Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test.

The degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive 'gas-distribution' type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on 'GOLD' classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ([Formula: see text]). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

Mental health improvements after elective spine surgery: a Canadian Spine Outcome Research Network (CSORN) study.

BACKGROUND CONTEXT: Spine patients have a higher rate of depression then the general population which may be caused in part by levels of pain and disability from their spinal disease. PURPOSE: Determination whether improvements in health-related quality of life (HRQOL) resulting from successful spine surgery leads to improvements in mental health. STUDY DESIGN/SETTING: The Canadian Spine Outcome Research Network prospective surgical outcome registry. OUTCOME MEASURES: Change between preoperative and postoperative SF12 Mental Component Score (MCS). Secondary outcomes include European Quality of Life (EuroQoL) Healthstate, SF-12 Physical Component Score (PCS), Oswestry Disability Index (ODI), Patient Health Questionaire-9 (PHQ9), and pain scales. METHODS: The Canadian Spine Outcome Research Network registry was queried for all patients receiving surgery for degenerative thoracolumbar spine disease. Exclusion criteria were trauma, tumor, infection, and previous spine surgery. SF12 Mental Component Scores (MCS) were compared between those with and without significant improvement in postoperative disability (ODI) and secondary measures. Multivariate analysis examined factors predictive of MCS improvement. RESULTS: Eighteen hospitals contributed 3222 eligible patients. Worse ODI, EuroQoL, PCS, back pain and leg pain correlated with worse MCS at all time points. Overall, patients had an improvement in MCS that occurred within 3 months of surgery and was still present 24 months after surgery. Patients exceeding Minimally Clinically Important Differences in ODI had the greatest improvements in MCS. Major depression prevalence decreased up to 48% following surgery, depending on spine diagnosis. CONCLUSIONS: Large scale, real world, registry data suggests that successful surgery for degenerative lumbar disease is associated with reduction in the prevalence of major depression regardless of the specific underlaying diagnosis. Worse baseline MCS was associated with worse baseline HRQOL and improved postoperatively with coincident improvement in disability, emphasizing that mental wellness is not a static state but may improve with well-planned spine surgery.

In Silico Finite Element Analysis of the Foot Ankle Complex Biomechanics: A Literature Review.

Computational approaches, especially finite element analysis (FEA), have been rapidly growing in both academia and industry during the last few decades. FEA serves as a powerful and efficient approach for simulating real-life experiments, including industrial product development, machine design, and biomedical research, particularly in biomechanics and biomaterials. Accordingly, FEA has been a "go-to" high biofidelic software tool to simulate and quantify the biomechanics of the foot-ankle complex, as well as to predict the risk of foot and ankle injuries, which are one of the most common musculoskeletal injuries among physically active individuals. This paper provides a review of the in silico FEA of the foot-ankle complex. First, a brief history of computational modeling methods and finite element (FE) simulations for foot-ankle models is introduced. Second, a general approach to build an FE foot and ankle model is presented, including a detailed procedure to accurately construct, calibrate, verify, and validate an FE model in its appropriate simulation environment. Third, current applications, as well as future improvements of the foot and ankle FE models, especially in the biomedical field, are discussed. Finally, a conclusion is made on the efficiency and development of FEA as a computational approach in investigating the biomechanics of the foot-ankle complex. Overall, this review integrates insightful information for biomedical engineers, medical professionals, and researchers to conduct more accurate research on the foot-ankle FE models in the future.

A Fibreless Multiwavelength NIRS System for Imaging Localised Changes in Cerebral Oxidised Cytochrome C Oxidase.

Measurement of the oxidation state of cytochrome c oxidase (oxCCO) can inform directly on neuronal metabolism. Conventionally this has been measured in vivo using benchtop broadband near infrared spectroscopy (NIRS) systems. Spatially resolved measures of oxCCO have recently been made possible using a multichannel fibre-based broadband NIRS system. We describe the use of a fibreless multiwavelength NIRS system using light emitting diodes (LED) designed specifically to image localised changes in oxCCO and hence neuronal metabolism. A fibreless system consisting of four modules, each containing two LED sources and four photodiode detectors, was developed. Each LED source contained eight LED dies (780, 811, 818, 842, 850, 882, 891 and 901 nm) assembled in an area of 1.5 × 1.5 mm. A well-established hyperoxia protocol was used to evaluate the oxCCO spatially resolved measurement capabilities of the system and, subsequently, its imaging capabilities were tested using a functional activation paradigm. A multi-spectral image reconstruction approach was used to provide images of Δ[HbO2], Δ[HHb] and Δ[oxCCO] from the multi-distance, multi-channel optical datasets. This novel fibreless multiwavelength NIRS system allows imaging of localised changes in oxCCO in the human brain, and has potential for development as an inexpensive, wearable, continuous monitor of cerebral energetics in a range of experimental and clinical scenarios.

Spatial Distribution of Changes in Oxidised Cytochrome C Oxidase During Visual Stimulation Using Broadband Near Infrared Spectroscopy Imaging.

Functional hyperaemia, characterised as an increase in concentration of oxyhaemoglobin [HbO2] and a decrease in concentration of deoxyhaemoglobin [HHb] in response to neuronal activity, can be precisely mapped using diffuse optical spectroscopy. However, such techniques do not directly measure changes in metabolic activity during neuronal activation. Changes in the redox state of cerebral oxidised cytochrome c oxidase Δ[oxCCO] measured by broadband spectroscopy may be a more specific marker of neuronal metabolic activity. This study aims to investigate the spatial distribution of Δ[oxCCO] responses during the activation of the visual cortex in the healthy adult human brain, and reconstruct images of these changes.Multi-channel broadband NIRS measurements were collected from the left visual cortex of four healthy volunteers using an in-house broadband spectrometer during an inverting checkerboard visual stimulation paradigm. Δ[HbO2], Δ[HHb] and Δ[oxCCO] were calculated by fitting the broadband spectra between 780 and 900 nm using the UCLn algorithm. Centre of gravity analysis was applied to the concentration data to determine the centres of activation for [HbO2], [HHb] and [oxCCO].All four subjects showed similar changes in [oxCCO] in the presence of a typical visual-evoked haemodynamic response in channels overlying the visual cortex. Image reconstruction of the optical data showed a clear and spatially localized activation for all three chromophores. Centre of gravity analysis showed different localisation of the changes in each of the three chromophores across the visual cortex with the x-y coordinates of the mean centres of gravity (across 4 subjects) of HbO2, HHb and oxCCO at (63.1 mm; 24.8 mm), (56.2 mm; 21.0 mm) and (63.7 mm; 23.8 mm), respectively.The spatial distribution of Δ[oxCCO] response appears distinct from the haemodynamic response in the human visual cortex. Image reconstruction of Δ[oxCCO] shows considerable promise as a technique to visualise regional variation in [oxCCO] in a range of scenarios.

A Kohonen neural network description of scoliosis fused regions and their corresponding Lenke classification.

PURPOSE: Surgical instrumentation for adolescent idiopathic scoliosis (AIS) is a complex procedure where selection of the appropriate curve segment to fuse, i.e., fusion region, is a challenging decision in scoliosis surgery. Currently, the Lenke classification model is used for fusion region evaluation and surgical planning. Retrospective evaluation of Lenke classification and fusion region results was performed. METHODS: Using a database of 1,776 surgically treated AIS cases, we investigated a topologically ordered self organizing Kohonen network, trained using Cobb angle measurements, to determine the relationship between the Lenke class and the fusion region selection. Specifically, the purpose was twofold (1) produce two spatially matched maps, one of Lenke classes and the other of fusion regions, and (2) associate these two maps to determine where the Lenke classes correlate with the fused spine regions. RESULTS: Topologically ordered maps obtained using a multi-center database of surgically treated AIS cases, show that the recommended fusion region agrees with the Lenke class except near boundaries between Lenke map classes. Overall agreement was 88%. CONCLUSION: The Lenke classification and fusion region agree in the majority of adolescent idiopathic scoliosis when reviewed retrospectively. The results indicate the need for spinal fixation instrumentation variation associated with the Lenke classification.

Avocado soybean unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages.

OBJECTIVE: To evaluate the effects of avocado soybean unsaponifiables (ASU) on proinflammatory mediators in chondrocytes and monocyte/macrophage-like cells. DESIGN: To determine the dose response of ASU, chondrocytes (5 x 10(5) cells/well) were incubated at 5% CO(2), 37 degrees C for 72 h with (1) control media alone or (2) ASU at concentrations of 0.3, 0.9, 2.7, 8.3, and 25 microg/ml. Cells were activated with 20 ng/ml lipopolysaccharide (LPS) for 24 h and cell supernatants were analyzed for prostaglandin E(2) (PGE(2)) and nitrite content. Chondrocytes and THP-1 monocyte/macrophages (5 x 10(5) cells/well) were incubated at 5% CO(2), 37 degrees C for 72 h with (1) control media alone or (2) ASU (25 mug/ml). One set of cells was activated for 1 h with LPS (20 ng/ml) for both reverse-transcriptase PCR and real-time PCR analysis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1beta), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression. One set of cells was activated for 24 h to analyze secreted PGE(2) and nitrite levels in the cellular supernatant. RESULTS: ASU reduced TNF-alpha, IL-1beta, COX-2, and iNOS expression in LPS-activated chondrocytes to levels similar to nonactivated control levels. The suppression of COX-2 and iNOS expression was paralleled by a significant reduction in PGE(2) and nitrite, respectively, in the cellular supernatant. ASU also reduced TNF-alpha and IL-1beta expression in LPS-activated monocyte/macrophage-like cells. CONCLUSION: The present study demonstrates that the anti-inflammatory activity of ASU is not restricted to chondrocytes, but also affects monocyte/macrophage-like cells that serve as a prototype for macrophages in the synovial membrane. These observations provide a scientific rationale for the pain-reducing and anti-inflammatory effects of ASU observed in osteoarthritis patients.

Kissing naevus of the penis.

Divided or 'kissing' naevus was first described on the eyelids in 1908. Other types of divided naevus reported include naevus spilus on the eyelids, mast cell naevus and epidermal naevus in a divided form on the fingers. Six cases of kissing naevus of the penis appear in the literature. In this paper, we discuss a seventh case.

Structural and functional characterization of second-coordination sphere mutants of soybean lipoxygenase-1.

Lipoxygenases are an important class of non-heme iron enzymes that catalyze the hydroperoxidation of unsaturated fatty acids. The details of the enzymatic mechanism of lipoxygenases are still not well understood. This study utilizes a combination of kinetic and structural probes to relate the lipoxygenase mechanism of action with structural modifications of the iron's second coordination sphere. The second coordination sphere consists of Gln(495) and Gln(697), which form a hydrogen bond network between the substrate cavity and the first coordination sphere (Asn(694)). In this investigation, we compared the kinetic and structural properties of four mutants (Q495E, Q495A, Q697N, and Q697E) with those of wild-type soybean lipoxygenase-1 and determined that changes in the second coordination sphere affected the enzymatic activity by hydrogen bond rearrangement and substrate positioning through interaction with Gln(495). The nature of the C-H bond cleavage event remained unchanged, which demonstrates that the mutations have not affected the mechanism of hydrogen atom tunneling. The unusual and dramatic inverse solvent isotope effect (SIE) observed for the Q697E mutant indicated that an Fe(III)-OH(-) is the active site base. A new transition state model for hydrogen atom abstraction is proposed.

Diagnostic odor recognition

Many diseases, toxic ingestions, and intoxications have characteristic odors. These odors may provide diagnostic clues that affect rapid treatment long before laboratory confirmation or clinical deterioration. Odor recognition skills, similar to auscultation and palpation skills, require teaching and practical exposure. Dr. Goldfrank and colleagues recognized the importance of teaching odor recognition to emergency service providers. They proposed the "sniffing bar" method for odor recognition training. OBJECTIVES: (1) To identify the recognition rates of medically important odors among emergency care providers. (2) To investigate the effectiveness of teaching odor recognition. Hypothesis: The recognition rates of medically important odors will increase after teaching exposure. METHODS: The study exposed emergency care providers to 11 tubes of odors. Identifications of each substance were recorded. After corrective feedback, subjects were re-tested on their ability to identify the odors. Analysis of odor recognition improvement after teaching was done via chi-square test. RESULTS: Improvement in identification after teaching was seen in all odors. However, the improvement was significant only in the lesscommon substances because their initial recognition was especially low. Significant changes may improve with a larger sample size. Subjects often confuse the odors of alcohol with acetone, and wintergreen with camphor. CONCLUSIONS: The recognition rates are higher for the more-common odors, and lower for the less-common odors. Teaching exposures to the less well-known odors are effective and can significantly improve the recognition rate of these substances. Because odor recognition may affect rapid diagnosis and treatment of certain medical emergencies such as toxic ingestion, future studies should investigate the correlation between odor recognition and the ability to identify corresponding medical emergencies.

Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila.

Asymmetric cell division generates daughter cells with different developmental fates. In Drosophila neuroblasts, asymmetric divisions are characterized by (1) a difference in size between the two daughter cells and (2) an asymmetric distribution of cell fate determinants, including Prospero and Numb, between the two daughter cells. In embryonic neuroblasts, the asymmetric localization of cell fate determinants is under the control of the protein Inscuteable (Insc), which is itself localized asymmetrically as an apical crescent. Here, we describe a new Drosophila protein, Rapsynoid (Raps), which interacts in a two-hybrid assay with the signal transduction protein Galpha(i). We show that Raps is localized asymmetrically in dividing larval neuroblasts and colocalizes with Insc. Moreover, in raps mutants, the asymmetric divisions of neuroblasts are altered: (1) Insc is no longer asymmetrically localized in the dividing neuroblast; and (2) the neuroblast division produces two daughter cells of similar sizes. However, the morphologically symmetrical divisions of raps neuroblasts still lead to daughter cells with different fates, as shown by differences in gene expression. Our data show that Raps is a novel protein involved in the control of asymmetric divisions of neuroblasts.

Validation of a controlled cortical impact model of head injury in mice.

A controlled cortical impact model of head injury was validated with mice. Mice were randomly assigned to moderate head injury, mild head injury, and sham injury groups. Beam balancing, open field activity, slant board inclination, grasp strength, and motor coordination were assessed prior to the injury and on days 1-5 postinjury. Morris water maze performance was evaluated on days 11-15 postinjury. Moderately head-injured mice took a significantly longer time to complete the motor coordination task and to find the hidden platform on the Morris water maze and had significantly fewer successful trials on both tasks than the mildly head-injured and sham-injured mice. Mildly head-injured and sham-injured mice performed similarly on both tasks. Contusion volume at the site of impact varied with severity of injury. Moderately head-injured mice had significantly larger contusions than mice with a mild head injury, and these mice in turn had significantly larger contusions than the sham-injured mice. Both moderately and mildly head injured mice had significantly fewer surviving cells in CA1 than the sham-injured mice but did not differ from each other in this regard. Although there was a group effect, only the mildly head-injured mice had significantly fewer surviving cells in CA3.

Overexpression, purification, and generation of a thermostable variant of Zymomonas mobilis fructokinase.

The gene encoding fructokinase (EC 2.7.1.4) from Zymomonas mobilis has been expressed at high level in Escherichia coli by modifying the ribosome binding site using the polymerase chain reaction. A simple two-step purification from extracts of the recombinant cells results in highly purified enzyme suitable for use in fructose determination. Using the polymerase chain reaction in mutagenic conditions, a variant of fructokinase was isolated which was more thermostable than the wild type, taking the 30 min half-life from 70.1 to 72.4 degrees C. The purified thermostable variant had the same specific activity as the wild type. Sequencing of the variant indicated that only one amino acid was changed, with Ser 69 becoming Ala. Searches of the mutant libraries for variants that were (a) active with glucose or (b) had reduced inhibition by glucose were unsuccessful.

The physiological and anatomical demonstration of functionally selective parasympathetic ganglia located in discrete fat pads on the feline myocardium.

Experiments utilizing surgical parasympathectomy of discrete fat pad ganglia on the surface of the heart have suggested that there are two anatomically segregated and physiologically independent parasympathetic intracardiac ganglia which are capable of selective control of sino-atrial (SA) rate and atrio-ventricular (AV) conduction. Some pharmacological data, however, are inconsistent with these conclusions. We have examined the cardiodynamic effects of discrete injections of a ganglionic blocking drug into two fat pads on the surface of the cat heart. These fat pads were shown to contain ganglion cells histologically. It was observed that vagal effects upon cardiac rate are selectively mediated by neurons located in ganglia overlying the right pulmonary veins at the junction of the right atrium and superior vena cava. On the other hand, vagal effects upon AV conduction were selectively mediated by neurons located in a fat pad at the junction of the inferior vena cava and the inferior left atrium. These pharmacological data support the concept that specific intracardiac ganglia are capable of selective control of SA rate and AV conduction.

[Acute hepatic insufficiency disclosing congenital syphilis]. / Insuffisance hépatique aiguë révélant une syphilis congénitale.

A breast-fed boy, born to first-cousin parents, had been vomiting since birth; his general condition remained good until age 6 weeks when vomiting became more frequent, and his status suddenly worsened, with polypnea, shock, hypothermia, jaundice, presence of blood in urine, gastric juice, stool, and bleeding tendency during veno-punctures. There was an huge hepatomegaly and a splenomegaly. Hypoglycaemia, metabolic acidosis, severe blood coagulation disturbances, elevated liver enzymes, hypoalbuminemia, pointed to an acute liver failure. He was resuscitated with current supportive measures, and was given a wide spectrum antibiotherapy. Because serologic tests for syphilis were positive in the child and his mother, including the presence of specific IgM the infant was then given Penicillin G therapy only, which resulted in a complete recovery. One month later, a needle liver biopsy showed residual signs of hepatitis. Other possible infectious or metabolic causes of acute liver failure occurring early in life had been excluded.