Biorelevant drug release of Metformin dosage forms using complementary in vitro tools

Drug release from immediate release (IR) and extended release (ER) metformin products was investigated using the Dow Chemical Company’s FloVitroTM biorelevant dissolution instrument. This was complemented by using the Sirius SDi2 (Surface Dissolution Imaging) platform to investigate mechanistic differences accounting for drug release. Level A IVIVC was demonstrated for metformin IR dosage forms, using FloVitroTM, whilst ER tablets demonstrated lower Cmax and Tmax using the same method. The SDi2 showed disintegration as the main release mechanism for IR tablets, whilst swelling and drug diffusion was observed for ER tablets. FloVitroTM and SDi2 technologies can be used to compare behaviour of formulations during dosage form selectio

Radiology for medical students (1925-2018): an overview

Objective: Radiology has been espoused as an excellent tool for educating medical students since 1925. Advances in technology and PACS mean it has never been easier to demonstrate living anatomy and clinical pathology in exquisite detail to students. The aim of this study was to provide an overview of radiologic publications related to teaching medical students and its evolution through time. Methods: A literature search was performed from inception to November 2018. The search strategies used both text words and relevant indexing related to “radiology”, “medical students” and “curriculum”. Results: 3589 records were identified of which 377 were included. There was a 100 fold increase in rate of publication over time—most were expository or surveys (60%), with few truly experimental articles. Radiology was used in clinical teaching (67%) and anatomy (33%). Almost half of radiologic anatomy teaching was conducted without the input of a Radiologist. Compulsory clinical clerkships/blocks in radiology was offered infrequently (35%). Female first authorship had increased in the last decade (47%). Conclusion: There is a significant increase in articles published on the role of radiology in medical student teaching in the last decade. Research in this area is required in order to investigate the role of radiology in improving the modern medical students’ education

Developing a fundamental understanding of biomass structural features responsible for enzymatic digestibility

Lignocellulosic biomass is one of the most valuable alternative energy sources because it is renewable, widely available, and environmentally friendly. Unfortunately, enzymatic hydrolysis of biomass has been shown to be a limiting factor in the conversion of biomass to chemicals and fuels. This limitation is due to inherent structural features (i.e., acetyl content, lignin content, crystallinity, surface area, particle size, and pore volume) of biomass. These structural features are barriers that prevent complete hydrolysis; therefore, pretreatment techniques are necessary to render biomass highly digestible. The ability to predict the biomass reactivity based solely on its structural features would be of monumental importance. Unfortunately, no study to date can predict with certainty the digestibility of pretreated biomass. A concerted effort with Auburn University and Michigan State University has been undertaken to study hydrolysis mechanisms on a fundamental level. Predicting enzymatic hydrolysis based solely on structural features (lignin content, acetyl content, and crystallinity index) would be a major breakthrough in understanding enzymatic digestibility. It was proposed to develop a fundamental understanding of the structural features that affect the enzymatic reactivity of biomass. The effects of acetyl content, crystallinity index (CrI), and lignin content on the digestibility of biomass (i.e., poplar wood, bagasse, corn stover, and rice straw) were explored. In this fundamental study, 147 poplar wood model samples with a broad spectrum of acetyl content, CrI, and lignin were subjected to enzymatic hydrolysis to determine digestibility. Correlations between acetyl, lignin, and CrI and linear hydrolysis profiles were developed with a neural network model in Matlabî. The average difference between experimentally measured and network-predicted data were ñ12%, ñ18%, and ñ27% for 1-, 6-, and 72-h total sugar conversions, respectively. The neural network models that included cellulose crystallinity as an independent variable performed better compared to networks with biomass crystallinity, thereby indicating that cellulose crystallinity is more effective at predicting enzymatic hydrolysis than biomass crystallinity. Additionally, including glucan slope in the 6-h and 72-h xylan slope networks and glucan intercept in the 6-h and 72-h xylan intercept networks improved their predictive ability, thereby suggesting glucan removal affects later-stage xylan digestibility

Radiology for medical students: do we teach enough? A national study

Objective: A recent study has shown that the averaged time tabled teaching for a medical student across 5 years in the UK was 4629 hours. Radiology has been demonstrated to be an excellent teaching source, yet the number of hours allocated to this has never been calculated. The aims of this study were to evaluate and quantify the hours allocated to radiology teaching in Scottish Medical Schools and to evaluate if they can fulfil requirements expected from other Clinical disciplines and the upcoming General Medical Council Medical Licensing Assessment (GMC MLA). Methods: Data pertaining to timetabled teaching for Radiology in Scottish Universities were obtained from the authors of the Analysis of Teaching of Medical Schools (AToMS) survey. In addition, University Lead Clinician Teachers were surveyed on the radiological investigations and skills medical students should have at graduation. Results: Medical students in Scottish Universities were allocated 59 h in Radiology (0.3%) out of a total 19,325 h of timetabled teaching. Hospital-based teaching was variable and ranged from 0 to 31 h. Almost half (15 of 31) of Clinician Teachers felt that there was insufficient radiology teaching in their specialty. Thirteen of 30 conditions included in the GMC MLA were listed by Clinician Teachers, while 23 others not listed by the GMC were considered important and cited by them. Conclusion: This study demonstrates that medical students do not receive enough radiology teaching. This needs to be addressed by Universities in collaboration with the NHS in an effort to bring up this up to line with other developed countries and prepare students for the GMC MLA. Advances in knowledge: (1) There is insufficient time allocated in Medical Students’ curriculum to Radiology. (2) Radiology teaching in medical schools fall short of University Lead Clinician Teachers’ and GMC expectations of medical students at graduation

Radiology and the medical student: do increased hours of teaching translate to more radiologists?

Objectives: The UK has a shortage of Radiologists to meet the increasing demand for radiologic examinations. To encourage more medical students to consider Radiology as a career, increased exposure at undergraduate level has been advocated. The aim of this study was to evaluate if formal Radiology teaching hours at medical school had any association with the number of qualified Radiologists joining the General Medical Council Specialist Register. Methods: Total number of doctors joining the GMC Specialist Register as Clinical Radiologists, and those with a primary medical qualifications awarded in Scotland, was obtained from the GMC (2010–2020). Graduate numbers from all 4 Scottish Medical Schools (2000–2011) were also obtained. Hours of Radiology teaching for medical schools in Scotland were obtained from validated AToMS study. Results: Two hundred and twenty three (6.6%) of 3347 Radiologists added to the GMC Specialist Register between 2010 and 2020 received their primary medical qualification (PMQ) from Scottish Universities. The number of Radiologists from Scottish Universities joining the GMC specialist register was 2.6% of the total number of Scottish Medical Graduates. There was no association between the number of hours (Range 1–30) Radiology was taught to medical students and the number that joined the specialist register as Radiologists (p = 0.54 chi square trend). Conclusion: Increased exposure to Radiology teaching does not influence medical students’ decision to take up Radiology as a career. While continued Radiology exposure remains important, other strategies are required in both the short and long term to ensure radiology services are maintained without detriment to patients

Standardization of research methods employed in assessing the interaction metallic-based nanoparticles and the blood-brain barrier: present and future perspectives

peer-reviewedThe full text of this article will not be available until the embargo expires on the 18/01/2020.Treating diseases of the central nervous system (CNS) is complicated by the presence of the blood-brain barrier (BBB), a semipermeable boundary layer protecting the CNS from toxins and homeostatic disruptions. However, this layer also excludes almost 100% of therapeutics, impeding the treatment of CNS diseases. The advent of nanoparticles, in particular metallic-based nanoparticles, presents the potential to overcome this barrier and transport drugs into the CNS. Recent interest in metallic-based nanoparticles has generated an immense array of information pertaining to nanoparticles of different materials, sizes, morphologies, and surface properties. Nanoparticles with different physico-chemical properties lead to distinct nanoparticle-host interactions; yet, comprehensive characterization is often not completed. Similarly, in vivo testing has involved a mixed evaluation of parameters, including: BBB permeability, integrity, biodistribution, and toxicity. The methods applied to assess these parameters are inconsistent; this complicates the comparison of different nanoparticle-host system responses. A systematic review was conducted to investigate the methods by which metallic-based nanoparticles are characterized and assessed in vivo. The introduction of a standardized approach to nanoparticle characterization and in vivo testing is crucial if research is to transition to a clinical setting. The approach suggested, herein, is based on equipment and techniques that are accessible and informative to facilitate the routine incorporation of this standardized, informative approach into different research settings. Thorough characterization could lead to improved interpretation of in vivo responses, which could clarify nanoparticle properties that result in favorable in vivo outcomes whilst exposing nanoparticle-specific weaknesses. Only then will researchers successfully identify nanoparticles capable of delivering life-saving therapeutics across the blood-brain barrier

Subcutaneous and visceral adipose tissue in patients with primary and recurrent incisional hernia

Purpose: Visceral obesity rather than body mass index has been reported to be associated with a higher incidence of incisional hernias. The aim of this study was to examine the relationship between CT measured adipose tissue and muscle in primary and recurrent incisional hernia. Methods: Patients with a ‘Primary’ or ‘Recurrent incisional hernia’ were obtained from a prospective cohort of patients who were being assessed for incisional hernia repair over a 2-year period. Computerised tomography (CT)-images were analysed using NIH Image-J software to quantify adipose tissue and skeletal muscle cross-sectional areas at the level of lumber vertebra 3/4 using standard Hounsfield units. To test inter-observer ‘absolute agreement’, each parameter was measured independently by two investigators and reliability analysis performed. Results: Thirty-six patients were included in the study: 15 had a Primary while 21 had a Recurrent incisional hernia. Both groups had similar baseline characteristics. Reliability analysis for CT-measured areas showed very high interclass correlation coefficient (ICC) between observers. Patients in the recurrent group had significantly greater subcutaneous adipose tissue (SAT) [median = 321.9cm2 vs 230.9cm2, p = 0.04] and visceral adipose tissue (VAT) [median = 221.1cm2 vs 146.8cm2, p = 0.03] than those in the primary group. There was no difference in skeletal muscle areas for right [median = 2.8cm2 vs 2.9cm2] and left [median = 3.7cm2 vs 4.1cm2] rectus muscles between groups. Conclusion: Our study shows that patients with a recurrent incisional hernia have significantly more subcutaneous and visceral adipose tissue than those with a primary incisional hernia. Further studies in this area are required if we are to reduce the burden of recurrent hernia following repair of a primary incisional hernia

Medical student assessments-frequency of radiological images used : a national study

Assessments are a key part of life for medical students at University. We know there is variation in these assessments across Universities. The aims of this study were to expatiate summative assessments in Scottish Medical Schools and to examine how frequently radiological images feature in them. All Scottish medical schools were invited to participate in the study. Data on objective structured clinical examinations (OSCEs; 5 years) and written assessments (3 years) were retrospectively collected for each university and results were collated. Each University was randomly assigned a letter from A to E and anonymised for data presentation. 10,534 multiple choice questions (MCQ) and 1083 OSCE stations were included in this study. There was wide variation in the number, type and timing of assessments across Scottish medical schools. There were highly significant differences in the number of OSCE stations and the number of MCQs set over the study period ( <0.0001). Radiological images were used on average 0.6 times (range 0-1.1) in each OSCE examination and 2.4 times (range 0.1-3.7) for written assessments. In this detailed study, we demonstrated significant differences in medical student assessments across Scottish Universities. Given the importance of Radiology in modern medicine, the frequency and differences in which radiological images were used in assessments across Universities should be addressed. This is the first national longitudinal study to quantify the role of radiological images in summative Medical Student Assessments. Great variability exists in the extent and how (clinical versus written assessments) radiological images are used to assess Scottish medical students. Radiological images are used infrequently in clinical assessments, but are present in every written assessment. These findings could help inform medical schools and academic radiologists as they prepare medical students for the imminent unified medical licensing examination, where Clinical Imaging is a subject with one of the highest number of associated conditions examinable. [Abstract copyright: © 2020 The Authors. Published by the British Institute of Radiology.]Publisher PDFPeer reviewe

Mal-positioned nasogastric feeding tubes: are medical students safe to identify them?

Objectives: Nasogastric tube (NGT) placement is listed against Clinical Imaging in the upcoming Medical Licensing Assessment – compulsory for every graduating UK medical student from 2025. This study aims to establish the ability of medical students to correctly identify the position of an NGT on Chest Xray (CXR) and to evaluate a learning tool to improve student outcome in this area. Materials and Methods: Fourth (MB4) and Fifth-year (MB5) medical students were invited to view 20 CXRs with 14 correctly sited and 6 mal-positioned NGT. MB5 students (Intervention) were exposed to an online interactive learning tool, with MB4 students kept as control. One week later, both groups of students were invited to view 20 more CXRs for NGT placement. Results: Only 12 (4.8%) of 249 MB5 students and 5 (3.1%) of 161 MB4 students correctly identified all the NGTs on CXRs. The number of students misidentifying 1 or more mal-position NGT as “safe to feed” was 129 (51.8%) for MB5 and 76 (47.2%) for MB4 students. This improved significantly (p&lt;0.001) following exposure to the learning tool with 58% scoring all CXRs correctly while 28% scored 1 or more mal-positioned NGT incorrectly. Students struggled to determine if the NGT tip had adequately passed into the stomach. However, they failed to identify an NG tube in the lung (“Never event”) in just one out of 1,108 opportunities. Conclusion: Medical students’ ability to determine if the NGT was in the stomach remains suboptimal despite exposure to over 60 CXRs. Feeding NGT should be formally reported before use. Advances in Knowledge: This is the first attempt at quantifying graduating medical students’, and by inference junior doctors’, competence in safely identifying misplaced nasogastric feeding tubes. An online, experiential learning resource significantly improved their ability

Applying computational predictions of biorelevant solubility ratio upon self-emulsifying lipid-based formulations dispersion to predict dose number

Computational approaches are increasingly utilised in development of bio-enabling formulations, including self-emulsifying drug delivery systems (SEDDS), facilitating early indicators of success. This study investigated if in silico predictions of drug solubility gain i.e. solubility ratios (SR), after dispersion of a SEDDS in biorelevant media could be predicted from drug properties. Apparent solubility upon dispersion of two SEDDS in FaSSIF was measured for 30 structurally diverse poorly water soluble drugs. Increased drug solubility upon SEDDS dispersion was observed in all cases, with higher SRs observed for cationic and neutral versus anionic drugs at pH 6.5. Molecular descriptors and solid-state properties were used as inputs during partial least squares (PLS) modelling resulting in predictive models for SRMC (r2 = 0.81) and SRLC (r2 = 0.77). Multiple linear regression (MLR) facilitated generation of simplified SR equations with high predictivity (SRMC r2 = 0.74; SRLC r2 = 0.69), requiring only three drug properties; partition coefficient at pH 6.5 (logD6.5), melting point (Tm) and aromatic bonds as fraction of total bonds (FArom_B). Through using the equations to inform drug developability classifications (DCS) for drugs that have already been licensed as lipid based formulations, merits for development with SEDDS was predicted for 2/3 drugs