CSF rhinorrhea: 95 consecutive surgical cases with long term follow-up at the Mayo Clinic.
A persistent cerebrospinal fluid (CSF) leak is potentially lethal, and surgical treatment is often required. CSF leak repair is an infrequently performed procedure, and only limited information is available on the long term success of the surgical techniques that are used. This retrospective chart review includes 95 patients who underwent various types of repair surgery for CSF rhinorrhea at the Mayo Clinic. The purpose of this study was to extract factors such as the choice of sealing material, etiology, location of defect(s), surgical approach, and previous procedures, and to analyze their association with the long term success and failure of surgical repair. The mean time interval in this study between unsuccessful surgery and recurrence was 50.8 months, and the mean follow-up 109 months. Among the various approaches, defects repaired endonasally had the lowest recurrence rate. Local nasal mucosa advancement flaps failed more frequently (83.3% failure) than other types of graft material (p = 0.023). These failures took place in a delayed fashion (mean interval until failure: 80 months). Local osteo-mucoperiosteal or chondro-mucoperichondrial flaps (22.2% recurrence rate) and free graft material (15.6% recurrence rate) had the best outcome. The use of fibrin glue to fixate free grafts did not improve the result in this series. Transcranial procedures were associated with a higher complication rate than extracranial procedures (12.9% versus 3.2%). Overall, successful repair was achieved in 91.6% of the patients. We discourage the use of mucosa advancement flaps and advocate free grafts or pedicled osteomucoperiosteal or chondro-mucoperichondrial flaps as sealing material of choice in the majority of cases. The occurrence of delayed failure has to be considered when evaluating reports of CSF rhinorrhea after surgical repair.


Quantum Droplets of Dipolar Mixtures.
Recently achieved two-component dipolar Bose-Einstein condensates open exciting possibilities for the study of mixtures of ultradilute quantum liquids. While nondipolar self-bound (without external confinement) mixtures are necessarily miscible with an approximately fixed ratio between the two densities, the density ratio for the dipolar case is free. Therefore, self-bound dipolar mixtures present qualitatively novel and much richer physics, characterized by three possible ground-state phases: miscible, symmetric immiscible, and asymmetric immiscible, which may in principle occur at any population imbalance. Self-bound immiscible droplets are possible due to mutual nonlocal intercomponent attraction, which results in the formation of a droplet molecule. Moreover, our analysis of the impurity regime shows that quantum fluctuations in the majority component crucially modify the miscibility of impurities. Our work opens intriguing perspectives for the exploration of spinor physics in ultradilute liquids, which should resemble to some extent that of ^{4}He-^{3}He droplets and impurity-doped helium droplets.


Carbon dioxide conversion over carbon-based nanocatalysts.
The utilization of carbon dioxide for the production of valuable chemicals via catalysts is one of the efficient ways to mitigate the greenhouse gases in the atmosphere. It is known that the carbon dioxide conversion and product yields are still low even if the reaction is operated at high pressure and temperature. The carbon dioxide utilization and conversion provides many challenges in exploring new concepts and opportunities for development of unique catalysts for the purpose of activating the carbon dioxide molecules. In this paper, the role of carbon-based nanocatalysts in the hydrogenation of carbon dioxide and direct synthesis of dimethyl carbonate from carbon dioxide and methanol are reviewed. The current catalytic results obtained with different carbon-based nanocatalysts systems are presented and how these materials contribute to the carbon dioxide conversion is explained. In addition, different strategies and preparation methods of nanometallic catalysts on various carbon supports are described to optimize the dispersion of metal nanoparticles and catalytic activity.


Horizontally staggered lightguide solar concentrator with lateral displacement tracking for high concentration applications.
We present the design of a horizontally staggered lightguide solar concentrator with lateral displacement tracking for high concentration applications. This solar concentrator consists of an array of telecentric primary concentrators, a horizontally staggered lightguide layer, and a vertically tapered lightguide layer. The primary concentrator is realized by two plano-aspheric lenses with lateral movement and maintains a high F-number over an angle range of ±23.5°. The results of the simulations show that the solar concentrator achieves a high concentration ratio of 500× with ±0.5° of acceptance angle by a single-axis tracker and dual lateral translation stages.


Octaketide Synthase from Polygonum cuspidatum Implements Emodin Biosynthesis in Arabidopsis thaliana.
Plant anthranoids are medicinally used for their purgative properties. Their scaffold was believed to be formed by octaketide synthase (OKS), a member of the superfamily of type III polyketide synthase (PKS) enzymes. Here, a cDNA encoding OKS of Polygonum cuspidatum was isolated using a homology-based cloning strategy. When produced in Escherichia coli, P. cuspidatum octaketide synthase (PcOKS) catalyzed the condensation of eight molecules of malonyl-CoA to yield a mixture of unphysiologically folded aromatic octaketides. However, when the ORF for PcOKS was expressed in Arabidopsis thaliana, the anthranoid emodin was detected in the roots of transgenic lines. No emodin was found in the roots of wild-type A. thaliana. This result indicated that OKS is the key enzyme of plant anthranoids biosynthesis. In addition, the root growth of the transgenic A. thaliana lines was inhibited to an extent that resembled the inhibitory effect of exogenous emodin on the root growth of wild-type A. thaliana. Immunochemical studies of P. cuspidatum plants detected PcOKS mainly in roots and rhizome, in which anthranoids accumulate. Co-incubation of E. coli - produced PcOKS and cell-free extract of wild-type A. thaliana roots did not form a new product, suggesting an alternative, physiological folding of PcOKS and its possible interaction with additional factors needed for anthranoids assembling in transgenic A. thaliana. Thus, transgenic A. thaliana plants producing PcOKS provide an interesting system for elucidating the route of plant anthranoid biosynthesis.


The role of succinate dehydrogenase and oxaloacetate in metabolic suppression during hibernation and arousal.
Hibernation elicits a major reduction in whole-animal O(2) consumption that corresponds with active suppression of liver mitochondrial electron transport capacity at, or downstream of, succinate dehydrogenase (SDH). During arousal from the torpor phase of hibernation this suppression is reversed and metabolic rates rise dramatically. In this study, we used the 13-lined ground squirrel (Ictidomys tridecemlineatus) to assess isolated liver mitochondrial respiration during the torpor phase of hibernation and various stages of arousal to elucidate a potential role of SDH in metabolic suppression. State 3 and state 4 respiration rates were seven- and threefold lower in torpor compared with the summer-active and interbout euthermic states. Respiration rates increased during arousal so that when body temperature reached 30 degrees C in late arousal, state 3 and state 4 respiration were 3.3- and 1.8-fold greater than during torpor, respectively. SDH activity was 72% higher in interbout euthermia than in torpor. Pre-incubating with isocitrate [to alleviate oxaloacetate (OAA) inhibition] increased state 3 respiration rate during torpor by 91%, but this rate was still fourfold lower than that measured in interbout euthermia. Isocitrate pre-incubation also eliminated differences in SDH activity among hibernation bout stages. OAA concentration correlated negatively with both respiration rates and SDH activity. These data suggest that OAA reversibly inhibits SDH in torpor, but cannot fully account for the drastic metabolic suppression observed during this hibernation phase.


Bacterial and Archaeal Communities Change With Intensity of Vegetation Coverage in Arenized Soils From the Pampa Biome.
Arenization occurs in regions that present sandy soils with normal rainfall levels. Predatory use of environmental sources, the dissolution of arenitic rocks and reworking of non-consolidated surface sands intensify this degradation scenario. Thus, this work aimed to evaluate the impact of the arenization process in the Brazilian Pampa Biome and how this phenomenon affects the soil microbial and plant communities. For this purpose, three arenized areas in Southern Brazil (Pampa Biome) were selected and, in each one, three sampling points were studied: arenized (ARA), arenized to grassland transition (AGT), and grassland (GRA) areas. In the three sampling points, soils presented low levels of nutrients, organic matter, mud and pH acidic in all regions but, the presence of vegetation coverage in AGT and GRA areas preserved the topsoil structure. Our study related ARA with bacterial families Alcaligenaceae, Pseudomonadaceae, and Xanthomonadaceae. AGT with bacterial families Bacillaceae and Burkholderiaceae, and plant species Melinis repens (Willd.) Zizka and Paspalum stellatum Humb. and Bonpl. ex Flüggé, and GRA with bacterial families Koribacteraceae, Hyphomicrobiaceae, and Chthoniobacteraceae, and plant species Croton subpannosus Müll.Arg. ex Griseb., Piptochaetium montevidense (Spreng.) Parodi and Elyonurus sp. The three studied areas (as well as sampling points) present soils extremely poor in nutrients with sandy texture, and the bacterial and plant composition well known to be resistant to environmental stresses were dominant. The vulnerability of these areas causes a degradation scenario, which is worsened by agricultural activities. However, in general, this phenomenon is a natural process that occurs mainly due to soil characteristics (poor soils) and climatic variations.


The effectiveness of teleconsultations in primary care: systematic review.
The COVID-19 pandemic has focussed attention on models of healthcare that avoid face-to-face contacts between clinicians and patients, and teleconsultations have become the preferred mode of primary care delivery. However, the effectiveness of remote consultations in this setting remains unclear. To evaluate the impact of telephone or video consultations compared to those conducted face-to-face on key patient-relevant outcomes and healthcare utilisation in primary care, mental health and allied health services, which have had a critical role in the management of the wider and longer-term consequences of COVID-19. A systematic review of primary studies comparing telephone or video consultations versus face-to-face visits, following the PRISMA guidelines. Overall, consultations delivered by telephone and videoconference were as effective as face-to-face in-person visits to improve clinical outcomes in adults with mental health conditions and those attending primary care services. Patient satisfaction with telephone and video consultations and the therapeutic alliance was high across the studies. However, high discontinuation rates in patients receiving teleconsultations indicate this may not be a suitable modality of healthcare delivery for all patients. Teleconsultations offer significant patient time savings in primary care, but appropriate implementation, including training of healthcare professionals and management of technical issues, is essential to ensure effective and valuable clinical interventions. Teleconsultations via telephone or videoconference are an effective alternative to face-to-face consultations for many patients attending primary care and mental health services. Teleconsultations have the potential to deliver time-efficient and lower-cost interventions at a distance while improving access to healthcare.


Modulation of endotoxin-induced andrological alterations by flunixin meglumine in the boar.
Flunixin meglumine (FM), an inhibitor of the cyclo-oxygenase pathway of the prostaglandin synthesis, was used to evaluate the andrological changes following an endotoxin (ET) administration in the boar. FM was injected as a single dose 10 min prior to an ET injection. Blood plasma was analysed for the contents of 15-ketodihydroprostaglandin (PG) F2 alpha LH, testosterone and cortisol. Twelve h after the ET administration, the boars were castrated and the testes examined by light and electron microscopy. The results were compared between controls, ET-, FM- and FM+ET-treated boars. An increase in 15-ketodihydro-PGF2 alpha levels was seen following ET administration. Pretreatment with FM decreased the levels of 15-ketodihydro-PGF2 alpha during 2 h. Following the ET administration a voluminous increase in testosterone levels as well as changed LH levels were seen. Similar alterations in hormonal levels were observed also after pretreatment with FM, however, delayed about 2 h, and during this time a marked decrease in testosterone levels was seen. In the testes an infiltration of polymorphonuclear neutrophils (PMN) in the interstitium and histological changes among the Leydig cells were seen after ET injection. Pretreatment with FM reduced the number of invading PMN and the Leydig cells appeared less affected. The results show that FM modulated the negative effects of ET on the testicular function in the boar, indicating that the initiation of the arachidonic acid cascade was of importance for the induction of the alterations following an ET injection.


Evolutionary Metal Oxide Clusters for Novel Applications: Toward High-Density Data Storage in Nonvolatile Memories.
Because of current fabrication limitations, miniaturizing nonvolatile memory devices for managing the explosive increase in big data is challenging. Molecular memories constitute a promising candidate for next-generation memories because their properties can be readily modulated through chemical synthesis. Moreover, these memories can be fabricated through mild solution processing, which can be easily scaled up. Among the various materials, polyoxometalate (POM) molecules have attracted considerable attention for use as novel data-storage nodes for nonvolatile memories. Here, an overview of recent advances in the development of POMs for nonvolatile memories is presented. The general background knowledge of the structure and property diversity of POMs is also summarized. Finally, the challenges and perspectives in the application of POMs in memories are discussed.


In situ passivation of GaAsP nanowires.
We report on the structural and optical properties of GaAsP nanowires (NWs) grown by molecular-beam epitaxy. By adjusting the alloy composition in the NWs, the transition energy was tuned to the optimal value required for tandem III-V/silicon solar cells. We discovered that an unintentional shell was also formed during the GaAsP NW growth. The NW surface was passivated by an in situ deposition of a radial Ga(As)P shell. Different shell compositions and thicknesses were investigated. We demonstrate that the optimal passivation conditions for GaAsP NWs (with a gap of 1.78 eV) are obtained with a 5 nm thick GaP shell. This passivation enhances the luminescence intensity of the NWs by 2 orders of magnitude and yields a longer luminescence decay. The luminescence dynamics changes from single exponential decay with a 4 ps characteristic time in non-passivated NWs to a bi-exponential decay with characteristic times of 85 and 540 ps in NWs with GaP shell passivation.


Vascular surgery resident education and hands-on training in vascular laboratory testing.
Diagnostic testing performed in the noninvasive vascular laboratory is a cornerstone of care for patients with suspected or known vascular disease. The Society for Vascular Surgery has mandated that vascular surgery resident training include mentored experience in performing vascular laboratory testing and interpreting its results. The trainee should be experienced with vascular laboratory instrumentation and testing protocols, be knowledgeable in ultrasound imaging of vascular anatomy, and be competent to classify disease severity relevant to the study indication. The scope of test interpretation should include peripheral arterial, peripheral venous, cerebrovascular, and visceral abdominal testing using duplex ultrasound supplemented by indirect physiologic testing for peripheral arterial and venous disease. The emergence of endovascular therapy has expanded duplex ultrasound applications in the areas of screening, procedural imaging, and surveillance following intervention. Pre-procedure testing to assess disease location and severity, and vein mapping for dialysis access or extremity bypass grafting provide important patient-specific information that can reduce the need for more invasive vascular imaging. It is recommended that trainees acquire the hand-on skills to perform duplex testing in vascular clinic and inpatient sites, such as the emergency department and operating room. Training programs should have a structured vascular laboratory curriculum that documents annual educational milestones that encompass both test interpretation aptitude and hands-on duplex scanning skills. Before completion of training, the resident should acquire documented experience in test interpretation sufficient to take the Physician Vascular Interpretation examination, which is required for American Board of Surgery certification as a vascular surgeon.


Functional outcomes of unilateral lower limb amputee soldiers in two districts of Sri Lanka.
The purpose of this study was to describe functional outcomes of unilateral lower limb amputee soldiers, in comparison to nonamputee male subjects, and to identify factors affecting functional outcomes. Selected lower limb amputee soldiers of the Sri Lanka Army (n = 461) and matched nonamputee male subjects (n = 461) were evaluated with the prevalidated self-administered version of Short-Form Health Survey-36. A majority were below-knee amputees (n = 413; 89.6%), and the mean age was 30.2 +/- 4.6 years. Short-Form Health Survey-36 health profile scores of amputees were significantly lower than those of nonamputees (p < 0.001). The differences in profiles were largest in scales sensitive to physical health. Higher levels of amputation and problems with the stump and sound leg were significantly associated with poor physical and mental health scores. Amputee soldiers' assessment of changes in health over the past year was significantly worse than that of nonamputees (p < 0.001). The study concluded that amputees have comparatively poor functional outcomes, which could be improved by modifying some associated factors.


Comparison of rat hepatocyte and differentiated hepatoma cell line cultures as bio indicators of CYP 1A1 inducers in urban air.
Cytochrome P450 1A1 CYP1A1 enzymatic activity was evaluated in cultured liver cells, and taken as a biological indicator of the presence of inducers of this isoform in urban airborne particulate matter fraction samples. It is known that CYP1A1 inducers can play an important role in the risk of mutagenesis and carcinogenesis by environmental pollution. A romatic polycyclic hydrocarbons PAH from urban air were collected in the city of Genoa Italy at two sites on two different days of the year. The objective of the study was to compare the inducibility of cultured rat hepatocytes with that of MH1C1 and FaO rat hepatoma cell lines after exposure to a PAH mixture and to a standard compound, such as benzo b fluoranthene B b F. Cytotoxic effects of the tested concentrations were evaluated by means of 3 4,5, dimenthylthyazol 2 yl 2,5 diphenyltetrazolium bromide MTT and lactate dehydrogenase release LDH tests, the potency of inducers by ethoxyresorufin O deethylase EROD assay. The results were in agreement in the three cellular systems: after exposure to the PAH mixture, an induction at low concentrations was observed; whereas no induction, but rather a decrease in activity was shown at higher concentrations; instead, the exposure to pure B b F showed a dose-response relationship in all cells, even at the highest doses. Such a difference between the toxicity of the complex mixture and that of the pure compound could be ascribed to the presence of drug metabolism inhibitors in the mixture, or to interactions between the original components and their metabolites. The finding that the cell lines responded to the CYP1A1 induction in a very efficient way gives further proof of the applicability of this system to environmental biomonitoring.


Pedicle Temporalis Fascial Flap with Axial Scalp Flap Obviates Need of Free Flap in Extensive Scalp Wound.
Extensive scalp defect with exposed bone is best reconstructed with flaps. Majority of these wounds are now routinely reconstructed with free flaps in many centers. Free flaps however require lengthy operative time and may not be available to all patients, where possible less extensive options should thus be encouraged. A sixty-eight-year-old patient presented to us with a Marjolin's ulcer on the vertex of the scalp. After wide local excision a defect of about 17 cm and 12 cm was left. The defect was successfully covered with a combination of an ipsilateral pedicle temporalis fascial flap and an axial supraorbital scalp flap with good outcome. In conclusion wide defects of the scalp can be fully covered with a combination of local flaps. The axial scalp flap and the pedicle temporalis fascial flap where applicable provide an easy and less demanding option in covering such wounds. These flaps are reliable with good blood supply and have got less donor side morbidity.


Assessing the frequency with which primary care providers address sleep of infants and young children.
Sleep problems during early development are common and associated with negative health outcomes. Earlier recognition of poor sleep health permits earlier intervention and improved outcomes. This retrospective cohort study aimed to identify the frequency with which primary care providers assessed sleep health when completing the Rourke Baby Record for infants and young children during routine well-baby visits from 2002 to 2019. Using 1180 electronic medical records from an academic family medicine teaching clinic, we identified the frequency with which primary care providers assessed sleep health at three time intervals in child development: 1 week to 1 month; 2 months to 6 months; and 9 months to 12-13 months. Sleep variables were night waking, healthy sleep habits, and safe sleep. The frequency of having any aspect of sleep addressed was 85.4%, 90.2% and 66.7% at the three respective time intervals. There were no differences in the frequency with which sleep was assessed based on birthweight or sex. Children born during 2002-2015 were approximately half as likely to be assessed for sleep compared with those born during 2016-2019 at the second and third time intervals. In the first and second time intervals, children who were not exclusively breastfed had their sleep assessed significantly less than children who were exclusively breastfed. To our knowledge this is the first study to explore the area of sleep discussions and breastfeeding status in primary care during routine well-baby visits. These results are clinically relevant for clinicians and parents, due to the known associations between sleep issues and sudden infant death syndrome, childhood injuries, and emotional dysregulation.


Usefulness of Tranexamic Acid Administration During Sagittal Split Ramus Osteotomy.
Tranexamic acid has been used to reduce intraoperative bleeding; however, its effect on anti-inflammation and the amount of drainage after orthognathic surgery is yet to be determined. Therefore, we aimed to examine the effect of tranexamic acid on intraoperative bleeding volume and operation time, amount of drainage, and anti-inflammation after orthognathic surgery. Forty healthy women who underwent bilateral sagittal split ramus osteotomy under general anesthesia participated in this study. The amount of intraoperative bleeding, the operation time, the amount of drainage, and the C-reactive protein level were compared between patients intravenously administered with tranexamic acid before surgery (before-surgery group) and those administered with the drug after surgery (after-surgery group). All data were analyzed using the Student t-test. Results were considered to be statistically significant when P < 0.05. Although no significant difference was found in the amount of drainage between the groups (P > 0.05), significant variations were detected in the amount of bleeding during surgery (before-surgery group: 161.7 ± 45.3 mL versus after-surgery group: 270.2 ± 24.0 mL; P = 0.0009), operation time (before-surgery group: 141.3 ± 16.8 min versus after-surgery group: 166.8 ± 24.9 min; P = 0.03), and postoperative C-reactive protein level (before-surgery group: 3.77 ± 0.40 mg/dL versus after-surgery group: 5.02 ± 0.75 mg/dL; P = 0.012) between the groups. In conclusion, administering tranexamic acid before surgery was found to significantly decrease bleeding, reduce operation time, and suppress postoperative inflammation.


Lectins implicate specific carbohydrate domains in electric field stimulated nerve growth and guidance.
Both endogenous lectins and DC electric fields may control aspects of early nerve growth and nerve guidance. To test whether such endogenous cues interact, lectins of varying sugar affinity and valency were studied for effects on electric field induced growth and reorientation of cultured Xenopus neurites. Concanavalin A (Con A), succinylated concanavalin A (S-Con A), and wheat germ agglutinin all completely inhibited field-induced cathodal reorientation. Lentil and pea lectins, which share the same sugar affinity as Con A/S-Con A, were only partially effective in inhibiting reorientation. Because S-Con A does not alter lateral mobility of membrane receptors, the previously accepted notion that Con A inhibited field-induced reorientation by preventing receptors from translocating and becoming redistributed asymmetrically in the membrane may be oversimplified. There are likely to be additional steric interactions that Con A and S-Con A share that inactivate asymmetrically redistributed receptors and prevent reorientation. Additionally, nerves growing in an applied field branch more commonly toward the cathode. Con A and S-Con A alone prevented this development of asymmetric branching. All the lectins tested prevented the normal field-induced increase in nerve growth rate, while all, except peanut agglutinin, prevented the usual faster growth cathodally than anodally. We suggest that lectin interactions with electric field effects in vitro may involve modulation of neuronal nicotinic acetylcholine receptors, neurotrophin receptors, or voltage-dependent calcium channels. Similar interactions between endogenous lectins and endogenous electric fields are to be expected.


Ecological Factors of Being Bullied Among Adolescents: a Classification and Regression Tree Approach.
Being bullied is a well-recognized trauma for adolescents. Bullying can best be understood through an ecological framework since bullying or being bullied involves risk factors at multiple contextual levels. The purpose of the study was to identify the risk and protective factors that best differentiate groups along with the outcome variable of interest (being bullied) using Classification and Regression Tree (CART) analysis. The study used the Health Behavior in School-Aged Children (HBSC) data collected from a nationally representative sample of students in grades six through ten during the 2005-2006 school years. This study identified that for adolescents 12 and younger, lower parental support is a critical risk factor associated with bullying and among those 13 to 14 with lower parent support, adolescent with higher academic pressure reported experiencing more bullying. For the older group of adolescents (aged 15 and older), school related factors were identified to increase the risk level of being bullied. There was a critical age (15 years old) for implementing victimization interventions to reduce the damage from being bullied. Service providers working with adolescents aged 14 and less should focus more on family-oriented intervention and those working with adolescents aged 15 and more should offer peer- or school-related interventions.


Facile Synthesis of ZnO Nanorods/GO Composite and Its Optical Performance.
The ZnO nanorods/GO composite was fabricated by facilely covering monolayer or few-layer graphene oxide (GO) film on the uniformly distributed ZnO nanorods, which was synthesized on Si substrate using a solution method. The as-synthesized products were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), as well as X-ray diffraction (XRD). The photoluminescence (PL) measurement indicates that the ZnO nanorods have a strong ultraviolet (UV) emission centered at ~391 nm attributed to the recombination of free excitons and a defect-related visible emission centered at ~530 nm. After the nanorods were covered with GO film, the PL intensity of the composite is quenched compared to that of the bare one at the same excitation condition. The fluorescence quenching mechanism suggests that there is an interfacial charge-transfer process between the excited ZnO and the GO film, and the composite fabricated in this experiment be possible to improve the photocatalysis performance.


[Recent advances in the structural biology of the class C G protein-coupled receptors: The metabotropic Glutamate receptor 5].
Class C GPCRs, that include metabotropic glutamate receptors (mGlu), taste receptors, GABAB receptor and Calcium-sensing receptor, are unusual in terms of their molecular architecture and allosteric regulation. They all form obligatory dimers, dimerization being fundamental for their function. More specifically, the mGlu are activated by the main excitatory neurotransmitter, L-glutamate. mGlu activation by glutamate binding in the venus flytrap domain (VFT) triggers conformational changes that are transmitted, through the Cystein-Rich Domain (CRD), to the conserved fold of 7 transmembrane helices (7TM), that couples to intracellular G protein. mGlu activity can also be allosterically modulated by positive (PAM) or negative (NAM) allosteric modulators binding to the 7TM. Recent progress in cryo-electron microscopy (cryoEM) has allowed unprecedented advances in deciphering the structural and molecular basis of their activation mechanism. The agonist induces a large movement between the subunits, bringing the 7TMs together and stabilizing a 7TM conformation structurally similar to the inactive state. The diversity of inactive conformations for the class C was unexpected but allows PAM stabilising a 7TM active conformation independent of the conformational changes induced by agonists, representing an alternative mode of mGlu activation. Here we present and discuss recent structural characterisation of mGlu receptors, highlighting findings that make the class C of GPCR unique. Understanding the structural basis of mGlu dimer signaling represents a landmark achievement and paves the way for structural investigation of GPCR dimer signaling in general. Structural information will open new avenues for structure-based drug design.


Impact of Alternate Gait Training Using Knee-Ankle-Foot Orthoses with Oil Damper Ankle Hinge in Patients with Subacute Severe Hemiplegia.
Patients with severe hemiplegia along with knee instability require knee-ankle-foot orthoses (KAFOs) for gait training. However, in these patients, it is unclear which type of walking training is more effective to improve gait function. Providing alternate gait training (AGT) improves walking function in patients with spinal cord injury, but it is still unclear whether this is effective in hemiplegic stroke patients. In this study, we defined "unified AGT" as AGT performed with the same therapeutic concept by physiotherapists. We then investigated whether AGT improved gait function quicker than our traditional gait training in hemiplegic stroke patients. We enrolled 15 subjects with severe hemiplegia and knee instability who had undergone unified AGT using KAFOs with hinged oil dampers at the ankles, and 30 historical control (HC) subjects who had undergone traditional gait training. We used multiple comparison and survival analyses to analyze the differences in the functional independence measure (FIM) gait score changes between the two groups. The multiple comparison revealed a significant increase (p < 0.05) in the FIM gait score compared with its initial score in the subjects with unified AGT. However, this improvement was not seen in the HC subjects. Additionally, the survival analysis of time taken to recover revealed a significant difference between the subjects with unified AGT and HC subjects (p < 0.05). These findings suggest that unified AGT using a KAFO facilitates gait improvement in patients with severe hemiplegia and knee instability.


Cervical necrotizing fasciitis.
Cervical necrotizing fasciitis (CNF) is an aggressive infection of the head and neck with high complication and mortality rates. Sixty-eight cases of CNF have been reported in the English-language literature. We present a series of 8 patients with CNF, including 5 men and 3 women ranging in age from 25 to 92 years. To the best of our knowledge, this is one of the largest case series reported. Six of the 8 patients had a predisposing odontogenic focus of infection. Four patients had mediastinal involvement. Two patients, both with significant comorbidity at the time of presentation, died of CNF.


Aortic Valve Replacement as a Trigger of Atypical Hemolytic Uremic Syndrome.
Mechanical hemolysis is a frequent but usually harmless complication of aortic valve replacement. The most common reason is valvular leakage. This report presents atypical hemolytic uremic syndrome (aHUS) as an alternative cause of mechanical hemolysis after this procedure. aHUS is a complement-mediated disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. It necessitates immediate specific treatment including plasma exchange or complement inhibition to avoid an adverse outcome. The present case identifies aortic valve replacement as a trigger of aHUS and shows that this disease must be taken into account in the differential diagnosis of hemolysis after valve surgery.


Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion.
Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs. Unlike other commonly used substances of abuse, cocaine has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anticocaine therapies; however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered vaccine translation. We have designed and synthesized a peptide-based anti-cocaine immunogen which we have shown is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59. We have demonstrated that immunization with the reported vaccine elicits high titers of anti-cocaine IgG and prevents cocaine-induced hyperlocomotion in an in vivo murine model. This peptide-hapten immunogen along with self-adjuvanting liposomal-based delivery system provides a platform for the development of effective anti-drug vaccines.


Utilization of Formal and Informal Care by Community-Living People with Dementia: A Comparative Study between Sweden and Italy.
Background: Dementia is a public health priority with a dramatic social and economic impact on people with dementia (PwD), their caregivers and societies. The aim of this study was to contribute to the knowledge on how utilization of formal and informal care varies between Sweden and Italy. Methods: Data were retrieved from two trials: TECH@HOME (Sweden) and UP-TECH (Italy). The sample consisted of 89 Swedish and 317 Italian dyads (PwD and caregivers). Using bivariate analysis, we compared demographic characteristics and informal resource utilization. Multiple linear regression was performed to analyze factors associated with time spent on care by the informal caregivers. Results: Swedish participants utilized more frequently health care and social services. Informal caregivers in Italy spent more time in caregiving than the Swedish ones (6.3 and 3.7 h per day, respectively). Factors associated with an increased time were country of origin, PwD level of dependency, living situation, use of formal care services and occupation. Conclusions: Care and service utilization significantly varies between Sweden and Italy. The level of formal care support received by the caregivers has a significant impact on time spent on informal care. Knowledge on the factors triggering formal care resources utilization by PwD and their caregivers might further support care services planning and delivery across different countries.


[Usefulness of percutaneous microwave tissue coagulation therapy for solitary liver cancer].
The possible use of percutaneous transhepatic microwave tissue coagulation therapy (PMCT) using ultra-sonography under local anesthesia for solitary liver cancer was studied. The subjects were 8 patients having primary or metastatic liver cancer with solitary liver tumor less than 4 cm in size, consisting of 2 hepatocellular carcinomas, and 6 metastatic carcinomas. PMCT was performed continuously 3 times at the output of 30 watts for 30 seconds at a time. Tumors less than 3 cm in size were completely coagulated by irradiation from 2 to 5 times judged by enhanced CT. No recurrence of tumor was recognized in the coagulation area. But in some cases, multiple metastases were found at another site in the liver by 3 months after PMCT. Thus, the results suggest that PMCT is a useful therapy for small liver tumor as a local control.


Two-tone suppression of inner hair cell and basilar membrane responses in the guinea pig.
Recordings of receptor potentials from inner hair cells (IHCs) and the basilar membrane (BM) motion were made in pigmented guinea pigs. The acoustic stimuli were single tones near best frequency (BF) and two-tone complexes. Single tone input/output (I/O) functions had a saturating growth for the magnitude and their phase shifts were strongly dependent on the tone frequency relative to BF. For IHCs, a BF tone stimulus produced no phase shift in the ac receptor potential response. Phase lag or lead occurred for tones below or above BF, respectively. BM velocity I/O functions were not as compressively saturating as IHC ac I/O curves. BM phase shifts (in relation to BF) were similar to those of the IHCs. Two-tone suppression was observed in both IHC and BM response measures. Suppressor tones on the low-frequency side of BF produced complex suppression results, which were inconsistent with a simple attenuation model for suppression. The growth of suppression was faster than the attenuation from equivalent level reductions of the probe tone, and phase shifts were phase lead. Depending upon experimental conditions, phase change with suppression may be in the opposite direction from phase change observed from pure attenuation of the probe tone. High-frequency suppressors (relative to BF) are consistent with an attenuation model of suppression for the IHCs of the current study. High side suppression of basilar membrane velocity, however, differed from the IHCs in a systematic way. The phase change caused by suppression of BM velocity was always smaller than that of an equivalent reduction in the probe tone level.


[Diabetic ketoacidosis].
Diabetic ketoacidosis is an emergency medical condition that can be life-threatening if not treated properly. Diabetic ketoacidosis occurs most often in patients with type 1 diabetes (formerly called insulin-dependent diabetes mellitus); however, its occurrence in patients with type 2 diabetes (formerly called noninsulin-dependent diabetes mellitus) is not as rare as was once thought. This article reviews data about precipitating events, pathogenesis, carbohydrate, lipid and ketone, water and electrolyte metabolism in this hyperglycemic crisis. The review discusses diagnostic procedures, laboratory evaluation, differential diagnosis and treatment: replacement of fluid and electrolytes, low-dose insulin therapy and recommendations for use of bicarbonate. A discussion of complications management of diabetic ketoacidosis (hypoglycemia, hypokalemia, cerebral edema, hyperchloremic metabolic acidosis, pulmonary edema, adult respiratory distress syndrome), mortality rate and prevention are included in this review.


"Notice how you feel": an alternative to detached concern among hospice volunteers.
Medical schools teach physicians to practice "detached concern," a simultaneous emotional distance from and sensitivity toward their patients. Medical students learn detachment to protect themselves from emotion-laden experiences, including death and dying, by employing mechanisms of defense and adjustment, such as suppression and repression of emotions. In this study, the author inquires whether hospice volunteers are trained for and practice detached concern and finds that hospice volunteers are trained for concern. They are concerned for the well-being of patients and their families. The author argues that concern is a social product that can be trained; hospice volunteers are not trained to suppress and repress their emotions, and the hospice as an institution produces and transmits cultural norms, values, and practices surrounding death and dying, thus maintaining a pool of concerned volunteers.


[Mitochondrial encephalomyopathies: pleomorphism of the mitochondrial DNA mutations and clinical features].
Recent studies analyzing mtDNA have established to elucidate the molecular pathology of mitochondrial encephalomyopathies. The human mitochondrial genome is 16,569 bp circular double-stranded molecule that is maternally inherited. Since the first report on large deletions of mtDNA in patients with progressive external ophthalmoplegia (PEO) by Holt et al in 1988, various mtDNA mutations were found. On the basis of the recent findings of mtDNA mutations, genetic classification of mitochondrial diseases has been proposed by S DiMauro in 1991. (1) large deletions or duplications of mtDNA were found in PEO and Pearson disease. (2) A single base substitution were reported in several mitochondrial encephalomyopathies as follows: (a) At nucleotide position 11778, 4136 or 4160......Leber's hereditary optic neuritis, (b) 8344......MERRF, (c) 3243 or 3271......MELAS, (d) 8993......Holt's disease.


Assessing PDB macromolecular crystal structure confidence at the individual amino acid residue level.
Approximately 87% of the more than 190,000 atomic-level three-dimensional (3D) biostructures in the PDB were determined using macromolecular crystallography (MX). Agreement between 3D atomic coordinates and experimental data for >100 million individual amino acid residues occurring within ∼150,000 PDB MX structures was analyzed in detail. The real-space correlation coefficient (RSCC) calculated using the 3D atomic coordinates for each residue and experimental-data-derived electron density enables outlier detection of unreliable atomic coordinates (particularly important for poorly resolved side-chain atoms) and ready evaluation of local structure quality by PDB users. For human protein MX structures in PDB, comparisons of the per-residue RSCC metric with AlphaFold2-computed structure model confidence (pLDDT-predicted local distance difference test) document (1) that RSCC values and pLDDT scores are correlated (median correlation coefficient ∼0.41), and (2) that experimentally determined MX structures (3.5 Å resolution or better) are more reliable than AlphaFold2-computed structure models and should be used preferentially whenever possible.


[Examination of visual evoked potentials in persons exposed to prolonged contact with ethyl benzene vapors].
The aim of this study is an estimation of the visual evoked potentials (VEP) of persons exposed to prolonged contact with leaded petrol. A group of 90 males aged between 22 and 53, exposed to prolonged contact with leaded petrol for the period of between a few months to 30 years, was examined. Those examined were divided into three groups depending on the length of exposure: group 1 up to 10 years, group II-11-20 years, group III-20 years and more. The results were compared with those obtained from a group of 40 healthy age-matched males, not exposed to leaded petrol. In neurological and ophthalmological examinations no pathological symptoms were detected in both groups. The VEP examination was executed using pattern reversal (pr) and pattern flash (pf) stimulation. The frequent pathological record of VEP was an elongation in the latency of P-100 and reduction of response amplitude. Using pr stimulation, the reduction of the mean value of the amplitude for group III was found statistically significant (p < 0.01). In pf examination in group III mean latency of the P-100 was significantly statistically (p < 0.01) longer than in the control group. Significant reduction of the response amplitude in groups II (p < 0.01) and III (p < 0.001) was found in this type of stimulation. The results of studies indicate subclinical damage of the visual pathway particularly of persons exposed to leaded petrol vapour during work for longer than 20 years.


Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain.
The utilization of physical activity as a therapeutic tool is rapidly growing in the medical community and the role exercise may offer in the alleviation of painful disease states is an emerging research area. The development of neuropathic pain is a complex mechanism, which clinicians and researchers are continually working to better understand. The limited therapies available for alleviation of these pain states are still focused on pain abatement and as opposed to treating underlying mechanisms. The continued research into exercise and pain may address these underlying mechanisms, but the mechanisms which exercise acts through are still poorly understood. The objective of this review is to provide an overview of how the peripheral nervous system responds to exercise, the relationship of inflammation and exercise, and experimental and clinical use of exercise to treat pain. Although pain is associated with many conditions, this review highlights pain associated with diabetes as well as experimental studies on nerve damages-associated pain. Because of the global effects of exercise across multiple organ systems, exercise intervention can address multiple problems across the entire nervous system through a single intervention. This is a double-edged sword however, as the global interactions of exercise also require in depth investigations to include and identify the many changes that can occur after physical activity. A continued investment into research is necessary to advance the adoption of physical activity as a beneficial remedy for neuropathic pain. The following highlights our current understanding of how exercise alters pain, the varied pain models used to explore exercise intervention, and the molecular pathways leading to the physiological and pathological changes following exercise intervention.


Longitudinal Intravital Imaging Through Clear Silicone Windows.
Intravital microscopy (IVM) enables visualization of cell movement, division, and death at single-cell resolution. IVM through surgically inserted imaging windows is particularly powerful because it allows longitudinal observation of the same tissue over days to weeks. Typical imaging windows comprise a glass coverslip in a biocompatible metal frame sutured to the mouse's skin. These windows can interfere with the free movement of the mice, elicit a strong inflammatory response, and fail due to broken glass or torn sutures, any of which may necessitate euthanasia. To address these issues, windows for long-term abdominal organ and mammary gland imaging were developed from a thin film of polydimethylsiloxane (PDMS), an optically clear silicone polymer previously used for cranial imaging windows. These windows can be glued directly to the tissues, reducing the time needed for insertion. PDMS is flexible, contributing to its durability in mice over time-up to 35 days have been tested. Longitudinal imaging is imaging of the same tissue region during separate sessions. A stainless-steel grid was embedded within the windows to localize the same region, allowing the visualization of dynamic processes (like mammary gland involution) at the same locations, days apart. This silicone window also allowed monitoring of single disseminated cancer cells developing into micro-metastases over time. The silicone windows used in this study are simpler to insert than metal-framed glass windows and cause limited inflammation of the imaged tissues. Moreover, embedded grids allow for straightforward tracking of the same tissue region in repeated imaging sessions.


The 5' flanking region of miR-378 is hypomethylated in acute myeloid leukemia.
Aberrant expression of miR-378 has been observed in various malignancies including acute myeloid leukemia (AML). However, the mechanism regulating of miR-378 expression remains unknown. This study was aimed to investigate miR-378 methylation and to explore its clinical significance in AML. Methylation status of miR-378 5'-flanking region was investigated by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite-sequencing PCR (BSP). The expression of miR-378 was evaluated by real-time quantitative PCR (RQ-PCR). The correlation between expression of miR-378 and 5'-flanking region methylation was analyzed using 5-aza-2'-deoxycytidine (5-aza-dC) treatment. miR-378 5'-flanking region was significantly hypomethylated in AML patients compared to controls (median 0.109 vs. 0.058) (P=0.048). miR-378 expression was correlated with miR-378 5'-flanking region in leukemic cell line treated with 5-aza-dC, but not in AML patients. The level of miR-378 hypomethylation significantly increased in M2 subtype compared to other subtypes. Moreover, patients with t(8;21) harbored the highest level of miR-378 hypomethylation. However, there was no significant difference in overall survival between patients with high and low miR-378 hypomethylation. The association of miR-378 expression with methylation was not observed in AML patients, but miR-378 expression in THP-1 line was increased while methylation status of miR-378 5-flanking region was decreased after 5-aza-dC treatment. Our findings suggest that miR-378 is reactivated by demethylation after 5-aza-dC treatment. 5'-flanking region of miR-378 is hypomethylated in AML especially in those with t(8;21).


Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR-ABL-positive cells.
The development of imatinib resistance has become a significant therapeutic problem in which the etiology seems to be multifactorial and poorly understood. As of today, clinical criteria to predict the development of imatinib resistance in chronic myelogenous leukemia (CML), other than rebound of the myeloproliferation, are under development. However, there is evidence that the control of glucose-substrate flux is an important mechanism of the antiproliferative action of imatinib because imatinib-resistant gastrointestinal stromal KIT-positive tumors reveal highly elevated glucose uptake in radiologic images. We used nuclear magnetic resonance spectroscopy and gas chromatography mass spectrometry to assess (13)C glucose uptake and metabolism (glycolysis, TCA cycle, and nucleic acid ribose synthesis) during imatinib treatment in CML cell lines with different sensitivities to imatinib. Our results show that sensitive K562-s and LAMA84-s BCR-ABL-positive cells have decreased glucose uptake, decreased lactate production, and an improved oxidative TCA cycle following imatinib treatment. The resistant K562-r and LAMA84-r cells maintained a highly glycolytic metabolic phenotype with elevated glucose uptake and lactate production. In addition, oxidative synthesis of RNA ribose from (13)C-glucose via glucose-6-phosphate dehydrogenase was decreased, and RNA synthesis via the nonoxidative transketolase pathway was increased in imatinib-resistant cells. CML cells which exhibited a (oxidative/nonoxidative) flux ratio for nucleic acid ribose synthesis of >1 were sensitive to imatinib. The resistant K562-r and LAMA84-r exhibited a (oxidative/nonoxidative) flux ratio of <0.7. The changes in glucose uptake and metabolism were accompanied by intracellular translocation of GLUT-1 from the plasma membrane into the intracellular fraction in sensitive cells treated with imatinib, whereas GLUT-1 remained located at the plasma membrane in LAMA84-r and K562-r cells. The total protein load of GLUT-1 was unchanged among treated sensitive and resistant cell lines. In summary, elevated glucose uptake and nonoxidative glycolytic metabolic phenotype can be used as sensitive markers for early detection of imatinib resistance in BCR-ABL-positive cells.


Identification of yeast meiosis-specific genes by differential display.
Meiosis, a specialized cell division process, occurs in all sexually reproducing organisms. During this process a diploid cell undergoes a single round of DNA replication followed by two rounds of nuclear division to produce four haploid gametes. In yeast, the meiotic products are packaged into four spores that are enclosed in a sac known as an ascus. To enhance our understanding of the meiotic developmental pathway and spore formation, we followed differential expression of genes in meiotic versus vegetatively growing cells in the yeast Saccharomyces cerevisiae. Such comparative analyses have identified five different classes of genes that are expressed at different stages of the sporulation program. We identified several meiosis-specific genes including some already known to be induced during meiosis. Here we describe one of these previously uncharacterized genes, SSP1, which plays an essential role in meiosis and spore formation. SSP1 is induced midway through meiosis, and the homozygous mutant-diploid cells fail to sporulate. In ssp1 cells, meiosis is delayed, nuclei fragment after meiosis II, and viability declines rapidly. The ssp1 defect is not related to a microtubule-cytoskeletal-dependent event and is independent of two rounds of meiotic divisions. Our results suggest that Ssp1 is likely to function in a pathway that controls meiotic nuclear divisions and coordinates meiosis and spore formation. Functional analysis of other uncharacterized genes is underway.


[Grand mal like attack by interferon injection in case of renal cell carcinoma].
We performed a radical nephrectomy for renal cell carcinoma on a 60-year-old female. We began to give alpha-interferon (natural type), she had an attack of tonic clonic convulsion (like grand mal attack). There were no abnormal findings in head computed tomography, nor hematologic tests. We ascribed the attack to interferon, and stopped giving it. Because there was an abnormal wave in EEG, she was given an anti-convulsant per os. One month later, the electroencephalogram became normal and she showed no neurological symptoms nor findings.


Specific psychological and behavioral symptoms of depression in patients with dementia.
Behavioral and psychological symptoms in dementia (BPSD) are very common, with 90% of patients experiencing at least one during the course of the disease. One-third of persons with dementia have depressive symptoms, and concomitant BPSD are very likely. This study aimed to characterize the psychological and behavioral manifestations of depression in patients with dementia. We recruited patients with dementia from several nursing homes in the Limousin region of France. Depression was as diagnosed by the Cornell Scale for Depression in Dementia (CSDD) with a cut-off of 7, and BPSD were assessed using the Neuropsychiatric Inventory (NPI). Of 319 patients with dementia, 42.9% (n =137) were depressed and 75.9% (n = 242) had BPSD. All BPSD were significantly (p < 0.0001) more prevalent among depressed patients, but no significant differences were observed according to sex and age. The NPI showed that the most common additional symptoms in depressed patients were agitation (43.2%), anxiety (42.3%) and irritability (40.1%). Four NPI-based factors were indentified (63.9% of the common variance): factor 1 (disinhibition, irritability, agitation, anxiety), factor 2 (sleep disturbance, aberrant motor behavior, apathy), factor 3 (elation, hallucination, delirium) and the last with eating disorders. Depression in dementia patients was significantly associated with disinhibition, irritability, agitation, and anxiety. BPSD are common and a major problem. Before addressing them as isolated symptoms, it is important to consider comorbidity with depression in order to optimize the therapeutic approach.


Determinants of migration values and expectations in rural Thailand.
"Based on the argument that values and expectations underlie behavioral motives, this study explores the determinants of migration-related values and expectations, and whether they are intervening factors in explaining intentions to move among residents of rural northeast Thailand. Data from the 1992 National Migration Survey of Thailand identify four migration-related value-expectancy dimensions: income, affiliation, stimulation, and comfort. Logistic regression analysis shows that landownership and being married are associated with higher expectations, while a diversified village economy, a village economy development program, and a younger and extended household structure are associated with lower expectations of attaining valued goals in the local rural village. The analysis also shows that value-expectancy concepts are only partial intervening explanations for intentions to move or stay."


[Radiation-induced leiomyosarcoma of the dura mater: a case report].
A 31-year-old man underwent total resection for a fibrillary astrocytoma in the right frontal lobe followed by 6MV x-ray radiotherapy. The portal field size was a square of 8 cm x 7 cm, and the total dose of irradiation was 50Gy, with single fractions of 2Gy. For the next 6.5 years there was no recurrence of the astrocytoma. At 38 years of age, the patient noticed a subcutaneous mass in the scar of the previous operation and developed generalized convulsive seizures. MRI revealed a dural tumor within the previous radiation field, and the tumor was partially removed. Histologically, it was diagnosed as a leiomyosarcoma. This dural sarcoma satisfies the widely used criteria for definition of radiation-induced malignancies first described by Cahan et al. Both the clinical features and the possible histogenesis of this secondary tumor are briefly discussed.


Evaluation of uncalibrated preferential flow models against data for isoproturon movement to drains through a heavy clay soil.
The uncalibrated predictive ability of four preferential flow models (CRACK-NP, MACRO/MACRO_DB, PLM, SWAT) has been evaluated against point rates of drainflow and associated concentrations of isoproturon from a highly structured and heterogeneous clay soil in the south of England. Data were available for four plots for a number of storm events in each of three successive growing seasons. The mechanistic models CRACK-NP and MACRO generally gave reasonable estimates of drainflow over the three seasons, but under-estimated concentrations of isoproturon over a prolonged period in the first season and over-estimated them in the two remaining seasons. CRACK-NP simulated maximum concentrations of isoproturon over the first two events of each of the three seasons of 156, 527 and 24.4 micrograms litre-1, respectively, and matched the observed data (465, 65.1 and 0.65 micrograms litre-1) slightly better than MACRO (69.1, 566 and 58.5 micrograms litre-1). Automatic selection of parameters from soils information within MACRO_DB reduced the emphasis on preferential flow relative to the stand-alone version of MACRO. This gave a poor simulation of isoproturon breakthrough and simulated maximum concentrations were 0, 50.1 and 35.1 micrograms litre-1, respectively. The capacity model PLM gave the best overall simulation of total drainflow for the first two events in each season, but over-estimated concentrations of isoproturon (967, 808 and 51.3 micrograms litre-1). The simple model SWAT represented total drainflow reasonably well and gave the best simulation of maximum isoproturon concentrations (140, 80.2 and 8.2 micrograms litre-1). There was no clear advantage here in using the mechanistic models rather than the simpler models. None of the models tested was able to simulate consistently the data set, and uncalibrated modelling cannot be recommended for such artificially drained heavy clay soils.


Antimicrobial Peptides and Macromolecules for Combating Microbial Infections: From Agents to Interfaces.
Bacterial resistance caused by the overuse of antibiotics and the shelter of biofilms has evolved into a global health crisis, which drives researchers to continuously explore antimicrobial molecules and strategies to fight against drug-resistant bacteria and biofilm-associated infections. Cationic antimicrobial peptides (AMPs) are considered to be a category of potential alternative for antibiotics owing to their excellent bactericidal potency and lesser likelihood of inducing drug resistance through their distinctive antimicrobial mechanisms. In this review, the hitherto reported plentiful action modes of AMPs are systematically classified into 15 types and three categories (membrane destructive, nondestructive membrane disturbance, and intracellular targeting mechanisms). Besides natural AMPs, cationic polypeptides, synthetic polymers, and biopolymers enable to achieve tunable antimicrobial properties by optimizing their structures. Subsequently, the applications of these cationic antimicrobial agents at the biointerface as contact-active surface coatings and multifunctional wound dressings are also emphasized here. At last, we provide our perspectives on the development of clinically significant cationic antimicrobials and related challenges in the translation of these materials.


Pseudoaneurysm of peroneal artery after ankle arthroscopy.
ankle arthroscopy increased its role in the diagnosis and treatment of pathology of the ankle since 1970s. Although the benefits are well established, ankle arthroscopy is associated with a definite risk of complications, especially neurological. The incidence rate of vascular complication after anterior ankle arthroscopy has been reported. we review the literature on vascular complications after anterior ankle arthroscopy especially pseudoaneurysm and a case report of a peronal artery pseudoaneurysm was reported. vascular complications after an anterior ankle arthroscopy are extremely rare but orthopaedic surgeons should be wary of this chance. Among vascular complications after an anterior ankle arthroscopy, peroneal artery pseudoaneurysm to our knowledge never has been described until now.


Electromotive drug administration to the urinary bladder: an animal model and preliminary results.
Electromotive drug delivery (EMDA) is the use of an electrical field to enhance penetration of ionized drugs into local tissues. Intraurinary EMDA may be of value in the treatment of various pathological conditions involving the urinary bladder, prostate gland and urethra. We have developed an animal model to study this hypothesis. Anesthetized adult mongrel dogs were studied. An intravesical anode was inserted through a Foley catheter into the urinary bladder. Two patch electrodes were positioned on the animals' abdominal skin. Both skin and intravesical electrodes were attached to a direct current generator. The bladder was then distended with an anionic blue dye (methylene blue). Fifteen milliamperes (15 mA) pulsed direct current was applied for 40 minutes. After EMDA, the bladder was surgically removed and representative sections of full thickness bladder wall were immediately frozen in liquid nitrogen. Methylene blue was used to visually demonstrate EMDA-enhanced anion penetration into bladder submucosa and muscularis. This experimental model demonstrates significant submucosal and muscularis methylene blue penetration in the presence of the electric field. Electromotive drug delivery technology may have applications for treating bladder pathology.


Clinical and functional outcomes of a novel transosseous device to treat rotator cuff tears: A minimum 2-year follow-up.
Despite the improvements in the repair equipment techniques of rotator cuff, a gold standard method has not been defined yet and transosseous fixation through deltoid-splitting (mini-open) approach is still regarded as a good option. The primary purpose of this study is to present satisfactory clinical and functional outcomes with a novel transosseous device in full-thickness rotator cuff tear through deltoid-splitting. This retrospective study was performed on 70 consecutive patients who underwent surgery by a single surgeon from June 2014 to June 2016 for a full-thickness rotator cuff tear and was managed with a novel transosseous device. Total number of patients, mean age, percentage of male and female patients, mean duration of follow-up, percentage of involvement of the dominant extremity, affected shoulder, and tear size were recorded. Functional and clinical outcomes were assessed baseline and postoperatively at 3 and 6 months and final follow-up using Disabilities of the Arm, Shoulder and Hand (Q-DASH) and Constant-Murley scores. A total of 70 (49 (70%) female, 21 (30%) male) patients whose mean age was 58.66 ± 9.19 (38-77) years were included. The mean surgery time was 35.33 ± 5.34 (28-55) min. The mean follow-up time was 28.31 ± 3.03 (24-36) months. According to the DeOrio and Cofield classification, 15 (21.43%) tears were small, 33 (47.14%) medium, 16 (22.86%) large, and 6 (8.57%) massive. By the final follow-up, the mean Constant-Murley score had significantly improved from 27.67 ± 7.46 (13-41) to 81.25 ± 3.77 (74-87; p = 0.0001) and the Q-DASH score had decreased from 82.34 ± 10.37 (65.91-100) to 10.28 ± 6.88 (0-23.45; p = 0.0001). There were no significant differences in the Constant-Murley or Q-DASH score at baseline-final follow-up between the small, medium, large, and massive tear groups (p > 0.05). Treatment of full-thickness rotator cuff tear using this novel transosseous device significantly improved functional and clinical scores. However, further long-term prospective randomized multicenter trials involving comparative studies are necessary to confirm these findings.


Influence of light and ambient carbon dioxide concentration on nitrate assimilation by intact barley seedlings.
The influence of light, dark, and ambient CO(2) on nitrate assimilation in 8- to 9-day-old barley seedlings was studied. To develop the photosynthetic apparatus fully, the seedlings were grown in nitrogen-free Hoagland solution for 5 days in darkness followed by 3 days in continuous light.The seedlings reduced nitrate and nitrite in both light and dark, although more slowly in darkness. The slower nitrate reduction in darkness was not due to decreased uptake, since the steady-state internal concentration of nitrate was doubled. The faster nitrate reduction in light was attributed to recent products of photosynthetic CO(2) fixation supplying reducing energy, possibly by shuttle reactions between chloroplasts and cytoplasm. In carbohydrate-deficient tissue, it appeared that recently fixed photosynthate could supply all of the energy required for nitrate reduction. When sufficient metabolites were present in the green tissue, light was not obligatory for the reduction of nitrate and nitrite.


Effect of alterations in blood volume on cardiac function during maximal exercise.
Recently, we proposed that the higher stroke volume (SV) and cardiac output (Q) of endurance-trained (ETR) versus untrained (UTR) individuals are attributable primarily to the enhanced diastolic filling of ETR consequent to a larger blood volume (BV). To test this hypothesis, we examined the effects of manipulating BV on the cardiac function of six ETR and six UTR males. Both groups were examined in the control BV condition (BVctl), then ETR were examined immediately following a 500 mL reduction in BV (BVred) and UTR were examined immediately following a 500 mL expansion of BV (BVexp). In BVctl, compared with UTR, ETR had significantly greater BV (16%), maximal diastolic filling rate (47.4%), maximal ventricular emptying rate (24.6%), SVmax (31.6%), Qmax (29%) and VO2max (54.5%). Following BVexp in UTR, there were immediate significant increases in maximal diastolic filling rate (22.5%), SVmax (9.1%), Qmax (8.9%), and VO2max (12.7%). Following BVred in ETR there were immediate significant decreases in maximal diastolic filling rate (27%), SVmax (14.3%), Qmax (14.7%), and VO2max (7.0%). Maximal systolic emptying rate did not change significantly following BVred or BVexp. We conclude that changes in SV and Q consequent to alterations in BV are attributable primarily to changes in diastolic function, and the majority of the higher diastolic filling rate of ETR is due to their larger BV.


Wake-promoting pharmacotherapy for psychiatric disorders.
Medications promoting wakefulness are currently used in psychopharmacology in different contexts and with different objectives. In particular, they may be used for the treatment of syndromes that primarily show significant impairment in alertness/wakefulness (e.g., excessive sleepiness and other sleep disorders) as well as for the symptomatic treatment of different neuropsychiatric disorders that, in turn, are not exclusively characterized by sleep-wake disturbances (like mood disorders, for instance). In addition, several psychotropic compounds, including some antipsychotics, mood stabilizers, antidepressants, and anxiolytics have well-established sedating side effects that may go beyond the therapeutic target and require the symptomatic use of wake-promoting agents. Even though such a clinical scenario reflects millions of individuals affected (alterations of wakefulness have a prevalence rate of 20-43% in the general population), relatively few pharmacotherapies are available, mainly including compounds with psychostimulating effects, such as methylphenidate, modafinil, and armodafinil and some amphetaminic agents. In light of their side effects and potential for abuse, such compounds have received FDA approval only for a limited number of psychiatric disorders. Nonetheless, their clinical application has recently become more widespread, including attention deficit hyperactivity disorder, narcolepsy, treatment-resistant depression, bipolar disorder, shift work sleep disorder, schizophrenia, and addictions. Wake-promoting agents have different mechanisms of action, peculiar clinical strengths and specific limitations, with novel drugs in the field under extensive investigation. The present review is aimed to provide an updated overview of the aforementioned compounds as well as investigational drugs in the field, in terms of mechanism of action, indications and use in clinical practice.


A Comparison of Common Plastic Surgery Operations Using the NSQIP and TOPS Databases.
Both the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and the American Society of Plastic Surgeons Tracking Operations and Outcomes for Plastic Surgeons (TOPS) databases track 30-day outcomes. Using the 2008-2016 TOPS and NSQIP databases, we compared patient characteristics and postoperative outcomes for 5 common plastic surgery procedures. A weighted TOPS population was used to mirror the NSQIP population in clinical and demographic characteristics to compare postoperative outcomes. We identified 154,181 cases. Compared with NSQIP patients, TOPS patients were more likely to be younger (47.9 versus 50.0 years), have American Society of Anesthesiologists class I-II (92.1% versus 74.6%), be outpatient (66.0% versus 49.3%), and be smokers (18.7% versus 11.7%). TOPS had extensive missing data: body mass index (40.6%), American Society of Anesthesiologists class (34.9%), diabetes (39.3%), and smoking status (37.2%). NSQIP was missing <1% of all shared categories except race (15.6%). The entire TOPS cohort versus only TOPS patients without missing data had higher rates of dehiscence (5.1% versus 3.5%) and infection (2.1% versus 1.7%). TOPS versus NSQIP patients had higher dehiscence rates (5.1% versus 1.0%) but lower rates of return to the operating room (3.1% versus 6.6%), infection (2.1% versus 3.0%), and medical complications (0.3% versus 2.2%). Nonweighted and weighted TOPS cohorts had similar 30-day outcomes. NSQIP and TOPS populations are different in characteristics and outcomes, likely due to differences in collection methodology and the types physicians using the databases. The strengths of each dataset can be used together for research and quality improvement.


The universally conserved prokaryotic GTPases.
Members of the large superclass of P-loop GTPases share a core domain with a conserved three-dimensional structure. In eukaryotes, these proteins are implicated in various crucial cellular processes, including translation, membrane trafficking, cell cycle progression, and membrane signaling. As targets of mutation and toxins, GTPases are involved in the pathogenesis of cancer and infectious diseases. In prokaryotes also, it is hard to overestimate the importance of GTPases in cell physiology. Numerous papers have shed new light on the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the stress response, and other cellular processes. Moreover, bacterial GTPases have been identified as high-potential drug targets. A key paper published over 2 decades ago stated that, "It may never again be possible to capture [GTPases] in a family portrait" (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature 348:125-132, 1990) and indeed, the last 20 years have seen a tremendous increase in publications on the subject. Sequence analysis identified 13 bacterial GTPases that are conserved in at least 75% of all bacterial species. We here provide an overview of these 13 protein subfamilies, covering their cellular functions as well as cellular localization and expression levels, three-dimensional structures, biochemical properties, and gene organization. Conserved roles in eukaryotic homologs will be discussed as well. A comprehensive overview summarizing current knowledge on prokaryotic GTPases will aid in further elucidating the function of these important proteins.


Use of a codified medication process for documentation of home medications.
To determine the quality and completeness of the list of home medications documented by nurses using a codified process, authors conducted a comparative study of home medications using a non-codified and codified process for documentation of required data fields including drug, dose, route of administration, frequency, and schedule. Each documented home medication (DHM) was evaluated based on the ability to convert to an inpatient medication order. The home medication was classified as non-convertible if one or more of the required data fields were missing, inaccurate, or incomplete. The study compared 176 patients with 1618 DHM in the non-codified group to 94 patients with 646 DHM in the codified group. All DHM could be converted to inpatient orders for 70% of the patients in the codified group compared with 42% in the non-codified group. Based on each DHM, the codified process resulted in 92% of the DHM being able to convert to inpatient orders compared with 82% for the non-codified process. Authors conclude that use of a codified process to document home medications has the potential to increase the number of complete drug entries and in the number of patients with a DHM list in which all of the medication entries have all of the dosing information.


The dynamics of goal-directed rhythmical aiming.
Based on the kinematics of goal-directed aiming movements in a reciprocal Fitts' task, a minimal limit cycle model is proposed that is capable of producing the behavior observed at levels of task difficulty ranging from 3 to 7. From graphical and statistical analyses of the phase planes, Hooke's planes and velocity profiles, we concluded that the minimal terms to be included in the model were (i) a nonlinear damping in the form of a self-sustaining, velocity-driven Rayleigh oscillator and (ii) a nonlinear stiffness in the form of a softening spring Duffing term. The model reproduced the kinematic patterns experimentally observed in rhythmical precision aiming, accounting for 95% of the variance. The coefficients in the model changed in a systematic way when distance and precision constraints were varied, and the meaning of these changes is discussed in the framework of the dynamical patterns approach.


Enhanced expression of the immunoregulator, p43-placental isoferritin, in Down's syndrome placentae and fetal kidneys.
Human placental isoferritin is composed of a 43 kDa subunit and ferritin light chains. It acts as an immunosuppressive cytokine in normal gestation and in some malignant conditions. We investigated p43-placental isoferritin expression at the maternal fetal tissue interface and in fetal kidneys in Down's syndrome (DS) compared with normal control samples. Following termination of mid-gestation pregnancies placental and fetal kidney tissue samples were collected. Immunohistochemical analysis of the specimens was performed using a monoclonal antibody generated against human p43-placental isoferritin protein (CM-H-9 mAb). Expression of p43-placental isoferritin was detected in Hofbauer cells and in the syncytial layer of placental tissue. Significantly higher numbers of positive Hofbauer cells were detected in DS placentae at 17 weeks gestation compared with the controls. The number of immunopositive Hofbauer cells decreased in DS placentae at 20 weeks gestation, 3 weeks later than in controls. In kidneys of fetuses at 17 weeks gestation, p43-placental isoferritin immunoreactivity was confined to the proximal tubules of the nephrons. DS kidneys had higher staining intensities compared with similar gestational age controls. Enhanced expression of p43-placental isoferritin was observed in DS placentae and fetal kidneys. This may explain the increased p43-placental isoferritin levels in the maternal serum of DS gestations.


Development of a CE-MS method for the study of riociguat and metabolite M1 in pharmaceutical analysis.
Riociguat is a novel antihypertensive drug for the treatment of pulmonary hypertension. We present electrophoretic characterization, i.e. migration behavior of riociguat and metabolite M1 as support for optimized CZE/MS assay. Fundamental separation parameters, such as peak width, symmetry, and resolution are studied in a series of ammonium formate buffers within pH range 2.60-5.61. The narrow region of peak symmetry lies close to pH 4.0 for both analytes. Accordingly, the value of resolution maximizes in a background electrolyte adjusted to pH 4.10. Basic calibration parameters estimated from CZE experiments with absorption photometric and mass spectrometric detection of riociguat and metabolite M1 were evaluated. More than three orders lower LOD was achieved with high resolution mass spectrometric detection. The observed difference in the sensitivity of both detection techniques gives priority to the utilization of CZE/MS in practice. The values of dissociation constants of riociguat and metabolite M1, pKBH , were determined from CZE measurements in lithium formate and lithium acetate background electrolytes with constant ionic strength. The value of pKBH = 4.30 ± 0.02 for riociguat corresponds well to the value already presented in the literature. According to our observation, metabolite M1 behaves like a slightly stronger base with estimated pKBH = 4.40 ± 0.02.


Collagen type III alpha I is a gastro-oesophageal reflux disease susceptibility gene and a male risk factor for hiatus hernia.
Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal disorder with a genetic component. Our aim was to identify genetic factors associated with GORD. Four separate patient cohorts were analysed using a step-wise approach. (1) Whole genome linkage analysis was performed in 36 families. (2) Candidate genes were tested for GORD association in a trio cohort. (3) Genetic association was replicated in a case-control cohort. We also investigated genetic association to hiatus hernia (HH). (4) Protein expression was analysed in oesophageal biopsies. A region on chromosome 2, containing collagen type III alpha 1 (COL3A1), was identified (LOD = 3.3) in families with dominant transmission of GORD, stratified for hiatus hernia (HH). COL3A1 showed significant association with GORD in an independent paediatric trio cohort (p(corr) = 0.003). The association was male specific (p(corr) = 0.018). The COL3A1 association was replicated in an independent adult case control cohort (p(corr) = 0.022). Moreover, male specific association to HH (p(corr) = 0.019) was found for a SNP not associated to GORD. Collagen type III protein was more abundant in oesophageal biopsies from male patients with GORD (p = 0.03). COL3A1 is a disease-associated gene in both paediatric and adult GORD. Furthermore, we show that COL3A1 is genetically associated with HH in adult males. The GORD- and HH-associated alleles are different, indicating two separate mechanisms leading to disease. Our data provides new insight into GORD aetiology, identifying a connective tissue component and indicating a tissue remodelling mechanism in GORD. Our results implicate gender differences in the genetic risk for both for GORD and HH.


Iatrogenic copper deficiency associated with long-term copper chelation for treatment of copper storage disease in a Bedlington Terrier.
A 9-year-old Bedlington Terrier was evaluated because of weight loss, inappetence, and hematemesis. Copper storage disease had been diagnosed previously on the basis of high hepatic copper concentration. Treatment had included dietary copper restriction and administration of trientine for chelation of copper. A CBC revealed microcytic hypochromic anemia. High serum activities of liver enzymes, high bile acid concentrations, and low BUN and albumin concentrations were detected. Vomiting resolved temporarily with treatment, but the clinicopathologic abnormalities persisted. Results of transcolonic portal scintigraphy suggested an abnormal shunt fraction. Results of liver biopsy and copper quantification revealed glycogen accumulation and extremely low hepatic copper concentration. Serum and hair copper concentrations were also low. Chelation and dietary copper restriction were tapered and discontinued. Clinical signs and all clinicopathologic abnormalities improved during a period of several months.


Development and feasibility of 4 checklists for the evaluation of comorbidity in patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis: GECOAI Project.
To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients' association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice.


Pre-eclampsia is a risk factor of carotid artery atherosclerosis.
A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007 to -0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. Our data suggest that pre-eclampsia is an independent risk factor as regards developing plaque later in life.


Cohesin biology meets the loop extrusion model.
Extensive research has revealed that cohesin acts as a topological device, trapping chromosomal DNA within a large tripartite ring. In so doing, cohesin contributes to the formation of compact and organized genomes. How exactly the cohesin subunits interact, how it opens, closes, and translocates on chromatin, and how it actually tethers DNA strands together are still being elucidated. A comprehensive understanding of these questions will shed light on how cohesin performs its many functions, including its recently proposed role as a chromatid loop extruder. Here, we discuss this possibility in light of our understanding of the molecular properties of cohesin complexes.


Inflammation-Stimulated MSC-Derived Small Extracellular Vesicle miR-27b-3p Regulates Macrophages by Targeting CSF-1 to Promote Temporomandibular Joint Condylar Regeneration.
Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied in recent years. sEV contents change with the secreting cell state. When MSCs are exposed to an inflammatory environment, they release more functional growth factors, exosomes, and chemokines. Herein, MSCs are stimulated to alter sEV cargos and functions to regulate the inflammatory microenvironment and promote tissue regeneration. Sequencing of sEV miRNAs shows that certain RNAs conducive to cell function are upregulated. In this study, in vitro cell function experiments show that both inflammation-stimulated adipose-derived MSC (ADSC)-derived sEV (IAE) and normal ADSC-derived sEV (AE) promote cell proliferation; IAE also significantly improves cell migration. Regarding macrophage polarization regulation, IAE significantly promotes M2 macrophage differentiation. RNA-sequencing analysis indicates that high miR-27b-3p expression levels in IAE may regulate macrophages by targeting macrophage colony-stimulating factor-1 (CSF-1). In vivo, a rabbit temporomandibular joint (TMJ) condylar osteochondral defect model shows that both AE and IAE promote TMJ regeneration, with IAE having the most significant therapeutic effect. Therefore, the authors confirm that exposing MSCs to an inflammatory environment can feasibly enhance sEV functions and that modified sEVs achieve better therapeutic effects.


Exencephaly-anencephaly sequence: proof by ultrasound imaging and amniotic fluid cytology.
We present and discuss major current theories about the developmental natural history of the anencephalic human fetus. We confirm previous observations made using transvaginal ultrasonography of exencephalic fetuses which were later imaged and/or delivered as anencephalic fetuses. We explore the possibility of proving the theory of the slowly rubbed-off exposed brain tissue by cytologic examination and special staining of aspirated cells in amniotic fluid. Three fetuses with a typical sonographic picture of exencephaly at 13-15 postmenstrual weeks underwent amniocentesis. The aspirated fluid contained pathognomonic neural cells. The same fetuses later showed the characteristic sonographic and postabortion picture of anencephaly. Our results support the theory that exencephaly is the forerunner of anencephaly.


Using reflective clothing to enhance the conspicuity of bicyclists at night.
Bicycling at night is more dangerous than in the daytime and poor conspicuity is likely to be a contributing factor. The use of reflective markings on a pedestrian's major joints to facilitate the perception of biological motion has been shown to greatly enhance pedestrian conspicuity at night, but few corresponding data exist for bicyclists. Twelve younger and twelve older participants drove around a closed-road circuit at night and indicated when they first recognized a bicyclist who wore black clothing either alone, or together with a reflective bicycling vest, or a vest plus ankle and knee reflectors. The bicyclist pedalled in place on a bicycle that had either a static or flashing light, or no light on the handlebars. Bicyclist clothing significantly affected conspicuity; drivers responded to bicyclists wearing the vest plus ankle and knee reflectors at significantly longer distances than when the bicyclist wore the vest alone or black clothing without a vest. Older drivers responded to bicyclists less often and at shorter distances than younger drivers. The presence of a bicycle light, whether static or flashing, did not enhance the conspicuity of the bicyclist; this may result in bicyclists who use a bicycle light being overconfident of their own conspicuity at night. The implications of our findings are that ankle and knee markings are a simple and very effective approach for enhancing bicyclist conspicuity at night.


RAP-011 augments callus formation in closed fractures in rats.
ACE-011 is a bone anabolic agent generated by fusing the extracellular domain of the Activin Type 2A receptor (ActRIIA) to an IgG-Fc. The orthopedic utility of ACE-011 was investigated using a murine analogue, RAP-011. Initially, a rat closed fracture model was tested using bi-weekly (biw) 10 mg/kg RAP-011. RAP-011 significantly increased callus length and callus bone volume (BV, +43% at 6w, p < 0.01). The polar moment of inertia was calculated to be substantively increased (+80%, p < 0.01), however mechanical bending tests showed a more modest increase in maximum load to failure (+24%, p < 0.05). Histology indicated enhanced appositional bone growth, but it was hypothesized that reduced remodeling, evidenced by decreased serum CTX (-16% at 6w, p < 0.01), could be compromising bone quality in the callus. A second closed fracture study was performed to examine lower "pulse" [RAP-011(p)] and "sustained" [RAP-011(s)] regimens of biw 0.6mg/kg × 2, 0.35mg/kg × 3 and 0.18mg/kg × 2, 0.1mg/kg × 7 respectively, compared with PTH(1-34) (25 μg/kg/d) and vehicle controls. RAP-011 treatments gave modest increases in callus length and callus BV at 6w (p < 0.01), but did not achieve an increase in maximum load over vehicle. In summary, RAP-011 is effective in promoting bone formation during repair, but optimizing callus bone quality will require further investigation.


Beyond Fetal Immunity: A Systematic Review and Meta-Analysis of the Association Between Antenatal Corticosteroids and Retinopathy of Prematurity.
Background: Retinopathy of prematurity (ROP) is a major cause of childhood blindness. Antenatal corticosteroids (ACS) exposure is known to ameliorate the risk of and mortality of neonatal morbidities. However, the effect of ACS on ROP development is currently unknown. We conducted a meta-analysis with up-to-date evidence to assess the association between ACS exposure and the development of ROP in at-risk preterm infants. Methods: PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were systematically searched from inception to May 2021, supplemented with manual search from reference lists. Studies with a control group reporting ROP rate in ACS-exposed infants were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated utilizing a random-effects model. The Newcastle-Ottawa Scale was used for assessment of risk of bias in the included studies. Meta-regressions were performed to explore the predictive role of confounders for between-study variance. Results: A total of 63 studies, involving 196,264 infants, were included. Meta-analysis showed ACS exposure was not associated with ROP occurrence (uOR 0.92, 95% CI 0.80-1.07; aOR 0.87, 95% CI 0.7-1.08). Results from extremely immature subgroups revealed significant reduced risks of ROP occurrence in ACS-exposed infants. ACS exposure was associated with significantly lower odds of ROP progression in adjusted analysis (aOR 0.48, 95% CI 0.26-0.89) instead of unadjusted analysis (uOR 0.86, 95% CI 0.68-1.08). Meta-regression showed birth weight and patent ductus arteriosus of the cohort were associated with ROP occurrence, sample size and study design strongly associated with ROP progression in ACS-exposed infants. Conclusion: ACS treatment may decrease, but not prevent, the severity of ROP. Findings from severe ROP should be interpreted with caution owing to limited studies and the possibility of false-positive results. Considering the particular benefits in extremely immature infants, we recommend routine usage of ACS in mothers with threatened delivery to this particular birth cohort to prevent ROP occurrence. Future studies adjusting for major confounders are warranted to mitigate risk of bias in such observational evidence.


Evaluation of clinical characteristics and pre-biopsy impressions of primary Merkel cell carcinoma of the skin.
Merkel cell carcinoma is an aggressive carcinoma of the skin notable for protean presentation on physical exam. A retrospective cohort of 232 patients with primary cutaneous Merkel cell carcinoma was reviewed for availability of data on pre-biopsy clinical differential diagnosis based on clinical exam. Data was available for 192 patients (83%). The three most common impressions were cyst (33.3%), basal cell carcinoma (31.8%), and squamous cell carcinoma (19.8%). Merkel cell carcinoma was correctly suspected in only 13 cases (6.8%). A greater proportion of lesions that were less than or equal to 2 cm in diameter (10.2%) or carried BCC as a co-diagnosis (11.5%) were correctly suspected as Merkel cell carcinoma prior to biopsy, versus lesions greater than 2 cm in diameter (1.6%) or carrying SCC as a co-diagnosis (2.6%), suggesting that clinicians may be anchoring on the well-publicized concept of Merkel cell carcinoma as a small, pearly papule in real-world practice.