Putting the Cart Before the Horse? Developing a Blended Anatomy Curriculum Supplemented by Cadaveric Anatomy.

Cadaveric anatomy is frequently described as the gold standard for anatomy education. Increasingly and especially following the COVID-19 pandemic, there is acceptance that a blended approach for anatomy curriculum delivery is optimal for learners.Setting up a new UK Medical School in 2019 necessitated building a new cadaveric anatomy facility. To enable anatomy curriculum delivery during the construction period (2019-2021), a technology-enhanced learning (TEL) anatomy curriculum was developed, as well as an anatomy laboratory suitable for TEL. Development of a TEL anatomy curriculum with the later inclusion of cadaveric anatomy is unusual since the typical model is to supplement cadaveric anatomy with TEL approaches.TEL solutions that provide digital visualisation of anatomy may support learners by reducing cognitive load. Examples include using colour and/or translucency features to highlight and signpost pertinent anatomy and constructing virtual anatomical models in real time, rather than dissection. Radiology and portable ultrasound provide clinically contextualised visualisations of anatomy; the latter offers a haptic learning experience too. A TEL anatomy laboratory can provide interactive learning experiences for engagement and outreach activities for young school children, where cadaveric anatomy is not suitable.

Multiple cranial nerve motor deficits, resembling polyneuritis cranialis, in a cat with hyperthyroidism.

A 14 plus-year-old (exact age unknown) neutered female domestic shorthair cat presented with a 6-day history of rapidly evolving difficulty in eating, dropped jaw, protrusion of the tongue, sialosis, change in voice (meow softer and higher pitched) and mild variable pelvic limb weakness. Salient clinical features were a left thyroid nodule, 2/6 systolic cardiac murmur, poor body condition, hypertension, bilateral retinal haemorrhages and an increased total thyroid hormone level consistent with a diagnosis of hyperthyroidism (HT). Neurological examination disclosed mild generalised weakness, bilateral visual deficits attributable to a hypertensive retinopathy and multiple cranial nerve (CN) motor deficits that included; mandibular paresis (CN V), bilateral external ophthalmoparesis (CNs III, IV, VI), bilateral facial paresis (CN VII), dysphagia (CNs IX, X), dysphonia (CN XI) and symmetrical paresis of the tongue (CN XII). Treatment with carbimazole, and subsequently, a modified extracapsular bilateral thyroidectomy resulted in a rapid improvement in neurological signs over 13 days and complete resolution by 100 days post thyroidectomy. To the best of the authors' knowledge, this is the first description of multiple CN motor deficits in a cat with HT and resembles polyneuritis crainialis that has recently been described in human patients with this disorder. It is suggested the underlying pathogenesis is a thyrotoxic polyneuropathy selectively affecting CN motor function, that HT needs to be considered in cats that might present with such signs and that resolution can occur with successful treatment of the HT.

Diffusion tensor imaging determines three-dimensional architecture of human cervix: a cross-sectional study.

OBJECTIVE: To determine the microarchitecture of the cervix using high-resolution diffusion tensor (DT) magnetic resonance imaging (MRI). DESIGN: Cross-sectional study. SETTING: Leeds, UK. SAMPLE: Women undergoing hysterectomy for benign pathology. METHODS: Ex-vivo DT-MRI measurements were obtained using a 9.4-T Bruker nuclear magnetic resonance (NMR) spectrometer on seven fixed human cervices obtained at hysterectomy. A deterministic fibre-tracking algorithm was used to indirectly visualise underlying fibre organisation. Inter-regional differences in tissue structure were sought using quantitative measurements of diffusion. MAIN OUTCOME MEASURE: The identification of an occlusive structure in the region corresponding to the internal cervical os. RESULTS: Fibre tracking demonstrated two regions: an outer circular and inner longitudinal layer. The total circumferential tract volume (TV) was greatest in the proximal region of the cervix (TV: proximal, 271 ± 198 mm3 ; middle, 186 ± 119 mm3 ; distal, 38 ± 36 mm3 ). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measurements were significantly different between regions in all samples (P < 0.0005), indicating greater tract density and organisation towards the internal os. CONCLUSION: Fibre tracking infers a system of dense, well-defined, encircling fibres in the proximal region of the cervix, corresponding to the location of the internal os. These findings may provide evidence of specific anatomic microarchitecture within the cervix able to resist intrauterine forces associated with pregnancy. TWEETABLE ABSTRACT: Diffusion-tensor MRI derived tractography identified well-defined encircling fibres at the internal os.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.(AU)

Adolescent sexual and reproductive health: the challenge for society.

Within almost all countries of the world there is a growing concern about the sexual and reproductive health of adolescents. This concern has resulted from either a real or a perceived increase in adolescent sexual activity, coupled with high rates of unplanned pregnancies, early childbearing and the transmission of sexually transmitted infections, including HIV. Although many adults have difficulties in accepting young people as sexual beings, there is now a growing consensus that young people need more information and services to help them ensure their sexual and reproductive health. Many of the programmes designed to make sexual and reproductive health information and services available to young people have used 'top down' approaches, based on adult-led risk and lifestyle orientation. In such programmes, young people are often looked upon negatively, in terms of their problems, rather than positively, in terms of their potential and capabilities. This article argues that a focus on the negative aspects of adolescent sexual and reproductive health means that young people are seen as collections of discrete problems. Furthermore, such approaches tend to view all young people as one homogeneous group when in reality adolescents are an enormously diverse group, not only in terms of age and gender, but also in terms of ability and beliefs. Such approaches therefore fail to address the vulnerabilities of particular young people and fail to contextualize sexual health within a wider framework of young people's lives. A challenge for the next century is to move away from focusing on risks, towards embracing needs and rights, and to involve young people in identifying issues and developing solutions.

High frequency of 'super-cyclones' along the Great Barrier Reef over the past 5,000 years.

Understanding long-term variability in the occurrence of tropical cyclones that are of extreme intensity is important for determining their role in ecological disturbances, for predicting present and future community vulnerability and economic loss and for assessing whether changes in the variability of such cyclones are induced by climate change. Our ability to accurately make these assessments has been limited by the short (less than 100 years) instrumented record of cyclone intensity. Here we determine the intensity of prehistoric tropical cyclones over the past 5,000 years from ridges of detrital coral and shell deposited above highest tide and terraces that have been eroded into coarse-grained alluvial fan deposits. These features occur along 1,500 km of the Great Barrier Reef and also the Gulf of Carpentaria, Australia. We infer that the deposits were formed by storms with recurrence intervals of two to three centuries, and we show that the cyclones responsible must have been of extreme intensity (central pressures less than 920 hPa). Our estimate of the frequency of such 'super-cyclones' is an order of magnitude higher than that previously estimated (which was once every several millennia), and is sufficiently high to suggest that the character of rainforests and coral reef communities were probably shaped by these events.

IMP dehydrogenase from Pneumocystis carinii as a potential drug target.

Mycophenolic acid, a specific inhibitor of IMP dehydrogenase (IMPDH; EC 1.1.1.205), is a potent inhibitor of Pneumocystis carinii growth in culture, suggesting that IMPDH may be a sensitive target for chemotherapy in this organism. The IMPDH gene was cloned as a first step to characterizing the enzyme and developing selective inhibitors. A 1.3-kb fragment containing a portion of the P. carinii IMPDH gene was amplified by PCR with two degenerate oligonucleotides based on conserved sequences in IMPDH from humans and four different microorganisms. Northern hybridization analysis showed the P. carinii IMPDH mRNA to be approximately 1.6 kb. The entire cDNA encoding P. carinii IMPDH was isolated and cloned. The deduced amino acid sequence of P. carinii IMPDH shared homology with bacterial (31 to 38%), protozoal (48 to 59%), mammalian (60 to 62%), and fungal (62%) IMPDH enzymes. The IMPDH cDNA was expressed by using a T7 expression system in an IMPDH-deficient strain of Escherichia coli (strain S phi 1101). E. coli S phi 1101 cells containing the P. carinii IMPDH gene were able to grow on medium lacking guanine, implying that the protein expressed in vivo was functional. Extracts of these E. coli cells contained IMPDH activity that had an apparent Km for IMP of 21.7 +/- 0.3 microM and an apparent Km for NAD of 314 +/- 84 microM (mean +/- standard error of the mean; n = 3), and the activity was inhibited by mycophenolic acid (50% inhibitory concentration, 24 microM; n = 2).

Cytology of pollutant metals in marine invertebrates: a review of microanalytical applications.

X-ray microanalysis (XRMA) is customized for investigations of the metabolic and detoxification strategies of heavy metals taken by marine organisms from polluted environments. Sites of uptake, intracellular accumulation, transport and excretion are visualized, analysed and quantified. Cryopreparation techniques are required to prevent the translocation or loss from specimens of soluble metal species. In marine invertebrates, metals are detoxified by systems of chemical binding and intracellular compartmentalization. XRMA investigations have concentrated on marine molluscs and crustaceans and even within these restricted groups there are marked inter-species differences in the biochemical and cytological processes which reduce metal bioavailability. Some detoxification systems also protect the carnivores which ingest the metal-laden tissues of the prey. This results in the bioreduction of metals along a food chain. These processes are investigated by XRMA which can be tuned to observe the complex interactions which operate at all levels within and between the biota and polluted environments.

Prostate-specific antigen: problems in analysis.

We have compared an "in-house" Tenovus Institute prostate-specific antigen (PSA) assay with four different commercial kits (ELSA-PSA, IRMA-Count PSA, PROS-CHECK PSA and TANDEM-R PSA) that are available in the UK. There was only good correlation and linear regression parameters between the in-house assay and one of the kit methods. The difference in values for the same sample ranged from 2 to 100-fold. These discrepancies are due, in part, to the specificity of the polyclonal and monoclonal antibodies used in the procedures and the differing "hook effects" caused by the binding capacity of the antibody pairs in the immunometric assays. Discrepancies will, however, result from the differing potencies of the standards used for the calibration curves. This data highlights the urgency for the introduction of an internationally accepted reference standard for PSA.

Heavy metal pollution induced by a ferro-nickel smelting plant in Greece.

Seven heavy metals, Co, Cr, Cu, Fe, Mn, Ni and Zn, were measured in marine sediments, plants and invertebrates in the vicinity of a ferro-nickel smelting plant in Greece. The concentrations of metals in the sediment were higher than those found in the average unpolluted Greek coastal sediment. High levels of metals were observed in the gastropod molluscs, particularly Cerithium vulgatum, which concentrated metals more than other invertebrates.

Comparison of prostate-specific antigen and prostatic acid phosphatase in the management of prostatic cancer.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostatic cancer. All patients, who participated in a phase III trial (n = 110), had disseminated disease and received first line endocrine treatment of either orchidectomy or a monthly injection of a depot luteinizing hormone-releasing hormone analogue (Zoladex). Serum samples were analyzed for PSA and PAP at 0, 3, 6, and 12 months and patients were clinically assessed at 6 and 12 months. At diagnosis, 72 and 97% of all patients had elevated PAP and PSA concentrations (greater than 4 ng/ml), respectively. Patients with progressive disease had significantly higher PSA and PAP levels at both assessments. A small number of patients in the "complete remission" group had both PSA and PAP levels within the normal range after 3 months of treatment. Similarly, both PSA and PAP levels steadily declined in the group of patients who had partial regression of the disease. The patients with stable disease, however, had a significant rise only in their PSA levels at the 12-month assessment. This data suggest that PSA is more sensitive than PAP in those patients who have a "slow progression" of the disease.

Effects of polycyclic aromatic hydrocarbons on molluscan lysosomes and endoplasmic reticulum.

Some effects of two isomeric polycyclic aromatic hydrocarbons, anthracene and phenanthrene, on the fine structure and cytochemistry of digestive cells in the marine mussel Mytilus edulis have been investigated. The cytochemical results show that increasing concentrations of anthracene and phenanthrene have different effects on the acid labilization time for latent beta-glucuronidase which is used to measure the stability of lysosomal membranes. At the ultrastructural level the limiting membranes of secondary lysosomes appear multilayered, with discontinuities and overlaps. Under the conditions of the experiment, only phenanthrene produces changes in this configuration. Both macroautophagic and microautophagic processes occur in the control and hydrocarbon treatments, and complementary data from other studies indicate that autophagic processes are enhanced by polycyclic aromatic hydrocarbons. Phenanthrene also causes proliferation of the smooth endoplasmic reticulum in the digestive cells, although cytochemical measurements of smooth endoplasmic reticulum-associated NADPH-ferrihemoprotein reductase show that anthracene stimulates activity over a greater range of concentrations than phenanthrene. The different effects of the two isomers is taken as evidence that the molecular configuration of the compound determines its reactivity with membranes and its subsequent effect on the physiology of the cells.

Adaptation of a quantitative programme for the X-ray analysis of solubilized tissue as microdroplets in the transmission electron microscope: application to the moult cycle of the shrimp Crangon crangon (L).

A quantitative programme for X-ray microanalysis is used in a non-standard manner on solubilized tissue which has been spiked with cobalt and sprayed as microdroplets on electron microscope grids. During the procedure the count time and the concentration of cobalt is related to the peak integral and, from the relative efficiencies, the concentrations of other elements are computed from the peak integrals. Absorption is taken into account but the X-ray background is not used to estimate the total mass and the beam current is not measured. The method is applied to the hepatopancreas and blood from individual shrimps, Crangon crangon, to give the concentrations of sodium, magnesium, silicon, phosphorus, sulphur, potassium and calcium at different stages of the moult cycle. In the hepatopancreas the absolute and relative quantities of phosphorus, sulphur and other elements change in phase with the moult cycle. This situation must be linked with fluctuations in levels of metabolic activity and may affect the metal-binding capacity of the tissue which is known to fluctuate. The hepatopancreas accumulates lipid and phosphorus during the intermoult period, but the level of phospholipid phosphorus remains as a constant proportion of the tissue wet weight. The gland does not store calcium for hardening the new exoskeleton after ecdysis. Magnesium is a more important and variable component and could be linked with metabolic activity. The blood composition remains more stable. However, sulphur concentration is high and variable and this may, to some extent, reflect changes in the concentration of taurine. The concentration of copper increases towards the end of the moult cycle and decreases during moulting; opposite changes occur in the hepatopancreas.

A rapid, routine technique for the X-ray microanalysis of microincinerated cryosections: an SEM study of inorganic deposits in tissues of the marine gastropod Littorina littorea (L.).

A procedure is described that prepares chemically untreated biological sections for X-ray microanalysis in the scanning electron microscope (SEM). The method aims to retain and localize labile components in tissue sections by a procedure that is both rapid and routine. Large quantities of fresh tissue can be processed for analysis within a single day. Thick cryosections are cut with a steel knife in a conventional cryostat, freeze-dried, and then ashed by either low or high temperature incineration procedures. Controlled microincineration attenuates the organic matrix to reveal sufficient surface relief for effective SEM of some cytological structure and microanalysis of the residual inorganic components. The detectability of various elements is enhanced because the relative concentrations in the residues are increased and the level of nonspecific background in the X-ray spectra is reduced. The technique is applied to different tissues from the visceral complex of the marine prosobranch Littorina littorea. In animals exposed to elevated levels of zinc it can be demonstrated tht the metal is localized both as an insoluble form in granules and as a labile form within the cytoplasm. Other metals, including magnesium, potassium, calcium, manganese, and iron, have been identified and localized. The effectiveness of this technique for retaining labile elements is compared, in outline, with that of conventional fixation procedures.