Retrospective study of outcomes of short versus long duration of antibiotic therapy for residual osteomyelitis in surgically resected diabetic foot infection.

INTRODUCTION: Optimal treatment duration for residual osteomyelitis (OM) post-amputation in diabetic foot infection (DFI) remains unclear, with resultant heterogeneity in prescribing noted in clinical practice. We aimed to identify a difference in outcomes of long duration of antibiotics (LD) with short duration (SD) in patients with culture-positive proximal bone specimen post-amputation. METHODS: In this single-centre retrospective cohort study (Melbourne, Australia), we analysed antibiotic duration of DFI patients requiring amputation with culture-positive proximal bone specimen over a 31 month period (January 2019-September 2021). Primary outcome was reamputation or debridement at the same and/or contiguous site of amputation at 6 months. Secondary outcomes were readmission to hospital and/or recommencement of antibiotics for DFI at the same and/or contiguous site at 6 months. RESULTS: Among 92 patients (83% male, median age 67 years), 26 received <4 weeks (SD) and 66 received ≥4 weeks (LD) antibiotic therapy. In the SD group, primary outcome occurred in 9 patients (35%) compared with 15 patients (23%) in the LD group (P = 0.246). Both secondary outcomes occurred in 12 patients (46%) in the SD group compared with 18 patients (27%) in the LD group (P = 0.086). Adjusted logistic regression analysis showed SD was not significantly associated with primary outcome [OR 1.12 (95% CI 0.38-3.31)] or secondary outcomes [OR 1.67 (95% CI 0.60-4.66)]. CONCLUSIONS: This single-centre experience did not demonstrate significant difference in outcomes between antibiotic duration of <4 weeks and ≥4 weeks in DFI patients with culture-positive proximal bone specimen post-amputation. These data provide background for larger international randomized control trials to establish optimal treatment duration.

General practice is "different": a qualitative study of adaptation experiences of East Staffordshire general practice speciality trainees.

BACKGROUND: Undergraduate medical education and foundation training are still largely hospital based. General practice trainees also spend nearly half of their speciality training in hospitals. Aims: To explore adaptation experiences of general practice speciality trainees throughout the training. Method: Semi-structured participant-observer interviews with 18 purposively selected trainees on the East Staffordshire vocational training scheme, observation, stakeholder discussions and concurrent inductive thematic analysis. Results: Undergraduate and early general practice experience during speciality training, general practice trainer role modelling and mastering core general practice skills, facilitated transition. An inclusive and supportive general practice environment, facilitating engagement with a community of practice involving peers, general practice trainers and vocational training programme fostered belongingness. A reduced sense of belongingness during hospital rotations impacted on training and work. Building bridging social connections, personal agency initiatives to bring general practice relevance into hospital training, signposting to general practice relevant duties and mastery of secondary care relevant competencies helped gain belongingness in hospital. While some international graduates required assistance in specific areas; overall, general practice trainees had optimistic views of their future. Conclusion: The main contribution of this study was to relate the adaptation experiences of trainees to learning and practice based on Wenger's communities of practice to enable a better understanding of how they can be influenced to enhance training.Abbreviations: CoP: Community of practice; GP: General practice; GPST: General practice speciality trainee; M: Male; F: Female; ST1: First-year GPST; ST2: Second-year GPST; ST3: Third-year GPST; UKG: UK-based primary medical qualification; IMG: Non-UK primary medical qualification.

Gender-Related Differences of Tachykinin NK2 Receptor Expression and Activity in Human Colonic Smooth Muscle.

The tachykinin NK2 receptor plays a key role in gastrointestinal motor function. Enteric neurons release neurokinin A (NKA), which activates NK2 receptors on gastrointestinal smooth muscle, leading to contraction and increased motility. In patients with diarrhea-predominant irritable bowel syndrome, the NK2 receptor antagonist ibodutant had a greater therapeutic effect in females than males. The present study aimed to determine whether gender influences the expression and activity of NK2 receptors in human colonic smooth muscle. In vitro functional studies were performed to examine the contractile responses of colonic muscle strips to NKA and the selective NK2 receptor agonist [Lys5,MeLeu9,Nle10]NKA(4-10). Contractions were also measured in the presence of ibodutant to determine its antagonistic potency. The signal transduction pathways coupled to NK2 receptor activation were investigated using second messenger inhibitors. Western blot and fluorescent immunohistochemistry were conducted to determine the protein expression and localization of NK2 receptors. NK2 receptor-mediated contractility was greater in females compared with males. When against NKA, ibodutant was more potent in females. NK2 receptor expression increased with age in females, but not in males. Phospholipase C-mediated signaling was less prominent in females compared with males, whereas Ca2+ sensitization via Rho kinase and protein kinase C appeared to be the dominant pathway in both genders. The distribution of NK2 receptors in the human colon did not differ between the genders. Overall, gender differences exist in the expression and activity of NK2 receptors in colonic smooth muscle. These gender distinctions should be considered in the therapeutic development of NK2 receptor agents. SIGNIFICANCE STATEMENT: The tachykinin NK2 receptor has been identified as a therapeutic target for the treatment of bowel and bladder dysfunctions. The present study has revealed gender-related variations in NK2 receptor activity, signaling transduction pathways, antagonist potency, and changes in expression with age. These factors may underlie the gender differences in the treatment of diarrhea-predominant irritable bowel syndrome with NK2 receptor antagonists. Our findings highlight that gender differences should be considered in the therapeutic development of NK2 receptor agents.

Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention.

BACKGROUND: Antibiotic allergy labels (AALs), reported by up to 25% of hospitalized patients, are a significant barrier to appropriate prescribing and a focus of antimicrobial stewardship (AMS) programmes. METHODS: A prospective audit of a pharmacist-led AMS penicillin allergy de-labelling ward round at Austin Health (Melbourne, Australia) was evaluated. Eligible inpatients with a documented penicillin allergy receiving an antibiotic were identified via an electronic medical report and then reviewed by a pharmacist-led AMS team. The audit outcomes evaluated were: (i) AMS post-prescription review recommendations; (ii) direct de-labelling; (iii) inpatient oral rechallenge referral; (iv) skin prick testing/intradermal testing referral; and (v) outpatient antibiotic allergy clinic assessment. RESULTS: Across a 5 month period, 106 patients were identified from a real-time electronic prescribing antibiotic allergy report. The highest rate of penicillin allergy de-labelling was demonstrated in patients who were referred for an inpatient oral rechallenge with 95.2% (n = 21) successfully having their penicillin AAL removed. From the 22 patients with Type A reactions, 63.6% had their penicillin AAL removed. We demonstrated a significant decrease in the prescribing of restricted antibiotics (defined as third- or fourth-generation cephalosporins, fluoroquinolones, glycopeptides, carbapenems, piperacillin/tazobactam, lincosamides, linezolid or daptomycin) in patients reviewed (pre 42.5% versus post 17.9%, P = 0.0002). CONCLUSIONS: A pharmacist-led AMS penicillin allergy de-labelling ward round reduced penicillin AALs and the prescribing of restricted antibiotics. This model could be implemented at other hospitals with existing AMS programmes.

Evaluation of the undergraduate family medicine programme of Faculty of Medicine, University of Kelaniya: quantitative and qualitative student feedback.

BACKGROUND: Worldwide there is an increasing emphasis on the importance of primary care. The ministry of health Sri Lanka issued a directive in 2016 that training of doctors in primary care should be strengthened. Medical students of the Faculty of Medicine, University of Kelaniya follow a 1 month long clinical appointment in family medicine in their fourth year of study. METHODS: Feedback is taken from students on completion of the appointment. Half the students from each group complete a pre tested structured feedback questionnaire that consists of answers to questions based on a likert scale with a space for free comments. The other half provide qualitative feedback. In this evaluation data were gathered from 185 (98%) students from all eight clinical groups throughout the year 2016. Quantitative data were analysed using SPSS version 22. Inductive thematic analysis was used to analyse the qualitative data from the Round Robin activity and free comments from the questionnaire. RESULTS: The qualitative feedback provided a richer indepth overview of student ideas on the appointment compared to the quantitative data. In reflection of a desire for learning to be of relevance students wanted clinically oriented teaching focused on management. They preferred active teaching learning methods such as the opportunity to conduct consultations and receive immediate feedback. Students had a high regard for the teaching sessions by general practitioners at their clinics. The appointment had created an interest in the discipline of family medicine which could have an impact on future choice of career. There were indications to suggest that student attitudes towards patients may have evolved to be more patient centred. Students appreciated the inclusive and low stress ambience of the learning environment. CONCLUSIONS AND RECOMMENDATIONS: Regular evaluation of teaching programmes helps maintain accountability of faculty and paves the way for more student centred teaching through the incorporation of students' views in devising teaching methods. This evaluation found that qualitative feedback provided more descriptive material to reflect on and therefore improve teaching on the programme. It is recommended that more use should be made of qualitative methodologies in programme evaluations.

Peer feedback for examiner quality assurance on MRCGP International South Asia: a mixed methods study.

BACKGROUND: The International Membership Examination (MRCGP[INT]) of the Royal College of General Practitioners UK is a unique collaboration between four South Asian countries with diverse cultures, epidemiology, clinical facilities and resources. In this setting good quality assurance is imperative to achieve acceptable standards of inter rater reliability. This study aims to explore the process of peer feedback for examiner quality assurance with regard to factors affecting the implementation and acceptance of the method. METHODS: A sequential mixed methods approach was used based on focus group discussions with examiners (n = 12) and clinical examination convenors who acted as peer reviewers (n = 4). A questionnaire based on emerging themes and literature review was then completed by 20 examiners at the subsequent OSCE exam. Qualitative data were analysed using an iterative reflexive process. Quantitative data were integrated by interpretive analysis looking for convergence, complementarity or dissonance. The qualitative data helped understand the issues and informed the process of developing the questionnaire. The quantitative data allowed for further refining of issues, wider sampling of examiners and giving voice to different perspectives. RESULTS: Examiners stated specifically that peer feedback gave an opportunity for discussion, standardisation of judgments and improved discriminatory abilities. Interpersonal dynamics, hierarchy and perception of validity of feedback were major factors influencing acceptance of feedback. Examiners desired increased transparency, accountability and the opportunity for equal partnership within the process. The process was stressful for examiners and reviewers; however acceptance increased with increasing exposure to receiving feedback. The process could be refined to improve acceptability through scrupulous attention to training and selection of those giving feedback to improve the perceived validity of feedback and improved reviewer feedback skills to enable better interpersonal dynamics and a more equitable feedback process. It is important to highlight the role of quality assurance and peer feedback as a tool for continuous improvement and maintenance of standards to examiners during training. CONCLUSION: Examiner quality assurance using peer feedback was generally a successful and accepted process. The findings highlight areas for improvement and guide the path towards a model of feedback that is responsive to examiner views and cultural sensibilities.

Inverse expression of prostaglandin E2-related enzymes highlights differences between diverticulitis and inflammatory bowel disease.

BACKGROUND: Prostaglandin E2 (PGE2) is the dominant prostaglandin in the colon and is associated with colonic inflammation. PGE2 levels are regulated not only by cyclooxygenases (COX-1 and COX-2) but also by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the major PGE2-degrading enzyme. Information about the involvement of 15-PGDH in colonic inflammation is sparse. AIM: We thus aimed to determine the gene expression and immunoreactivity (IR) of COX-1, COX-2, and 15-PGDH in colonic mucosa from patients with diverse inflammatory disorders: ulcerative colitis (UC), Crohn's disease (CD), and acute diverticular disease (DD). METHODS: RNA from human colonic mucosa was extracted and assessed for gene expression by real-time PCR. Intact colon sections were processed for immunohistochemistry with immunostaining of the mucosal areas quantified using ImageJ. RESULTS: In colonic mucosa of both UC and CD, COX-2 mRNA and COX-2-IR were significantly increased, whereas 15-PGDH mRNA and 15-PGDH-IR were significantly reduced. In macroscopically undamaged acute DD mucosa, the opposite findings were seen: for both gene expression and immunoreactivity, there was a significant downregulation of COX-2 and upregulation of 15-PGDH. COX-1 mRNA and COX-1-IR remained unchanged in all diseases. CONCLUSIONS: Our study for the first time demonstrated differential expression of the PGE2-related enzymes COX-2 and 15-PGDH in colonic mucosa from UC, CD, and acute DD. The reduction of 15-PGDH in IBD provides an additional mechanism for PGE2 increase in IBD. With respect to DD, alterations of PGE2-related enzymes suggest that a low PGE2 level may precede the onset of inflammation, thus providing new insight into the pathogenesis of DD.

Road rage in Sri Lanka: prevalence and psychiatric distress.

INTRODUCTION: Road traffic accidents are a major public health concern in Sri Lanka. Aggressive and reckless driving is an important contributor to the high rate of road traffic accidents. OBJECTIVE: We studied prevalence, nature, determinants and associated psychiatric morbidity of road rage among motorists in Sri Lanka. Methods Data were gathered from 238 randomly selected motorists in Sri Lanka using a modified questionnaire regarding road rage and the 6-item version of Kessler's psychological distress scale. RESULTS: While 98.7% participants reported being victims of road rage, 85.3% were involved in offending behaviour. However actual physical assault (0.8%) and damage to vehicles (2.5%) were rare. Male gender, young age, increased traffic density and driving a three-wheeler or bus were associated with daily road rage victimisation and perpetration. Psychiatric distress was associated with being a victim of road rage. CONCLUSIONS: High prevalence of road rage in Sri Lanka and significant psychiatric distress associated with it indicate the necessity of interventions at least for target groups.

The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71.

Enterovirus 71 (EV71) is responsible for frequent large-scale outbreaks of hand, foot, and mouth disease worldwide and represent a major etiological agent of severe, sometimes fatal neurological disease. EV71 variants have been classified into three genogroups (GgA, GgB, and GgC), and the latter two are further subdivided into subgenogroups B1 to B5 and C1 to C5. To investigate the dual roles of recombination and evolution in the epidemiology and transmission of EV71 worldwide, we performed a large-scale genetic analysis of isolates (n = 308) collected from 19 countries worldwide over a 40-year period. A series of recombination events occurred over this period, which have been identified through incongruities in sequence grouping between the VP1 and 3Dpol regions. Eleven 3Dpol clades were identified, each specific to EV71 and associated with specific subgenogroups but interspersed phylogenetically with clades of coxsackievirus A16 and other EV species A serotypes. The likelihood of recombination increased with VP1 sequence divergence; mean half-lives for EV71 recombinant forms (RFs) of 6 and 9 years for GgB and GgC overlapped with those observed for the EV-B serotypes, echovirus 9 (E9), E30, and E11, respectively (1.3 to 9.8 years). Furthermore, within genogroups, sporadic recombination events occurred, such as the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization.

Rate of stunting among a sample of postwar resettled families in the Vanni Region: a study from the Mullaitivu District.

The Department of Family Medicine, University of Kelaniya conducted a health camp in Puthukudiyiruppu in March 2011. Height and weight measurements were carried out and data of 303 participants were analysed. The rate of stunting among children below six years in this population was 62% compared to 19.3% nationally. Thirty four percent of children and adolescents (6-18yrs) were underweight and 21.4% of adults had a BMI less than 18.5kg/m2.

Knowledge of diabetes among type 2 diabetes patients attending a primary health care clinic in Sri Lanka.

Patients' knowledge about their illness is considered important in controlling diabetes and preventing complications. A descriptive, cross-sectional study was conducted among patients attending the diabetes clinic of a primary care level hospital in Moratuwa, Sri Lanka. During a 1-month period in 2009 all consenting patients diagnosed with type 2 diabetes who had been attending the clinic for more than 3 months were included in the study. Using an interviewer administered, structured questionnaire 150 patients (135 females, 15 males) answered 25 questions about diabetes knowledge (scored x4 to give score range 0-100). A majority of patients (70.0%) had a good score (> 65) on the knowledge test but critical gaps in knowledge were revealed, especially regarding knowledge about symptoms of poor control and importance of regular follow-up. Although patients with longer duration of diabetes had higher mean knowledge scores, they also had higher fasting blood glucose levels. Education programmes are needed to address critical gaps in patients' knowledge.

Duplication errors due to brand name confusion; It is not always the name-Short case series.

Confusion of drug names has been identified as a leading cause of medication errors and potential iatrogenic harm. Most of these errors occur because of look-alike or sound-alike drugs. This case series gives examples of duplication errors due to brand confusion, where there are no similarities in the names.

Multimodal Precision Prevention - A New Direction in Alzheimer's Disease.

At least 40% of all dementia has been linked to modifiable risk factors suggesting a clear potential for preventative approaches targeting these factors. Despite the recent promising findings from anti-amyloid monoclonal antibodies, a limited proportion of patients are expected to be eligible for these novel AD treatments. Given the heterogeneous nature of AD and the complex multi-level pathological processes leading to dementia (involving, e.g., shared risk factors, interaction of different pathology mechanisms, and their putative synergistic effects on cognition), targeting a single pathology may not be sufficient to halt or significantly impact disease progression. With exponentially increasing numbers of patients world-wide, in parallel to the unprecedented population ageing, new multimodal therapy approaches targeting several modifiable risk factors and disease mechanisms simultaneously are urgently required. Developing the next generation of combination therapies with lifestyle intervention and pharmacological treatments, implementing the right interventions for the right people at the right time, and defining accessible and sustainable strategies worldwide are crucial. Here, we summarize the state-of-the-art multimodal lifestyle-based approaches, especially findings and lessons learned from the FINGER trial, for prevention and risk reduction of cognitive impairment and dementia. We also discuss some emerging underlying biological mechanisms and the current development of precision prevention approaches. We present an example of a novel trial design combining healthy lifestyle changes with a repurposed putative disease-modifying drug and place this study in the context of the World-Wide FINGERS, the first interdisciplinary network of multimodal trials dedicated to the prevention and risk reduction of cognitive impairment and dementia.

Impact of a sustained, collaborative antimicrobial stewardship programme in spinal cord injury patients.

Background: In patients with spinal cord injuries (SCIs), infections continue to be a leading cause of morbidity, mortality and hospital admission. Objectives: This study evaluated the long-term impact of a weekly, multidisciplinary Spinal/Antimicrobial Stewardship (AMS) meeting for acute-care SCI inpatients, on antimicrobial prescribing over 3 years. Methods: A retrospective, longitudinal, pre-post comparison of antimicrobial prescribing was conducted at our tertiary hospital in Melbourne. Antimicrobial prescribing was audited in 6 month blocks pre- (25 April 2017 to 24 October 2017), immediately post- (27 March 2018 to 25 September 2018) and 3 years post-implementation (2 March 2021 to 31 August 2021). Antimicrobial orders for patients admitted under the spinal unit at the meeting time were included. Results: The number of SCI patients prescribed an antimicrobial at the time of the weekly meeting decreased by 40% at 3 years post-implementation [incidence rate ratio (IRR) 0.63; 95% CI 0.51-0.79; P ≤ 0.001]. The overall number of antimicrobial orders decreased by over 22% at 3 years post-implementation (IRR 0.78; 95% CI 0.61-1.00; P = 0.052). A shorter antimicrobial order duration in the 3 year post-implementation period was observed (-28%; 95% CI -39% to -15%; P ≤ 0.001). This was most noticeable in IV orders at 3 years (-36%; 95% CI -51% to -16%; P = 0.001), and was also observed for oral orders at 3 years (-25%; 95% CI -38% to -10%; P = 0.003). Antimicrobial course duration (days) decreased for multiple indications: skin and soft tissue infections (-43%; 95% CI -67% to -1%; P = 0.045), pulmonary infections (-45%; 95% CI -67% to -9%; P = 0.022) and urinary infections (-31%; 95% CI -47% to -9%; P = 0.009). Ninety-day mortality rates were not impacted. Conclusions: This study showed that consistent, collaborative meetings between the Spinal and AMS teams can reduce antimicrobial exposure for acute-care SCI patients without adversely impacting 90 day mortality.

Detection of intracoronary thrombus by magnetic resonance imaging in patients with acute myocardial infarction.

BACKGROUND: Persistent intracoronary thrombus after plaque rupture is associated with an increased risk of subsequent myocardial infarction and mortality. Coronary thrombus is usually visualized invasively by x-ray coronary angiography. Non-contrast-enhanced T1-weighted magnetic resonance (MR) imaging has been useful for direct imaging of carotid thrombus and intraplaque hemorrhage by taking advantage of the short T1 of methemoglobin present in acute thrombus and intraplaque hemorrhage. The aim of this study was to investigate the use of non-contrast-enhanced MR for direct thrombus imaging (MRDTI) in patients with acute myocardial infarction. METHODS AND RESULTS: Eighteen patients (14 men; age, 61±9 years) underwent MRDTI within 24 to 72 hours of presenting with an acute coronary syndrome before invasive x-ray coronary angiography; MRDTI was performed with a T1-weighted, 3-dimensional, inversion-recovery black-blood gradient-echo sequence without contrast administration. Ten patients were found to have intracoronary thrombus on x-ray coronary angiography (left anterior descending, 4; left circumflex, 2; right coronary artery, 4; and right coronary artery-posterior descending artery, 1), and 8 had no visible thrombus. We found that MRDTI correctly identified thrombus in 9 of 10 patients (sensitivity, 91%; posterior descending artery thrombus not detected) and correctly classified the control group in 7 of 8 patients without thrombus formation (specificity, 88%). The contrast-to-noise ratio was significantly greater in coronary segments containing thrombus (n=10) compared with those without visible thrombus (n=131; mean contrast-to-noise ratio, 15.9 versus 2.6; P<0.001). CONCLUSION: Use of MRDTI allows selective visualization of coronary thrombus in a patient population with a high probability of intracoronary thrombosis.

Hemokinin-1 stimulates prostaglandin E2 production in human colon through activation of cyclooxygenase-2 and inhibition of 15-hydroxyprostaglandin dehydrogenase.

Hemokinin-1 (HK-1) is a newly identified tachykinin, originating from the immune system rather than neurons, and may participate in the immune and inflammatory response. In colonic mucosa of patients with inflammatory bowel disease (IBD), up-regulation of the TAC4 gene encoding HK-1 and increased production of prostaglandin E2 (PGE2) occur. Our aim was to examine the mechanistic link between human HK-1 and PGE2 production in normal human colon. Exogenous HK-1 (0.1 µM) for 4 h evoked an increased PGE2 release from colonic mucosal and muscle explants by 10- and 3.5-fold, respectively, compared with unstimulated time controls. The HK-1-stimulated PGE2 release was inhibited by the tachykinin receptor antagonists (S)1-2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl-4-phenyl-l azonia-bicyclo[2.2.2]octane (SR140333) [neurokinin-1 (NK1)] and N-[(2S)-4-(4-acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide (SR48968) [neurokinin-2 (NK2)] and was also inhibited by the cyclooxygenase (COX)-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) (NS-398) but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560). A parallel study with substance P showed similar results. Molecular studies with HK-1-treated explants demonstrated a stimulatory effect on COX-2 expression at both transcription and protein levels. It is noteworthy that this was coupled with HK-1-induced down-regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA and protein expression. Immunoreactivity for 15-PGDH occurred on inflammatory cells, epithelial cells, platelets, and ganglia. This finding provides an additional mechanism for HK-1-evoked PGE2 increase, in which HK-1 may interfere with the downstream metabolism of PGE2 by suppressing 15-PGDH expression. In conclusion, our results uncover a novel inflammatory role for HK-1, which signals via NK1 and NK2 receptors to regulate PGE2 release from human colonic tissue, and may further explain a pathological role for HK-1 in IBD when abnormal levels of PGE2 occur.

Value of biomedical scientists providing on-site specimen adequacy assessment for fine-needle aspirations.

Fine-needle aspiration (FNA) is accepted as a first-line investigation in patients with superficial or deep-seated mass lesions. One of the fundamental principles of successful aspiration is harvesting sufficient numbers of cells that are representative of the lesion being investigated. Central Manchester University Hospitals NHS Foundation Trust provides FNA services to Christie Hospital, including non-attended and biomedical scientist-attended aspirations, some of which are assessed on-site for specimen adequacy. This study audits the FNA coverage provided to Christie Hospital by exploring the contribution of biomedical scientist on-site specimen adequacy assessment to successful aspirations and identifies potential areas for service improvement such that unsatisfactory sampling is reduced. Satisfactory sampling rates varied between biomedical scientist-attended (79%) and non-attended (70%) procedures. Within the former group, 100% satisfactory sampling was achieved with on-site assessment, falling to 77% without on-site assessment. The highest unsatisfactory sampling rate was identified at 33% for thyroid aspirations in endocrinology, while rates elsewhere varied between 21% and 23%. This audit demonstrated the value of on-site specimen adequacy assessment as the ultimate goal of any FNA is to negate the need for more invasive procedures. In terms of flexibility and economic value, having adequately trained biomedical scientists to perform on-site assessment is quite feasible. Extending this biomedical scientist-led service to other departments would reduce unsatisfactory sample rates and the requirement for more invasive procedures.

Antimicrobial activity of Plumbago indica and ligand screening of plumbagin against methicillin-resistant Staphylococcus aureus.

In this study, the antimicrobial properties of Plumbago indica root bark against bacterial strains and a fungal strain were investigatedusing the disc diffusion and minimum inhibitory concentration assays. Gas chromatography/mass spectrometry, nuclear magnetic resonance spectrometry, and column chromatography analyses were conducted to identify and isolate the active compounds. A docking study was performed to identify possible interactions between the active compound and DNA gyrase using the Schrödinger Glide docking program. Both methanol extract and the ethyl acetate fraction of the root bark showed significant antimicrobial activity against the gram-positive bacteria than against the gram-negative bacteria and the fungal strain. The active compound was identified as plumbagin. A disc diffusion assay of plumbagin revealed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus. Molecular docking of plumbagin revealed high specificity towards the DNA gyrase binding site with a high fitness score and a minimum energy barrier of -7.651 kcal/mol. These findings indicate that P. indica exhibits significant antimicrobial activity, primarily due to the presence of plumbagin. The specificity of plumbagin toward DNA gyrase in S. aureus indicates the feasibility of utilizing P. indica for developing new drug leads against drug resistant microbial strain. Communicated by Ramaswamy H. Sarma.

Electrochemical impedance spectroscopy studies of organic-solvent-induced permeability changes in nanoporous films derived from a cylinder-forming diblock copolymer.

In this paper we report electrochemical investigations of the influence of organic solvents dissolved in aqueous solution on the permeability of nanoporous films derived from a cylinder-forming polystyrene-poly(methyl methacrylate) diblock copolymer (CF-PS-b-PMMA). The nanoporous films (ca. 30 nm in pore diameter) were prepared on planar gold electrodes via UV-based degradation of the cylindrical PMMA domains of annealed CF-PS-b-PMMA films (30-45 nm thick). The permeability of the electrode-supported nanoporous films was assessed using cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The faradic current of Fe(CN)(6)(3-/4-) decreased upon immersion in aqueous solutions saturated with toluene or methylene chloride (5.8 mM and 0.20 M, respectively). EIS data indicated that the decrease in faradic current mainly reflected an increase in the pore resistance (R(pore)). In contrast, R(pore) did not change in a saturated n-heptane solution, 0.17 M ethanol, or 5.8 mM aqueous solutions of methylene chloride, diethyl ether, methyl ethyl ketone, or ethanol. Atomic force microscopy images of a nanoporous film in aqueous solution with and without 5.8 mM toluene showed a reversible change in the surface morphology, which was consistent with a toluene-induced change in R(pore). The solvent-induced increase in R(pore) was attributed to the swelling of the nanoporous films by the organic solvents, which decreased the effective pore diameter. The reversible permeability changes suggest that the surface of CF-PS-b-PMMA-derived nanoporous films can be functionalized in organic environments without destroying the nanoporous structure. In addition, the solvent-induced swelling may provide a simple means for controlling the permeability of such nanoporous films.