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The diagnosis and treatment of vocal fold disorders heavily rely on the use of laryngoscopy. A comprehensive vocal fold diagnosis requires accurate identification of crucial anatomical structures and potential lesions during laryngoscopy observation. However, existing approaches have yet to explore the joint optimization of the decision-making process, including object detection and image classification tasks simultaneously. In this study, we provide a new dataset, VoFoCD, with 1724 laryngology images designed explicitly for object detection and image classification in laryngoscopy images. Images in the VoFoCD dataset are categorized into four classes and comprise six glottic object types. Moreover, we propose a novel Multitask Efficient trAnsformer network for Laryngoscopy (MEAL) to classify vocal fold images and detect glottic landmarks and lesions. To further facilitate interpretability for clinicians, MEAL provides attention maps to visualize important learned regions for explainable artificial intelligence results toward supporting clinical decision-making. We also analyze our model's effectiveness in simulated clinical scenarios where shaking of the laryngoscopy process occurs. The proposed model demonstrates outstanding performance on our VoFoCD dataset. The accuracy for image classification and mean average precision at an intersection over a union threshold of 0.5 (mAP50) for object detection are 0.951 and 0.874, respectively. Our MEAL method integrates global knowledge, encompassing general laryngoscopy image classification, into local features, which refer to distinct anatomical regions of the vocal fold, particularly abnormal regions, including benign and malignant lesions. Our contribution can effectively aid laryngologists in identifying benign or malignant lesions of vocal folds and classifying images in the laryngeal endoscopy process visually., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Independent Ethics Committee of Cho Ray Hospital (Date: March 9th, 2022/No.1280/GCN-HĐĐĐ). Consent to Participate: Informed consent was waived in this study. Because the study only uses the historical data of laryngoscopy images, there will be no interaction with or impact on patients. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Purpose: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18 F-labeled 2'-deoxy-2'- 18 F-fluoro-9-β-d-arabinofuranosylguanine ([ 18 F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI., Procedure: To test whether the myocardial [ 18 F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [ 18 F]F-AraG uptake in normal heart by comparing [ 18 F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [ 18 F]F-AraG and 2-deoxy-2[ 18 F]fluoro-D-glucose ([ 18 F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [ 18 F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis., Results: The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [ 18 F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [ 18 F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [ 18 F]FDG signals showed wider variability at different time points. Noticeable [ 18 F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates., Conclusions: Our preliminary preclinical data show that [ 18 F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [ 18 F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders., (© 2024. The Author(s).)

Purpose: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18 F-labeled 2'-deoxy-2'- 18 F-fluoro-9-β-d-arabinofuranosylguanine ([ 18 F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI., Procedure: To test whether the myocardial [ 18 F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout ( Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [ 18 F]F-AraG uptake in normal heart by comparing [ 18 F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [ 18 F]F-AraG and 2-deoxy-2[ 18 F]fluoro-D-glucose ([ 18 F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [ 18 F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis., Results: The difference in %ID/cc for Rag1 KO and WT mice was not significant ( p = ns) indicating that the [ 18 F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [ 18 F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides ( p = ns). The [ 18 F]FDG signals showed wider variability at different time points. Noticeable [ 18 F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates., Conclusions: Our preliminary preclinical data show that [ 18 F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI., Competing Interests: Declarations Conflicts of Interest JL and HC are employed by CellSight Technologies, Inc., which is developing [18F]F-AraG for commercial use. JL holds patents related to [18F]F-AraG.

The enzyme choline acetyltransferase (ChAT) synthesizes acetylcholine from acetyl-CoA and choline at the neuromuscular junction and at the nerve terminals of cholinergic neurons. Mutations in the ChAT gene ( CHAT ) result in a presynaptic congenital myasthenic syndrome (CMS) that often associates with life-threatening episodes of apnea. Knockout mice for Chat (Chat -/- ) die at birth. To circumvent the lethality of this model, we crossed mutant mice possessing loxP sites flanking Chat exons 4 and 5 with mice that expressed Cre-ER T2 . Injection of tamoxifen (Tx) at postnatal (P) day 11 in these mice induced downregulation of Chat , autonomic failure, weakness, and death. However, a proportion of Chat flox/flox -Cre-ER T2 mice receiving at birth an intracerebroventricular injection of 2 × 10 13 vg/kg adeno-associated virus type 9 (AAV9) carrying human CHAT (AAV9- CHAT ) survived a subsequent Tx injection and lived to adulthood without showing signs of weakness. Likewise, injection of AA9- CHAT by intracisternal injection at P28 after the onset of weakness also resulted in survival to adulthood. The expression of Chat in spinal motor neurons of Chat flox/flox -Cre-ER T2 mice injected with Tx was markedly reduced, but AAV-injected mice showed a robust recovery of ChAT expression, which was mainly translated by the human CHAT RNA. The biodistribution of the viral genome was widespread but maximal in the spinal cord and brain of AAV-injected mice. No significant histopathological changes were observed in the brain, liver, and heart of AAV-injected mice after 1 year follow-up. Thus, AAV9-mediated gene therapy may provide an effective and safe treatment for patients severely affected with CHAT- CMS.

The detection of smoky diesel vehicles is a key step in reducing air pollution from transportation. We propose a new method for identifying smoky vehicles that proceeds in three stages: (1) the detection of vehicle shapes, license plates, and smoke regions; (2) the implementation of the two matching techniques based on the smoke region-vehicle shape and smoke region-license plate relationships; and (3) the refinement of the smoke region detected. The first stage involves the evaluation of various You Only Look Once (YOLO) models to identify the best-fit model for object detection. YOLOv5s was the most effective, particularly for the smoke region prediction, achieving a precision of 91.4% and a mean average precision at 0.5 (mAP@0.5) of 91%. It also had the highest mean mAP@0.5 of 93.9% across all three classes. The application of the two matching techniques significantly reduced the rate of false negatives and enhanced the rate of true positives for the smoky diesel vehicles through the detection of their license plates. Moreover, a refinement process based on image processing theory was implemented, effectively eliminating incorrect smoke region predictions caused by vehicle shadows. As a result, our method achieved a detection rate of 97.45% and a precision of 93.50%, which are higher than that of the two existing popular methods, and produced an acceptable false alarm rate of 5.44%. Particularly, the proposed method substantially reduced the processing time to as low as 85 ms per image, compared to 140.3 and 182.6 ms per image in the two reference studies. In conclusion, the proposed method showed remarkable improvements in the accuracy, robustness, and feasibility of smoky diesel vehicle detection. Therefore, it offers potential to be applied in real-world situations.

Kelp forests are highly productive and economically important ecosystems worldwide, especially in the North Pacific Ocean. However, current hypotheses for their evolutionary origins are reliant on a scant fossil record. Here, we report fossil hapteral kelp holdfasts from western Washington State, USA, indicating that kelp has existed in the northeastern Pacific Ocean since the earliest Oligocene. This is consistent with the proposed North Pacific origin of kelp associated with global cooling around the Eocene-Oligocene transition. These fossils also support the hypotheses that a hapteral holdfast, rather than a discoid holdfast, is the ancestral state in complex kelps and suggest that early kelps likely had a flexible rather than a stiff stipe. Early kelps were possibly grazed upon by mammals like desmostylians, but fossil evidence of the complex ecological interactions known from extant kelp forests is lacking. The fossil record further indicates that the present-day, multi-story kelp forest had developed at latest after the mid-Miocene climate optimum. In summary, the fossils signify a stepwise evolution of the kelp ecosystem in the North Pacific, likely enabled by changes in the ocean-climate system., Competing Interests: Competing interests statement:The authors declare no competing interest.

Synthesis of the acetylcholinesterase inhibitor paraoxon (POX) as a carbon-11 positron emission tomography tracer ([ 11 C]POX) and profiling in live rats is reported. Naïve rats intravenously injected with [ 11 C]POX showed a rapid decrease in parent tracer to ∼1%, with an increase in radiolabeled serum proteins to 87% and red blood cells (RBCs) to 9%. Protein and RBC leveled over 60 minutes, reflecting covalent modification of proteins by [ 11 C]POX. Ex vivo biodistribution and imaging profiles in naïve rats had the highest radioactivity levels in lung followed by heart and kidney, and brain and liver the lowest. Brain radioactivity levels were low but observed immediately after injection and persisted over the 60-minute experiment. This showed for the first time that even low POX exposures (∼200 ng tracer) can rapidly enter brain. Rats given an LD 50 dose of nonradioactive paraoxon at the LD 50 20 or 60 minutes prior to [ 11 C]POX tracer revealed that protein pools were blocked. Blood radioactivity at 20 minutes was markedly lower than naïve levels due to rapid protein modification by nonradioactive POX; however, by 60 minutes the blood radioactivity returned to near naïve levels. Live rat tissue imaging-derived radioactivity values were 10%-37% of naïve levels in nonradioactive POX pretreated rats at 20 minutes, but by 60 minutes the area under the curve (AUC) values had recovered to 25%-80% of naïve. The live rat imaging supported blockade by nonradioactive POX pretreatment at 20 minutes and recovery of proteins by 60 minutes. SIGNIFICANCE STATEMENT: Paraoxon (POX) is an organophosphorus (OP) compound and a powerful prototype and substitute for OP chemical warfare agents (CWAs) such as sarin, VX, etc. To study the distribution and penetration of POX into the central nervous system (CNS) and other tissues, a positron emission tomography (PET) tracer analog, carbon-11-labeled paraoxon ([ 11 C]POX), was prepared. Blood and tissue radioactivity levels in live rats demonstrated immediate penetration into the CNS and persistent radioactivity levels in tissues indicative of covalent target modification., (Copyright © 2024 by The Author(s).)

Right ventricle-pulmonary artery (RV-PA) conduits are used in the treatment of certain congenital heart disease (CHD). RV-PA conduit complications might develop over time and require intervention. To evaluate how well cardiac computed tomographic angiography (CCTA) performs compared to transthoracic echocardiography (TTE) in evaluating RV-PA conduit complications by using surgical findings as the reference standard. A retrospective chart review of all patients over a 5-year period who underwent CCTA for RV-PA conduit evaluation was performed. Patient demographics and clinical data were recorded. Preoperative CCTA and TTE findings were compared to the operative findings for concordance or discordance. Forty-one patients were included, 51% females. The complications were conduit stenosis (28.68%), infection (7.17%) and aneurysm/pseudoaneurysm (6.15%). TTE and CCTA were consistently able to visualize focal conduit stenosis (96%). The greatest discrepancy between TTE and CCTA was in evaluating for aneurysm/pseudoaneurysm, where TTE detected only 2/6 (33%) compared to CCTA which detected 6/6 (100%) of the cases. However, TTE was slightly better at detecting conduit infection (3/7, 43%) compared to CCTA (2/7, 29%). Note that 5 out of 7 patients with endocarditis had bovine jugular graft. CCTA and TTE provide similar diagnostic accuracy evaluating certain types of RV-PA conduit complications. However, certain complications were only visualized on CCTA or TTE making both modalities complementary to each other during diagnostic evaluation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, the features of resistive random access memory (RRAM) employing a straightforward Cr/MAPbI 3 /FTO three-layer structure have been examined and clarified. The device displays various resistance switching (RS) behavior at various sweep voltages between 0.5 and 5 V. The RS effect has a conversion in the direction of the SET and RESET processes during sweeping for a number of cycles at a specific voltage. The directional change of the RS processes corresponds to the dominant transition between the generation/recombination of iodide ion and vacancy in the MAPbI 3 perovskite layer and the electrochemical metallization of the Cr electrode under the influence of an electric field, which results in the conductive filament (CF) formation/rupture. At each stage, these processes are controlled by specific charge conduction mechanisms, including Ohmic conduction, space-charge-limited conduction (SCLC), and variable-range hopping (VRH). By identifying the biased voltage and the quantity of voltage sweep cycles, one can take a new approach to control or modulate the pathways for effective charge transport. This new approach is made possible by an understanding of the RS characteristics and the corresponding mechanisms causing the variation of RS behavior in the structure., (© 2023 Wiley-VCH GmbH.)

Background: Several inherited metabolic diseases are underreported in Vietnam, namely glucose-6-phosphate dehydrogenase deficiency (G6PDd), phenylketonuria (PKU) and galactosemia (GAL). Whilst massively parallel sequencing (MPS) allows researchers to screen several loci simultaneously for pathogenic variants, no screening programme uses MPS to uncover the variant spectra of these diseases in the Vietnamese population., Methods: Pregnant women (mean age of 32) from across Vietnam attending routine prenatal health checks agreed to participate and had their blood drawn. MPS was used to detect variants in their G6PD, PAH and GALT genes., Results: Of 3259 women screened across Vietnam, 450 (13.8%) carried disease-associated variants for G6PD, PAH and GALT. The prevalence of carriers was 8.9% (291 of 3259) in G6PD and 4.6% (152 of 3259) in PKU, whilst GAL was low at 0.2% (7 of 3259). Two GALT variants, c.593 T > C and c.1034C > A, have rarely been reported., Conclusion: This study highlights the need for routine carrier screening, where women give blood whilst receiving routine prenatal care, in Vietnam. The use of MPS is suitable for screening multiple variants, allowing for identifying rare pathogenic variants. The data from our study will inform policymakers in constructing cost-effective genetic metabolic carrier screening programmes., (© 2022 Gene Solutions. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Purpose: To evaluate radiolabeled doxorubicin (Dox) analogs as tracers of baseline Dox biodistribution in vivo during hepatic intra-arterial chemotherapy and to assess the efficacy of ChemoFilter devices to bind Dox in vitro., Materials and Methods: In an in vitro static experiment, [fluorine-18]N-succinimidyl 4-fluorobenzoate ([ 18 F]SFB) and [fluorine-18]fluorobenzoyl-doxorubicin ([ 18 F]FB-Dox) were added to a beaker containing a filter material (Dowex cation exchange resin, single-stranded DNA (ssDNA) resin, or sulfonated polymer coated mesh). In an in vitro flow model, [ 18 F]FB-Dox was added into a Dox solution in phosphate-buffered saline, and the solution flowed via a syringe column containing the filter materials. In an in vitro flow experiment, using micro-positron emission tomography (PET), images were taken as [ 18 F]SFB and [ 18 F]FB-Dox moved through a phantom. For in vivo biodistribution testing, a catheter was placed into the common hepatic artery of a swine, and [ 18 F]FB-Dox was infused over 30 seconds. A 10-minute dynamic image and three 20-minute static images were acquired using 3T PET/MR imaging., Results: In the in vitro static experiment, [ 18 F]FB-Dox demonstrated 76.7%, 88.0%, and 52.4% binding to the Dowex resin, ssDNA resin, and coated mesh, respectively. In the in vitro flow model, the first-pass binding of [ 18 F]FB-Dox to the Dowex resin, ssDNA resin, and coated mesh was 76.7%, 74.2%, and 76.2%, respectively, and the total bound fraction was 80.9%, 84.6%, and 79.9%, respectively. In the in vitro flow experiment using micro-PET, the phantom demonstrated a greater amount of [ 18 F]FB-Dox bound to both filter cartridges than of the control [ 18 F]SFB. In in vivo biodistribution testing, the first 10 minutes depicted [ 18 F]FB-Dox moving through the right upper quadrant of the abdomen. A region-of-interest analysis showed that the relative amount increased by 2.97 times in the gallbladder and 1.08 times in the kidney. The amount decreased by 0.74 times in the brain and 0.57 times in the heart., Conclusions: [ 18 F]FB-Dox can be used to assess Dox binding to ChemoFilters as well as in vivo biodistribution. This sets the stage for the evaluation of ChemoFilter effectiveness in reducing systemic toxicity from intra-arterial chemotherapy., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Sonneratia caseolaris leaf extract was characterized for its mitigation of the electrochemical corrosion of steel in naturally aerated hydrochloric acid environments by electrochemical methods and surface analysis. The presence of S. caseolaris leaf extract (SCLE) in the hydrochloric acid medium ameliorated the corrosion resistance of steel via the adsorption of SCLE species to form a barrier layer. The improved inhibition effectiveness was demonstrated to be independent of the SCLE concentration and the corrosive environment. The highest inhibition performance of approximately 98% was reached for steel in a 1 M HCl medium containing 2500 ppm SCLE. The performance significantly decreased with a decrease in the HCl concentration from 1.00 to 0.01 M with the same SCLE concentration. In addition, severe corrosion occurred on the uninhibited steel surface but was significantly reduced on the inhibited steel surface. The analyzed results also indicated the existence of electronegative functional groups in SCLE, which could promote the adsorption process for the self-formation of the barrier layer on the steel surface. The work reported herein suggested a powerful strategy to mitigate electrochemical corrosion by adding an effective new inhibitor to achieve a green inhibitor system., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Lymphocytes and innate immune cells are key drivers of multiple sclerosis (MS) and are the main target of MS disease-modifying therapies (DMT). Ex vivo analyses of MS lesions have revealed cellular heterogeneity and variable T cell levels, which may have important implications for patient stratification and choice of DMT. Although MRI has proven valuable to monitor DMT efficacy, its lack of specificity for cellular subtypes highlights the need for complementary methods to improve lesion characterization. Here, we evaluated the potential of 2'-deoxy-2'- 18 F-fluoro-9-β-d-arabinofuranosylguanine ( 18 F-FAraG) PET imaging to noninvasively assess infiltrating T cells and to provide, in combination with MRI, a novel tool to determine lesion types. Methods: We used a novel MS mouse model that combines cuprizone and experimental autoimmune encephalomyelitis to reproducibly induce 2 brain inflammatory lesion types, differentiated by their T cell content. 18 F-FAraG PET imaging, T2-weighted MRI, and T1-weighted contrast-enhanced MRI were performed before disease induction, during demyelination with high levels of innate immune cells, and after T cell infiltration. Fingolimod immunotherapy was used to evaluate the ability of PET and MRI to detect therapy response. Ex vivo immunofluorescence analyses for T cells, microglia/macrophages, myelin, and blood-brain barrier (BBB) integrity were performed to validate the in vivo findings. Results: 18 F-FAraG signal was significantly increased in the brain and spinal cord at the time point of T cell infiltration. 18 F-FAraG signal from white matter (corpus callosum) and gray matter (cortex, hippocampus) further correlated with T cell density. T2-weighted MRI detected white matter lesions independently of T cells. T1-weighted contrast-enhanced MRI indicated BBB disruption at the time point of T cell infiltration. Fingolimod treatment prevented motor deficits and decreased T cell and microglia/macrophage levels. In agreement, 18 F-FAraG signal was decreased in the brain and spinal cord of fingolimod-treated mice; T1-weighted contrast-enhanced MRI revealed intact BBB, whereas T2-weighted MRI findings remained unchanged. Conclusion: The combination of MRI and 18 F-FAraG PET enables detection of inflammatory demyelination and T cell infiltration in an MS mouse model, providing a new way to evaluate lesion heterogeneity during disease progression and after DMT. On clinical translation, these methods hold great potential for stratifying patients, monitoring MS progression, and determining therapy responses., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: There is interest in the application of behavioral interventions based on theory for increasing physical activity among adults with multiple sclerosis (MS). To date, researchers have applied theory such as Social Cognitive Theory (SCT) for identifying correlates of physical activity that can then inform the design and delivery of behavioral interventions. Such research often has been conducted in heterogeneous samples of persons with MS without a focus on those with a specific symptom, such as fatigue, that may be targeted by physical activity behavioral interventions. To that end, this study examined SCT variables (i.e., self-efficacy, barriers, outcome expectations, goal-setting, planning, social support, and functional limitations) as correlates of physical activity in persons with MS who self-reported elevated fatigue., Methods: Persons with MS (N=210; aged 49.6[13.2] years) who ambulated with or without assistance participated in the study. Participants completed self-report measures of fatigue, physical activity, and SCT variables and wore an ActiGraph GT3X+ accelerometer on a belt around the waist for 7 days. The accelerometer data were processed and delineated into time spent in light and moderate-to-vigorous physical activity (MVPA) based on MS-specific cut-points. We generated groups of fatigued (n=134) and non-fatigued (n=76) persons with MS based on the cut-off score of 4 for the Fatigue Severity Scale., Results: There were differences in physical activity and SCT variables between fatigued and non-fatigued persons with MS. Among those with fatigue, functional limitations (ρ=0.52), self-efficacy (ρ=0.31), and goal-setting (ρ=0.25) were associated with device-measured MVPA, and all SCT variables except outcome expectations were associated with self-reported physical activity. The regression analyses indicated self-efficacy, functional limitations, and goal-setting as significant correlates of MVPA in those with fatigue., Conclusion: Self-efficacy, goal-setting, and social support may be important targets of SCT-based behavioral interventions for increasing physical activity among persons with MS who have fatigue., (Copyright © 2021. Published by Elsevier B.V.)

A total of 1,318 wild geckos were collected in Cambodia, Thailand and Vietnam (Hue and the Mekong Delta) from 2012 to 2015 to determine the prevalence of Salmonella Weltevreden. Those geckos belong to three species: common house gecko (Hemidactylus frenatus), flat-tailed house gecko (Hemidactylus platyurus) and four-clawed gecko (Gehyra mutilata). Of 1,318 gecko samples, 293 (22.2%) samples were positive for Salmonella in this study. The prevalence of Salmonella in geckos was 46.0% in Thailand, 17.3% in Cambodia and 16.3% in Vietnam. Among the Salmonella isolates, S. Weltevreden was the most predominant serovar (32.1%) isolated from wild geckos in these countries. There was no significant difference in the prevalence of Salmonella among gecko species. All S. Weltevreden isolates (100%) were susceptible to the nine antibiotics examined in this study. The PFGE assay by XbaI enzyme identified 19 different patterns from 75 S. Weltevreden isolates. These isolates showed high genetic heterogenicity, and there were specific types prevalent in each region. Furthermore, S. Weltevreden has been prevalent since the ancient times in this region. The results indicate that wild gecko seems to be an important natural reservoir for S. Weltevreden as well as a source of Salmonella infections in humans in Southeast Asian countries., (© 2021 Wiley-VCH GmbH.)

Brain oscillations have been hypothesized to support cognitive function by coordinating spike timing within and across brain regions, yet it is often not known when timing is either critical for neural computations or an epiphenomenon. The entorhinal cortex and hippocampus are necessary for learning and memory and exhibit prominent theta oscillations (6-9 Hz), which are controlled by pacemaker cells in the medial septal area. Here we show that entorhinal and hippocampal neuronal activity patterns were strongly entrained by rhythmic optical stimulation of parvalbumin-positive medial septal area neurons in mice. Despite strong entrainment, memory impairments in a spatial working memory task were not observed with pacing frequencies at or below the endogenous theta frequency and only emerged at frequencies ≥10 Hz, and specifically when pacing was targeted to maze segments where encoding occurs. Neural computations during the encoding phase were therefore selectively disrupted by perturbations of the timing of neuronal firing patterns., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Cold-induced thermogenesis in endotherms demands adaptive thermogenesis fueled by mitochondrial respiration and Ucp1-mediated uncoupling in multilocular brown adipocytes (BAs). However, dietary regulation of thermogenesis in BAs isn't fully understood. Here, we describe that the deficiency of Leucine-rich pentatricopeptide repeat containing-protein (Lrpprc) in BAs reduces mtDNA-encoded ETC gene expression, causes ETC proteome imbalance, and abolishes the mitochondria-fueled thermogenesis. BA-specific Lrpprc knockout mice are cold resistant in a 4°C cold-tolerance test in the presence of food, which is accompanied by the activation of transcription factor 4 (ATF4) and proteome turnover in BAs. ATF4 activation genetically by BA-specific ATF4 overexpression or physiologically by a low-protein diet feeding can improve cold tolerance in wild-type and Ucp1 knockout mice. Furthermore, ATF4 activation in BAs improves systemic metabolism in obesogenic environment regardless of Ucp1's action. Therefore, our study reveals a diet-dependent but Ucp1-independent thermogenic mechanism in BAs that is relevant to systemic thermoregulation and energy homeostasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Most clinical trials exploring various combinations of chemo- and immunotherapy rely on serial biopsy to provide information on immune response. The aim of this study was to assess the value of 18 F-arabinosyl guanine ( 18 F-AraG) as a noninvasive tool that profiles tumors on the basis of the key player in adaptive antitumor response, CD8+ cells, and evaluates the immunomodulatory effects of chemotherapy. Methods: To evaluate the ability of 18 F-AraG to report on the presence of CD8+ cells within the tumor microenvironment, we imaged a panel of syngeneic tumor models (MC38, CT26, LLC, A9F1, 4T1, and B16F10) and correlated the signal intensity with the number of lymphocytes found in the tumors. The capacity of 18 F-AraG to detect immunomodulatory effects of chemotherapy was determined by longitudinal imaging of tumor-bearing mice (MC38 and A9F1) undergoing 2 types of chemotherapy: oxaliplatin/cyclophosphamide, shown to induce immunogenic cell death, and paclitaxel/carboplatin, reported to cause immunogenically silent tumor cell death. Results: In the tumor panel, 18 F-AraG revealed strikingly different uptake patterns resembling cancer-immune phenotypes observed in the clinic. A statistically significant correlation was found between the 18 F-AraG signal and the number of PD-1-positive CD8+ cells isolated from the tumors ( r 2 = 0.528, P < 0.0001). In the MC38 model, paclitaxel/carboplatin did not result in an appreciable change in signal after therapy (1.69 ± 0.25 vs. 1.50 ± 0.33 percentage injected dose per gram), but oxaliplatin/cyclophosphamide treatment led to close to a 2.4-fold higher 18 F-AraG signal (1.20 ± 0.31 vs. 2.84 ± 0.93 percentage injected dose per gram). The statistically significant increase in signal after oxaliplatin/cyclophosphamide was also observed in the A9F1 model (0.95 ± 0.36 vs. 1.99 ± 0.54 percentage injected dose per gram). Conclusion: The ability of 18 F-AraG PET to assess the location and function of CD8+ cells, as well immune activity within tumors after immune priming therapy, warrants further investigation into its utility for patient selection, evaluation of optimal time to deliver immunotherapies, and assessment of combinatorial therapies., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The role of integrins, in particular αv integrins, in regulating insulin resistance is incompletely understood. We have previously shown that the αvβ5 integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) regulates cellular uptake of fatty acids. In this work, we evaluated the impact of MFGE8 on glucose homeostasis. We show that acute blockade of the MFGE8/β5 pathway enhances while acute augmentation dampens insulin-stimulated glucose uptake. Moreover, we find that insulin itself induces cell-surface enrichment of MFGE8 in skeletal muscle, which then promotes interaction between the αvβ5 integrin and the insulin receptor leading to dampening of skeletal-muscle insulin receptor signaling. Blockade of the MFGE8/β5 pathway also enhances hepatic insulin sensitivity. Our work identifies an autoregulatory mechanism by which insulin-stimulated signaling through its cognate receptor is terminated through up-regulation of MFGE8 and its consequent interaction with the αvβ5 integrin, thereby establishing a pathway that can potentially be targeted to improve insulin sensitivity., Competing Interests: The authors declare no competing interest.

Porcine epidemic diarrhoea virus (PEDV) is one of the major pathogens causing acute enteritis, which is characterised by vomiting and watery diarrhoea and commonly leads to high rates of mortality and morbidity in suckling piglets. Chitosan has been regarded as a promising natural disinfectant. In this study, the disinfectant effect and mammalian-cell toxicity of chitosan were evaluated against PEDV using Vero cells. A 0.01% solution of chitosan was determined to be an effective disinfectant. In addition, no evidence of toxicity was observed during the cell toxicity test; on the contrary, chitosan promoted cell proliferation. In conclusion, chitosan is a promising candidate for an effective and safe disinfectant against PEDV as well as other coronaviruses.

Purpose: We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [ 89 Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models., Experimental Design: [ 89 Zr]DFO-YS5 was prepared and its in vitro binding affinity for CD46 was measured. ImmunoPET imaging was conducted in male athymic nu/nu mice bearing DU145 [AR - , CD46 + , prostate-specific membrane antigen-negative (PSMA - )] or 22Rv1 (AR + , CD46 + , PSMA + ) tumors, and in NOD/SCID gamma mice bearing patient-derived adenocarcinoma xenograft, LTL-331, and neuroendocrine prostate cancers, LTL-331R and LTL-545., Results: [ 89 Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [ 89 Zr]DFO-YS5 was 13.3 ± 3.9 and 11.2 ± 2.5 %ID/g, respectively, in DU145 and 22Rv1 xenografts, 4 days postinjection. Notably, [ 89 Zr]DFO-YS5 demonstrated specific uptake in the PSMA- and AR-negative DU145 model. [ 89 Zr]DFO-YS5 also showed uptake in the patient-derived LTL-331 and -331R models, with particularly high uptake in the LTL-545 neuroendocrine prostate cancer tumors (18.8 ± 5.3, 12.5 ± 1.8, and 32 ± 5.3 %ID/g in LTL-331, LTL-331R, and LTL-545, respectively, at 4 days postinjection)., Conclusions: [ 89 Zr]DFO-YS5 is an excellent PET imaging agent across a panel of prostate cancer models, including in both adenocarcinoma and neuroendocrine prostate cancer, both cell line- and patient-derived xenografts, and both PSMA-positive and -negative tumors. It demonstrates potential for clinical translation as an imaging agent, theranostic platform, and companion biomarker in prostate cancer., (©2020 American Association for Cancer Research.)

Organophosphorus esters (OPs) were originally developed as pesticides but were repurposed as easily manufactured, inexpensive, and highly toxic chemical warfare agents. Acute OP toxicity is primarily due to inhibition of acetylcholinesterase (AChE), an enzyme in the central and peripheral nervous system. OP inhibition of AChE can be reversed using oxime reactivators but many show poor CNS penetration, indicating a need for new clinically viable reactivators. However, challenges exist on how to best measure restored AChE activity in vivo and assess the reactivating agent efficacy. This work reports the development of molecular imaging tools using radiolabeled OP analog tracers that are less toxic to handle in the laboratory, yet inhibit AChE in a similar fashion to the actual OPs. Carbon-11 and fluorine-18 radiolabeled analog tracers of VX and sarin OP agents were prepared. Following intravenous injection in normal Sprague-Dawley rats ( n = 3-4/tracer), the tracers were evaluated and compared using noninvasive microPET/CT imaging, biodistribution assay, and arterial blood analyses. All showed rapid uptake and stable retention in brain, heart, liver, and kidney tissues determined by imaging and biodistribution. Lung uptake of the sarin analog tracers was elevated, 2-fold and 4-fold higher uptake at 5 and 30 min, respectively, compared to that for the VX analog tracers. All tracers rapidly bound to red blood cells (RBC) and blood proteins as measured in the biodistribution and arterial blood samples. Analysis of the plasma soluble activity (nonprotein/cell bound activity) showed only 1-6% parent tracer and 88-95% of the activity in the combined solid fractions (RBC and protein bound) as early as 0.5 min post injection. Multivariate analysis of tracer production yield, molar activity, brain uptake, brain area under the curve over 0-15 min, and the amount of parent tracer in the plasma at 5 min revealed the [ 18 F]VX analog tracer had the most favorable values for each metric. This tracer was considered the more optimal tracer relative to the other tracers studied and suitable for future in vivo OP exposure and reactivation studies.

Oxime antidotes regenerate organophosphate-inhibited acetylcholinesterase (AChE). Although they share a common mechanism of AChE reactivation, the rate and amount of oxime that enters the brain are critical to the efficacy, a process linked to the oxime structure and charge. Using a platform based on the organophosphate [ 18 F]-VXS as a positron emission tomography tracer for active AChE, the in vivo distribution of [ 18 F]-VXS was evaluated after an LD 50 dose (250 μg/kg) of the organophosphate paraoxon (POX) and following oximes as antidotes. Rats given [ 18 F]-VXS tracer alone had significantly higher radioactivity (two- to threefold) in the heart and lung than rats given LD 50 POX at 20 or 60 min prior to [ 18 F]-VXS. When rats were given LD 50 POX followed by 2-PAM (cationic), RS194b (ionizable), or monoisonitrosoacetone (MINA) (neutral), central nervous system (CNS) radioactivity returned to levels at or above untreated naive rats (no POX), whereas CNS radioactivity did not increase in rats given the dication oximes HI-6 or MMB-4. MINA showed a significant, pairwise increase in CNS brain radioactivity compared with POX-treated rats. This new in vivo dynamic platform using [ 18 F]-VXS tracer measures and quantifies peripheral and CNS relative changes in AChE availability after POX exposure and is suitable for comparing oxime delivery and AChE reactivation in rats., (© 2020 New York Academy of Sciences.)

Although environmental training program has become a vital solution to minimize environmental challenges, the existing literature has paid little attention to (1) the connection between environmental training and employee in-role green performance (EIGP), (2) the mediating role of employee environmental commitment in this environmental training-EIGP connection, and (3) the cultural perspective (Western and Local) influences on interrelationships between environmental training, EIGP, and employee environmental commitment. Drawing on the social exchange theory and cultural perspective, a quantitative study based on survey data collected from 301 respondents at hotels in Vietnam was employed to fill these research gaps. Findings reveal that environmental training program is as an important tool to drive EIGP directly, and this environmental training-EIGP relationship is significantly mediated by employee environmental commitment. Interestingly, the study indicates support for our prediction that the mediating role of employee environmental commitment on the environmental training-EIGP link is stronger at hotels managed by Western hospitality companies. However, unexpectedly, cultural influence does not moderate the effect of environmental training on EIGP. Other than theoretical contributions, our study carries important practical implications that can help organizations reduce their carbon footprint. Limitations and further research directions have also been discussed., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This paper empirically investigates the effect of carbon emissions on sovereign risk? To answer this question, we use fixed effects model by using annual data from G7 advanced economies, which includes Canada, France, Germany, Italy, Japan, UK and USA, for the period from 1996 to 2014. We employ a novel extreme value theory to measure sovereign risk. The results indicate that climate change (carbon emissions) are likely to increase sovereign risk significantly. We also expand our analysis to some specific sectors, as some of the sectors emit more carbon than others. Specifically, we take top three polluting sectors namely: transportation, electricity and industry and show that they are more likely to increase the sovereign risk. Our results are robust to change in risk measures, estimation in differences and dynamic version of econometric models. Therefore, we have robust consideration that the carbon emissions significantly explain the sovereign risk., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Incorporation of d-amino acids into peptidoglycan is a unique metabolic feature of bacteria. Since d-amino acids are not metabolic substrates in most mammalian tissues, this difference can be exploited to detect living bacteria in vivo . Given the prevalence of d-alanine in peptidoglycan muropeptides, as well as its role in several antibiotic mechanisms, we targeted this amino acid for positron emission tomography (PET) radiotracer development. d-[3- 11 C]Alanine and the dipeptide d-[3- 11 C]alanyl-d-alanine were synthesized via asymmetric alkylation of glycine-derived Schiff-base precursors with [ 11 C]methyl iodide in the presence of a cinchonidinium phase-transfer catalyst. In cell experiments, both tracers showed accumulation by a wide variety of both Gram-positive and Gram-negative pathogens including Staphylococcus aureus and Pseudomonas aeruginosa . In a mouse model of acute bacterial myositis, d-[3- 11 C]alanine was accumulated by living microorganisms but was not taken up in areas of sterile inflammation. When compared to existing clinical nuclear imaging tools, specifically 2-deoxy-2-[ 18 F]fluoro-d-glucose and a gallium citrate radiotracer, d-alanine showed more bacteria-specific uptake. Decreased d-[3- 11 C]alanine uptake was also observed in antibiotic-sensitive microbes after antimicrobial therapy, when compared to that in resistant organisms. Finally, prominent uptake of d-[3- 11 C]alanine uptake was seen in rodent models of discitis-osteomyelitis and P. aeruginosa pneumonia. These data provide strong justification for clinical translation of d-[3- 11 C]alanine to address a number of important human infections., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Purpose: Tumor necrosis factor alpha (TNFα) drives inflammation and bone degradation in patients with rheumatoid arthritis (RA). Some RA patients experience a rapid clinical response to TNFα inhibitors such as certolizumab pegol (CZP) while other patients show limited to no response. Current methods for imaging RA have limited sensitivity and do not assist in the selection of patients most likely to respond to immune-mediated therapy. Herein, we developed a novel positron emission tomography (PET) radiotracer for immuno-PET imaging of TNFα in transgenic human TNFα-expressing mice., Procedures: CZP was modified with p-isothiocyanatobenzyl-deferoxamine (DFO) and radiolabeled with Zr-89. The biological activity of [ 89 Zr]DFO-CZP was evaluated by HPLC and binding assay using human recombinant TNFα (hTNFα). The feasibility of specific immuno-PET imaging of human TNFα was assessed in a transgenic mouse model of RA that expresses human TNFα. This model resembles the progression of RA in humans by maintaining lower levels of circulating hTNFα and exhibits chronic arthritis in the forepaw and hind paw joints. The dosimetry of [ 89 Zr]DFO-CZP in humans was estimated using microPET/CT imaging in Sprague Dawley rats., Results: [ 89 Zr]DFO-CZP was isolated with radiolabeling yields of 85 ± 6 % (n = 5) and specific activities ranging from 74 to 185 MBq/mg (n = 5). Following size exclusion purification, the radiochemical purity of [ 89 Zr]DFO-CZP was greater than 97 %. [ 89 Zr]DFO-CZP retained high immunoreactivity with more than 95 % of the radioactivity shifted into higher molecular weight complexes. Images showed increasing uptake of the tracer in forepaw and hind paw joints with disease progression. No uptake was observed in the model previously administered with an excess amount of unmodified CZP and in normal control mice, demonstrating in vivo specific uptake of [ 89 Zr]DFO-CZP., Conclusion: The feasibility of immuno-PET imaging of human TNFα with [ 89 Zr]DFO-CZP has been demonstrated in a preclinical model of RA.

Interstitial cells of Cajal, which express the calcium-activated chloride channel transmembrane member 16A (TMEM16A), are an important determinant of gastrointestinal (GI) motility. We previously identified the acylaminocycloalkylthiophene class of TMEM16A inhibitors, which, following medicinal chemistry, gave analog 2-bromodifluoroacetylamino-5,6,7,8-tetrahydro-4 H -cyclohepta[ b ]thiophene-3-carboxylic acid o -tolylamide (TM inh -23) with 30 nM half-maximal inhibitory concentration. Here, we tested the efficacy of TM inh -23 for inhibition of GI motility in mice. In isolated murine gastric antrum, TM inh -23 strongly inhibited spontaneous and carbachol-stimulated rhythmic contractions. Pharmacokinetic analysis showed predicted therapeutic concentrations of TM inh -23 for at least 4 h following a single oral or intraperitoneal dose at 10 mg/kg. Gastric emptying, as assessed following an oral bolus of phenol red or independently by [ 99m Tc]-diethylenetriamine pentaacetic acid scintigraphy, was reduced by TM inh -23 by ∼60% at 20 min. Interestingly, there was little effect of TM inh -23 on baseline whole-gut transit time or time to diarrhea induced by castor oil. Consequent to the delay in gastric emptying, TM inh -23 administration significantly reduced the elevation in blood sugar in mice following an oral but not intraperitoneal glucose load. These results provide pharmacological evidence for involvement of TMEM16A in gastric emptying and suggest the utility of TMEM16A inhibition in disorders of accelerated gastric emptying, such as dumping syndrome, and potentially for improving glucose tolerance in diabetes mellitus/metabolic syndrome and enhancing satiety in obesity.-Cil, O., Anderson, M. O., Yen, R., Kelleher, B., Huynh, T. L., Seo, Y., Nilsen, S. P., Turner, J. R., Verkman, A. S. Slowed gastric emptying and improved oral glucose tolerance produced by a nanomolar-potency inhibitor of calcium-activated chloride channel TMEM16A.

In the context of remarkable economic growth and financial development in the emerging economies of East Asia, this paper attempts to shed light on the ecological consequences (CO2 emission) of economic growth, foreign direct investment and financial development in the selected ASEAN-5 economies. Drawing on the data from 1982 to 2014, we employed a set of quantitative techniques for panel data analysis which entailed Dynamic Ordinary Least Squares (DOLS) and Fully Modified OLS (FMOLS) approaches. Our findings indicate that financial and economic development, as well as FDI, have a statistically significant long-run co-integrating relationship with environmental degradation (CO 2 emissions) in the under analysis economies. It showed that in ASEAN-5 countries, economic growth, financial development and FDI leads to an increase in environmental degradation. The quadratic term for economic growth showed a negative impact on environmental degradation i.e. Environmental Kuznets Curve (EKC). Our key findings manifest and emphasise the importance of appropriate policies for more inclusive economic and financial development and sustainable foreign direct investment which does not impede on the environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. In this study, we evaluate a T-cell-specific PET agent, [18F]F-AraG, as an imaging biomarker predictive of response to checkpoint inhibitor therapy. We determined the specificity of the tracer for activated T cells in vitro and in a virally induced model of rhabdomyosarcoma. Of all immune cells tested, activated human CD8 + effector cells showed the highest accumulation of [18F]F-AraG. Isolation of lymphocytes from the rhabdomyosarcoma tumors showed that more than 80% of the intratumoral signal came from accumulation of [18F]F-AraG in immune cells, primarily CD8 + and CD4 + . Longitudinal monitoring of MC38 tumor-bearing mice undergoing anti-PD-1 treatment revealed differences in signal between PD-1 and isotype antibody-treated mice early into treatment. The differences in [18F]F-AraG signal were also apparent between responders and nonresponders to anti-PD-1 therapy. Importantly, we found that the signal in the tumor-draining lymph nodes provides key information about response to anti-PD-1 therapy. Overall, [18F]F-AraG has potential to serve as a much needed immunomonitoring clinical tool for timely evaluation of immunotherapy. SIGNIFICANCE: These findings reveal differences in T-cell activation between responders and nonresponders early into anti-PD-1 treatment, which may impact many facets of immuno-oncology, including patient selection, management, and development of novel combinatorial approaches., (©2019 American Association for Cancer Research.)

Quaternary ammonium salts are widely used in consumer products and industrial processes, where their instability at elevated temperatures limits their range of applications. In this work, the thermal behavior of a new class of quaternary ammonium salts was investigated using differential scanning calorimetry. These salts contain a sulfur atom in each chain at the fourth position from the central nitrogen and are thus termed thiaquats. The temperatures at which these salts melt and thermally degrade were determined, and enthalpies and entropies of fusion were evaluated. Their melting points increase with chain lengths, in contrast to the behavior of traditional quaternary ammonium salts. Furthermore, they exhibit enthalpies and entropies of fusion significantly lower than corresponding tetraalkyl analogues. These trends provide physical insight into the molecular-level behavior of these salts, suggesting that they do not fully dissociate upon melting. The thiaquats also exhibit thermal stability to markedly higher temperatures than traditional quaternary ammonium bromides, a phenomenon that can be explained in by strong pairing between the quaternary cation and bromide anion, which inhibits possible decomposition mechanisms. This enhanced thermal stability may enable applications of these salts in processes where traditional salts are not viable, such as phase-transfer-catalyzed systems performed at elevated temperatures.

Clostridium tetani is the etiologic agent of the muscle-spasming disease tetanus. Despite an effective vaccine, tetanus is an ongoing problem in some developing countries. Diagnosis by bacterial culture is not done because it is generally unnecessary and the entry of route of the bacteria can be inapparent. We attempted to isolate and evaluate C. tetani from the wounds of 84 patients with tetanus. We effectively isolated C. tetani from 45 patients. All strains tested positive by polymerase chain reaction for the gene encoding tetanus neurotoxin. Antimicrobial susceptibilities were determined by disc diffusion and E-test. All C. tetani isolates were susceptible to penicillin and metronidazole but resistant to co-trimoxazole. Despite treatment with high doses of penicillin, C. tetani was isolated after 16 days of intravenous penicillin in two cases. These data show that the intravenous route for penicillin may be inadequate for clearing the infection and emphasizes wound debridement in the treatment of tetanus.

Self-organisation and self-assembly are critical to the stability of synthetic and biological membranes. Of particular importance is consideration of the packing arrangements of the various molecular species. Both phospho- and glycolipids can pack in ways in which curvature can be introduced into self-organised or self-assembled systems. For instance, it is known that the degree of curvature can affect the structures of any condensed phases that are formed. In this article we report on a systematic study in which we have varied the shapes of glycolipids and examined the condensed phases that they form. In doing so, we have also unified the shape dependency of lyotropic liquid crystals with those of thermotropic liquid crystals. In order to undertake this systematic study a range of different pentaerythritol derivatives was synthesized, which covers combinations of one to three alkyl chains of different lengths (6,7,9,10,11,12,14,16 carbon atoms) and three to one galactosyl heads. Mono- and di-O-galactosyl derivatives were prepared directly by glycosylation of the corresponding alcohols using 2,3,4,6-tetra-O-benzoyl or acetyl-alpha-D-galactopyranosyl trichloroacetimidate or bromide as the donors; the tri-O-galactosyl derivatives were synthesized from O-alkyl-O-benzyl di-O-galactosyl pentaerythritol intermediates, followed by de-O-benzylation and glycosylation steps. All of the fully deprotected products were obtained by standard methods, and their self-organising and self-assembling properties examined.

This retrospective study was performed to precise indications of emergency CT in a general hospital over a 30 months period. We tried to determine, with help of prior studies, the indications for CT of the brain in the management of acute meningitis, acute headache, and in the management of head injury. In acute meningitis, there is no evidence to recommend CT of the brain before lumbar puncture, except to identify patients at increased risk of cerebral herniation. The imaging study of choice in subarachnoid hemorrhage is non enhanced CT scan. This exam has to be performed in case of acute headache. The CT evaluation of patients with minor head injury remains controversial.

A considerable loss of substance of the duodenal wall makes its repair very difficult especially if this exceeds two-thirds of its circumference and is located around its entire second portion. Such a pathological or traumatic localization calls for extensive surgery-cephalic duodenopancreatectomy requiring several gastrojejunal, biliodigestive and the pancreaticodigestive shunts. If straightforward repair was possible, this could lead to stenosis and to a fistula producing complications and the death of the patient through peritonitis and hydroelectrolytic and metabolic imbalance. The mucous patch seems to us the last and only solution after other known techniques.