Community based study to assess the prevalence of diabetic foot syndrome and associated risk factors among people with diabetes mellitus.
Diabetic foot is one of the most significant and devastating complication of diabetes. The objective of this study was to assess the prevalence of diabetic foot syndrome (DFS) and the associated risk factors among people with diabetes mellitus. A community based cross-sectional study was carried out among 620 subjects with diabetes mellitus (DM) in rural areas of Udupi district. The Michigan Neuropathy Screening Instrument was used to identify peripheral neuropathy. Ankle brachial index was used to identify peripheral arterial disease (PAD). Subjects with diabetic foot syndrome were classified according to the International Working Group on Diabetic Foot (IWGDF) classification system. The overall prevalence of DFS was 51.8%. Among them 31.3, 11.9 and 8.5% belonged to category 1, 2 and 3 respectively. Multivariate logistic regression analysis showed advancing age, low socio-economic status, sedentary physical activity and longer duration of DM were significant independent correlates of DFS. The overall prevalence of DFS was high among the study population; hence the screening for foot complications should start at the time of diagnosis of diabetes integrated with sustainable patient education at primary care level by training of health care providers at primary care level.


Total synthesis of (-)-xyloketal A.
[reaction: see text] The first total synthesis of the C(3)-symmetric and biologically active natural product, (-)-xyloketal A, has been accomplished in one step from phloroglucinol (1,3,5-trihydroxybenzene) and (4R)-3-hydroxymethyl-2,4-dimethyl-4,5-dihydrofuran. This remarkably direct process involved an exceedingly facile and diastereoselective boron trifluoride diethyl etherate-promoted triple electrophilic aromatic substitution reaction that was coupled to three bicyclic acetal formation reactions.


Forecasting volatility with neural regression: a contribution to model adequacy.
Neural nets' usefulness for forecasting is limited by problems of overfitting and the lack of rigorous procedures for model identification, selection and adequacy testing. This paper describes a methodology for neural model misspecification testing. We introduce a generalization of the Durbin-Watson statistic for neural regression and discuss the general issues of misspecification testing using residual analysis. We derive a generalized influence matrix for neural estimators which enables us to evaluate the distribution of the statistic. We deploy Monte Carlo simulation to compare the power of the test for neural and linear regressors. While residual testing is not a sufficient condition for model adequacy, it is nevertheless a necessary condition to demonstrate that the model is a good approximation to the data generating process, particularly as neural-network estimation procedures are susceptible to partial convergence. The work is also an important step toward developing rigorous procedures for neural model identification, selection and adequacy testing which have started to appear in the literature. We demonstrate its applicability in the nontrivial problem of forecasting implied volatility innovations using high-frequency stock index options. Each step of the model building process is validated using statistical tests to verify variable significance and model adequacy with the results confirming the presence of nonlinear relationships in implied volatility innovations.


Digital health app development standards: a systematic review protocol.
There is currently a lack of clear and accepted standards for the development (planning, requirement analysis and research, design and application testing) of apps for medical and healthcare use which poses different risks to developers, providers, patients and the public. The aim of this work is to provide an overview of the current standards, frameworks, best practices and guidelines for the development of digital health apps. This review is a critical 'stepping stone' for further work on producing appropriate standards that can help mitigate risks (eg, clinical, privacy and economic risks). A systematic review identifying criteria from applicable standards, guidelines, frameworks and best practices for the development of health apps. We will draw from standards for software for medical devices, clinical information systems and medicine because of their relatedness and hope to apply lessons learnt to apps. We will exclude other types of publications, and those published in languages other than English. We will search websites of relevant regulatory and professional organisations. For health apps, we will also search electronic research databases (eg, MEDLINE, Embase, SCOPUS, ProQuest Technology Collection and Engineering Index) because relevant publications may not be found on other websites. We will hand-search reference lists of included publications. The review will focus on international, USA, European and UK standards because these are the markets of primary interest to the majority of app developers currently. We will provide a narrative overview of findings and tabular summaries of extracted data. Also, we will examine the relationship between different standards and compare USA and European Union standards. No ethics approval is required. The review will be disseminated through peer-reviewed publications, conference presentations and inform efforts that aim to improve the quality of health apps through existing links with relevant organisations.


Spontaneous hemopneumothorax requiring thoracotomy.
A spontaneous pneumothorax complicated by severe bleeding presents a potentially grave emergency. If bleeding continues, thoracotomy becomes necessary to control the hemorrhage, to evacuate residual blood and clots, and to repair the break in the continuity of the lung.


Interaction between neurons in different laminae of the dorsal horn of the spinal cord. A correlation study in normal and neuropathic rats.
Simultaneous recordings of 135 pairs of units, located respectively in the superficial (I-IIo) and deep (V) laminae of the dorsal horn of the lumbar spinal cord of anaesthetized and paralysed animals, were performed both from normal (62 pairs) and from peripherally injured (chronically constricted sciatic nerve) rats (73 pairs). In each pair, one neuron was classified as nociceptive, responding only to noxious stimuli, and the other as a wide dynamic range neuron, responding to both non-noxious and noxious stimuli. To understand if some interaction was present between diverse neurons modulated by noxious inputs, we used cross-correlation techniques. The responses of simultaneously recorded pairs of units to suprathreshold (5 mA, 0.5 ms) electrical stimuli were used. A clearly delayed peak in the cross-correlograms of recordings from normal animals was present, indicating connectivity of superficial and deep-layer cells. This feature was not present in the cross-correlograms obtained from nerve-injured animals. Even if a specific pathway cannot be explicitly assigned to support these functional results, an overall connection between superficial and deep layers of the spinal cord is suggested. These connections are supposed to be either inactive or rearranged in the nerve-injured rats, thus suppressing a well timed coordinated connectivity. This anomaly could underlie a reduced degree of functional coherence in the modulation of nociceptive spinal inputs in cases of chronic pain.


Cardiac biomagnetic source estimation with a heart-torso model and a trained neural network.
The intensity of the cardiac sources for normal adult subjects was estimated from given magnetic field profiles with a trained neural network based on the relationship of the electrical activity of the heart to the cardiac magnetic fields. The input for training the neural network consisted of the magnetic field profiles above the torso during the heartbeat. The outputs were the dipole intensities which produced those magnetic field profiles. A back propagating algorithm with bias and momentum was utilized for training. The measured and simulated torso magnetic field profiles and magnetocardiograms were used for training the neural network. Estimation of the dipole intensities was performed for unknown magnetic field profiles with the trained neural network. The estimated cardiac dipole intensities were reasonably close to the true dipole intensities. These results show the feasibility of the estimation of cardiac dipole intensities with a trained neural network under a very restricted forward model of the cardiac magnetic fields. Generalization of the results to cover a large population base could be difficult because the activation isochrones are different from subject to subject.


Hypertension in Northern Angola: prevalence, associated factors, awareness, treatment and control.
Seventy-five million people are estimated to be hypertensive in sub-Saharan Africa. This translates in high morbidity and mortality, as hypertension is now considered to be the number one single risk factor for death worldwide. Accurate data from countries lacking national disease surveillance is needed to guide future evidence-driven health policies. The authors aimed to estimate the prevalence, awareness, management and control of hypertension and associated factors in an adult population of Angola. A community-based survey of 1,464 adults, following the World Health Organization's Stepwise Approach to Chronic Disease Risk Factor Surveillance, was conducted to estimate the prevalence of hypertension, awareness, treatment and control in Dande, Northern Angola. Using a demographic surveillance system database, a representative sample of subjects, stratified by sex and age (18-40 and 41-64 years old), was selected. Prevalence of hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or hypertensive therapy) was of 23% (95% CI: 21% to 25.2%). A follow-up consultation confirmed the hypertensive status in 82% of the subjects who had a second measurement on average 23 days after the first. Amongst hypertensive individuals, 21.6% (95% CI: 17.0% to 26.9%) were aware of their status. Only 13.9% (95% CI: 5.9% to 29.1%) of the subjects aware of their condition were under pharmacological treatment, of which approximately one-third were controlled. Older age, lower level of education, higher body mass index and abdominal obesity were found to be significantly (p<0.01) associated with hypertension. Our survey is the first to provide insightful data on hypertension prevalence in Angola. There is an urgent need for strategies to improve prevention, diagnosis and access to adequate treatment in this country, where a massive economic growth and consequent potential impact on lifestyle risk factors could lead to an increase in the prevalence of hypertension and cardiovascular disease.


Effect of AHA dietary counselling on added sugar intake among participants with metabolic syndrome.
High added sugar consumption has been associated with the development of metabolic syndrome (MetS). The American Heart Association (AHA) diet is designed to prevent and treat MetS; however, it remains unclear whether the AHA diet is effective on decreasing added sugar consumption. The aim of our study was to evaluate the effect of the AHA dietary counselling on added sugar consumption among participants with MetS. The AHA dietary counselling was conducted among 119 participants with MetS from June 2009 to January 2014 (ClinicalTrials.gov: NCT00911885). Unannounced 24-hour recalls were collected at baseline, 3, 6 and 12 months. Added sugar consumption patterns over time were examined using linear mixed models. After 1-year dietary counselling, intake of added sugars decreased by 23.8 g/day (95% CI 15.1, 32.4 g/day); intake of nonalcoholic beverages dropped from the leading contributor of added sugar intake to number 7 (from 11.9 to 4.4%); the Alternative Healthy Eating Index (AHEI) score increased by 5.4 (95% CI 2.9, 8.0); however, added sugar intake for 48% participants still exceeded the recommendation. Added sugar intake per meal among different meal type was similar (24.2-25.8%) at baseline. After the 1-year dietary counselling, breakfast became the major resource of added sugar intake (33.3%); the proportion of added sugar intake from snacks decreased from 25.8% (CI 23.1, 28.5%) to 20.9% (CI 19.6, 22.3%). Although the consumption of added sugars in participants with MetS decreased after the 1-year AHA dietary counselling, added sugar intake from majority of participants still exceeds recommended limits. Actions of successful public health strategies that focus on reducing added sugar intake are needed.


Azotobacter bryophylli sp. nov., isolated from the succulent plant Bryophyllum pinnatum.
A Gram-stain-negative, aerobic, nitrogen-fixing bacterium, designated strain L461T, was isolated from leaves of Bryophyllum pinnatum growing at the South China Agricultural University. Phylogenetic analysis of the 16S rRNA gene sequence indicated it as a member of the genus Azotobacter closely related to Azotobacter beijerinckii JCM 20725T (97.82 % similarity) and Azotobacter chroococcum ATCC 9043T (97.34 %). Its major fatty acid components were C16 : 1 ω9c and C16 : 0. Its predominant isoprenoid quinone was Q-9. Its major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, aminophospholipid, phospholipid and one unknown lipid. Its DNA G+C content was 64.9 mol% (Tm). DNA-DNA relatedness values between strain L461T and the reference strains of A. beijerinckii and A. chroococcum were 46.43 and 28.23 %, respectively. Biological and biochemical tests, protein patterns, genomic DNA fingerprinting, and comparison of cellular fatty acids distinguished strain L461T from the closely related Azotobacter species. Based on these data, the novel species Azotobacter bryophylli sp. nov. is proposed, with the type strain L461T (=KCTC 62195T=GDMCC 1.1250T).


Microbial synergy via an ethanol-triggered pathway.
We have discovered a microbial interaction between yeast, bacteria, and nematodes. Upon coculturing, Saccharomyces cerevisiae stimulated the growth of several species of Acinetobacter, including, A. baumannii, A. haemolyticus, A. johnsonii, and A. radioresistens, as well as several natural isolates of Acinetobacter. This enhanced growth was due to a diffusible factor that was shown to be ethanol by chemical assays and evaluation of strains lacking ADH1, ADH3, and ADH5, as all three genes are involved in ethanol production by yeast. This effect is specific to ethanol: methanol, butanol, and dimethyl sulfoxide were unable to stimulate growth to any appreciable level. Low doses of ethanol not only stimulated growth to a higher cell density but also served as a signaling molecule: in the presence of ethanol, Acinetobacter species were able to withstand the toxic effects of salt, indicating that ethanol alters cell physiology. Furthermore, ethanol-fed A. baumannii displayed increased pathogenicity when confronted with a predator, Caenorhabditis elegans. Our results are consistent with the concept that ethanol can serve as a signaling molecule which can affect bacterial physiology and survival.


Accuracy of Clinician Predictions of Future Self-Harm: A Systematic Review and Meta-Analysis of Predictive Studies.
Assessment of a patient after hospital-treated self-harm or psychiatric hospitalization often includes a risk assessment, resulting in a classification of high risk versus low risk for a future episode of self-harm. Through systematic review and a series of meta-analyses looking at unassisted clinician risk classification (eight studies; N = 22,499), we found pooled estimates for sensitivity 0.31 (95% CI: 0.18-0.50), specificity 0.85 (0.75-0.92), positive predictive value 0.22 (0.21-0.23), and negative predictive value 0.89 (0.86-0.92). Clinician classification was too inaccurate to be clinically useful. After-care should therefore be allocated on the basis of a needs rather than risk assessment.


Antitoxin MqsA decreases antibiotic susceptibility through the global regulator AgtR in Pseudomonas fluorescens.
Type II toxin-antitoxin systems are highly prevalent in bacterial genomes and play crucial roles in the general stress response. Previously, we demonstrated that the type II antitoxin PfMqsA regulates biofilm formation through the global regulator AgtR in Pseudomonas fluorescens. Here, we found that both the C-terminal DNA-binding domain of PfMqsA and AgtR are involved in bacterial antibiotic susceptibility. Electrophoretic mobility shift assay (EMSA) analyses revealed that AgtR, rather than PfMqsA, binds to the intergenic region of emhABC-emhR, in which emhABC encodes an resistance-nodulation-cell division efflux pump and emhR encodes a repressor. Through quantitative real-time reverse-transcription PCR and EMSA analysis, we showed that AgtR directly activates the expression of the emhR by binding to the DNA motif [5´-CTAAGAAATATACTTAC-3´], leading to repression of the emhABC. Furthermore, we demonstrated that PfMqsA modulates the expression of EmhABC and EmhR. These findings enhance our understanding of the mechanism by which antitoxin PfMqsA contributes to antibiotic susceptibility.


An expression signature of estrogen-regulated genes predicts disease-free survival in tamoxifen-treated patients better than progesterone receptor status.
We have used data derived from hormonal responses in human breast cancer cell lines to develop a panel of 36 genes which can robustly identify patients who will or will not benefit from tamoxifen treatment. These genes had the following characteristics: 1) induction by 17beta-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cell lines in vitro, 2) under-expression in ER-negative breast tumors, and 3) correlation with PR mRNA expression in breast tumors. The average expression of these 36 genes was used as a "risk index" for assessing disease-specific survival in two independent tumor profile datasets of 60 and 67 patients treated with tamoxifen (these data not having been used to initially select the 36 genes), with a high risk group in each dataset defined as those with the bottom 25% of risk index values. This combined biological and informatic analysis is potentially applicable to many other cancer therapeutics.


Tibor Greenwalt Award. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry: a program for patient care, education and research.
The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry was created by collaboration of the Oklahoma Blood Institute and the Colleges of Medicine and Public Health of the University of Oklahoma Health Sciences Center, combining their respective strengths of community service, patient care, education, and clinical research methodology. The organization of the Registry is based on the fundamental principles of patient-oriented research: 1) all consecutive patients are identified at a uniform time early in the course of their disease; 2) analysis of clinical data requires quantitative and reproducible definitions; 3) patient follow-up is complete; and 4) therefore the data are generalizable to community practice. A summary of 15 years experience with 301 consecutive patients is presented. Some of these results and interpretations are different from other case series. These differences emphasize the distinct perspective of the Registry that includes all patients in the community who have had a clinical diagnosis of TTP or HUS and for whom plasma-exchange treatment was requested. The Oklahoma TTP-HUS Registry provides educational and research opportunities, in addition to improved patient care, and serves as a model for productive collaboration of community blood centers and universities.


XMAP230 is required for normal spindle assembly in vivo and in vitro.
XMAP230 is a high molecular mass microtubule-associated protein isolated from Xenopus oocytes and eggs, and has been recently shown to be a homolog of mammalian MAP4. Confocal immunofluorescence microscopy revealed that XMAP230 is associated with microtubules throughout the cell cycle of early Xenopus embryos. During interphase XMAP230 is associated with the radial arrays of microtubules and midbodies remaining from the previous division. During mitosis, XMAP230 is associated with both astral microtubules and microtubules of the central spindle. Microinjection of affinity-purified anti-XMAP230 antibody into blastomeres severely disrupted the assembly of mitotic spindles during the rapid cleavage cycles of early development. Both monopolar half spindles and bipolar spindles were assembled from XMAP230-depleted extracts in vitro. However, spindles assembled in XMAP230-depleted extracts exhibited a reduction in spindle width, reduced microtubule density, chromosome loss, and reduced acetylation of spindle MTs. Similar defects were observed in the spindles assembled in XMAP230-depleted extracts that had been cycled through interphase. Depletion of XMAP230 had no effect on the pole-to-pole length of spindles, and depletion of XMAP230 from both interphase and M-phase extracts had no effect on the rate of microtubule elongation. From these results, we conclude that XMAP230 plays an important role in normal spindle assembly, primarily by acting to stabilize spindle microtubules, and that the observed defects in spindle assembly may result from enhanced microtubule dynamics in XMAP230-depleted extracts.


Types and epidemiology of cancer-related neuropathic pain: the intersection of cancer pain and neuropathic pain.
Neuropathic pain--pain resulting from a lesion, damage, or dysfunction of the somatosensory nervous system--can arise through several distinct etiologies ranging from toxicity, surgery, radiation, and trauma to congenital disorders. Neuropathic pain is widely recognized as a common consequence of cancer and results from administration of several common oncology drugs. It not only impacts quality of life, but it also impacts patient outcomes because of resulting treatment delays, dose reductions, and discontinuations. We estimate that the cost of the problem in the U.S. alone is approximately $2.3 billion. Despite its widely recognized importance, there is a paucity of reliable information available regarding the incidence, prevalence of patient-and physician-reported severity, and time course of cancer-related neuropathic pain. To address this severe knowledge gap, we need new, high-quality, population-based studies of individual cancer pain syndromes and conditions. However, in order to gather this information, we also need substantial improvements in the specific classification of cancer-related neuropathic syndromes and better validated diagnostic tools that can help to elucidate the incidence, prevalence, severity, and potential economic impact of cancer-associated neuropathies.


Six-year follow-up of the Norwegian Multicenter Study on Timolol after Acute Myocardial Infarction.
The original Norwegian Multicenter Study on Timolol after Myocardial Infarction was a double-blind, randomized study comparing the effect of timolol with that of placebo for up to 33 months after acute myocardial infarction. The initial results showed that the cumulated mortality rate was 39.4 per cent lower among 945 patients randomly assigned to timolol treatment than among 939 patients randomly assigned to placebo (P = 0.0003). After the end of the double-blind period the majority of participating patients in the timolol group continued to receive beta-adrenergic blockade, whereas the majority of placebo-treated patients continued without such blockade. During an extended follow-up of participating patients up to 72 months after randomization, the mortality curves of the two groups continued to rise in parallel. Cumulated mortality rates were 32.3 per cent in the placebo group and 26.4 per cent in the timolol group (P = 0.0028). We conclude that the previously observed early beneficial effect of beta-adrenergic blocking therapy is maintained for at least six years after infarction.


Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics.
Convergent lines of evidence suggest potentiation of glutamatergic synapses after chronic ethanol exposure, and indicate that the presynaptic effect hereof is on modulators of synaptic strength rather than on executors of glutamate release. To address this hypothesis in the context of ethanol dependence in humans, we used semiquantitative immunoblotting to compare the immunoreactivities of synaptophysin I, syntaxin 1A, synaptosome-associated protein 25, and vesicle-associated membrane protein in the prefrontal and motor cortices between chronic alcoholics and control subjects. We found a region-specific elevation in synaptophysin I immunoreactivity in the prefrontal cortex of alcoholics, but detected no significant differences between the groups in the immunoreactivities of the other three proteins. Our findings are consistent with an effect of repeated ethanol exposure on modulators of synaptic strength but not on executors of glutamate release, and suggest a role for synaptophysin I in the enduring neuroplasticity in the prefrontal cortical glutamate circuitry that is associated with ethanol dependence.


Controllable Frontal Polymerization and Spontaneous Patterning Enabled by Phase-Changing Particles.
Frontal polymerization provides a rapid, economic, and environmentally friendly methodology to manufacture thermoset polymers and composites. Despite its efficiency and reduced environmental impact, the manufacturing method is underutilized due to the limited fundamental understanding of its dynamic control. This work reports the control and patterning of the front propagation in a dicyclopentadiene resin by immersion of phase-changing polycaprolactone particles. Predictive and designed patterning is enabled by multiphysical numerical analyses, which reveal that the interplay between endothermic phase transition, exothermic chemical reaction, and heat exchange govern the temperature, velocity, and propagation path of the front via two different interaction regimes. To pattern the front, one can vary the size and spacing between the particles and increase the number of propagating fronts, resulting in tunable physical patterns formed due to front separation and merging near the particles. Both single- and double-frontal polymerization experiments in an open mold are performed. The results confirm the front-particle interaction mechanisms and the shapes of the patterns explored numerically. The present study offers a fundamental understanding of frontal polymerization in the presence of heat-absorbing second-phase materials and proposes a potential one-step manufacturing method for precisely patterned polymeric and composite materials without masks, molds, or printers.


Actomyosin networks and tissue morphogenesis.
Tissue morphogenesis is driven by coordinated cellular deformations. Recent studies have shown that these changes in cell shape are powered by intracellular contractile networks comprising actin filaments, actin cross-linkers and myosin motors. The subcellular forces generated by such actomyosin networks are precisely regulated and are transmitted to the cell cortex of adjacent cells and to the extracellular environment by adhesive clusters comprising cadherins or integrins. Here, and in the accompanying poster, we provide an overview of the mechanics, principles and regulation of actomyosin-driven cellular tension driving tissue morphogenesis.


A multi-institutional review of outcomes of endometrial stromal sarcoma.
To compare the clinical behavior and outcomes of low- and high-grade endometrial stromal sarcomas (LGESS and HGESS), respectively. Patients with endometrial stromal sarcoma from five different institutions were identified and reviewed for clinicopathologic variables, surgical management and outcomes. Statistical calculations including Chi-square, t-test and survival using the Kaplan-Meier method with the log rank test were performed. One hundred and five patients were identified with 72 having LGESS, 31 with HGESS and 2 having unclassified tumors. The mean age was 50 years for patients with LGESS and 64 years for those with HGESS (p<0.0001). In patients with LGESS, 68% (49 patients) had disease confined to the uterine corpus or cervix compared to 39% (12 patients) in HGESS (p=0.002). The median overall survival was 53 months for HGESS and had not yet been reached in LGESS with 87.8% alive at 80 months (p<0.0001). In HGESS patients with extrauterine disease, the presence of residual disease greater than 2 cm had a significant effect on median survival. Median survival was 52 months for those who underwent optimal cytoreduction versus 2 months for those with suboptimal residual disease (p=0.007). The impact of cytoreduction was not seen in LGESS patients with extrauterine disease with 82.1% alive at 78 months. Low-grade and high-grade endometrial stromal sarcomas represent two distinct clinical entities and should be treated as such. Survival in patients with high-grade tumors appears to be related to amount of residual disease at the completion of initial surgery and would suggest the need for aggressive cytoreduction. The role of surgical staging and optimal adjuvant therapy remains unclear.


Atrophy of the residual alveolar ridge following tooth loss in an historical population.
To study the natural aetiopathology of jaw atrophy after tooth loss, unaltered by prosthetic procedures, an historical population without modern dental treatment was examined. Based on the hypothesis that there are predictable changes in shape during jaw-atrophy, frequency and degree of atrophy as well as clinical aspects of bone quality and resorption were determined in the skeletal remains of 263 individuals. The potential association between age and frequency/severity of atrophy was analysed. Atrophy in at least one jaw segment was present in 45.2% of the analysed jaw specimens. The residual ridge underwent a series of changes in shape and height following the pattern of resorption described for modern populations. The severity of these alterations was associated with the age of the individual and the region within the jaw. Atrophy was frequently related to structural degradation of the covering cortical layer. These findings prove that atrophy of the jaw evidently does occur, displaying similar patterns of resorption in a population without modern prosthetics, where the negative effect of ill-fitting dentures is excluded. The basic information about alterations of shape and the cortical layer covering the residual crest might help to provide a deeper insight into aetiopathological mechanisms of this common oral disease.


Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity.
alpha-Conotoxins are disulfide-rich peptides that are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Despite their small size, different alpha-conotoxins are able to discriminate among different subtypes of mammalian nAChRs. In this report, the activity of two peptides from the venom of Conus pennaceus, alpha-conotoxins PnIA and PnIB, are examined. Although the toxins differ in only two residues, PnIA preferentially blocks alpha3beta2 nAChRs, whereas PnIB prefers the alpha7 subtype. Point mutation chimeras of these alpha-conotoxins were synthesized and their activities assessed on Xenopus oocytes expressing specific nAChRs. Change of a single residue, Ala10 to Leu, in PnIA (to form PnIA [A10L]) converts the parent peptide from alpha3beta2-preferring to alpha7-preferring; furthermore, PnIA [A10L] blocks the alpha7 receptor with an IC(50) (12.6 nM) that is lower than that of either parent peptide. Kinetic analysis indicates that differences in affinity among the analogues are primarily due to differences in off-rate, with PnIA [A10L]'s interaction with alpha7 having the smallest off-rate (k(off) = 0.17 min(-)(1)). Thermodynamic analysis indicates that Leu10 enhances the peptide's interaction with alpha7, but not alpha3beta2, receptors, whereas Ser11 (in PnIA [N11S]) reduces its affinity for both alpha7 and alpha3beta2 nAChRs.


Optical properties of the scales of Morpho rhetenor butterflies: theoretical and experimental investigation of the back-scattering of light in the visible spectrum.
A study of the optical properties of the largely periodic microstructure occurring on the wings of the iridescent tropical butterfly Morpho rhetenor and responsible for its structural colouration is reported. An extensive measurement of the back-scattering of visible light from butterfly scales was performed for various angles of incidence. Efficient low-pass filter behaviour was observed for all angles of incidence and polarizations, with near-complete transmission at wavelengths above the threshold of 550 nm. The angular spread of the back-scattered light was found to be organized in lobes with total extinction of the specular reflection for all conditions of incidence. Retro-reflector behaviour was also observed for angles of incidence of 30 degrees and above. Additionally, the role of periodic geometrical features found in the microstructure for the generation of its spectral response was analysed theoretically. Using finite-difference time-domain and near-field to far-field transformation techniques, the back-scattering of visible light by models was computed numerically and the relevance of geometrical features for the production of structural colour and diffraction was demonstrated.


[Postoperative anesthesia by the extrapulmonary administration of cycloporpane].
According to the author's data postoperatively in patients receiving cyclopropane a much more early restoration of the renal excretory function was noted, postoperative intestinal paresis is liquidated more rapidly, the number of complications on the part of the respiratory and cardiovascular systems is diminished up to a minimum. There was less degree of postoperative metabolic alkalosis under the influence of cyclopropane, and it was also more rapidly eliminated.


Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers.
Increased rates of either oxalate absorption or endogenous oxalate synthesis can contribute to hyperoxaluria, a primary risk factor for the formation of calcium oxalate-containing kidney stones. This study involves a comparative assessment of oxalate absorption and endogenous oxalate synthesis in subpopulations of stone formers (SFs) and non-stone formers (NSFs) and an assessment of the effect of ascorbate supplementation on oxalate absorption and endogenous oxalate synthesis. Twenty-nine individuals with a history of calcium oxalate kidney stones (19 men, 10 women) and 19 age-matched NSFs (8 men, 11 women) participated in two 6-day controlled feeding experimental periods: ascorbate-supplement (2 g/d) and no-supplement treatments. An oxalate load consisting of 118 mg of unlabeled oxalate and 18 mg of 13C2 -oxalic acid was administered the morning of day 6 of each experimental period. Mean 13C2 -oxalic acid absorption averaged across the ascorbate and no-supplement treatments was significantly greater in SFs (9.9%) than NSFs (8.0%). SFs also had significantly greater 24-hour post-oxalate load urinary total oxalate and endogenous oxalate levels with both treatments. Twenty-four-hour urinary total oxalate level correlated strongly with both 13C2 -oxalic acid absorption (SFs, r = 0.76; P < 0.01; NSFs, r = 0.62; P < 0.01) and endogenous oxalate synthesis (SFs, r = 0.95; P < 0.01; NSFs, r = 0.92; P < 0.01). SFs are characterized by greater rates of both oxalate absorption and endogenous oxalate synthesis, and both these factors contribute to the hyperoxaluric state. The finding that ascorbate supplementation increased urinary total and endogenous oxalate levels suggested that this practice is a risk factor for individuals predisposed to kidney stones.


The relation between infant indoor environment and subsequent asthma.
Our aim was to examine the contribution of an infant's indoor environment to childhood asthma using prospective data. We conducted a cross-sectional asthma survey in 1995 on 92% (6,378/6,911) of 7-year-olds in Tasmania, Australia. We linked these data with data collected in 1988 as part of the Tasmanian Infant Health Survey, which was designed to investigate sudden infant death. We were able to match 863 records out of the 1,111 in the 1988 survey and the 6,378 in the 1995 survey. The former group was interviewed at home at 1 month of age. In homes where at least one adult smoked in 1988, reported infant exposure to smoking in the same room in 1988 was associated with increased asthma by 1995 (relative risk = 1.52; 95% confidence interval = 1.01-2.29) after adjustment for confounders. The associations between infant exposure to environmental tobacco smoke and asthma were not consistent, however. Gas heater use in 1988 was associated with asthma (relative risk = 1.92; 95% confidence interval = 1.33-2.76). Markers of aeroallergen exposure at 1 month of age were not materially associated with asthma or wheeze. In some settings, air circulation practice with regard to bedroom door closure appeared important. Poor indoor air quality may play an important role in the development of childhood asthma.


Systematic overrepresentation of DNA termini and underrepresentation of subterminal regions among sequencing templates prepared from hydrodynamically sheared linear DNA molecules.
Analysis of fungal genome sequence assemblies reveals that telomeres are poorly represented even though telomeric reads tend to be superabundant. We surmised that the problem might lie in the DNA shearing conditions used to create clone libraries for genome sequencing. A shotgun strategy was used to sequence and assemble circular and linear cosmid DNAs sheared using conditions typical for a genome project. The DNA sheared in circular form assembled into a single sequence contig. However, the linearized cosmid produced an incomplete assembly because the two DNA termini, though greatly overrepresented in the clone library used for sequencing, were separated from neighboring sequences by gaps of approximately 1.4 and 1.8 kb. These gap sizes were reduced, but not eliminated, by shearing the linear cosmid into smaller fragments. Mapping of shearing breakpoints revealed a paucity of breaks in the subterminal regions of the linearized cosmid and also near chromosome ends of the fungus Neurospora crassa. Together, our data indicate that the ends of linear DNA molecules are recalcitrant to hydrodynamic shearing. We propose that this causes DNA termini to be overrepresented in the resulting fragment population but ultimately prevents their incorporation into sequence assemblies.


Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.
Mps1, a dual-specificity kinase, is required for the proper functioning of the spindle assembly checkpoint and for the maintenance of chromosomal stability. As Mps1 function has been implicated in numerous phases of the cell cycle, the development of a potent, selective small-molecule inhibitor of Mps1 should facilitate dissection of Mps1-related biology. We describe the cellular effects and Mps1 cocrystal structures of new, selective small-molecule inhibitors of Mps1. Consistent with RNAi studies, chemical inhibition of Mps1 leads to defects in Mad1 and Mad2 establishment at unattached kinetochores, decreased Aurora B kinase activity, premature mitotic exit and gross aneuploidy, without any evidence of centrosome duplication defects. However, in U2OS cells having extra centrosomes (an abnormality found in some cancers), Mps1 inhibition increases the frequency of multipolar mitoses. Lastly, Mps1 inhibitor treatment resulted in a decrease in cancer cell viability.


An in vitro model for Extracellular DNA Traps (ETs)-rich Human Thrombus Analogs.
Extracellular DNA traps (ETs) have important implications in both thrombosis and thrombolysis. Thus, developing benchtop thrombus analogs that recapitulate clinical ETs is potentially of great value for preclinical development and testing of thrombolytic agents and thrombectomy devices. In this study, we aimed to develop ETs-rich thrombus analogs for preclinical testing. Red blood cell (RBC)-rich, fibrin-rich, and platelet-rich thrombus analogs were created using human whole blood, platelet-poor plasma, and platelet-rich plasma obtained from the blood bank following institutional approval. Peripheral blood mononuclear cells (9.9×106 cells/mL) isolated from human whole blood and lipopolysaccharide (1 µg/mL) were added to induce ETs. Histochemical, immunohistochemistry and immunofluorescence were used to identify thrombus components and ETs. Scanning electronic microscopy was used to investigate the ultrastructure of the thrombus analogs. The thrombus compositions, morphologic features of ETs and citrullinated histone H3 (H3Cit) expression were compared with those of thrombi retrieved from patients by thrombectomy. ETs-rich thrombus analogs were more compacted th-an the ETs-poor thrombus analogs. ETs were identified in both ETs-rich thrombus analogs and patient thrombi showing morphologic features including nuclear lobulation, nuclear swelling, diffused chromatin within cytoplasm, DNA/chromatin extending intracellularly and extracellularly, and extracellular chromatin patches and bundles. In the ETs-poor thrombus analogs, ETs were not observed and H3Cit expression was absent to minimal. The compositions and H3Cit expression in the ETs-rich thrombus analogs fell in the range of patient thrombi. ETs-rich thrombus analogs can be consistently created in vitro and may benefit the preclinical development and testing of new thrombolytic agents and thrombectomy devices.


A comparative molecular field analysis of cytotoxic beta-carboline analogs.
To derive a model that could be used in drug design. Beta-carbolines are reported to have antitumor activities on cultured cancer cell lines. A comparative molecular field analysis (CoMFA) was undertaken to elucidate the correlation of cytotoxities and structural parameters of 16 beta-carboline analogs (1-16). The compound 12 was finally used as a template for the other compounds in the dataset because of its highest biological activity. The CoMFA applied to the final alignment resulted in a q2(cv) of 0.656 and it showed that the steric fields contributed 43.3% of the model information while the electrostatic fields represented the other 56.7%. Three designed compounds, which were predicted to have high, moderate and low activities respectively, were synthesized. The IC50 values of these compounds indicated the significance of the analysis in this study. The model derived from the current study could be further used in design for more active compounds.


Early signature in the blood lipidome associated with subsequent cognitive decline in the elderly: A case-control analysis nested within the Three-City cohort study.
Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level. We studied participants from the Three-City study, a multicentric cohort of older persons, free of dementia at time of blood sampling, and who provided repeated measures of cognition over 12 subsequent years. We measured 189 serum lipids from 13 lipid classes using shotgun lipidomics in a case-control sample on cognitive decline (matched on age, sex and level of education) nested within the Bordeaux study center (discovery, n = 418). Associations with cognitive decline were investigated using bootstrapped penalized regression, and tested for validation in the Dijon study center (validation, n = 314). Among 17 lipids identified in the discovery stage, lower levels of the triglyceride TAG50:5, and of four membrane lipids (sphingomyelin SM40:2,2, phosphatidylethanolamine PE38:5(18:1/20:4), ether-phosphatidylethanolamine PEO34:3(16:1/18:2), and ether-phosphatidylcholine PCO34:1(16:1/18:0)), and higher levels of PCO32:0(16:0/16:0), were associated with greater odds of cognitive decline, and replicated in our validation sample. These findings indicate that in the blood lipidome of non-demented older persons, a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts, is associated with subsequent cognitive decline. The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.


Comparative evaluation to study the effect of implant support on complete fixed dental prosthesis fabricated with peek framework when implants placed in all-on-4 and all-on-6 situation, by strain gauge analysis and finite element analysis - An in vitro study.
To evaluate and compare the strain development and distribution of maxillary implant-supported complete fixed dental prosthesis (ISCFDP) with computer-aided design-computer-aided manufacturing milled PEEK BIO-HPP superstructure when placed using All-on-4 and All-on-6 situation using a strain gauge and finite element analysis (FEA). This is an in vitro study to evaluate and compare the stress minimization and strain developed at implant in premolar and in two clinically simulated situation of All-on-4 and All-on -6 ISCFDP. The study involved converting a human skull into. stl format to create 3D-printed stereolithography models with a modulus of elasticity closer to bone. Implants were placed in two models (M1 nad M2) in incisor, premolar, and pterygoid regions. A fixed dental prosthesis framework was fabricated on both models, and strain gauge sensors were attached. Descriptive and analytical statistics were done. The normality of data was analyzed by the Shapiro-Wilk test. The results obtained were tabulated and it showed strain around the neck of ISCFDP under 100N configuration in strain gauge analysis. Stress was found more in the molar region when compared to the premolar region. This design showed that the largest stress around the neck of ISFDP under 100 N load was found more in the premolar region when compared to the molar region due to the reduction of stresses in the pterygoid region in FEA. In the present study, strain gauge analysis at 100 N for loading at the premolar and molar region shows the reduced strain on tilted implants in All-on-6 situation due to stress dissipation to the terminal pterygoid implant using strain gauge.


Effect of fermented soy milk on the intestinal bacterial ecosystem.
To investigate the effect of fermented soy milk on human ecosystem in the intestinal tract by way of examining the population of different microorganisms isolated from fecal samples. A crossover experimental design was applied. Twenty-eight healthy adults completed this experiment. Each subject consumed 250 mL, twice a day between meals, of either fermented soy milk or regular soy milk first for 2 wk, then switched to the other drink after 2 wk. Fecal samples were collected from all subjects every week starting from the second week to the end of the experiment. The microorganisms analyzed were Bifidobacterium spp., Lactobacillus spp., Clostridium perfringens, coliform organisms, and total anaerobic organisms. In the period of fermented soy milk consumption, the populations of Bifidobacterium spp. and Lactobacillus spp. increased (P<0.05) as well as the ratios of Bifidobacterium spp. and Lactobacillus spp. to Clostridium perfringens (P<0.05). The population of coliform organisms decreased (P<0.05) when subjects were in the period of fermented soy milk consumption. Intake of fermented soy milk significantly improved the ecosystem of the intestinal tract in the body by increasing the amount of probiotics.


Regulation of cancer aggressive features in melanoma cells by microRNAs.
MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here we focus on identification of miRNAs that regulate the aggressive phenotype of melanoma cells. To avoid differences due to genetic background, a comparative high-throughput miRNA profiling was performed on two isogenic human melanoma cell lines that display major differences in their net proliferation, invasion and tube formation activities. This screening revealed two major cohorts of differentially expressed miRNAs. We speculated that miRNAs up-regulated in the more-aggressive cell line contribute oncogenic features, while the down-regulated miRNAs are tumor suppressive. This assumption was further tested experimentally on five candidate tumor suppressive miRNAs (miR-31, -34a, -184, -185 and -204) and on one candidate oncogenic miRNA (miR-17-5p), all of which have never been reported before in cutaneous melanoma. Remarkably, all candidate Suppressive-miRNAs inhibited net proliferation, invasion or tube formation, while miR-17-5p enhanced cell proliferation. miR-34a and miR-185 were further shown to inhibit the growth of melanoma xenografts when implanted in SCID-NOD mice. Finally, all six candidate miRNAs were detected in 15 different metastatic melanoma specimens, attesting for the physiological relevance of our findings. Collectively, these findings may prove instrumental for understanding mechanisms of disease and for development of novel therapeutic and staging technologies for melanoma.


Asymptomatic carotid disease in patients undergoing major cardiovascular operations: can prophylactic endarterectomy be justified?
This article reviews the published experience supporting or refuting the value of prophylactic endarterectomy in patients with asymptomatic carotid disease who are candidates for major cardiovascular operations. Reports of 1,483 patients subjected to staged or concomitant carotid endarterectomy and coronary artery bypass grafting reveal a perioperative stroke rate of 2.9%. Timing of carotid endarterectomy did not influence stroke rate, but staged procedures were associated with a significantly greater incidence of perioperative myocardial infarction and death. Studies of patients undergoing major cardiovascular surgical operations without prophylactic carotid endarterectomy reported a perioperative stroke rate of 2.7%, which is not significantly different from that of patients undergoing prophylactic carotid endarterectomy. However, the author's prospective study of such patients showed a significant incidence of late postoperative neurologic deficits, which are usually transient ischemic attacks. There is no evidence to justify routine prophylactic carotid endarterectomy of asymptomatic carotid disease before major cardiovascular operations. Patients not undergoing endarterectomy, however, should be given careful postoperative follow-up, because transient ischemic attacks may occur that require surgical intervention.


Time required to achieve maximum amikacin concentration in the synovial fluid of the tarsocrural joint following administration of the drug by intravenous regional limb perfusion in horses.
To determine the median time to maximum concentration (tmax) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses. 7 healthy adult horses. With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrural synovial fluid samples were collected at 5, 10, 15, 20, 25, and 30 minutes after completion of IVRLP. The tourniquet was removed after collection of the last sample. Amikacin concentration was quantified by a fluorescence polarization immunoassay. Median maximum amikacin concentration and tmax were determined. 1 horse was excluded from analysis because an insufficient volume of synovial fluid for evaluation was obtained at multiple times. The median maximum synovial fluid amikacin concentration was 450.5 μg/mL (range, 304.7 to 930.7 μg/mL), and median tmax was 25 minutes (range, 20 to 30 minutes). All horses had synovial fluid amikacin concentrations ≥ 160 μg/mL (therapeutic concentration for common equine pathogens) at 20 minutes after IVRLP. Results suggested that, in healthy horses, maintaining the tourniquet for 20 minutes after IVRLP of amikacin in a saphenous vein was sufficient to achieve therapeutic concentrations of amikacin in the tarsocrural joint.


Helping people is a democratic process. 1948.
Editor's Note Deciding when to assist and when to stand back so that individuals may follow their own desires has been a source of much public debate in the last few years with respect to health behaviors, social structures, and also political beliefs. The following short essay, published in the July 1948 issue of the first Public Health Nursing, illustrates, first, that from flawed logic we derive flawed conclusions, but also maybe a modicum of truth. Secondly, it aptly highlights the conundrum of "incentives" and the disillusionment of well-meaning "givers" when the recipients do not view our "gifts" through the same lens. We do not subscribe to the views of Ms. King, but rather raise the following questions for your consideration, "When we give, how much are we meeting our own needs rather than the needs of others?""Can a society be empathic without losing its own sense of identity?" Things to ponder in this holiday season ...


Close or positive resection margins are not associated with an increased risk of chest wall recurrence in women with DCIS treated by mastectomy: a population-based analysis.
Mastectomy is effective treatment for ductal carcinoma in situ (DCIS) but some women will develop chest wall recurrence. Most chest wall recurrences that develop after mastectomy are invasive cancer and are associated with poorer prognosis. Past studies have been unable to identify factors predictive of chest wall recurrence. Therefore, it remains unclear if a subset exists of women with DCIS treated by mastectomy experience a high rate of recurrence in whom more aggressive treatment may be of benefit. We report outcomes of all women in Ontario (N = 1,546) diagnosed with pure DCIS from 1994 to 2003 treated with mastectomy without radiotherapy and evaluate factors associated with the development of chest wall recurrence. Treatments and outcomes were validated by chart review. Proportional differences were compared using Chi square analyses. Survival analyses were used to study the development of chest wall recurrence in relation to patient and tumor characteristics. Median follow-up was 10.1 years. Median age was 57.1 years. 36 patients (2.3%) developed chest wall recurrence. The 10-year actuarial chest wall recurrence-free survival rates and invasive chest wall recurrence-free survival rates were 97.6 and 98.6%, respectively. There was no difference in cumulative 10 year rates of chest wall recurrence by age at diagnosis (<40 years = 5.2%, 40-44 years = 1.3%, 45-50 years = 2.9%, >50 years = 2.1%; p = 0.19), nuclear grade (high = 3.0%, intermediate = 1.4%, low = 1.0%, unreported = 2.5%; p = 0.41), or among women with close or positive resection margins (positive = 3.0%, 2 mm or less = 1.4%, >2 mm = 1.5%, unreported = 2.8%; p = 0.51). On univariate and multivariable analysis, none of the factors were significantly associated with the development of chest wall recurrence. In this population cohort, individuals treated by mastectomy experienced low rates of chest wall recurrence. We did not identify a subset of patients with a high rate of chest wall recurrence, including those with positive margins.


Magnetic properties of coordination clusters with {Mn4} and {Co4} antiferromagnetic cores.
We present a joint experimental and theoretical characterization of the magnetic properties of coordination clusters with an antiferromagnetic core of four magnetic ions. Two different compounds are analyzed, with Co and Mn ions in the core. While both molecules are antiferromagnetic, they display different sensitivities to external magnetic field, according to the different atomic magnetic moments and strength of the intra-molecular magnetic couplings. In particular, the dependence of the magnetization versus field of the two molecules switches with temperature: at low temperature the magnetization is smaller in {Mn4} than in Co4, while the opposite happens at high temperature. Through a detailed analysis of the electronic and magnetic properties of the two compounds we identify a stronger magnetic interaction between the magnetic ions in {Mn4} with respect to {Co4}. Moreover {Co4} displays not negligible spin-orbit related effects that could affect the spin lifetime in future antiferromagnetic spintronic applications. We highlight the necessity to account for these spin-orbit effects together with electronic correlation effects for a reliable description of these compounds.


Positive and negative regulation of basal expression of a yeast HSP70 gene.
The SSA1 gene, one of the heat-inducible HSP70 genes in the yeast Saccharomyces cerevisiae, also displays a basal level of expression during logarithmic growth. Multiple sites related to the heat shock element (HSE) consensus sequence are present in the SSA1 promoter region (Slater and Craig, Mol. Cell. Biol. 7:1906-1916, 1987). One of the HSEs, HSE2, is important in the basal expression of SSA1 as well as in heat-inducible expression. A promoter containing a mutant HSE2 showed a fivefold-lower level of basal expression and altered kinetics of expression after heat shock. A series of deletion and point mutations led to identification of an upstream repression sequence (URS) which overlapped HSE2. A promoter containing a mutation in the URS showed an increased level of basal expression. A URS-binding activity was detected in yeast whole-cell extracts by a gel electrophoresis DNA-binding assay. The results reported in this paper indicate that basal expression of the SSA1 promoter is determined by both positive and negative elements and imply that the positively acting yeast heat shock factor HSF is responsible, at least in part, for the basal level of expression of SSA1.


SAFARI: a structured approach for automatic rule.
This paper describes a new algorithm for obtaining rules automatically from training examples. The algorithm is applicable to examples involving both objects: with discrete and continuous-valued attributes. The paper explains a new quantization procedure fur continuous-valued attributes and shows how appropriate ranges of values of various attributes are obtained. The algorithm uses a decision-tree-based approach for obtaining rules, but unlike other tree-based algorithms such as ID3, it allows more than one attribute at a node which greatly improves its performance. The ability of the algorithm to obtain a measure of partial match further enhances its generalization characteristic. The algorithm produces the same rules irrespective of the order of presentation of training examples. The algorithm has been demonstrated on classification problems. The results have compared favorably with those obtained by existing inductive learning algorithms.


A new kinetic model of protein adsorption on suspended anion-exchange resin particles.
The kinetics of adsorption of bovine serum albumin on an anion-exchange resin were measured in a batch system using a flow cell and ultraviolet absorbance, as a function of initial liquid-phase protein concentration and solid-to-liquid phase ratio. A new mathematical model for adsorption kinetics is presented that fits the experimental data to give a highly linear relationship with time, following a short transient period. Numerical integration of the differential form of the new composite nonlinear (CNL) kinetic model, containing three independent parameters, is shown to describe the dynamics of batch adsorption much better than alternative lumped parameter models. Although the new model is phenomenological rather than mechanistic, its principal parameter is shown to be a direct linear function of a physically measurable quantity. This study demonstrates that the model can accurately simulate protein concentration-time profiles using parameter estimates derived from correlations over a wide range of initial protein concentrations and phase ratios. The new CNL model is shown to be considerably superior to the Langmuir and solid-film linear kinetic models in this regard, having the additional advantage that an equilibrium isotherm for the system is not required.


Growing and Shaping Metal-Organic Framework Single Crystals at the Millimeter Scale.
Controlling and understanding the mechanisms that harness crystallization processes is of utmost importance in contemporary materials science and, in particular, in the realm of reticular solids where it still remains a great challenge. In this work, we show that environments mimicking microgravity conditions can harness the size and shape of functional biogenic crystals such as peptide-based metal-organic frameworks (MOFs). In particular, we demonstrate formation of the largest single crystals with controlled nonequilibrium shapes of peptide-based MOFs reported to date (e.g., those featuring curved crystal habits), as opposed to the typical polyhedral microcrystals obtained under bulk crystallization conditions. Such unique nonequilibrium morphologies arise from the interplay between the diffusion-controlled supply of precursors in simulated microgravity environments and the physical constraints imposed during crystal growth. In fact, our method mimics two main strategies of morphogenesis in biomineralization, i.e., spatial and morphological control, both being largely unexplored in the field of self-assembled functional materials. The presented results may open new opportunities to study and understand fundamental questions of relevance to materials science, such as how the size and shape of artificial crystals can influence their properties and functions while providing a strategy to tailor the size and shape of peptide-based MOF single crystals to specific applications.


Choline: Dietary Requirements and Role in Brain Development.
Choline is needed for the maintenance of the structural integrity and signaling functions of cell membranes, for neurotransmission, and for transport of lipids and as a source of methyl groups. Choline can be made de novo in the body, but some individuals must also obtain choline in the diet to prevent deficiency symptoms. A number of environmental and genetic factors influence dietary requirements for choline, and average intakes in the population vary widely. Therefore, certain individuals may be at greater risk of choline deficiency. Choline is critical during fetal development, particularly during the development of the brain, where it can influence neural tube closure and lifelong memory and learning functions.


Optimization of transient Agrobacterium-mediated gene expression system in leaves of Nicotiana benthamiana.
Here we report on a simple and reproducible system of Agrobacterium-mediated transient gene expression assay that utilizes infiltration of young Nicotiana benthamiana leaves. Although some of the phenomena described in this paper have been already reported by other researchers, here we have further developed them. The highest level of transient gfp gene expression was detected in the youngest leaves of N. benthamiana infiltrated with A. tumefaciens strains AGL0 and EHA105 precultured in the presence of 450-600 microM acetosyringone. Although the maximum level of transient gfp gene expression was restricted presumably by RNA silencing, it was completely suppressed in the presence of the viral protein HC-Pro. The transient expression system described here can be used to identify new viral suppressors of RNA silencing, for detailed analysis of unidentified genes and for industrial production of proteins in plants as well.


Generation and coordination of heartbeat timing oscillation in the medicinal leech. II. Intersegmental coordination.
1. A network of four pairs of interneurons, HN(1)-HN(4), times the heartbeat of the medicinal leech. The following model accounts for the stable phase relationships in the network and the network's response to perturbation, entrainment, and stimulation. 2. There are two centers of oscillation, one the HN(3) pair in the third ganglion, the other the HN(4) pair in the fourth ganglion. 3. The two other pairs, HN(1) and HN(2), couple the oscillation of the HN(3) pair with that of the HN(4) pair, thereby guaranteeing that a coherent time signal is sent to the rest of the heartbeat system. 4. The HN(1) and HN(2) pairs can play this coupling role because they have impulse-initiation sites in the third and fourth ganglia and have input and output connections with the HN(3) and HN(4) pairs. 5. In the context of the network, the intrinsic frequency of the HN(4) pair appears to be higher than that of the HN(3) pair. Coupled, the two pairs strike a stable compromise in which the HN(4) pair leads the HN(3) pair.


The risk of acute myocardial infarction: interactions of types of physical activity.
Leisure time physical activity has previously been shown to be protective against cardiovascular disease. We estimated the influence of exercise, occupational physical activity, and household work with regard to risk of acute myocardial infarction (MI). Special interest was focused on potential interaction among these aspects of physical activity. We analyzed data from a large population-based case-control study conducted in Stockholm, Sweden, 1992-1994. Cases comprised 1204 men and 550 women, age 45-70 years, who experienced their first MI during the study period. The controls, 1538 men and 777 women, were randomly selected from the study base, matched on sex, age, and hospital catchment area. The results were adjusted for several potential confounding factors. Exercise, walking or standing at work, and doing demanding household work were all associated with decreased risk of acute MI; the estimated relative risks (RRs) ranged from 0.31 to 0.90 when all cases (fatal and nonfatal) were considered. In contrast, lifting or carrying at work, and an occupational workload perceived to be strenuous, were related to an increased risk of MI (RRs ranging from 1.10-1.57). We observed a synergistic benefit from exercise and walking or standing at work, and from household work and walking or standing at work. Aerobic physical activities such as exercise or walking at work seemed to reduce the risk of MI, whereas anaerobic activities such as heavy lifting at work were related to increased risk of MI.


RNA processing in the minimal organism Nanoarchaeum equitans.
The minimal genome of the tiny, hyperthermophilic archaeon Nanoarchaeum equitans contains several fragmented genes and revealed unusual RNA processing pathways. These include the maturation of tRNA molecules via the trans-splicing of tRNA halves and genomic rearrangements to compensate for the absence of RNase P. Here, the RNA processing events in the N. equitans cell are analyzed using RNA-Seq deep sequencing methodology. All tRNA half precursor and tRNA termini were determined and support the tRNA trans-splicing model. The processing of CRISPR RNAs from two CRISPR clusters was verified. Twenty-seven C/D box small RNAs (sRNAs) and a H/ACA box sRNA were identified. The C/D box sRNAs were found to flank split genes, to form dicistronic tRNA-sRNA precursors and to be encoded within the tRNAMet intron. The presented data provide an overview of the production and usage of small RNAs in a cell that has to survive with a highly reduced genome. N. equitans lost many essential metabolic pathways but maintains highly active CRISPR/Cas and rRNA modification systems that appear to play an important role in genome fragmentation.


In vivo biomicroscopy and photography of meibomian glands in a rabbit model of meibomian gland dysfunction.
The usefulness of transillumination and biomicroscopy of the lid margin in assessing meibomian gland dysfunction was studied in a rabbit model. Transillumination of rabbit lids treated with topical epinephrine for 2 to 3 months revealed plugging of the meibomian gland orifice. Plugging appeared to be correlated histopathologically with increased thickness and hyperkeratinization of the ductal epithelium at the orifice. Continued treatment resulted in microcystic changes within the duct, which were not easily discernible by routine examination without the aid of a transilluminator. Cystic changes were correlated with dilation of the duct by retained desquamated cornified cells. Biomicroscopy proved valuable in identifying and documenting early lesions associated with epinephrine-induced meibomian gland dysfunction.


Prescription opioid related misuse, harms, diversion and interventions in Canada: a review.
The non-medical use of and harms related to prescription opioid (PO) analgesics - key medications to treat severe and chronic pain - are an emerging public health concern globally. PO use is proportionally highest in North America, where, consequently, nonmedical PO use (NMPOU) and morbidity/mortality are high and well documented for the United States. Canada is the country with the second highest PO consumption rate in the world - with steeper recent increases in PO use than the US - mainly driven by substantial increases in the use of strong opioids (e.g., oxycodone). Indications and select data of NMPOU and PO-related morbidity and mortality have emerged in recent years, yet a systematic and comprehensive collection of relevant data to characterize the phenomenon in Canada does not exist. This paper comprehensively reviews the available data in Canada regarding NMPOU, and PO-related harms, diversion, and interventions, and discusses implications for interventions and policy. Narrative literature/data review. Canada. Publicly available data and information - either from journal publications, "grey literature" (e.g., government/technical reports) or Web sites reporting relevant data on Canada - were searched and narratively reviewed. Indicators on NMPOU and PO-related harms in Canada are highly fragmented, and not nearly as systematic and comprehensive as they are in the US; virtually no national statistics/data are collected. Available -largely provincial/local - data indicate that PO misuse is increasingly common in key populations, including general adult and student populations, street-drug users, First Nations/Aboriginal Peoples, and correctional populations. Co-morbidities - e.g., pain, mental health problems, polysubstance use - among people reporting NMPOU appear to be high. Substance use treatment admissions for those with problematic PO use have risen substantially where reported. Opioid-related mortality (and oxycodone-related mortality, specifically) have increased considerably in Ontario where relevant data from the mid-1990s onward have been examined. In Canadian populations reporting NMPOU, sourcing of POs occurs through various diversion routes, including from family/friends, "double-doctoring," or street drug markets. In addition, losses and theft/robberies from pharmacies and licensed medications dealers appear to be on the rise. Finally, interventions (i.e., provincial PO guidelines, prescription monitoring programs, substance use treatment services) are fragmented and inconsistently applied throughout the country, and currently fail to effectively address the growing problem of NMPOU and PO-related harms across Canada. This review did not rely on systematic review methodologies. Corresponding to its increasing and high overall PO consumption levels, NMPOU and PO-related harms in Canada are high based on available data, and likely now constitute the third highest level of substance use burden of disease (after alcohol and tobacco). The data and monitoring situation in Canada regarding NMPOU and PO-related harms are fragmented, un-systematic, and insufficient. While major and concerted policy initiatives - primarily from the federal level - are absent to date, these urgently require vastly improved national data indicators and monitoring in order to allow for and evaluate evidence-based interventions on this urgent and extensive public health problem.


The veridicality of addicts' self-reports in social research.
This report examines the accuracy or veridicality of information obtained through interviews with drug addicts. Comparisons were made between the self-reports on six items of the interview and official records of the Baltimore City Police Department, the Baltimore City Juvenile Court, and the Federal Bureau of Investigation. The findings provide no evidence of systematic distortion intended to "cover-up" the criminal side of addict life. While errors of recall probably do affect self-reports, the incomplete status of official records frequently used to validate self-reports should be of equal concern.


Rous sarcoma virus nucleic acid-binding protein p12 is necessary for viral 70S RNA dimer formation and packaging.
To study the function(s) of the Rous sarcoma virus nucleic acid-binding protein p12, we constructed mutants by using two restriction sites in the p12 proviral coding sequence of the Prague C strain to insert KpnI synthetic linkers. The two restriction sites are in the same reading frame, which allowed us to construct a deletion mutant lacking the two conserved Cys-His regions and a duplication mutant containing three intact Cys-His boxes. These mutant DNAs were transfected into chicken embryo fibroblasts, and the viral particles produced in a transient assay were characterized biochemically and for infectivity. Our results indicate that the Rous sarcoma virus nucleic acid-binding protein p12 is necessary for genomic RNA packaging but not for particle assembly and is implicated in the formation of a stable 70S dimeric RNA. Moreover, the fact that one mutant was apparently able to package normal 70S RNA but was not infectious suggests a role for p12 during the infection process.


Knowledge translation strategies to support service providers' implementation of the "F-words in Childhood Disability".
Service providers are adopting the "F-words" in practice as a strengths-based approach to childhood disability. This study aimed to gain insight into service providers' uses of the "F-words", associated barriers, and knowledge translation strategies needed to support implementation. Service providers were invited to participate in an interview after completing an online survey on their clinical implementation of the "F-words". Content analysis provided insight into use of the "F-words" and perceived barriers; and to identify knowledge translation strategies to facilitate implementation. Twenty-one service providers from nine countries participated in interviews. Applications of the "F-words" included its use as a conceptual framework, directly in practice, and in teaching/training. Barriers included conflicting attitudes, insufficient funding, language, and misalignment with organizational/government priorities. To support the adoption of the "F-words", participants recommended knowledge translation strategies including local opinion leaders, linkage and exchange, educational outreach and meetings, and distribution of educational materials. Understanding uses, barriers to use, and knowledge translation strategies will inform future directions to move the "F-words" into practice. A critical step in bridging the research-to-practice gap and encouraging more widespread adoption requires collaboration with service providers to tailor knowledge translation strategies to fit the local context.Implications for RehabilitationService providers around the world are interested in the ICF-based "F-words" and are adopting them in clinical practice to support a holistic, strengths-based approach to childhood disability.While there is considerable uptake of the "F-words", service providers have experienced barriers including conflicting attitudes of families and colleagues, insufficient funding, lack of translations, and misalignment with organizational and government priorities.To further support implementation and overcome perceived barriers, service providers recommended using four knowledge translation strategies: (i) local opinion leaders; (ii) linkage and exchange; (iii) educational outreach/meetings; and (iv) the distribution of educational materials.Service providers and researchers must partner together to tailor knowledge translation strategies to the local context in order to address the needs and priorities of service providers' specific settings and bridge the gap between research evidence and practice.


Ten-Year Retention Rate of Infliximab in Patients with Behçet's Disease-Related Uveitis.
To evaluate the 10-year drug retention rate of infliximab (IFX) in Behçet's disease (BD)-related uveitis, the effect of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on drug survival and differences according to the lines of biologic treatment. Cumulative survival rates were studied using the Kaplan-Meier plot, while the Log-rank (Mantel-Cox) test was used to compare survival curves. Forty patients (70 eyes) were eligible for analysis. The drug retention rates at 12-, 24-, 60- and 120-month follow-up were 89.03%, 86.16%, 75.66% and 47.11% respectively. No differences were identified according to the use of concomitant DMARDs (p = 0.20), while a statistically significant difference was observed in relation to the different lines of IFX treatment (p = 0.014). Visual acuity improved from baseline to the last follow-up visit (p = 0.047) and a corticosteroid-sparing effect was observed (p < 0.0001). IFX retention rate in BD-uveitis is excellent and is not affected by concomitant DMARDs.


Novel intrinsic neurogenic and myogenic mechanisms underlying the formation of faecal pellets along the large intestine of guinea-pigs.
Soft faecal material is transformed into discrete, pellet-shaped faeces at the colonic flexure. Here, analysis of water content in natural faecal material revealed a decline from cecum to rectum without significant changes at the flexure. Thus, pellet formation is not explained by changes in viscosity alone. We then used video imaging of colonic wall movements with electromyography in isolated preparations containing guinea-pig proximal colon, colonic flexure and distal colon. To investigate the pellet formation process, the colonic segments were infused with artificial contents (Krebs solution and 4-6% methylcellulose) to simulate physiological faecal content flow. Remarkably, pellet formation took place in vitro, without extrinsic neural inputs. Infusion evoked slowly propagating neurogenic contractions, the proximal colon migrating motor complexes (∼0.6 cpm), which initiated pellet formation at the flexure. Lesion of the flexure, but not the proximal colon, disrupted the formation of normal individual pellets. In addition, a distinct myogenic mechanism was identified, whereby slow phasic contractions (∼1.9 cpm) initiated at the flexure and propagated short distances retrogradely into the proximal colon and antegradely into the distal colon. There were no detectable changes in the density or distribution of pacemaker-type interstitial cells of Cajal across the flexure. The findings provide new insights into how solid faecal content is generated, suggesting the major mechanisms underlying faecal pellet formation involve the unique interaction at the colonic flexure between antegrade proximal colon migrating motor complexes, organized by enteric neurons, and retrograde myogenic slow phasic contractions. Additional, as yet unidentified extrinsic and/or humoral influences appear to contribute to processing of faecal content in vivo. KEY POINTS: In herbivores, including guinea-pigs, clearly defined faecal pellets are formed at a distinct location along the large intestine (colonic flexure). The mechanism underlying the formation of these faecal pellets at this region has remained unknown. We reveal a progressive and gradual reduction in water content of faecal content along the bowel. Hence, the distinct transition from amorphous to pellet shaped faecal content could not be explained by a dramatic increase in water reabsorption from a specific site. We discovered patterns of anterograde neurogenic and retrograde myogenic motor activity that facilitate the formation of faecal pellets. The formation of 'pellet-like' boluses at the colonic flexure involves interaction of an antegrade migrating motor complex in the proximal colon and retrograde myogenic slow phasic contractions that emerge from the colonic flexure. The findings uncover intrinsic mechanisms responsible for the formation of discrete faecal scybala in the large intestine of a vertebrate.


Activation of the integrated stress response rewires cardiac metabolism in Barth syndrome.
Barth Syndrome (BTHS) is an inherited cardiomyopathy caused by defects in the mitochondrial transacylase TAFAZZIN (Taz), required for the synthesis of the phospholipid cardiolipin. BTHS is characterized by heart failure, increased propensity for arrhythmias and a blunted inotropic reserve. Defects in Ca2+-induced Krebs cycle activation contribute to these functional defects, but despite oxidation of pyridine nucleotides, no oxidative stress developed in the heart. Here, we investigated how retrograde signaling pathways orchestrate metabolic rewiring to compensate for mitochondrial defects. In mice with an inducible knockdown (KD) of TAFAZZIN, and in induced pluripotent stem cell-derived cardiac myocytes, mitochondrial uptake and oxidation of fatty acids was strongly decreased, while glucose uptake was increased. Unbiased transcriptomic analyses revealed that the activation of the eIF2α/ATF4 axis of the integrated stress response upregulates one-carbon metabolism, which diverts glycolytic intermediates towards the biosynthesis of serine and fuels the biosynthesis of glutathione. In addition, strong upregulation of the glutamate/cystine antiporter xCT increases cardiac cystine import required for glutathione synthesis. Increased glutamate uptake facilitates anaplerotic replenishment of the Krebs cycle, sustaining energy production and antioxidative pathways. These data indicate that ATF4-driven rewiring of metabolism compensates for defects in mitochondrial uptake of fatty acids to sustain energy production and antioxidation.


Risk factors for breast cancer mortality among the National Breast Screening Study of Canada participants.
We studied the relationship between risk factor information and breast cancer mortality by means of a case control study, nested within the population of the National Breast Screening Study of Canada (NBSS). The characteristics of women aged 40-59 years, identified at the initial screen, who subsequently died of breast cancer up to 7 years from the initial screen, were compared with those of controls drawn from the same population. Among the factors evaluated in this study, number of live births and presence of symptoms in the breast revealed on direct questioning were found to be significantly related to breast cancer mortality. The results suggest a decrease in risk of dying of breast cancer associated with one or more live births (OR: 0.79, 95% CI: 0.68, 0.93), and an increase in risk of dying of breast cancer associated with symptoms in the breast revealed on direct questioning at the initial screen (OR: 2.01, 95% CI: 1.20, 3.37).


Amino acid composition and digestible amino acid content in animal protein by-product meals fed to growing pigs1.
An industry survey and animal experiment were conducted to evaluate the amino acid (AA) compositional variability and standardized ileal digestibility (SID) of AA in animal protein by-products fed to growing pigs. Animal protein by-product meals (212) were categorized into 8 groupings (blood meal, chicken by-product meal, chicken meal, feather meal, meat and bone meal, meat meal, poultry by-product meal, and poultry meal) and analyzed for total AA. Amino acid analysis among (e.g., Lys in blood meal averaged 9.20% compared with 2.31% for feather meal, DM basis) and within (e.g., Lys range of 1.54% in blood meal and 1.44% in feather meal, DM basis) the by-product classifications varied as expected, but on average the total AA values were similar to that reported in the literature. For the determination of the SID of AA, 15 barrows (average initial and final BW of 31.6 and 78.7 kg, respectively) were fitted with a T-cannula in the distal ileum and allotted to 15 diets over nine 7-d periods, resulting in 9 replications per diet. Pigs were fed a basal diet based on soybean meal and dehulled-degermed corn, 13 diets containing 17.5% animal protein by-product meal to partially replace a portion of the soybean meal and dehulled-degermed corn in the basal diet, or a N-free diet. Pigs were re-allotted to diets based on minimizing the number to times that the N-free diet would precede or follow feeding either of the blood or feather meal diets because of concern with inadequate diet consumption, as well as to prevent diets from being re-fed to the same pig during the next or subsequent periods. Values for the apparent ileal AA digestibility of each diet were determined, adjusted to SID based upon the endogenous AA losses determined by feeding the N-free diet, and the SID of AA in each animal protein by-product meal calculated using the difference procedure. The SID of AA varied among (e.g., SID of Lys averaged 91% in chicken meal but 47% in feather meal) and within (e.g., SID of Lys in three meat and bone meals was 80%, 71%, and 54%) the animal protein by-product meals, as would be expected and are consistent with variation reported in the literature. Overall, the data provide total AA composition for 212 samples and SID of AA for 13 samples of animal protein by-product meals, including data on their variability, which is critical for their use in feed formulation programs.


Lifelong Classification in Open World With Limited Storage Requirements.
This letter focuses on the problem of lifelong classification in the open world, the goal of which is to achieve an endless process of learning. However, incremental data sets (like the streaming data) in the open world, where the new classes may be emerging, are unsuited for classical classification methods. For addressing this problem, existing methods usually retrain the whole observed data sets with the complex computation and the expensive storage cost. This letter attempts to improve the performance of classification in the open world and decomposes the problem into three subproblems: (1) to reject unknown instances, (2) to classify accepted instances, and (3) to cut the cost of learning. Rejecting unknown instances refers to recognize those instances whose classes are unknown according to the learner, which could reduce the computation of the retraining process and eliminate the storage of historical data sets. We employ outlier detection for rejecting instances and a variant artificial neural network for classifying with fewer weights. Results on several experiments show that the work is effective. Source code can be found at https://github.com/wangbi1988/Lifelong-learning-in-Open-World-Classification.


Reanalysis of Epidemiological Investigation of Cancer Risk among People Residing near Nuclear Power Plants in South Korea.
Background: A 20-year follow-up study on cancer incidence among people living near nuclear power plants in South Korea ended in 2011 with a finding of significantly, but inconsistently, elevated thyroid cancer risk for females. Reanalysis of the original study was carried out to examine the dose-response relationship further, and to investigate any evidence of detection bias. Methods: In addition to replicating the original Cox proportional hazards models, nested case-control analysis was carried out for all subjects and for four different birth cohorts to examine the effects of excluding participants with pre-existing cancer history at enrollment. The potential for detection bias was investigated using the records of medical utilization and voluntary health checks of comparison groups. Results: The overall risk profile of the total sample was similar to that of the original study. However, in the stratified analysis of four birth cohorts, the cancer risk among people living near nuclear power plants became higher in younger birth cohorts. This was especially true for thyroid cancers of females (hazard ratio (HR) 3.38) and males (HR 1.74), female breast cancers (HR 2.24), and radiation-related cancers (HR 1.59 for males, HR 1.77 for females), but not for radiation-insensitive cancers (HR 0.59 for males, HR 0.98 for females). Based on medical records and health check reports, we found no differences between comparison groups that could have led to detection bias. Conclusions: The overall results suggest elevated risk of radiation-related cancers among residents living near nuclear power plants, controlling for the selective survival effect. This is further supported by the lack of evidence of detection bias and by records of environmental exposure from radiation waste discharge.


Parental concerns and attributions of food pickiness and its consequences for the parent-child relationship: A qualitative analysis.
A qualitative study was conducted to identify how parents describe and attribute their toddler's food pickiness, a common pediatric problem during childhood. Parental strategies to respond to picky behaviors were also explored in this study. Focus groups were used with 38 parents of children aged 18-38 months. Results highlighted several consequences of child pickiness such as parental concerns about child's growth and health, conflicts at mealtime, and feelings of guilt. Parents attributed food pickiness mainly as a manifestation of opposition and assertiveness by their child. Some strategies known to be effective were applied by parents (such as repeated exposure, modeling, co-preparing meals, and using a flavor-based approach) but some strategies that are counterproductive were also highlighted (such as rewards for eating). Parents need to be better informed about food pickiness and the strategies that help to overcome it. Understanding parental beliefs may help pediatricians to offer appropriate guidance adapted to parental experiences and feelings.


Coding of mechanical stimulus velocity and indentation depth by squirrel monkey and raccoon glabrous skin mechanoreceptors.
1. A sample of 113 large, myelinated first-order afferent fibers innervating the glabrous skin of the squirrel monkey's hand proved to consist primarily of two basic types. In a sample where the only known source of sampling bias is a greater likelihood to record from larger diameter fibers, 40% of the fibers were rapidly adapting (RA) and 60% were very slowly adapting (VSA). Two units were moderately slowly adapting (MSA), and one had the properties of a Pacinian afferent (Pc). 2. The RA and VSA resemble those in the glabrous skin of other mammalian species in terms of thresholds, receptive-field areas, conduction velocities, and the coding of velocity of mechanical displacement of the skin. Mean instantaneous frequency during ramp stimulation is a power function of ramp velocity for both RA and VSA, with exponents generally less than 1.00. However, ramp discharge patterns differ for RA and VSA. 3. The VSA exhibit a wide range of coefficients of variation (CV) of their interspike-interval distributions, but form a continuous distribution with respect to this statistic. In other respects the VSA are more similar to slowly adapting type I than to slowly adapting type II. They lack spontaneous activity, have restricted receptive fields, and are relatively insensitive to skin stretch. 4. Effects of mechanical stimulus velocity and static indentation depth on static discharge rate were examined in 23 squirrel monkey and 22 raccoon SA units having receptive fields on glabrous skin of the hand. 5. Discharge rate during static indentation is a monotonic, increasing function of identation depth. However, the nature of the best-fitting function (highest r) varies from unit to unit. Using a set of standard conditions (milliseconds 100-500 of static displacements up to 960 mum, following a ramp velocity of 100 mum/ms, interstimulus interval of at least 10 s), the ratio of units for which linear, as opposed to logarithmic, functions provided the best fit was 4:3 for squirrel monkeys and 1:3 for raccoons. Few units had power functions as best fits in either species. Differences between fits for different functions within the same unit, however, were often trivial and insignificant. 6. Response rate during static skin displacement is also strongly influenced by prior stimulus ramp velocity. For at least the first 500 ms, discharge rate is positively related to onset velocity but, in many units, within the first 1 s of static displacement, this relationship reverses itself, and the inverse relationship may persist for at least 5 s.


[Analysis of maternal mortality during three periods at Hospital de Ginecología y Obstetricia del Centro Médico Nacional de Occidente].
Most of deceases due to pregnancy, delivery, puerperium and them attention are avoidable with current medicine resources. To analyze some basic elements of epidemiologic behavior of a hospital environment maternal mortality in a third level hospital during a period of 21 years. Analytical cross-sectional study, 222 maternal deaths registered at Hospital de Ginecologia y Obstetricia, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, were included, during the period 1985-2005. Deaths were analyzed in three periods of 7 years each one. The analysis of results was made based on descriptive statistic. chi2 was used for comparison between periods. Maternal death ratio was 73 per 100,000 live births during the 21 years. Maternal mortality was lower in the group of women under 20 years and increase agreed maternal age. Frequency of direct obstetric deaths decreased when comparing the 3 periods. The main causes of maternal death were preeclampsia/eclampsia and obstetric hemorrhage, which were responsible for almost 50% of maternal deaths. There was no significant difference to anticipation by comparing periods, between 28 and 37% of deaths were foreseen. 98% of deaths occurred at Intensive Care Units. Direct and indirect maternal deaths show very similar values in the third period, which translates in an improvement in anticipation. It must be reinforce the simple and opportune information to the patient with regard to warning signs and the permanent medical training must be a priority at the 3 medical levels.


Conflicts of interest among academic dermatologists: freedom or constraint?
Intangible and institutional conflicts of interest can particularly affect academia. Academic scientists have peculiar social responsibilities with respect to education and research. These responsibilities may conflict with the increased presence of industry in academia and commercialization of academic research through patents and royalties. Drug approval is almost entirely dependent worldwide on data produced in studies led by pharmaceutical industries. A reflection of the increasing role of the market in academic research is given by exaggerated claims in press releases by academic institutions. In consideration of the extensive presence of industry in academia, there is a need for a move from individual to institutional conflicts of interest disclosure, defining institutional policies for regulating conflicts of interest and developing an 'ethically credible partnership'.


[An automated expert system for medical professional orientation of teenagers and youth].
The paper outlines a concept of the automatic medical examination system (MES) designed to aid a physician during his/her medical professional orientation. The authors propose a general MES schedule, define the term "professional inability" (in the medical sense). They provide evidence for that it is necessary to use the assessments made experts as to the professional disability of adolescents and young people who have chronic diseases and dysfunctions. The common principles in the construction of expert MES matrices are outlined. After its completion, MES may be used for purposes of medical professional orientation.


Vincristine neurotoxicity. Pathophysiology and management.
Vincristine is an antineoplastic drug with a broad spectrum of activity against haematological malignancies and childhood sarcomas. Besides useful activity, it lacks the usual emetic and myelotoxicity of anticancer drugs, but its use is limited by neurotoxicity. The neurotoxicity commonly manifests as reduced motility of the intestines resulting in constipation, and peripheral neuropathy which is predominantly sensory in nature. The early symptoms include numbness and tingling of hands and feet which is accompanied by loss of deep tendon reflexes. In its more severe form, muscle weakness develops which is more marked in distal muscles of the hands and feet. Other manifestations of neurotoxicity include ocular palsies, hoarseness of voice, and autonomic neuropathy in the form of postural hypotension and atony of the urinary bladder. The neurotoxicity is dose related and cumulative with repeated dosage such that the drug therapy has to be stopped after a cumulative dose of 30 to 50 mg. The neurotoxicity is usually reversible on interruption of the therapy, but the recovery is slow and takes several months. There are no specific antidotes which have established usefulness against neurotoxicity.