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Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight‐week‐old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post‐surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin‐1β levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non‐ischaemic limbs of HLI mice by day 7 (7.3‐ and 2.3‐fold greater than Sham, respectively, P < 0.0001). In HLI mice, muscle from the ischaemic limb had 21% lower fibre cross‐sectional area than the non‐ischaemic limb (724 ± 28 vs. 916 ± 46 μm2, P = 0.01), but the non‐ischaemic limb of HLI mice was no different from Sham. This shows that HLI induces acute systemic inflammation accompanied by immune infiltration in both ischaemic and remote skeletal muscle; however, this did not induce skeletal muscle atrophy in remote muscle within the 7‐day time course of this study. This effect of local skeletal muscle ischaemia on the inflammatory status of remote skeletal muscle may signal a priming of muscle for subsequent atrophy over a longer time course. Highlights: What is the central question of this study?Does hindlimb ischaemia‐induced inflammation cause acute immune, inflammatory and morphological alterations in remote non‐ischaemic skeletal muscle?What is the main finding and its importance?Hindlimb ischaemia induced systemic inflammation with subsequent neutrophil and macrophage infiltration in both ischaemic and non‐ischaemic skeletal muscle; however, morphological changes did not occur in non‐ischaemic muscle within 7 days. These immune alterations may have functional implications that take longer than 7 days to manifest, and subsequent or prolonged systemic inflammation and immune infiltration of muscle could lead to morphological changes and functional decline. [ABSTRACT FROM AUTHOR]

Background and aims: Drug‐related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15–64 from 2014/15 to 2019/20. Design: We fitted a Bayesian multi‐parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid‐related mortality and hospital admissions data. Estimates are stratified by age group, sex and year. Setting: Scotland, 2014/15 to 2019/20. Participants: People with opioid dependence and potential to benefit from OAT, whether ever treated or not. Using data from the Scottish Public Health Drug Linkage Programme, we identified a baseline cohort of individuals who had received OAT within the last 5 years, and all opioid‐related deaths and hospital admissions (whether among or outside of this cohort). Measurements Rates of each adverse event type and (unobserved) prevalence were jointly modelled. Findings The estimated number and prevalence of people with opioid dependence in Scotland in 2019/20 was 47 100 (95% Credible Interval [CrI] 45 700 to 48 600) and 1.32% (95% CrI 1.28% to 1.37%). Of these, 61% received OAT during 2019/20. Prevalence in Greater Glasgow and Clyde was estimated as 1.77% (95% CrI 1.69% to 1.85%). There was weak evidence that overall prevalence fell slightly from 2014/15 (change −0.07%, 95% CrI ‐0.14% to 0.00%). The population of people with opioid dependence is ageing, with the estimated number of people aged 15–34 reducing by 5100 (95% CrI 3800 to 6400) and number aged 50–64 increasing by 2800 (95% CrI 2100 to 3500) between 2014/15 and 2019/20. Conclusions: The prevalence of opioid dependence in Scotland remained high but was relatively stable, with only weak evidence of a small reduction, between 2014/15 and 2019/20. Increased numbers of opioid‐related deaths can be attributed to increased risk among people with opioid dependence, rather than increasing prevalence. [ABSTRACT FROM AUTHOR]

Mitochondria within skeletal muscle cells are located either between the muscle contractile apparatus (interfibrillar mitochondria, IFM) or beneath the cell membrane (subsarcolemmal mitochondria, SSM), with several structural and functional differences reported between IFM and SSM. However, recent 3D imaging studies demonstrate that mitochondria are particularly concentrated in the proximity of capillaries embedded in sarcolemmal grooves rather than in proximity to the sarcolemma itself (paravascular mitochondria, PVM). To evaluate the impact of capillary vs. sarcolemmal proximity, we compared the structure and function of skeletal muscle mitochondria located either lateral to embedded capillaries (PVM), adjacent to the sarcolemma but not in PVM pools (SSM) or interspersed between sarcomeres (IFM). Mitochondrial morphology and interactions were assessed by 3D electron microscopy coupled with machine learning segmentation, whereas mitochondrial energy conversion was assessed by two‐photon microscopy of mitochondrial membrane potential, content, calcium, NADH redox and flux in live, intact cells. Structurally, although PVM and SSM were similarly larger than IFM, PVM were larger, rounder and had more physical connections to neighbouring mitochondria compared to both IFM and SSM. Functionally, PVM had similar or greater basal NADH flux compared to SSM and IFM, respectively, despite a more oxidized NADH pool and a greater membrane potential, signifying a greater activation of the electron transport chain in PVM. Together, these data indicate that proximity to capillaries has a greater impact on resting mitochondrial energy conversion and distribution in skeletal muscle than the sarcolemma alone. Key points: Capillaries have a greater impact on mitochondrial energy conversion in skeletal muscle than the sarcolemma.Paravascular mitochondria are larger, and the outer mitochondrial membrane is more connected with neighbouring mitochondria.Interfibrillar mitochondria are longer and have greater contact sites with other organelles (i.e. sarcoplasmic reticulum and lipid droplets).Paravascular mitochondria have greater activation of oxidative phosphorylation than interfibrillar mitochondria at rest, although this is not regulated by calcium. [ABSTRACT FROM AUTHOR]

Skeletal muscle cellular development requires the integrated assembly of mitochondria and other organelles adjacent to the sarcomere in support of muscle contractile performance. However, it remains unclear how interactions among organelles and with the sarcomere relates to the development of muscle cell function. Here, we combine 3D volume electron microscopy, proteomic analyses, and live cell functional imaging to investigate the postnatal reorganization of mitochondria–organelle interactions in skeletal muscle. We show that while mitochondrial networks are disorganized and loosely associated with the contractile apparatus at birth, contact sites among mitochondria, lipid droplets and the sarcoplasmic reticulum are highly abundant in neonatal muscles. The maturation process is characterized by a transition to highly organized mitochondrial networks wrapped tightly around the muscle sarcomere but also to less frequent interactions with both lipid droplets and the sarcoplasmic reticulum. Concomitantly, expression of proteins involved in mitochondria–organelle membrane contact sites decreases during postnatal development in tandem with a decrease in abundance of proteins associated with sarcomere assembly despite an overall increase in contractile protein abundance. Functionally, parallel measures of mitochondrial membrane potential, NADH redox status, and NADH flux within intact cells revealed that mitochondria in adult skeletal muscle fibres maintain a more activated electron transport chain compared with neonatal muscle mitochondria. These data demonstrate a developmental redesign reflecting a shift from muscle cell assembly and frequent inter‐organelle communication toward a muscle fibre with mitochondrial structure, interactions, composition and function specialized to support contractile function. Key points: Mitochondrial network organization is remodelled during skeletal muscle postnatal development.The mitochondrial outer membrane is in frequent contact with other organelles at birth and transitions to more close associations with the contractile apparatus in mature muscles.Mitochondrial energy metabolism becomes more activated during postnatal development.Understanding the developmental redesign process within skeletal muscle cells may help pinpoint specific areas of deficit in muscles with developmental disorders. [ABSTRACT FROM AUTHOR]

Mitochondrial calcium concentration ([Ca2+]m) plays an essential role in bioenergetics, and loss of [Ca2+]m homeostasis can trigger diseases and cell death in numerous cell types. Ca2+ uptake into mitochondria occurs via the mitochondrial Ca2+ uniporter (MCU), which is regulated by three mitochondrial Ca2+ uptake (MICU) proteins localized in the intermembrane space, MICU1, 2, and 3. We generated a mouse model of systemic MICU3 ablation and examined its physiological role in skeletal muscle. We found that loss of MICU3 led to impaired exercise capacity. When the muscles were directly stimulated there was a decrease in time to fatigue. MICU3 ablation significantly increased the maximal force of the KO muscle and altered fibre type composition with an increase in the ratio of type IIb (low oxidative capacity) to type IIa (high oxidative capacity) fibres. Furthermore, MICU3‐KO mitochondria have reduced uptake of Ca2+ and increased phosphorylation of pyruvate dehydrogenase, indicating that KO animals contain less Ca2+ in their mitochondria. Skeletal muscle from MICU3‐KO mice exhibited lower net oxidation of NADH during electrically stimulated muscle contraction compared with wild‐type. These data demonstrate that MICU3 plays a role in skeletal muscle physiology by setting the proper threshold for mitochondrial Ca2+ uptake, which is important for matching energy demand and supply in muscle. Key points: Mitochondrial calcium uptake is an important regulator of bioenergetics and cell death and is regulated by the mitochondrial calcium uniporter (MCU) and three calcium sensitive regulatory proteins (MICU1, 2 and 3).Loss of MICU3 leads to impaired exercise capacity and decreased time to skeletal muscle fatigue.Skeletal muscle from MICU3‐KO mice exhibits a net oxidation of NADH during electrically stimulated muscle contractions, suggesting that MICU3 plays a role in skeletal muscle physiology by matching energy demand and supply. [ABSTRACT FROM AUTHOR]

We study the role that recourse plays in the commercial real estate loan contracts of the largest U.S. banks. We find that recourse is valued by lenders as a substitute for conventional equity. At origination, recourse loans have rate spreads that are about 20 basis points lower and loan‐to‐value ratios that are almost 3 percentage points higher than nonrecourse loans. Dynamically, recourse affects loan modification negotiations by providing additional bargaining power to the lender. Recourse loans were half as likely to receive accommodation during the COVID‐19 pandemic, and the modifications that did occur entailed a relatively smaller reduction in payments. [ABSTRACT FROM AUTHOR]

Background: Patient‐reported outcome measures place the patient at the centre of his/her care. There are calls to introduce child‐reported outcome measures to mental health services. We aimed to (a) develop an age‐appropriate patient‐reported outcome measure for children's mental health, and (b) validate this in a primary school and Child and Adolescent Mental Health Service (CAMHS). Methods: A list of items to measure children's mental health was proposed (Draft 1) and revised to 14 items following focus group and user consultation (Draft 2). A colourful, cartoon and emoji version was created in consultation with children (Draft 3); a professional cartoon artist created the final 'My Feelings Form' (MFF), with usability feedback (Draft 4). The MFF was tested by 317 children aged 4–13 years from one mixed‐gender primary school at two time points in 1 day, and 25 children aged 4–13 years from CAMHS. Results were analysed using test–retest reliability and exploratory factor analysis; a receiver operator characteristic curve was constructed. Results: The CAMHS group scored significantly higher than the school group for the mean total score (23.5 ± 11.3 vs. 16.1 ± 6.2) and for 10 items. Test–retest reliability was acceptable (correlation = 0.74, p <.001). Exploratory factor analysis using 10 informative items identified two factors – emotional factor (Cronbach's alpha = 0.74) and function factor (Cronbach's alpha = 0.59). The revised 10‐item form has a Cronbach's alpha of 0.77; a cut‐off of 12 has a sensitivity of 80% and specificity of 60%, indicating that it correctly identified 80% of those who were attending CAMHS and gave 60% of the schoolchildren a negative result. Conclusions: The colourful MFF was co‐produced with children, and preliminary data suggest that it is a useful patient‐reported outcome measure for children's mental health. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) is associated with increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC) in people with chronic liver diseases, particularly non‐alcoholic fatty liver disease (NAFLD). However, the absolute risk of progression is low. So, it is crucial to accurately identify patients who would benefit most from hepatology referral and intensified management. Current risk‐stratification tools are suboptimal and perform worse in people with diabetes. Aims: To determine whether the addition of complementary biomarker(s) to current NAFLD risk‐stratification tools in people with T2D could improve the identification of people who are at increased risk of developing incident cirrhosis or HCC. Methods: The Edinburgh Type 2 diabetes Study (ET2DS) is a cohort study of men and women with T2D (n = 1066, age 60–75 at baseline). Cases of cirrhosis and HCC were identified over 11 years of follow‐up. Biomarkers were measured at baseline and year 1 and association with incident disease was assessed using logistic regression. Results: Of existing risk‐stratification scores tested, the Fibrosis‐4 (FIB‐4) index and the AST:platelet ratio index (APRI) performed best in this cohort. Addition of hyaluronic acid (cut‐point ≥ 50 μ g/L) to FIB‐4 (cut‐point ≥ 1.3) maintained a false negative rate of ≤25% and reduced the number of people incorrectly identified as "high risk" for incident disease by ∼50%. Conclusions: The addition of hyaluronic acid to FIB‐4 reduced the proportion of people inappropriately identified as "high risk" for development of cirrhosis/HCC in a community population of otherwise asymptomatic people with T2D. These findings require a validation in independent cohorts. [ABSTRACT FROM AUTHOR]

Aim: The dramatic curtailment of endoscopy and CT colonography capacity during the coronavirus pandemic has adversely impacted timely diagnosis of colorectal cancer (CRC). We describe a rapidly implemented COVID‐adapted diagnostic pathway to mitigate risk and maximize cancer diagnosis in patients referred with symptoms of suspected CRC. Method: The 'COVID‐adapted pathway' integrated multiple quantitative faecal immunochemical tests (qFIT) to enrich for significant colorectal disease with judicious use of CT with oral contrast to detect gross pathology. Patients reporting 'high‐risk' symptoms were triaged to qFIT+CT and the remainder underwent an initial qFIT to inform subsequent investigation. Demographic and clinical data were prospectively collected. Outcomes comprised cancer detection frequency. Results: Overall, 422 patients (median age 64 years, 220 women) were triaged using this pathway. Most (84.6%) were referred as 'urgent suspicious of cancer'. Of the 422 patients, 202 (47.9%) were triaged to CT and qFIT, 211 (50.0%) to qFIT only, eight (1.9%) to outpatient clinic and one to colonoscopy. Fifteen (3.6%) declined investigation and seven (1.7%) were deemed unfit. We detected 13 cancers (3.1%), similar to the mean cancer detection rate from all referrals in 2017–2019 (3.3%). Compared with the period 1 April–31 May in 2017–2019, we observed a 43% reduction in all primary care referrals (1071 referrals expected reducing to 609). Conclusion: This COVID‐adapted pathway mitigated the adverse effects on diagnostic capacity and detected cancer at the expected rate within those referred. However, the overall reduction in the number of referrals was substantial. The described risk‐mitigating measures could be a useful adjunct whilst standard diagnostic services remain constrained due to the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Research ethics boards would not be disputed however, in the case of Oak Ridge, the defendants maintained they were not doing research but "treatment". Thus, the case was reconstituted as a group action, styled I Barker v Barker, i as the lead plaintiff was called Reginald Barker and the lead defendant was Dr. Elliott Barker (not blood relatives). In his article 'Misplaced Enthusiasm, a Neglect of Human Rights - Beneficence is Not Enough' (2021), John Gunn eloquently reviews a group action lawsuit in which 28 individuals (eight deceased prior to the judgement) who had been detained by the state (the Province of Ontario, Canada) at a maximum-security facility known as Oak Ridge were abused in the name of "treatment" and "research". [Extracted from the article]

Mitochondrial structures were probably observed microscopically in the 1840s, but the idea of oxidative phosphorylation (OXPHOS) within mitochondria did not appear until the 1930s. The foundation for research into energetics arose from Meyerhof's experiments on oxidation of lactate in isolated muscles recovering from electrical contractions in an O2 atmosphere. Today, we know that mitochondria are actually reticula and that the energy released from electron pairs being passed along the electron transport chain from NADH to O2 generates a membrane potential and pH gradient of protons that can enter the molecular machine of ATP synthase to resynthesize ATP. Lactate stands at the crossroads of glycolytic and oxidative energy metabolism. Based on reported research and our own modelling in silico, we contend that lactate is not directly oxidized in the mitochondrial matrix. Instead, the interim glycolytic products (pyruvate and NADH) are held in cytosolic equilibrium with the products of the lactate dehydrogenase (LDH) reaction and the intermediates of the malate‐aspartate and glycerol 3‐phosphate shuttles. This equilibrium supplies the glycolytic products to the mitochondrial matrix for OXPHOS. LDH in the mitochondrial matrix is not compatible with the cytoplasmic/matrix redox gradient; its presence would drain matrix reducing power and substantially dissipate the proton motive force. OXPHOS requires O2 as the final electron acceptor, but O2 supply is sufficient in most situations, including exercise and often acute illness. Recent studies suggest that atmospheric normoxia may constitute a cellular hyperoxia in mitochondrial disease. As research proceeds appropriate oxygenation levels should be carefully considered. [ABSTRACT FROM AUTHOR]

Background: The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non‐alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. American guidelines, while not advocating a screening protocol, suggest using non‐invasive markers of fibrosis for risk‐stratification and guiding onward referral. Aims: To test the ability of individual fibrosis scores and the European screening algorithm to predict 11‐year incident cirrhosis/HCC in an asymptomatic community cohort of older people with Type 2 diabetes. Methods: The Edinburgh Type 2 Diabetes Study investigated men and women with Type 2 diabetes (n = 1066, aged 60–75 at baseline). Liver markers were measured at baseline and year 1; steatosis and fibrosis markers were calculated according to independently published calculations. During 11 years of follow‐up, cases of cirrhosis and HCC were identified. Results: Forty‐three out of 1059 participants with no baseline cirrhosis/HCC developed incident disease. All scores were significantly associated with incident liver disease by odds ratio (P <.05). The ability of the risk‐stratification tools to accurately identify those who developed incident cirrhosis/HCC was poor with low‐positive predictive values (5‐46%) and high false‐negative and ‐positive rates (up to 60% and 77%) respectively. When fibrosis risk scores were used in conjunction with the European algorithm, they performed modestly better than when applied in isolation. Conclusions: In a cohort with a moderately low incidence of cirrhosis/HCC, existing risk scores did not reliably identify participants at high risk. Better prediction models for cirrhosis/HCC in people with Type 2 diabetes are required. [ABSTRACT FROM AUTHOR]

Background and aims Design Setting Participants Measurements Findings Conclusion Opioid dependence is associated with an increased risk of suicide. Drug‐related mortality among people with opioid dependence in Scotland has more than tripled since 2010; less is known about changes in suicide risk. We aimed to determine if opioid agonist therapy (OAT) in Scotland is protective against suicide and to measure trends in suicide rates in those with opioid dependence over time.Retrospective cohort study.Scotland, UK.46 453 individuals in Scotland who received at least one prescription for OAT between 2011 and 2020 with over 304 000 person‐years (pys) of follow‐up.We calculated standardised mortality ratios (SMR) using the age‐ and sex‐specific suicide rates in Scotland for years 2011–2020. We fitted multivariable competing‐risk regression models to estimate suicide rates by OAT exposure and to estimate trends over time, adjusting for potential confounders.There were 575 deaths classed as suicide among the cohort and the overall suicide rate was 1.89 (95% confidence interval [CI] = 1.74–2.05) per 1000 pys. Age and sex SMR for suicide was 7.05 times (95% CI = 6.50–7.65) higher than in the general population. After adjustment, OAT was shown to be highly protective against suicide, with rates more than three times greater (adjusted hazard ratio: 3.07; 95% CI = 2.60–3.62) off OAT compared with on OAT. Suicide rates decreased over time, falling from 2.57 (95% CI = 2.19–3.02) per 1000 pys in 2011–12 to 1.48 (95% CI = 1.21–1.82) in 2019–20.People with opioid dependence in Scotland appear to have a greater risk of suicide than the general population. Treatment is protective, with rates of suicide lower among those on opioid agonist therapy. Suicide rates have decreased over time, during a period in which drug‐related death rates in Scotland have risen to globally high levels. [ABSTRACT FROM AUTHOR]

Key points: We developed a novel metabolic imaging approach that provides direct measures of the rate of mitochondrial energy conversion with single‐cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE).Measures of mitochondrial NADH flux by mitoRACE are sensitive to physiological and pharmacological perturbations in vivo.Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells with potential for broad applications in the study of energy metabolism. Mitochondria play a critical role in numerous cell types and diseases, and structure and function of mitochondria can vary greatly among cells or within different regions of the same cell. However, there are currently limited methodologies that provide direct assessments of mitochondrial function in vivo, and contemporary measures of mitochondrial energy conversion lack the spatial resolution necessary to address cellular and subcellular heterogeneity. Here, we describe a novel metabolic imaging approach that provides direct measures of mitochondrial energy conversion with single‐cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). MitoRACE measures the rate of NADH flux through the steady‐state mitochondrial NADH pool by rapidly inhibiting mitochondrial energetic flux, resulting in an immediate, linear increase in NADH fluorescence proportional to the steady‐state NADH flux rate, thereby providing a direct measure of mitochondrial NADH flux. The experiments presented here demonstrate the sensitivity of this technique to detect physiological and pharmacological changes in mitochondrial flux within tissues of living animals and reveal the unique capability of this technique to evaluate mitochondrial function with single‐cell and subcellular resolution in different cell types in vivo and in cell culture. Furthermore, we highlight the potential applications of mitoRACE by showing that within single neurons, mitochondria in neurites have higher energetic flux rates than mitochondria in the cell body. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells, with potential for broad applications in the study of energy metabolism. Key points: We developed a novel metabolic imaging approach that provides direct measures of the rate of mitochondrial energy conversion with single‐cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE).Measures of mitochondrial NADH flux by mitoRACE are sensitive to physiological and pharmacological perturbations in vivo.Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells with potential for broad applications in the study of energy metabolism. [ABSTRACT FROM AUTHOR]

Key points: Muscle mitochondrial networks changed from a longitudinal, fibre parallel orientation to a perpendicular configuration during postnatal development.Mitochondrial dynamics, mitophagy and calcium uptake proteins were abundant during early postnatal development.Mitochondrial biogenesis and oxidative phosphorylation proteins were upregulated throughout muscle development.Postnatal muscle mitochondrial network formation is accompanied by a change in protein expression profile from mitochondria designed for co‐ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism. Striated muscle mitochondria form connected networks capable of rapid cellular energy distribution. However, the mitochondrial reticulum is not formed at birth and the mechanisms driving network development remain unclear. In the present study, we aimed to establish the network formation timecourse and protein expression profile during postnatal development of the murine muscle mitochondrial reticulum. Two‐photon microscopy was used to observe mitochondrial network orientation in tibialis anterior (TA) muscles of live mice at postnatal days (P) 1, 7, 14, 21 and 42, respectively. All muscle fibres maintained a longitudinal, fibre parallel mitochondrial network orientation early in development (P1–7). Mixed networks were most common at P14 but, by P21, almost all fibres had developed the perpendicular mitochondrial orientation observed in mature, glycolytic fibres. Tandem mass tag proteomics were then applied to examine changes in 6869 protein abundances in developing TA muscles. Mitochondrial proteins increased by 32% from P1 to P42. In addition, both nuclear‐ and mitochondrial‐DNA encoded oxidative phosphorylation (OxPhos) components were increased during development, whereas OxPhos assembly factors decreased. Although mitochondrial dynamics and mitophagy were induced at P1–7, mitochondrial biogenesis was enhanced after P14. Moreover, calcium signalling proteins and the mitochondrial calcium uniporter had the highest expression early in postnatal development. In conclusion, mitochondrial networks transform from a fibre parallel to perpendicular orientation during the second and third weeks after birth in murine glycolytic skeletal muscle. This structural transition is accompanied by a change in protein expression profile from mitochondria designed for co‐ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism. Key points: Muscle mitochondrial networks changed from a longitudinal, fibre parallel orientation to a perpendicular configuration during postnatal development.Mitochondrial dynamics, mitophagy and calcium uptake proteins were abundant during early postnatal development.Mitochondrial biogenesis and oxidative phosphorylation proteins were upregulated throughout muscle development.Postnatal muscle mitochondrial network formation is accompanied by a change in protein expression profile from mitochondria designed for co‐ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism. [ABSTRACT FROM AUTHOR]

Key points Heart function is critically dependent upon the balance of energy production and utilization. Sarcolemmal ATP-sensitive potassium channels (KATP channels) in cardiac myocytes adjust contractile function to compensate for the level of available energy., Understanding the activation of KATP channels in working myocardium during high-stress situations is crucial to the treatment of cardiovascular disease, especially ischaemic heart disease., Using a new optical mapping approach, we measured action potentials from the surface of excised contracting rabbit hearts to assess when sarcolemmal KATP channels were activated during physiologically relevant workloads and during gradual reductions in myocardial oxygenation., We demonstrate that left ventricular pressure is closely linked to KATP channel activation and that KATP channel inhibition with a low concentration of tolbutamide prevents electromechanical decline when oxygen availability is reduced. As a result, KATP channel inhibition probably exacerbates a mismatch between energy demand and energy production when myocardial oxygenation is low., Abstract Sarcolemmal ATP-sensitive potassium channel (KATP channel) activation in isolated cells is generally understood, although the relationship between myocardial oxygenation and KATP activation in excised working rabbit hearts remains unknown. We optically mapped action potentials (APs) in excised rabbit hearts to test the hypothesis that hypoxic changes would be more severe in left ventricular (LV) working hearts (LWHs) than Langendorff (LANG) perfused hearts. We further hypothesized that KATP inhibition would prevent those changes. Optical APs were mapped when measuring LV developed pressure (LVDP), coronary flow rate and oxygen consumption in LANG and LWHs. Hearts were paced to increase workload and perfusate was deoxygenated to study the effects of myocardial hypoxia. A subset of hearts was perfused with 1 μ m tolbutamide (TOLB) to identify the level of AP duration (APD) shortening attributed to KATP channel activation. During sinus rhythm, APD was shorter in LWHs compared to LANG hearts. APD in both LWHs and LANG hearts dropped steadily during deoxygenation. With TOLB, APDs in LWHs were longer at all workloads and APD reductions during deoxygenation were blunted in both LWHs and LANG hearts. At 50% perfusate oxygenation, APD and LVDP were significantly higher in LWHs perfused with TOLB (199 ± 16 ms; 92 ± 5.3 mmHg) than in LWHs without TOLB (109 ± 14 ms, P = 0.005; 65 ± 6.5 mmHg, P = 0.01). Our results indicate that KATP channels are activated to a greater extent in perfused hearts when the LV performs pressure-volume work. The results of the present study demonstrate the critical role of KATP channels in modulating myocardial function over a wide range of physiological conditions. [ABSTRACT FROM AUTHOR]

This paper investigates a postprocessing approach to correct spatial distortion in two-photon fluorescence microscopy images for vascular network reconstruction. It is aimed at in vivo imaging of large field-of-view, deep-tissue studies of vascular structures. Based on simple geometric modelling of the object-of-interest, a distortion function is directly estimated from the image volume by deconvolution analysis. Such distortion function is then applied to subvolumes of the image stack to adaptively adjust for spatially varying distortion and reduce the image blurring through blind deconvolution. The proposed technique was first evaluated in phantom imaging of fluorescent microspheres that are comparable in size to the underlying capillary vascular structures. The effectiveness of restoring three-dimensional (3D) spherical geometry of the microspheres using the estimated distortion function was compared with empirically measured point-spread function. Next, the proposed approach was applied to in vivo vascular imaging of mouse skeletal muscle to reduce the image distortion of the capillary structures. We show that the proposed method effectively improve the image quality and reduce spatially varying distortion that occurs in large field-of-view deep-tissue vascular dataset. The proposed method will help in qualitative interpretation and quantitative analysis of vascular structures from fluorescence microscopy images. [ABSTRACT FROM AUTHOR]

New Findings What is the topic of this review? This review discusses how the function and electrophysiology of isolated perfused hearts are affected by oxygenation and energy utilization. The impact of oxygenation on fluorescence measurements in perfused hearts is also discussed., What advances does it highlight? Recent studies have illuminated the inherent differences in electromechanical function, energy utilization rate and oxygen requirements between the primary types of excised heart preparations. A summary and analysis of how these variables affect experimental results are necessary to elevate the physiological relevance of these approaches in order to advance the field of whole-heart research., The ex vivo perfused heart recreates important aspects of in vivo conditions to provide insight into whole-organ function. In this review we discuss multiple types of ex vivo heart preparations, explain how closely each mimic in vivo function, and discuss how changes in electromechanical function and inadequate oxygenation of ex vivo perfused hearts may affect measurements of physiology. Hearts that perform physiological work have high oxygen demand and are likely to experience hypoxia when perfused with a crystalloid perfusate. Adequate myocardial oxygenation is critically important for obtaining physiologically relevant measurements, so when designing experiments the type of ex vivo preparation and the capacity of perfusate to deliver oxygen must be carefully considered. When workload is low, such as during interventions that inhibit contraction, oxygen demand is also low, which could dramatically alter a physiological response to experimental variables. Changes in oxygenation also alter the optical properties of cardiac tissue, an effect that may influence optical signals measured from both endogenous and exogenous fluorophores. Careful consideration of oxygen supply, working condition, and wavelengths used to acquire optical signals is critical for obtaining physiologically relevant measurements during ex vivo perfused heart studies. [ABSTRACT FROM AUTHOR]

Recent documents pertaining to K-12 education have fostered a connection between engineering and science education to help better prepare our students and future citizens to better meet the current and future challenges of our modern and technological society. With that connection, there has been a concerted effort to raise the visibility of engineering within K-12 science education, which is reflected in the Framework for K-12 Science Education and the recently released Next Generation Science Standards. As states look towards the adoption and implementation of the Next Generation Science Standards, it is important to take a deeper look at the shift in K-12 science education that is being suggested by these documents and what that means in terms of the potential changes for states that have chosen to adopt these standards. The main research question that has guided the work for this paper is: What is the extent and quality of the engineering that is present in state science standards and the Next Generation Science Standards? This paper will present a detailed analysis of the landscape of engineering in K-12 policy before and after the release of the NGSS through a comparative case study of academic state science standards and Next Generation Science Standards. This comparison provides insight into what the widespread adoption of the NGSS would mean in terms of potential changes in the way we implement science education in the United States. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 52: 296-318, 2015 [ABSTRACT FROM AUTHOR]

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Background & Aims Type 2 diabetes is an established risk factor for the presence and progression of fatty liver. Little is known about the distributions and correlates of hepatic non-invasive biomarkers in community-based populations with diabetes, unselected for liver disease. We aimed to identify the distribution of, and metabolic risk factors associated with serum cytokeratin-18 ( CK18) and the Enhanced Liver Fibrosis score ( ELF), in a large, representative cohort of people with type 2 diabetes (the Edinburgh Type 2 Diabetes Study, ET2 DS). Methods Nine hundred and thirty-nine ET2 DS participants, aged 60-74 years underwent physical examination including ultrasound for assessment of liver fat. Representative subgroups were assessed for markers of chronic liver disease ( CK18 and ELF). Results CK18 values ranged from 29-993 U/L (median 102, IQR 76-137 U/L) and ELF scores ranged from 6.9-11.6 (mean 8.9, SD 0.8). Statistically significant associations were found between both biomarkers and a number of metabolic risk factors. Neither CK18 nor ELF was consistently or strongly associated with established hepatic risk factors (alcohol excess, hepatotoxic medication use and positive immunology titres). Conclusions We identified the distribution of CK18 and ELF in a large cohort of older people with type 2 diabetes and showed that these markers are associated with an adverse metabolic risk factor profile, although much of the variation in biomarkers remained unexplained. Prospective studies are required to determine the extent to which CK18 and/or ELF predict the development of symptomatic liver disease and to identify additional risk factors which may influence the development of advanced liver disease in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective To provide insight into mitochondrial function in vivo, we evaluated the 3D spatial relationship between capillaries, mitochondria, and muscle fibers in live mice. Methods 3D volumes of in vivo murine TA muscles were imaged by MPM. Muscle fiber type, mitochondrial distribution, number of capillaries, and capillary-to-fiber contact were assessed. The role of Mb-facilitated diffusion was examined in Mb KO mice. Distribution of GLUT4 was also evaluated in the context of the capillary and mitochondrial network. Results MPM revealed that 43.6 ± 3.3% of oxidative fiber capillaries had ≥50% of their circumference embedded in a groove in the sarcolemma, in vivo. Embedded capillaries were tightly associated with dense mitochondrial populations lateral to capillary grooves and nearly absent below the groove. Mitochondrial distribution, number of embedded capillaries, and capillary-to-fiber contact were proportional to fiber oxidative capacity and unaffected by Mb KO. GLUT4 did not preferentially localize to embedded capillaries. Conclusions Embedding capillaries in the sarcolemma may provide a regulatory mechanism to optimize delivery of oxygen to heterogeneous groups of muscle fibers. We hypothesize that mitochondria locate to PV regions due to myofibril voids created by embedded capillaries, not to enhance the delivery of oxygen to the mitochondria. [ABSTRACT FROM AUTHOR]

We describe a compact, non-contact design for a total emission detection (c-TED) system for intra-vital multiphoton imaging. To conform to a standard upright two-photon microscope design, this system uses a parabolic mirror surrounding a standard microscope objective in concert with an optical path that does not interfere with normal microscope operation. The non-contact design of this device allows for maximal light collection without disrupting the physiology of the specimen being examined. Tests were conducted on exposed tissues in live animals to examine the emission collection enhancement of the c-TED device compared to heavily optimized objective-based emission collection. The best light collection enhancement was seen from murine fat (5×-2× gains as a function of depth), whereas murine skeletal muscle and rat kidney showed gains of over two and just under twofold near the surface, respectively. Gains decreased with imaging depth (particularly in the kidney). Zebrafish imaging on a reflective substrate showed close to a twofold gain throughout the entire volume of an intact embryo (approximately 150 μm deep). Direct measurement of bleaching rates confirmed that the lower laser powers, enabled by greater light collection efficiency, yielded reduced photobleaching in vivo. The potential benefits of increased light collection in terms of speed of imaging and reduced photo-damage, as well as the applicability of this device to other multiphoton imaging methods is discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle-aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis. [ABSTRACT FROM AUTHOR]

When conducting optical imaging experiments, in vivo, the signal to noise ratio and effective spatial and temporal resolution is fundamentally limited by physiological motion of the tissue. A three-dimensional (3D) motion tracking scheme, using a multiphoton excitation microscope with a resonant galvanometer, (512 × 512 pixels at 33 frames s−1) is described to overcome physiological motion, in vivo. The use of commercially available graphical processing units permitted the rapid 3D cross-correlation of sequential volumes to detect displacements and adjust tissue position to track motions in near real-time. Motion phantom tests maintained micron resolution with displacement velocities of up to 200 μm min−1, well within the drift observed in many biological tissues under physiologically relevant conditions. In vivo experiments on mouse skeletal muscle using the capillary vasculature with luminal dye as a displacement reference revealed an effective and robust method of tracking tissue motion to enable (1) signal averaging over time without compromising resolution, and (2) tracking of cellular regions during a physiological perturbation. [ABSTRACT FROM AUTHOR]

Aim Concerns exist regarding laparoscopic rectal cancer surgery due to increased rates of open conversion, complications and circumferential resection margin positivity. This study reports medium-term results from consecutive unselected cases in a single surgeon series. Method The results of laparoscopic total mesorectal excision (TME) for rectal cancer over a 9-year period within the context of an evolving 'enhanced recovery protocol' (ERP) were reviewed from analysis of a prospectively maintained database. Results One hundred and fifty patients (91 male, median age 69 years, median BMI 26) underwent laparoscopic TME over 9 years. Median follow up was 28.5 months (range 0-88). Sixteen (10.6%) patients underwent neoadjuvant radiotherapy. Six (4.0%) required open conversion and 13 (9.0%) had an anastomotic leakage. The proportion of Dukes stages were: A, 33.3%; B, 30.7%; C, 31.3%; D, 4.7%. Five (3.3%) patients had an R1 and one an R2 resection. Median length of postoperative stay was 6 days. Three (2.0%) patients died within 30 days. Four (2.7%) developed local recurrence and 14 (9.3%) developed distant metastases. Predicted 5-year disease-free and overall survival rates by Kaplan-Meier analysis were 85.8% and 78.7%, respectively. Conclusion Laparoscopic TME surgery can safely be offered to unselected patients with rectal cancer with excellent medium-term results. [ABSTRACT FROM AUTHOR]

Aim The safety and short-term outcome of laparoscopic surgery for recurrent ileocolic Crohn's disease was compared with the outcome following primary resection. Method Between June 2002 and June 2010, 59 consecutive unselected patients (30 of whom had recurrent disease) underwent laparoscopic ileocolic resection. Four primary resections and one revision were performed as a single incision laparoscopic surgery (SILS) procedure. Results There was no difference between the two groups in terms of age, body mass index, American Society of Anesthesiology (ASA) grade or the presence or absence of fistulating disease. The median operating time was significantly longer for the revision group (125 min vs 85 min; P < 0.001). The rate of conversion was 8.5%, morbidity was 20% and mortality was 0% ( P = not significant between groups). Risk factors for conversion included a complex fistula, fibrosis and the need to carry out multiple stricturoplasty. Patients in whom surgery was converted had a longer hospital stay and a higher morbidity (40%). The median hospital stay was 3 days, the return to theatre rate was 5% and the re-admission rate was 5% ( P = not significant between groups). Conclusion Laparoscopic surgery for recurrent ileocolic Crohn's disease is safe and can lead to significant short-term benefit, including earlier discharge. Conversion increases the length of stay in hospital and the overall morbidity. [ABSTRACT FROM AUTHOR]

Aim Stapled transanal rectal resection (STARR) is an increasingly accepted treatment for obstructed defaecation syndrome (ODS) associated with internal rectal prolapse (IRP) and rectocoele. The aim of this study is to evaluate the medium to long-term outcomes of STARR for ODS. Method The intermediate-term results of STARR used over a 9 -year period were reviewed from the analysis of a prospectively maintained database. Patients were followed for a median period of 98 (95% CI 85-112, range 5-386) weeks. Results Three hundred and forty-four (234 woman) patients of median age 54 (19-90) years underwent STARR over a 9- year period. Preoperative symptoms included pelvic pain (93%), incomplete evacuation (90%), urgency (74%), a sensation of obstruction (65%) and rectal digitation (27%). Thirteen had the solitary rectal ulcer syndrome. Of 326 patients with follow-up data, 249 (76%) were followed beyond 1 year and 149 (43%) beyond 2 years. The ODS score improved [14.6 ± 5.4 pre vs 1.6 ± 3.1 post ( P < 0.0001)] as did the faecal incontinence (FI) score [3.5 ± 3.3 pre vs 0.4 ± 1.3 post ( P < 0.0001)]. Fifteen (4.3%) patients reported deterioration in FI, and 11 (3.2%) experienced new onset minor incontinence. Urgency was 72% at 8 weeks, 20% at 16 weeks, 11.5% at 52 weeks and 5% at 1.5 years. None of the 29 patients followed beyond 4 years reported urgency. Urgency was unrelated to sex, age or preoperative ODS symptoms (Mantel-Cox log-rank). Recurrent symptoms of ODS occurred in 4.9%. Eighty-one per cent of patients were highly satisfied with STARR and would recommend or have it again. Conclusion STARR was successful for the treatment of selected patients with ODS and IRP. Postoperative faecal urgency rapidly decreases with time. It is not possible to predict who will develop urgency. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the left-ventricular diastolic chamber size in patients with a normal ejection fraction and elevated left-sided filling pressures. Background: The consensus view that patients with normal left ventricular ejection fraction (LVEF) and elevated left-sided filling pressures have a normal left ventricular diastolic size is a point of controversy. Methods: We reviewed the coded database of echocardiographic studies performed at one institution between July 2007 and July 2008. We performed a retrospective descriptive study of 35 patients with normal ejection fraction (≥55%) and elevated left-sided filling pressures. We looked at their left ventricular internal diastolic diameter (LVIDD). Results: Our population had a high prevalence of hypertension (100%), obesity (63%), diabetes (40%), chronic kidney disease (51%), coronary artery disease (25%), anemia (43%), and left ventricular hypertrophy (65%). Clinical diagnosis of heart failure was documented in 63% of the patients. LVIDD was mildly increased in comparison to a normal historical population: 4.85 ± 0.5 cm for females, 5.3 ± 0.5 cm for males, as compared to 4.6 ± 0.3 cm for normal females (P = 0.045) and 5 ± 0.4 cm for normal males (P < 0.001). However, the distribution of the indexed LVIDDs in these patients was comparable to the normal population (2.6 ± 0.4 cm/m2 for the study population, as compared to 2.7± 0.2 cm/m2 for the normal population, P = 0.16). Conclusion: In a population of patients with a normal LVEF and high left ventricular filling pressures, the indexed LV diastolic size is not increased in comparison to a normal population. (Echocardiography 2010;27:501-504) [ABSTRACT FROM AUTHOR]

The article reports the clinical case of a female patient who suffered a sudden speech difficulty, facial weakness, and dysphasia. Diagnostic tests including chest x-ray, pulmonary arteriogram and Transesophageal echocardiography revealed Arteriovenous (AV) Fistula which was surgically repaired. The diagnostic findings from the Magnetic Resonance Imaging suggest that pulmonary AV fistula in the patient occured due to earlier arterial embolism and multiple strokes.

Discusses findings of echocardiographic abnormalities in patients infected with HIV. Prevalence of pericardial effusion (PE) in HIV patients; Type of PE seen in HIV patients; Incidence of asymptomatic and symptomatic left ventricular dysfunction among the patients; Risk for development of pulmonary arterial hypertension among HIV infected patients.

To meet the introduction of the two-week wait (TWW) rule for patients with suspected colorectal cancer, a fast-track barium enema (FTBE) service was set up. This study was conducted to evaluate the success of this approach in preparation for meeting the forthcoming targets on waiting times to treatment from referral and diagnosis.All patients were offered a double-contrast barium enema within two-weeks, except those with a palpable rectal mass. FTBE were double-reported by specialist gastrointestinal radiologists. Patients with a suspected malignancy were booked for an urgent staging CT and outpatient appointment, whilst the remaining patients were referred back to their general practitioner with a report. Prospective data were collected and two 16-month periods analysed.Three hundred and nine patients had a FTBE over the first 16-month period and 277 (89.6%) were seen within two-weeks. Mean times from initial referral to staging CT and first outpatient appointment were 30.7 and 36.0 days, respectively. Cancer was confirmed histologically in 32 (10.4%) patients. Of 267 patients without a malignancy, 46 (17.2%) were referred back to the colorectal outpatient or endoscopy service within 6-months. The number of referrals increased with time from a mean of 19.3 per month in the first period to 27.8 in the second, but the percentage with a suspected malignancy remained similar at 13.6% and 10.1%, respectively.FTBE diagnosed malignancy accurately and facilitated rapid staging. The TWW target was met in almost 90% of patients, whilst the impact on the colorectal outpatient and endoscopy service was minimized. [ABSTRACT FROM AUTHOR]

Background:Glutaraldehyde-preserved bioprosthetic heart valve substitutes have limited performance and longevity due to tissue degeneration and calcification. The Freestyle valve (Medtronic Heart Valves, Inc, Minneapolis, MN) combines zero fixation pressure and∝-amino oleic acid (AOA) as antidegeneration and antimineralization measures. The aim of this study was to compare the calcification behavior of glutaraldehyde-preserved kangaroo aortic valves with Freestyle stentless bioprostheses in a juvenile sheep model.Methods:Pulmonary artery and valve replacements were performed in juvenile sheep with Freestyle stentless aortic valves (n= 4) or glutaraldehyde-preservedkangaroo stentless aortic valves with no antimineralization measures (n= 6), and explanted at 200 postoperative days.Results:Freestyle stentless valves and stentlesskangaroo aortic valves showed normal valve function immediately postoperatively and up to 120 days. Valve leaflets of all valves were macroscopically free of visible calcification with normal histology. Valve leaflet calcification (μg Ca/mg tissue) was less inkangaroo than Freestyle (1.27± 0.43 versus 2.38± 1.37, p= 0.856). Aortic wall tissue calcification was severe inkangaroo and Freestyle (127.93± 12.22 versus 122.19± 11.99, p= 0.596).Conclusions:We conclude that glutaraldehyde-preserved kangaroo aortic valve leaflets are equal to AOA-treated Freestyle stentless valve leaflets with regard to calcification in juvenile sheep. Both bioprostheses are prone to aortic wall calcification. The low calcification features of the kangaroo aortic valve leaflets without antimineralization treatment may benefit the longevity of the valve.(J Card Surg 2005;20:29-34) [ABSTRACT FROM AUTHOR]

Introduction: QTc dispersion has traditionally been calculated from all 12 leads of a standard electrocardiogram (ECG). It is possible that alternative, quicker methods using fewer than 12 leads could be used to provide the same information. Methods and Results: We have previously shown a difference in QTc dispersion from ECGs recorded at least 1 month after myocardial infarction between patients who subsequently died and long-term survivors. In the current study, we recalculated QTc dispersion in these ECGs using different methods to determine if the observed difference in QTc dispersion measurements between the two groups, as calculated from 12-lead ECGs, persisted when using smaller sets of leads. QTc dispersion was recalculated by four methods: (1) with the two extreme QTc intervals excluded; (2) from the six precordial leads; (3) from the three leads most likely to contribute to QTc dispersion (aVF, V1, V4); and (4) from the three quasi-orthogonal leads (aVF, I, V2). For each of the 270 12-lead ECGs examined, a mean of 9.9 leads (SD 1.5 leads) had a QT interval analyzed; the QT interval could not be accurately measured in the remaining leads. Using the standard 12-lead measurement of QTc dispersion, there was a difference in the fall in QTc dispersion from early to late ECG between the groups: 9.1 (SD 60.8) msec for deaths versus 34.4 (55.2) msec for survivors (P = 0.016). This difference in QTc dispersion between early and late ECGs was maintained using either three-lead method (quasi-orthogonal leads: -2.6 [56.2] msec for deaths vs 26.9 [54.3] msec for survivors [P = 0.003]; "likeliest" leads: 8.6 [64.9] msec vs 29.5 [54.2] msec [P = 0.05]), but not when using the other two methods (precordial leads: 19.1 [55.5] msec vs 22 [50.8] msec [P = 0.76]; extreme leads removed: 9.2 [50.1] msec vs 21.8 [42] msec [P = 0.13]). Conclusion: QTc dispersion calculated from three leads may be as useful a measurement as QTc dispersion calculated from all leads of a standard ECG. Its advantages over the standard measurement are its simplicity and the lack of problems with lead adjustment. [ABSTRACT FROM AUTHOR]

ABSTRACT Sixty eight impotent men underwent corpora cavernosography and corpora cavernosal pressure measurements during saline infusion. Nineteen of the men had internal pudendal arteriograms. Correlation between the cavernosograms and saline infusion induced pressure measurements was 'good' in 56/66(84%), 'approximate' in 5/66(8%) and there was no correlation in 5/66(8%). Two patients were excluded for technical reasons. The spread of results and the good correlation of the two tests speaks for the accuracy of the method. It was of value in diagnosis and will be of paramount importance if veno occlusive surgery becomes a reliable method of treatment. [ABSTRACT FROM AUTHOR]

SUMMARY The radiological findings are described in 12 cases of malignant pleural mesothelioma diagnosed over a three-year period at the Sir Charles Gairdner Hospital in Western Australia. At presentation all showed a unilateral pleural effusion ranging from small to massive in size, with a right: left ratio of 2:1; in 8 cases a massive effusion developed at some time in the course of the disease. Pulmonary embolism was initially suspected in two cases and both underwent lower limb venography, emphasizing the similarities in presentation, with chest pain, dyspnoea and a serosanguineous pleural effusion. The sex and age distribution corresponds to that seen in series from other countries, and the radiological findings also closely conform to those reported elsewhere. Pleural nodules were evident in 9 cases, although only in one at presentation, and hilar enlargement was seen in only 4 cases. Soft tissue invasion by neoplasm was uncommonly seen on the x-rays, and rib erosion was not observed in any patient. Other radiological evidence of previous asbestos exposure or other pneumoconiosis was also uncommon and was noted in three cases. An unusual presentation of a malignant pleural mesothelioma in a 27-year-old woman with environmental childhood exposure to asbestos is described in detail, and illustrates the importance of considering mesothelioma in the differential diagnosis of any pleural effusion. [ABSTRACT FROM AUTHOR]

Selective use of catheter embolic therapy both prior to tumour resection and in control of bleeding from recurrent and irresectable tumour is discussed. Experience with pre-operative infarction of renal carcinomas and selective occlusion of the internal maxillary artery in troublesome epistaxis following radiotherapy and excision of an angiofibroma of the nasopharynx is presented. Excision of bulky vascular renal tumours was achieved with minimal blood loss and with shortening of operating time. Catheter occlusion of the internal maxillary artery obviated a further attempt at operative ligation of this vessel. Two cases (multifocal hepatoma and carcinoma in a solitary kidney) were considered for C.E.T. but in each case relative benefits appeared to be outweighed by potential risks. Further clinical experience with C.E.T. for inoperable hepatoma and multiple hypervas-cular liver metastases is required. These results, together with other reports, suggest a useful role for C.E.T. in selected cases. [ABSTRACT FROM AUTHOR]