Automatic brain segmentation in preterm infants with post-hemorrhagic hydrocephalus using 3D Bayesian U-Net.
Post-hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH) in very preterm infants. PHH monitoring and treatment decisions rely heavily on manual and subjective two-dimensional measurements of the ventricles. Automatic and reliable three-dimensional (3D) measurements of the ventricles may provide a more accurate assessment of PHH, and lead to improved monitoring and treatment decisions. To accurately and efficiently obtain these 3D measurements, automatic segmentation of the ventricles can be explored. However, this segmentation is challenging due to the large ventricular anatomical shape variability in preterm infants diagnosed with PHH. This study aims to (a) propose a Bayesian U-Net method using 3D spatial concrete dropout for automatic brain segmentation (with uncertainty assessment) of preterm infants with PHH; and (b) compare the Bayesian method to three reference methods: DenseNet, U-Net, and ensemble learning using DenseNets and U-Nets. A total of 41 T2 -weighted MRIs from 27 preterm infants were manually segmented into lateral ventricles, external CSF, white and cortical gray matter, brainstem, and cerebellum. These segmentations were used as ground truth for model evaluation. All methods were trained and evaluated using 4-fold cross-validation and segmentation endpoints, with additional uncertainty endpoints for the Bayesian method. In the lateral ventricles, segmentation endpoint values for the DenseNet, U-Net, ensemble learning, and Bayesian U-Net methods were mean Dice score = 0.814 ± 0.213, 0.944 ± 0.041, 0.942 ± 0.042, and 0.948 ± 0.034 respectively. Uncertainty endpoint values for the Bayesian U-Net were mean recall = 0.953 ± 0.037, mean negative predictive value = 0.998 ± 0.005, mean accuracy = 0.906 ± 0.032, and mean AUC = 0.949 ± 0.031. To conclude, the Bayesian U-Net showed the best segmentation results across all methods and provided accurate uncertainty maps. This method may be used in clinical practice for automatic brain segmentation of preterm infants with PHH, and lead to better PHH monitoring and more informed treatment decisions.


Challenges and leadership strategies for managers of nurse practitioners.
The aim of this paper is to report on the findings from our research into the recent introduction of nurse practitioners in Alberta, Canada. Through an organizational research perspective, we identify the critical role of health care managers in developing a sustainable nurse practitioner role. Previous literature has focused on nurse practitioners themselves as the key factor in their integration into the health care system. Although they are qualified and organizationally well placed, managers of nurse practitioners have been overlooked as a critical part of implementation strategies. We interviewed 25 nurse practitioners and seven of their managers. Through our data analysis we identified three major challenges for managers: (1) clarifying the reallocation of tasks; (2) managing altered working relationships within the team; (3) continuing to manage the team in an evolving situation. Associated with these challenges, we propose leadership strategies that managers may find useful as they work through the consequences of introducing the nurse practitioner role. These strategies are: * encourage all team members to sort out 'who does what'; * ensure that task reallocation preserves job motivating properties; * give consideration to how tasks have been allocated when issues identified as 'personal conflict' arise; * pay attention to all perspectives of the working relationships within the team; * facilitate positive relationships between team members; * lead from a 'balcony' perspective; * work with the team to develop goals that are not over focused on the nurse practitioner; * regularly share with other managers the experiences and lessons learned in introducing nurse practitioners. For managers to be most effective, they need to address three challenges that are of a managerial, not clinical, nature. By implementing specific leadership strategies, managers of nurse practitioners can facilitate the introduction of the new role and improve its sustainability in health organizations.


The role of integrins in the trabecular meshwork.
Integrins are a family of heterodimeric transmembrane receptors that mediate adhesion to the extracellular matrix (ECM). However, integrins are not just adhesion receptors. They can act as "bidirectional signal transducers" that coordinate a large number of cellular activities in response to the extracellular environment and intracellular signaling events. Among the activities regulated by integrins are cell adhesion, assembly of the ECM, growth factor signaling, apoptosis, organization of the cytoskeleton, and cytoskeleton-mediated processes such as contraction, endocytosis, and phagocytosis. Integrins regulate these activities through a complex network of intracellular signaling kinases and adaptor proteins that associate with the transmembrane and cytoplasmic domains of the integrin subunits. In this review, we will discuss how some of the known integrin-mediated activities can control the function of the trabecular meshwork. We will also discuss how integrin activity is a tightly regulated process that involves conformation changes within the heterodimer which are mediated by specific integrin-binding proteins.


Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer's Disease.
Alzheimer's disease (AD) is associated with the inflammatory response in response to amyloid β-peptide (Aβ). Previous studies have suggested that paeoniflorin (PF) shows anti-inflammatory and neuroprotective effects in inflammation-related diseases. However, the impacts of PF on AD have not been investigated. In the present study, we showed that a 4-week treatment with PF could significantly inhibit Aβ burden, Aβ-induced over activation of astrocytes and microglia, downregulation of proinflammatory cytokines, and upregulation of anti-inflammatory cytokines in the brain. In addition, we demonstrated that chronic treatment with PF inhibited the activation of glycogen synthase kinase 3β (GSK-3β) and reversed neuroinflammtory-induced activation of nuclear factor-kappa B (NF-κB) signaling pathways. Moreover, PF exerted inhibitory effects on NALP3 inflammasome, caspase-1, and IL-1β. Collectively, in the present study, we demonstrated that PF exhibits neuroprotective effects in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice via inhibiting neuroinflammation mediated by the GSK-3β and NF-κB signaling pathways and nucleotide-binding domain-like receptor protein 3 inflammasome. Thus, these results suggest that PF might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.


Sensory-motor equivalence: manual aiming in C6 tetraplegics following musculotendinous transfer surgery at the elbow.
Cervical spinal lesions at C6 result in paralysis of the triceps brachii while leaving deltoid and elbow flexor function intact. We examined the spatial-temporal characteristics of goal-directed aiming movements performed by C6 tetraplegics who had undergone musculotendinous transfer surgery in which the posterior deltoid replaces the triceps as the elbow extensor. On some trials, liquid crystal goggles were used to eliminate vision of the limb and target upon movement initiation. Although tetraplegic participants achieved the same degree of movement accuracy/consistency as control participants, their movement times were longer regardless of whether the movements were made away from (elbow extension) or towards the body (elbow flexion). Longer movement times were related to lower peak velocities, and not the symmetry of the aiming profiles. The tetraplegic participants were no more dependent on visual feedback for limb regulation than control participants. Although the characteristics of the movement trajectories were surprisingly similar, in both vision conditions, tetraplegics required more real and proportional time to reduce spatial variability in the limb's trajectory for elbow extensions. Our results indicate that the sensorimotor system is adaptable and that the representations governing limb control are not muscle specific.


Purification and characterization of novel ribosome inactivating proteins, alpha- and beta-pisavins, from seeds of the garden pea Pisum sativum.
Two ribosome inactivating proteins designated alpha- and beta-pisavins were isolated from seeds of the garden pea Pisum sativum var. arvense Poir with a procedure involving affinity chromatography on Affi-gel Blue gel, immobilized metal ion affinity chromatography on Iminodiacetic acid-agarose, cation exchange chromatography on Resource-S, and gel filtration on Superose 12. alpha- and beta-pisavins are nonglycoproteins with a molecular weight of 20.5 kDa and 18.7 kDa respectively. The sequences of the first sixty N-terminal amino acids of alpha- and beta-pisavins were identical. In isoelectric focusing these two proteins merged into one band with a pI greater than 9.3. Inhibition of protein synthesis by a rabbit reticulocyte lysate system was achieved at an IC50 of approximately 0.5 nM. Activity of the proteins toward tRNA was observed. The proteins acted on ribosomal RNA through its RNA N-glycosidase activity to release an Endo's fragment, and converted the conformation of DNA from supercoiled and circular forms into a linear form.


Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion.
Dynamin-related GTPase proteins (DRPs) are main players in membrane remodelling. Conserved DRPs called mitofusins (Mfn1/Mfn2/Fzo1) mediate the fusion of mitochondrial outer membranes (OM). OM fusion depends on self-assembly and GTPase activity of mitofusins as well as on two other proteins, Ugo1 and Mdm30. Here, we define distinct steps of the OM fusion cycle using in vitro and in vivo approaches. We demonstrate that yeast Fzo1 assembles into homo-dimers, depending on Ugo1 and on GTP binding to Fzo1. Fzo1 homo-dimers further associate upon formation of mitochondrial contacts, allowing membrane tethering. Subsequent GTP hydrolysis is required for Fzo1 ubiquitylation by the F-box protein Mdm30. Finally, Mdm30-dependent degradation of Fzo1 completes Fzo1 function in OM fusion. Our results thus unravel functions of Ugo1 and Mdm30 at distinct steps during OM fusion and suggest that protein clearance confers a non-cycling mechanism to mitofusins, which is distinct from other cellular membrane fusion events.


Comparative analgesic and mental effects of increasing plasma concentrations of dexmedetomidine and alfentanil in humans.
In animals, systemic and intrathecal administration of the alpha2 -adrenergic receptor agonist dexmedetomidine results in robust antinociceptive effects in models of heat pain. In humans, systemically administered dexmedetomidine is approved for sedating patients in the intensive care unit. However, whether systemic administration of dexmedetomidine in humans produces significant analgesia at doses causing sedation but not unconsciousness remains controversial. This study in human volunteers used a placebo-controlled, double-blind, and randomized design to examine whether dexmedetomidine at doses causing mild to severe sedation produces analgesia in experimental models of heat and electrical pain. Results were compared to the effects of the mu-opioid receptor agonist alfentanil. A computer-controlled infusion provided four median step-up plasma concentrations of dexmedetomidine (0.09, 0.24, 0.54, and 1.23 ng/ml) and alfentanil (13.4, 33.8, 67.8, and 126.1 ng/ml). Sedative and cognitive effects of dexmedetomidine were dose-dependent, resulting in a median sedation score of 95 of 100 and slowing of cognitive speed (reaction time, trail-making test) by a factor of about two at the highest plasma concentration. Dexmedetomidine did not attenuate heat or electrical pain. Alfentanil caused severe sedation (median sedation score 88 of 100) and slowed cognitive speed by a factor of approximately 1.4 at the highest plasma concentration. Alfentanil attenuated heat and electrical pain dose dependently. This study documents that systemic dexmedetomidine lacks analgesic efficacy for heat and electrical pain at doses causing mild to severe sedation. These results provide further evidence suggesting that systemic administration of dexmedetomidine lacks broad analgesic activity in models of acute pain at doses not rendering humans unconscious.


Sturge-Weber syndrome: cerebral haemodynamics during seizure activity.
The aim of this study was to examine the haemodynamic response to seizures in three infants with Sturge-Weber syndrome by measuring regional cerebral blood flow using transcranial Doppler sonography and 99mTc HMPAO SPECT. Time-locked video/digital EEG recording was carried out for ictal studies. MRI was performed in all subjects. SPECT showed hemispheric hypoperfusion interictally in all three patients and also ictally in one of the three; a small region of hyperperfusion was seen on the same ictal scan in the latter, ie. the patient with interictal and ictal hypoperfusion. In the two older children middle cerebral artery velocity (MCAV) was reduced by between 29 and 62% in the middle cerebral artery of the predominantly affected hemisphere compared with the contralateral side. During seizures, increases of 6 to 30% in MCAV were recorded for the clinically seizing hemisphere compared with 24 to 170% for the contralateral side in four of the seizures recorded. In one infant, MCAV fell bilaterally during a seizure that generalized (-18 and -43% in the predominantly affected and contralateral side respectively). Sequential recordings in one infant suggested that, with time, the haemodynamic response to seizures of the unaffected hemisphere may decrease. These findings suggest that the venous malformation in SWS is associated with an impairment of the cerebral haemodynamic response to seizure activity.


Assessing risk for complications in acute hematogenous osteomyelitis in children. Validation of two predictive scores.
Acute hematogenous osteomyelitis (AHO) can be associated with severe complications which can be difficult to predict in the clinical setting. The previously published predictive acute complication score ("A-SCORE") and chronic complication score ("C-SCORE") show promise, however, further external validation is needed. We performed a retrospective study of 418 children with AHO and analyzed the performance of A-SCORE (variables included bone abscess, fever after 48 hours of starting antibiotics, suppurative arthritis, disseminated disease and delayed source control) to predict risk for acute complicated course (treatment failure, prolonged admission, and/or need for ≥ 2 bone debridements) and C-SCORE (includes disseminated disease, bone debridement and CRP ≥10 mg/dl at 2-4 days after starting antibiotics) to predict chronic complications (growth restriction, pathologic fracture, chronic osteomyelitis, avascular necrosis, joint deformity and/or frozen joint). An acute complicated course occurred in 106/418 (25.4%); 51/380 (13.5%) with complete follow-up data had a chronic complication. The A-SCORE performed with similar specificity (78%) and negative predictive value (NPV) (92%), and higher sensitivity (81%) and increased area under the receiver operating curve (AUC) (0.87) in our population. The C-SCORE performed with similar sensitivity (64%) and NPV (94%) but had lower specificity (86%) and AUC (0.71) than originally reported. Other variables associated with development of complications such as tibia involvement and bacteremia ≥ 2 days were identified but did not result in significantly improved predictive scores. Predictive A-SCORE and C-SCORE for AHO complications in children may help guide acute management and long-term follow up decisions. Prospective studies are needed to determine their applicability.


Laguerre-Gaussian mode sorter.
Exploiting a particular wave property for a particular application necessitates components capable of discriminating in the basis of that property. While spectral or polarisation decomposition can be straightforward, spatial decomposition is inherently more difficult and few options exist regardless of wave type. Fourier decomposition by a lens is a rare simple example of a spatial decomposition of great practical importance and practical simplicity; a two-dimensional decomposition of a beam into its linear momentum components. Yet this is often not the most appropriate spatial basis. Previously, no device existed capable of a two-dimensional decomposition into orbital angular momentum components, or indeed any discrete basis, despite it being a fundamental property in many wave phenomena. We demonstrate an optical device capable of decomposing a beam into a Cartesian grid of identical Gaussian spots each containing a single Laguerre-Gaussian component, using just a spatial light modulator and mirror.


Learning from the Field and Its Listserv: Issues That Concern Health Literacy Practitioners.
This study assesses the content of email messages posted to the Health Literacy Discussion List (HLDL) during a two-year period. The study identifies issues of concern to list subscribers, describes the purposes the list serves for health professionals, and contributes to the health literacy literature by providing an email listserv as a research corpus. The authors conducted an inductive qualitative analysis of email posts to the HLDL from October 2013 to October 2015. Using an iterative process, the authors identified descriptive categories for types of posts and topics of posts. The first (SKR) and second (JM) authors reviewed subject lines of all 2,036 posts and brainstormed type and topic categories, independently read and sorted a random sample of 200 posts into those categories, and then discussed discrepancies. Based on the latter experience, the authors combined, added, or excluded certain categories and jointly created a detailed description for each type and topic category. We then sorted another random sample of 200 posts and generated a list of key words relating emails to topic categories. A Cohen's kappa reliability coefficient was calculated to establish intercoder reliability. The third author (RVR) then conducted key word searches for sorting the remaining 1,836 email posts. The existence and frequency of email clusters and the content of emails in these clusters were used to identify and explore in greater detail the "hot topics" of interest to the field. Our analysis suggests the utility of the HLDL as a platform for sharing information and resources, announcements and calls for action, technical assistance and professional discourse.


Simultaneous Antegrade-Retrograde Subintimal Revascularization of a Femoropopliteal Chronic Total Occlusion by a Reentry Device-Facilitated Puncture of a Retrogradely Inserted Balloon.
To report a rendezvous technique for subintimal revascularization of a chronic total occlusion (CTO) of the superficial femoral artery (SFA). This maneuver is appropriate after failure to cross a long SFA CTO via intra- and subintimal approaches from the ipsilateral femoral as well as retrograde posterior tibial artery (PTA) access sites. After predilation of the subintimal space from the femoral access, a reentry device was placed at the level of the first popliteal artery segment. A balloon was delivered via the retrograde PTA access and inflated at the corresponding level of the reentry device. The balloon was punctured with the needle of the reentry device under fluoroscopic control, and a 0.014-inch guidewire was placed within the punctured balloon. The balloon and the antegrade guidewire were retracted from the retrograde access while the guidewire was gently pushed from the femoral site. Conventional balloon angioplasty of the SFA occlusion was performed via the femoral access, followed by overlapping stent-graft implantation. Complete revascularization of the CTO was documented. In selected cases a transfemoral reentry device-assisted puncture of a retrogradely inserted balloon within the subintimal space may facilitate a rendezvous and revascularization if standard techniques to cross long CTOs have failed.


Rediscovering hermaphroditism in Grammatidae with the description of the testicular gland in Brazilian Basslet Gramma brasiliensis.
Many aspects of sex change in reef fishes have been studied, including behavior and social organization. However, gonad histology remains the most robust way to identify sexual patterns in fishes. Some uncommon tissues remain poorly described, such as the accessory gonadal structures found in species from the Gobiidae family, which are rare in other bony fishes. This is the first report of the testicular gland in Gramma brasiliensis and for the Grammatidae family. Between April 2011 and February 2012 eighty specimens were collected during four dive campaigns on the Taipus de Fora reef (13°56'20"S 38°55'32"W), Bahia, Northeast Brazil, and their sex was determined. Thirteen per cent of the active-females and 90% of the active-males had testicular gland tissue in their ovotestis. This discovery led to additional research into the characteristics of the gland tissue and its relationship with gonadal maturation. Three patterns of testicular gland development were found in Brazilian basslet ovotestis. Both ova and sperm-producing gonad contained testicular gland tissue, and the appearance of this tissue seems to be the first modification of ovotestis tissue marking the beginning of the protogynous sex-change process in G. brasiliensis.


The role of EUS in diagnosis and treatment of liver disorders.
Background and aim Transabdominal ultrasound (US), computed tomographic scanning (CT) and magnetic resonance imaging (MRI) are established diagnostic tools for liver diseases. Percutaneous transhepatic cholangiography is used to perform hepatic interventional procedures including biopsy, biliary drainage procedures, and radiofrequency ablation. Despite their widespread use, these techniques have limitations. Endoscopic ultrasound (EUS), a tool that has proven useful for evaluating the mediastinum, esophagus, stomach, pancreas, and biliary tract, has an expanding role in the field of hepatology complementing the traditional investigational modalities. This review aimed to assess the current scientific evidence regarding diagnostic and therapeutic applications of EUS for hepatic diseases.


Cholesterol esterification plays a major role in determining low-density-lipoprotein receptor activity in primary monolayer cultures of rat hepatocytes.
1. We have previously shown that the capacity for specific binding of human 125I-labelled low-density lipoprotein (LDL) to rat hepatocytes increases with time in culture [Salter, Bugaut, Saxton, Fisher & Brindley (1987) Biochem. J. 247, 79-84]. 2. In the present study we show that this up-regulation is accompanied by a rise in the cholesterol ester content of the cells. 3. Inhibition of cholesterol esterification with the drug 58-035 (Sandoz) significantly decreases the time-dependent 'up-regulation' of LDL receptors. 4. Incubation of hepatocytes with LDL itself has little effect on subsequent LDL binding. However, when cholesterol esterification is inhibited, incubation with LDL decreases binding below that attained with the drug alone. 5. Inhibition of cholesterol synthesis with Lovastatin significantly increases LDL binding and antagonizes the effect of 58-035. 6. We conclude that in hepatocytes the rate of cellular cholesterol esterification can become the major determinant of LDL-receptor activity.


Ozone in the adjunct medical treatment. The round personality of a molecule with hormetic properties.
Ozone, an allotrope of oxygen, is enjoying an increasing interest in the setting and management of the medical adjunct treatment, which is called, maybe too simplistically, "ozone therapy". Ozone is not a medicine, so the word therapy does not properly fit this gaseous molecule. Like many natural compounds, for example plant flavonoids, even ozone interacts with aryl hydrocarbon receptors (AhRs) and, at low doses, it works according to the paradoxical mechanism of hormesis, involving mitochondria (mitohormesis). Ozone, in the hormetic range, exerts cell protective functions via the Nrf2-mediated activation of the anti-oxidant system, then leading to anti-inflammatory effects, also via the triggering of low doses of 4-HNE. Moreover, its interaction with plasma and lipids forms reactive oxygen species (ROS) and lipoperoxides (LPOs), generally called ozonides, which are enabled to rule the major molecular actions of ozone in the cell. Ozone behaves as a bioregulator, by activating a wide population of reactive intermediates, which usually target mitochondria and their turnover/biogenesis, often leading to a pleiotropic spectrum of actions and behaving as a tuner of the fundamental mechanisms of survival in the cell. In this sense, ozone can be considered a novelty in the medical sciences and in the clinical approach to pharmacology and medical therapy, due to its ability to target complex regulatory systems and not simple receptors.


[ESWL for urolithiasis in a patient with transileal ureterocutaneostomy].
We present a case of urinary stone originated in the upper urinary tract and impacted within the ureteroileal anastomosis, in a patient with ileal conduit urinary diversion. Extracorporeal shock wave lithotripsy (ESWL) showed itself resolutive. Patients with urinary diversion have multiple risk factor for calculi formation (acidosis with concomitant hypercalciuria, upper urinary tract infections with urease producing bacteria, urostasis due to ureterointestinal anastomosis or ureteral narrowing), as well as predisposing conditions for stones to impact along the ureter or within the ureterointestinal anastomosis. Follow-up of these patients has to be very careful in order to avoid obliterative pyeloureteritis, the major complication of stone disease in patients with urinary conduit diversion.


Statistical significance of seasonal warming/cooling trends.
The question whether a seasonal climate trend (e.g., the increase of summer temperatures in Antarctica in the last decades) is of anthropogenic or natural origin is of great importance for mitigation and adaption measures alike. The conventional significance analysis assumes that (i) the seasonal climate trends can be quantified by linear regression, (ii) the different seasonal records can be treated as independent records, and (iii) the persistence in each of these seasonal records can be characterized by short-term memory described by an autoregressive process of first order. Here we show that assumption ii is not valid, due to strong intraannual correlations by which different seasons are correlated. We also show that, even in the absence of correlations, for Gaussian white noise, the conventional analysis leads to a strong overestimation of the significance of the seasonal trends, because multiple testing has not been taken into account. In addition, when the data exhibit long-term memory (which is the case in most climate records), assumption iii leads to a further overestimation of the trend significance. Combining Monte Carlo simulations with the Holm-Bonferroni method, we demonstrate how to obtain reliable estimates of the significance of the seasonal climate trends in long-term correlated records. For an illustration, we apply our method to representative temperature records from West Antarctica, which is one of the fastest-warming places on Earth and belongs to the crucial tipping elements in the Earth system.


Skin-inspired flexible and high-sensitivity pressure sensors based on rGO films with continuous-gradient wrinkles.
Flexible electronic devices have received more and more attention. In particular, for pressure sensors, traditional methods for improving sensing performances are mostly based on the construction of microstructured templates. However, it still remains significantly challenging to conveniently fabricate thin-film sensors which possess flexibility, high sensitivity and location detection ability. Inspired by the microstructure of the human skin surface, herein, a new pressure sensor with a hierarchical structure and gradient reduced graphene oxide (rGO) wrinkles is reported. Benefiting from the skin-like structure, the pressure sensor demonstrates outstanding sensitivity, reaching 178 kPa-1; it can also detect pressure as small as 42 Pa. Furthermore, the concept of designing and constructing a gradient structure has been applied to achieve position detection, which is expected to find practical applications in human motion detection.


Magnitude of error: a review of wrong dose medication incidents reported to a UK hospital voluntary incident reporting system.
Our aim was to review medication-related incidents reported to a hospital voluntary incident reporting system to identify and quantify the magnitude of wrong dose errors. The study was a retrospective review of medication-related incidents reported over a 7-year period at a large acute teaching hospital in the UK, providing secondary and tertiary care for a range of clinical specialties. Medication-related incident reports submitted from all clinical settings were reviewed. Incidents submitted under the categories 'wrong dose', 'wrong dose preparation', 'wrong rate' or 'wrong quantity' and describing situations where incorrect doses were prescribed, dispensed or administered were analysed. Magnitudes of medication overdoses and underdoses reported from adult and paediatric settings were calculated. Stage of the medicines process and drug classes most commonly involved in wrong dose errors were described. Of 12 006 reported medication incidents, 1568 described 'wrong-dose' errors: 702 (44.8%) were prescribing errors, 223 (14.2%) were dispensing errors and 643 (41%) were administration errors. Overdoses were reported more frequently than underdoses. 926 (59%) of reported wrong dose errors were overdoses, 464 (29.6%) were underdoses; the magnitude could not be determined in 178 (11.4%) of reports. Twofold and 10-fold overdoses and underdoses were the most commonly reported error magnitude, although dosing errors across a wide range of magnitudes were reported. Incidents were reported from paediatric wards (491, 31.3%), non-paediatric wards and clinical settings (880, 56.1%) and pharmacy (197, 12.6%). Prescribing errors (702, 45.9%) were reported more commonly than administration (643, 41%) and dispensing errors (223, 14.2%). Drugs acting on the central nervous system, cardiovascular drugs and anti-infectives were the drug classes most commonly involved. Wrong dose errors occur across all inpatient settings. Wrong dose errors of all magnitudes are possible, but twofold and 10-fold errors occur most frequently. Drug classes involved in wrong dose incidents reported to a voluntary reporting system in a large acute hospital are similar to those identified using other methodologies. Harms and potential harms associated with specific drugs and error magnitudes need to be identified to inform quality improvement work to reduce the risk of patient harm.


Mate choice and the origin of menopause.
Human menopause is an unsolved evolutionary puzzle, and relationships among the factors that produced it remain understood poorly. Classic theory, involving a one-sex (female) model of human demography, suggests that genes imparting deleterious effects on post-reproductive survival will accumulate. Thus, a 'death barrier' should emerge beyond the maximum age for female reproduction. Under this scenario, few women would experience menopause (decreased fertility with continued survival) because few would survive much longer than they reproduced. However, no death barrier is observed in human populations. Subsequent theoretical research has shown that two-sex models, including male fertility at older ages, avoid the death barrier. Here we use a stochastic, two-sex computational model implemented by computer simulation to show how male mating preference for younger females could lead to the accumulation of mutations deleterious to female fertility and thus produce a menopausal period. Our model requires neither the initial assumption of a decline in older female fertility nor the effects of inclusive fitness through which older, non-reproducing women assist in the reproductive efforts of younger women. Our model helps to explain why such effects, observed in many societies, may be insufficient factors in elucidating the origin of menopause.


Estimation of factors contributing to level differences in Japanese university decathlon athletes.
This study aimed to estimate the factors that cause differences in competition level based on the competition performance structure among university student decathletes in Japan. The results of factor analysis using the maximum likelihood method (Oblimin rotation), assuming a five-factor structure estimated from parallel analysis and the information criterion, revealed the following competitive performance structures: "running speed and body projection," "running endurance," "rotational throwing power," "translational throwing power," and "vertical leaping power." Some of these were similar to the competitive performance structures of the world's top athletes, but they were found to have a unique structure: two throwing powers. The analysis results using latent rank theory allowed us to evaluate them on a seven-point scale. The calculated item reference profile, difficulty index, and discrimination index for each rank indicated that shot put and 100 and 400 m performance formed the basis of decathlon performance. In addition, high jump and pole vault, which fall under the category of "vertical leaping power," retained high difficulty and discrimination and were revealed to affect the stage of achievement of overall performance in the decathlon.


Primary Health Care and Community Pharmacy in Ireland: a lot of visions but little progress.
Ireland is small country with a population of 4.8M which spent 6.9% of its gross domestic product on healthcare in 2018. Health services are provided through a twin track approach - all public services are largely free to those eligible (32.44% in 2019) and private patients pay for most services. Most of the expenditure on medicines is paid by the government while visits to General Practitioners (GPs) are an out-of-pocket expense for private patients under 70 years of age, and private health insurance provides cover for most hospital services. Healthcare professionals in the primary care sector contract to provide public services with the Health Services Executive (HSE) which is responsible for the day-to-day running of the service. Primary care teams began to be formed in 2001 to try to link and integrate the provision of care but since these are led by GPs neither community pharmacists nor dentists joined these teams. The focus of policy remained the primary care team until a proposal to create a public health service to provide universal health coverage called Sláintecare was agreed in 2017. However, implementation of Sláintecare has been slow and piecemeal. The government regularly devises policies to control prescribing and the HSE, together with other regulators has implemented generic substitution and preferred drugs and limited access to expensive drugs through schemes for particular patient groups. A programme called Healthy Ireland has taken on the health promotion policies but pharmacists have been excluded from most programmes although some campaigns have included them. Community pharmacy organisations have tried to develop pharmacy services and while a few which are targeted at specified patient groups, such as opioid substitution, emergency administration of certain drugs, emergency hormonal contraception and seasonal influenza vaccination have been remunerated for public patients by the HSE, other services have not. GP organisations defend their members' scope of practice and seek to influence policy makers to channel schemes and services through general practice. There is no professional body to represent pharmacists that is independent of any trade union responsibilities and this has weakened the profession's advocacy. Pharmacists are one of the most trusted group of professionals in Ireland and have maintained their practices throughout periods of recession and declining income from government. Whether pharmacists can argue that the optimisation of a patient's medicines depends upon their contribution and will benefit the health service remains an open question.


COVID-19 vaccine hesitancy among Ethiopian healthcare workers.
COVID-19 poses significant health and economic threat prompting international firms to rapidly develop vaccines and secure quick regulatory approval. Although COVID-19 vaccination priority is given for high-risk individuals including healthcare workers (HCWs), the success of the immunization efforts hinges on peoples' willingness to embrace these vaccines. This study aimed to assess HCWs intention to be vaccinated against COVID-19 and the reasons underlying vaccine hesitancy. A cross-sectional survey was conducted among HCWs in Addis Ababa, Ethiopia from March to July 2021. Data were collected from eligible participants from 18 health facilities using a pre-tested semi-structured questionnaire. Data were summarized using descriptive statistics and multivariable logistic regression was performed to explore factors associated with COVID-19 vaccine hesitancy. A p<0.05 was considered statistically significant. A total of 614 HCWs participated in the study, with a mean age of 30.57±6.87 years. Nearly two-thirds (60.3%) of HCWs were hesitant to use the COVID-19 vaccine. Participants under the age of 30 years were approximately five times more likely to be hesitant to be vaccinated compared to those over the age of 40 years. HCWs other than medical doctors and/or nurses (AOR = 2.1; 95%CI; 1.1, 3.8) were more likely to be hesitant for COVID-19 vaccine. Lack of believe in COVID-19 vaccine benefits (AOR = 2.5; 95%CI; 1.3, 4.6), lack of trust in the government (AOR = 1.9; 95%CI; 1.3, 3.1), lack of trust science to produce safe and effective vaccines (AOR = 2.6; 95%CI; 1.6, 4.2); and concern about vaccine safety (AOR = 3.2; 95%CI; 1.9, 5.4) were also found to be predictors of COVID-19 vaccine hesitancy. COVID-19 vaccine hesitancy showed to be high among HCWs. All concerned bodies including the ministry, regional health authorities, health institutions, and HCWs themselves should work together to increase COVID-19 vaccine uptake and overcome the pandemic.


Rehabilitating equipoise.
When may a physician legitimately offer enrollment in a randomized clinical trial (RCT) to her patient? Two answers to this question have had a profound impact on the research ethics literature. Equipoise, as originated by Charles Fried, which we term Fried's equipoise (FE), stipulates that a physician may offer trial enrollment to her patient only when the physician is genuinely uncertain as to the preferred treatment. Clinical equipoise (CE), originated by Benjamin Freedman, requires that there exist a state of honest, professional disagreement in the community of expert practitioners as to the preferred treatment. FE and CE are widely understood as competing concepts. We argue that FE and CE offer separable and, in themselves, incomplete justifications for the conduct of clinical trials. FE articulates conditions under which the fiduciary duties of physician to patient may be upheld in the conduct of research. CE sets out a standard for the social approval of research by institutional review boards. Viewed this way, FE and CE are not necessarily competing notions, but rather address complementary moral concerns.


Reclassification of Arthrobacter enclensis as Pseudarthrobacter enclensis comb. nov., and emended descriptions of the genus Pseudarthrobacter, and the species Pseudarthrobacter phenanthrenivorans and Pseudarthrobacter scleromae.
Arthrobacterenclensis was reported to cluster with species of the genus Pseudarthrobacter but the peptidoglycan containing lysine, alanine and glutamic acid and the presence of minor amounts of menaquinone MK-8(H4) were not in line with the description of the genus. Re-analysis of these traits revealed a peptidoglycan with l-Lys-l-Ser-l-Thr-l-Ala and no MK-8(H4), but major amounts of MK-9(H2) in the quinone system of A. enclensis DSM 25279T. These data demonstrate that A. enclensis shares the characteristics of the genus Pseudarthrobacter. Since the reported quinone systems of Pseudarthrobacterphenanthrenivorans [MK-8 and MK-9(H2)] and Pseudarthrobacterscleromae [MK-8(H2] were clearly different from those of other species of the genus, the quinone systems of the two species were re-analyzed. Since the polar lipid profile of P. phenanthrenivorans was reported to contain phosphatidylethanolamine, which is unusual for a member of the Micrococcaceae, and the polar lipid profile of P. scleromae was unknown, the polar lipids of these two species were also analysed. The quinone system of P. phenanthrenivorans DSM 18606T was composed of the major menaquinones MK-9(H2), MK-8(H2) and MK-10(H2) and that of P. scleromae DSM 17756T was composed of the major menaquinones MK-9(H2) and MK-8(H2) and MK-9. In the polar lipid profile of P. phenanthrenivorans DSM 18606T no phosphatidylethanolamine could be detected. Based on these results we here propose the reclassification of A. enclensis as Pseudarthrobacterenclensis comb. nov. and emend the descriptions of the genus Pseudarthrobacter and the two species P. phenanthrenivorans and P. scleromae.


Mesial temporal lobe epilepsy: a proton magnetic resonance spectroscopy study and a histopathological analysis.
Proton magnetic resonance (MR) spectroscopy imaging of the ratio of N-acetylaspartate (NAA) to creatine (Cr) has proved efficacious as a localizing tool in demonstrating the metabolic changes associated with temporal lobe epilepsy. To analyze the significance of these MR spectroscopy findings further, the authors explored the relationship between regional alterations in the NAA/Cr ratio in hippocampi measured preoperatively and histopathological findings in hippocampi resected in patients with intractable mesial temporal lobe epilepsy (MTLE). Twelve patients in whom the diagnosis of MTLE had been made and 12 healthy volunteers with no known history of neurological disease underwent high-resolution 1H MR spectroscopy imaging of NAA and Cr (0.64 cm3 nominal voxel resolution) in five voxels spanning the anteroposterior length of the hippocampus. The authors correlated the NAA/Cr ratio with neuropathological findings in resected hippocampi, specifically glial fibrillary acidic protein (GFAP) immunoreactivity and pyramidal neuronal loss. A linear regression analysis of the ipsilateral NAA/Cr ratio revealed a statistically significant relation to the extent of hippocampal neuronal loss in only the CA2 sector (correlation coefficient [r] = -0.66, p < 0.03). The ipsilateral NAA/Cr ratio displayed significant regressions with GFAP immunoreactivity from all the CA sectors (r values ranged from -0.69 and p < 0.01 for the CA4 sector to -0.88 and p < 0.001 for the CA2 sector) except for the CA1. The extent of neuronal cell loss in every hippocampal subfield (r = 0.71-0.74, p < 0.007), except the CA2 (p = 0.08), correlated to the extent of neuronal cell loss in the dentate gyrus. There was no significant relationship between the duration or frequency of seizures and the mean ipsilateral NAA/Cr ratio; however, the mean density of GFAP-immunopositive cells correlated with seizure frequency (p < 0.03). The NAA/Cr ratio may not measure the full extent of hippocampal neuronal cell loss. The significant association of the NAA/Cr ratio with the GFAP immunoreactivity of most CA sectors indicates that the NAA/Cr ratio may provide a more accurate measurement of recent neuronal injury caused by epileptic activity. The coupling between neuronal impairment and astroglial GFAP expression may indicate the close association between neuronal and glial dysfunction in patients with epilepsy.


Processing, localization and binding activity of zonadhesin suggest a function in sperm adhesion to the zona pellucida during exocytosis of the acrosome.
Zonadhesin is a sperm protein that binds in a species-specific manner to the extracellular matrix ZP (zona pellucida) of the mammalian oocyte. The pig zonadhesin precursor is a 267000-Da mosaic protein with a Type I membrane topology and a large extracellular region comprising meprin/A5 antigen/mu receptor tyrosine phosphatase, mucin and five tandem von Willebrand D (VWD) domains. Multiple mature forms of zonadhesin in the sperm head differ in their avidities for the ZP. To determine the potential functions of zonadhesin forms in gamete adhesion, we characterized the processing, activation and localization of protein in pig spermatozoa. The predominant polypeptides of processed zonadhesin were M(r) 300000 (p300), 105000 (p105) and 45000 (p45). p45 and p105, comprised primarily the D1, D2-D3 domains respectively, and were N-glycosylated. p300 was heavily O-glycosylated, and spanned the meprin/A5 antigen/mu receptor tyrosine phosphatase, mucin and D0 domains. Hydrolysis of the precursor polypeptide occurred in the testis, and N-terminal sequencing of p45 and p105 identified Asp806-Pro and Asp1191-Pro in the D1 and D2 domains respectively as bonds cleaved in the protein's functional maturation. Testicular zonadhesin was extractable with non-ionic detergents, and localized to the developing outer acrosomal membrane of round and elongating spermatids. As spermatozoa transited the epididymis, most of the protein became incorporated into an extraction-resistant fraction, and the proportions of active and of multimeric zonadhesins in the cells increased. Zonadhesin localized to the perimeter of the acrosome in intact ejaculated spermatozoa and to the leading edge of acrosomal matrix overlying cells with disrupted acrosomal membranes. We conclude that the zonadhesin precursor is specifically proteolysed, glycosylated and assembled into particulate structures in the distal parts of the acrosome where it may mediate specific adhesion to the ZP during the initial stages of acrosomal exocytosis.


Online decision support for persons having a genetic predisposition to cancer and their partners during reproductive decision-making.
A nationwide pretest-posttest study was conducted in all clinical genetic centres in the Netherlands, to evaluate the effects of an online decision aid to support persons who have a genetic predisposition to cancer and their partners in making an informed decision regarding reproductive options. Main outcomes (decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self-efficacy) were measured before use (T0), immediately after use (T1), and at 2 weeks (T2) after use of the decision aid. Paired sample t tests were used to compute differences between the first and subsequent measurements. T0-T1 and T0-T2 comparisons indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline decisional conflict. Furthermore, use of the decision aid resulted in increased knowledge levels and improved realistic expectations. Level of deliberation only increased for participants with lower baseline levels of deliberation. Decision self-efficacy increased for those with low baseline scores, whereas those with high baseline scores showed a reduction at T2. It can be concluded that use of the decision aid resulted in several positive outcomes indicative of informed decision-making. The decision aid is an appropriate and highly appreciated tool to be used in addition to reproductive counseling.


ENHANCED GRAVITROPISM 2 encodes a STERILE ALPHA MOTIF-containing protein that controls root growth angle in barley and wheat.
The root growth angle defines how roots grow toward the gravity vector and is among the most important determinants of root system architecture. It controls water uptake capacity, nutrient use efficiency, stress resilience, and, as a consequence, yield of crop plants. We demonstrated that the egt2 (enhanced gravitropism 2) mutant of barley exhibits steeper root growth of seminal and lateral roots and an auxin-independent higher responsiveness to gravity compared to wild-type plants. We cloned the EGT2 gene by a combination of bulked-segregant analysis and whole genome sequencing. Subsequent validation experiments by an independent CRISPR/Cas9 mutant allele demonstrated that egt2 encodes a STERILE ALPHA MOTIF domain-containing protein. In situ hybridization experiments illustrated that EGT2 is expressed from the root cap to the elongation zone. We demonstrated the evolutionary conserved role of EGT2 in root growth angle control between barley and wheat by knocking out the EGT2 orthologs in the A and B genomes of tetraploid durum wheat. By combining laser capture microdissection with RNA sequencing, we observed that seven expansin genes were transcriptionally down-regulated in the elongation zone. This is consistent with a role of EGT2 in this region of the root where the effect of gravity sensing is executed by differential cell elongation. Our findings suggest that EGT2 is an evolutionary conserved regulator of root growth angle in barley and wheat that could be a valuable target for root-based crop improvement strategies in cereals.


Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration.
Mitotic inheritance of the DNA methylome is a challenging task for the maintenance of cell identity. Whether DNA methylation pattern in different genomic contexts can all be faithfully maintained is an open question. A replication-coupled DNA methylation maintenance model was proposed decades ago, but some observations suggest that a replication-uncoupled maintenance mechanism exists. However, the capacity and the underlying molecular events of replication-uncoupled maintenance are unclear. By measuring maintenance kinetics at the single-molecule level and assessing mutant cells with perturbation of various mechanisms, we found that the kinetics of replication-coupled maintenance are governed by the UHRF1-Ligase 1 and PCNA-DNMT1 interactions, whereas nucleosome occupancy and the interaction between UHRF1 and methylated H3K9 specifically regulate replication-uncoupled maintenance. Surprisingly, replication-uncoupled maintenance is sufficiently robust to largely restore the methylome when replication-coupled maintenance is severely impaired. However, solo-WCGW sites and other CpG sites displaying aging- and cancer-associated hypomethylation exhibit low maintenance efficiency, suggesting that although quite robust, mitotic inheritance of methylation is imperfect and that this imperfection may contribute to selective hypomethylation during aging and tumorigenesis.


Pediococcus lolii DSM 19927T and JCM 15055T are strains of Pediococcus acidilactici.
Strain NGRI 0510Q(T), isolated from ryegrass silage, was recently classified as a representative of a novel Pediococcus species, Pediococcus lolii Doi et al. 2009. It was deposited in the DSMZ and JCM culture collections as DSM 19927(T) and JCM 15055(T), respectively. A polyphasic taxonomic study, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, pheS and 16S rRNA gene sequence analysis, fluorescent amplified fragment length polymorphism and DNA-DNA hybridization, was used to prove that both subcultures of the type, and only, strain of this species are strains of Pediococcus acidilactici.


Chikungunya Virus Infection: Why Should U.S. Geriatricians Be Aware of It?
Chikungunya virus (CHIKV) was until recently perceived only as a tropical disease. Since the first report of a case in Saint Martin Island in 2013, it has spread to South, Central, and North America. The first local transmission in the continental United States was reported in Florida in July 2014. CHIV infection is known to cause debilitating rheumatologic disease. Older adults are particularly susceptible to severe and chronic infection. Without an effective vaccine and antiviral therapy to prevent and control CHIKV, U.S. geriatricians could soon be confronted with major clinical, functional, and therapeutic challenges. After a general overview of CHIKV infection, this review will examine reasons why it has become such a threat to the United States and consider factors that contribute to the greater burden and effect of this disease in elderly adults. Consideration will be given to how aging and immunosenescence may contribute to CHIKV's atypical and more-severe clinical features in older adults. This review concludes with possible therapeutic approaches that best fit the unique needs of older adults, especially with regard to multimorbidity and polypharmacy.


Personal and perceived peer use and attitudes towards the use of nonmedical prescription stimulants to improve academic performance among university students in seven European countries.
Overestimations of non-prescribed stimulant use of peers are well documented in the USA and have also been identified as predictive of personal stimulant consumption. This study aimed to examine whether overestimations of peer use and approval of the use are associated with personal use and attitude towards the use of non-prescribed stimulants among European university students. The EU funded 'Social Norms Intervention for the prevention of Polydrug usE (SNIPE)' study was conducted in seven European countries. In a web-based questionnaire, 4482 students were asked about their personal use and their attitude towards non-prescribed stimulant use, as well as the perceived peer use and peer attitude. 59% of students thought that the majority of their peers used non-prescribed stimulants more frequently than themselves, and only 4% thought that the use of the majority was lower than their personal use. The perception that the majority of peers had used non-prescribed stimulants at least once was significantly associated with higher odds for personal use of non-prescribed stimulants (OR: 3.30, 95% CI: 2.32-4.71). In addition, the perception that the majority of peers approved of the non-prescribed use of stimulants was associated with a 4.03 (95% CI: 3.35-4.84) times higher likelihood for personal approval. European university students generally perceived the non-prescribed use of stimulants of peers to be higher than their personal use. This perception, as well as a perception of higher approval in the peer group, was associated with a higher likelihood of personal non-prescribed stimulant medication use and approval.


Ankle arthrodesis using an anterior AO T plate.
We describe a surgical technique for ankle arthrodesis using an anterior approach to the ankle and internal fixation with an anteriorly-placed AO T plate. A total of 33 patients who had ankle arthrodeses have been followed retrospectively. Thirty-one (94%) of the ankles fused although two patients developed tibial stress fractures. Four patients had a superficial infection which did not prevent union. The surgical technique is simple, easily reproducible and gives excellent clinical results with a high rate of union.


Catastrophic extinctions follow deforestation in Singapore.
The looming mass extinction of biodiversity in the humid tropics is a major concern for the future, yet most reports of extinctions in these regions are anecdotal or conjectural, with a scarcity of robust, broad-based empirical data. Here we report on local extinctions among a wide range of terrestrial and freshwater taxa from Singapore (540 km2) in relation to habitat loss exceeding 95% over 183 years. Substantial rates of documented and inferred extinctions were found, especially for forest specialists, with the greatest proportion of extinct taxa (34-87%) in butterflies, fish, birds and mammals. Observed extinctions were generally fewer, but inferred losses often higher, in vascular plants, phasmids, decapods, amphibians and reptiles (5-80%). Forest reserves comprising only 0.25% of Singapore's area now harbour over 50% of the residual native biodiversity. Extrapolations of the observed and inferred local extinction data, using a calibrated species-area model, imply that the current unprecedented rate of habitat destruction in Southeast Asia will result in the loss of 13-42% of regional populations over the next century, at least half of which will represent global species extinctions.


Adolescent bystanders' perspectives of aggression in the online versus school environments.
Researchers' understanding of bystanders' perspectives in the cyber-environment fails to take young people's perceptions into account and remains imperfect. Interventions encouraging adolescents to help targets of cyber-aggression are therefore typically based upon traditional school-based aggression research. Twenty-four in-depth interviews with Australian 13-16 year-olds revealed two themes that reflect how young bystanders perceive differences between aggression online and at school. The physical presence theme suggests that young bystanders struggle to determine online intentions in the absence of body language, leading to hesitancy in reactions and furthermore make it easier for them to ignore online transgressions and avoid becoming involved. The authority theme indicates young bystanders perceive that, compared to the school environment, the online environment lacks clearly established rules, authority figures and formal reporting mechanisms. These differences indicate that unique strategies should be developed to encourage young bystanders to intervene in cyber-aggression situations.


Candida albicans and Antifungal Peptides.
Candida albicans, a ubiquitous opportunistic fungal pathogen, plays a pivotal role in human health and disease. As a commensal organism, it normally resides harmlessly within the human microbiota. However, under certain conditions, C. albicans can transition into a pathogenic state, leading to various infections collectively known as candidiasis. With the increasing prevalence of immunocompromised individuals and the widespread use of invasive medical procedures, candidiasis has become a significant public health concern. The emergence of drug-resistant strains further complicates treatment options, highlighting the urgent need for alternative therapeutic strategies. Antifungal peptides (AFPs) have gained considerable attention as potential candidates for combating Candida spp. infections. These naturally occurring peptides possess broad-spectrum antimicrobial activity, including specific efficacy against C. albicans. AFPs exhibit several advantageous properties, such as rapid killing kinetics, low propensity for resistance development, and diverse mechanisms of action, making them promising alternatives to conventional antifungal agents. In recent years, extensive research has focused on discovering and developing novel AFPs with improved efficacy and selectivity against Candida species. Advances in biotechnology and synthetic peptide design have enabled the modification and optimization of natural peptides, enhancing their stability, bioavailability, and therapeutic potential. Nevertheless, several challenges must be addressed before AFPs can be widely implemented in clinical practice. These include optimizing peptide stability, enhancing delivery methods, overcoming potential toxicity concerns, and conducting comprehensive preclinical and clinical studies. This commentary presents a short overview of candidemia and AFP; articles and reviews published in the last 10 years were searched on The National Library of Medicine (National Center for Biotechnology Information-NIH-PubMed). The terms used were C. albicans infections, antimicrobial peptides, antifungal peptides, antifungal peptides mechanisms of action, candidemia treatments and guidelines, synthetic peptides and their challenges, and antimicrobial peptides in clinical trials as the main ones. Older publications were cited if they brought some relevant concept or helped to bring a perspective into our narrative. Articles older than 20 years and those that appeared in PubMed but did not match our goal to bring updated information about using antifungal peptides as an alternative to C. albicans infections were not considered.


Polyhedral Oligomeric Silsesquioxane (POSS) Surface Grafting: A Novel Method to Enhance Polylactide Hydrolysis Resistance.
Abstract: This work considers the development of an easy and scalable approach to change the features of poly(l-lactide) (PLLA) films, which is based on the application of a surface treatment with an amino-functionalized polyhedral oligomeric silsesquioxane (POSS). Indeed, the developed approach is based on the potential reactivity of POSS amino group towards the polymer functionalities to produce an aminolysis reaction, which should promote the direct grafting of the silsesquioxane molecules on the polymer surface. Neat and treated films were studied by infrared spectroscopy and X-ray photoelectron spectroscopy, which proved the effectiveness of POSS grafting. Moreover, scanning electron microscopy measurements demonstrated the homogeneous distribution of Si on the film surface treated with the silsesquioxane. The influence of the film treatment on the surface wettability was evidenced by contact angle measurements. These findings demonstrated a relevant enhancement of the surface hydrophobicity, which increase turned out to depend on the conditions applied, as it increased by increasing the reaction temperature and the contact time. Finally, in order to evaluate the stability of neat and of the treated PLLA films the surface morphology of the samples treated with pH 7.4 buffer at 50 °C was studied.


Clinical inquiries. Which vaccinations are indicated after splenectomy?
Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Pneumococcal, meningococcal, and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day (strength of recommendation [SOR]: A, based on systematic review of RCTs for the pneumococcal vaccine; SOR: B, based on systematic review of clinical trials for meningococcal and Hib vaccines).


A formative evaluation of nurses' use of electronic devices in a home care setting.
The purpose of this study was to evaluate the implementation of a clinical information system (CIS) in a community setting. The researchers used a mixed-method design involving interviews, focus groups, and surveys. An independent cross-sectional sample of nurses was surveyed. At time 1 a total of 118 nurses responded and at time 2 a total of 81. Respondents were moderately satisfied with features of the CIS. User satisfaction was positively associated with access to structural and electronic resources and social capital and negatively associated with nurses' age at time 1. Social capital was positively associated with user satisfaction at time 2. Younger age was associated with overall research use at both time 1 and time 2. Research use was negatively associated with evaluation and feedback but positively associated with formal interactions. This evaluation identified the importance of educational support, user-centred design, and responsiveness to successful implementation of CISs in a community setting.


Retina specialists treating cystoid macular oedema secondary to retinal vein occlusion recommend different treatments for patients than they would choose for themselves.
To evaluate the presence of cognitive bias among retinal specialists when recommending treatment options for cystoid macular oedema (CMO) secondary to retinal vein occlusion (RVO). Two randomly chosen samples of retina specialists were surveyed regarding their treatment and dosing regimen choices among three antivascular endothelial growth factor (anti-VEGF) biologics (aflibercept, bevacizumab and ranibizumab), intravitreal steroid, focal laser and observation for the treatment of CMO secondary to RVO. The first group was asked to make recommendations for two hypothetical patients: one with CMO secondary to branch RVO (BRVO) and the second with CMO secondary to central RVO (CRVO). The second group was asked to make recommendations as if they themselves were the hypothetical patient with the same disease processes. The survey was completed by 492 respondents (20.1%). When comparing anti-VEGF agents for patients with BRVO, a majority of physicians recommended bevacizumab (60.5%) over ranibizumab (37.8%) and aflibercept (1.7%; p<0.0001). For themselves, physicians were more likely to recommend ranibizumab (44.9%) over bevacizumab (39.2%) and aflibercept (15.9%; p<0.0001). When comparing among the anti-VEGF agents chosen for patients with CRVO, a majority of physicians recommended bevacizumab (56.7%) over ranibizumab (28.2%) and aflibercept (15.1%; p<0.0001), but when choosing for themselves, retina specialists were equally divided among the three biologics (aflibercept 30.6%, bevacizumab 36.5% and ranibizumab 32.9%; p=0.559). The results were influenced by geographical location but not by the gender, the length of practice or the type of practice. Physicians should be aware that cognitive biases exist and take this into consideration when making treatment recommendations for their patients.


Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX.
A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.


Nanomechanical properties of wing membrane layers in the house cricket (Acheta domesticus Linnaeus).
Many insect wings change shape dynamically during the wingbeat cycle, and these deformations have the potential to confer energetic and aerodynamic benefits during flight. Due to the lack of musculature within the wing itself, the changing form of the wing is determined primarily by its passive response to inertial and aerodynamic forces. This response is in part controlled by the wing's mechanical properties, which vary across the membrane to produce regions of differing stiffness. Previous studies of wing mechanical properties have largely focused on surface or bulk measurements, but this ignores the layered nature of the wing. In our work, we investigated the mechanical properties of the wings of the house cricket (Acheta domesticus) with the aim of determining differences between layers within the wing. Nanoindentation was performed on both the surface and the interior layers of cross-sectioned samples of the wing to measure the Young's modulus and hardness of the outer- and innermost layers. The results demonstrate that the interior of the wing is stiffer than the surface, and both properties vary across the wing.


Upscaling DAC Hubs with Wind Energy and CO2 Mineral Storage: Considerations for Large-Scale Carbon Removal from the Atmosphere.
Continued fossil fuel emissions will increase CO2 concentrations in the atmosphere and could require removal of 10 Gt of CO2 per year or more to reach IPCC global climate goals. Large-scale construction of direct air capture (DAC) hubs to scrub CO2 from the atmosphere paired with geological storage is a prominent approach to potentially meet this target. We consider one location for theoretical scale-up of a DAC hub: the Kerguelen plateau in the Southern Indian Ocean which has high-potential renewable energy resources (wind) and large volumes of basalt rock for mineral storage. With consistent wind, previous studies indicate a hub in this location could collect approximately 75 Mt of CO2 annually, with conservative storage resources for 150-300 Mt of CO2 each year. Even with its immense wind and storage potentials, 14 Kerguelen-scale hubs would be needed to capture and store 1 Gt of CO2 per year. This brings into focus the important social, economic, and environmental trade-offs that must be considered in finding an acceptable balance between climate solutions, renewable energy requirements, and nature. Engaging public groups on these trade-off considerations will be crucial for gigaton scale-up of CO2 removal in just and responsible ways.


Validation of Anthropometric Measures Self-Reported in a Randomized Controlled Trial of a Web-Based Platform for Weight Loss.
A great number of weight loss interventions have been delivered through digital solutions. Analysis of the effectiveness in terms of weight loss is fundamental to understand the real potential of digital technologies as tools for delivery of weight loss interventions. For this, we need accurate and reliable anthropometric data. For reasons of convenience, self-reported weight and height often replace actual measurements in these interventions. This might lead to misclassification of BMI status during selection of participants and to bias in the assessment of the outcomes. Therefore, it is fundamental to have validation studies of self-reported web-based data. We aimed to validate online self-reported height, weight and BMI in a POEmaS trial subsample. We included 12.5% of the POEmaS' population (n=159). Anthropometric data reported on the web-platform were compared to measured data by paired T-tests. Agreement was assessed by Bland-Altman plots. Multinomial regression was used to investigate factors associated with self-reported weight validity. There was no significant difference between reported and measured weight (0.4 kg, SD 1.7; p=0.13) and BMI (0.03 kg/m2, SD 0.87; p=0.06). Reported height was on average 0.4 cm (SD 1.2) higher than the measured ones (p<0.001). For all anthropometric data, >=95% of the cases were within the limits of agreement. Higher measured BMI was the only factor associated with low accuracy of weight report. Each unit increase in BMI increased the odds that the reported weight was lower than the one measured (OR 1.13; 95%CI 1.01-1.26). Self-reported weight and BMI change showed good agreement with measured ones. Since these are the primary outcomes of the POEmaS trial, the findings of the validation study suggest that the outcomes' accuracy is high and that it does not vary across gender, age, study group. These findings are relevant to digital health researchers and assessors and suggest that digital health interventions for weight loss might rely on self-reported assessment of outcomes. This might be particularly useful when other modes of assessment, such as anthropometry and e-scales, are not feasible or not available. However, we acknowledge that these results might not be applicable to low educated populations.


CXCL13 Is A Biomarker Of Anti-Leucine-Rich Glioma-Inactivated Protein 1 Encephalitis Patients.
Although antibody-mediated immune responses are considered pathogenic and responsible for neural injury in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis, previous studies have indicated that cytokines and chemokines might play roles in the pathogenic process by serving as B cell enhancers. In this study, we detected the profiles of cytokines and chemokines in the cerebral fluid (CSF) and serum of patients with anti-LGI1 encephalitis to identify potential biomarkers. Sixteen patients diagnosed with anti-LGI1 encephalitis and nine patients diagnosed with noninflammatory neurologic disorders were included in the study. Cytokines and chemokines including IL-6, IL-10, IL-17, CXCL12, CXCL13, BAFF and HMGB1 in serum and CSF were measured. The serum and CSF levels of CXCL13 were significantly higher in patients with anti-LGI1 encephalitis (36.32±34.71 pg/mL and 2.23±2.41 pg/mL, respectively) than in controls (10.84±5.02 pg/mL and 0.34±0.21 pg/mL, respectively). There was no significant difference in serum or CSF levels of IL-6, IL-10, IL-17, CXCL12, BAFF and HMGB1 between the two groups. CXCL13 is a potential biomarker of active inflammation in anti-LGI1 encephalitis. The distinctive response of cytokines and chemokines might be closely linked to the mechanisms underlying this condition.


Differential Interaction of Synthetic Glycolipids with Biomimetic Plasma Membrane Lipids Correlates with the Plant Biological Response.
Natural and synthetic amphiphilic molecules including lipopeptides, lipopolysaccharides, and glycolipids are able to induce defense mechanisms in plants. In the present work, the perception of two synthetic C14 rhamnolipids, namely, Alk-RL and Ac-RL, differing only at the level of the lipid tail terminal group have been investigated using biological and biophysical approaches. We showed that Alk-RL induces a stronger early signaling response in tobacco cell suspensions than does Ac-RL. The interactions of both synthetic RLs with simplified biomimetic membranes were further analyzed using experimental and in silico approaches. Our results indicate that the interactions of Alk-RL and Ac-RL with lipids were different in terms of insertion and molecular responses and were dependent on the lipid composition of model membranes. A more favorable insertion of Alk-RL than Ac-RL into lipid membranes is observed. Alk-RL forms more stable molecular assemblies than Ac-RL with phospholipids and sterols. At the molecular level, the presence of sterols tends to increase the RLs' interaction with lipid bilayers, with a fluidizing effect on the alkyl chains. Taken together, our findings suggest that the perception of these synthetic RLs at the membrane level could be related to a lipid-driven process depending on the organization of the membrane and the orientation of the RLs within the membrane and is correlated with the induction of early signaling responses in tobacco cells.


Compliance, adherence, and concordance: implications for asthma treatment.
Good-quality outcomes in asthma hinge not just on the availability of medications but also on their appropriate use by patients: optimal "self-management." In asthma, low rates of adherence to prophylactic (preventer) medication are associated with higher rates of hospitalization and death. Many patients choose not to take their medication because they perceive it to be unnecessary or because they are concerned about potential adverse effects. Approximately one third of asthma patients have strong concerns about adverse effects from inhaled corticosteroids (ICS). These concerns are not just related to the experience of local symptoms attributed to ICS side effects, but also include more abstract concerns about the future, arising from the belief that regular use of ICS will result in adverse long-term effects or dependence. We need more effective ways of eliciting and addressing patients' concerns about ICS. The development of ICS options with an improved safety profile remains a key objective. However, the ideal solution is not just pharmacologic. We also need more effective ways of communicating the relative benefits and risks to patients in order to facilitate informed adherence. Clinicians must be prepared to work in an ongoing partnership with patients to ensure that they are offered a clear rationale as to why ICS are necessary and to address their concerns about potential adverse effects. This approach, based on a detailed examination of patients' perspectives on asthma and its treatment, and an open, nonjudgmental manner on the part of the clinician, is consistent with the idea of concordance.


Pharmacologic treatment of pediatric headaches: a meta-analysis.
OBJECTIVE To assess the effectiveness of prophylactic headache treatment in children and adolescents. DATA SOURCES PubMed, EMBASE, Cochrane Database of Clinical Trials, and bibliography of retrieved articles through August 11, 2012. STUDY SELECTION Randomized trials of headache treatment among children and adolescents (<18 years old). INTERVENTION Any placebo-controlled trial or comparisons between 2 or more active medications. MAIN OUTCOME MEASURE Number of headaches per month. RESULTS Among 21 included trials, there were 13 placebo-controlled and 10 active comparator trials (2 also included placebo). Twenty trials focused on episodic migraines and 1 on chronic daily headaches. Drugs more effective than placebo for episodic migraines (<15 headaches per month) included topiramate (difference in headaches per month, -0.71; 95% CI, -1.19 to -0.24) and trazodone (-0.60; 95% CI, -1.09 to -0.11). Ineffective drugs included clonidine, flunarizine, pizotifen, propranolol, and valproate. A single trial of fluoxetine for chronic daily headaches found it ineffective. Patients given placebo experienced a significant (P = .03) decline in headaches, from 5.6 (95% CI, 4.52-6.77; Q = 8.14 [Cochran Q is a measure of the heterogeneity of the included studies]) to 2.9 headaches per month (95% CI, 1.66-4.08; Q = 4.72). Among the 10 active comparator trials, flunarizine was more effective than piracetam (difference in headaches per month, -2.20; 95% CI, -3.93 to -0.47) but no better than aspirin, dihydroergotamine, or propranolol. Propranolol was compared with valproate as well as behavioral treatment, and 2 studies compared different doses of topiramate; none of these trials showed significant differences. CONCLUSIONS Topiramate and trazodone have limited evidence supporting efficacy for episodic migraines. Placebo was effective in reducing headaches. Other commonly used drugs have no evidence supporting their use in children and adolescents. More research is needed.


Transplantation of young ovaries restored cardioprotective influence in postreproductive-aged mice.
The female cardioprotective advantage, present in mammals of a reproductively competent age, is lost during the transition to a postreproductive state. The role of reproductive hormones in this transition is most evident in women with premature ovarian failure, where reduced estrogen production has been associated with an increased incidence of early death from cardiovascular disease. Previously, we reported that postreproductive-aged mice that received young ovaries displayed an increased life span. Subsequent histopathological analysis suggested the presence of a cardioprotective effect associated with the restoration of ovarian influence. This restoration in postreproductive-aged mice produced a sharp decrease in evidence of significant cardiomyopathy at death, compared with sham-transplanted mice (36.0% vs. 73.3%, respectively). Within the intact transplant group, evidence of cardiomyopathy at death was decreased in mice that were reproductively cycling at the time of transplant, compared with acyclic mice (26.7% vs. 50.0%, respectively). This observation reflects the importance of timing in restoration of ovarian influence in this study. Transplantation of young ovaries to intact, postreproductive-aged female mice provided significant, long-term restoration of a cardioprotective benefit, similar to that previously present during a reproductively competent age. In these mice, restoration of ovarian influence through ovarian transplantation may, in effect, have postponed the advance of age-associated cardiomyopathy to a point where the disease did not reach a clinically relevant threshold during the lifetime of the recipients. These results offer support for previous clinical observations suggesting that hormone replacement therapy can produce divergent results if initiated during the perimenopausal period, compared with the postmenopausal ages.


Estimation of Young's modulus and Poisson's ratio of soft tissue from indentation using two different-sized indentors: finite element analysis of the finite deformation effect.
Young's modulus and Poisson's ratio of a tissue can be simultaneously obtained using two indentation tests with two different sized indentors in two indentations. Owing to the assumption of infinitesimal deformation of the indentation, the finite deformation effect of indentation on the calculated material parameters was not fully understood in the double indentation approach. However, indentation tests with infinitesimal deformation are not practical for the measurement of real tissues. Accordingly, finite element models were developed to simulate the indentation with different indentor diameters and different deformation ratios to investigate the finite deformation effect of indentation. The results indicated that Young's modulus E increased with the increase in the indentation deformation w, if the finite deformation effect of indentation was not considered. This phenomenon became obvious when Poisson's ratio v approached 0.5 and/or the ratio of indentor radius and tissue thickness a/h increased. The calculated Young's modulus could be different by 23% at 10% deformation in comparison with its real value. The results also demonstrated that the finite deformation effect to indentation on the calculation of Poisson's ratio v was much smaller. After the finite deformation effect of indentation was considered, the error of the calculated Young's modulus could be controlled within 5% (a/h = 1) and 2% (a/h = 2) for deformation up to 10%.


Editorial: One Reason Why Not.
After declining modestly from 1999 to 2007, death rates from suicide in adolescents increased 56% from 2007 to 2016.1 Suicide continues to be the second leading cause of death in this age group. Risk factors for suicidal thoughts and behavior in adolescents are not altogether different from those in adulthood, with potent risk factors including depression, a history of abuse, and, of course, prior suicidal ideation.2 One risk factor to which youth may be more susceptible than adults is media reports of suicide, including fictional stories. This effect whereby vulnerable youths imitate the suicidal behavior of celebrities, other youths, or fictional characters has referred to as "suicide contagion" or "copycat suicide." The study "Association Between the Release of Netflix's 13 Reasons Why and Suicide Rates in the United States: An Interrupted Time Series Analysis" in this issue tests whether this effect was observed in response to the release of the Netflix series 13 Reasons Why.3.


Cloning and sequencing of the granulin gene from the Trichoplusia ni granulosis virus.
A restriction fragment containing the granulin gene from the Trichoplusia ni granulosis virus was located in a blot of viral genomic DNA using a cloned polyhedrin gene as a probe. This fragment was cloned, mapped, subcloned, and the sequence of the coding region and 5' and 3' flanking regions was determined. Although granulin is very similar in size to nuclear polyhedrosis virus polyhedrins, the N-terminal region of granulin demonstrated a high degree of variability with the first 60 amino acids only 28% homologous to the Autographa californica nuclear polyhedrosis virus (AcMNPV) polyhedrin sequence. Between amino acid 60 and the carboxyterminus at amino acid 248, the sequence was very similar (64%) to polyhedrin sequences. Overall the nucleotide and amino acid sequences were 58 and 53%, respectively, related to those of AcMNPV. No introns were evident in the gene.


Comparison of phenotypic and functional dendritic cells derived from human umbilical cord blood and peripheral blood mononuclear cells.
Dendritic cells (DC) are important accessory cells that are capable of initiating an immune response. Generation of functional DC has potential clinical use in treating diseases such as cancer. In this report, we have demonstrated the generation of functional DC from mononuclear cells isolated from human umbilical cord blood cells (UCBC) and peripheral blood cells (PBC) using a defined medium Prime Complete Growth Medium (PCGM) (GenePrime LLC, Gaithersburg, MD). DC generated using PCGM showed the typical phenotype of DC as determined by flow cytometry and electron microscopy. Further analysis of the DC using confocal microscopy showed localization of the antigen and major histocompatibility complex (MHC) molecules in the cytoplasm 3-5 days following tumor antigen loading into DC. Subsequently, the tumor antigen-MHC complex was localized on the surface of DC. DC generated from UCBC or PBC also increased (p < 0.001) the allogeneic mixed lymphocyte reaction, confirming their immune accessory functions compared to a control mixed lymphocyte reaction (MLR) without DC added. Interestingly, DC generated using PCGM medium also significantly enhanced the hematopoietic colony (CFU-C)-forming ability. Furthermore, addition of 5% DC derived from cord blood loaded with tumor antigen also significantly (p < 0.001) increased peripheral and cord blood-derived antigen-specific cytotoxic T lymphocyte (CTL)-mediated killing of human leukemic cells (K562) and breast cancer cells (MDA-231). Thus, these results show that functional DC generated from cord blood using a defined medium are a useful source of accessory cells for augmenting CTL-mediated cytotoxicity and have potential use in cellular therapy for human leukemia and breast cancer.


Aseptic barriers in surgery: their present status.
Aseptic barriers are employed in the form of surgical gowns, drapes, and wrappers for sterile goods. They possess many of the attributes of textiles, but must also protect sterile zones from microbial invasion. Surgeons rely on them to resist penetration by liquids and other bacterial vehicles. A large variety of both woven and nonwoven materials are being produced for this purpose. The user is faced with difficult choices. The provider of the barrier materials must assure the surgeon of their barrier quality under the usual conditions of their use in operating rooms. Identical standards of quality can be and should be applicable whether these materials are created to be used once and discarded or are reusable.


Prognostic value of interim positron emission tomography in patients with peripheral T-cell lymphoma.
The definition of the role of positron emission tomography (PET) in peripheral T-cell lymphomas (PTCLs) is still under investigation. The purpose of the present observational retrospective study was to assess the early prognostic value of PET after the first three cycles of therapy (PET+3), evaluating visual data in de novo PTCL patients treated in first line with standard chemotherapy and followed by both PET and computed tomography scan. Of 27 PET+3-negative patients, 19 also had a negative PET at the end of treatment (PET+6), whereas 8 of 27 had a positive final one; 6 of 7 PET+3-positive patients had a positive PET+6, whereas only 1 patient had a negative PET+6. Estimated overall survival plotted according to PET+3 results showed 78.6% for negative patients and 21.4% for positive patients at 88.7 months with a significant difference. Patients with negative PET+3 had superior progression-free survival of 72.6% compared with 16.7% of PET+3-positive patients. At the time of this analysis, 17 of 19 (89.5%) patients with negative PET+3 are in continuous complete response (CCR) and only 1 of 7 (14.2%) patients with positive PET+3 is still in CCR. In conclusion, our results indicate that positive PET+3 is predictive of a worse outcome in PTCL, and this significant statistical difference between the two curves could be clinically informative. Larger and prospective studies and harmonization of PET reading criteria are needed.


Matrix metalloproteinase 12 overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis.
Matrix metalloproteinase 12 (MMP12) is a macrophage-secreting proteinase. To fully understand the function of MMP12 in myeloid lineage cells, a myeloid-specific c-fms-rtTA/(TetO)₇-CMV-MMP12 bitransgenic mouse model was created. In this bitransgenic system, induction of MMP12 abnormally elevated frequencies and numbers of common myeloid progenitor (CMP) and granulocyte/macrophage progenitor (GMP) populations, and decreased the frequency and number of the megakaryocyte/erythrocyte progenitor (MEP) population in the bone marrow (BM). The CD11b(+)/Gr-1(+) immature cell population was systemically increased in multiple organs. Both in vitro and in vivo studies showed an immunosuppressive function on T-cell proliferation and function by CD11b(+)/Gr-1(+) immature cells from MMP12-overexpressing bitransgenic mice. MMP12 directly stimulated lineage-negative (Lin⁻) progenitor cells to differentiate into CD11b(+)/Gr-1(+) immature cells that showed immunosuppression on T-cell proliferation and function in vitro. Regulatory T cells (Tregs) were increased. In the lung, the concentration of IL-6 was increased, which aberrantly activated oncogenic Stat3 and increased expression of Stat3 downstream genes in epithelial tumor progenitor cells. Spontaneous emphysema and lung adenocarcinoma were sequentially developed after MMP12 overexpression. BM chimeras confirmed that the MMP12-induced myeloid cell autonomous defect led to abnormal myelopoiesis, immune suppression, and lung adenocarcinoma.


Accuracy of Components of SCAT to Identify Children With Concussion.
The Sport Concussion Assessment Tool version 3 (SCAT3) and its child version (ChildSCAT3) are composite physical and neuropsychological scoring systems used to assess athletes after sport-related concussion. Based on limited validation data, we aimed to evaluate the ability of SCAT3 and ChildSCAT3 to differentiate children aged 5 to 16 years with concussion from controls. Prospective observational study of children in the emergency department with concussion (CONC group) and 2 control groups ([1] upper-limb injury [ULI] and [2] Well children) with equal-sized subgroups in 3 age bands of 5 to 8, 9 to 12, and 13 to 16 years. ChildSCAT3 was used for participants aged 5 to 12 years, and SCAT3 was used for participants aged 13 to 16 years. Differences between study groups were analyzed by using analysis of variance models, adjusting for age and sex. We enrolled 264 children (90 CONC, 90 ULI, and 84 Well) in equal-sized age bands. The number and severity of child- and parent-reported symptom scores were significantly higher in the CONC group than either control group (P < .001). Mean double (ChildSCAT3 P < .001) and tandem stance errors (both P ≤ .01) were also significantly higher, and immediate memory was significantly lower for the CONC group (P < .01). No statistically significant group differences were found for orientation and digit backward tasks. There were no significant differences between ULI and Well control groups. Overall, SCAT3 and ChildSCAT3 can differentiate concussed from nonconcussed patients, particularly in symptom number and severity.


Skeletal muscle MRI differentiates SBMA and ALS and correlates with disease severity.
To investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disorders: spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS). We applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA. Quantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thigh: p < 0.001; calf: p = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA. Our findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.


Assessment and certification of neonatal incubator sensors through an inferential neural network.
Measurement and diagnostic systems based on electronic sensors have been increasingly essential in the standardization of hospital equipment. The technical standard IEC (International Electrotechnical Commission) 60601-2-19 establishes requirements for neonatal incubators and specifies the calibration procedure and validation tests for such devices using sensors systems. This paper proposes a new procedure based on an inferential neural network to evaluate and calibrate a neonatal incubator. The proposal presents significant advantages over the standard calibration process, i.e., the number of sensors is drastically reduced, and it runs with the incubator under operation. Since the sensors used in the new calibration process are already installed in the commercial incubator, no additional hardware is necessary; and the calibration necessity can be diagnosed in real time without the presence of technical professionals in the neonatal intensive care unit (NICU). Experimental tests involving the aforementioned calibration system are carried out in a commercial incubator in order to validate the proposal.


Promoter analysis of the cell surface-abundant and hypoviral-regulated cryparin gene from Cryphonectria parasitica.
Cryparin, encoded as a single copy gene (Crp) of the chestnut blight fungus Cryphonectria parasitica, is the most abundant protein produced by this fungus. However, its accumulation is decreased remarkably in C. parastica strains containing the double-stranded (ds) RNA virus Cryphonectria hypovirus 1. To characterize the transcriptional regulatory element(s) for strong expression and viral regulation, promoter analysis was conducted. Serial deletion of the Crp promoter region resulted in a step-wise decrease in promoter activity, indicating a localized distribution of genetic elements in the cryparin promoter. Promoter analysis indicated two positive and a repressive cis-acting elements. Among them, the promoter region between nt -1,282 and -907 appeared to be necessary for hypoviral-mediated down-regulation. An electrophoretic mobility shift assay (EMSA) on the corresponding promoter region (-1,282/-907) indicated two regions at (-1257/-1158) and (-1107/-1008) with the characteristic AGGAGGA-N42-GAGAGGA and its inverted repeat TCCTCTC-N54-TCCTCCT, respectively, appeared to be specific binding sites for cellular factors.


Kinetics and toxicological potential of heavy metal leaching from asphalt pavements.
The leaching of heavy metals from asphalt pavement has attracted increasing attention due to its associated environmental risks. Comprehending the leaching process is crucial for ensuring the safe utilization of asphalt pavement. This study investigates heavy metal leaching kinetics from asphalt pavements using tank-leaching tests and dynamic simulations employing both first and second-order kinetic models. Furthermore, this study reveals the toxicological potential of heavy metal leaching from asphalt pavement by assessing its temporal metal accessibility based on the obtained kinetic attributes. Six distinct asphalt mixtures were prepared and tested, each exhibiting two different gradations. The findings demonstrated that both kinetic models effectively elucidated the leaching process. Notably, the relatively stable final leaching stages primarily adhered to first-order kinetics, while the second-order kinetics provided a superior description of the more intricate initial leaching stages. In terms of toxicological potential, the results indicated that recycled waste-incorporated asphalt pavements, specifically bottom ash-incorporated asphalt and asphalt rubber, exhibited excessive heavy metal leaching for varying durations, ranging from several days to months under specific conditions. This study has provided valuable insights into the metal leaching kinetics of asphalt pavements and their associated toxicological impact, significantly advancing the current understanding of the consequences of heavy metal leaching from asphalt pavements.