Ubiquitous Superconducting Diode Effect in Superconductor Thin Films.
The macroscopic coherence in superconductors supports dissipationless supercurrents that could play a central role in emerging quantum technologies. Accomplishing unequal supercurrents in the forward and backward directions would enable unprecedented functionalities. This nonreciprocity of critical supercurrents is called the superconducting (SC) diode effect. We demonstrate the strong SC diode effect in conventional SC thin films, such as niobium and vanadium, employing external magnetic fields as small as 1 Oe. Interfacing the SC layer with a ferromagnetic semiconductor EuS, we further accomplish the nonvolatile SC diode effect reaching a giant efficiency of 65%. By careful control experiments and theoretical modeling, we demonstrate that the critical supercurrent nonreciprocity in SC thin films could be easily accomplished with asymmetrical vortex edge and surface barriers and the universal Meissner screening current governing the critical currents. Our engineering of the SC diode effect in simple systems opens the door for novel technologies while revealing the ubiquity of the Meissner screening effect induced SC diode effect in superconducting films, and it should be eliminated with great care in the search for exotic superconducting states harboring finite-momentum Cooper pairing.


'Wrongful life' lawsuits for faulty genetic counselling: should the impaired newborn be entitled to sue?
A "wrongful life" suit is based on the purported tortious liability of a genetic counsellor towards an infant with hereditary defects, with the latter asserting that he or she would not have been born at all if not for the counsellor's negligence. This negligence allegedly lies in the failure on the part of the defendant adequately to advice the parents or to conduct properly the relevant testing and thereby prevent the child's conception or birth (where unimpaired life was not possible). This paper will offer support for the thesis that it would be both feasible and desirable to endorse "wrongful life" compensation actions. The genetic counsellor owed a duty of due professional care to the impaired newborn who now claims that but for the counsellor's negligence, he or she would not have been born at all. The plaintiff's defective life (where healthy life was never an option) constitutes a compensable injury. A sufficient causal link may exist between the plaintiff's injury and the defendant's breach of duty of due professional care and an appropriate measure of damages can be allocated to the disabled newborn. Sanctioning a "wrongful life" cause of action does not necessarily entail abandoning valuable constraints with regard to abortion and euthanasia. Nor does it inevitably lead to an uncontrolled slide down a "slippery slope".


Ca(2+)-induced light adaptation in retinal ON-bipolar cells.
Retinal ON-bipolar cells possess a metabotropic glutamate receptor linked to the control of a cGMP cascade, which functions to generate high synaptic amplification of rod signals under dark-adapted conditions. We report that a major component of light adaptation of the rod visual system results from a reduction in gain in synaptic transmission from rods to ON-bipolar cells, initiated by Ca(2+)-loading when the cGMP-activated channels of the postsynaptic cell open with light. When intracellular Ca(2+)-buffering was reduced adaptation was induced in ON-bipolar cells by background light too weak to significantly desensitize rods, a property absent in OFF-bipolar cells. Desensitization of ON-bipolar cell flash responses was induced by raising intracellular free Ca2+.


Depressive and anxiety disorders predicting first incidence of alcohol use disorders: results of the Netherlands Study of Depression and Anxiety (NESDA).
Depressive and anxiety disorders may predict first incidence of alcohol abuse and alcohol dependence. This study aims to identify those persons who are at an increased risk of developing alcohols abuse or alcohol dependence by considering the heterogeneity of depressive and anxiety disorders and exploring the role of other risk factors. In a large sample of persons with and without baseline DSM-IV depressive or anxiety disorders (n = 2,676; 18-65 years; assessed in 2004-2007), the first incidences of DSM-IV alcohol abuse and alcohol dependence during a 4-year follow-up were considered as primary outcomes. Status (remitted or current disorder), severity, and type (specific disorders) of depressive and anxiety disorders were assessed, as well as other risk factors, such as sociodemographic, vulnerability, and addiction-related factors. Cumulative first-incidence rates of alcohol abuse and alcohol dependence were 2.0% and 3.0%, respectively. Persons with current, but not remitted, depressive or anxiety disorders were at an increased risk of a first incidence of alcohol dependence (hazard ratio [HR] = 2.69; 95% CI, 1.37-5.29), but not first incidence of alcohol abuse (HR = 0.55; 95% CI, 0.28-1.09). Although this association was not conditional on the type of disorder, first-incidence rates of alcohol dependence gradually increased with the number of depressive and anxiety disorders (HR per SD increase = 1.65; 95% CI, 1.37-2.00). Subthreshold alcohol problems especially (P < .001), but also recent negative life events (P = .06), were additional independent predictors of first incidence of alcohol dependence. Current depressive disorder, anxiety disorder, or both significantly predicted first incidence of alcohol dependence, which stresses the importance of addiction prevention strategies for depressed and anxious patients in mental health settings. Subthreshold alcohol problems and recent negative life events may help to identify persons at an increased risk for developing alcohol dependence.


Five focus strategies to organize health care delivery.
The focused factory is one of the concepts that decision-makers have adopted for improving health care delivery. However, disorganized definitions of focus have led to findings that cannot be utilized systematically. The purpose of this paper is to discuss strategic options to focus health care operations. First the literature on focus in health care is reviewed revealing conceptual challenges. Second, a definition of focus in terms of demand and requisite variety is defined, and the mechanisms of focus are explicated. A classification of five focus strategies that follow the original idea to reduce variety in products and markets is presented. Finally, the paper examines managerial possibilities linked to the focus strategies. The paper proposes a framework of five customer-oriented focus strategies which aim at reducing variety in different characteristics of care pathways: population; urgency and severity; illnesses and symptoms; care practices and processes; and care outcomes. Empirical research is needed to evaluate the costs and benefits of the five strategies and about system-level effects of focused units on competition and coordination. Focus is an enabling condition that needs to be exploited using specific demand and supply management practices. It is essential to understand how focus mechanisms differ between strategies, and to select focus that fits with organization's strategy and key performance indicators. Compared to previous more resource-oriented approaches, this study provides theoretically solid and practically relevant customer-oriented framework for focusing in health care.


Carbohydrate-protein interactions that drive processive polysaccharide translocation in enzymes revealed from a computational study of cellobiohydrolase processivity.
Translocation of carbohydrate polymers through protein tunnels and clefts is a ubiquitous biochemical phenomenon in proteins such as polysaccharide synthases, glycoside hydrolases, and carbohydrate-binding modules. Although static snapshots of carbohydrate polymer binding in proteins have long been studied via crystallography and spectroscopy, the molecular details of polysaccharide chain processivity have not been elucidated. Here, we employ simulation to examine how a cellulose chain translocates by a disaccharide unit during the processive cycle of a glycoside hydrolase family 7 cellobiohydrolase. Our results demonstrate that these biologically and industrially important enzymes employ a two-step mechanism for chain threading to form a Michaelis complex and that the free energy barrier to chain threading is significantly lower than the hydrolysis barrier. Taken with previous studies, our findings suggest that the rate-limiting step in enzymatic cellulose degradation is the glycosylation reaction, not chain processivity. Based on the simulations, we find that strong electrostatic interactions with polar residues that are conserved in GH7 cellobiohydrolases, but not in GH7 endoglucanases, at the leading glucosyl ring provide the thermodynamic driving force for polysaccharide chain translocation. Also, we consider the role of aromatic-carbohydrate interactions, which are widespread in carbohydrate-active enzymes and have long been associated with processivity. Our analysis suggests that the primary role for these aromatic residues is to provide tunnel shape and guide the carbohydrate chain to the active site. More broadly, this work elucidates the role of common protein motifs found in carbohydrate-active enzymes that synthesize or depolymerize polysaccharides by chain translocation mechanisms coupled to catalysis.


Surgical treatment of double-orifice mitral valve in atrioventricular canal defects. Experience in 25 patients.
Double-orifice mitral valve is an uncommon but surgically important condition. The experience in 25 cases of double-orifice mitral valve associated with atrioventricular canal defects was reviewed. This constituted 4.3% of the 581 cases of atrioventricular canal defects operated upon between 1961 and July, 1984. The combined mitral orifice area ranged from 85% to 91% of normal in those patients whose valves were sized intraoperatively. Ten associated cardiac defects were repaired in six patients. Of 23 patients having cleft mitral valve, 21 had partial closure of the cleft. There was one operative death (4.0%), which occurred early in the series in a patient in whom the tissue bridge was severed and massive mitral regurgitation resulted. In the remaining 24 patients the tissue bridge was left intact, and all survived operation. No patient had clinically significant mitral stenosis during a follow-up of 1 to 14 years (mean 4.9 years). Two patients (8%) developed progressive mitral regurgitation and required mitral valve replacement 3 and 11 years postoperatively. One of these patients died and a second death occurred suddenly 2 years following operation. All survivors are in Functional Class I or II. The noncleft orifice of a double-orifice mitral valve usually is competent and rarely requires closure. The cleft, because it constitutes a type of parachute (single papillary muscle) valve, should be closed partially so as to relieve valve incompetence without causing undue stenosis. The incidence of late development of mitral regurgitation is similar to that of atrioventricular canal without double-orifice mitral valve. Repair of atrioventricular canal associated with double-orifice mitral valve can be achieved with a low operative mortality and excellent late results.


Analysis of Sensitivity, Linearity, Hysteresis, Responsiveness, and Fatigue of Textile Knit Stretch Sensors.
Wearable technology is widely used for collecting information about the human body and its movement by placing sensors on the body. This paper presents research into electronic textile strain sensors designed specifically for wearable applications which need to be lightweight, robust, and comfortable. In this paper, sixteen stretch sensors, each with different conductive stretch fabrics, are evaluated: EeonTex (Eeonyx Corporation), knitted silver-plated yarn, and knitted spun stainless steel yarn. The sensors' performance is tested using a tensile tester while monitoring their resistance with a microcontroller. Each sensor was analyzed for its sensitivity, linearity, hysteresis, responsiveness, and fatigue through a series of dynamic and static tests. The findings show that for wearable applications a subset of the silver-plated yarn sensors had better ranked performance in terms of sensitivity, linearity, and steady state. EeonTex was found to be the most responsive, and the stainless steel yarn performed the worst, which may be due to the characteristics of the knit samples under test.


The epigenetics of aging and neurodegeneration.
Epigenetics is a quickly growing field encompassing mechanisms regulating gene expression that do not involve changes in the genotype. Epigenetics is of increasing relevance to neuroscience, with epigenetic mechanisms being implicated in brain development and neuronal differentiation, as well as in more dynamic processes related to cognition. Epigenetic regulation covers multiple levels of gene expression; from direct modifications of the DNA and histone tails, regulating the level of transcription, to interactions with messenger RNAs, regulating the level of translation. Importantly, epigenetic dysregulation currently garners much attention as a pivotal player in aging and age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, where it may mediate interactions between genetic and environmental risk factors, or directly interact with disease-specific pathological factors. We review current knowledge about the major epigenetic mechanisms, including DNA methylation and DNA demethylation, chromatin remodeling and non-coding RNAs, as well as the involvement of these mechanisms in normal aging and in the pathophysiology of the most common neurodegenerative diseases. Additionally, we examine the current state of epigenetics-based therapeutic strategies for these diseases, which either aim to restore the epigenetic homeostasis or skew it to a favorable direction to counter disease pathology. Finally, methodological challenges of epigenetic investigations and future perspectives are discussed.


Gaps in Preexposure Prophylaxis Uptake for HIV Prevention in the Veterans Health Administration.
To report demographics, regional variations, and indications for preexposure prophylaxis (PrEP) use for HIV prevention in the Veterans Health Administration (VHA). We identified persons initiating tenofovir/emtricitabine for the PrEP indication in the United States between July 2012 and April 2016 in a VHA national database. We stratified PrEP use by provider type and VHA region. We calculated PrEP initiation rate for each region with VHA population data. Of the 825 persons who initiated PrEP during the observation period, 67% were White and 76% were men who have sex with men. People who inject drugs and transgender persons represented less than 1% each of the cohort. The majority of PrEP initiations were clustered in 3 states, leading with California (28%) followed by Florida (9%) and Texas (8%). The Southeast had one of the lowest PrEP rates at 10 PrEP initiations per 100 000 persons in care. Infectious disease specialists issued more than two thirds of index PrEP prescriptions. Uptake of PrEP in the VHA is uneven along geographic and risk categories. Understanding the reasons behind these gaps will be key in expanding the use of this important prevention tool.


Retinoic acid functions as a key GABAergic differentiation signal in the basal ganglia.
Although retinoic acid (RA) has been implicated as an extrinsic signal regulating forebrain neurogenesis, the processes regulated by RA signaling remain unclear. Here, analysis of retinaldehyde dehydrogenase mutant mouse embryos lacking RA synthesis demonstrates that RA generated by Raldh3 in the subventricular zone of the basal ganglia is required for GABAergic differentiation, whereas RA generated by Raldh2 in the meninges is unnecessary for development of the adjacent cortex. Neurospheres generated from the lateral ganglionic eminence (LGE), where Raldh3 is highly expressed, produce endogenous RA, which is required for differentiation to GABAergic neurons. In Raldh3⁻/⁻ embryos, LGE progenitors fail to differentiate into either GABAergic striatal projection neurons or GABAergic interneurons migrating to the olfactory bulb and cortex. We describe conditions for RA treatment of human embryonic stem cells that result in efficient differentiation to a heterogeneous population of GABAergic interneurons without the appearance of GABAergic striatal projection neurons, thus providing an in vitro method for generation of GABAergic interneurons for further study. Our observation that endogenous RA is required for generation of LGE-derived GABAergic neurons in the basal ganglia establishes a key role for RA signaling in development of the forebrain.


Gelled non-toxic microemulsions: phase behavior & rheology.
Bicontinuous microemulsions gelled with a low molecular weight gelator have been shown to be an orthogonally self-assembled system. With the mechanical stability provided by the gel network, gelled non-toxic bicontinuous microemulsions have the potential to be an efficient transdermal drug delivery carrier. However, up to now no suitable system has been formulated for transdermal drug delivery. To fill this gap, we formulated and characterized a gelled non-toxic bicontinuous microemulsion suitable for the mentioned application. Starting from a previously studied scouting system, namely, H2O-n-octane-n-octyl β-d-glucopyranoside (β-C8G1)-1-octanol, the co-surfactant and the oil were replaced by non-toxic components. Subsequently, the expensive pure surfactant was replaced by cheap technical-grade surfactants (Plantacare® series) to make the system economical. Having formulated the non-toxic microemulsion H2O-IPM-Plantacare 1200 UP-1,2-octanediol, three low molecular weight gelators were studied with regard to the gelation of both the scouting system and the non-toxic system. The chosen gelators were 12-hydroxyoctadecanoic acid (12-HOA), 1,3:2,4-dibenzylidene-d-sorbitol (DBS), and N,N'-dibenzoyl-l-cystine (DBC). We found that only DBS gels the non-toxic microemulsion. The gelled non-toxic bicontinuous microemulsion H2O-IPM-Plantacare 1200 UP-1,2-octanediol was characterized with oscillatory shear rheometry and small-angle neutron scattering (SANS) at a DBS concentration of 0.3 wt% to verify that the system is indeed a gel and that the microstructure of the microemulsion is not altered by the gel network.


Early developmental milestones and risk of schizophrenia: a 45-year follow-up of the Copenhagen Perinatal Cohort.
The aim of the present study was to investigate the relationship between age of neuromotor milestone attainment and risk of adult schizophrenia. 5765 mothers of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year of life. Cohort members were followed until they were 46-48 years old through record linkage with the Danish Psychiatric Central Research Register. The age at which milestones were met in the 92 individuals who later developed schizophrenia was compared with milestone attainment in the 691 individuals who developed other psychiatric disorders and in the 4982 cohort controls who were never admitted to a psychiatric department. Group comparisons were adjusted for gender, mother's age, father's age, parental social status, breadwinner's education, single mother status and parity. Individuals who developed schizophrenia reached all developmental milestones later than controls and differed significantly from the controls with respect to the mean age of reaching the 12 milestones. Five developmental milestones in particular (smiling, lifting head, sitting, crawling, and walking) differed significantly. Individuals who later developed psychiatric disorders other than schizophrenia reached most developmental milestones earlier than those who developed schizophrenia, but later than the controls. The two psychiatric groups only differed significantly with respect to age of walking without support. The findings corroborate and methodologically extend previous research from prospective longitudinal cohort studies suggesting developmental delays observable as early as within the first year of life. These early developmental delays may not only characterize schizophrenia, but may be associated with a range of psychiatric disorders.


Disgust sensitivity and kosher food preferences among the non-Jewish population in the US.
About $200 billion of kosher-certified foods are purchased each year in the US, and companies can pay up to $100,000 to private agencies to certify that their products meet kosher standards. Although kosher certification is ostensibly for the purpose of Jewish religious observance, the vast majority of people who buy kosher food are not Jewish. In this study, we examine the psychological drivers of these purchases among people who are not Jewish. Our study found that people with high levels of contamination disgust sensitivity were more likely to prefer kosher food, which is often marketed in a manner that implies that it has fewer contaminants. The effect of contamination disgust sensitivity on preference for kosher food was partially mediated by perceptions that kosher food rated highly on dimensions related to oral disgust (food rejection) rather than on dimensions related to moral disgust. Moderated mediation was significant for the factor of subjective knowledge, such that the mediation effect only occurred among participants who reported high levels of knowledge about kosher food. Strength of religious affiliation was a marginally significant covariate, as people who reported high levels of affiliation with organized religion had a greater preference for kosher food.


Radiation-Induced Glandular Malignant Peripheral Nerve Sheath Tumor.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors. They can occur in patients with neurofibromatosis type-1 (NF-1) or as sporadic tumors. Only 10% of MPNSTs are radiation induced. Divergent differentiation in MPNSTs can occur in 15% of cases and may include cartilage, bone, skeletal muscle, blood vessels, and very rarely well-formed glands, the latter typically described in NF-1-associated MPNSTs. We report an exceedingly rare case of radiation induced glandular MPNST arising in a neurofibroma of the femoral nerve in a patient previously irradiated for endometrial carcinoma.


Emotion regulation therapy for social anxiety disorder: a single case series study.
Despite the vast majority of evidence indicating the efficacy of traditional and recent cognitive behaviour therapy (CBT) therapies in treating social anxiety disorder (SAD), some individuals with SAD do not improve by these interventions, particularly when co-morbidity is present. It is not clear how emotion regulation therapy (ERT) can improve SAD co-morbid with symptoms of generalized anxiety disorder (GAD) and depression. This study investigated this gap. Treatment efficacy was assessed using a single case series methodology. Four clients with SAD co-occurring with GAD and depression symptoms received a 16-session version of ERT in weekly individual sessions. During the treatment, self-report measures and clinician ratings were used to assess the symptom intensity, model-related variables, and quality of life, work and social adjustment of participants every other week throughout the treatment. Follow-up was also conducted at 1, 2 and 3 months after treatment. Data were analysed using visual analysis, effect size (Cohen's d) and percentage of improvement. SAD clients with depression and GAD symptoms demonstrated statistically and clinically significant improvements in symptom severity, quality of life, work, social adjustment and model-related measures (i.e. negative emotionality/safety motivation, emotion regulation strategies). The improvements were largely maintained during the follow-up period and increased for some variables. These findings showed preliminary evidence for the role of emotion dysregulation and motivational factors in the aetiology and maintenance of SAD and the efficacy of ERT in the treatment of co-morbid SAD.


Is fibromyalgia a distinct clinical entity? The epidemiologist's evidence.
The key features of fibromyalgia are chronic widespread pain, general distress and enhanced pain sensitivity as revealed by a tender point count. Fibromyalgia could be considered a distinct entity if the key features defined a patient group with any one of the following: a characteristics feature or cluster of features with a distribution clearly demarcating the group from the rest of the population, identifiable risk factors, a characteristic natural course or prognosis, or a specific response to treatment. This should be seen in population studies, not only in selected clinic series. The available epidemiological evidence suggests that the distributions of the key features are continuous and no clear population groups can be defined. Also, difficulties in identifying changes such as incidence and recovery, and unreliable measurements of the key features themselves, detract from the utility of the concept of fibromyalgia as an epidemiological entity.


Non-biodegradable objects may boost microbial growth in water bodies by harnessing bubbles.
Given the ubiquity of bubbles and non-biodegradable wastes in aqueous environments, their transport through bubbles should be widely extant in water bodies. In this study, we investigate the effect of bubble-induced waste transport on microbial growth by using yeasts as model microbes and a silicone rubber object as model waste. Noteworthily, this object repeatedly rises and sinks in fluid through fluctuations in bubble-acquired buoyant forces produced by cyclic nucleation, growth and release of bubbles from object's surface. The rise-sink movement of the object gives rise to a strong bulk mixing and an enhanced resuspension of cells from the floor. Such spatially dynamic contaminant inside a nutrient-rich medium also leads to an increment in the total microbe concentration in the fluid. The enhanced concentration is caused by strong nutrient mixing generated by the object's movement which increases the nutrient supply to growing microbes and thereby, prolonging their growth phases. We confirm these findings through a theoretical model for cell concentration and nutrient distribution in fluid medium. The model is based on the continuum hypothesis and it uses the general conservation law which takes an advection-diffusion growth form. We conclude the study with the demonstration of bubble-induced digging of objects from model sand.


A Heart Rate Monitoring Framework for Real-World Drivers Using Remote Photoplethysmography.
Remote photoplethysmography (rPPG) is an unobtrusive solution to heart rate monitoring in drivers. However, disturbances that occur during driving such as driver behavior, motion artifacts, and illuminance variation complicate the monitoring of heart rate. Faced with disturbance, one commonly used assumption is heart rate periodicity (or spectrum sparsity). Several methods improve stability at the expense of tracking sensitivity for heart rate variation. Based on statistical signal processing (SSP) and Monte Carlo simulations, the outlier probability is derived and ADaptive spectral filter banks (AD) is proposed as a new algorithm which provides an explicable tuning option for spectral filter banks to strike a balance between robustness and sensitivity in remote monitoring for driving scenarios. Moreover, we construct a driving database containing over 23 hours of data to verify the proposed algorithm. The influence on rPPG from driver habits (both amateurs and professionals), vehicle types (compact cars and buses), and routes are also evaluated. In comparison to state-of-the-art rPPG for driving scenarios, the mean absolute error in the Passengers, Compact Cars, and Buses scenarios is 3.43, 7.85, and 5.02 beats per minute, respectively. Moreover, AD also won the top third place in the first challenge on remote physiological signal sensing (RePSS) with relative low computational complexity.


Genito-urological cancers in elderly patients.
Age is now widely accepted as the greatest single risk factor for developing cancer, and cancer is considered primarily as a disease of the elderly. Furthermore, a characteristic of aging is the progressive deterioration of immune function known as immunosenescence. In addition to the increased risk of occurrence of cancer among older patients, they are more predisposed to poor outcomes after definitive treatment. Therapies, outcomes and mortality are often influenced by age and elderly must have a specific and a multidisciplinary approach. It is obvious to consider that one should not consider "age" as the only risk factor, but the condition that this determines to the organism, like the presence of co-morbidities and the consequent poor response to treatment. Cancer occurs frequently in association of one or more other chronic diseases, that affect the efficacy of various treatment interventions. Because of the potential morbidity associated with surgery, the use of mini-invasive techniques have expanded considerably. Aging should not be viewed as a difficulty to definitive therapeutic option. For these reason, it should be correct to value the physiologic capabilities of each organ system and all co-morbidities in the elderly, in order to face possible risks of treatment or improbable benefits. This review takes a look to the tumor biology and to the morbidity of cancer treatment in elderly patients affected by genito-urological cancer like prostate, bladder and renal cancer.


Channel-independent function of UNC-9/Innexin in spatial arrangement of GABAergic synapses in C. elegans.
Precise synaptic connection of neurons with their targets is essential for the proper functioning of the nervous system. A plethora of signaling pathways act in concert to mediate the precise spatial arrangement of synaptic connections. Here we show a novel role for a gap junction protein in controlling tiled synaptic arrangement in the GABAergic motor neurons in Caenorhabditis elegans, in which their axons and synapses overlap minimally with their neighboring neurons within the same class. We found that while EGL-20/Wnt controls axonal tiling, their presynaptic tiling is mediated by a gap junction protein UNC-9/Innexin, that is localized at the presynaptic tiling border between neighboring dorsal D-type GABAergic motor neurons. Strikingly, the gap junction channel activity of UNC-9 is dispensable for its function in controlling tiled presynaptic patterning. While gap junctions are crucial for the proper functioning of the nervous system as channels, our finding uncovered the novel channel-independent role of UNC-9 in synapse patterning.


[Development of dry acidophilic mixtures for feeding young infants].
A procedure for dry acidophilic mixtures for feeding infants has been devised. Two methods for drying the mixtures, atomization and sublimation, have been studied. Comparative characteristics of the acidophilic mixtures are presented and the time course of self-oxidation of their fatty components during 6-month storage is described.


A facile deoxyuridine/biotin-modified molecular beacon for simultaneous detection of proteins and nucleic acids via a label-free and background-eliminated fluorescence assay.
Simultaneous detection of different types of cancer biomarkers (nucleic acids and proteins) could facilitate early diagnosis of cancer and clinical treatment. Herein, a simultaneous detection platform of proteins and nucleic acids has been developed using a single substrate probe combining a label-free and background-eliminated fluorescence assay. Telomerase and telomerase RNA (TR) were chosen as the models. The molecular beacon (dU-BIO-HP) that contains deoxyuridine/biotin in its side arm, a TR recognition sequence in the loop and a telomerase substrate primer at the stem end was ingeniously designed. In the presence of telomerase, the stem of dU-BIO-HP is elongated by the addition of telomere repeats complementary to the assistant DNA. Furthermore, the formed dsDNA performed as engaging primers to initiate a SDA reaction, generating abundant G-quadruplex monomers. Similarly, on TR, the hybridization between TR and dU-BIO-HP can open its stem, triggering another SDA reaction, producing abundant short ssDNAs. With the G-quadruplex binding with ZnPPIX and ssDNA binding with SG for specific fluorescence responses, the label-free multiple detection can be achieved. In our strategy, the deoxyuridine of dU-BIO-HP acts as a barrier to block the DNA extension due to its strong inhibitory effects on DNA polymerase activity and to make sure that the two SDA reactions occurred independently. The biotin of dU-BIO-HP enables the reduction of the background from the binding between SG, ZnPPIX and dU-BIO-HP through streptavidin-biotin interaction. This method showed an excellent sensitivity with telomerase and TR detection limit of 2.18 HeLa cells per mL and 0.16 × 10-12 M, respectively. Furthermore, the telomerase and TR in different cell lines have been evaluated as powerful tools for biomedical research and clinical diagnosis.


Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models.
Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferase-transfected U251 cells by bioluminescence and magnetic resonance imaging. Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6-methylguanine methyltransferase-negative and -positive cell lines.


Attitudes of dental patients towards participation in research.
The attitudes of dental patients towards participation in research and the independent socioeconomic factors associated with these attitudes are not known. A self-administered questionnaire was distributed to 120 patients attending dental clinics in Amman, Jordan. For patients who had previously participated in research (n = 28), motivating factors for most (> 75%) included a desire to help others and to advance science. Most respondents (81.7%) showed interest in participating in questionnaire-based research, but fewer would participate in invasive research, e.g. biopsies (22.0%) and drilling teeth (21.2%). Reasons given for not participating in research included fear of infectious diseases (71.3%) and pain (62.1%). Factors considered important in enhancing research participation included being asked to give informed consent (98.2%), fairness in selection of participants (97.3%) and the prospect of humanitarian benefit (96.5%). Sex and education level were significantly associated with patients' perceptions for several of items. To enhance recruitment, researchers should be aware of people's perspectives regarding participation in research.


Revised tumor and node categorization for rectal cancer based on surveillance, epidemiology, and end results and rectal pooled analysis outcomes.
The sixth edition of the American Joint Committee on Cancer (AJCC) rectal cancer staging subdivided stage II into IIA (T3N0) and IIB (T4N0) and stage III into IIIA (T1-2N1M0), IIIB (T3-4N1M0), and IIIC (anyTN2M0). Subsequent analyses supported revised substaging of stage III as a result of improved survival with T1-2N2 versus T3-4N2 and survival of T4N1 more similar to T3-4N2 than T3N1. The AJCC Hindgut Taskforce sought population-based validation that depth of invasion interacts with nodal status to affect survival. Surveillance, Epidemiology, and End Results (SEER) population-based data from January 1992 to December 2004 for 35,829 patients with rectal cancer were compared with rectal pooled analysis data (3,791 patients). T4N0 cancers were stratified by tumors that perforate visceral peritoneum (T4a) versus tumors that invade or are adherent to adjacent organs or structures (T4b). N1 and N2 were stratified by number of positive nodes as follows: N1a/N1b (one v two to three nodes) and N2a/N2b (four to six v > or = seven nodes). Five-year observed and relative survival rates were obtained for each TN category. SEER rectal cancer analyses confirm that T1-2N2 cancers have better prognosis than T3-4N2, T4bN1 have similar prognosis to T4N2, T1-2N1 have similar prognosis to T2N0/T3N0, and T1-2N2a have similar prognosis to T2N0/T3N0 (T1N2a) or T4aN0 (T2N2a). Prognosis for T4a lesions is better than T4b by N category. The number of positive nodes affects prognosis. This SEER population-based rectal cancer analysis validates the rectal pooled analyses and supports the shift of T1-2N2 lesions from IIIC to IIIA or IIIB and T4bN1 from IIIB to IIIC. SEER outcomes support subdividing T4, N1, and N2 and revised substaging of stages II and III. Survival by TN category suggests a complex biologic interaction between depth of invasion and nodal status.


The Genetics of Keratoconus: A Review.
Keratoconus is the most common ectatic disorder of the corneal. Genetic and environmental factors may contribute to its pathogenesis. The focus of this article is to summarize current research into the complex genetics of keratoconus. We discuss the evidence of genetic etiology including family-based linkage studies, twin studies, genetic mutations, and genome-wide association studies. The genes implicated potentially include VSX1, miR-184, DOCK9, SOD1, RAB3GAP1, and HGF. Besides the coding mutations, we also highlight the potential contribution of DNA copy number variants in the pathogenesis of keratoconus. Finally, we present future directions for genetic research in the understanding of the complex genetics of keratoconus and its clinical significance. As new functional, candidate genes for keratoconus are being discovered at a rapid pace, the molecular genetic mechanisms underlying keratoconus pathogenesis will advance our understanding of keratoconus and promote the development of a novel therapy.


[Liver involvement in patients with dengue hemorrhagic fever: a rare phenomenon?].
Hepatic manifestations are described as unusual complications of dengue and may lead to severe and potentially lethal conditions. Liver abnormalities in 41 patients diagnosed with dengue hemorrhagic fever in Campo Grande, Mato Grosso do Sul, Brazil, between January 1 and March 31, 2002, were evaluated. All were serologically positive for dengue in laboratory tests (IgM ELISA). ALT alterations were observed in 61% (25/41) and AST alterations in 80.5% (33/41), but there were no statistically significant differences between the various clinical forms. The range in ALT levels was 14-547 U/l and in AST levels was 11-298 U/l. Nausea and/or vomiting were reported by 90% (37/41) of the patients; 46.3% (19/41) had abdominal pain and 10% (3/29) presented hepatomegaly at clinical examination. The patients' ages ranged from 18 to 88 years; 23 (56%) were female and 18 (44%) were male.


In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice.
Pomegranate (Punica granatum L.) fruits are widely consumed as juice (PJ). The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA). Punicalagin is the major antioxidant polyphenol ingredient in PJ. Punicalagin, EA, a standardized total pomegranate tannin (TPT) extract and PJ were evaluated for in vitro antiproliferative, apoptotic and antioxidant activities. Punicalagin, EA and TPT were evaluated for antiproliferative activity at 12.5-100 microg/ml on human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, 22Rv1) tumor cells. Punicalagin, EA and TPT were evaluated at 100 microg/ml concentrations for apoptotic effects and at 10 microg/ml concentrations for antioxidant properties. However, to evaluate the synergistic and/or additive contributions from other PJ phytochemicals, PJ was tested at concentrations normalized to deliver equivalent amounts of punicalagin (w/w). Apoptotic effects were evaluated against the HT-29 and HCT116 colon cancer cell lines. Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 microg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.


[Bonded amalgams. An important change in operatory dentistry].
The incorporation of new adhesives which are able to bond amalgam to the dental structure means a hopeful and encouraging advance in Operative Dentistry. The present study has been done from the point of view of the general practitioner, and lets us check the efficacy of the bonded amalgam and compare it with the techniques and materials traditionally used.


Real-World Vehicle Emissions Characterization for the Shing Mun Tunnel in Hong Kong and Fort McHenry Tunnel in the United States.
Motor vehicle exhaust is an important source of air pollutants and greenhouse gases. Concerns over the health and climate effects of mobile-source emissions have prompted worldwide efforts to reduce vehicle emissions. Implementation of more stringent emission standards have driven advances in vehicle, engine, and exhaust after-treatment technologies as well as fuel formulations. On the other hand, vehicle numbers and travel distances have been increasing because of population and economic growth and changes in land use. These factors have resulted in changes to the amount and chemical composition of vehicle emissions. Roadway tunnel studies are a practical way to characterize real-world emissions from the on-road vehicle fleet in an environment isolated from other combustion pollution sources. Measurements in the same tunnel over time allow evaluation of vehicle emission changes and the effectiveness of emission reduction measures. Tunnel studies estimate the impacts of vehicle emissions on air quality and traffic-related exposures, generate source profile inputs for receptor-oriented source apportionment models, provide data to evaluate emission models, and serve as a baseline for future comparisons. The present study characterized motor vehicle emission factors and compositions in two roadway tunnels that were first studied over a decade ago. The specific aims were to (1) quantify current fleet air pollutant emission factors, (2) evaluate emission change over time, (3) establish source profiles for volatile organic compounds (VOCs) and particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), (4) estimate contributions of fleet components and non-tailpipe emissions to VOCs and PM2.5, and (5) evaluate the performance of the latest versions of mobile-source emission models (i.e., the EMission FACtors vehicle emission model used in Hong Kong [EMFAC-HK] and the MOtor Vehicle Emission Simulator used in the United States [MOVES]). Measurements were conducted in the Shing Mun Tunnel (SMT) in Hong Kong and the Fort McHenry Tunnel (FMT) in Baltimore, Maryland, in the United States, representing the different fleet compositions, emission controls, fuels, and near-road exposure levels found in Hong Kong and the United States. These tunnels have extensive databases acquired in 2003-2004 for the SMT and 1992 for the FMT. The SMT sampling was conducted during the period from 1/19/2015 to 3/31/2015, and the FMT sampling occurred during the periods from 2/8/2015 to 2/15/2015 (winter) and 7/31/2015 to 8/7/2015 (summer). Concentrations of criteria pollutants (e.g., carbon monoxide [CO], nitrogen oxides [NOx], and particulate matter [PM]) were measured in real time, and integrated samples of VOCs, carbonyls, polycyclic aromatic hydrocarbons (PAHs), and PM2.5 were collected in canisters and sampling media for off-line analyses. Emission factors were calculated from the tunnel measurements and compared with previous studies to evaluate emission changes over time. Emission contributions by different vehicle types were assessed by source apportionment modeling or linear regression. Vehicle emissions were modeled by EMFAC-HK version 3.3 and MOVES version 2014a for the SMT and the FMT, respectively, and compared with measured values. The influences of vehicle fleet composition and environmental parameters (i.e., temperature and relative humidity) on emissions were evaluated. In the SMT, emissions of PM2.5, sulfur dioxide (SO2), and total non-methane hydrocarbons (NMHCs) markedly decreased from 2003-2004 to 2015: SO2 and PM2.5 were reduced by ~80%, and total NMHCs was reduced by ~44%. Emission factors of ethene and propene, key tracers for diesel vehicle (DV) emissions, decreased by ~65%. These reductions demonstrate the effectiveness of control measures, such as the implementation of low-sulfur fuel regulations and the phasing out of older DVs. However, the emission factors of isobutane and n-butane, markers for liquefied petroleum gas (LPG), increased by 32% and 17% between 2003-2004 and 2015, respectively, because the number of LPG vehicles increased. Nitrogen dioxide (NO2) to NOx volume ratios increased between 2003-2004 and 2015, indicating an increased NO2 fraction in primary exhaust emissions. Although geological mineral concentrations were similar between the 2003-2004 and 2015 studies, the contribution of geological materials to PM2.5 increased from 2% in 2003-2004 to 5% in 2015, signifying the continuing importance of non-tailpipe PM emissions as tailpipe emissions decrease. Emissions of CO, ammonia (NH3), nitric oxide (NO), NO2, and NOx, as well as carbonyls and PAHs in the SMT did not show statistically significant (at P < 0.05 based on Student's t-test) decreases from 2003-2004 to 2015. The reason for this is not clear and requires further investigation. A steady decrease in emissions of all measured pollutants during the past 23 years has been observed from tunnel studies in the United States, reflecting the effect of emission standards and new technologies that were introduced during this period. Emission reductions were more pronounced for the light-duty (LD) fleet than for the heavy-duty (HD) fleet. In comparison with the 1992 FMT study, the 2015 FMT study demonstrated marked reductions in LD emissions for all pollutants: emission factors for naphthalene were reduced the most, by 98%; benzene, toluene, ethylbenzene, and xylene (BTEX), by 94%; CO, NMHCs, and NOx, by 87%; and aldehydes by about 71%. Smaller reductions were observed for HD emission factors: naphthalene emissions were reduced by 95%, carbonyl emissions decreased by about 75%, BTEX by 60%, and NOx 58%. The 2015 fleet-average emission factors were higher in the SMT for CO, NOx, and summer PM2.5 than those in the FMT. The higher CO emissions in the SMT were possibly attributable to a larger fraction of motorcycles and LPG vehicles in the Hong Kong fleet. DVs in Hong Kong and the United States had similar emission factors for NOx. However, the non-diesel vehicles (NDVs), particularly LPG vehicles, had higher emission factors than those of gasoline cars, contributing to higher NOx emissions in the SMT. The higher PM2.5 emission factors in the SMT were probably attributable to there being more double-deck buses in Hong Kong. In both tunnels, PAHs were predominantly in the gas phase, with larger (four and more aromatic rings) PAHs mostly in the particulate phase. Formaldehyde, acetaldehyde, crotonaldehyde, and acetone were the most abundant carbonyl compounds in the SMT. In the FMT, the most abundant carbonyls were formaldehyde, acetone, acetaldehyde, and propionaldehyde. HD vehicles emitted about threefold more carbonyl compounds than LD vehicles did. In the SMT, the NMHC species were enriched with marker species for LPG (e.g., n-butane, isobutane, and propane) and gasoline fuel vapor (e.g., toluene, isopentane, and m/p-xylene), indicating evaporative losses. Source contributions to SMT PM2.5 mass were diesel exhaust (51.5 ± 1.8%), gasoline exhaust (10.0 ± 0.8%), LPG exhaust (5.0 ± 0.5%), secondary sulfate (19.9 ± 1.0%), secondary nitrate (6.3 ± 0.9%), and road dust (7.3 ± 1.3%). In the FMT, total NMHC emissions were 14% and 8% higher in winter than in summer for LD and HD vehicles, respectively. Elemental carbon (EC) and organic carbon (OC) were the major constituents of tunnel PM2.5. De-icing salt contributions to PM2.5 were observed in the FMT in winter. Emission estimates by the EMFAC-HK agreed with SMT measurements for CO2; the modeled emission factors for CO, NOx, and NMHCs were 1.5, 1.6, and 2.2 times the measurements, respectively; and the modeled emission factor for PM2.5 was 61% of the measured value in 2003. The EMFAC-HK estimates and SMT measurements for 2015 differed by less than 35%. The MOVES2014a model generally overestimated emissions of most of the pollutants measured in the FMT. No pollutants were significantly underestimated. The largest overestimation was observed for emissions measured during HD-rich driving conditions in winter. Significant reductions in SO2 and PM2.5 emissions between 2003 and 2015 were observed in the SMT, indicating the effectiveness of control measures on these two pollutants. The total NMHC emissions in the SMT were reduced by 44%, although isobutane and n-butane emissions increased because of the increase in the size of the LPG fleet. No significant reductions were observed for CO and NOx, results that differed from those for roadside ambient concentrations, emission inventory estimates, and EMFAC-HK estimates. In contrast, there was a steady decrease in emissions of most pollutants in the tunnels in the United States.


Twisting a Cylindrical Sheet Makes It a Tunable Locking Material.
A buckled sheet offers a reservoir of material that can be unfurled at a later time. For sufficiently thin yet stiff materials, this geometric process has a striking mechanical feature: when the slack runs out, the material locks to further extension. Here, we establish a simple route to a tunable locking material: a system with an interval where it is freely deformable under a given deformation mode, and where the endpoints of this interval can be changed continuously over a wide range. We demonstrate this type of mechanical response in a thin sheet formed into a cylindrical shell and subjected to axial twist and compression, and we rationalize our results with a simple geometric model.


The impact on accuracy and cost of ligase chain reaction testing by pooling urine specimens for the diagnosis of Chlamydia trachomatis infections.
Nucleic acid amplification testing is the most accurate approach to diagnosing Chlamydia trachomatis infections. Our objective was to compare the accuracy and cost savings of pooling urines as opposed to individual testing. Strategies of pooling urine specimens into groups of four (4x pool) or eight (8x pool) followed by testing the positive pools individually were compared to individual specimen testing to determine if significant cost savingS could be realized without compromising the sensitivity and specificity of the LCx C. trachomatis Assay (Abbott Laboratories, Abbott Park, Chicago, IL) performed in a busy private medical laboratory. A total of 1,220 patient urine samples, 1,187 male (97%) and 33 female (3%), were tested using the normal LCx specimen to cutoff ratio (S/CO) of 1.0 and a decreased S/CO value of 0.2. Individual testing identified 98.2% (109/111) of positive urines. The 4x pooling maneuver identified 92.8% (103/111) of positive patients with the regular cutoff and 96.4% (107/111) when the cutoff was decreased. These values were 95.9% (47/49) and 97.9% (48/49), respectively, when eight urines were pooled. Both pooling and individual testing strategies identified all the negative samples accurately. Cost savings of pooling were calculated to be 44.5% for pools of four and 37.5% for pools of eight, applying the lowered cutoff. Pooling urine specimens for testing with the C. trachomatis LCx system is a simple, accurate, and cost-saving approach that can significantly reduce the cost of amplified nucleic acid testing with minimal sacrifice of testing accuracy.


Review of rapid diagnostic tests used by antimicrobial stewardship programs.
Rapid microbiologic tests provide opportunities for antimicrobial stewardship programs to improve antimicrobial use and clinical and economic outcomes. Standard techniques for identification of organisms require at least 48-72 hours for final results, compared with rapid diagnostic tests that provide final organism identification within hours of growth. Importantly, rapid microbiologic tests are considered "game changers" and represent a significant advancement in the management of infectious diseases. This review focuses on currently available rapid diagnostic tests and, importantly, the impact of rapid testing in combination with antimicrobial stewardship on patient outcomes.


Predicting risk of dyslexia with an online gamified test.
Dyslexia is a specific learning disorder related to school failure. Detection is both crucial and challenging, especially in languages with transparent orthographies, such as Spanish. To make detecting dyslexia easier, we designed an online gamified test and a predictive machine learning model. In a study with more than 3,600 participants, our model correctly detected over 80% of the participants with dyslexia. To check the robustness of the method we tested our method using a new data set with over 1,300 participants with age customized tests in a different environment -a tablet instead of a desktop computer- reaching a recall of over 78% for the class with dyslexia for children 12 years old or older. Our work shows that dyslexia can be screened using a machine learning approach. An online screening tool in Spanish based on our methods has already been used by more than 200,000 people.


Design and Performance of a Multi-Point Scan Confocal Microendoscope.
Confocal fluorescence microendoscopy provides high-resolution cellular-level imaging via a minimally invasive procedure, but requires fast scanning to achieve real-time imaging in vivo. Ideal confocal imaging performance is obtained with a point scanning system, but the scan rates required for in vivo biomedical imaging can be difficult to achieve. By scanning a line of illumination in one direction in conjunction with a stationary confocal slit aperture, very high image acquisition speeds can be achieved, but at the cost of a reduction in image quality. Here, the design, implementation, and experimental verification of a custom multi-point aperture modification to a line-scanning multi-spectral confocal microendoscope is presented. This new design improves the axial resolution of a line-scan system while maintaining high imaging rates. In addition, compared to the line-scanning configuration, previously reported simulations predicted that the multi-point aperture geometry greatly reduces the effects of tissue scatter on image quality. Experimental results confirming this prediction are presented.


Older Patient and Surrogate Attitudes Toward Deprescribing During the Transition From Acute to Post-Acute Care.
Attitudes toward deprescribing among hospitalized older patients transitioning to post-acute care in the United States are less known. This study describes older patients' and their surrogate's attitudes using all items of the Patient Attitudes Toward Deprescribing (PATD) questionnaire and compares perceived pill burden to the actual count of total daily pills and potentially inappropriate medications (PIMs). Overall, 93% of participants were willing to deprescribe if their physician agreed. Compared to patients, surrogates had 64% reduced odds (95% CI: 0.18-0.74) of believing that all of the care recipient's medications were necessary and 61% reduced odds (95% CI: 0.17-0.88) of attributing cost as a factor in deprescribing. Perceptions of medication burden were associated with patients' total daily pills (median 16) and PIMS (median 7), yet 61% agreed that all their medicines were necessary. Patients and surrogates typically express a willingness to deprescribe but have differing perceptions of medication appropriateness.


Health practitioner regulation and national health goals.
The role of health practitioner regulation in ensuring patient safety is well recognized. Less recognized is the role of regulation in addressing broader health system priorities. These goals include managing the costs, capacities and distribution of health professional education institutions; ensuring the competence and equitable distribution of health workers; informing workforce planning and mobilization; enabling the use of digital technologies; and addressing challenges related to the international mobility of health workers. Even where health practitioner regulation is designed to advance these goals, important gaps exist between the potential of regulatory systems and their performance. The response to the coronavirus disease 2019 (COVID-19) pandemic led many countries to introduce regulatory changes to allow more flexibility and innovations in the mobilization of health practitioners. Building on this experience, we need to critically re-examine health practitioner regulatory systems to ensure that these systems support rather than impede progress towards national health goals. We discuss the role of health practitioner regulation in contemporary health systems, highlighting recent regulatory reforms in selected countries, including during the COVID-19 pandemic. We identify the importance of dynamic, effective and flexible health practitioner regulatory systems in progress towards universal health coverage and health security.


Microscopic velocimetry with a scaled-up model for evaluating a flow field over cultured endothelial cells.
A microscopic velocimetry technique for evaluating the flow field over cultured endothelial cells was developed. Flow around a cell model scaled up by a factor of 100 was visualized by using an optical microscope and was quantified by using particle-tracking velocimetry. Wall shear stress on the model surface was determined from a two-dimensional velocity field interpolated from measured velocity vectors. Accuracy of the velocimetry was verified by measuring the flow over a sinusoidal cell model that had a wall shear stress profile analytically determined with linear perturbation theory. Comparison of the experimental results with the analytical solution revealed that the total error of the measured wall shear stress was 6 percent.


A translational and systemic approach to transferring liver transplant recipients from pediatric to adult-oriented care settings.
The purpose of this review is to (i) describe systemic changes made in our clinical practice to facilitate transfer of transplant recipients from the pediatric to the adult service and (ii) provide the rationale for instituting these organizational changes. To determine specific areas patients struggle to master, a survey assessing behaviors indicative of health care management was administered in pediatrics. Based on the results of the survey, all liver transplant recipients who transfer out of pediatrics are given a comprehensive clinical protocol, which includes a transfer checklist containing prerequisite items derived from our prior work. Patients are furthermore invited to enroll in a research study prospectively tracking both medical and psychosocial outcomes at six-month intervals. Data are discussed by the pediatric and adult teams, and additional adjustments to the transfer process are implemented in response. A summary of our clinical interventions and the resources required for implementation are presented. In conclusion, preliminary studies have demonstrated that transplant recipients are vulnerable to disruptions in health care management when they transfer out of pediatrics. This study describes one site's translational efforts to improve the transfer process for both the recipients and the clinicians, thus improving outcomes.


IS SAME-DAY INGUINAL HERNIA SURGERY POSSIBLE?
1-INTRODUCTION: The Lichtenstein hernia repair is associated with low recurrence rates and short operation times, and can be performed under local anaesthesia. Thus, this is among the most-preferred methods used in recent years. Our objective was to explore the same-day discharge rates, and the causes of delayed discharge and re-admission to hospital, of patients treated using the Lichtenstein repair method, to evaluate the feasibility of performing same-day hernia surgery in clinical practice. 2. . One hundredof a total of 236 patients diagnosed with unilateral inguinal or femoral hernias, who required surgical treatment, and who agreed with the conditions of the study, were prospectively included. All patients were treated using the Lichtenstein mesh repair method, under local anaesthesia between June 2006 and January 2008. We investigated the types and locations of hernias, duration of surgery, seniority of the surgeon, the feasibility of same-day surgery in subgroups stratified by ASA risk scores, and postoperative complication rates, in patients who underwent inguinal surgery under local anaesthesia 3. RESULTS , DISCUSSION AND CONCLUSIONS:. The rates of pain and post-operative complications were very low in hernia patients who underwent same-day surgery under local anaesthesia. The operation reduces the length of hospital stay and helps patients mobilise earlier. Both the literature, and our data, indicate that inguinal hernia repair under local anaesthesia is safe and effective, reducing anaesthesia-related complications and the length of hospital stay; is cost-effective; and is applicable in all patients.


Phytase improves iron bioavailability for hemoglobin synthesis in young pigs.
Dietary phytase supplementation improves bioavailabilities of phytate-bound minerals such as P, Ca, and Zn to pigs, but its effect on Fe utilization is not clear. The efficacy of phytase in releasing phytate-bound Fe and P from soybean meal in vitro and in improving dietary Fe bioavailability for hemoglobin repletion in young, anemic pigs was examined. In Exp. 1, soybean meal was incubated at 37 degrees C for 4 h with either 0, 400, 800, or 1,200 units (U) of phytase/kg, and the released Fe and P concentrations were determined. In Exp. 2, 12 anemic, 21-d-old pigs were fed either a strict vegetarian, high-phytate (1.34%) basal diet alone, or the diet supplemented with 50 mg Fe/kg diet (ferrous sulfate) or phytase at 1,200 U/kg diet (Natuphos, BASF, Mt. Olive, NJ) for 4 wk. In Exp. 3, 20 anemic, 28-d-old pigs were fed either a basal diet with a moderately high phytate concentration (1.18%) and some animal protein or the diet supplemented with 70 mg Fe/kg diet, or with one of two types of phytase (Natuphos or a new phytase developed in our laboratory, 1,200 U/kg diet) for 5 wk. In Exp. 2 and 3, diets supplemented with phytase contained no inorganic P. In Exp. 1, free P concentrations in the supernatant increased in a phytase dose-dependent fashion (P<.05), whereas free Fe concentrations only increased at the dose of 1,200 U/kg (P<.10). In Exp. 2 and 3, dietary phytase increased hemoglobin concentrations and packed cell volumes over the unsupplemented group; these two measures, including growth performance, were not significantly different than those obtained with dietary supplemental Fe. In conclusion, both sources of phytase effectively degraded phytate in corn-soy diets and subsequently released phytate-bound Fe from the diets for hemoglobin repletion in young, anemic pigs.


Computerised EEG monitoring for carotid endarterectomy.
A prospective study was undertaken in twenty patients undergoing carotid endarterectomy using computerised EEG monitoring in the form of a density-modulated spectral array, spectral edge frequency and integrated EEG power for monitoring cerebral ischaemia. This form of monitoring proved to be easy to use and understand. Because ischaemic EEG events longer than one minute were not necessarily followed by postoperative deficits, the definition of significant events that would cause ischaemia may need to be modified.


Occupational determinants for rheumatoid arthritis.
The aim of the present study was to evaluate possible occupational determinants for rheumatoid arthritis according to lifetime occupational history. The cases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected referents. Exposure data were collected through a postal questionnaire. For men, occupations with increased, although nonsignificant, odds ratios (OR) were farmers or farm workers [OR 1.8, 95% confidence interval (95% CI) 1.0-3.5], textile workers (OR 2.0, 95% CI 0.3-16.2), asphalters (OR 14.0, 95% CI 1.2-799.0 without latency requirement), and employees at service stations (OR 2.2, 95% CI 0.5-9.5). Among the women, hairdressers and beauticians (OR 2.7, 95% CI 0.8-8.6) had an increased risk for rheumatoid arthritis, as well as those exposed to hairdressing chemicals (OR 3.0, 95% CI 1.0-9.4) and meat products (OR 2.0, 95% CI 1.0-4.0). Several of the findings in this study are in accordance with those of previous studies. The increased risks of rheumatoid arthritis for asphalters and employees at service stations are however new associations previously not described in the literature.


Mutations in rpoBC suppress the defects of a Sinorhizobium meliloti relA mutant.
The nitrogen-fixing symbiosis between Sinorhizobium meliloti and Medicago sativa requires complex physiological adaptation by both partners. One method by which bacteria coordinately control physiological adaptation is the stringent response, which is triggered by the presence of the nucleotide guanosine tetraphosphate (ppGpp). ppGpp, produced by the RelA enzyme, is thought to bind to and alter the ability of RNA polymerase (RNAP) to initiate and elongate transcription and affect the affinity of the core enzyme for various sigma factors. An S. meliloti relA mutant which cannot produce ppGpp was previously shown to be defective in the ability to form nodules. This mutant also overproduces a symbiotically necessary exopolysaccharide called succinoglycan. The work presented here encompasses the analysis of suppressor mutants, isolated from host plants, that suppress the symbiotic defects of the relA mutant. All suppressor mutations are extragenic and map to either rpoB or rpoC, which encode the beta and beta' subunits of RNAP. Phenotypic, structural, and gene expression analyses reveal that suppressor mutants can be divided into two classes; one is specific in its effect on stringent response-regulated genes and shares striking similarity with suppressor mutants of Escherichia coli strains that lack ppGpp, and another reduces transcription of all genes tested in comparison to that in the relA parent strain. Our findings indicate that the ability to successfully establish symbiosis is tightly coupled with the bacteria's ability to undergo global physiological adjustment via the stringent response.


End TB strategy: the need to reduce risk inequalities.
Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle.


Factors correlating with failure to control intraocular pressure in primary angle-closure glaucoma eyes with coexisting cataract treated by phacoemulsification or combined phacotrabeculectomy.
To identify clinical factors correlating with failure to control intraocular pressure (IOP) in primary angle-closure glaucoma (PACG) eyes with cataract after phacoemulsification or phacotrabeculectomy. Retrospective analysis of two prospective randomized controlled clinical trials. Primary angle-closure glaucoma eyes with cataract received phacoemulsification or phacotrabeculectomy. Failure was defined as having IOP of 21mm Hg or greater, or requiring glaucoma drugs to maintain an IOP of less than 21 mm Hg, or having had additional IOP-lowering surgery. Factors correlating with failure at 24 months after surgery were identified using logistic regression model. One hundred twenty-three PACG eyes with cataract and receiving phacoemulsification (n = 62) and phacotrabeculectomy (n = 61) were analyzed. With univariate analysis, factors associated with failure included a higher preoperative IOP, a higher preoperative requirement for glaucoma drugs, absence of plateau iris configuration, and phacoemulsification alone. With multivariate analysis, factors associated with failure included a higher preoperative IOP [odds ratio (OR), 1.732 per increase in IOP of 5 mm Hg], a higher preoperative requirement for glaucoma drugs (OR, 1.913), and performance of phacoemulsification alone (OR, 10.24). In PACG eyes with cataract, higher preoperative IOP and increased requirement for glaucoma drugs correlate with failure to control IOP after phacoemulsification or phacotrabeculectomy. Phacotrabeculectomy is more likely than phacoemulsification to achieve IOP control.


Antimicrobial use in outpatient hemodialysis units.
To quantify and characterize overall antimicrobial use, including appropriateness of indication, among patients receiving chronic hemodialysis. Retrospective and prospective observational study. Two outpatient hemodialysis units. All patients receiving chronic hemodialysis. The rate of parenteral antimicrobial use (number of doses per 100 patient-months) was calculated retrospectively from September 2008 through July 2011. Indication and appropriateness of antimicrobial doses were characterized prospectively from August 2010 through July 2011. Inappropriate administration was defined as occasions when criteria for infection based on national guidelines were not met, failure to choose a more narrow-spectrum antimicrobial on the basis of culture data, or occasions when indications for surgical prophylaxis were not met. Over the 35-month retrospective study period, the rate of parenteral antimicrobial use was 32.9 doses per 100 patient-months. Vancomycin was the most commonly prescribed antimicrobial, followed by cefazolin and third- or fourth-generation cephalosporins. Over the 12-month prospective study, 1,003 antimicrobial doses were prescribed. Among the 926 (92.3%) doses for which an indication for administration was available, 276 (29.8%) were classified as inappropriate. Of these, a total of 146 (52.9%) did not meet criteria for infection, 74 (26.8%) represented failure to choose a more narrow-spectrum antimicrobial, and 56 (20.3%) did not meet criteria for surgical prophylaxis. The most common inappropriately prescribed antimicrobials were vancomycin and third- or fourth- generation cephalosporins. Parenteral antimicrobial use was extensive, and as much as one-third was categorized as inappropriate. The findings of this study provide novel information toward minimizing inappropriate antimicrobial use.


Sexual overperception: power, mating motives, and biases in social judgment.
Results from 4 experiments suggest that power motivates heightened perceptions and expectations of sexual interest from subordinates. Having power over a member of the opposite sex activated sexual concepts that persisted across a temporal delay, indicating the activation of a mating goal (Study 1). Having power increased participants' expectations of sexual interest from a subordinate (Study 2) but only when a mating goal was attainable (i.e., when the subordinate was romantically available; Study 3). In a face-to-face interaction between 2 participants, power heightened perceptions of sexual interest and sexualized behavior among participants with chronically active mating goals (i.e., sexually unrestricted individuals; Study 4). Tests of mediation demonstrated that sexual overperception mediated power's effect on sexually tinged behavior. Through its capacity to induce goal pursuit, power can activate mating goals that sexualize interactions between men and women. This research demonstrates one route through which power might lead to sexual harassment.


The Relationship between the Sugar Preference of Bacterial Pathogens and Virulence on Plants.
Plant pathogenic bacteria colonize plant surfaces and inner tissues to acquire essential nutrients. Nonstructural sugars hold paramount significance among these nutrients, as they serve as pivotal carbon sources for bacterial sustenance. They obtain sugar from their host by diverting nonstructural carbohydrates en route to the sink or enzymatic breakdown of structural carbohydrates within plant tissues. Despite the prevalence of research in this domain, the area of sugar selectivity and preferences exhibited by plant pathogenic bacteria remains inadequately explored. Within this expository framework, our present review endeavors to elucidate the intricate variations characterizing the distribution of simple sugars within diverse plant tissues, thus influencing the virulence dynamics of plant pathogenic bacteria. Subsequently, we illustrate the apparent significance of comprehending the bacterial preference for specific sugars and sugar alcohols, postulating this insight as a promising avenue to deepen our comprehension of bacterial pathogenicity. This enriched understanding, in turn, stands to catalyze the development of more efficacious strategies for the mitigation of plant diseases instigated by bacterial pathogens.


[Analysis of HKαα Genotype and Hematological Characteristics in South Guangxi].
To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region. Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed. A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--SEA, βN/ βN, HKαα/αα, β-28/ βN, HKαα/αα, β-50/ βN, HKαα/αα, βCD17/ βN, HKαα/αα, βCD27/28/β N, HKαα/αα, βCD41-42/ βN, HKαα/αα, βCD71-72/ βN, and HKαα/αα, βN/ βN). Except for most cases with HKαα/αα, βN/ βN genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia. HKαα carrier is often misdiagnosed as -α3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.


The Effect of Neural Therapy on Long-Term Postoperative Discomforts after Bilateral Tubal Ligation.
In this study, we aimed to assess the effect of neural therapy in the prevention of post-tubal syndrome, which is the combination of dysmenorrhea, bloating, dyspareunia, heavy menstrual bleeding, chronic vaginitis, and cystitis, after elective bilateral tubal ligation with modified Pomeroy technique. In total, 113 patients who have undergone bilateral tubal ligation with modified Pomeroy technique between January 2016 and December 2018 in our clinic have been included. Postoperatively, patients were divided into two groups. One group received neural therapy (n = 52), and the other group did not receive neural therapy (control group, n = 61). Both groups were evaluated in terms of preoperative and postoperative symptoms. One year after surgery, patients' pain levels were evaluated using visual analog scale (VAS). When both groups were compared in terms of symptoms, dysmenorrhea, dyspareunia, bloating, frequency of vaginitis, and cystitis per year and pain perception using VAS, the symptoms were significantly less in the neural therapy group. However, there was no difference between the groups in terms of the amount of menstrual bleeding. Patients who received neural therapy showed less pain symptoms (dysmenorrhea and dyspareunia), and their VAS scores were lower when compared to the control group. Thus, we concluded that neural therapy is effective in the treatment of post-tubal syndrome.


LINC00908 Promotes Diffuse Large B-Cell Lymphoma Development by Down-Regulating miR-671-5p.
Emerging evidence has revealed that long noncoding RNA (lncRNA) play important role in almost all kinds of human cancers. LINC00908 has been reported to be involved in the development of prostate cancer, colorectal cancer and gastric cancer which was functioned as an oncogene. However, the potential biology role and molecular mechanism of LINC00908 in diffuse large B-cell lymphoma are still unclear. LINC00908 and miR-671-5p expression were evaluated in DLBCL tissues and cell lines using RT-qPCR. CCK-8 and transwell assay were used to analyze the in vitro role of LINC00908 in DLBCL progression. The xenograft model was used to explore the in vivo role of LINC00908 in DLBCL growth. The physical interaction between LINC00908 and miR-671-5p was confirmed using bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down. The expression of LINC00908 was markedly up-regulated in diffuse large B-cell lymphoma tissues and cell lines, and the decreased expression of LINC00908 significantly inhibited diffuse large B-cell lymphoma cell proliferation and invasion. Then, we revealed that LINC00908 directly interacted with miR-671-5p, which was down-regulated in diffuse large B-cell lymphoma cells and highly expressed with LINC00908 knockdown. Moreover, luciferase reporter assays and RNA immunoprecipitation (RIP) assay further proved that miR-671-5p is a direct target of LINC00908 in diffuse large B-cell lymphoma cells. Rescue experiments were also performed, and we confirmed that LINC00908 acts as an oncogene role in diffuse large B-cell lymphoma through miR-671-5p. Finally, the influence of LINC00908 silence significantly inhibited diffuse large B-cell lymphoma growth in vivo. LINC00908 promotes malignancy of diffuse large B-cell lymphoma through regulating miR-671-5p.


Comparing Homicide-Suicides in the United States and Sweden.
Research on homicides followed by suicides has largely relied on very localized samples and relatively short time spans of data. As a result, little is known about the extent to which patterns within cases of homicide-suicides are geographically specific. The current study seeks to help fill this gap by comparing twenty years of homicide-suicide data for Sweden and a large U.S. county. Although some of the underlying patterns in the two countries are similar (e.g., decreasing rates), a number of important differences emerge, particularly with respect to incidence, weapons used, perpetrator age, and relationship of the perpetrator to the victim.


The impact of feedback on metacognition: Enhancing in easy tasks, impeding in difficult ones.
Metacognition refers to the ability to monitor and introspect upon cognitive performance. Abundant research suggests that individual metacognition is easily affected by feedback in daily life, but how feedback affects metacognition in perceptual decision-making remains unclear. Here we investigated how trial-by-trial feedback shapes perceptual metacognition in two experiments with either high (n = 82) or low difficulty (n = 90). Participants were randomly divided into a feedback group in which participants received trial-by-trial performance feedback or a no-feedback group. Results showed that, in the high-difficulty task, participants in the feedback group revealed inferior metacognitive performance than the no-feedback group, manifested as decreased metacognitive efficiency while controlling for performance sensitivity. In the low-difficulty task, however, participants in the feedback group had higher metacognitive efficiency than the no-feedback group. The distinct patterns of findings in the two experiments indicate that whether feedback promotes or impedes metacognition is adjusted by task difficulty.


Epidemiology of stroke and high blood pressure in Africa.
Stroke and high blood pressure are major causes of death and disability worldwide. Although comprehensive stroke surveillance data for Africa are lacking, the available data show that age-standardised mortality, case fatality and prevalence of disabling stroke in Africa are similar to or higher than those measures in most high-income regions. In Africa, more than 90% of patients with haemorrhagic stroke and more than half with ischaemic stroke are found to have high blood pressure. However, awareness of hypertension and its prevention, treatment and control remain very low in Africa even though recent surveys show an increasing prevalence of the disease consistent with the nutritional and epidemiological transition in the region. Renewed emphasis on improved surveillance and the prevention and control of high blood pressure and stroke in Africa is needed.


Attenuation of Streptozotocin-Induced Lipid Profile Anomalies in the Heart, Brain, and mRNA Expression of HMG-CoA Reductase by Diosgenin in Rats.
Diabetes mellitus is associated with significant morbidity and mortality that contributes to pathogenesis of cardiovascular diseases. Diosgenin, a naturally occurring aglycone, is present abundantly in fenugreek. The steroidal saponin is being used as a traditional medicine for diabetes. The present study has investigated the effects of diosgenin on lipid profile in the heart and brain, mRNA expression, and hepatic HMG-CoA reductase (HMGR) activity of streptozotocin-induced diabetic rats. In our study, diosgenin was administered (40 mg/kg b.w.) orally for 45 days to control animals and experimentally induced diabetic rats. The effects of diosgenin on glucose, plasma insulin, cholesterol, triglycerides, free fatty acids, and phospholipids (PLs) in the heart and brain were studied. The levels of glucose, cholesterol, triglycerides, free fatty acids, PLs, and HMGR activity were increased significantly (P < 0.05) whereas plasma insulin level was decreased in diabetic rats. Administration of diosgenin to diabetic rats significantly reduced blood glucose, cholesterol, triglycerides, free fatty acids, PLs levels, and also HMGR activity. In addition, the plasma insulin level was increased in diosgenin-treated diabetic rats. The above findings were correlated with histological observations of the heart and brain. The results showed that administration of diosgenin remarkably increased plasma insulin level with absolute reduction of blood glucose, lipid profile, and HMGR level when compared to diabetic control rats. The results have suggested that diosgenin prevents hypercholesterolemia and hepatosteatosis by modulation of enzymatic expression that is associated with cholesterol metabolism.


Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.
The coordinating role of nuclear factor erythroid-2-related factor 2 (Nrf2) in cellular function is undeniable. Evidence indicates that this transcription factor exerts massive regulatory functions in multiple signaling pathways concerning redox homeostasis and xenobiotics, macromolecules, and iron metabolism. Being the master regulator of antioxidant system, Nrf2 controls cellular fate, influencing cell proliferation, differentiation, apoptosis, resistance to therapy, and senescence processes, as well as infection disease success. Because Nrf2 is the key coordinator of cell defence mechanisms, dysregulation of its signaling has been associated with carcinogenic phenomena and infectious and age-related diseases. Deregulation of this cytoprotective system may also interfere with immune response. Oxidative burst, one of the main microbicidal mechanisms, could be impaired during the initial phagocytosis of pathogens, which could lead to the successful establishment of infection and promote susceptibility to infectious diseases. There is still a knowledge gap to fill regarding the molecular mechanisms by which Nrf2 orchestrates such complex networks involving multiple pathways. This review describes the role of Nrf2 in non-pathogenic and pathogenic cells.


Association of Smoking Status With Long-Term Mortality and Health Status After Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.
Background Smoking is a significant risk factor for aortic stenosis but its impact on clinical and health status outcomes after transcatheter aortic valve replacement (TAVR) has not been described. Methods and Results Patients (n=72 165) undergoing TAVR at 457 US sites in the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between November 2011 and June 2016 were categorized at the time of TAVR as current/recent smokers versus prior/nonsmokers. A series of multivariable models examined the association between smoking status and outcomes, including 1-year mortality, rehospitalization, mean gradient, and health status (measured by the 12-item Kansas City Cardiomyopathy Questionnaire-Overall Summary Score [KCCQ-OS]) and in-hospital outcomes. A total of 4063 patients (5.6%) were smokers. Smokers presented for TAVR at a younger age (75 [68-81] years versus 83 [77-88] years) but with a greater burden of cardiovascular and lung disease. In adjusted models, smoking was associated with lower in-hospital mortality (relative risk, 0.74; 95% CI, 0.62-0.89 [P=0.001]) but not with in-hospital stroke/transient ischemic attack or myocardial infarction. Smoking status had no association with postdischarge mortality, stroke, myocardial infarction, or heart failure (HF) but was associated with slightly lower 1-year KCCQ-OS scores (2.4-point lower KCCQ-OS; 95% CI, -4.6 to -0.2 [P=0.031]) and higher mean aortic valve gradients (11.1 versus 10.2 mm Hg, P<0.001) in adjusted models. Conclusions The current/recent smoking rate in US patients with TAVR is 5.6% and smokers present at a younger age for TAVR. Smoking was associated with lower in-hospital but similar long-term survival after TAVR, slightly worse long-term health status, and marginally higher mean aortic valve gradients. Further research is needed to understand the effect of smoking cessation on outcomes.


[Acquired cutis laxa associated with monoclonal gammopathy and lambda light chain deposition disease].
Cutis laxa is a rare entity characterized clinically by redundant skin that gives an appearance of premature aging. The appearance relates to a loss of elasticity because of the destruction of elastic fibers that affects the skin and other organs. It may be associated with inflammatory conditions or diseases, such as plasma cell dyscrasias. We report the case of a 54-year-old man with acquired cutis laxa, which preceded the development of IgG-lambda monoclonal gammopathy with lambda light chain deposits in the kidney. The patient had a fatal outcome owing to severe and rapidly progressive renal failure. We emphasize the importance of recognizing a plasma cell dyscrasia in a patient with cutis laxa, although this association is rare.


The development and malleability of executive control abilities.
Executive control (EC) generally refers to the regulation of mental activity. It plays a crucial role in complex cognition, and EC skills predict high-level abilities including language processing, memory, and problem solving, as well as practically relevant outcomes such as scholastic achievement. EC develops relatively late in ontogeny, and many sub-groups of developmental populations demonstrate an exaggeratedly poor ability to control cognition even alongside the normal protracted growth of EC skills. Given the value of EC to human performance, researchers have sought means to improve it through targeted training; indeed, accumulating evidence suggests that regulatory processes are malleable through experience and practice. Nonetheless, there is a need to understand both whether specific populations might particularly benefit from training, and what cortical mechanisms engage during performance of the tasks used in the training protocols. This contribution has two parts: in Part I, we review EC development and intervention work in select populations. Although promising, the mixed results in this early field make it difficult to draw strong conclusions. To guide future studies, in Part II, we discuss training studies that have included a neuroimaging component - a relatively new enterprise that also has not yet yielded a consistent pattern of results post-training, preventing broad conclusions. We therefore suggest that recent developments in neuroimaging (e.g., multivariate and connectivity approaches) may be useful to advance our understanding of the neural mechanisms underlying the malleability of EC and brain plasticity. In conjunction with behavioral data, these methods may further inform our understanding of the brain-behavior relationship and the extent to which EC is dynamic and malleable, guiding the development of future, targeted interventions to promote executive functioning in both healthy and atypical populations.


Nausea and vomiting of pregnancy and resource implications: the NVP Impact Study.
Nausea and vomiting of pregnancy (NVP) is the most prevalent medical condition associated with pregnancy. The Royal College of Obstetricians and Gynaecologists published its first guidelines for management of NVP in 2016, although many current treatments are off label, with only one recently licensed treatment for NVP in the UK. To identify the current practices for NVP management across the patient pathway, and estimate the economic burden to NHS services. This was an observational, retrospective research study conducted in the Newcastle Gateshead Clinical Commissioning Group (CCG) health economy area in England. Data were collected from GP practices, local hospital datasets, ambulance services (April 2013-March 2016), and the Hospital Episode Statistics dataset (2006-2016). Eight GP practices participated in the study. In all, 15.2% of the total pregnant population presented with NVP. Treatment varied significantly between GP practices, and 33.6% of women re-presented to their GP. There was an annual increase in women admitted to hospital for NVP symptoms, with increasing length of stay per admission. Almost half (44.6%) of the calls to 999/111 from women experiencing NVP symptoms resulted in an ambulance dispatch. The annual cost of NVP to this health economy was estimated to be £199 804, which crudely extrapolates to £25 758 731 at UK level. Due to underestimations of costs, the impact to the UK NHS could be up to £62 373 961. There is considerable variation in current management practices for NVP outside of recently published guidelines, and this may result in substantial resource use and avoidable financial impact to the NHS.


The Peru Approach against the COVID-19 Infodemic: Insights and Strategies.
The COVID-19 epidemic has spawned an "infodemic," with excessive and unfounded information that hinders an appropriate public health response. This perspective describes a selection of COVID-19 fake news that originated in Peru and the government's response to this information. Unlike other countries, Peru was relatively successful in controlling the infodemic possibly because of the implementation of prison sentences for persons who created and shared fake news. We believe that similar actions by other countries in collaboration with social media companies may offer a solution to the infodemic problem.


Correlates of decline in gross motor capacity in adolescents with cerebral palsy in Gross Motor Function Classification System levels III to V: an exploratory study.
To explore associations between clinical variables and decline in motor capacity in adolescents with cerebral palsy (CP). Participants included 76 males and 59 females, whose mean age at the beginning of the study was 14 years 6 months (SD 2.4, range 11.6-17.9); 51 at Gross Motor Function Classification System (GMFCS) level III, 47 at level IV, and 37 at level V. Ninety-six participants had tetraplegia, 32 had diplegia, and one had hemiplegia. Types of motor disorder were spastic n=98; mixed, n=11; dystonic, n=9; hypotonic, n=7; and ataxic n=3 (seven participants were not classified). Reliable raters collected data annually for 4 years on anthropometric characteristics, the Spinal Alignment and Range of Motion Measure, as well as the Gross Motor Function Measure, 66 items (GMFM-66); participants or their parents reported on health status (using the Health Utilities Questionnaire), pain, and exercise participation (using measures developed for this study). The predicted drop in GMFM-66 scores after childhood was calculated using data on the same children from an earlier study. Correlations were calculated between the drop in GMFM-66 scores and the average and change scores of the clinical variables (the alpha level for statistical significance of this exploratory study was 0.10). The drop in GMFM-66 score was significantly correlated with limitations in range of motion (r=0.42) and spinal alignment (r=0.28), and pain (r=0.16). Increases in triceps skinfold (r=-0.19), mid-arm circumference (r=-0.23), and the ratio of mid-arm circumference to knee height (r=-0.23) were associated with less decline. Preventing range-of-motion limitations and pain experiences and optimizing nutrition might contribute to less decline in the gross motor capacity of adolescents with CP. Further investigation is required to clarify the role other factors that contribute to maintained function over time.


Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy.
In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages' polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy.