A smart and active film with tunable drug release and color change abilities for detection and inhibition of bacterial growth.
Antimicrobial resistance has become a global issue and thus the development of natural products/biomedical materials composites with antibacterial activities is urgently needed. When acute wounds develop into chronic wounds, the wound environments become alkaline. As long as infections occur, the wound pH further increases, making the wounds difficult to heal. Besides, bacterial growth in poultry, meat, fish and seafood products is usually reflected in a marked increase of pH values. Herein, smart, stimuli responsive self-assembled multilayer and complex film were constructed through the formation of hydrogen bonds and hydrophobic interactions between hydroxypropyl methylcellulose (HPMC) and epigallocatechin-3-gallate (EGCG), thereby greatly reducing the hydrophilicity of HPMC and offering enhanced mechanical strength, superior free radical scavenging capability, and improved water vapor and light barrier properties. The EGCG/HPMC complex film was able to control EGCG release by tuning pH or temperature of the release medium. Furthermore, incorporation of CuS nanoparticles into the film allowed it to triggers EGCG release in an on-demand fashion under near-infrared (NIR) exposure. Bacterial growth in glucose-free nutrient broth medium caused pH to rise (near pH 8.0), leading to transformation of EGCG from phenol type to phenolate ion and then quinone, allowing for spontaneous generation of H2O2 to kill bacteria. The complex films changed their color in response to bacterial growth because EGCG transformed from phenol type to quinone type under alkaline condition. The green synthesized EGCG/HPMC complex films can be used as a colorimetric pH indicator and an antibacterial material for wound dressing and food packaging applications.


Regulation of cognition and symptoms of psychosis: focus on GABA(A) receptors and glycine transporter 1.
Adaptive purposeful behaviour depends on appropriate modifications of synaptic connectivity that incorporate an organism's past experience. At least some forms of such synaptic plasticity are believed to be mediated by NMDA receptors (NMDARs). Complementary interaction with inhibitory neurotransmission mediated by GABA(A) receptors, and upstream control of the excitability of NMDARs by glycine availability can greatly influence the efficacy of NMDAR mediated neuroplasticity, and thereby exert significant effects on cognition. Memory, selective attention or sensorimotor gating functions can be modified in mice with a reduction of alpha(5)GABA(A) receptors in the hippocampus or a selective deletion of glycine transporter 1 (GlyT1) in the forebrain. Both genetic manipulations altered the formation or persistence of associative links leading to distinct phenotypes on trace conditioning, extinction learning, latent inhibition, working memory, and object recognition. Behavioural assays of latent inhibition, prepulse inhibition, working memory, and sensitivity to psychostimulants in particular suggest that alpha(3) and alpha(5) subunit-containing GABA(A) receptors as well as GlyT1 are potential sites for ameliorating psychotic-like behaviour. Taken together, these results qualify distinct GABA-A receptor subtypes and GlyT1 as molecular targets for the development of a new pharmacology in the treatment of cognitive decline and psychotic symptoms.


Food consumption of Sri Lankan adults: an appraisal of serving characteristics.
The main aim of the present study was to identify food consumption in Sri Lankan adults based on serving characteristics. Cross-sectional study. Fruits, vegetables, starch, meat, pulses, dairy products and added sugars in the diet were assessed with portion sizes estimated using standard methods. Twelve randomly selected clusters from the Sri Lanka Diabetes and Cardiovascular Study. Six hundred non-institutionalized adults. The daily intake of fruit (0·43), vegetable (1·73) and dairy (0·39) portions were well below national recommendations. Only 3·5 % of adults consumed the recommended 5 portions of fruits and vegetables/d; over a third of the population consumed no dairy products and fewer than 1 % of adults consumed 2 portions/d. In contrast, Sri Lankan adults consumed over 14 portions of starch and 3·5 portions of added sugars daily. Almost 70 % of those studied exceeded the upper limit of the recommendations for starch intake. The total daily number of meat and pulse portions was 2·78. Dietary guidelines emphasize the importance of a balanced and varied diet; however, a substantial proportion of the Sri Lankan population studied failed to achieve such a recommendation. Nutrition-related diseases in the country may be closely correlated with unhealthy eating habits.


Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi.
There is no effective cure for Chagas disease, which is caused by infection with the arthropod-borne parasite, Trypanosoma cruzi. In the search for new drugs to treat Chagas disease, potential therapeutic targets have been identified by exploiting the differences between the mechanisms involved in intracellular Ca2+ homeostasis, both in humans and in trypanosomatids. In the trypanosomatid, intracellular Ca2+ regulation requires the concerted action of three intracellular organelles, the endoplasmic reticulum, the single unique mitochondrion, and the acidocalcisomes. The single unique mitochondrion and the acidocalcisomes also play central roles in parasite bioenergetics. At the parasite plasma membrane, a Ca2+--ATPase (PMCA) with significant differences from its human counterpart is responsible for Ca2+ extrusion; a distinctive sphingosine-activated Ca2+ channel controls Ca2+ entrance to the parasite interior. Several potential anti-trypansosomatid drugs have been demonstrated to modulate one or more of these mechanisms for Ca2+ regulation. The antiarrhythmic agent amiodarone and its derivatives have been shown to exert trypanocidal effects through the disruption of parasite Ca2+ homeostasis. Similarly, the amiodarone-derivative dronedarone disrupts Ca2+ homeostasis in T. cruzi epimastigotes, collapsing the mitochondrial membrane potential (ΔΨm), and inducing a large increase in the intracellular Ca2+ concentration ([Ca2+]i) from this organelle and from the acidocalcisomes in the parasite cytoplasm. The same general mechanism has been demonstrated for SQ109, a new anti-tuberculosis drug with potent trypanocidal effect. Miltefosine similarly induces a large increase in the [Ca2+]i acting on the sphingosine-activated Ca2+ channel, the mitochondrion and acidocalcisomes. These examples, in conjunction with other evidence we review herein, strongly support targeting Ca2+ homeostasis as a strategy against Chagas disease.


2,5-Dihydroxyterephthalic Acid: A Matrix for Improved Detection and Imaging of Amino Acids.
Amino acids (AAs), which are low-molecular-weight (low-MW) metabolites, serve as essential building blocks not only for protein synthesis but also for maintaining the nitrogen balance in living systems. In situ detection and imaging of AAs are crucial for understanding more complex biological processes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a label-free mass spectrometric imaging technique that enables the simultaneous detection and imaging of the spatial distribution and relative abundance of different endogenous/exogenous compounds in biological samples. The excellent efficiency of MALDI-MSI is attributed to the choice of the MALDI matrix. However, to the best of our knowledge, no matrix has been specifically developed for AAs. Herein, we report a MALDI matrix, 2,5-dihydroxyterephthalic acid (DHT), which can improve the detection and imaging of AAs in biological samples by MALDI-MS. Our results indicated that DHT exhibited strong ultraviolet-visible (UV-vis) absorption, uniform matrix deposition, and high vacuum stability. Moreover, the matrix-related ion signals produced from DHT were reduced by 50 and 71.8% at m/z < 500 compared to the commonly used matrices of 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA), respectively, in their respective organic solvents. In terms of quantitative performance, arginine, glutamic acid, glutamine, and proline can be detected with limits of detection of 6, 4, 6, and 4 ng/mL, respectively, using the DHT as the matrix. Using DHT as the matrix, all 20 protein AAs were successfully detected in human serum by MALDI-MS, whereas only 7 and 10 AAs were detected when DHB and CHCA matrices were used, respectively. Furthermore, 20 protein AAs and taurine were successfully detected and imaged in a section of edible Crassostrea gigas (oyster) tissue for the first time. Our study demonstrates that using DHT as a matrix can improve the detection and imaging of AAs in biological samples by MALDI-MS.


Stimulation of bumetanide-sensitive Na+/K+/Cl- cotransport by different mitogens in synchronized human skin fibroblasts is essential for cell proliferation.
In this study, we examined the role of the bumetanide-sensitive Na+/K+/Cl- cotransport in the mitogenic signal of human skin fibroblast proliferation. The Na+/K+/Cl- cotransport was dramatically stimulated by either fetal calf serum, or by recombinant growth factors, added to quiescent G0/G1 human skin fibroblasts. The following mitogens, FGF, PDGF, alpha-thrombin, insulin-like growth factor-1, transforming growth factor-alpha, and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate, all stimulated the Na+/K+/Cl- cotransport. In addition, all the above mitogens induced DNA synthesis in the synchronized human fibroblasts. In order to explore the role of the Na+/K+/Cl- cotransport in the mitogenic signal, the effect of two specific inhibitors of the cotransport, furosemide and bumetanide, was tested on cell proliferation induced by the above recombinant growth factors. Bumetanide and furosemide inhibited synchronized cell proliferation as was measured by (a) cell exit from the G0/G1 phase measured by the use of flow cytometry, (b) cell entering the S-phase, determined by DNA synthesis, and (c) cell growth, measured by counting the cells. The inhibition by furosemide and bumetanide was reversible, removal of these compounds, completely released the cells from the block of DNA synthesis. In addition, the two drugs inhibited DNA synthesis only when added within the first 2-6 h of cell release. These results indicate that the effect of these drugs is specific, and is not due to an indirect toxic effect. This study clearly demonstrates that the growth factor-induced activation of the Na+/K+/Cl- cotransport plays a major role in the mitogenic signaling pathway of the human fibroblasts.


Targeted delivery of microRNA-29b by transferrin-conjugated anionic lipopolyplex nanoparticles: a novel therapeutic strategy in acute myeloid leukemia.
miR-29b directly or indirectly targets genes involved in acute myeloid leukemia (AML), namely, DNMTs, CDK6, SP1, KIT, and FLT3. Higher miR-29b pretreatment expression is associated with improved response to decitabine and better outcome in AML. Thus, designing a strategy to increase miR-29b levels in AML blasts may be of therapeutic value. However, free synthetic miRs are easily degraded in bio-fluids and have limited cellular uptake. To overcome these limitations, we developed a novel transferrin-conjugated nanoparticle delivery system for synthetic miR-29b (Tf-NP-miR-29b). Delivery efficiency was investigated by flow cytometry, confocal microscopy, and quantitative PCR. The expression of miR-29b targets was measured by immunoblotting. The antileukemic activity of Tf-NP-miR-29b was evaluated by measuring cell proliferation and colony formation ability and in a leukemia mouse model. Tf-NP-miR-29b treatment resulted in more than 200-fold increase of mature miR-29b compared with free miR-29b and was approximately twice as efficient as treatment with non-transferrin-conjugated NP-miR-29b. Tf-NP-miR-29b treatment significantly downregulated DNMTs, CDK6, SP1, KIT, and FLT3 and decreased AML cell growth by 30% to 50% and impaired colony formation by approximately 50%. Mice engrafted with AML cells and then treated with Tf-NP-miR-29b had significantly longer survival compared with Tf-NP-scramble (P = 0.015) or free miR-29b (P = 0.003). Furthermore, priming AML cell with Tf-NP-miR-29b before treatment with decitabine resulted in marked decrease in cell viability in vitro and showed improved antileukemic activity compared with decitabine alone (P = 0.001) in vivo. Tf-NP effectively delivered functional miR-29b, resulting in target downregulation and antileukemic activity and warrants further investigation as a novel therapeutic approach in AML.


Non-Destructive Evaluation of Mortar with Ground Granulated Blast Furnace Slag Blended Cement Using Ultrasonic Pulse Velocity.
Non-destructive evaluation using ultrasonic pulse velocity (Vp) testing has extensive applications in the concrete industry. With advances in construction technology, the use of ground granulated blast furnace slag (GGBFS) as a partial replacement to cement in a concrete mix is growing in popularity primarily because it reduces the initial capital cost of raw materials and the associated energy costs. This paper investigates the effect of the water-to-cement (wc) ratio and the cement content replaced by GGBFS on the development with time of the ultimate compressive strength (fc') and the compression wave velocity (Vp) of mortar. The results showed that in the case of mortar with higher percentages of GGBFS replacement (where nucleation surfaces are more abundant), increasing wc can increase fc' but cause a decrease in Vp. The posterior hydration process is highly dependent upon the water particles in the mixture after the first stage of hydration. After 7 days of curing, experimental results show that the fc' of slag blended cement mix design wc ratio of 0.6 surpassed the fc' value of an Ordinary Portland cement. A regression model correlating the fc' and Vp of slag blended mortar is developed, which can be used to predict fc' at concrete ages ranging from 1 day to 28 days for mixes with GGBFS percentage replacement values ranging from 15% to 45%.


Role of central dopaminergic pathways in the neural control of growth hormone secretion in normal men: studies with metoclopramide.
The aim of this study was to gain further insight into the role that central dopaminergic pathways play in GH neuroregulation in man. Our experimental hypothesis was based on the possibility that most of the controversies on DA role could be due to the fact that the hypothalamic somatotroph rhythm (HSR) was not taken into account when interpreting the GH responses after pharmacological manipulations on dopaminergic pathways. In 10 normal subjects we monitored the effect of central dopaminergic blockade, achieved with metoclopramide (MCP; 10 mg, i.v. bolus), on the pattern of spontaneous GH secretion and the GH responses to a GHRH challenge (GRF1-29, 1 microgram/kg, i.v. bolus) administered together with MCP or 60 min after this drug was given. The study of HSR was made according to our previous postulate. Our results indicate that MCP administration, either prior to or together with the GHRH bolus, significantly increased GHRH-induced GH release during a refractory HSR phase; but not when the GHRH challenge took place during a spontaneous secretory phase. The strong relationship between pre-GHRH plasma GH values and GHRH-elicited GH peaks was lost when MCP was given. These data indicate that MCP was able to disrupt the intrinsic HSR by inhibiting the hypothalamic release of somatostatin (SS). While a main conclusion would be that central DA is a secretagogue for SS secretion, our results also suggest that this role could be dependent on its effects on the adrenergic inputs to SS neurons.


Pain Trajectory After Ankle Surgeries for Osteoarthritis.
The pain trajectory after ankle surgeries for osteoarthritis is relevant to describe. The purpose of this prospective study was to describe pain after ankle surgery and explore the link between perioperative factors and the development of postoperative pain. Duration, severity, type of preoperative pain, psychological distress, opioid consumption, and type of surgery were evaluated in 49 patients who were followed for 18 months. Acute postoperative pain in the first 10 days after surgery was modeled by a pain trajectory. Univariate analysis was conducted to identify predictors of acute pain trajectory and chronic pain. Eighty-seven percent of patients had preoperative chronic pain, 34% had a high postoperative pain trajectory, 44% of whom reported chronic pain at 18 months. The patients who developed a high acute pain trajectory had higher preoperative opioid consumption (50% vs 19.4%, P = .04), a higher incidence of preoperative neuropathic pain (68.8% vs 32.3%, P = .02), a higher brief pain inventory score (51.5 vs 34, P = .01), and a higher psychological distress score (8 vs 3, P = .002). The patients who developed chronic pain had a higher brief pain inventory score (42 vs 33, P = .04), a higher psychological distress score (6 vs 4, P = .04), and a higher preoperative pain intensity (8 vs 6, P = .008). No association was found between the type of ankle surgery and pain. Patients with psychological distress and more severe preoperative pain were more at risk to develop acute pain and chronic pain after ankle surgery regardless of the surgery performed. Level II, prospective comparative study.


Perspective of vaccine manufacturers on financing pediatric and adolescent vaccines in the United States.
The goal was to understand vaccine manufacturers' perspectives on vaccine financing as a barrier to immunization. Individual telephone interviews with representatives of the 6 manufacturers that produce routinely recommended vaccines for children and adolescents in the United States were conducted in November and December 2006. Although manufacturers acknowledged that the price of newer vaccines presents challenges to optimal vaccine use, they asserted that children and adolescents have access to vaccinations through public and private insurance. Respondents suggested that the system could be improved through adequate funding of the public-sector safety net. Respondents stated that providers should receive timely reimbursement for the full costs of vaccine purchase and administration, and manufacturers who sell directly to health care providers may provide flexible payment terms for vaccine purchases. Manufacturers supported targeted expansion of the Vaccines for Children program to allow children with incomplete insurance coverage for vaccines to receive vaccines at health department clinics. Manufacturers perceived delays in publication of Advisory Committee on Immunization Practices recommendations as a potential barrier to vaccine uptake. They viewed the perceived lack of public value for vaccines as a potential barrier to adequate reimbursement and optimal utilization. Respondents also maintained that their ability to negotiate vaccine prices through the private market is a crucial priority. Manufacturers assert that children and adolescents have access to immunizations through public and private insurance. Manufacturers think that they have mitigated the challenge most directly in their control: the large financial outlays required for up-front vaccine purchases.


The effect of process and outcome feedback in highly distressed outpatients: A randomized controlled trial.
Objectives: Although process and outcome feedback is considered to be facilitative of psychotherapeutic processes, recent studies have suggested that such feedback may not produce the same effect when applied to highly distressed patients. This study examined the effect of process and outcome feedback in highly distressed patients treated in a public mental health center in Israel.Method: Patients (n = 197) were randomly allocated to receive feedback, or to treatment as usual. Therapists in the feedback condition received weekly reports, whereas therapists in the control group received no feedback. After attrition from study and treatment, a total of 123 cases were analyzed.Results: Feedback had no significant effect on either symptom reduction or on well-being. However, patients in the feedback group showed higher gains in alliance as compared to the treatment as usual group.Conclusion: Process and outcome feedback might have a potential beneficial effect of improving alliance for patients with severe symptomatology, with whom the establishment of an alliance can be challenging. The current findings also stress the need to continue to study the effect of feedback on therapy outcomes in diverse clinical settings. Limitations and directions for future research are discussed.


[Suicidal calls to a telephone emergency service].
Suicidal threats and suicidal ideation among callers to the Israeli hot-line (ERAN) were investigated, using 2 methods of analysis. The first, an epidemiological survey based on 8,272 calls received by all 8 ERAN posts during 2 years, reported on their standard form for recording interactions with suicidal callers. The second is content analysis of 42 detailed reports of interactions with such callers. Epidemiological analysis revealed a higher rate of suicidal ideation among callers with a psychiatric history, compared with those without a history. However, the 2 groups did not differ in rate of suicidal threats. In addition, suicidal threats of adolescents were related mainly to problems of identity and self-image, while mental disorders were the main problems among adults. Content analysis identified 2 patterns of terminating the interaction, which represent 2 strategies of intervention to prevent suicide. The first is establishing a contact between the caller and an appropriate individual in the caller's environment who undertakes responsibility to help the caller. The second strategy is reducing the caller's tension, leading to a withdrawal of the suicidal threat. The first pattern is more characteristic of interactions with psychiatric callers, while the second is more frequent among non-psychiatric callers to ERAN. The hot-line makes a unique contribution in helping those threatening suicide, which constitutes a real emergency.


A subfamily of the small heat shock proteins of the marine red alga Neopyropia yezoensis localizes in the chloroplast.
Small heat shock proteins (sHSPs) play a crucial role under abiotic stress and are present in all organisms, from eukaryotes to prokaryotes. However, studies on the sHSP gene family in red alga are limited. In this study, we aimed to identify and characterize NysHSP genes from the genome of N. yezoensis, a marine red alga adapted to the stressful intertidal zone. We identified seven NysHSP genes distributed on all three chromosomes. Expression analysis revealed that all NysHSP genes responded to H2O2 and heat stress in the gametophytic thalli, but these genes responded only to heat stress in the sporophytic conchocelis. NysHSP20.3, which has an acidic isoelectric point (pI) and short N-terminal region, was localized as granules in the cytosol. Fluorescence imaging of the NysHSP25.8-GFP and NysHSP28.4-GFP fusion proteins revealed that these proteins were located in the chloroplast. Based on their characteristics and cellular localization, the NysHSPs are divided into two subfamilies. Subfamily I includes four sHSP genes that strongly respond to heat stress and encode a protein localized in the cytosol. The NysHSP gene of subfamily II encodes a polypeptide with a long N-terminal region located in the chloroplast. This study provides insights into the evolution and function of the sHSP gene family of the marine red alga N. yezoensis and how it adapts to the stressful intertidal zone.


Automated coring and apical connector insertion device for aortic valve bypass surgery.
The technical difficulty of performing the left ventricular apical anastomosis has limited the adoption of aortic valve bypass surgery for the treatment of aortic stenosis. We report the successful use of an automated coring and apical connector device to perform aortic valve bypass surgery. A 74-year-old man, with a history of prior coronary bypass surgery with patent grafts and a porcelain ascending aorta, presented with symptomatic critical aortic stenosis. Through a left anterolateral thoracotomy, a valved conduit was anastomosed to the descending thoracic aorta. The automated coring and apical connector insertion device was used to core a plug of apical myocardium and simultaneously insert an 18-mm apical connector into the left ventricular apex. There were no procedural complications, cardiopulmonary bypass was not used, and estimated blood loss was minimal. The patient was discharged on postoperative day 5, and at 3-month follow-up demonstrated significant clinical and hemodynamic improvement. The automated coring and apical connector insertion device facilitated the safe and effective performance of aortic valve bypass surgery.


An evaluation of monovalent, divalent, and trivalent cations as aggregating agents for surface enhanced Raman spectroscopy (SERS) analysis of synthetic cannabinoids.
In this study monovalent, divalent, and trivalent chloride, sulfate and nitrate salts were examined to determine the critical coagulation concentration (CCC) for each salt and its corresponding effect on detection limits for SERS analysis of cannabinoid extracts. The CCC of each salt was determined using UV-vis, particle size and zeta potential measurements. The results demonstrated that the divalent and trivalent cations produce a lower CCC when compared to monovalent cations. The data indicate the effect that cation valence has on nanoparticle destabilization. This information is essential because it permits the user to develop optimal conditions for aggregation of salts used in SERS. Tests were then performed to determine the best conditions for SERS detection of a small set of cannabinoids with naphthyl indole moieties. The results demonstrate the importance of salt concentration for colloid aggregation and illustrate the effect of aggregation on sensitivity for the SERS experiment.


Visual fields in patients with posterior GPi pallidotomy.
The objective of this study was to describe the incidence and types of visual field defects after posterior globus pallidus internus (GPi) pallidotomy for Parkinson's disease. The creation of the pallidotomy lesion carries a risk of damaging neighboring structures such as the optic tract. The reported frequency of visual field defects in patients after pallidotomy varies from 0 to 40%. Goldmann visual field testing was performed on 40 patients who underwent microelectrode-guided posterior GPi pallidotomy. The optic tract was identified during the procedure by listening during microelectrode recording for the evoked responses to light flashes and by assessing stimulation-induced subjective responses. After the first 18 patients, lesioning thresholds were increased from 0.5 to > or =1.0 mA so that the lesion was placed more distant from the optic tract. The location of individual lesions was determined on postsurgical MRI. Three patients (7.5%) had visual field defects likely related to the pallidotomy. These were contralateral homonymous superior quadrantanopias, associated in two patients with small paracentral scotomas. The incidence of visual field defects with the early technique was 11% (2/18) and decreased to 4.5% (1/22) after thresholds for lesioning were increased. Except for the location of the lesion relative to the optic tract (more ventral, adjacent to or extending into the optic tract), no other variable correlated with a post-pallidotomy visual field defect. Microelectrode-guided GPi pallidotomy is a relatively safe procedure as regards visual function even when the optic tract is used as a guide for lesion placement.


[The social and work activities of patients after the radical treatment of lung cancer].
One hundred and twenty-six radically treated patients with lung cancer showed a decrease in the majority of parameters of socio-occupational activity. A comparative study in two groups of patients (lobectomy-95 and pneumonectomy-31) established a correlation between the extent of surgery and degree of socio-occupational activity rehabilitation which was most pronounced in terms of patients' intercourse, resumption of occupational activity and duration of rehabilitation and invalidity periods. Psychoemotional status of lobectomized patients proved better than that in cases having undergone pneumonectomy.


Visual and vestibular cue integration for heading perception in extrastriate visual cortex.
Natural behaviours, and hence neuronal populations, often combine multiple sensory cues to improve stimulus detectability or discriminability as we explore the environment. Here we review one such example of multisensory cue integration in the dorsal medial superior temporal area (MSTd) of the macaque visual cortex. Visual and vestibular cues about the direction of self-motion in the world (heading) are encoded by single multisensory neurons in MSTd. Most neurons tend to prefer lateral stimulus directions and, as they are broadly tuned, are most sensitive in discriminating heading directions around straight forward. Decoding of MSTd population activity shows that these neuronal properties can account for the fact that heading perception in humans and macaques is most precise for directions around straight forward, whereas heading sensitivity declines with increasing eccentricity of the reference direction. Remarkably, when heading is specified by both cues simultaneously, behavioural precision is improved in a manner that is predicted by statistically optimal (Bayesian) cue integration models. A subpopulation of multisensory MSTd cells with congruent visual and vestibular heading preferences also combines the cues near-optimally, establishing a potential neural substrate for behavioral cue integration.


National Hospital Ambulatory Medical Care Survey: 2004 outpatient department summary.
This report describes ambulatory care visits to hospital OPDs in the United States. Statistics are presented on selected hospital, patient, and visit characteristics. Selected trends in OPD utilization from 1994 through 2004 are also presented. The data presented in this report were collected in the 2004 NHAMCS, a national probability sample survey of visits to emergency and outpatient departments of nonfederal, short-stay, and general hospitals in the United States. Selected comparisons are also made with data from the 2004 National Ambulatory Medical Care Survey (NAMCS), a national probability sample survey of visits to office-based physicians in the United States. Sample data are weighted to produce annual national estimates. During 2004, an estimated 85.0 million visits were made to hospital OPDs in the United States, about 29.5 visits per 100 persons. Females (35.1 per 100 persons) had higher OPD visit rates than males (23.6 per 100 persons), and black or African American persons (50.3 per 100 persons) had higher OPD visit rates than white persons (27.0 visits per 100 persons). The overwhelming majority of visits to hospital OPDs were made by established patients (85.4 percent). Females made 75.5 percent of preventive care visits. The preventive care visit rate by Hispanic or Latino patients was twice the rate of non-Hispanic patients. Diagnostic and screening services were ordered at 90.3 percent of visits, therapeutic and preventive services were ordered at 50.0 percent of visits, and medications were ordered at 67.4 percent of visits. The proportion of visits involving only midlevel providers increased from 5.9 in 1993-94 to 11.4 percent of visits in 2003-04.


Assessment of the Impact of Scientific Reports Published by EFSA and GIS on Functional Foods Newly Placed on the Market in Poland.
Dietary supplements are health-promoting products. The legal categorization of dietary supplements as foods does not raise concerns, but a general understanding of how they work in the human body seems to deviate from the official definition. Thus, it is necessary to establish effective methods of market control related to dietary supplements. This research aims at assessing the impact of recommendations by various food safety authorities on ingredients used in newly registered products. It probes how the proportions of utilized product ingredients were modified after the European Food Safety Authority (EFSA) and Chief Sanitary Inspector in Poland (GIS) published their recommendations. Research data on the composition of products comes from the Polish national register of dietary supplements and covers the period from 2012 to 28 November 2021. Note that 103,102 products were analysed for the presence of thirty-seven ingredients, and the joinpoint regression method was applied to assess changing trends related to the use of ingredients. As our research points out, most often, changes in the trend appeared in product ingredients for which the European Food Safety Authority and Chief Sanitary Inspector in Poland issued the recommendation of having the safest level of consumption. However, these changes seem to emerge randomly and should not be unquestionably considered as the result of the published recommendations.


Protection of copper surface with phytic acid against corrosion in chloride solution.
Phytic acid (inositol hexaphosphate) was tested as a corrosion inhibitor for copper in 3% sodium chloride. Phytic acid is a natural compound derived from plants, it is not toxic and can be considered as a green inhibitor. Electrochemical methods of linear polarization and potentiodynamic polarization were used to study the electrochemical behaviour and evaluate the inhibition effectiveness. To obtain the optimal corrosion protection the following experimental conditions were investigated: effect of surface pre-treatment (abrasion and three procedures of surface roughening), pre-formation of the layer of phytic acid, time of immersion and concentration of phytic acid. To evaluate the surface pre-treatment procedures the surface roughness and contact angle were measured. Optimal conditions for formation of phytic layer were selected resulting in the inhibition effectiveness of nearly 80%. Morphology and composition of the layer were further studied by scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The layer of phytic acid with thickness in the nanometer range homogeneously covers the copper surface. The obtained results show that this natural compound can be used as a mildly effective corrosion inhibitor for copper in chloride solution.


Interaction of atriopeptin III and vasopressin on calcium kinetics and contraction of aortic smooth muscle cells.
The cellular mechanism of the vasodilatory action of atriopeptin III (APIII) on vasopressin (AVP)-induced Ca2+ mobilization and cell shape change in cultured vascular smooth muscle cells (VSMC) was studied. APIII (10(-8) M) attenuated the increase of intracellular free Ca2+, [Ca2+]i, induced by 10(-8) M AVP (234.0 +/- 14.8 vs. 310.0 +/- 28.4 nM, P less than 0.01). Similar results were obtained in 45Ca2+ efflux experiments. APIII (10(-7) M), however, did not alter AVP-induced inositol trisphosphate (IP3) production, although the levels of inositol-1-phosphate were significantly reduced. The effect of APIII to block or attenuate AVP-induced Ca2+ mobilization was associated with an inhibition of AVP-stimulated cell shape change. The effect of atrial natriuretic factor (ANF) on cell shape, however, occurred at lower ANF concentrations than the effect on the Ca2+ mobilization. APIII stimulated production of cyclic guanosine monophosphate (cGMP) in VSMC. The effect of APIII on AVP-stimulated Ca2+ mobilization was partially mimicked by the stable nucleotide 8-bromo cGMP and was not affected by the soluble guanylate cyclase inhibitor, methylene blue (10(-4) M). These results suggest that APIII exerts its vasodilatory effect, in part, by interference with vasopressor-stimulated Ca2+ mobilization in vascular smooth muscle cells, perhaps by stimulating particulate guanylate cyclase and cGMP. However, an effect of ANF on the contractile mechanism at a site independent of Ca2+ release is also suggested by the present results.


Prevalence of post-stroke cognitive impairment and associated risk factors in Chinese stroke survivors.
Post-stroke cognitive impairment (PSCI) adversely affects survivors' recovery trajectory and overall health outcomes. This study aimed to investigate the prevalence of PCSI and its associated risk factors. A cross-sectional study was conducted with stroke survivors recruited from the neurology units of three hospitals in Yunnan, China. Measures included the Frenchay Aphasia Screening Test (FAST), Apathy Evaluation Scale (AES), Fatigue Severity Scale (FSS), Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE), Montreal Cognitive Assessment (MoCA), and Charlson Comorbidity Index (CCI). Logistic regression analysis was carried out to identify risk factors significantly and independently associated with PSCI. Of 389 stroke participants studied, 139 (36%) were found to have PSCI. Every 10-year increase in age [odds ratio (OR) =1.69, 95% confidence interval (CI): 1.27-2.24, p < 0.001], and 1-point increase in the AES (OR = 1.13, 95% CI: 1.07-1.18, p < 0.001) and FSS scores (OR = 1.06, 95% CI: 1.03-1.10, p < 0.001) were significantly associated with higher odds of PSCI. Conversely, a 1-point increase in the MoCA score (OR = 0.91, 95% CI: 0.87-0.95, p < 0.001) and having an undergraduate education (OR = 0.45, 95% CI: 0.24-0.84, p = 0.013) or postgraduate education (OR = 0.18, 95% CI: 0.06-0.50, p = 0.001) were associated with reduced odds of PSCI. PSCI is prevalent in the Chinese population, with advanced age, lower education levels, lower MoCA scores, and higher fatigue and apathy scores identified as strong risk factors. It is recommended that psychological and cognitive assessment be routinely incorporated into post-stroke rehabilitation pathways to mitigate cognitive decline.


Statistical models for local occurrences of RNA structures.
We develop in this article the necessary statistical theory for computing, for instance, E-values when searching long sequences for the occurrences of local RNA-structures. We show in particular how the theory can be used for estimating scoring parameters with the purpose of optimizing the discriminative performance of the algorithm. The results are implemented in the program StemSearch, which can search for stem loop structures that are formed by, for example, micro RNA precursors. We illustrate the use of the estimation method in practice by considering three miRNA target datasets from Human, Arabidopsis, and C. elegans and by optimizing three penalty parameters in StemSearch. We show that the optimization can improve the discriminative performance considerably when using a first order Markov model as null-distribution. Finally, we compare the output from StemSearch with that of RNALfold, and we discuss some notable differences that are primarily due to fundamental differences in the choice of parameters.


Feet, heat and scallops: what is the cost of anthropogenic disturbance in bivalve aquaculture?
The effects of unnatural disturbances on the behaviour and energetics of animals are an important issue for conservation and commercial animal production. Biologging enables estimation of the energy costs of these disturbances, but not specifically the effect these costs have on growth; a key outcome measure for animal farming enterprises. We looked at how natural and anthropogenically induced activity and energy expenditure of king scallops Pecten maximus varies with temperature. These data were then used to model growth time of king scallops reared in an aquaculture facility under different temperatures and anthropogenic disturbance levels. The scallops exhibited a typical total metabolic rate (MR)-temperature curve, with a peak reached at a middling temperature. The percentage of their total MR associated with spinning and swimming, behavioural responses to disturbance, was considerable. Interestingly, as temperature increased, the activity MR associated with a given level of activity decreased; a hitherto unreported relationship in any species. The model results suggest there is a trade-off in the ambient temperature that should be set by hatcheries between the optimal for scallop growth if completely undisturbed versus mitigating against the energy costs elicited by anthropogenic disturbance. Furthermore, the model indicates that this trade-off is affected by scallop size. Aquaculture facilities typically have controls to limit the impact of human activities, yet the present data indicate that hatcheries may be advised to consider whether more controls could further decrease extraneous scallop behaviours, resulting in enhanced scallop yields and improved financial margins.


Evaluation of a novel intervention providing insight into the tobacco industry to prevent the uptake of smoking in school-aged children: a mixed-methods study.
Evidence from the US Truth campaign suggests that interventions focusing on tobacco industry practices and ethics may be effective in preventing youth smoking uptake. We developed, piloted and evaluated a school-based intervention based on this premise. Exploratory study students in years 7-8 (aged 11-13) in two UK schools received Operation Smoke Storm, comprising three 50 min classroom-based sessions in year 7, an accompanying family booklet and a 1-hour classroom-based booster session in year 8. We compared the risk and odds of ever smoking and susceptibility to smoking in year 8 students in study schools postintervention with students in control schools. Focus groups and interviews with students, teachers and parents evaluated the acceptability of the intervention. In intervention schools, the combined prevalence of ever smoking and susceptibility increased from 18.2% in year 7 to 33.8% in year 8. There was no significant difference in the odds of a year 8 student in an intervention school being an ever smoker or susceptible never smoker compared with controls (adjusted OR (aOR) 1.28, 95% CI 0.83 to 1.97, p=0.263) and no significant difference in the odds of ever smoking (aOR 0.82, 95% CI 0.42 to 1.58, p=0.549). Teachers highlighted differences by academic ability in how well the messages presented were understood. Use of the family component was low but was received positively by parents who engaged with it. Operation Smoke Storm is an acceptable resource for delivering smoking-prevention education, but it does not appear to have reduced smoking and susceptibility.


Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver.
Sirtuin (SIRT1) is a nicotinamide adenine dinucleotide-dependent protein deacetylase that regulates hepatic lipid metabolism by modifying histones and transcription factors. Ethanol exposure disrupts SIRT1 activity and contributes to alcoholic liver disease in rodents, but the exact pathogenic mechanism is not clear. We compared mice with liver-specific deletion of Sirt1 (Sirt1LKO) mice with their LOX littermates (controls). We induced alcoholic liver injury in male Sirt1LKO and control mice, placing them on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Liver and serum samples were collected. We also measured messenger RNA levels of SIRT1, SFRS10, and lipin-1β and lipin-1α in liver samples from patients with alcoholic hepatitis and individuals without alcoholic hepatitis (controls). On the ethanol-containing diet, livers of Sirt1LKO mice accumulated larger amounts of hepatic lipid and expressed higher levels of inflammatory cytokines than control mice; serum of Sirt1LKO mice had increased levels of alanine aminotransferase and aspartate aminotransferase. Hepatic deletion of SIRT1 exacerbated ethanol-mediated defects in lipid metabolism, mainly by altering the function of lipin-1, a transcriptional regulator of lipid metabolism. In cultured mouse AML-12 hepatocytes, transgenic expression of SIRT1 prevented fat accumulation in response to ethanol exposure, largely by reversing the aberrations in lipin-1 signaling induced by ethanol. Liver samples from patients with alcoholic hepatitis had reduced levels of SIRT1 and a higher ratio of Lpin1β/α messenger RNAs than controls. In mice, hepatic deletion of Sirt1 promotes steatosis, inflammation, and fibrosis in response to ethanol challenge. Ethanol-mediated impairment of hepatic SIRT1 signaling via lipin-1 contributes to development of alcoholic steatosis and inflammation. Reagents designed to increase SIRT1 regulation of lipin-1 can be developed to treat patients with alcoholic fatty liver disease.


Pseudomonas putrefaciens from clinical material.
Three strains of Pseudomonas putrefaciens were isolated from routine clinical specimens at the University Hospital, Kuala Lumpur, Malaysia. Their cultural and biochemical characteristic, and antibiotic susceptibilities are presented. Characteristics of diagnostic value were stressed. Two isolates appeared to have played a pathogenic role in chronic otitis media.


Compartmental chest wall volume changes during volitional normocapnic hyperpnoea.
During increased ventilation, inspiratory rib cage muscles have been suggested to take over part of diaphragmatic work after the diaphragm fatigues. We investigated the extent to which this proposed change in muscle recruitment is associated with changes in the relative contribution of chest wall compartments to tidal volume (V(T)). Thirteen healthy subjects performed 1 h of fatiguing normocapnic hyperpnoea. Chest wall volumes were assessed by optoelectronic plethysmography. While breathing frequency increased (43±3 to 56±5 breaths min(-1), p=0.006) and V(T) decreased during normocapnic hyperpnoea (2.6±0.2 to 1.9±0.1l, p<0.001), the relative contribution of chest wall compartments to V(T) remained unchanged (pulmonary rib cage: 48±9 versus 51±14%; abdominal rib cage: 24±4 versus 23±9%; abdomen: 28±8 versus 26±9%; all p>0.05). In conclusion, fatiguing respiratory work is not associated with a change in compartmental contribution to V(T), even in the presence of a change in breathing pattern.


Associations between vision, hearing and tooth loss and social interactions: the JAGES cross-sectional study.
Difficulties in communication due to vision, hearing and tooth loss have a serious impact on health. We compared the association between and attribution of each of these factors on social interaction. This cross-sectional study examined data from the 2016 Japan Gerontological Evaluation Study (n=22 295) on community-dwelling people aged ≥65 years in Japan. The dependent variable was the frequency of meeting friends as a measure of social interaction, and less-than-monthly was defined as fewer social interactions. The independent variables were self-reported degrees of vision, hearing (5-point Likert scale) and tooth loss (five categories), with 'poor' or '0 teeth' defined as the worst category. Sex, age, educational attainment, comorbidity and residential area were used as covariates. Poisson regression analysis with multiple imputations was used to estimate the prevalence ratios (PRs) of fewer social interactions by each status. Subsequently, the population attributable fraction (PAF) was calculated to assess the public health impact. The number of participants with fewer social interactions was 5622 (26.9%). Proportions of fewer social interactions among those with the worst vision, hearing and number of teeth categories were 48.7%, 40.1% and 32.0%, respectively. Their corresponding PRs of fewer social interactions were 1.72 (95% CI 0.97 to 3.05), 1.35 (95% CI 0.99 to 1.85) and 1.23 (95% CI 1.10 to 1.37), respectively. The total PAF for vision, hearing and number of teeth was 8.3%, 5.0% and 6.4%, respectively. Self-reported vision, hearing and tooth loss were associated with fewer social interactions. The magnitude of these impairments was largest in vision, followed by tooth and hearing loss.


Scopolamine-induced deficits in social memory in mice: reversal by donepezil.
Deficits in social behaviour is a characteristic of numerous mental disorders including autism, schizophrenia, depression and Alzheimer's disease. For the assessment of pharmacological and genetic experimental disease models, conventional social interaction tasks bear the uncertainty that any drug-induced abnormality of the investigator may feed back to the drug-free companion modifying its reactions. A considerable technical improvement was recently reported by Moy et al. [Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson T, et al. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behaviours in mice. Genes Brain Behav 2004;3:287-302] in which the drug free partner is confined to a small cage and social contacts of the investigator are recorded uncontaminated of any social reactions of the stranger. Using this novel behavioural paradigm, we here show in C57Bl/6 female mice that sociability (social interaction with a stranger mouse) is not impaired after administration of the anxiolytic diazepam (0.1-1 mg/kg) or the muscarinic antagonist scopolamine hydrobromide (0.1-1 mg/kg). However, social memory tested after a short time interval was impaired by both drugs in a dose-dependent manner (diazepam: > or = 0.5mg/kg; scopolamine: > or = 0.3mg/kg). The scopolamine-induced short-term memory deficit was reversed to normal by the choline esterase inhibitor donepezil (1 mg/kg). Given this dependence of social recognition on the cholinergic system, combined with the clinical observation of reduced social contacts in dementia patients, sociability may offer a novel endpoint biomarker with translational value in experimental models of cognitive dysfunction.


[Ultrasound diagnosis of the stomach wall--experimental studies].
The gastrointestinal wall can be separated into 5 layers by means of ultrasonic endoscopy and also by external ultrasound when using a probe of 5 Mhz. We studied the relationship between these echographic layers and the real anatomical structures by means of in-vitro examination of surgical specimens. The anatomical layers were separated in these specimens step by step. We found that the first and the fifth hyperechoic layers are border echos. The 2. (inner echopoor layer), the 3. (middle echogenic layer) and the 4. (outer echopoor layer) correspond to the mucosa, the submucosa and the muscularis propria, respectively. In so far, the differentiation between early cancer and advanced cancer of the stomach should be possible by endoscopic ultrasonography.


Paradox and promise: research on the role of recent advances in paleodemography and paleoepidemiology to the study of "health" in Precolumbian societies.
Bioarcheology has made tremendous strides since the subdiscipline's inception, subsequent syntheses, the standardization of data collection methods, and analytical advances ranging from molecular analyses through age-estimation and biodistance. Concurrently, health and the adaptive success of past populations have remained primary concerns. However, questions are routinely raised about lesions and whether or not changing frequencies are synonymous with increases or decreases in stress, morbidity, and overall health. These include how and why healed lesions can simultaneously represent stress and survival, demanding that researchers understand how population dynamics influence skeletal sample formation. In this study, methods to analyze age- and sex-specific mortality patterns prior to, and in conjunction with, the analysis of linear enamel hypoplasias are demonstrated. Paleodemographic and paleoepidemiological models are presented for late Pre-Columbian skeletal samples from the Eastern Woodlands. Results of hazard modeling demonstrate that elevated mortality rates were commonplace during the latter half of the Mississippian period (AD 1200-1450) with reproductive-age females experiencing high age-specific risk of death attributed to the development of fortified villages and novel environments for increased pathogen loads. Corollary results are presented for the age-specificity of linear enamel hypoplasias in the central Illinois River valley. The epidemiological models demonstrate that the relationship between adult mortality and early childhood stress varied through space, culture, and time. These findings highlight the need to effectively operationalize measurements related to health and stress in past populations and support the adoption of selective mortality and heterogeneity in frailty as key concepts in bioarcheological research. Am J Phys Anthropol 155:268-280, 2014. © 2014 Wiley Periodicals, Inc.


A non-nucleotide agonist that binds covalently to cysteine residues of STING.
Stimulator of interferon genes (STING) is an ER-localized transmembrane protein and the receptor for 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which is a second messenger produced by cGAMP synthase (cGAS), a cytosolic double-stranded DNA sensor. The cGAS-STING pathway plays a critical role in the innate immune response to infection of a variety of DNA pathogens through the induction of the type I interferons. Pharmacological activation of STING is a promising therapeutic strategy for cancer, thus the development of potent and selective STING agonists has been pursued. Here we report that mouse STING can be activated by phenylarsine oxide (PAO), a membrane permeable trivalent arsenic compound that preferentially reacts with thiol group of cysteine residue (Cys). The activation of STING with PAO does not require cGAS or cGAMP. Mass spectrometric analysis of the peptides generated by trypsin and chymotrypsin digestion of STING identifies several PAO adducts, suggesting that PAO covalently binds to STING. Screening of STING variants with single Cys to serine residues (Ser) reveals that Cys88 and Cys291 are critical to the response to PAO. STING activation with PAO, as with cGAMP, requires the ER-to-Golgi traffic and palmitoylation of STING. Our results identify a non-nucleotide STING agonist that does not target the cGAMP-binding pocket, and demonstrate that Cys of STING can be a novel target for the development of STING agonist.Key words: STING agonist, cysteine modification, innate immunity, phenylarsine oxide.


FGF2 Inhibits Early Pancreatic Lineage Specification during Differentiation of Human Embryonic Stem Cells.
Growth factors are important regulators during organ development. For many vertebrates (but not humans) it is known how they contribute to the formation and expansion of PDX1-positive cells during pancreas organogenesis. Here, the effects of the fibroblast growth factors FGF2, FGF7, FGF10, and epidermal growth factor (EGF) on pancreas development in humans were assessed by using human pluripotent stem cells (hPSCs). During this, FGF2 was identified as a potent anti-pancreatic factor whereas FGF7, FGF10, and EGF increased the cell mass while retaining PDX1-positivity. FGF2 increased the expression of the anti-pancreatic factor sonic hedgehog (SHH) while suppressing PDX1 in a dose-dependent manner. Differentiating cells secreted SHH to the medium and we interrogated the cells' secretome during differentiation to globally examine the composition of secreted signaling factors. Members of the TGF-beta-, Wnt-, and FGF-pathways were detected. FGF17 showed a suppressive anti-pancreatic effect comparable to FGF2. By inhibition of specific branches of FGF-receptor signaling, we allocated the SHH-induction by FGF2 to MEK/ERK-signaling and the anti-pancreatic effect of FGF2 to the receptor variant FGFR1c or 3c. Altogether, we report findings on the paracrine activity of differentiating hPSCs during generation of pancreatic progenitors. These observations suggest a different role for FGF2 in humans compared to animal models of pancreas organogenesis.


Cigarette smoke extract induced exosome release is mediated by depletion of exofacial thiols and can be inhibited by thiol-antioxidants.
Airway epithelial cells have been described to release extracellular vesicles (EVs) with pathological properties when exposed to cigarette smoke extract (CSE). As CSE causes oxidative stress, we investigated whether its oxidative components are responsible for inducing EV release and whether this could be prevented using the thiol antioxidants N-acetyl-l-cysteine (NAC) or glutathione (GSH). BEAS-2B cells were exposed for 24h to CSE, H2O2, acrolein, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), bacitracin, rutin or the anti-protein disulfide isomerase (PDI) antibody clone RL90; with or without NAC or GSH. EVs in media were measured using CD63+CD81+ bead-coupled flow cytometry or tunable resistive pulse sensing (TRPS). For characterization by Western Blotting, cryo-transmission electron microscopy and TRPS, EVs were isolated using ultracentrifugation. Glutathione disulfide and GSH in cells were assessed by a GSH reductase cycling assay, and exofacial thiols using Flow cytometry. CSE augmented the release of the EV subtype exosomes, which could be prevented by scavenging thiol-reactive components using NAC or GSH. Among thiol-reactive CSE components, H2O2 had no effect on exosome release, whereas acrolein imitated the NAC-reversible exosome induction. The exosome induction by CSE and acrolein was paralleled by depletion of cell surface thiols. Membrane impermeable thiol blocking agents, but not specific inhibitors of the exofacially located thiol-dependent enzyme PDI, stimulated exosome release. Thiol-reactive compounds like acrolein account for CSE-induced exosome release by reacting with cell surface thiols. As acrolein is produced endogenously during inflammation, it may influence exosome release not only in smokers, but also in ex-smokers with chronic obstructive pulmonary disease. NAC and GSH prevent acrolein- and CSE-induced exosome release, which may contribute to the clinical benefits of NAC treatment.


Lymphocyte subsets in the young and aging marmoset (Callithrix jacchus).
T lymphocytes were studied in healthy young and old marmosets (Callithrix jacchus). Data indicate that monoclonal antisera to human T lymphocyte antigens can be used to identify these cells in marmosets. Total T and suppressor T cells were lower in the older group; there were no differences in helper T or in B cells. Helper/suppressor ratios (T4/T8) were increased in the older group. Thus, immune system alternations with aging and/or immune deficiency syndromes may be studied in this animal model using available reagents.


GLI1 is a direct transcriptional target of EWS-FLI1 oncoprotein.
Ewing sarcoma family of tumors (ESFT) is an undifferentiated neoplasm of the bone and soft tissue. ESFT is characterized by a specific chromosomal translocation occurring between chromosome 22 and (in most cases) chromosome 11, which generates an aberrant transcription factor, EWS-FLI1. The function of EWS-FLI1 is essential for the maintenance of ESFT cell survival and tumorigenesis. The Hedgehog pathway is activated in several cancers. Oncogenic potential of the Hedgehog pathway is mediated by increasing the activity of the GLI family of transcription factors. Recent evidence suggests that EWS-FLI1 increases expression of GLI1 by an unknown mechanism. Our data from chromatin immunoprecipitation and promoter reporter studies indicated GLI1 as a direct transcriptional target of EWS-FLI1. Expression of EWS-FLI1 in non-ESFT cells increased GLI1 expression and GLI-dependent transcription. We also detected high levels of GLI1 protein in ESFT cell lines. Pharmacological inhibition of GLI1 protein function decreased proliferation and soft agar colony formation of ESFT cells. Our results establish GLI1 as a direct transcriptional target of EWS-FLI1 and suggest a potential role for GLI1 in ESFT tumorigenesis.


Distinguishing the early-onset/persistent and adolescence-onset antisocial behavior types: from birth to 16 years.
Moffitt's theory regarding two types of adolescent antisocial behavior was investigated using a prospective, longitudinal study of normal and abnormal development in a primarily low socioeconomic status, ethnically diverse sample. Results supported the presence of an early-onset/persistent (EOP) group and an adolescence-onset (AO) group. Groups were most reliably and significantly distinguished by indices of socioemotional history within the first 3 years, but no significant differences were found on early measures of temperament or neuropsychological functioning. EOPs scored significantly lower than other groups on measures of neuropsychological functioning only during late childhood and adolescence, suggesting that the declines in verbal functioning that have been so reliably found in this and other samples of early-starting antisocial adolescents are progressive and consequent to adverse experience. In adolescence, AOs were significantly more likely to report high levels of internalizing symptoms and life stress, suggesting that AO antisocial behavior is not a benign phenomenon. Implications of these findings for etiologic theories of adolescent antisocial behavior are discussed.


The prognostic value of amplitude-integrated electroencephalography in neonates with hypoxic-ischemic encephalopathy.
Diagnosis of perinatal hypoxic-ischemic encephalopathy (HIE) and early prediction neurological outcome is important and difficult. The aim of this study was to determine the prognostic value of amplitude-integrated electroencephalography (aEEG) for abnormal neurodevelopment outcome in a neonate with HIE. A total of 90 neonates > 32 gestational age (GA) with HIE were enrolled prospectively. All neonates with HIE were categorized into three grades according to the Sarnat and Sarnat clinical scoring system (mild HIE, moderate HIE and severe HIE). aEEG traces were recorded with a cerebral function monitor (CFM) during the first 72 h of life. The neurodevelopment outcome was assessed at 12 months of age of corrected gestational age. The pattern of aEEG correlated with the severity of HIE (p < 0.0001) and subsequent neurodevelopment outcome (p < 0.001). We found that aEEG background patterns exhibited superior prediction of abnormal outcomes at 12 months of age (sensitivity of 91.7% and specificity of 94.3%, positive predictive value of 78.6% and negative predictive value of 98.1%) when compared to aEEG seizure (sensitivity of 94% and specificity of 48%, positive predictive value of 57% and a negative predictive value of 92%). Electroclinical dissociation seizure was detected in 28% of the neonates with HIE. Our results confirm that aEEG is simple and accurate bedside diagnostic method for assessing extension of hypoxic-ischemic brain damage and early identification of neonates with perinatal HIE who are at high risk of neurodevelopmental impairment.


[Reverse meridional cyclodialysis ab interno with implantation of a metallic implant in patients with glaucoma of different etiology].
To evaluate the safety and effectiveness of reverse meridional cyclodialysis (RMC) ab interno with implantation of a metallic implant into the supraciliary space for decreasing intraocular pressure in glaucoma patients. RMC was performed ab interno in 51 patients, among which 30 patients had a metallic implant inserted into the supraciliary space (implant group). Twenty-one patients who underwent RMC ab interno without implant comprised the control group. The outcomes were evaluated after 12 months. RMC was performed through a clear corneal incision using a special spatula at 4-5 o'clock reaching 5-6 mm deep, width of the cleft was 11-12o of the iridocorneal angle. The evaluation criteria included adverse events, postoperative IOP changes, need for hypotensive medications and repeat surgery. The results were analyzed using variational statistics. Baseline mean IOP was 28.8±4.7 mmHg and 30.2±7.2 mmHg in implant and control groups, respectively, and at 12 months it decreased by 28.7±12.0% and 29.1±17.1%. Baseline mean medication usage was 2.7±0.8 and 2.6±0.9 in respective groups, at 12 months it decreased to 1.1±0.9 and 0.8±0.9. In the implant group, overall success was achieved in 93.3% of cases (complete success - 33.3%, partial success - 60.0%), while in the control group it was 66.7% (complete success - 28.6%, partial success - 38.1%) (p=0.03). In terms of IOP decrease, medication usage and adverse events the difference between the groups was statistically insignificant. Repeat surgery was required 5 times more frequently in the control group (33.3% vs 6.7%, p=3E-05). Implantation of a metallic implant into the supraciliary space to keep the cyclodialysis cleft open is safe and effective and substantially decreases the need for repeat surgery.


Prevalence and predictors of long-acting reversible contraceptive use among sexually active women in 26 sub-Saharan African countries.
Long-acting reversible contraceptives (LARCs) are associated with high efficacy rates and continuity of use. Based on the foregoing, we sought to examine the prevalence and factors associated with LARC use among sexually active women in 26 countries in sub-Saharan Africa(SSA). Secondary data from Demographic and Health Surveys conducted in 26 countries in SSA between January 2010 and December 2019 were pooled and analysed. A total of 56 067 sexually active women 15-49 y of age met the inclusion criteria. Bivariate and multivariate regression analyses were performed to examine the association between selected factors and the use of LARCs in SSA. Results were presented as crude odds ratios and adjusted odds ratios (aORs) with statistical precision at <0.05. The prevalence of LARC use was 21.73%, ranging from 1.94% in Namibia to 54.96% in Benin. Sexually active women with secondary or higher education (aOR 1.19 [95% confidence interval {CI} 1.08 to 1.32]), those cohabiting (aOR 1.25 [95% CI 1.06 to 1.47]) and those with four or more children (aOR 2.22 [95% CI 1.78 to 2.78]) were more likely to use LARCs compared with those without education, never married and with no biological child. The use of LARCs in the 26 countries in SSA was relatively low. Hence, the identified contributory factors of LARC use should be tackled with appropriate interventions. These include continuous campaigns on the efficacy of LARCs in reducing unintended pregnancy, maternal mortality and morbidity.


Alcohol consumption, types of alcoholic beverages and risk of venous thromboembolism - the Tromsø Study.
Moderate alcohol consumption has been shown to protect against cardiovascular diseases. The association between alcohol consumption, especially types of alcoholic beverages, and venous thromboembolism (VTE) is less well described. The aim of this study was to investigate the impact of alcohol consumption and different alcoholic beverages on risk of VTE. Information on alcohol consumption was collected by a self-administrated questionnaire in 26,662 subjects, aged 25-97 years, who participated in the Tromsø Study, in 1994-1995. Subjects were followed through September 1, 2007 with incident VTE as the primary outcome. There were 460 incident VTE-events during a median of 12.5 years of follow-up. Total alcohol consumption was not associated with risk of incident VTE. However, subjects consuming ≥ 3 units of liquor per week had 53% increased risk of VTE compared to teetotalers in analyses adjusted for age, sex, body mass index, smoking, diabetes, cancer, previous cardiovascular disease, physical activity and higher education (HR: 1.53, 95% CI: 1.00-2.33). Contrary, subjects with a wine intake of ≥ 3 units/week had 22% reduced risk of VTE (HR: 0.78, 95% CI: 0.47-1.30), further adjustment for liquor and beer intake strengthened the protective effect of wine (HR: 0.53, 95% CI: 0.30-1.00). Frequent binge drinkers (≥ 1/week) had a 17% increased risk of VTE compared to teetotallers (HR 1.17, 95% CI: 0.66-2.09), and a 47% increased risk compared to non-binge drinkers (HR 1.47, 95% CI: 0.85-2.54). In conclusion, liquor consumption and binge drinking was associated with increased risk of VTE, whereas wine consumption was possibly associated with reduced risk of VTE.


On the relation between action selection and movement control in 5- to 9-month-old infants.
Although 5-month-old infants select action modes that are adaptive to the size of the object (i.e., one- or two-handed reaching), it has largely remained unclear whether infants of this age control the ensuing movement to the size of the object (i.e., scaling of the aperture between hands). We examined 5-, 7-, and 9-month-olds' reaching behaviors to gain more insight into the developmental changes occurring in the visual guidance of action mode selection and movement control, and the relationship between these processes. Infants were presented with a small set of objects (i.e., 2, 3, 7, and 8 cm) and a large set of objects (i.e., 6, 9, 12, and 15 cm). For the first set of objects, it was found that the infants more often performed two-handed reaches for the larger objects based on visual information alone (i.e., before making contact with the object), thus showing adaptive action mode selection relative to object size. Kinematical analyses of the two-handed reaches for the second set of objects revealed that inter-trial variance in aperture between the hands decreased with the approach toward the object, indicating that infants' reaching is constrained by the object. Subsequent analysis showed that between hand aperture scaled to object size, indicating that visual control of the movement is adjusted to object size in infants as young as 5 months. Individual analyses indicated that the two processes were not dependent and followed distinct developmental trajectories. That is, adaptive selection of an action mode was not a prerequisite for appropriate aperture scaling, and vice versa. These findings are consistent with the idea of two separate and independent visual systems (Milner and Goodale in Neuropsychologia 46:774-785, 2008) during early infancy.


Uterine osseous metaplasia.
A rare case of osseous metaplasia of the endocervix and endometrium is discussed with both macroscopic and microscopic evidence of new bone formation in the uterus. History of menstrual irregularities, repeated abortions, infertility with histopathologic evidence of chronic inflammation, and bone formation may be evident in these cases. Various theories of the pathogenesis of benign uterine bone formation are discussed.


MR imaging of hepatocellular carcinoma.
Forty-two patients with hepatocellular carcinoma (HCC) were examined by magnetic resonance (MR) imaging. The presence of tumor was suggested in 41 of 42 cases by a high-intensity area on T2 weighted spin-echo (SE) images with a repetition time (TR) of 1.6 s. Specific findings of HCC such as the presence of a capsule, mosaic pattern, and tumor thrombus in major veins were noted in 10, two, and seven cases, respectively. In six cases the tumor pattern changed from a well-defined mass to an irregular, ill-defined one according to pulse sequence (SE: echo time 35 and 70 ms; TR 1.6 and 0.4 s). In our early experience MR was almost equal to conventional X-ray CT in the detection of main or daughter lesions and in the determination of extent and characterization of HCC.


Porosity of the yeast cell wall and membrane.
The limiting sizes of molecules that can permeate the intact cell wall and protoplast membrane of Saccharomyces cerevisiae were determined from the inflection points in a triphasic pattern of passive equilibrium uptake values obtained with a series of inert probing molecules varying in molecular size. In the phase identified with the yeast protoplast, the uptake-exclusion threshold corresponded to a monodisperse ethylene glycol of molecular weight = 110 and Einstein-Stokes hydrodynamic radius (r(ES)) = 0.42 nm. In the cell wall phase, the threshold corresponded to a polydisperse polyethylene glycol of number-average molecular weight ( M(n)) = 620 and average radius (r(ES)) = 0.81 nm. The third phase corresponded to complete exclusion of larger molecules. The assessment of cell wall porosity was confirmed by use of a second method involving analytical gel chromatographic analyses of the molecular weight distribution for a single polydisperse polyglycol before and after uptake by the cells, which indicated a quasi-monodisperse threshold for the cell wall of M(n) = 760 and r(ES) = 0.89 nm. The results were reconciled with two situations in which much larger protein molecules previously have been reported able to penetrate the yeast cell wall.


Architectural Changes in Superficial and Deep Compartments of the Tibialis Anterior During Electrical Stimulation Over Different Sites.
Electrical stimulation is widely used in rehabilitation to prevent muscle weakness and to assist the functional recovery of neural deficits. Its application is however limited by the rapid development of muscle fatigue due to the non-physiological motor unit (MU) recruitment. This issue can be mitigated by interleaving muscle belly (mStim) and nerve stimulation (nStim) to distribute the temporal recruitment among different MU groups. To be effective, this approach requires the two stimulation modalities to activate minimally-overlapped groups of MUs. In this manuscript, we investigated spatial differences between mStim and nStim MU recruitment through the study of architectural changes of superficial and deep compartments of tibialis anterior (TA). We used ultrasound imaging to measure variations in muscle thickness, pennation angle, and fiber length during mStim, nStim, and voluntary (Vol) contractions at 15% and 25% of the maximal force. For both contraction levels, architectural changes induced by nStim in the deep and superficial compartments were similar to those observed during Vol. Instead, during mStim superficial fascicles underwent a greater change compared to those observed during nStim and Vol, both in absolute magnitude and in their relative differences between compartments. These observations suggest that nStim results in a distributed MU recruitment over the entire muscle volume, similarly to Vol, whereas mStim preferentially activates the superficial muscle layer. The diversity between spatial recruitment of nStim and mStim suggests the involvement of different MU populations, which justifies strategies based on interleaved nerve/muscle stimulation to reduce muscle fatigue during electrically-induced contractions of TA.


Habit formation following routine-based versus time-based cue planning: A randomized controlled trial.
Habit formation has been identified as one of the key determinants of behaviour change. To initiate habit formation, self-regulation interventions can support individuals to form a cue-behaviour plan and to repeatedly enact the plan in the same context. This randomized controlled trial aimed to model habit formation of an everyday nutrition behaviour and examined whether habit formation and plan enactment differ when individuals plan to enact their behaviour in response to a routine-based versus time-based cue. Following a baseline assessment, N = 192 adults (aged 18-77 years) were randomly assigned to a routine-based cue or a time-based cue planning intervention, in which they selected an everyday nutrition behaviour and linked it to a daily routine or a time cue. Participants responded to daily questionnaires over 84 days assessing plan enactment and the behaviour's automaticity (as an indicator of habit formation). Multilevel models with days nested in participants were fitted. As indicated by asymptotic curves, it took a median of 59 days for participants who successfully formed habits to reach peak automaticity. Group-level analyses revealed that both routine-based and time-based cue planning led to increases in automaticity and plan enactment, but no between-condition differences were found. Repeated plan enactment was a key predictor for automaticity. Linking one's nutrition behaviour to a daily routine or a specific time was similarly effective for habit formation. Interventions should encourage persons to repeatedly carry out their planned behaviour in response to the planned cue to facilitate habit formation.


Mechanisms of the Ba2+-induced contraction in smooth muscle cells of the rabbit mesenteric artery.
The mechanism of the Ba2+-induced contraction was investigated using intact and saponin-treated skinned smooth muscle (skinned muscle) strips of the rabbit mesenteric artery. After depletion of Ca2+ stored in the caffeine-sensitive site, greater than 0.65 mM Ba2+ evoked contraction in muscle strips depolarized with 128 mM K+ in Ca2+-free solution in a dose-dependent fashion, and the ED50 values for Ca2+ and Ba2+ were 0.5 mM and 1.2 mM in intact muscle strips, respectively. Nisoldipine (10 nM) blocked the contraction evoked by high K+ or 10 microM norepinephrine (NE) in the presence of 2.6 mM Ba2+, but did not block the contraction evoked in the presence of 2.6 mM Ca2+. These results may indicate that Ba2+ permeates the voltage-dependent Ca2+ channel. In skinned muscle strips, the ED50 values for Ca2+ and Ba2+ were 0.34 and 90 microM, respectively, as estimated from the pCa- and pBa-tension relationships. Calmodulin enhanced and trifluoperazine inhibited the Ba2+- and Ca2+-induced contractions. After the application of Ba2+ or Ca2+ with ATP gamma S in rigor solution, myosin light chain (MLC) was irreversibly thiophosphorylated, as estimated from the Ba2+- or Ca2+-independent contraction. Furthermore, both divalent cations phosphorylated MLC, as measured using two-dimensional gel electrophoresis, to the extent expected from the amplitudes of the contraction evoked by these cations. Thus, Ba2+ is capable of activating the contractile proteins as Ca2+ does. The amount of Ca2+ or Ba2+ stored in cells was estimated from the caffeine response evoked in Ca2+-free solution in intact and skinned muscle strips. After the application of 0.3 microM Ca2+ or 0.1 mM Ba2+ for 60 s to skinned muscle strips after the depletion of Ca2+ stored in cells, caffeine produced a contraction only upon pretreatment with Ca2+ but not with Ba2+. When Ba2+ was applied successively just after the application of Ca2+, the subsequently evoked caffeine-induced contraction was much smaller than that evoked by pretreatment with Ca2+ alone. The above results indicate that Ba2+ permeates the voltage-dependent Ca2+ channel but may not permeate the receptor-operated Ca2+ channel, it releases Ca2+ from store sites but is not accumulated into the store site, and it directly activates the contractile proteins via formation of a Ba2+-calmodulin complex.


EMR-Based Phenotyping of Ischemic Stroke Using Supervised Machine Learning and Text Mining Techniques.
Ischemic stroke is a major cause of death and disability in adulthood worldwide. Because it has highly heterogeneous phenotypes, phenotyping of ischemic stroke is an essential task for medical research and clinical prognostication. However, this task is not a trivial one when the study population is large. Phenotyping of ischemic stroke depends primarily on manual annotation of medical records in previous studies. This article evaluated various strategies for automated phenotyping of ischemic stroke into the four subtypes of the Oxfordshire Community Stroke Project classification based on structured and unstructured data from electronical medical records (EMRs). A total of 4640 adult patients who were hospitalized for acute ischemic stroke in a teaching hospital were included. In addition to the structured items in the National Institutes of Health Stroke Scale, unstructured clinical narratives were preprocessed using MetaMap to identify medical concepts, which were then encoded into feature vectors. Various supervised machine learning algorithms were used to build classifiers. The study results indicate that textual information from EMRs could facilitate phenotyping of ischemic stroke when this information was combined with structured information. Furthermore, decomposition of this multi-class problem into binary classification tasks followed by aggregation of classification results could improve the performance.


Light microscopic localization of brain opiate receptors: a general autoradiographic method which preserves tissue quality.
A general technique is described for using slide-mounted unfixed tissue sections to characterize and visualize drug and neurotransmitter receptors in brain or other tissues. The preparation of material, from fresh frozen, unfixed brain to dried sections securely attached to slides, is described in detail. The tissue can be kept intact during incubation at varying temperatures in solutions containing radiolabeled ligand, ions, buffers, and allosteric effectors. Strategies are described for determining optimal stereospecific binding with highest signal-to-noise ratios and for determining that a "meaningful" receptor is being studied. Dry formaldehyde fixation by vapors from heated paraformaldehyde preserves the tissue quality and traps the ligand near its site on the receptor, permitting subsequent histological processing through alcohols, solvents, and aqueous media, including liquid nuclear track emulsion. Visualization of [3H]naloxone- or [3H]enkephalin-labeled opiate receptor distributions in rat and human brains is achieved by tritium-sensitive film or by classical "wet" emulsion autoradiography. The advantages of the film include its ease of use and the ability to quantify receptor density by densitometry which can be computer-assisted. The advantage of the emulsion is the greater resolution and the concomitant appearance of morphology in cell-stained sections. Examples of correlations of opiate receptor distributions which underlying cytoarchitecture illustrate the potential for receptor localization studies.


The relevance of Nash equilibrium to psychiatric disorders.
In game theory, the word 'game' is used to describe any interdependence between interacting parties, and the Nash equilibrium is a prominent tool for analysing such interactions. I argue that the concept of the Nash equilibrium may also be used in non-gaming contexts. An individual is in a Nash equilibrium if his or her beliefs are consistent with his or her actions. Given that discordance between beliefs and behaviour is a typical cause of psychiatric disorders, individuals who are not in a Nash equilibrium are likely to be affected by such disorders. In this regard, the concept of the Nash equilibrium could aptly be introduced into the medical practitioner's vocabulary for describing a patient's mental health status.


Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.
A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.


Toward an enhanced understanding of psychological resilience for HIV youth populations.
Though mother-to-child HIV transmission has been dramatically reduced in the past decade, there are currently an estimated 1.8 million children living with HIV across the globe, and over 30% of all new HIV infections occur among youth ages 15-25. While all youth experience developmental challenges, children and adolescents who are living with HIV must navigate these challenges within the context of high HIV stigma and must cope with a host of psychosocial and health-related challenges. In addition, because HIV disproportionately impacts individuals from minority statuses (e.g., race, ethnicity, gender, sexuality) and people living in poverty, vulnerabilities are often compounded. Resilience frameworks emphasize the capacity for positive adaptation to adversity, and thus provide a useful lens to identify and build upon individual and community strengths. This article introduces a special issue of AIDS Care that examines factors associated with resilience among children and adolescents affected by or living with HIV, as well as innovative interventions designed to build resilience among HIV youth populations. The articles highlighted within this issue examine the possibility of building resilience across diverse settings (e.g., schools, communities, healthcare clinics) and with varied populations (e.g., youth living with HIV, AIDS orphans, young men who have sex with men). We also highlight innovative approaches to resilience-building, including a new mobile Health (mHealth) smartphone game that aims to improve adherence among youth living with HIV in the United States.


Nonhuman primate models in type 1 diabetes research.
The recent success of "steroid-free" immunosuppressive protocols and improvements in islet preparation techniques have proven that pancreatic islet transplantation (PIT) is a valid therapeutic approach for patients with type 1 diabetes. However, there are major obstacles to overcome before PIT can become a routine therapeutic procedure, such as the need for chronic immunosuppression, the loss of functional islet mass after transplantation requiring multiple islet infusion to achieve euglycemia without exogenous administration of insulin, and the shortage of human tissue for transplantation. With reference to the first obstacle, stable islet allograft function without immunosuppressive therapy has been achieved after tolerance was induced in diabetic primates. With reference to the second obstacle, different strategies, including gene transfer of antiapoptotic genes, have been used to protect isolated islets before and after transplantation. With reference to the third obstacle, pigs are an attractive islet source because they breed rapidly, there is a long history of porcine insulin use in humans, and there is the potential for genetic engineering. To accomplish islet transplantation, experimental opportunities must be balanced by complementary characteristics of basic mouse and rat models and preclinical large animal models. Well-designed preclinical studies in primates can provide the quality of information required to translate islet transplant research safely into clinical transplantation.


Leveraging the Incidence, Burden, and Fiscal Implications of Unplanned Hospital Revisits for the Prioritization of Prevention Efforts in Pediatric Surgery.
To characterize procedure-level burden of revisit-associated resource utilization in pediatric surgery with the goal of establishing a prioritization framework for prevention efforts. Unplanned hospital revisits are costly to the health care system and associated with lost productivity on behalf of patients and their families. Limited objective data exist to guide the prioritization of prevention efforts within pediatric surgery. Using the Pediatric Health Information System (PHIS) database, 30-day unplanned revisits for the 30 most commonly performed pediatric surgical procedures were reviewed from 47 children's hospitals between January 1, 2012 and March 31, 2015. The relative contribution of each procedure to the cumulative burden of revisit-associated length of stay and cost from all procedures was calculated as an estimate of public health relevance if prevention efforts were successfully applied (higher relative contribution = greater potential public health relevance). 159,675 index encounters were analyzed with an aggregate 30-day revisit rate of 10.8%. Four procedures contributed more than half of the revisit-associated length of stay burden from all procedures, with the highest relative contributions attributable to complicated appendicitis (18.4%), gastrostomy (13.4%), uncomplicated appendicitis (13.0%), and fundoplication (9.4%). Four procedures contributed more than half of the revisit-associated cost burden from all procedures, with the highest relative contributions attributable to complicated appendicitis (18.8%), gastrostomy (14.6%), fundoplication (10.4%), and uncomplicated appendicitis (10.2%). A small number of procedures account for a disproportionate burden of revisit-associated resource utilization in pediatric surgery. Gastrostomy, fundoplication, and appendectomy should be considered high-priority targets for prevention efforts within pediatric surgery.


Comparative genome analysis of Campylobacter fetus subspecies revealed horizontally acquired genetic elements important for virulence and niche specificity.
Campylobacter fetus are important animal and human pathogens and the two major subspecies differ strikingly in pathogenicity. C. fetus subsp. venerealis is highly niche-adapted, mainly infecting the genital tract of cattle. C. fetus subsp. fetus has a wider host-range, colonizing the genital- and intestinal-tract of animals and humans. We report the complete genomic sequence of C. fetus subsp. venerealis 84-112 and comparisons to the genome of C. fetus subsp. fetus 82-40. Functional analysis of genes predicted to be involved in C. fetus virulence was performed. The two subspecies are highly syntenic with 92% sequence identity but C. fetus subsp. venerealis has a larger genome and an extra-chromosomal element. Aside from apparent gene transfer agents and hypothetical proteins, the unique genes in both subspecies comprise two known functional groups: lipopolysaccharide production, and type IV secretion machineries. Analyses of lipopolysaccharide-biosynthesis genes in C. fetus isolates showed linkage to particular pathotypes, and mutational inactivation demonstrated their roles in regulating virulence and host range. The comparative analysis presented here broadens knowledge of the genomic basis of C. fetus pathogenesis and host specificity. It further highlights the importance of surface-exposed structures to C. fetus pathogenicity and demonstrates how evolutionary forces optimize the fitness and host-adaptation of these pathogens.


Mobile dental units: leasing or buying? A dollar-cost analysis.
The decision to acquire a mobile dental unit is based on a standard capital budgeting analysis. The next step is to determine whether to obtain the use of the mobile dental unit by borrowing and purchasing or by leasing. As a financing mechanism, leases are simply another way of borrowing money to pay for the asset. To compare lease vs. debt as financial vehicles to acquiring a mobile dental unit. An estimate for a new mobile unit was obtained. Lease and loan proposals from financial lenders were collected. A cost of capital rate was chosen for comparison. Cash flows associated with borrowing and leasing vs. buying were determined fortwo different scenarios: for profit (FP) vs. not-for-profit (NFP), at 5 years. A dollar-cost analysis was utilized to determine the option with the lowest capitalized value. There was a net advantage to buying vs. leasing for both for FP and NFP organizations. Due to tax advantages, owning and leasing were substantially less expensive for FP than for NFP. Slight decreases in the monthly lease payments would make leasing competitive to the buying approach. Exploring alternative financing vehicles may allow dental programs to expand their services through the acquisition of a mobile unit. Though programs generally own assets, it is the use of the asset which is important rather than the ownership. Dental programs can find leasing an attractive alternative by offering access to capital with cash-flow advantages.


Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy.
Advances in the design of chimeric antigen receptors (CARs) have improved the antitumor efficacy of redirected T cells. However, functional heterogeneity of CAR T cells limits their therapeutic potential and is associated with toxicity. We proposed that CAR expression in Vα24-invariant natural killer T (NKT) cells can build on the natural antitumor properties of these cells while their restriction by monomorphic CD1d limits toxicity. Primary human NKT cells were engineered to express a CAR against the GD2 ganglioside (CAR.GD2), which is highly expressed by neuroblastoma (NB). We compared CAR.GD2 constructs that encoded the CD3ζ chain alone, with CD28, 4-1BB, or CD28 and 4-1BB costimulatory endodomains. CAR.GD2 expression rendered NKT cells highly cytotoxic against NB cells without affecting their CD1d-dependent reactivity. We observed a striking T helper 1-like polarization of NKT cells by 4-1BB-containing CARs. Importantly, expression of both CD28 and 4-1BB endodomains in the CAR.GD2 enhanced in vivo persistence of NKT cells. These CAR.GD2 NKT cells effectively localized to the tumor site had potent antitumor activity, and repeat injections significantly improved the long-term survival of mice with metastatic NB. Unlike T cells, CAR.GD2 NKT cells did not induce graft-versus-host disease. These results establish the potential of NKT cells to serve as a safe and effective platform for CAR-directed cancer immunotherapy.


Lower operation voltage in dual-frequency cholesteric liquid crystals based on the thermodielectric effect.
Dual-frequency cholesteric liquid crystal (DFCLC) devices characteristically require high operation voltage, which hinders their further development in thin-film-transistor driving. Here we report on a lower-voltage switching method based on the thermodielectric effect. This technique entails applying a high-frequency voltage to occasion dielectric oscillation heating so to induce the increase in crossover frequency. The subsequent change in dielectric anisotropy of the DFCLC allows the switching, with a lower operation voltage, from the planar state to the focal conic or homeotropic state. The temperature rise incurred by the dielectric heating is described.


The significance of Survivin and Nectin-4 expression in the prognosis of breast carcinoma.
To investigate the prognostic significance of Survivin and Nectin-4 expression in breast carcinomas. Imprint smears were obtained from 140 breast carcinoma specimens and studied immunocytochemically for the expression of Survivin and Nectin-4. The results were correlated with several clinicopathological parameters, including five-year survival. Increased Survivin staining pattern correlated with increased grade (p < 0.0001), increased lymph node invasion (p < 0.0001), increased tumor size and reduced survival (p < 0.0001). Elevated Nectin-4 expression also correlated significantly with increased grade (p < 0.0001), increased tumor size (p < 0.0001) and reduced survival (p < 0.0001). In addition, Survivin and Nectin-4 staining patterns correlated strongly with one another (p < 0.0001). However, on multivariate analysis, neither Survivin nor Nectin-4 expression seemed to have an independent impact on survival in our study cases. The findings of our study suggest that increased expression of Survivin and Nectin-4 may indicate a worse prognosis in breast cancer patients. The exact implications of the expression of these markers in breast cancer prognosis and treatment remain to be clarified.


Hip and knee extensor moments predict vertical jump height in adolescent girls.
Biomechanical factors, such as hip and knee extensor moments, related to drop jump (DJ) performance have not been investigated in adolescent girls. The purpose of this study was to determine the key independent biomechanical variables that predict overall vertical jump performance in adolescent girls. Sixteen high school adolescent girls from club-sponsored and high school-sponsored volleyball teams performed DJ at 3 different drop heights (15, 30, and 45 cm). A motion analysis system consisting of 10 digital cameras and a force platform was used to calculate vertical jump height, joint angles, and joint moments during the tasks. A multiple linear regression was used to determine the biomechanical parameters that were best predictive of vertical jump height at each box drop distance. The 2 predictor variables in all 3 models were knee and hip extensor moments. The models predicted 82.9, 81.9, and 88% of the vertical jump height variance in the 15, 30, and 45 cm trials, respectively. The results of the investigation indicate that knee and hip joint moments are the main contributors to vertical jump height during the DJ in adolescent girls. Strength and conditioning specialists attempting to improve vertical jump performance should target power and strength training to the hip and knee extensors in their athletes.