-cultural activity theory

Engeström’s (1987) second generation activity theory is used within this research as a conceptual lens through which to explore the practice of EP consultation. Consultation has become a key means of service delivery in many psychological services. However, despite the accepted notion that EP practice and consultation exist in tandem, there is a dearth of research into what it is that EPs actually do when they say they are ‘having a consultation’. In addition, EP consultation has not yet been fully explored as a phenomenon which operates within the wider social, cultural and organisational constraints of a school system. Thus, by using Engeström’s (1987) second generation activity theory as a framework for data collection and analysis, a micro and macro level analysis of the activity of EP consultation was enabled. Data were collected from six EPs working in one Educational Psychology Service (EPS) through the use of semi-structured interviews. In line with Engeström’s (1987) second generation activity theory, the ‘object’, ‘outcome’, ‘tools’, ‘rules’ and ‘division of labour’ within the activity of EP consultation were explored. Thematic analysis (Braun and Clarke, 2006) was used to analyse the data across the interviews, from which numerous themes emerged. Building on the work of Leadbetter (2006), an activity theoretical conceptualisation of EP consultation is presented and proposed as a detailed and functional model which can be used by trainee EPs, and those who are qualified, to make sense of the phenomenon on which much of their practice is based

Metastatic Insulinoma in a Patient with Type 2 Diabetes Mellitus: Case Report and Review of the Literature

Pancreatic neuroendocrine tumors (NETs) are extremely rare, and although insulinomas are the commonest, less than 10% of insulinomas are malignant. Most patients with insulinomas present with neuroglycopenic symptoms and weight gain attributable to insulin excess. Here, we report a case where a 67-year-old lady with a background history of type 2 diabetes mellitus and breakthrough hyperinsulinism who presented with coma. The biochemical profile revealed features typical of insulinoma, and CT and endosonography confirmed a pancreatic tumor with large volume right-sided liver metastases (biopsy confirming a neuroendocrine tumor). The patient underwent successful one-step RO surgical resection, distal pancreatectomy, splenectomy, and right hepatectomy, and 9 months postoperatively, she remains free of recurrent disease. She remains a diabetic

Direct Lysis RT-qPCR of SARS-CoV-2 in Cell Culture Supernatant Allows for Fast and Accurate Quantification

Studying the entire virus replication cycle of SARS-CoV-2 is essential to identify the host factors involved and treatments to combat infection. Quantification of released virions often requires lengthy procedures, whereas quantification of viral RNA in supernatant is faster and applicable to clinical isolates. Viral RNA purification is expensive in terms of time and resources, and is often unsuitable for high-throughput screening. Direct lysis protocols were explored for patient swab samples, but the lack of virus inactivation, cost, sensitivity, and accuracy is hampering their application and usefulness for in vitro studies. Here, we show a highly sensitive, accurate, fast, and cheap direct lysis RT-qPCR method for quantification of SARS-CoV-2 in culture supernatant. This method inactivates the virus and permits detection limits of 0.043 TCID(50) virus and <1.89 copy RNA template per reaction. Comparing direct lysis with RNA extraction, a mean difference of +0.69 ± 0.56 cycles was observed. Application of the method to established qPCR methods for RSV (-ve RNA), IAV (segmented -ve RNA), and BHV (dsDNA) showed wider applicability to other enveloped viruses, whereby IAV showed poorer sensitivity. This shows that accurate quantification of SARS-CoV-2 and other enveloped viruses can be achieved using direct lysis protocols, facilitating a wide range of high- and low-throughput applications

Effects of a water-soluble formulation of tylvalosin on disease caused by porcine reproductive and respiratory syndrome virus alone in sows or in combination with Mycoplasma hyopneumoniae in piglets

BACKGROUND: The effect of a water-soluble formulation of tylvalosin (Aivlosin® 625 mg/g granules) on disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhyop) was investigated in two animal studies. In a PRRSV challenge model in pregnant sows (n = 18), six sows received water medicated at target dose of 5 mg tylvalosin/kg body weight/day from 3 days prior to challenge until the end of gestation. Six sows were left untreated, with a third group remaining untreated and unchallenged. Sows were challenged with PRRSV-2 at approximately 85 days of gestation. Cytokines, viremia, viral shedding, sow reproductive parameters and piglet performance to weaning were evaluated. In a dual infection study (n = 16), piglets were challenged with Mhyop on days 0, 1 and 2, and with PRRSV-1 on day 14 and euthanized on day 24. From day 10 to 20, eight piglets received water medicated at target dose of 20 mg tylvalosin/kg body weight/day and eight piglets were left untreated. Cytokines, viremia, bacteriology and lung lesions were evaluated. RESULTS: In the PRRSV challenge study in pregnant sows, tylvalosin significantly reduced the levels of serum IL-8 (P < 0.001), IL-12 (P = 0.032), TNFα (P < 0.001) and GM-CSF (P = 0.001). IL-8 (P = 0.100) tended to be lower in uterus of tylvalosin sows. All piglets from tylvalosin sows surviving to weaning were PRRSV negative in faecal swabs at weaning compared to 33.3% PRRSV positive piglets from untreated sows (P = 0.08). In the dual challenge study in piglet, tylvalosin reduced serum IL1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-1α, IL-13, IL-17A, IL-18, GM-CSF, TGFβ1, TNFα, CCL3L1, MIG, PEPCAM-1 (P < 0.001) and increased serum IFNα, IL-1ra and MIP-1b (P < 0.001). In the lungs, tylvalosin reduced IL-8, IL-10 and IL-12 compared to untreated pigs (P < 0.001) and tended to reduce TNFα (P = 0.082). Lung lavage samples from all tylvalosin treated piglets were negative for Mhyop (0 cfu/mL) compared to the untreated piglets which had mean Mhyop counts of 2.68 × 10(4) cfu/mL (P = 0.023). CONCLUSION: Overall, tylvalosin reduced both local and systemic proinflammatory cytokines after challenge with respiratory pathogens in sows and in piglets. Tylvalosin was effective in reducing Mhyop recovery from the lungs and may reduce virus shedding in piglets following transplacental PRRSV infection in sows

Coping with stressful events: a pre-post-test of a psycho-educational intervention for undergraduate nursing and midwifery students

Background: Knowledge of coping mechanisms is important for nursing and midwifery students to cope with stressful events during undergraduate education. Objectives: To evaluate the impact of a psycho-educational intervention “Coping with Stressful Events” with first year undergraduate nursing and midwifery students. Design: A quasi-experimental, one-group pre-post-test. Settings: One school of nursing/midwifery in one university in Ireland. Participants: A convenience sample of all first year undergraduate nursing and midwifery students (n = 197). Of these 166 completed the pretest and 138 students completed the post test. Methods: Using the COPE Inventory questionnaire (Carver et al., 1989) data was collected pre and post-delivery of the psycho-educational intervention “Coping with Stressful Events” by two research assistants. Data were analysed using the IBM SPSS Statistics version 22 (NY, USA). Results: Results demonstrated improved coping skills by students. There were statistically significant differences between pre and post intervention for some coping subscales. For example, the mean subscale scores were lower post-intervention for restraint and mental disengagement, and higher for use of emotional and instrumental social support indicating improved coping strategies. Conclusions: This intervention has the potential to influence undergraduate nursing and midwifery students coping skills during their first year of an undergraduate programme