INDISIM-Denitrification, an individual-based model for study the denitrification process.
Denitrification is one of the key processes of the global nitrogen (N) cycle driven by bacteria. It has been widely known for more than 100 years as a process by which the biogeochemical N-cycle is balanced. To study this process, we develop an individual-based model called INDISIM-Denitrification. The model embeds a thermodynamic model for bacterial yield prediction inside the individual-based model INDISIM and is designed to simulate in aerobic and anaerobic conditions the cell growth kinetics of denitrifying bacteria. INDISIM-Denitrification simulates a bioreactor that contains a culture medium with succinate as a carbon source, ammonium as nitrogen source and various electron acceptors. To implement INDISIM-Denitrification, the individual-based model INDISIM was used to give sub-models for nutrient uptake, stirring and reproduction cycle. Using a thermodynamic approach, the denitrification pathway, cellular maintenance and individual mass degradation were modeled using microbial metabolic reactions. These equations are the basis of the sub-models for metabolic maintenance, individual mass synthesis and reducing internal cytotoxic products. The model was implemented in the open-access platform NetLogo. INDISIM-Denitrification is validated using a set of experimental data of two denitrifying bacteria in two different experimental conditions. This provides an interactive tool to study the denitrification process carried out by any denitrifying bacterium since INDISIM-Denitrification allows changes in the microbial empirical formula and in the energy-transfer-efficiency used to represent the metabolic pathways involved in the denitrification process. The simulator can be obtained from the authors on request.


Early childhood amnesia: a quantitative study with implications for the study of retrograde amnesia after brain injury.
Measurement of retrieval of episodic memories ascribed to the various years of early childhood was made over a three-month period of search by 17 normal young adults. The distribution of episodes ascribed to various ages is described, and it is shown that the recovery of memory from early childhood tends to show features of shrinking retrograde amnesia. Methods which were used to recover very early episodes are described, and implications for the study of shrinking retrograde amnesia in brain-damaged patients are discussed.


Linking pyrolysis and anaerobic digestion (Py-AD) for the conversion of lignocellulosic biomass.
Biogas is a mixture of CO2 and CH4 produced by a consortia of Bacteria and Archeae operating in anaerobic digestion (AD) plants. Biogas can be burnt as such in engines to produce electricity and heat or upgraded into biomethane. Biomethane is a drop-in fuel that can be injected in the natural gas grid or utilised as a transport fuel. While a wide array of biomass feedstock can be degraded into biogas, unconverted lignin, hemicellulose and cellulose end up in the co-product digestate leaving a large portion of chemical energy unutilised. Pyrolysis (Py) transforms in a single step and without chemical reagents the lignocellulose matrix into gaseous (syngas), liquid (bio-oil, pyrolysis oil) and solid (biochar) fractions for the development of renewable fuels and materials. The Py route applied downstream to AD is actively investigated in order to valorise the solid digestate presently destined only for soil applications. Coupling Py upstream to AD is an emerging field of research aimed at expanding the feedstock towards biologically recalcitrant substrates (wood, paper, sludge). The biomethanation potential was demonstrated for gaseous (H2/CO) and water soluble pyrolysis products, while the influence of insoluble pyrolytic lignin remains fairly unexplored. Biochar can promote the production of biomethane by acting as a support for microorganism colonisation, conductor for direct interspecies electron transfer, sorbent for hydrophobic inhibitors, and reactant for in situ biogas upgrading. Enhancing the advantages (carbon source) over the side effects (toxicity) of Py fractions represents the main challenge of Py-AD. This can be addressed by increasing the selectivity of the thermochemical process or improving the ecological flexibility of mixed bacterial consortia towards chemically complex environments.


GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro.
Microglia are immunologically competent cells in the central nervous system and considered to be a key player in brain inflammation. The morphological change of microglia has been shown to be linked to functional phenotypes both in vivo and in vitro. As an attempt to identify factors that regulate microglial morphology, we investigated the effect of gangliosides on microglial ramification in vitro. Brain gangliosides mixture and GM1 induced typical ramification of cultured rat primary microglia, however, GD1a and GT1b did not. Although GM1 significantly induced the expression of neurotrophin-3 (NT-3), NT-3 did not induce typical morphological changes in cultured rat primary microglia. SB203580 (an inhibitor of p38), and paclitaxel and nocodazole (microtubule-disrupting drugs) inhibited GM1-induced microglial ramification, but Jaki (an inhibitor of JAK), PD98059 (an inhibitor of Erk1/2), SP600125 (an inhibitor of JNK), and cytochalasin B and latrunculin B (actin polymerization inhibitors) did not, suggesting that GM1 induced ramification of microglia in p38- and microtubule-dependent manner. This in vitro system would be helpful in understanding the mechanisms of microglial ramification and physiological roles of gangliosides in microglia.


Double-orifice mitral valve: a study of 27 postmortem cases with developmental, diagnostic and surgical considerations.
What is double-orifice mitral valve anatomically and embryologically? In 27 postmortem cases, an anomaly of the tensor apparatus was always found. These malformations may be summarized as: (1) chordal ring; (2) accessory papillary muscle or muscles; (3) subdividing muscular ridge; (4) fused papillary muscles (parachute mitral valve); (5) crossing chordae tendineae; and (6) central fibrous subdivision. More than 1 of these anomalies often coexisted per case. Double-orifice mitral valve almost always consisted of abnormal holes in essentially normal leaflets, rather than of abnormal fibrous bridges or adhesions between normal leaflets. Since these fibrous "bridges" between the smaller accessory orifice and the larger main orifice are composed of mitral leaflet tissue and chordae, not fibrous adhesions, these bridges should not be transected surgically, to avoid iatrogenic mitral regurgitation. The accessory (smaller) orifice was at the anterolateral commissure in 11 cases (41%), at the posteromedial commissure in 12 (44%) and there was a central fibrous subdivision with approximately equal-sized orifices in 4 (15%). The atrioventricular (AV) canal was normally divided in 12 cases (44%) and a common AV canal was present in 15 (56%). When the accessory orifice was at the anterolateral commissure, the AV canal usually was normally divided (8 of 11, 73%). But when the accessory orifice was at the posteromedial commissure, a common AV canal almost always was present (11 of 12, 92%). Functionally, the mitral valve was normal in 13 (48%), regurgitated in 7 (26%) and stenotic in 7 (26%). The key to the diagnostic and surgical understanding of the double-orifice mitral valve is the underlying tensor apparatus.


The influence of teacher support on vocational college students' information literacy: The mediating role of network perceived usefulness and information and communication technology self-efficacy.
This paper uses the network perceived usefulness scale, Information and Communication Technology (ICT) self-efficacy scale, teacher support questionnaire and higher vocational students' information literacy scale to explore the multiple intermediary functions of network perceived usefulness and ICT self-efficacy in teacher support and higher vocational students' information literacy from the perspective of multiple intermediary effects, and uses structural equation model for data modeling and analysis. The results show that the information literacy of higher vocational students is positively correlated with teacher support, usefulness of network perception and ICT self-efficacy. Teachers' support is positively correlated with ICT self-efficacy and network perceived usefulness, and network perceived usefulness and ICT self-efficacy play a significant mediating role between teachers' support and information literacy of higher vocational students. Based on the research results, some suggestions are put forward to guide teachers to help students clearly recognize the role of information technology, improve ICT self-efficacy, improve information literacy and better integrate into digital society.


Heritability of refractive astigmatism: a population-based twin study among 63- to 75-year-old female twins.
To examine the heritability of refractive astigmatism in older women. Astigmatism was measured with an autorefractor in 88 monozygotic and 82 dizygotic female twin pairs aged 63 to 75 years. The prevalence and distribution of astigmatism and polar values J0 and J45 were estimated by standard statistical methods. Bivariate maximum likelihood model fitting was used to estimate genetic and environmental variance components using information from both eyes. Mean astigmatism of the more astigmatic eye was 0.93 diopters (D; SD ±0.58). Astigmatism of at least 0.25 D, 0.5 D, 0.75 D, or 1.0 D in either eye was present in 99.7%, 88.5%, 66.5%, and 46.2% of cases, respectively. The main direction of astigmatism was against the rule. The age-adjusted quantitative genetic modeling revealed that additive genetic effects accounted for 33.3% (95% confidence interval [CI], 21.9%-43.8%) of the total variance of astigmatism and for 18% (95% CI, 4%-31%) of the total variance of polar value J45 of both eyes (bivariate model), with the remaining variances due to nongenetic effects. There were no significant correlations between the twin pairs for polar value J0. In elderly female twins, additive genetic effects accounted for one-third of the variance of the amount of astigmatism and only a small fraction of the total variance of polar value J45.


Migratory appendicular muscles precursor cells in the common ancestor to all vertebrates.
In amniote embryos, skeletal muscles in the trunk are derived from epithelial dermomyotomes, the ventral margin of which extends ventrally to form body wall muscles. At limb levels, ventral dermomyotomes also generate limb-muscle precursors, an Lbx1-positive cell population that originates from the dermomyotome and migrates distally into the limb bud. In elasmobranchs, however, muscles in the paired fins were believed to be formed by direct somitic extension, a developmental pattern used by the amniote body wall muscles. Here we re-examined the development of pectoral fin muscles in catsharks, Scyliorhinus, and found that chondrichthyan fin muscles are indeed formed from Lbx-positive muscle precursors. Furthermore, these precursors originate from the ventral edge of the dermomyotome, the rest of which extends towards the ventral midline to form body wall muscles. Therefore, the Lbx1-positive, de-epithelialized appendicular muscle precursors appear to have been established in the body plan before the divergence of Chondrichthyes and Osteichthyes.


[The dimension of the body and its significance in the catathymic picture perception. Suggestions for its therapeutic use with hypochondriasis as an example].
After a short presentation of the waking dream therapy of the guided affective imagery (GAI) and various theoretical comments, it is postulated according to both of Freud's reality conceptions, that also the dimensions of the bodily experience, as it expresses itself in the course of a therapy with GAI, must be split into two conceptions from psychic body reality and material body reality. Based on the therapy minutes of a serious hypochondriac an illustration of both body reality conceptions is given. In conclusion, based on eight finished therapies of hypochondriacs, it was described how hypochondriac patients describe and experience their bodies in GAI. From this it is then evident that hypochondriacs can be helped with the aid of GAI thus going against the general opinion.


Simulation of the fate of selected pharmaceuticals and personal care products in a highly impacted reach of a Canadian watershed.
Municipal wastewater treatment plants (WWTPs) dispose of numerous trace organic contaminants in the receiving waters that can impact biological function in aquatic organisms. However, the complex nature of WWTP effluent mixtures and a wide variety of potential mechanisms that can alter physiological and reproductive development of aquatic organisms make it difficult to assess the linkages and severity of the effects associated with trace organic contaminants. This paper describes a surface water quality modeling exercise that was performed to understand the relevant contaminant fate and transport processes necessary to accurately predict the concentrations of trace organic compounds present in the aquatic environment. The target compounds modeled include a known antiandrogenic personal care product (triclosan) and selected pharmaceuticals (venlafaxine, naproxen, and carbamazepine). The WASP 7.5 model was adapted and calibrated to reflect approximately ten kilometers of reach of the Grand River watershed that is highly influenced by a major urban WWTP. Simulation of the fate and transport of the target compounds revealed that flow-driven transport processes (advection and dispersion) greatly influenced the behavior of the target contaminants in the aquatic environment. However, fate mechanisms such as photolysis and biodegradation can play an important role in the attenuation of some compounds. The exception was carbamazepine where it was shown to act as a conservative tracer compound for wastewater specific contaminants in the water phase. The calibrated water quality model can now be employed in a number of future applications. Prediction of fate and transport of other trace organic contaminants across the watershed and assessment of the performance of WWTP infrastructure upgrades in the removal of these compounds are just a few examples.


Host Cell-Virus Interaction 2.0: Viral Stratagems of Immune Evasion, Host Cellular Responses and Antiviral Counterattacks.
As rightly stated by the author Mira Grant in her novel Countdown, "There is nothing so patient, in this world or any other, as a virus searching for a host" [...].


Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices.
Breast-cancer incidence and mortality rates in different countries were found to be correlated with height, weight and age at menarche, all of which have been identified as risk factors in cohort or case-control studies of breast cancer. There were, however, correlations with total fat and animal protein consumption per capita even after controlling for the 3 anthropometric variables. This suggests that, while some of the effects of diet on breast-cancer rates may be mediated through effects on these known risk factors, there may be more direct effects as well.


Cortisol reactivity and negative affect among preterm infants at 12 months during a mother-infant interaction task.
The purpose of this study was to investigate correlates of preterm (PT) infant's cortisol reactivity and the association to infant negative affect, during a mother-infant interaction procedure. Participants included 48 infants born prematurely (gestational age < 37 weeks) and their mothers, assessed when infants were 12 months old corrected for prematurity. The examined variables comprised both neonatal and environmental dimensions including maternal interactive behavior. Infant negative affect and maternal interactive behavior were assessed with a standardized mother-infant interaction task. A baseline infant saliva sample was collected before the interaction began, and a second sample after the interaction episodes ended. Results revealed that decrease of infant's cortisol concentration was significantly associated with the exposure to more sensitive, and less intrusive maternal behaviors. However, once controlled for neonatal risk, family SES and maternal psychological distress, the associations were rendered non-significant. Although the association between cortisol reactivity and negative affect trended toward significance, maternal intrusiveness was the only significant predictor of observed infant negative affect. Findings suggest the importance of primary relational experiences on PT infants' early regulatory competencies.


Platelet-Rich Plasma and Cartilage Repair.
To assess the utilization and efficacy of platelet-rich plasma (PRP), for the treatment of articular cartilage injury, most commonly characterized by progressive pain and loss of joint function in the setting of osteoarthritis (OA). PRP modulates the inflammatory and catabolic environment through a locally applied concentrate of platelets, leukocytes, and growth factors. Clinically, PRP has been shown to be possibly a viable treatment adjuvant for a variety of inflammatory and degenerative conditions. Recent efforts have focused on optimizing delivery methods that enable platelets to slowly degranulate their biological constituents, which may promote healing and improve OA symptoms for a longer duration. There are various factors that affect the progression of OA within joints, including inhibition of inflammatory cytokines and altering the level of enzymatic expression. PRP therapy aims to mediate inflammatory and catabolic factors in a degenerative environment through the secretion of anti-inflammatory factors and chemotaxic effects. There are a growing number of studies that have demonstrated the clinical benefit of PRP for non-operative management of OA. Additional randomized controlled trials with long-term follow-up are needed in order to validate PRP's therapeutic efficacy in this setting. Additionally, continued basic research along with well-designed pre-clinical studies and reporting standards are necessary in order to clarify the effectiveness of PRP for cartilage repair and regeneration for future clinical applications.


Classification-based machine learning approaches to predict the taste of molecules: A review.
The capacity to discriminate safe from dangerous compounds has played an important role in the evolution of species, including human beings. Highly evolved senses such as taste receptors allow humans to navigate and survive in the environment through information that arrives to the brain through electrical pulses. Specifically, taste receptors provide multiple bits of information about the substances that are introduced orally. These substances could be pleasant or not according to the taste responses that they trigger. Tastes have been classified into basic (sweet, bitter, umami, sour and salty) or non-basic (astringent, chilling, cooling, heating, pungent), while some compounds are considered as multitastes, taste modifiers or tasteless. Classification-based machine learning approaches are useful tools to develop predictive mathematical relationships in such a way as to predict the taste class of new molecules based on their chemical structure. This work reviews the history of multicriteria quantitative structure-taste relationship modelling, starting from the first ligand-based (LB) classifier proposed in 1980 by Lemont B. Kier and concluding with the most recent studies published in 2022.


Associations of Maternal Use of Benzodiazepines or Benzodiazepine-like Hypnotics During Pregnancy With Immediate Pregnancy Outcomes in Norway.
Understanding the safety profile of medications used in pregnancy is crucial for clinical decision-making. Few studies exist on the associations of exposure to benzodiazepines and benzodiazepine-like hypnotic drugs (z-hypnotics) in pregnancy with pregnancy outcomes. To determine whether exposure to benzodiazepines or z-hypnotics in pregnancy is associated with greater risk of negative immediate pregnancy outcomes compared with nonexposure. This questionnaire-based cohort study used data from the Norwegian Mother, Father and Child cohort study (MoBa), which also includes data from the Medical Birth Registry of Norway. Pregnant women were recruited from all over Norway from 1999 and 2008. The first child was born in October 1999 and the last in July 2009. This analysis included women who completed 3 questionnaires, twice during pregnancy and once 6 months after delivery. Data analyses were conducted from September to November 2019. Self-reported exposure to benzodiazepines or z-hypnotics during pregnancy, characterized in terms of any exposure, timing (ie, early, middle, or late), and duration of exposure. The main outcomes were gestational age at delivery, risk of preterm delivery, birth weight, birth weight relative to gestational age and sex, risk of being small for gestational age, head circumference, Apgar score less than 7 at 5 minutes, and risk of neonatal respiratory distress. Continuous outcomes are reported using effect estimates as mean differences, and binary outcomes are reported using risk ratios. The MoBa study included 114 234 mother-child dyads. This analysis of MoBa data includes 82 038 singleton pregnancies among 69 434 unique women. Mean (SD) maternal age was 30.2 (4.5) years, and 37 641 pregnancies (45.9%) were in primiparous women. Exposure to benzodiazepines or z-hypnotics was reported in 679 pregnancies (0.8%). After adjusting for all measured baseline and postbaseline confounders, benzodiazepine or z-hypnotic use during pregnancy was associated with lower birth weight (mean difference, -79.3 [95% CI, -126.7 to -31.9] g), lower gestational age at birth (mean difference, -2.1 [95% CI, -3.3 to -0.9] days), and higher risk of preterm birth (risk ratio, 1.41 [95% CI, 1.03 to 1.94]). We found no significant association of exposure to benzodiazepines or z-hypnotics with the child's birth weight relative to gestational age and sex (z score), or any of the other immediate birth outcomes. These findings suggest that the magnitude of the association of exposure to benzodiazepines or z-hypnotics with gestational age is not necessarily clinically significant. The absence of an association of exposure to benzodiazepines or z-hypnotics with z score for birth weight relative to gestational age and sex suggests that association of exposure to benzodiazepines or z-hypnotics with birth weight could be explained by earlier delivery rather than impaired intrauterine growth.


Volumetric memory network for interactive medical image segmentation.
Despite recent progress of automatic medical image segmentation techniques, fully automatic results usually fail to meet clinically acceptable accuracy, thus typically require further refinement. To this end, we propose a novel Volumetric Memory Network, dubbed as VMN, to enable segmentation of 3D medical images in an interactive manner. Provided by user hints on an arbitrary slice, a 2D interaction network is firstly employed to produce an initial 2D segmentation for the chosen slice. Then, the VMN propagates the initial segmentation mask bidirectionally to all slices of the entire volume. Subsequent refinement based on additional user guidance on other slices can be incorporated in the same manner. To facilitate smooth human-in-the-loop segmentation, a quality assessment module is introduced to suggest the next slice for interaction based on the segmentation quality of each slice produced in the previous round. Our VMN demonstrates two distinctive features: First, the memory-augmented network design offers our model the ability to quickly encode past segmentation information, which will be retrieved later for the segmentation of other slices; Second, the quality assessment module enables the model to directly estimate the quality of each segmentation prediction, which allows for an active learning paradigm where users preferentially label the lowest-quality slice for multi-round refinement. The proposed network leads to a robust interactive segmentation engine, which can generalize well to various types of user annotations (e.g., scribble, bounding box, extreme clicking). Extensive experiments have been conducted on three public medical image segmentation datasets (i.e., MSD, KiTS19, CVC-ClinicDB), and the results clearly confirm the superiority of our approach in comparison with state-of-the-art segmentation models. The code is made publicly available at https://github.com/0liliulei/Mem3D.


Circularly polarized differential intra-oral antenna design validation and characterization for tongue drive system.
Assistive devices are becoming increasingly popular for physically disabled persons suffering tetraplegia and spinal cord injuries. Intraoral tongue drive system (iTDS) is one of the most feasible and non-invasive assistive technology (AT), which utilises the transferring and inferring of user intentions through different tongue gestures. Wireless transferring is of prime importance and requires a suitable design of the intra-oral antenna. In this paper, a compact circularly polarized differential intra-oral antenna is designed, and its performance is analysed within heterogeneous multilayer mouth and head models. It works at 2.4 GHz in the Industrial, Scientific, and Medical (ISM) band. The footprint of the differential antenna prototype is 0.271 λg [Formula: see text] 0.271 λg [Formula: see text] 0.015 λg. It is achieved using two pairs of spiral segments loaded in diagonal form near the edges of the central rotated square slot and a high dielectric constant substrate. Its spiral-slotted geometry further provides the desired swirling and miniaturization at the desired frequency band for both mouth scenarios. Additionally, corner triangular slits on the radiating patch assist in tuning the axial ratio (< 3 dB) in the desired ISM band. To validate the performance of the proposed in-mouth antenna, the measurement was carried out using the minced pork and the saline solution for closed and opened mouth cases, respectively. The measured - 10 dB impedance bandwidth and peak gain values in the minced pork are from 2.28 to 2.53 GHz (10.39%) and - 18.17 dBi, respectively, and in the saline solution, are from 2.3 to 2.54 GHz (9.92%) and - 15.47 dBi, respectively. Further, the specific absorption rate (SAR) is estimated, and the data communication link is computed with and without a balun loss. This confirms that the proposed differential intraoral antenna can establish direct interfacing at the RF front end of the intraoral tongue drive system.


A mitochondrial STAT3-methionine metabolism axis promotes ILC2-driven allergic lung inflammation.
Group 2 innate lymphoid cells (ILC2s), the innate counterpart of TH2 cells, play a critical role in type 2 immune responses. However, the molecular regulatory mechanisms of ILC2s are still unclear. The aim of this study was to explore the importance of signal transducer and activator of transcription 3 (STAT3) to ILC2 function in allergic lung inflammation. Acute and chronic asthma models were established by intranasal administration of the protease allergen papain in VavicreStat3fl/fl, Il5tdtomato-creStat3fl/fl, and RorccreStat3fl/fl mice to verify the necessity of functional STAT3 for ILC2 allergic response. The intrinsic role of STAT3 in regulating ILC2 function was examined by generation of bone marrow chimera mice. The underlying mechanism was studied through confocal imaging, metabolomics analysis, and chromatin immunoprecipitation quantitative PCR. STAT3 is essential for ILC2 effector function and promotes ILC2-driven allergic inflammation in the lung. Mechanistically, the alarmin cytokine IL-33 induces a noncanonical STAT3 phosphorylation at serine 727 in ILC2s, leading to translocation of STAT3 into the mitochondria. Mitochondrial STAT3 further facilitates adenosine triphosphate synthesis to fuel the methionine cycle and generation of S-adenosylmethionine, which supports the epigenetic reprogramming of type 2 cytokines in ILC2s. STAT3 deficiency, inhibition of STAT3 mitochondrial translocation, or blockade of methionine metabolism markedly dampened the ILC2 allergic response and ameliorated allergic lung inflammation. The mitochondrial STAT3-methionine metabolism pathway is a key regulator that shapes ILC2 effector function through epigenetic regulation, and the related proteins or metabolites represent potential therapeutic targets for allergic lung inflammation.


Growth-rate dependency of de novo resveratrol production in chemostat cultures of an engineered Saccharomyces cerevisiae strain.
Saccharomyces cerevisiae has become a popular host for production of non-native compounds. The metabolic pathways involved generally require a net input of energy. To maximize the ATP yield on sugar in S. cerevisiae, industrial cultivation is typically performed in aerobic, sugar-limited fed-batch reactors which, due to constraints in oxygen transfer and cooling capacities, have to be operated at low specific growth rates. Because intracellular levels of key metabolites are growth-rate dependent, slow growth can significantly affect biomass-specific productivity. Using an engineered Saccharomyces cerevisiae strain expressing a heterologous pathway for resveratrol production as a model energy-requiring product, the impact of specific growth rate on yeast physiology and productivity was investigated in aerobic, glucose-limited chemostat cultures. Stoichiometric analysis revealed that de novo resveratrol production from glucose requires 13 moles of ATP per mole of produced resveratrol. The biomass-specific production rate of resveratrol showed a strong positive correlation with the specific growth rate. At low growth rates a substantial fraction of the carbon source was invested in cellular maintenance-energy requirements (e.g. 27 % at 0.03 h(-1)). This distribution of resources was unaffected by resveratrol production. Formation of the by-products coumaric, phloretic and cinnamic acid had no detectable effect on maintenance energy requirement and yeast physiology in chemostat. Expression of the heterologous pathway led to marked differences in transcript levels in the resveratrol-producing strain, including increased expression levels of genes involved in pathways for precursor supply (e.g. ARO7 and ARO9 involved in phenylalanine biosynthesis). The observed strong differential expression of many glucose-responsive genes in the resveratrol producer as compared to a congenic reference strain could be explained from higher residual glucose concentrations and higher relative growth rates in cultures of the resveratrol producer. De novo resveratrol production by engineered S. cerevisiae is an energy demanding process. Resveratrol production by an engineered strain exhibited a strong correlation with specific growth rate. Since industrial production in fed-batch reactors typically involves low specific growth rates, this study emphasizes the need for uncoupling growth and product formation via energy-requiring pathways.


ETCNN: Extra Tree and Convolutional Neural Network-based Ensemble Model for COVID-19 Tweets Sentiment Classification.
Pandemics influence people negatively and people experience fear and disappointment. With the global outspread of COVID-19, the sentiments of the general public are substantially influenced, and analyzing their sentiments could help to devise corresponding policies to alleviate negative sentiments. Often the data collected from social media platforms is unstructured leading to low classification accuracy. This study brings forward an ensemble model where the benefits of handcrafted features and automatic feature extraction are combined by machine learning and deep learning models. Unstructured data is obtained, preprocessed, and annotated using TextBlob and VADER before training machine learning models. Similarly, the efficiency of Word2Vec, TF, and TF-IDF features is also analyzed. Results reveal the better performance of the extra tree classifier when trained with TF-IDF features from TextBlob annotated data. Overall, machine learning models perform better with TF-IDF and TextBlob. The proposed model obtains superior performance using both annotation techniques with 0.97 and 0.95 scores of accuracy using TextBlob and VADER respectively with Word2Vec features. Results reveal that use of machine learning and deep learning models together with a voting criterion tends to yield better results than other machine learning models. Analysis of sentiments indicates that predominantly people possess negative sentiments regarding COVID-19.


Fetal cardiac stroke volume determination by four-dimensional ultrasound with spatio-temporal image correlation compared with two-dimensional and Doppler ultrasonography.
To assess the agreement of stroke volume (SV) measured with two-dimensional (2D) ultrasonography with Doppler capability (vs) four-dimensional (4D) with spatiotemporal image correlation (STIC) in normal and growth restricted fetuses. 2D Doppler and 4D STIC were used to measure SV of 40 normal fetuses at 20 to 22 and 28 to 32 weeks, and 16 growth-restricted fetuses at 26 to 34 weeks of gestation. Intraclass correlation was used to evaluate the agreement between left and right SV obtained by the two techniques, and proportionate Bland-Altman plots constructed. The time necessary to obtain SV was analyzed. The intraclass correlation coefficient between 2D Doppler and 4D STIC measurements for the left ventricle were 0.977 and 0.980 for the right ventricle. The proportionate limits of agreement between the two methods were 18.7 to 23.9% for the left ventricle and - 20.9 to 21.7% for the right ventricle. The time necessary to measure SV was significantly shorter with 4D STIC (3.1 (vs) 7.9 min p < 0.0001) than with 2D Doppler. There is a good agreement between SV measured either by 2D Doppler or by 4D STIC. The 4D STIC represents a simple and rapid technique to estimate fetal SV and promises to become the method of choice.


An extended Monod-Wyman-Changeaux-model expressed in terms of the Herzfeld-Stanley formalism applied to oxygen and carbonmonoxide binding curves of hemoglobin trout IV.
An extended Monod, Wyman, Changeaux (MWC)-model, the mathematical basis of which had been formulated by Herzfeld and Stanley (J. Mol. Blol. 82:231. 1974.) was used to fit oxygen and CO-binding curves of hemoglobin trout IV measured at different pH-values between pH = 8.0 and 6.0. From this calculation one obtains that even the fully liganded molecule exhibits a R----T quaternary transition upon approaching the acid pH-region. In the case of O2-binding, the cooperativity becomes negative below pH = 6.5. This can be related to the difference between the equilibrium constants of proton binding to the alpha- and beta-subunits. Furthermore, it can be shown that the interaction between the quaternary T----R- and the tertiary t----r-transitions is different for the alpha- and beta-subunits.


The effects of poor sleep on cognitive, affective, and physiological responses to a laboratory stressor.
Recent research suggests that poor sleep may be associated with altered stress regulation. This study aims to examine the associations between prior-night and prior-month sleep measures and affective, cognitive, and physiological responses to a laboratory stressor. Ninety-eight (50 % female) young adults completed measures of sleep quality in the context of a laboratory stress study. Measures included positive (PA) and negative affects (NA) and blood pressure (BP) reactivity, as well as change in pre-sleep arousal. Prior-month poor sleep quality and sleep disturbances predicted dampened BP reactivity. Both prior-night and prior-month sleep quality predicted greater decrease in PA. Sleep-associated monitoring predicted NA reactivity and prolonged cognitive and affective activation. Prior-month sleep continuity predicted greater cognitive pre-sleep arousal change, and prior-month sleep quality, daytime dysfunction, and disturbances predicted prolonged cognitive and affective activation. Findings suggest that inadequate sleep confers vulnerability to poor cognitive, affective, and physiological responses to stress.


Comparative pharmacokinetic evaluation of lopinavir and lopinavir-loaded solid lipid nanoparticles in hepatic impaired rat model.
Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats. Isolated perfused liver (IPL) model (n = 3) and cycloheximide intervened lymphatic uptake studies (n = 3) were conducted to appreciate disposition pattern of LPV. In contrary to free LPV, pharmacokinetic results demonstrated no significant (P > 0.05) difference in drug plasma profile of LPV SLNs in normal and impaired rats. IPL model demonstrated trivial role of liver in disposition of LPV SLNs. Tissue distribution studies of SLNs showed higher (P < 0.05) LPV accumulation in lymphoidal organs. Pretreatment of cycloheximide significantly (P < 0.05) reduced AUC and Cmax of LPV SLNs. From the results, we conclude that unlike conventional formulations of LPV, disposition characteristics of LPV SLNs were similar both in normal and hepatic impaired rats.


An injectable extracellular matrix for the reconstruction of epidural fat and the prevention of epidural fibrosis.
Extensive epidural fibrosis is a common complication following spinal surgery and can cause pain and limited mobility. In the present study, a novel biomimetic approach was developed to prevent postsurgical adhesion of the dura. We aimed to reconstruct epidural fat, which prevents scar-tissue adhesion, through the development of an injectable decellularized adipose matrix (DAM)-containing hyaluronic acid (HA) hydrogel loaded with adipose stromal cells (ASCs). Injectable DAM was prepared from porcine adipose tissue by four freeze-thaw cycles with subsequent pepsin digestion. Residual analyses confirmed the efficacy of detergent-free decellularization, while most sulfated glycosaminoglycans and collagen were preserved. The Transwell migration assay demonstrated the anti-infiltrative property of the DAM-containing HA hydrogel. After 14 d of 3D culture, the DAM-containing HA hydrogel showed inductive potential in the adipogenic differentiation of ASCs. For an in vivo study, the ASC-loaded DAM-containing HA hydrogel (DAM/ASC-incorporated HA hydrogel) was injected into adult laminectomized male rats, and the results were assessed by microscopic histological examination. The in vivo data indicated that HA hydrogel, DAM, and ASCs were all required for the ability of the engineered fat tissue to block the invasion of the fibrous tissue. Our results suggested that this injectable DAM/ASC-incorporated HA hydrogel has potential applications in minimally invasive surgery for soft-tissue reconstruction and epidural fibrosis prevention.


Obsessive-compulsive symptoms and resting-state functional characteristics in pre-adolescent children from the general population.
While functional brain characteristics of obsessive-compulsive disorder have been extensively studied, literature on network topology and subnetwork connectivity related to obsessive-compulsive symptoms (OCS) is sparse. Here we investigated the functional brain characteristics of OCS in children from the general population using a multiscale approach. Since we previously observed OCS-related differences in thalamus morphology, we also focused on the network participation of thalamic subregions. The study included 1701 participants (9-12 years) from the population-based Generation R study. OCS were measured using the Short Obsessive-Compulsive Disorder Screener. We studied the brain network at multiple scales: global network topology, subnetwork connectivity and network participation of thalamic nodes (pre-registration: https://osf.io/azr9c ). Modularity, small-worldness and average participation coefficient were calculated on the global scale. We used a data-driven consensus community approach to extract a partition of five subnetworks involving thalamic subregions and calculate the within- and between-subnetwork functional connectivity and topology. Multiple linear regression models were fitted to model the relationship between OCS and functional brain measures. No significant associations were found when using our preregistered definition of probable OCS. However, post-hoc analyses showed that children endorsing at least one OCS (compared with controls) had higher modularity, lower connectivity between frontoparietal, limbic and visual networks as well as altered participation of the lateral prefrontal thalamus node. Our results suggest that network characteristics of OCS in children from the general population are partly symptom-specific and severity-dependent. Thorough assessment of symptom dimensions can deepen our understanding of OCS-related brain networks.


Genetics of rickettsiae.
Classical genetic approaches useful with free-living bacteria are difficult to apply to the rickettsiae. Although rickettsial mutants have been isolated over the years, the genetic basis of these mutants is unknown, limiting their usefulness. The application of molecular biological techniques to rickettsial studies has provided the opportunity to isolate and study specific genes. Genes encoding metabolic enzymes from rickettsiae were cloned in Escherichia coli and shown to retain their regulatory properties, suggesting that recombinant DNA technology may be useful for studies of rickettsial enzymes and regulatory mechanisms. The potential use of rickettsial surface components, or virulence factors as possible antigens for protective subunit vaccines, has led to the cloning and expression in E. coli, of rickettsial chromosomal and plasmid genes encoding outer membrane proteins. The number of genes characterized in recent years has increased dramatically giving rise to an increasing source of information on rickettsial gene structure. Plasmids have only been identified in C. burnetii and possibly Rochalimaea quintana. The plasmid sequences present in C. burnetii are highly conserved suggesting that they are important to the growth and virulence of this organism. To understand the role of genes in the rickettsia-host relationship, it is critical that a genetic exchange system be developed. The recent description of transformation of R. quintana by electroporation is an important first step in this direction. The ability to introduce genetic material is necessary to address questions that cannot be resolved by studying rickettsial gene expression in E. coli.


Preparative-scale isolation and purification of procaryotic and eucaryotic ribosomal 5 S RNA: Bacillus subtilis, Neurospora crassa, and wheat germ.
Ribosomal 5 S RNA from three different organisms has been isolated in high yield and purity. Without prior isolation of ribosomes, a presoak in buffer followed by phenol extraction, DE-32 ion-exchange chromatography, and Sephadex G-75 gel-permeation chromatography yields at least 5-10 mg of electrophoretically homogeneous 5 S RNA from 100 g of cells. Ribonuclease activity is eliminated by various combinations of low temperature, sodium dodecyl sulfate, phenol, and bentonite. High-molecular-weight contaminants are suppressed by either 65 degrees C heat treatment or lowered sodium dodecyl sulfate concentration. For the eucaryotes, 5.8 S RNA contamination is reduced either by low temperature in the initial solubilization or by postponing 65 degrees C heat treatment until after the phenol extraction step.


Evaluation of the mode of action of mouse lung tumors induced by 4-methylimidazole.
4-Methylimidazole (4-MEI) occurs in certain foods and beverages as a product of browning reactions. An increased incidence of lung tumors was reported in mice, but not rats, exposed to levels of 4-MEI in their diet that far exceed human dietary intake. This investigation evaluated the hypothesis that 4-MEI induces mouse lung tumors by the same mode of action (MOA) as styrene: CYP2F2 metabolic activation and increased BrdU labeling. Using styrene (200 mg/kg/day by gavage) as a positive control, histopathology and DNA synthesis (measured by BrdU incorporation) in the bronchiolar region were evaluated in: (1) a 5-day comparative toxicity study in C57BL/6 "wild type" and CYP2F2 "knock out" (KO) mice given 4-MEI at the same dietary concentrations used in the NTP cancer bioassay, and (2) a 13-week comparative toxicity study of C57BL/6 and B6C3F1 mice receiving 0, 1250 or 2500 ppm of 4-MEI in the diet for 6, 15, 34 and 91 days. In contrast to styrene, 4-MEI had no consistent effect on BrdU labeling or histopathology in the lungs of mice in the dose range that had been shown to produce lung tumors in another study. The results of these studies do not support the hypothesis that 4-MEI and styrene induce lung tumors by the same MOA.


Effect of early Class II treatment on the incidence of incisor trauma.
Many researchers have examined the prevalence of dental injuries in children and adolescents. The purpose of this study was to examine the prevalence and incidence of incisor trauma in subjects who participated in a randomized clinical trial designed to investigate early growth modifications in the treatment of Class II malocclusion. The subjects were randomized to 3 treatment groups during the initial phase of the study: (1) headgear or biteplane, (2) bionator, and (3) observation (no treatment). All 3 groups underwent phase 2 treatment with fixed appliances. Incisor injury was scored at every data collection point with the Ellis index by a blinded examiner using dental casts, intraoral photos, and panoramic and periapical x-rays. Twenty-five percent of the subjects had incisor trauma at the baseline examination, and 28% experienced new or worsening maxillary incisor injury during the study. No significant differences were found with regard to sex and prevalence of injury at baseline. No differences in incidence of trauma were found between the 3 treatment groups throughout the study (P = 0.19); however, boys were more likely to experience maxillary incisor injury (odds ratio estimate, 2.37; 95% CI, 1.33, 4.21), and those with an injury at baseline were more likely to experience an additional injury (odds ratio estimate, 1.81; 95% CI, 1.03, 3.17). Early orthodontic treatment did not affect the incidence of incisor injury. The majority of the injuries before and during treatment were minor; therefore, the cost-benefit ratio of orthodontic treatment primarily to prevent incisor trauma is unfavorable.


Predictors of post-operative mortality following treatment for non-ruptured abdominal aortic aneurysm.
The aim of this prospective study of patients undergoing repair of non-ruptured abdominal aortic aneurysm between 1999 and 2003 was to evaluate and compare risk factors for mortality after surgery, to determine a complex of informative factors for lethal outcome, and to define patient risk groups. Logistic regression analysis revealed a complex of informative factors, including female gender, previous myocardial infarction, age greater than 75 years, and clinical course of abdominal aortic aneurysm as important indicators for lethal outcome. A risk score model identified low-, moderate- and high-risk groups with mortality rates of 2.9%, 8.0% and 44.4%, respectively.


Black thyroid: report of an autopsy case.
A distinctive but very rare side effect of exposure to minocycline is black pigmentation of the thyroid gland. Until 2002, not more than 30 cases of black thyroid had been reported in the English literature. We report on a 24-year-old woman with known antemortem ingestion of minocycline. The woman suffered from a depressive disorder with repeated suicide attempts and committed suicide by a gunshot to the head. At autopsy, the thyroid gland showed coal-black coloration. Upon histology, clumps of black-brown pigment were seen in the colloid, and a granular precipitate of this pigment was noted in the apical portions of the follicular epithelial cells. The diagnosis of minocycline-associated black thyroid was established. Forensic pathological significance of black thyroid may arise from the fact that hypothyroidism has been occasionally associated with minocycline-related black thyroid and that hypothyroidism may contribute to the development of depressive disorders (and thus, in given cases, may be responsible for suicide attempts). Under this assumption, the presence of black thyroid would represent more than just a morphological curiosity in specific cases.


Environmental and sociodemographic factors associated with household malaria burden in the Congo.
Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The 'malaria indicator questionnaire' (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p < 0.01). In addition, 96.7% of households were affected by malaria (at least one malaria case), and malaria frequency per household was relatively high (mean: 4.5 ± 3.1 cases reported) in the last 12 months. The mean individual malaria care expenditure was relatively high (101.6 ± 10.6 USD) in the previous 12 months; however, the majority of households (74.5%) earned less than 50 USD monthly. In addition, of the responders who suffered from malaria, 24.1% did not have access to malaria care at a health setting. Furthermore, a multivariate analysis with adjustment for age, education level and occupation showed that household size (OR = 1.43 ± 0.13; 95% CI 1.18-1.73; p < 0.001), inappropriate water source (OR = 2.41 ± 0.18; 95% CI 1.17-2.96; p < 0.05) absence of periodic water, sanitation and hygiene (WASH) intervention in residential area (OR = 1.63 ± 1.15; 95% CI 1.10-2.54; p < 0.05), and rural residence (OR = 4.52 ± 2.47; 95% CI 1.54-13.21; p < 0.01) were associated with household malaria. This study showed that household size, income, WASH status and rural site were malaria-associated factors. Scaling up malaria prevention through improving WASH status in the residential environment may contribute to reducing the disease burden.


Dibutyryladenosine 3':5'-cyclic monophosphate-mediated changes in rat cells involve macromolecular alterations in vinblastine-precipitable proteins.
ts-NT3-KR rat cell cultures show the loss of three components in the molecular-weight region 200,000--250,000 when exposed to dibutyryl cyclic AMP, under conditions of both restriction and expression of the transformed phenotype. Vinblastine is able to precipitate preferentially from control cultures the species that are decreased by exposure to the cyclic nucleotide. Serum-starved cultures exposed to dibutyryl cyclic AMP reveal differences in their vinblastine precipitates, depending on whether the expression of the transformation phenotype is restricted or not.


Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells.
Paragangliomas (PGLs) are infiltrating autonomic nervous system tumors that cause important morbidity. At present, surgery is the only effective therapeutic option for this rare tumor. Thus, new agents for PGL treatment should be identified. Using unique PGL cell models established in our laboratory, we evaluated the effect of dichloroacetate (DCA) as single agent or in a novel combination with other metabolic drugs, including GW6471 and metformin. DCA and metformin had not been tested before in PGL. DCA reduced PGL cell viability and growth through mechanisms involving reactivation of PDH complex leading to promotion of oxidative metabolism, with lowering of lactate and enhanced ROS production. This resulted in cell cycle inhibition and induction of apoptosis in PGL cells, as shown by flow cytometry and immunoblot analyses. Moreover, DCA drastically impaired clonogenic activity and migration of PGL cells. Also metformin reduced PGL cell viability as single agent and the combinations of DCA, GW6471 and metformin had strong effects on cell viability. Furthermore, combined treatments had drastic and synergistic effects on clonogenic ability. In conclusion, DCA, GW6471 and metformin as single agents and in combination appear to have promising antitumor effects in unique cell models of PGL.


[A genetic and hormonal study of 5 patients with the nonclassical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency].
To study the association between the 21-hydroxylase deficiency with the HLA histocompatibility complex in a mediterranean ethnic group. 5 patients with late-onset 21-hydroxylase deficiency, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, along with 23 family members were typed. 17-hydroxyprogesterone response to iv ACTH stimulus was measured too in the family members. We found a genetic linkage disequilibrium between the late-onset 21-hydroxylase deficiency and the HLA antigen B51. Moreover, similar biologic profiles were observed in the patients and those of their siblings who were HLA identical. The heterozygous carriers showed a intermediate 17-hydroxyprogesterone response to ACTH between propositus and homozygotes and their family members who had no HLA haplotype identical to those of the propositus. These observations tend to confirm that a close linkage exits between the gene (or genes) for 21-hydroxylase deficiency in late-onset adrenal hyperplasia and the HLA genes. This association may change in the different ethnic groups.


[Inhibitory effects of lovastatin on the proliferation and cell cycle phase of cultured human glomerular mesangial cells in vitro].
To study the effects and mechanism of lovastatin on cell cycle phase and proliferation of cultured human glomerular mesangial cells in vitro. HMC proliferation was determined by 3H-Thymidine incorporation. HMC cell cycle was measured by flow cytometric analysis. Lovastatin was found to inhibit HMC proliferation in a dose-dependent manner. Flow cytometric analysis demonstrated that lovstatin induced G1/S transition arrest. Concomitant addition of mevalonate or farnesol restored all the inhibitory effect of lovstatin on HMC. Lovastatin is a HMC proliferation inhibitor. It provides an experimental evidence for re-evaluate renal protective effect of HRI, which has already been widely used in clinical treatment.


PTPIP51 in protein interactions: regulation and in situ interacting partners.
This study investigated the regulation of 14-3-3β binding to PTPIP51 by the tyrosine phosphorylation status of PTPIP51. The tyrosine 176 residue is phosphorylated by c-Src. Up to now, nothing is known about the impact of such well-established phosphorylation events on the interaction profile of PTPIP51 with its partners of the mitogen-activated protein kinase (MAPK) pathway. In human keratinocytes the PTPIP51 phosphorylation was varied by inhibiting the phosphatase activity, thus enhancing the phosphorylation of PTPIP51. Differential blocking of Src kinase family members (despite c-Src) by PP2 increased the activity of c-Src and the tyrosine phosphorylation of PTPIP51 at position 176, which is the substrate of c-Src kinase. The amount of PTPIP51 interactions with 14-3-3β, Raf-1, PTP1B and c-Src was evaluated and the resulting data were compared to an untreated control group. The increased phosphorylation level resulted in a sharp drop of the 14-3-3β/PTPIP51 and 14-3-3β/Raf-1 interaction. Besides the 14-3-3 interaction of PTPIP51, the interaction with the two MAPK modulators, protein kinase A (PKA) and diacylglycerol kinase alpha (DAGKα), are also regulated by the tyrosine phosphorylation status of PTPIP51. Additional immunostaining experiments were done investigating the functional implication on these interactions of the phosphorylation in apoptotic processes. In the pervanadate- and PP2-treated HaCaT cells, higher amounts of apoptotic cells were not detected as compared to the control group. The presented data confirms a tyrosine phosphorylation-dependent interaction of PTPIP51 with 14-3-3β and Raf-1 in vivo and a tyrosine-dependent interaction profile with DAGKα and PKA. The non-interaction of PTPIP51 with 14-3-3 is not sufficient for triggering apoptosis.


Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data.
Primary-care physicians continue to overprescribe antibiotics for acute rhinosinusitis because distinction between viral and bacterial sinus infection is difficult. We undertook a meta-analysis of randomised trials based on individual patients' data to assess whether common signs and symptoms can be used to identify a subgroup of patients who benefit from antibiotics. We identified suitable trials--in which adult patients with rhinosinusitis-like complaints were randomly assigned to treatment with an antibiotic or a placebo--by searching the Cochrane Central Register of Controlled Trials, Medline, and Embase, and reference lists of reports describing such trials. Individual patients' data from 2547 adults in nine trials were checked and re-analysed. We assessed the overall effect of antibiotic treatment and the prognostic value of common signs and symptoms by the number needed to treat (NNT) with antibiotics to cure one additional patient. 15 patients with rhinosinusitis-like complaints would have to be given antibiotics before an additional patient was cured (95% CI NNT[benefit] 7 to NNT[harm] 190). Patients with purulent discharge in the pharynx took longer to cure than those without this sign; the NNT was 8 patients with this sign before one additional patient was cured (95% CI NNT[benefit] 4 to NNT[harm] 47). Patients who were older, reported symptoms for longer, or reported more severe symptoms also took longer to cure but were no more likely to benefit from antibiotics than other patients. Common clinical signs and symptoms cannot identify patients with rhinosinusitis for whom treatment is clearly justified. Antibiotics are not justified even if a patient reports symptoms for longer than 7-10 days.


In the media: Burns as a method of assault.
The aims of this study were to determine whether a change occurred in the pattern of assault burn injury cases hospitalised to the adult state burns unit, Western Australia, from 2004 to mid-year of 2012, and to compare patient and burn characteristics of adult assault burns with those admitted for unintentional burns. Study data were obtained from the Royal Perth Hospital (RPH) Burns Minimum Dataset (BMDS). Aggregated data of unintentional burn admissions during the same period were provided by the BMDS data manager to enable comparisons with assault burn patients. Assault burn admissions during 2004-2012 accounted for approximately 1% of all adult burn hospitalisations. All assault victims were burned by either thermal or scald agents. A high rate of intubation (24%) and ICU admission (1 in 3 cases) was observed in the fire assault group. The six assault cases undergoing intubation were severe burns, median TBSA 50%, most commonly affecting the face, head and torso, half of these cases had inhalational injuries and also required escharotomies. Comparison of admissions by calendar period showed no statistically significant differences in demographic, burn cause or TBSA%. However, statistically significant differences were found for pre-morbid psychiatric history (15% vs. 58%, p=0.025) and concomitant fractures or dislocations (46% vs. 2%), p=0.011). While the proportion of assault burn admissions per total burn admissions steadily increased from 0.4% in 2009 to 1.5% in mid-2012, this proportion did not exceed that peak level observed of 2.1% for 2004.


Palladium-catalyzed anti-Markovnikov hydroalkylation of homoallylic alcohols bearing β-fluorines.
A palladium-catalyzed anti-Markovnikov hydroalkylation of β,β-difluorinated homoallylic alcohols with alkylzinc reagents has been developed. This method affords a wide range of synthetically useful gem-difluorinated compounds with good functional group compatibility.


Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form.
Gap junctions (GJs) are aqueous channels that allow cells to communicate via physiological signals directly. The role of gap junctional connectivity in determining single-cell functions has long been recognized. However, GJs have another important role: the regulation of large-scale anatomical pattern. GJs are not only versatile computational elements that allow cells to control which small molecule signals they receive and emit, but also establish connectivity patterns within large groups of cells. By dynamically regulating the topology of bioelectric networks in vivo, GJs underlie the ability of many tissues to implement complex morphogenesis. Here, a review of recent data on patterning roles of GJs in growth of the zebrafish fin, the establishment of left-right patterning, the developmental dysregulation known as cancer, and the control of large-scale head-tail polarity, and head shape in planarian regeneration has been reported. A perspective in which GJs are not only molecular features functioning in single cells, but also enable global neural-like dynamics in non-neural somatic tissues has been proposed. This view suggests a rich program of future work which capitalizes on the rapid advances in the biophysics of GJs to exploit GJ-mediated global dynamics for applications in birth defects, regenerative medicine, and morphogenetic bioengineering. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 643-673, 2017.


Independent evaluation of a defibrillation outcome predictor for out-of-hospital cardiac arrested patients.
We evaluated the ability of a previously derived outcome predictor to discriminate between ECG segments corresponding to return of spontaneous circulation (ROSC) or not in validation data from 136 patients with cardiac arrest. The new data used for validation were totally independent from the predictor derivation data used in the original study. Features corresponding to those used in the development of the original outcome predictor, centroid frequency, peak power frequency, spectral flatness and energy, were computed following which a second decorrelated feature set was generated. The outcome predictor was applied to the new data with good correspondence in performance (testing) to what was expected (training) with receiver operator characteristics (ROC) areas of 0.80 and 0.79, respectively. Outcome predictor performance was reproducible. As in the present study, future testing should be performed on totally independent data not included in the design of the outcome predictor to get a reliable impression of expected performance.


Paradoxical tensions in exploiting data to implement circular economy in the textile industry.
Increasing utilization of data, enabled by digitalization, constitutes a major driver toward circular economy but is not without potential paradoxical tensions. A two-round disaggregative Delphi study and analysis of the qualitative material generated in it explored these tensions. They were found to cohere around three themes: consumer concurrence, business transparency, and technology relevance. The first theme is connected with consumers' behavior and their perceptions as to data's value, the transparency one involves alignment of business interests and practices with data-driven developments, and the third pertains to the actual environmental impact of digital technologies used to initiate data-driven circular economy. Business decision-making should address both the positive and the negative effects, in both the short and long term. Insight as to these tensions supports discovering how businesses can successfully utilize data in their efforts promoting circular economy within the complex reality of dynamically changing business environments.


Long-term stormwater quantity and quality analysis using continuous measurements in a French urban catchment.
The assessment of urban stormwater quantity and quality is important for evaluating and controlling the impact of the stormwater to natural water and environment. This study mainly addresses long-term evolution of stormwater quantity and quality in a French urban catchment using continuous measured data from 2004 to 2011. Storm event-based data series are obtained (716 rainfall events and 521 runoff events are available) from measured continuous time series. The Mann-Kendall test is applied to these event-based data series for trend detection. A lack of trend is found in rainfall and an increasing trend in runoff is detected. As a result, an increasing trend is present in the runoff coefficient, likely due to growing imperviousness of the catchment caused by urbanization. The event mean concentration of the total suspended solid (TSS) in stormwater does not present a trend, whereas the event load of TSS has an increasing tendency, which is attributed to the increasing event runoff volume. Uncertainty analysis suggests that the major uncertainty in trend detection results lies in uncertainty due to available data. A lack of events due to missing data leads to dramatically increased uncertainty in trend detection results. In contrast, measurement uncertainty in time series data plays a trivial role. The intra-event distribution of TSS is studied based on both M(V) curves and pollutant concentrations of absolute runoff volumes. The trend detection test reveals no significant change in intra-event distributions of TSS in the studied catchment.


Acute infectious supraglottitis in adult population: epidemiology, management, outcomes and predictors of airway intervention.
The purpose is to analyze the incidence of acute infectious supraglottitis in our center between 2010 and 2020, define the characteristics and trends of those patients and identify factors associated with the need of airway intervention. A retrospective single-center observational study of a cohort of patients diagnosed with acute infectious supraglottitis between January 2010 and December 2020. Patients were stratified according to airway management. Eighty eight patients were included: 59 men (67%) and 29 women (33%). A significant upward trend of 9% in the annual incidence rate of supraglottitis was seen during 2010-2020, with an important increase in cases during 2019. Muffled voice (41%) and respiratory distress (38%) were the most common presenting symptoms; and the median duration of symptoms before hospital admission was 2 days [IQR 1; 3]. Airway intervention was performed in fifteen patients (17%). Nine patients (10%) were intubated and six required tracheotomy (7%). Comparing the patients who required airway intervention with those who received a conservative treatment, younger patients (p < 0.01) were more likely to need airway intervention. In logistic regression analysis, we found that epiglottic abscess (p = 0.015), hypersalivation (p = 0.027) and smoking (p = 0.036) were independent factors with a significant association with airway intervention. There was an important increase in cases and its severity in 2019, but due to COVID-19 pandemic, it was not possible to define if it was an isolate event or an upward trend. Epiglottic abscess, hypersalivation and smoking could be possible risk factors for airway intervention.


gamma delta T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium.
We have investigated the expression of the alpha beta and the gamma delta T cell receptor (TCR) in the human intestine. By immunohistology we found that 39% of CD3+ intraepithelial lymphocytes (IEL) expressed the gamma delta TCR compared to 3% of CD3+ lamina propria lymphocytes (LPL). Cytofluorometric analysis of isolated cells revealed a significantly higher proportion of gamma delta T cells among CD3+ IEL compared to LPL and peripheral blood lymphocytes. This was due to an increase in both CD8+ (low density) and CD4-CD8- gamma delta T cells in IEL. Most alpha beta IEL expressed high-density CD8. About 30% of both IEL and LPL expressed CD25 (alpha-chain of the IL-2 receptor). HML-1 expression was detected on nearly all IEL and on 27% of LPL. CD25 and HML-1 were preferentially expressed on intestinal alpha beta and gamma delta T cells, respectively. Thus, human gamma delta T cells are located preferentially in the gut epithelium and are phenotypically different from alpha beta T cells, which constitute the majority of both LPL and IEL.


Azygos tip placement for hemodialysis catheters in patients with superior vena cava occlusion.
Chronic central venous access is necessary for numerous life-saving therapies. Repeated access is complicated by thrombosis and occlusion of the major veins, such as the superior vena cava (SVC), which then require novel vascular approaches if therapy is to be continued. We present two cases of catheterization of the azygos system in the presence of an SVC obstruction. We conclude that the azygos vein may be used for long-term vascular access when other conduits are unavailable and that imaging studies such as magnetic resonance venography, contrast-enhanced computed tomography or conventional venography can be employed prior to the procedure to aid with planning and prevent unforeseen complications.


Comparison of warm vertical compaction protocols to obturate artificially created defects in the apical one-third.
The purpose of this study was to evaluate the ability of 4 different warm vertical compaction protocols to obturate artificially created defects in the apical one-third of a root canal system by using a split-tooth model. Four warm vertical protocols used (A) continuous down-pack and continuous backfill, (B) continuous down-pack and incremental backfill, (C) incremental down-pack and continuous backfill, and (D) incremental down-pack and incremental backfill. Three artificially created defects were placed 2, 3, and 4 mm from the apex of the split-tooth model. Before obturations, a fine-medium System B plugger was prefitted 4 mm from the working length. The root canal system was obturated according to each of the experimental protocols. Resultant obturations (N = 10/protocol) were separated from the model, and replicated defects were assessed by a blinded evaluator who used an ordinal scale (0-4) that was based on how much each defect was replicated by GP. By using nonparametric analyses with Bonferroni adjustment (α = 0.01), with the apical 2-mm defect, protocol D demonstrated significantly (P ≤ .01) better defect replication as compared with protocols A, B, and C. For the apical 3-mm defect, protocols B and D were significantly better (P ≤ .01) than protocols A and C. However, there was no difference (P > .01) between protocols with apical 4-mm defect (100% replication). The incremental down-pack with incremental backfill appears better able to replicate the most apical defect, which suggests benefits of repeated heat application and packing force to manipulate the GP in the apical plug area.


Plasmodium falciparum: cloning by single-erythrocyte micromanipulation and heterogeneity in vitro.
Natural isolates of Plasmodium falciparum represent a genetically heterogeneous population of parasites. To obtain stable strains of the parasites for long term experiments, a rapid and definitive method of cloning was developed using micropipets and a micromanipulator. Homogeneous parasite clones prepared by this technique were characterized and compared with the parent isolates during 4 years of continuous culture. The process of phenotypic dominance and selection of drug resistance which occur in nature was also simulated in vitro by evaluating population dynamics of two cocultured isolates of P. falciparum.


Amphiphilic copolymer grafted "smart surface" enhanced by surface roughness.
Polystyrene-poly(acrylic acid) (PS-PAA) block copolymers polymerized by atom transfer radical polymerization were covalently grafted to both smooth and microtextured surfaces. These amphiphilic copolymers were utilized to create smart surfaces, which can be responsive to external stimuli, e.g., pH values or organic solvent. Atom force microscopy, field emission scanning electron microscopy, and contact angle measurements were employed to investigate the physiochemical features of the copolymer brushes. It was found that the wettability of surfaces depended on both the PS/PAA molar ratio and external solvent properties. Hydrophilic surfaces were obtained after treatment with basic solution, as well as a polar solvent, such as ethanol. With treatment with acidic solution or toluene, the surface could be reversibly turned relatively hydrophobic, probably due to the rearrangement or reorganization of polymer chains. Moreover, rougher surfaces, which were microtextured by ZnO nanorods, were incorporated into this adaptive system to enhance the tunable range of wettability.


Coagulation factor XII activity, but not an associated common genetic polymorphism (46C/T),is linked to recurrent miscarriage.
To investigate whether a factor XII genetic polymorphism is associated with first-trimester embryonal loss. Prospective case-control study. SETTING; Nagoya City University Hospital. Eighty-three patients with a history of two or more unexplained first-trimester recurrent miscarriages and 67 controls with no obstetric complications or history of miscarriage. Plasma factor XII activity, a genetic polymorphism (46 C-->T) of factor XII, lupus anticoagulant, and beta(2)glycoprotein I dependent anticardiolipin antibodies. Ten of the 83 patients and 1 of the 67 controls had decreased factor XII activity; the difference in frequency was statistically significant. Wild-type (CC), heterozygote (CT), and homozygote (TT) allele patterns were observed in 8, 36, and 39 patients, respectively, compared with 11, 20, and 36 of the patients and controls, respectively. The mean (+/- SD) corresponding factor XII activity was 154.8 +/- 44.8%, 112.7 +/- 30.2%, and 66.2 +/- 29.2% in patients and 164.6 +/- 26.7%, 114.3 +/- 28.1%, and 70.4 +/- 18.1% in controls. The two groups did not differ in the frequency of the T allele or categories of factor XII activity. Factor XII activity overall, but not the 46C/T common genetic polymorphism, is associated with recurrent miscarriage.


Angiotensin 1-7 significantly reduces diabetes-induced leukocyte recruitment both in vivo and in vitro.
Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion. Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects. Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro. These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis.


[Development and validating of a three-dimensional finite element model of total human pelvis].
To develop a three-dimensional finite element model of normal total adult human pelvis and to establish a platform for biomechanical research of human pelvis. 186 series of traverse CT images of the pelvis, from the third lumbar vertebra (L3) to the upper third of femur, obtained with spiral CT scanning on a healthy man, aged 42, without diseases of lumbar vertebrae and pelvis, were processed. A three-dimensional finite element model of pelvis was constructed directly by producing the units and nodes with the pixels of the original CT films, using ANSYS finite analytical system. A three-dimensional finite element model of normal human pelvis was constructed including lumbar and proximal femur, which could be divided into 207,248 nodes and 721,820 units. The established three-dimensional finite element model of normal adult is valid and reasonable, and can be used for biomechanical analysis.


Editorial Commentary: Stem Cell Research in Arthroscopy Is Scant and Requires Basic Science Review.
Stem cell research in Arthroscopy is rare, but review of journals beyond orthopaedics yields many interesting highlights. The key points are that sources of stem cells vary with regard to cellular yield, but manipulation to improve the yield is severely limited by the United States Food and Drug Administration.


Duplex ultrasonography as a noninvasive technique for assessing portal hemodynamics.
Duplex ultrasonography was evaluated as a noninvasive, quantitative technique of assessing portal hemodynamic characteristics. Portal blood flow measured by duplex ultrasonography was significantly decreased in patients with portal hypertension (450 +/- 86 ml/min) compared with control subjects (874 +/- 44 ml/min; p less than 0.001). Quantitative assessment of portal blood flow by duplex ultrasound correlated with qualitative portal perfusion grading by angiography, and direction of flow was always accurately determined by duplex ultrasonography. Although the angiographic portal perfusion grade did not change significantly in the early postoperative period after distal splenorenal shunting, a decrease in mean portal blood flow of more than 50 percent was documented by duplex ultrasonography. Duplex ultrasonography appears to be at least as accurate as angiography and is an acceptable alternative to this more invasive technique for the longitudinal assessment of portal blood flow.


Examination of PACAP-Like Immunoreactivity in Urogenital Tumor Samples.
Numerous studies investigated the localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in different tumors and described the effects of analogs on tumor growth to show its potential role in oncogenesis. Recently, our research group has found significantly lower levels of PACAP27-like immunorreactivity (LI) and PACAP38-LI in different human samples of primary small cell lung cancer and colon cancer compared to normal healthy tissues. There are only few human studies showing the presence of PACAP and its receptors in urogenital tumors; therefore, the aim of the present study was to compare PACAP-LI in different healthy and pathological human samples from urogenital organs (kidney, urinary bladder, prostate, testis) with radioimmunoassay (RIA) method. Similar to our earlier observations, the PACAP27-LI was significantly lower compared to PACAP38-LI in all samples. We did not find significant alterations in PACAP-LI between healthy and tumoral samples from the urinary bladder and testis. On the other hand, we found significantly lower PACAP38-LI level in kidney tumors compared with healthy tissue samples, and we showed higher PACAP27-LI in prostatic cancer compared to samples from benign prostatic hyperplasia. These data indicate that PACAP levels of different tissue samples are altered under pathological conditions suggesting a potential role of PACAP in the development of different urogenital tumors.


Intrapartum asphyxia: a rare cause of cerebral palsy.
Data on all children with spastic cerebral palsy (N = 183) and on a matched group of control children (N = 549) born in Western Australia between 1975 and 1980 were compared to investigate the relationship between birth asphyxia and spastic cerebral palsy. Information on perinatal events for both the children with cerebral palsy and the control subjects was collected by means of epidemiologic methods to reduce bias. An association between clinically observed perinatal signs of birth asphyxia and spastic cerebral palsy was found (relative risk 2.84; 95% confidence interval 1.85 to 4.37). The population-attributable risk proportion was 14.1%. The likelihood of birth asphyxia's causing perinatal brain damage was assessed by two independent observers using defined criteria. It was estimated that in only about 8% (15/183) of all the children with spastic cerebral palsy was intrapartum asphyxia the possible cause of their brain damage. The contribution of intrapartum events and obstetric mismanagement to overall cerebral palsy rates is probably less than was previously thought.


The neuroendocrinology of stress: Glucocorticoid signaling mechanisms.
Glucocorticoid signaling plays major roles in energy homeostasis and adaptation to adversity, and dysregulation of this process is linked to systemic and psychological pathology. Over the last several decades, new work has challenged many of the long-standing assumptions regarding regulation of glucocorticoid secretion and glucocorticoid signaling mechanisms, revealing an exquisite complexity that accompanies the important and perhaps global role of these hormones in physiological and psychological regulation. New findings have included discovery of membrane signaling, direct neural control of the adrenal, a role for pulsatile glucocorticoid release in glucocorticoid receptor signaling, marked sex differences in brain glucocorticoid biology, and salutary as well as deleterious roles for glucocorticoids in long- and short-term adaptations to stress. This review covers some of the major lessons learned in the area of mechanisms of glucocorticoid signaling, and discusses how these may inform the field moving forward.


Observations on the electrophoretic and immunoelectrophoretic appearance of the prealbumin region in biological fluids.
Variations in the level of prealbumin in serum and spinal fluid were noted on routine electrophoresis. Low serum levels were associated with infection, liver disorders, and malignant disease, whereas high levels were seen in inflammatory disorders. A high spinal fluid prealbumin was noted in a young child with a disseminated medulloblastoma. A second arc with prealbumin mobility was seen on immunoelectrophoresis of one urine specimen and four sera from patients with varied pathologies. Sixteen duplicated arcs were seen in the spinal fluid of patients with neoplastic disorders, multiple sclerosis, suspected multiple sclerosis, epilepsy, cerebellar and cerebral atrophy, and chronic renal failure.


Phylogenetic relationships between spiny, slipper and coral lobsters (Crustacea, Decapoda, Achelata).
Molecular data can aid in the resolution of conflicting hypotheses generated through difficulties in the interpretation of morphological data and/or an incomplete fossil record. Moreover, the reconstruction of phylogenetic relationships using molecular data may help to trace back the origin of morphological innovations which had a major impact on the radiation of a taxonomical group. In this work, different nuclear (18S, 28S, and H3) and mitochondrial (16S and COI) gene regions were sequenced in a total of 35 Achelatan species to test conflicting hypotheses of evolutionary relationships within the Achelata infraorder and solve the taxonomic disagreements in the group. The combined molecular dataset strongly supports the hypothesis that Achelata is a monophyletic group composed of two main families: Palinuridae and Scyllaridae. Synaxidae is found to be a polyphyletic group, which should be included within Palinuridae. Consequently, our results indicate that the origin of the stridulating organ occurred only once during Achelata evolution. Finally, the two main clades found within the Scyllaridae are in agreement with previous inferences based on adult morphological data. The dating of divergence of Achelata obtained with a relaxed-clock model is compatible with previous hypotheses of a Triassic origin of the Achelata.


Facing the ongoing challenge of the febrile young infant.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .


Altered levels of circulating mitochondrial DNA in elderly people with sarcopenia: Association with mitochondrial impairment.
Age-related chronic inflammatory process is often referred to as "inflammaging", which had been described in several human disorders, including sarcopenia. Recently, mitochondrial DNA (MtDNA) has moved into the spotlight as a "damage-associated molecular pattern" (DAMP) agent that can potentially elicit inflammation. Yet, the roles of this mitochondrial DAMP have never been investigated in sarcopenia. Cross-sectional study. From January 2021 to June 2021, elderly outpatients ≥65 years and able to finish a comprehensive geriatric assessment were recruited in our study. Participants were divided into sarcopenia group and non-sarcopenia group according to the DXA scans and grip strength. Genomic DNA was extracted from plasma and peripheral blood mononuclear cells (PBMCs), and changes in MtDNA copies were quantified using qPCR. Plasma levels of inflammatory cytokines were measured using ELISA kits. Loss of mitochondrial membrane potential (Δψm) in PBMCs was analyzed using the fluorescent probe JC-1. Participants with sarcopenia were significantly older, more likely to be physically inactive, and had higher levels of circulating cell-free MtDNA (ccf-MtDNA) (all p < 0.05). After adjusting for potential confounders, ccf-MtDNA was independently associated with increased odds of sarcopenia (adjusted odds ratio (AOR), 1.576; p = 0.009). Furthermore, ROC curve analysis showed that ccf-MtDNA had an area under the curve (AUC) of 0.726 (95% CI: 0.607-0.844; p < 0.05) for distinguishing elderly subjects from sarcopenia. Compared with non-sarcopenia subjects, plasma interleukin (IL)-6 and IL-8 were significantly higher in sarcopenia subjects (both p < 0.05). By performing a correlation test, it was found that the level of IL-6 was positively correlated with ccf-MtDNA (r = 0.301; p < 0.05). Then, PBMCs were used as surrogates for mitochondria-rich cells, and the results showed that the relative amplification of MtDNA in PBMCs was significantly reduced (p < 0.05), whereas the depolarization of Δψm was significantly increased in sarcopenia subjects (p < 0.05). Taken together, our data suggested that circulating MtDNA might be a novel and important source of inflammatory stimuli potentially relevant for sarcopenia in elderly people, and this would provide an attractive therapeutic target to improve this disease.


The effect of alcohol consumption on all-cause mortality in 70-year-olds in the context of other lifestyle risk factors: results from the Gothenburg H70 birth cohort study.
In this study, we examined the effect of alcohol, as well as the combined effect of seven lifestyle factors, on all-cause mortality in older adults (baseline age 70 years). Data was derived from the population-based Gothenburg H70 Birth Cohort study, including 1124 participants from the 2014-16 examination. Risk consumption was defined as > 98 g alcohol per week, and hazardous drinking was based on the Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C). Cox regression models were used to examine the individual effect of alcohol consumption, as well as the combined effect of seven lifestyle risk factors (high alcohol consumption, lifetime smoking, unhealthy Body Mass Index, insufficient physical activity, sedentary behavior, insufficient/prolonged sleep, unhealthy dietary pattern) on all-cause mortality. During a mean follow-up of 7.7 years, 81 (7.2%) participants died. Neither risk consumption nor hazardous drinking were associated with elevated mortality, but hazardous drinking was associated with an increased risk of mortality in those with insufficient physical activity. Those with at least five lifestyle risk factors had an increased all-cause mortality compared to those fulfilling criteria for a maximum of one lifestyle risk factor. High alcohol consumption showed a relatively minor impact on this risk, while physical activity and unhealthy dietary pattern had an independent effect on mortality. In this particular sample, there was no independent effect of alcohol on the risk of 8-year all-cause mortality. However, an interaction effect of physical activity was observed. It may be that high alcohol consumption per se is less important for mortality among older adults. However, a combination of several unhealthy lifestyle behaviors was linked to a substantial increase in the risk of mortality in Swedish older adults. Also, it has to be emphasized that high alcohol consumption may have other adverse health effects apart from mortality among older adults.


The effect of oxidant gases on membrane fluidity and function in pulmonary endothelial cells.
Free radicals and oxidant gases, such as oxygen (O2) and nitrogen dioxide (NO2), are injurious to mammalian lung cells. One of the postulated mechanisms for the cellular injury associated with these gases and free radicals involves peroxidative cleavage of membrane lipids. We have hypothesized that oxidant-related alterations in membrane lipids may result in disordering of the plasma membrane lipid bilayer, leading to derangements in membrane-dependent functions. To test this hypothesis, we examined the effect of exposure to high partial pressures of O2 or NO2 on the physical state and function of pulmonary endothelial cell plasma membranes. Both hyperoxia (95% O2 at 1 ATA) and NO2 exposure (5 ppm) caused early and significant decreases in fluidity in the hydrophobic interior of the plasma membrane lipid bilayer and subsequent depressions in plasma membrane-dependent transport of 5-hydroxytryptamine. Lipid domains at the surface of pulmonary endothelial cell plasma membranes are more susceptible to NO2-induced injury than to hyperoxic injury. Alterations in the fluidity of these more superficial domains are associated with derangements in surface dependent functions, such as receptor-ligand interaction. These results support our hypothesis and advance our understanding of how the chemical events of free radical injury associated with high O2 and NO2 tensions are translated into functional manifestations of O2 and NO2-induced cellular injury.


Climate change: impacts on and implications for global health.
The most severe consequences of climate change will accrue to the poorest people in the poorest countries, despite their own negligible contribution to greenhouse gas emissions. In recent years, global health efforts in those same countries have grown dramatically. However, the emerging scientific consensus about climate change has not yet had much influence on the routine practice and strategies of global health. We review here the anticipated types and global distribution of health impacts of climate change, discuss relevant aspects of current global interventions for health in low-income countries, and consider potential elements of a framework for appropriately and efficiently mainstreaming global climate change-mitigation and -adaptation strategies into the ongoing enterprise of global health. We propose a collaborative learning initiative involving four areas: (1) increased awareness among current global health practitioners of climate change and its potential impacts for the most disadvantaged, (2) strengthening of the evidence base, (3) incorporation now of climate change-mitigation and -adaptation concerns into design of ongoing global health programs, and (4) alignment of current global health program targets and methods with larger frameworks for climate change and sustainable development. The great vulnerability to climate change of populations reached by current global health efforts should prompt all concerned with global health to take a leading role in advocating for climate change mitigation in their own countries.


Diagnostic findings caused by cutting of the iliotibial tract and anterolateral ligament in an ACL intact knee using a standardized and automated clinical knee examination.
The purpose of this study was to evaluate the separate contribution of the two definitions of the anterolateral ligament (ALL), the mid-third lateral capsular ligament (MTLCL) and deep capsule-osseous layer of the iliotibial tract (dcITT) in addition to the superficial iliotibial tract (sITT) to the control of tibial motion with respect to the femur during the application of force/torque seen during the three tests of the standard clinical knee examination (AP Lachman test, tibial axial rotation test and varus-valgus stress test). Six pelvis-to-toe cadaveric specimens were examined using an automated testing device that carried out the three components of the clinical knee examination. Internal/external rotation torque, anteroposterior load and adduction/abduction torque were applied, while torque/force and positional measurements were recorded. Sequential sectioning of the structures followed the same order for each knee, sITT, dcITT and MTLCL. Testing was repeated after release of each structure. During the tibial axial rotation test, releasing the sITT caused an increase in internal rotation of 2.6° (1.4-4.1°, p < 0.0005), while release of the dcITT increased internal rotation an additional 0.8° (0.4-1.1°, p < 0.0015). Changes in secondary motions of the tibia after sITT release demonstrated an increase in anterior translation of 1.2 mm (0.6-2.0 mm, p < 0.0005) during internal rotation, while release of the dcITT increased the same motion an additional 0.4 mm (0.2-0.5 mm, p < 0.0005). During the AP Lachman test, release of the sITT caused the tibia to move more anteriorly by 0.7 mm (0.4-1.1 mm, p < 0.0005) and increased internal rotation by 2.7° (0.9-5.2°, p < 0.004). The additional release of the dcITT resulted in more anterior translation by 0.3 mm (0.1-0.4 mm, p < 0.002) and internal rotation by 0.9° (0.2-1.7°, p < 0.005). During the varus-valgus stress test, release of the sITT permitted 0.9° (0.4-1.4°, p < 0.0005) more adduction of the tibia, while the additional release of the dcITT significantly increased adduction by 0.4° (0.2°-0.5°, p < 0.001). Release of the MTLCL had a nominal but significant increase in internal rotation, 0.6° (0.1-1.1°, p < 0.0068) and external rotation, -0.1° (-0.1° to -0.2°, p < 0.0025) during the tibial axial rotation test, anterior translation of 0.2 mm (0.0-0.4 mm, p < 0.021) only during the AP Lachman test, and adduction rotation, 0.2° (0.0-0.3°, p < 0.034) only during the varus-valgus stress test. The presence of increased adduction during an automated knee examination provides unique information identifying the release of the sITT, dcITT and the MTLCL in this cadaveric study. While their sequential release caused similar pattern changes in the three components of the automated knee examination, the extent of change due to release of the MTLCL was markedly less than after release of the dcITT which was markedly less than after release of the sITT.