Reporting standards for studies of diagnostic test accuracy in dementia: The STARDdem Initiative.
To provide guidance on standards for reporting studies of diagnostic test accuracy for dementia disorders. An international consensus process on reporting standards in dementia and cognitive impairment (STARDdem) was established, focusing on studies presenting data from which sensitivity and specificity were reported or could be derived. A working group led the initiative through 4 rounds of consensus work, using a modified Delphi process and culminating in a face-to-face consensus meeting in October 2012. The aim of this process was to agree on how best to supplement the generic standards of the STARD statement to enhance their utility and encourage their use in dementia research. More than 200 comments were received during the wider consultation rounds. The areas at most risk of inadequate reporting were identified and a set of dementia-specific recommendations to supplement the STARD guidance were developed, including better reporting of patient selection, the reference standard used, avoidance of circularity, and reporting of test-retest reliability. STARDdem is an implementation of the STARD statement in which the original checklist is elaborated and supplemented with guidance pertinent to studies of cognitive disorders. Its adoption is expected to increase transparency, enable more effective evaluation of diagnostic tests in Alzheimer disease and dementia, contribute to greater adherence to methodologic standards, and advance the development of Alzheimer biomarkers.


Vasopressin release during nonhypotensive hemorrhage and angiotensin II infusion.
These experiments were designed to determine whether angiotensin II (AII) could potentiate the increase in plasma vasopressin (ADH) concentration produced by continuous, nonhypotensive hemorrhage in nephrectomized dogs. Infusion of AII (10 ng/kg.min) into a common carotid artery in nonbled dogs did not increase plasma ADH levels, suggesting that increases in carotid arterial plasma AII concentration alone do not stimulate an increase in ADH release. Subsequently, nephrectomized dogs subjected to nonhypotensive hemorrhage (0.44 ml/kg.min) were infused as follows: 0.9% saline intravenously, AII (10 ng/kg.min) intravenously, or AII (10 ng/kg.min) into the carotid. The Plasma ADH concentration increased in all three groups of dogs during hemorrhage. Although the AII-infused dogs demonstrated significant increases in plasma ADH levels earlier during hemorrhage, these changes were small; there were no statistically significant differences in plasma ADH concentrations among the three groups. These results suggest that increases in plasma AII concentration have little or no significant effect on the volume control of ADH release.


Socioeconomic Inequalities and Factors Associated with the Use of Modern Contraceptive Methods in Women of Childbearing Age in Ecuador, 2018.
The objective of this study was to determine the socioeconomic inequalities and factors associated with the use of modern contraceptive methods (MCM) in the population of sexually active women of childbearing age in Ecuador. This was an analytical observational study, based on a secondary data analysis of the 2018 National Health and Nutrition Survey (ENSANUT). Information on 19,106 sexually active, married, or cohabiting women between the ages of 15 and 49 were included. Concentration curves (CC) and Erreygers concentration indices (ECI) were calculated, taking into account the use of MCM as the dependent variable and the wealth index as the independent variable. Crude and adjusted prevalence ratios with 95% confidence intervals were calculated using generalized linear models of the Poisson family. We found that 92.8% of the women surveyed used some type of MCM in the last month. A higher educational level presented a significant pro-rich concentration in the use of MCM (EIC: 0.05; p = 0.004). On the other hand, women belonging to the age group of 20 to 29 years (ECI: -0.027; p = 0.027), women with no job (ECI: -0.025; p = 0.004), and non-indigenous women (EIC: -0.031; p < 0.001), presented a pro-poor concentration. Factors significantly associated with MCM use were age, marital status, occupation, parity, ethnicity, area of residence, and living on the coast. In Ecuador, there are socioeconomic inequalities at different levels of population subgroups in women of childbearing age. Measures to promote the use of MCM are required, focusing on groups that present inequality, taking into account the factors associated with their use.


Surgical management of recurrent postinfarction ventricular septal defect.
A 57 year old man presented with postinfarction ventricular septal infarct (VSD) a week after myocardial infarction and thrombolytic therapy. Coronary angiography confirmed double vessel disease. He underwent surgical repair of the VSD and coronary artery bypass grafting. Two days postoperatively, he deteriorated due to recurrence of VSD. Reoperation was carried out with satisfactory results. The surgical management is described with a review of the relevant literature.


Metabolism and biologic effects of 5-oxoeicosanoids on human neutrophils.
5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a recently discovered metabolite of arachidonic acid that activates human neutrophils by a mechanism independent of the receptor for leukotriene B4 (LTB4). The objectives of this study were to identify the major metabolites of 5-oxo-ETE in neutrophils and to compare the biologic activities of 5-oxo-ETE with those of its metabolites and other 5-oxoeicosanoids. Neutrophils rapidly converted 5-oxo-ETE to its omega-oxidation product, 5-oxo-20-hydroxy-6E,8Z,11Z,14Z- eicosatetraenoic acid. This compound was nearly 100 times less potent than 5-oxo-ETE in elevating cytosolic calcium levels in neutrophils. Methylation of the carboxyl group of 5-oxo-ETE resulted in a 20-fold loss of potency, whereas replacement of the 8,9-cis double bond by a trans double bond reduced potency by about sixfold. Similar results were obtained for the effects of the above compounds on neutrophil migration. 5-Oxo-20-hydroxy-6E,8Z,11Z,14Z- eicosatetraenoic acid, 5-oxo-8-trans-ETE, and 5-oxo-ETE methyl ester desensitized neutrophils to 5-oxo-ETE. 5-Oxo-ETE-induced calcium mobilization was inhibited by pretreatment of the cells with pertussis toxin. 5-Oxo metabolites of 6-trans-LTB4 and 12-epi-6-trans-LTB4 had weak stimulatory effects on calcium levels and migration that appeared to be mediated primarily by stimulation of LTB4 receptors. These studies indicate that the 5-oxo group, the omega-end of the molecule, and the carboxyl group are all important for the biologic activity of 5-oxo-ETE, which may be mediated by a G protein-linked receptor. The biologic activity of 5-oxo-ETE can be terminated by omega-oxidation.


Hepatic differentiation of human iPSCs in different 3D models: A comparative study.
Human induced pluripotent stem cells (hiPSCs) are a promising source from which to derive distinct somatic cell types for in vitro or clinical use. Existent protocols for hepatic differentiation of hiPSCs are primarily based on 2D cultivation of the cells. In the present study, the authors investigated the generation of hiPSC-derived hepatocyte-like cells using two different 3D culture systems: A 3D scaffold-free microspheroid culture system and a 3D hollow-fiber perfusion bioreactor. The differentiation outcome in these 3D systems was compared with that in conventional 2D cultures, using primary human hepatocytes as a control. The evaluation was made based on specific mRNA expression, protein secretion, antigen expression and metabolic activity. The expression of α-fetoprotein was lower, while cytochrome P450 1A2 or 3A4 activities were higher in the 3D culture systems as compared with the 2D differentiation system. Cells differentiated in the 3D bioreactor showed an increased expression of albumin and hepatocyte nuclear factor 4α, as well as secretion of α-1-antitrypsin as compared with the 2D differentiation system, suggesting a higher degree of maturation. In contrast, the 3D scaffold-free microspheroid culture provides an easy and robust method to generate spheroids of a defined size for screening applications, while the bioreactor culture model provides an instrument for complex investigations under physiological-like conditions. In conclusion, the present study introduces two 3D culture systems for stem cell derived hepatic differentiation each demonstrating advantages for individual applications as well as benefits in comparison with 2D cultures.


Multiscale mechanical design of the lightweight, stiff, and damage-tolerant cuttlebone: A computational study.
Cuttlebone, the endoskeleton of cuttlefish, offers an intriguing biological structural model for designing low-density cellular ceramics with high stiffness and damage tolerance. Cuttlebone is highly porous (porosity ∼93%) and lightweight (density less than 20% of seawater), constructed mainly by brittle aragonite (95 wt%), but capable of sustaining hydrostatic water pressures over 20 atmospheres and exhibits energy absorption capability under compression comparable to many metallic foams (∼4.4 kJ/kg). In this work, we computationally investigate how such remarkable mechanical efficiency is enabled by the multiscale structure of cuttlebone. Using the common cuttlefish, Sepia Officinalis, as a model system, we first conducted high-resolution synchrotron micro-computed tomography (µ-CT) and quantified the cuttlebone's multiscale geometry, including the 3D asymmetric shape of individual walls, the wall assembly patterns, and the long-range structural gradient of walls across the entire cuttlebone (ca. 38 chambers). The acquired 3D structural information enables systematic finite-element simulations, which further reveal the multiscale mechanical design of cuttlebone: at the wall level, wall asymmetry provides optimized energy absorption while maintaining high structural stiffness; at the chamber level, variation of walls (number, pattern, and waviness amplitude) contributes to progressive damage; at the entire skeletal level, the gradient of chamber heights tailors the local mechanical anisotropy of the cuttlebone for reduced stress concentration. Our results provide integrated insights into understanding the cuttlebone's multiscale mechanical design and provide useful knowledge for the designs of lightweight cellular ceramics. STATEMENT OF SIGNIFICANCE: Cuttlebone has been demonstrated to be a biological ceramic cellular material with remarkable lightweight, high stiffness and energy absorption. However, our knowledge on how such mechanical properties are enabled by cuttlebone's multiscale structure is not complete. Here, we combine systematic tomography-based 3D structural analysis and finite-element simulations to reveal how the hierarchical structure of cuttlebone at multiple length scales synergistically contribute to cuttlebone's impressive mechanical efficiency. These findings have important implications for designing biomimetic low-density cellular ceramic materials.


Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy.
Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours.


An Initial Pilot Study Examining Child Social Skills, Caregiver Styles, and Family Functioning in the PEERS® for Preschoolers Program for Young Autistic Children and their Caregivers.
Social impairments characteristic of autism spectrum disorder (ASD) are evident in early childhood and worsen as the child matures. Though many interventions for young children exist, few specifically target social skills and involve caregivers. This pilot study examined PEERS® for Preschoolers, focusing on temporal change in child social skills, caregiver style, and family functioning in the context of a caregiver-assisted social skills intervention. This extension of the PEERS® program builds on the success of the intervention for older children, presenting skills in a developmentally appropriate manner to young autistic children and their caregivers. The present pilot study used a non-concurrent multiple baseline design to examine the above variables with 15 autistic children (Mage = 4.87, SD = 1.25; 11 boys). Children and caregivers participated in PEERS® for Preschoolers groups, with each group randomly assigned three different baseline periods (1.5, 2, or 2.5 weeks) before beginning. Simulation Modeling Analysis (SMA) revealed concurrent improvements in social and caregiving skills, with subsequent changes in family functioning occurring over the course of this 16-session intervention. Future research will need to examine mechanisms of change in PEERS® for Preschoolers for children and caregivers. There is a dearth of research that specifically examines social skills interventions for young autistic children that incorporates caregivers and examines family functioning as well. This paper is one of the first to evaluate the PEERS® for Preschoolers (P4P) intervention by: 1) exploring changes in child social skills, caregiver efficacy, and family functioning, and 2) analyzing the sequence of improvements in the aforementioned variables to measure systematic change. This pilot study presents results using appropriate methodology for a small sample size of children and caregivers. Results suggested concurrent improvements in social and caregiving skills and subsequent changes in family functioning. These can be built upon for further research on the PEERS® for Preschoolers intervention. This study supports PEERS® for Preschoolers as a feasible intervention that likely contributes to improvements for the child, caregiver in their relationship with their child and parenting styles in general, as well as functioning of the entire family. In sum, this work is essential to furthering the provision of a much needed service of social skills interventions for young autistic children.


The Development of DNA Based Methods for the Reliable and Efficient Identification of Nicotiana tabacum in Tobacco and Its Derived Products.
Reliable methods are needed to detect the presence of tobacco components in tobacco products to effectively control smuggling and classify tariff and excise in tobacco industry to control illegal tobacco trade. In this study, two sensitive and specific DNA based methods, one quantitative real-time PCR (qPCR) assay and the other loop-mediated isothermal amplification (LAMP) assay, were developed for the reliable and efficient detection of the presence of tobacco (Nicotiana tabacum) in various tobacco samples and commodities. Both assays targeted the same sequence of the uridine 5'-monophosphate synthase (UMPS), and their specificities and sensitivities were determined with various plant materials. Both qPCR and LAMP methods were reliable and accurate in the rapid detection of tobacco components in various practical samples, including customs samples, reconstituted tobacco samples, and locally purchased cigarettes, showing high potential for their application in tobacco identification, particularly in the special cases where the morphology or chemical compositions of tobacco have been disrupted. Therefore, combining both methods would facilitate not only the detection of tobacco smuggling control, but also the detection of tariff classification and of excise.


[Equity of outpatient service utilization for hypertensive patients in community].
To analyze the equity of outpatient service utilization for hypertensive patients (HPs) under 3 kinds of social medical insurance, and to explore its influential factors. Methods: A total of 8 670 HPs (aged at 15 years old from 28 sub-centers) in 14 provinces were selected. Indirectly standardized method and concentration index were used to analyze the equity of outpatient utilization in HPs, and decomposition analysis was used to explore the impact factors of outpatient treatment among the whole sample population, population with urban employees' basic medical insurance (UEBMI), and population with urban residents' basic medical insurance (URBMI) and new rural cooperative medical systems (NCMS). Results: The overall concentration index (CI) for the whole sample population was 0.2378. After the standardizing "need" variable, horizontal inequity (HI) was 0.2360, indicating that the outpatient service of HPs was inequity and that the higher economic level, the more outpatient services received. The decomposition of overall CI results showed that the positive factors for contribution were gross domestic product (GDP) level, retired, UEBMI and URBMI, and the negative factors for contribution were NCMS. The CI of UEBMI, URBMI and NCMS was 0.2017, 0.1208 and 0.0288, respectively; the HI was 0.1889, 0.1215 and 0.0219, respectively. The inequity in UEBMI is the most serious, followed by NRCMS and URBMI. The economic level was the main factor that caused inequity in the outpatient services utilization in three social medical insurance. In addition to the economic level, a common positive factor for the contribution to UEBMI and URBMI was district of residence, and the age was the positive factor to UEBMI as well. Conclusion: There are different levels of inequity in the HPs covered by 3 kinds of social medical insurance, and the inequity of UEBMI is the highest one among 3 kinds social medical insurance. The economic level is the main factor that affects the equity of outpatient in the HPs under 3 kinds of social medical insurance.


MR coronary angiography with breath-hold targeted volumes: preliminary clinical results.
To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. Thirty-eight patients referred for elective coronary angiography were included. The coronary arteries were localized during single-breath-hold, three-dimensional imaging of the entire heart. MR coronary angiography was then performed along the major coronary branches with a double-oblique, three-dimensional, gradient-echo sequence. Conventional coronary angiography was the reference-standard method. Adequate visualization was achieved with MR coronary angiography in 85%-91% of the proximal coronary arterial branches and in 38%-76% of the middle and distal branches. Overall, 187 (69%) of 272 segments were suitable for comparison between conventional and MR coronary angiography. The diagnostic accuracy of MR coronary angiography for the detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the specificity was 94%-100%. Adequate visualization of the major coronary arterial branches was possible in the majority of patients. The observed accuracy of MR coronary angiography for detection of hemodynamically significant coronary arterial stenosis is promising, but it needs to be higher before this modality can be used reliably in a clinical setting.


Physician-patient communication about complementary and alternative medical therapies: a survey of physicians caring for patients with human immunodeficiency virus infection.
To examine frequency and correlates of physicians' reports of discussions with patients with human immunodeficiency virus (HIV) about complementary and alternative medical (CAM) therapies. Mailed physician survey. The setting was Eastern Massachusetts. Participants included 89 physicians caring for patients with HIV. Physicians were asked how common the use of CAM therapies was among their patients, how useful these therapies were, how often they discussed the use of CAM therapies with new and follow-up patients, and whether they had used a CAM therapy themselves in the last year. We also collected information on physicians' sociodemographic and practice characteristics. Sixty-eight percent (89/130) of physicians responded, and 26% and 5% reported discussing CAM therapies with HIV-infected patients at most new and follow-up visits, respectively. Respondents' attitudes toward the use of CAM therapies were generally positive, and they believed their HIV-infected patients used CAM therapies more than their non-HIV infected patients. The majority (63%) believed that CAM therapies may be helpful for HIV-infected patients. Thirty-six percent (36%) had used a CAM therapy themselves in the last year. In multivariate analyses, only the belief that CAM therapies are helpful was correlated with discussion of CAM therapies (p = 0.006). Respondents' demographic characteristics, training, personal use of CAM therapies, reported visit length, and satisfaction with visit length were not associated with discussion of CAM therapies. Despite awareness that their HIV-infected patients commonly use CAM therapies and positive attitudes towards such therapies, most of these physicians did not routinely discuss CAM therapies with them. Barriers to physician-patient communication about CAM therapies merit further investigation.


How do traits vary across ecological scales? A case for trait-based ecology.
Despite the increasing importance of functional traits for the study of plant ecology, we do not know how variation in a given trait changes across ecological scales, which prevents us from assessing potential scale-dependent aspects of trait variation. To address this deficiency, we partitioned the variance in two key functional traits (leaf mass area and leaf dry matter content) across six nested ecological scales (site, plot, species, tree, strata and leaf) in lowland tropical rainforests. In both traits, the plot level shows virtually no variance despite high species turnover among plots and the size of within-species variation (leaf + strata + tree) is comparable with that of species level variation. The lack of variance at the plot level brings substantial support to the idea that trait-based environmental filtering plays a central role in plant community assembly. These results and the finding that the amount of within-species variation is comparable with interspecific variation support a shift of focus from species-based to trait-based ecology.


A Real-World Evaluation of Clinical Outcomes of Biologicals and Bronchial Thermoplasty for Severe Refractory Asthma (BIOTERM).
The important progress made on asthma phenotyping encouraged the development of new therapeutic strategies, such as monoclonal antibodies (mAbs) and bronchial thermoplasty (BT). The aim of this study is to compare patients diagnosed with severe refractory asthma (SRA) who are currently being treated with omalizumab, mepolizumab, benralizumab or BT and to evaluate the efficacy of these treatments over a 12-month observation period. Overall, 199 consecutive patients with SRA were included. The cohort was selected referring to the eligibility criteria for all available biologics and BT. Among 32 patients treated with benralizumab, we found a 16.7% reduction in hospitalizations, a 66.6% reduction in exacerbations (p = 0.0001) and the greater improvement in FEV1 (+ 37.4%, p < 0.0001). Among omalizumab group (54 patients), there was a 85.7% (p = 0.012) reduction in hospitalizations and a 88.8% (p < 0.0001) reduction in exacerbations. In the mepolizumab group (83 patients), we found a 89.5% (p = 0.02) reduction in hospitalizations and a 92.1% (p < 0.0001) reduction in exacerbations. BT subgroup (30 patients) showed a 93.7% (p = 0.001) reduction in hospitalizations and a 73.5% (p < 0.0001) reduction in exacerbations. The best results in terms of OCS sparing effect were obtained by BT (- 76%, p < 0.0001) and mepolizumab (- 90.2%, p = 0.002). Omalizumab showed the highest percentage of super responder patients. To our knowledge, this is the first study to compare all marketed mAbs with BT, ending in more comprehensive and applicable results to clinical practice. All biologics, to varying degrees, reduced hospitalizations, exacerbations, and OCS use. The starting point for patients in the BT group was worse regarding hospitalizations, exacerbations and OCS, but despite this, even this non-pharmacological option obtained positive results, comparable to biologics.


The relationship between social capital and self-rated health in a Japanese population: a multilevel analysis.
The aim of this study was to use a multilevel analysis to examine whether cognitive and structural dimensions of regional social capital were associated with individual health outcomes after adjusting for compositional factors. Data from the Japanese General Social Surveys project, a nationwide study with a two-stage stratified random sampling method conducted in 2000, 2001, 2002, 2005, and 2006, were aggregated and used for the multilevel analysis (n = 11,702). We examined whether both cognitive and structural aspects of social capital (social trust, neighborhood safety, and social participation) were associated with the self-rated health (SRH) of residents from 118 regions after adjustment for compositional factors. Social trust and existing neighborhood safety were negatively associated with poor SRH, whereas the effect of social participation was not significant. Social trust was still negatively associated with poor SRH after adjusting for individual demographic factors and socioeconomic status (p = 0.001). In contrast, neighborhood safety and social participation did not reach significance after adjusting for compositional factors. Based on the results of this study, social trust was associated with health outcomes. Further study is needed to clarify the path linking regional trust in others to individual health outcomes in the Japanese population.


A nurse-led evidence-based practice project to monitor and improve the management of chemotherapy-induced nausea and vomiting.
Chemotherapy-induced nausea and vomiting (CINV) is a common and severe symptom experienced by patients undergoing cancer treatment during the acute or delayed period. Individual characteristics can compound risk for CINV. Identification of risk factors for CINV and structured, nurse-led telephone follow-up are effective, evidence-based methods to support patients undergoing cancer treatment. The authors successfully implemented a structured, nurse-led CINV intervention to improve assessment, follow-up, and support for 30 patients undergoing chemotherapy within an adult ambulatory oncology clinic.


Spinal versus general anesthesia for patients undergoing outpatient total knee arthroplasty: a national propensity matched analysis of early postoperative outcomes.
A comparison of different anesthetic techniques to evaluate short term outcomes has yet to be performed for patients undergoing outpatient knee replacements. The aim of this investigation was to compare short term outcomes of spinal (SA) versus general anesthesia (GA) in patients undergoing outpatient total knee replacements. The ACS NSQIP datasets were queried to extract patients who underwent primary, elective, unilateral total knee arthroplasty (TKA) between 2005 and 2018 performed as an outpatient procedure. The primary outcome was a composite score of serious adverse events (SAE). The primary independent variable was the type of anesthesia (e.g., general vs. spinal). A total of 353,970 patients who underwent TKA procedures were identified comprising of 6,339 primary, elective outpatient TKA procedures. Of these, 2,034 patients received GA and 3,540 received SA. A cohort of 1,962 patients who underwent outpatient TKA under GA were propensity matched for covariates with patients who underwent outpatient TKA under SA. SAE rates at 72 h after surgery were not greater in patients receiving GA compared to SA (0.92%, 0.66%, P = 0.369). In contrast, minor adverse events were greater in the GA group compared to SA (2.09%, 0.51%), P < 0.001. The rate of postoperative transfusion was greater in the patients receiving GA. The type of anesthetic technique, general or spinal anesthesia does not alter short term SAEs, readmissions and failure to rescue in patients undergoing outpatient TKR surgery. Recognizing the benefits of SA tailored to the anesthetic management may maximize the clinical benefits in this patient population.


Cystic fibrosis Delta F508 heterozygotes, smoking, and reproduction: studies of 9141 individuals from a general population sample.
Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested this hypothesis. An adult Danish general population sample of 9141 individuals was screened for cystic fibrosis DeltaF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In the total sample DeltaF508 heterozygotes did not have more children than noncarriers; however, smoking interacted with genotype in predicting number of children (ANOVA: P < 0.001). Among nonsmokers, heterozygotes had more children than noncarriers (Wilcoxon: P = 0.03). Among smokers, the opposite was found: heterozygotes had fewer children than noncarriers (Wilcoxon: P = 0. 001). These findings remained significant after allowing for gender and the potential confounders of age, income, and education. Finally, after allowing for these covariates, number of children in DeltaF508 heterozygotes decreased with increasing extent of smoking (trend test: P = 0.003), while the opposite was true for noncarriers (trend test: P < 0.001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 heterozygotes experience the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes.


Optical realization of Viterbi decoder for communication network.
The advantages of optics that include processing speed and information throughput, modularity and versatility could be incorporated into one of the most interesting and applicable topics of digital communication related to Viterbi decoders. We aim to accelerate the processing rate and capabilities of Viterbi decoders applied for convolution codes, speech recognition, inter symbol interference (ISI) mitigation problems. The suggested configuration for realizing the decoder is based upon fast optical switches. The configuration is very modular and can easily be increased to Viterbi decoder based upon state machine with larger number of states and depth of the trellis diagram.


Exploring the Relevance of Items in the Communicative Participation Item Bank (CPIB) for Individuals With Hearing Loss.
The Communicative Participation Item Bank (CPIB) was developed to evaluate participation restrictions in communication situations for individuals with speech and language disorders. This study evaluated the potential relevance of CPIB items for individuals with hearing loss. Cognitive interviews were conducted with 17 adults with a range of treated and untreated hearing loss, who responded to 46 items. Interviews were continued until saturation was reached and prevalent trends emerged. A focus group was also conducted with 3 experienced audiologists to seek their views on the CPIB. Analysis of data included qualitative and quantitative approaches. The majority of the items were applicable to individuals with hearing loss; however, 12 items were identified as potentially not relevant. This was largely attributed to the items' focus on speech production rather than hearing. The results from the focus group were in agreement for a majority of items. The next step in validating the CPIB for individuals with hearing loss is a psychometric analysis on a large sample. Possible outcomes could be that the CPIB is considered valid in its entirety or the creation of a new questionnaire or a hearing loss-specific short form with a subset of items is necessary.


[Reactive changes in circulating neutrophilic granulocytes in physiologic and complicated gestational process].
A comparative study of the morpho-functional characteristics of the circulating neutrophils was carried out by the electron microscopy method on women with physiological pregnancy and pregnancy-induced hypertension or EPH gestosis. Some leukocyte reactions were observed, and their intensity depended on the clinical manifestation of the EPH gestosis. In neutrophils there were detected reformation in the nucleus in the form of redistribution of the ratio between heterochromatin and euchromatin, as well as changes in the ultrastructure of nucleolemma. Both an amount of glycogen and initial or azurophil granules in the cytoplasm decreased very much but solubilization of their enzymes in cytosol did not occur. Such degranulation was due to the features of exocytosis which determined an extraleukocytic release of the content from the primary granules. The data obtained evidence that neutrophils are functionally active in the vascular bed and are likely to take part in the humoral regulation of the whole organism.


Effects of depression pharmacotherapy in fertility treatment on conception, birth, and neonatal health: A systematic review.
While antidepressant medications are currently used during conception, gestation and post-partum, considerable uncertainty exists regarding the benefits and harms conferred to mothers and their offspring. A significant body of evidence has focused on antidepressant use during pregnancy and post-partum. However, it is difficult to know if this translates to specific populations. Women receiving treatment for infertility are especially vulnerable to symptoms of depression and adverse perinatal outcomes. This systematic review aimed to determine the effects of antidepressants taken during the perinatal period by women receiving fertility treatment on conception, birth, and long-term maternal and child health outcomes. We searched MEDLINE, EMBASE, CINAHL, the Cochrane Library, PsycINFO, ProQuest Dissertation & Theses, and Pubmed databases from January 1950 to November 2015. Articles were screened for inclusion independently by two reviewers. Studies were included if they enrolled women of reproductive age exposed to pharmacotherapy for depression and infertility at any point during the perinatal period. A total of 8587 unique citations, and 83 full-text articles were reviewed. Of these, two randomized controlled trials and two retrospective chart reviews were included in the narrative synthesis. While most studies reported on assisted reproduction processes and birth outcomes, none examined long-term impacts on maternal-child health. The few included studies did not find that antidepressant use by women receiving fertility therapy impacted gamete quality or pregnancy success. Currently, no studies address whether pharmacotherapy for the treatment of depression in women undergoing assisted reproduction affects their health or that of their offspring long-term. It appears that much like antidepressant use in fertile women, there are risks associated with both antidepressant use and untreated depression. Decisions regarding the treatment of depression should be made taking into account clinical presentation and illness severity. Given the complexities of conducting research in this population, future research should attempt to leverage health registry data, to increase sample sizes and follow mothers and children longitudinally.


Inflammatory bowel disease and the risk of fracture after controlling for FRAX.
Subjects with inflammatory bowel disease (IBD) are at increased risk for hip and other major osteoporotic fractures. However, previous analyses have not fully accounted for differences in bone mineral density (BMD) and other clinical factors that affect the risk of fracture. The World Health Organization Fracture Risk Assessment tool (FRAX) can be used to predict the 10-year fracture risk from BMD and clinical risk factors. A population-based database containing clinical information on all IBD subjects in the province of Manitoba, Canada, was linked with the Manitoba Bone Mineral Density Database, which contains results of all dual X-ray absorptiometry (DXA) scans in the province. FRAX probabilities were calculated for all subjects aged 50 years or more undergoing baseline DXA testing. Subjects were followed for occurrence of major osteoporotic fractures (MOF; hip, clinical spine, wrist, humerus). Cox proportional hazards models were used to determine whether IBD was independently predictive of MOF or hip fracture. After controlling for FRAX fracture probability computed with BMD, IBD was not associated with a significantly increased risk for MOF (hazard ratio [HR] = 1.12, 95% confidence interval [CI], 0.83-1.55) but was associated with an increased risk for hip fracture (HR = 2.14; 95% CI, 1.26-3.65). The addition of femoral neck T-score to FRAX probability without knowledge of BMD had a negligible effect on the estimated HRs for IBD, suggesting that IBD mediates any effect on fracture risk independently of femoral neck BMD. After controlling for FRAX probability, subjects with IBD are not at an increased risk for overall MOF, but may be at increased risk of hip fracture.


Contextual template matching: a distance measure for patterns with hierarchically dependent features.
Contextual template matching refers to situations where the feature sets of the two templates under consideration may not be identical, but are rather contingent on the context within which these templates are observed. This paper addresses context-dependent template matching where the relevancy of certain features to a given object is contingent on the value of higher level features. In such situations portions of the patterns for two objects X and Y may not be comparable, and therefore classical distance measures are not applicable. A framework for describing pattern spaces with hierarchically dependent features-named conditional pattern spaces (CPS)-is presented, and a distance measure for comparing objects in a CPS is developed and illustrated on archaeological objects. This measure satisfies several desired properties of distance measures, such as the metric requirements.


Inhibition of acetylcholine induced intestinal motility by interleukin 1 beta in the rat.
The fact that raised interleukin 1 beta (IL 1 beta) concentrations have been found in the colonic mucosa of rats with experimentally induced colitis and of patients with inflammatory bowel disease indicates that this cytokine may participate in the disturbed intestinal motility seen during inflammatory bowel disease. This study investigated whether IL 1 beta could change the contractility of (a) a longitudinal muscle-myenteric plexus preparation from rat jejunum, ileum, and colon and (b) isolated jejunal smooth muscle cells. Isometric mechanical activity of intestinal segments was recorded using a force transducer. Moreover, smooth muscle cell length was measured by image analysis. Although IL 1 beta did not affect jejunal, ileal, and colonic basal contractility, it significantly reduced contractile response to acetylcholine (ACh). This significant inhibition was seen only after 90 or 150 minutes of incubation with IL 1 beta. Pretreatment with cycloheximide blocked IL 1 beta induced inhibition of ACh stimulated jejunal contraction, suggesting that a newly synthesised protein was involved in the effect. NW-nitro-L-arginine (a nitric oxide synthase inhibitor) did not prevent the inhibition induced by IL 1 beta. Blocking neural transmission with tetrodotoxin abolished the IL 1 beta effect on jejunal contractile activity, whereas IL 1 beta had no effect on isolated and dispersed smooth muscle cells. IL 1 beta inhibits ACh induced intestinal contraction and this inhibitory effect involves protein synthesis but is independent of nitric oxide synthesis. This effect does not involve a myogenic mechanism but is mediated through the myenteric plexus.


Management of patients with chronic lymphocytic leukemia treated with lenalidomide.
Lenalidomide is an immunomodulatory drug that has shown preliminary activity in the treatment of chronic lymphocytic leukemia (CLL). Much is known about the safety profile of lenalidomide from experience in other hematologic malignancies, such as myelodysplastic syndromes and multiple myeloma. In addition to the known adverse effects associated with lenalidomide (e.g., myelosuppression, rash, fatigue), some unique effects (e.g., tumor flare reactions, tumor lysis syndrome) have arisen during clinical studies of CLL. Typical signs of tumor flare reactions include early onset of painful enlargement of the lymph nodes or spleen, with or without low-grade fever, rash, and bone pain. Management may require nonsteroidal anti-inflammatory drugs or a short course of corticosteroids. Dose delays or reductions usually are not required for tumor flare reactions. Signs of tumor lysis syndrome may include shortness of breath, peripheral edema, generalized weakness, sweating, fever, and tachycardia. Untreated tumor lysis syndrome can result in renal impairment and congestive heart failure. Careful monitoring and appropriate management of treatment-related side effects can help ensure that patients with CLL achieve maximum therapeutic benefit from lenalidomide therapy.


Vascular-mineral spatial correlation in the calcifying turkey leg tendon.
Certain avian tendons are known to mineralize normally in a gender-related manner. These tendons have unique properties, as well as several features common to calcifying cartilage and bone in other vertebrate species. In cartilage and bone, mineralization has been associated with a vascular and microvascular origin, but such a relationship has not been established in the avian tendon. Here the vasculature and mineral deposition in the calcifying leg tendon of the turkey have been documented for the first time utilizing a combination of histology, immunochemistry, radiology, and novel three-dimensional image reconstruction methods based on computed tomography. The data describe the blood supply to turkey leg tendon and show that the vascularity of this tissue is correlated with the onset of mineralization: At local levels of structural hierarchy, a vascular bed precedes mineral formation and the sites of vascular invasion correspond spatially with those of mineral deposition. Relatively unvascularized tendon regions remain uncalcified. These results support the concept that vascularization and mineralization are functionally related in the tendon, and they suggest that vascular invasion provides a mechanism underlying subsequent mineral deposition in this tissue.


Early assessment of myocardial salvage by contrast-enhanced magnetic resonance imaging.
Myocardial salvage after acute myocardial infarction is defined clinically by early restoration of flow and long-term improvement in contractile function. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI), performed early after myocardial infarction, indexes myocardial salvage. We studied the relationship between the transmural extent of hyperenhancement by contrast-enhanced MRI, restoration of flow, and recovery of function. The left anterior descending coronary artery was occluded in dogs (n=15) for either 45 minutes, 90 minutes, or permanently. Cine and contrast-enhanced MRI were performed 3 days after the procedure; cine MRI was also done 10 and 28 days after the procedure. The transmural extent of hyperenhancement and wall thickening were determined using a 60-segment model. The mean transmural extent of hyperenhancement for the 45-minute occlusion group was 22% of the 90-minute group and 18% of the permanent occlusion group (P:<0.05 for both). The transmural extent of hyperenhancement on day 3 was related to future improvement in both wall thickening score and absolute wall thickening at 10 and 28 days (P:<0.0001 for each). For example, of the 415 segments on day 3 that were dysfunctional and had <25% transmural hyperenhancement, 362 (87%) improved by day 28. Conversely, no segments (0 of 9) with 100% hyperenhancement improved. The transmural extent of hyperenhancement on day 3 was a better predictor of improvement in contractile function than occlusion time (P:<0.0001). A reduction in the transmural extent of hyperenhancement by contrast-enhanced MRI early after myocardial infarction is associated with an early restoration of flow and future improvement in contractile function.


Density of convex intersections and applications.
In this paper, we address density properties of intersections of convex sets in several function spaces. Using the concept of Γ-convergence, it is shown in a general framework, how these density issues naturally arise from the regularization, discretization or dualization of constrained optimization problems and from perturbed variational inequalities. A variety of density results (and counterexamples) for pointwise constraints in Sobolev spaces are presented and the corresponding regularity requirements on the upper bound are identified. The results are further discussed in the context of finite-element discretizations of sets associated with convex constraints. Finally, two applications are provided, which include elasto-plasticity and image restoration problems.


Depression and suicide in young children.
Despite the dramatic increase of depression and suicidal behavior in children, research within this field is limited. Suicide is the 10th leading cause of death in children aged 1 through 14 years. For each child who completes the act of suicide, there are at least 50 more who attempt it. It is difficult to collect statistics on suicide in children owing to the lack of standard criteria for determining suicide in this age group and the myths that surround childhood suicide deaths. Children of all ages, including infants, can experience depression, but it will be manifested differently across each age group, especially from the infant to the school-aged child. Factors that identify children at risk for suicide include family history, loss of a loved one before the age of 12, violence, decreased family ties, and increased family pressures. Prevention strategies need to be accessible to the child both at home and in school. A variety of community-based suicide prevention programs are available for children and adults to assist children in overcoming suicidal feelings.


HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death.
Linear ubiquitination is crucial for innate and adaptive immunity. The linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP, and SHARPIN, is the only known ubiquitin ligase that generates linear ubiquitin linkages. HOIP is the catalytically active LUBAC component. Here, we show that both constitutive and Tie2-Cre-driven HOIP deletion lead to aberrant endothelial cell death, resulting in defective vascularization and embryonic lethality at midgestation. Ablation of tumor necrosis factor receptor 1 (TNFR1) prevents cell death, vascularization defects, and death at midgestation. HOIP-deficient cells are more sensitive to death induction by both tumor necrosis factor (TNF) and lymphotoxin-α (LT-α), and aberrant complex-II formation is responsible for sensitization to TNFR1-mediated cell death in the absence of HOIP. Finally, we show that HOIP's catalytic activity is necessary for preventing TNF-induced cell death. Hence, LUBAC and its linear-ubiquitin-forming activity are required for maintaining vascular integrity during embryogenesis by preventing TNFR1-mediated endothelial cell death.


Fracture of femoral neck in modular total hip arthroplasty: a systematic review of the literature.
Modular femoral stems have the advantage of anatomic hip reconstruction by restoring the femoral offset thus minimising the bearing surface wear, implant loosening and dislocation. This study aims to investigate the existing literature on modular neck fractures, to identify predisposing factors and guide the decision-making process in the management of these difficult cases. A systematic literature review was conducted until July 2022. PRISMA guidelines were followed, eligibility criteria were set, and methodology assessment of included studies was conducted based on MINORS criteria, size and primary outcome. Data were extracted and analysed thoroughly. 5657 studies were initially screened; the full texts of 124 records were assessed and finally, 32 reports were included. There were 7 clinical studies and 25 case reports. A total of 4825 patients (5204 hips) with a mean age 62.38 years and a mean BMI 29.06 kg/m2 were analysed in the 7 clinical studies. The reported overall weighted revision rate was 0.86%, while the weighted mean modular neck fracture rate was 0.26%. The usual history was sudden experience of hip pain and instability. The average time interval to neck fracture was 4.57 (range 3-4.7) years and a long modular neck was identified in 91.17% of them. Data from case reports showed a mean age and average BMI of 55.85 and 31.63 kg/m2. 82.35% of the patients were male. Necks were fractured after an average time interval of 64.5 ± 8.8 months. The incidence of modular neck fracture is significant. The profile of a male, obese patient with a long modular neck increased risk of neck fracture. Microstructural investigation of the retrieved implants demonstrated a higher incidence of fracture line in the base of the neck junction and at its anterolateral distal part. Surgeons should be aware of this complication while using or revising such protheses.


Combined inhibition of PDE4 and PI3Kδ modulates the inflammatory component involved in the progression of chronic obstructive pulmonary disease.
Chronic Obstructive Pulmonary Disease (COPD) represents a group of disorders with several underlying causes that hamper airflow into the lungs. Despite current intervention therapies, COPD remains a disease with a significant unmet medical need. Treatment with Phosphodiesterase (PDE) 4 inhibitors results in modest efficacy at clinically relevant doses. The objective of the current study is to evaluate the combination of a PDE4 (Roflumilast) and a Phosphoinositide-3-kinase (PI3K) δ (IC87114) inhibitor for their therapeutic potential in diminishing the inflammatory response associated with COPD. Due to their divergent and independent pathways, we hypothesize that the combination would be efficacious at low concentrations in an in vitro setting. Inhibition of TNFα, pAkt, MMP-9 in differentiated U937 macrophages upon stimulation with LPS/CSE was determined. Neutrophil functionality manifested by a modulation of elastase activity was estimated. Protective effect of drug combination on CSE induced apoptosis of lung epithelial cells was also determined. Data demonstrated that the combination of Roflumilast and IC87114 reduced TNFα, pAkt and MMP-9 at nanomolar concentrations and was several fold potent than either of the compounds alone. Inhibition of neutrophil elastase was also increased significantly with the combination along with a better protection against CSE induced apoptosis in alveolar epithelial cells, thereby providing a rationale for their evaluation in COPD patients.


Codominance of Lactobacillus plantarum and obligate heterofermentative lactic acid bacteria during sourdough fermentation.
Fifteen sourdoughs produced in western Sicily (southern Italy) were analysed by classical methods for their chemico-physical characteristics and the levels of lactic acid bacteria (LAB). pH and total titratable acidity (TTA) were mostly in the range commonly reported for similar products produced in Italy, but the fermentation quotient (FQ) of the majority of samples was above 4.0, due to the low concentration of acetic acid estimated by high performance liquid chromatography (HPLC). Specific counts of LAB showed levels higher than 10(8) CFU g(-1) for many samples. The colonies representing various morphologies were isolated and, after the differentiation based on phenotypic characteristics, divided into 10 groups. The most numerous group was composed of facultative heterofermentative isolates, indicating a relevance of this bacterial group during fermentation. The genetic analysis by randomly amplified polymorphic DNA (RAPD)-PCR, 16S rRNA gene sequencing and species-specific PCRs identified 33 strains as Lactobacillus plantarum, Lactobacillus curvatus and Lactobacillus graminis. Due to the consistent presence of L. plantarum, it was concluded that this species codominates with obligate heterofermentative LAB in sourdough production in this geographical area. In order to evaluate the performances at the basis of their fitness, the 29 L. plantarum strains were investigated for several technological traits. Twelve cultures showed good acidifying abilities in vitro and L. plantarum PON100148 produced the highest concentrations of organic acids. Eleven strains were positive for extracellular protease activity. Bacteriocin-like inhibitory substances (BLIS) production and antifungal activity was scored positive for several strains, included L. plantarum PON100148 which was selected as starter for experimental sourdough production. The characteristics of the sourdoughs and the resulting breads indicated that the best productions were obtained in presence of L. plantarum PON100148.


Juvenile gambling in North America: an analysis of long term trends and future prospects.
Long term trends, based on findings from twenty independent prevalence studies surveying middle and high school youth in North America, suggest that within the past year two out of three legally underage youth have gambled for money. In the United States and Canada as many as 15.3 million 12-17 year olds have been gambling with or without adult awareness or approval, and 2.2 million of these are experiencing serious gambling-related problems. Lottery play dominates legalized forms of gambling among juveniles in both the United States and Canada. Trends between 1984-1999 indicate a substantial increase in the proportion of juveniles who report gambling within the past year, and a parallel increase in the proportion of juveniles reporting serious gambling-related problems. Yet, there continues to be little public awareness or concern about the extent, or the potential hazards associated with juvenile gambling. A composite profile of juveniles reporting numerous gambling problems is contrasted with their peers who reported few or none. Future prospects concerning this growing problem are offered.


The impact of manual spinal traction therapy on the pain and Oswestry disability index of patients with chronic back pain.
[Purpose] The purpose of this study was to examine the effect of manual spinal traction therapy on the pain and Oswestry disability index of patients with chronic back pain. [Participants and Methods] In this study, 30 patients with chronic back pain were evenly divided into an experimental group 1, who received manual traction therapy, and an experimental group 2, who received intermittent traction therapy. Both groups received therapy three times a week for eight weeks. A visual analogue scale was used to measure participants' back pain, and the Oswestry disability index was used to check the functional impediment they experienced as a result. [Results] In a within-group comparison, visual analogue scale and Oswestry disability index significantly decreased in both the experimental 1 and experimental 2. In a between-group comparison after treatment, there was a significantly greater decrease in visual analogue scale and Oswestry disability index in the experimental group 1 compared to the experimental 2. [Conclusion] The manual spinal traction therapy was an effective intervention scheme for the treatment of pain and disorder in patients with chronic back pain.


Antidiabetic Activity, Molecular Docking, and ADMET Properties of Compounds Isolated from Bioactive Ethyl Acetate Fraction of Ficus lutea Leaf Extract.
Diabetes contributes to the rising global death rate. Despite scientific advancements in understanding and managing diabetes, no single therapeutic agent has been identified to effectively treat and prevent its progression. Consequently, the exploration for new antidiabetic therapeutics continues. This study aimed to investigate the antidiabetic bioactive ethyl acetate fraction of F. lutea at the molecular level to understand the molecular interactions and ligand-protein binding. To do this, the fraction underwent column chromatography fractionation to yield five compounds: lupeol, stigmasterol, α-amyrin acetate, epicatechin, and epiafzelechin. These compounds were evaluated in vitro through α-glucosidase inhibition and glucose utilization assays in C2C12 muscle and H-4-11-E liver cells using standard methods. In silico analysis was conducted using molecular docking and ADMET studies. Epicatechin exhibited the most potent α-glucosidase inhibition (IC50 = 5.72 ± 2.7 µg/mL), while epiafzelechin stimulated superior glucose utilization in C2C12 muscle cells (33.35 ± 1.8%) and H-4-11-E liver cells (46.7 ± 1.2%) at a concentration of 250 µg/mL. The binding energies of the isolated compounds for glycogen phosphorylase (1NOI) and α-amylase (1OSE) were stronger (<-8.1) than those of the positive controls. Overall, all tested compounds exhibited characteristics indicative of their potential as antidiabetic agents; however, toxicity profiling predicted epiafzelechin and epicatechin as better alternatives. The ethyl acetate fraction and its compounds, particularly epiafzelechin, showed promise as antidiabetic agents. However, further comprehensive studies are necessary to validate these findings.


Reliability of Repeated Nordic Hamstring Strength in Rugby Players Using a Load Cell Device.
Hamstring strain injuries are one of the most common injuries in Rugby Union players, representing up to 15% of all sustained injuries. The Nordic eccentric hamstring test assesses the maximal hamstring eccentric strength and imbalances between limbs. Asymmetries and deficits in hamstring strength between legs are commonly assessed and used as screening methods to prevent injuries which can only be proven effective if hamstring strength measures are reliable over time. We conducted a repeated-measures reliability study with 25 male Rugby Union players. Nordic eccentric strength and bilateral strength balance was assessed. Three testing sessions were undertaken over three consecutive weeks. Intrasession and intersession reliabilities were assessed using typical errors (TE), coefficient of variations (CV), and intraclass correlation coefficients (ICC). Our results showed good intrasession reliability (ICC = 0.79-0.90, TE = 26.8 N to 28.9 N, CV = 5.5% to 6.7%), whilst intersession reliability was fair for mean and the max (ICC = 0.52-0.64, TE = 44.1 N to 55.9 N, CV from 7.4% to 12.5%). Regarding the bilateral strength balance ratios, our results showed good intrasession reliability (ICC = 0.62-0.89, TE = 0.5, CV = 4.4% to 7.2%), whilst the intersession reliability for mean and max values was fair (ICC = 0.52-0.54) with a good absolute intersession reliability CV ranging from 8.2% to 9.6%. Assessing the Nordic eccentric hamstring strength and the bilateral strength balance in Rugby players using a load cell device is a feasible method to test, and demonstrated good intrasession and fair intersession reliability. Nordic eccentric strength assessment is a more practical and functional test than isokinetic; we provide data from Rugby Union players to inform clinicians, and to establish normative values in this cohort.


Route selection for double balloon enteroscopy in patients with obscure gastrointestinal bleeding: experience from a single center.
This study was performed to clarify the best insertion route of double-balloon enteroscopy and to report the characteristics and proportions of small bowel pathologies detected by double-balloon enteroscopy in our patients with obscure gastrointestinal bleeding. Between January 2006 and December 2009, 75 patients with obscure gastrointestinal bleeding were enrolled into this study. The procedure was performed by oral route in 60 patients, anal route in 5 patients and both in 10 patients. Mean age of the patients was 50.8 years, and 57.3% of them were male. The main outcome measurements were total length of insertion, total time of double-balloon enteroscopy, diagnostic rates, anatomic location of the lesions, and final diagnosis of lesions detected. Double-balloon enteroscopy was diagnostic in 75% of the patients. This rate was significantly higher in overt bleeding (91.7%). The source of bleeding could not be detected in 19 patients. Mean times of procedures were 119, 144 and 154 minutes for oral route, anal route and both, respectively. The mean insertion length was 310.65 cm (beyond the pylorus)for oral and 166.8 cm (beyond the ileocecal valve) for anal route. The most frequent pathologies were vascular malformations (n=20) and tumors (n=19). All malignant lesions were detected in the proximal part of the small intestine. Vascular malformations were distributed equally through the small intestine. Endoscopic treatment was performed in 30% of patients. Double-balloon enteroscopy is a safe and feasible examination for obscure gastrointestinal bleeding. Most lesions were localized in the proximal part of the small intestine. The oral route may be preferred as a first choice, if the imaging modalities including capsuleendoscopy cannot detect the lesion.


Risk stratification for arrhythmic death in an emergency department cohort: a new method of nonlinear PD2i analysis of the ECG.
Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, approximately 15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment.


Clinical efficacy of a degradable film-forming product containing carbamide peroxide to reduce tooth discolouration.
The methods used to lighten tooth discolouration while conserving the tooth structure have attracted much attention in a society which places a high value on esthetics. The purpose of this article is to present a home bleaching agent that uses a film-forming preparation containing carbamide peroxide (CP) which, while degrading, serves as a slow release delivery system of the bleaching agent. The efficacy of the preparation containing 3% CP and 10% CP on reduction of tooth discolouration is evaluated by a Chromameter in a double-blind placebo-controlled study. The effect of the tested bleaching agent on the gingival status, plaque accumulation and pulp sensitivity is also assessed.


History of depression and smoking cessation outcome: a meta-analysis.
The authors conducted a meta-analysis of published studies to (a) evaluate the premise that a history of major depression is associated with failure to quit smoking and (b) identify factors that moderate the relationship between history of depression and cessation outcome. Fifteen studies met the selection requirements and were coded for various study methodology and treatment characteristics. DSTAT was used to calculate individual study effect sizes, determine the mean effect size across studies, and test for moderator effects. No differences in either short-term (< or = 3 months) or long-term abstinence rates (> or = 6 months) were observed between smokers positive versus negative for history of depression. Lifetime history of major depression does not appear to be an independent risk factor for cessation failure in smoking cessation treatment.


Verbal memory impairments in mood disorders and psychotic disorders: A systematic review of comparative studies.
Mood and psychotic disorders are both associated with verbal memory impairments. Verbal memory represents an important treatment target for both disorders. However, whether the neurocognitive and neurophysiological profiles of verbal memory impairments differ between specific disorders within these two diagnostic categories and healthy controls remains unclear. The current systematic review synthesized findings from comparative studies which used behavioural and neuroimaging tasks to investigate verbal memory impairments between: (1) mood disorder, psychotic disorder, and healthy control groups; and (2) mood disorder without psychotic features, mood disorder with psychotic features, and healthy control groups. The search strategy combined terms related to three main concepts: 'mood disorders', 'psychotic disorders', and 'verbal memory'. Searches were executed in Embase, MEDLINE, PsycInfo, and PubMed databases. A total of 38 articles met the full eligibility criteria and were included in the final narrative synthesis. Findings were stratified by memory domain (overall composite score, verbal working memory, immediate recall, delayed recall, and recognition memory) and by illness phase (acute and non-acute). Mood and psychotic disorders displayed consistent verbal memory impairments compared to healthy controls during the acute and non-acute phases. Few significant differences were identified in the literature between mood and psychotic disorders, and between mood disorders with and without psychotic features. Individuals with schizophrenia were found to have decreased immediate and delayed verbal recall performance compared to bipolar disorder groups during the acute phase. Major depressive disorder groups with psychotic features were also found to have decreased delayed verbal recall performance compared to those without psychosis during the acute phase. No consistent differences were identified between mood and psychotic disorders during the non-acute phase. Finally, preliminary evidence suggests there may be functional abnormalities in important frontal and temporal brain regions related to verbal memory difficulties in both mood and psychotic disorders. The current findings have potential implications for the diagnosis and treatment of cognitive impairments in mood and psychotic disorders. Verbal recall memory may serve as a sensitive tool in the risk stratification of cognitive impairments for certain mood and psychotic disorders. Moreover, since no widespread differences between clinical groups were identified, the evidence supports providing targeted interventions for verbal memory, such as pharmacological and non-pharmacological interventions, through a trans-diagnostic approach in mood and psychotic disorders.


Educational interventions to advance children's scientific thinking.
The goal of science education interventions is to nurture, enrich, and sustain children's natural and spontaneous interest in scientific knowledge and procedures. We present taxonomy for classifying different types of research on scientific thinking from the perspective of cognitive development and associated attempts to teach science. We summarize the literature on the early--unschooled--development of scientific thinking, and then focus on recent research on how best to teach science to children from preschool to middle school. We summarize some of the current disagreements in the field of science education and offer some suggestions on ways to continue to advance the science of science instruction.


The effects of extracorporeal shock wave therapy on pain, disability, and depression of chronic low back pain patients.
[Purpose] The purpose of this study was to examine the effects of extracorporeal shock wave therapy on pain, disability, and depression of chronic low back pain patients. [Subjects] In this study, 30 chronic low back pain patients were divided into an extracorporeal shock wave therapy group (ESWTG, n=15) and a conservative physical therapy group (CPTG, n=15). [Methods] The ESWTG received extracorporeal shock wave therapy and the CPTG received general conservative physical therapy two times per week for six weeks. Pain was measured using a visual analog scale (VAS), the degree of disability of the patients was assessed using the Oswestry Disability Index (ODI), and their degree of depression was measured using the Beck depression index (BDI). [Results] In intra-group comparisons, ESWTG and CPTG showed significant decreases in VAS, ODI, and BDI scores. Intergroup comparisons revealed that these decreases in VAS, ODI, and BDI scores were significantly larger in ESWTG than in CPTG. [Conclusion] Extracorporeal shock wave therapy is an effective intervention for the treatment of pain, disability, and depression in chronic low back pain patients.


Online Consumer Survey Comparing Different Front-of-Pack Labels in Greece.
According to the WHO, front-of-pack nutrition labeling provides simplified nutrition information in the form of symbols, colors or words that can help consumers understand the nutritional quality of food, thus leading them to healthier food choices. It is considered of the utmost importance to explore the knowledge and understanding of consumers about this form of nutrition labeling. The aim of this study was to investigate the understanding and perceptions of Greek consumers in response to five different front-of-pack nutrition labels (FoPLs): the Multiple Traffic Lights, Health Star Rating System, Guideline Daily Amounts, Warning Symbols and Nutri-Score. From April 2021 to June 2021, 1278 participants from Greece took part in an online survey where they were asked to rank three products according to their nutritional quality. The classification process was performed first without FoPLs and then with FoPLs. The ability to classify products according to their nutritional quality was evaluated with multinomial logistic regression models, and the Nutri-Score label presented greater improvements when compared to the GDA label for Greek consumers. The Nutri-Score seemed to better help the Greek consumers rank foods according to their nutritional value.


Could the Food Neophobia Scale be adapted to pregnant women? A confirmatory factor analysis in a Portuguese sample.
The Food Neophobia Scale (FNS) is widely used in different countries, however appropriate psychometric analyses are required to allow cross-cultural comparisons. To our knowledge, most studies have been conducted among children and adult populations, with no reference to pregnant women. The objective of this study was to translate and test the psychometric properties of a Portuguese version of the FNS, and to identify clusters of food neophobia during pregnancy. The FNS was translated into Portuguese by three health researchers, and back-translated into English by an independent native English speaker and professional translator. The scale was self-administered in a sample of 219 women from the baseline evaluation of the Taste intervention study (HabEat project: http://www.habeat.eu/), who attended medical visits in two hospitals from Porto, Portugal, reporting food neophobia during the last trimester of pregnancy. The FNS consists of 10 items with a 7-point rating scale. An exploratory analysis was performed to evaluate the scale's dimensionality, followed by a confirmatory factor analysis to test the fit of the previous model by using different indexes. Cronbach's alpha coefficient was calculated to evaluate the internal reliability of the scale. The construct validity was assessed by comparing the FNS scores by categories of education, age and fruit and vegetables intake by ANOVA. A Model-based clustering was used to identify patterns of food neophobia; the number of latent classes was defined according to the Bayesian information criterion. A two-factor model solution was obtained (after excluding item 8 with a factor loading <0.4), explaining 51% of the total variance. Cronbach's alpha was 0.75 for factor 1 (5 items) and 0.71 for factor 2 (4 items). Items 1, 4, 6, 9 and 10 loaded into the first factor (i.e. more willingness to try new foods; less neophobic traits) and items 2, 3, 5 and 7 loaded into a second factor (i.e. more neophobic traits). A good global of fitness of the model was confirmed by fit indexes: TLI=0.876, CFI=0.911, RMSEA=0.088 and SRMR=0.051. The higher the education, age, and fruit and vegetables intake the lower the neophobic tendency, measured by the Portuguese FNS. Three patterns (i.e. clusters) of food neophobia, characterizing neophobia traits of pregnant women were identified: Moderate Neophilic, Moderate Neophobic, and Extreme Neophilic (cut-off points were provided). The Portuguese version of the FNS has the basic requirements of a valid and reliable measure of food neophobia and permits the identification of clusters of neophobic traits during pregnancy.


A Unique Institutional Response to the Zika Virus Epidemic.
In 2015, Zika virus rapidly emerged as a concern for obstetric patients and health care providers as the disease spread geographically and it was discovered that Zika virus infection had the potential to cause devastating birth defects. Essentially overnight, obstetric care providers were faced with an influx of rapidly evolving information and an increased workload. New systems, workflows, and personnel were needed to effectively address the new patient care needs fueled by the burgeoning Zika virus epidemic. The University of California, San Francisco responded by filling a Zika Response Nurse Coordinator position to take on tasks necessary to design a systematic approach for Zika virus management. The Zika Response Coordinator at the University of California, San Francisco serves as a subject matter expert who counsels patients and health care providers, arranges testing and follow-up care after potential Zika virus exposure, and helps design the screening tools, protocols, and educational material needed to manage the evolving Zika virus response. The position has enabled a Zika virus response that has been tightly coordinated, consistent, and thorough without overburdening health care providers. The Zika Response Nurse Coordinator Role serves as a template for how institutions can model coordinated Zika virus care and prepare for future threats that will necessitate a focused and rapid response. Timely institutional financial support is critical for an appropriate response to emerging diseases for not only Zika virus but future epidemics as well.


Functional reconstitution of the gamma-aminobutyric acid transporter from synaptic vesicles using artificial ion gradients.
The gamma-aminobutyric acid transporter of rat brain synaptic vesicles was reconstituted in proteoliposomes, and its activity was studied in response to artificially created membrane potentials or proton gradients. Changes of the membrane potential were monitored using the dyes oxonol VI and 3,3'-diisopropylthiodicarbocyanine iodide, and changes of the H+ gradient were followed using acridine orange. An inside positive membrane potential was generated by the creation of an inwardly directed K+ gradient and the subsequent addition of valinomycin. Under these conditions, valinomycin evoked uptake of [3H]GABA which was saturable. Similarly, [3H]glutamate uptake was stimulated by valinomycin, indicating that both transporters can be driven by the membrane potential. Proton gradients were generated by the incubation of K(+)-loaded proteoliposomes in a buffer free of K+ or Na+ ions and the subsequent addition of nigericin. Proton gradients were also generated via the endogenous H+ ATPase by incubation of K(+)-loaded proteoliposomes in equimolar K+ buffer in the presence of valinomycin. These proton gradients evoked nonspecific, nonsaturable uptake of GABA and beta-alanine but not of glycine in proteoliposomes as well as protein-free liposomes. Therefore, transporter activity was monitored using glycine as an alternative substrate. Proton gradients generated by both methods elicited saturable glycine uptake in proteoliposomes. Together, our data confirm that the vesicular GABA transporter can be energized by both the membrane potential and the pH gradient and show that transport can be achieved by artificial gradients independently of the endogenous proton ATPase.


Trends in cigarette smoking: the Minnesota Heart Survey, 1980-1982 through 2000-2002.
This paper reports population-based secular trends in smoking prevalence and tobacco exposure among smokers. The Minnesota Heart Survey (MHS) assessed smoking in probability samples in the seven-county Minneapolis-St. Paul metropolitan area. Five surveys were conducted in 1980-1982, 1985-1987, 1990-1992, 1995-1997, and 2000-2002 using similar sampling strategies and consistent protocols. Participants were metropolitan area residents of Minnesota, aged 25-74 years, with the addition of 75-84-year-olds in the last three surveys. In men, age-adjusted self-reported prevalence of current smoking steadily declined from 32.9% in 1980-1982, to 23.0% in 1995-1997, and to 20.6% in 2000-2002. In women, self-reported smoking was 31.8% in 1980-1982, 18.5% in 1995-1997, and 19.5% in the latest survey. Age-adjusted self-reported quantity of cigarettes consumed among smokers declined over the same period. Changes from 1995-1997 to 2000-2002 were not significant. Compared with Whites, Black participants had higher levels of smoking and later onset of the decline in smoking prevalence. A decline in smoking prevalence seems to have leveled off or reversed between the two most recent survey periods (1995-1997 through 2000-2002). Focus on smoking cessation should continue, especially in the subpopulation that smokes more than the majority.


Automatic recovery of missing amplitudes and phases in tilt-limited electron crystallography of two-dimensional crystals.
Electron crystallography of 2D protein crystals provides a powerful tool for the determination of membrane protein structure. In this method, data is acquired in the Fourier domain as randomly sampled, uncoupled, amplitudes and phases. Due to physical constraints on specimen tilting, those Fourier data show a vast un-sampled "missing cone" of information, producing resolution loss in the direction perpendicular to the membrane plane. Based on the flexible language of projection onto sets, we provide a full solution for these problems with a projective constraint optimization algorithm that, for sufficiently oversampled data, produces complete recovery of unmeasured data in the missing cone. We apply this method to an experimental data set of Bacteriorhodopsin and show that, in addition to producing superior results compared to traditional reconstruction methods, full, reproducible, recovery of the missing cone from noisy data is possible. Finally, we present an automatic implementation of the refinement routine as open source, freely distributed, software that will be included in our 2dx software package.


Management of anticoagulant and antiplatelet therapy in patients undergoing interventional pulmonary procedures.
There has been great progress in antithrombotic therapy over the past several years. Its use has increased with the advent of novel anticoagulants, as these medications do not require frequent blood tests for monitoring. Antithrombotic therapy is aimed at reducing the risk of thromboembolic events in patients with atrial fibrillation, coronary artery disease, deep vein thrombosis, valvular heart disease and pulmonary embolism. These patients are often critically ill and frequently undergo urgent interventions requiring discontinuation of anticoagulant or antiplatelet therapy which can increase the risk of thrombosis; however, continuing these agents can lead to increased risk of haemorrhage.The purpose of this article is to summarise the literature surrounding the safety of using antiplatelet and anticoagulant therapies in patients undergoing interventional pulmonary procedures.


Delamination Does Not Affect Outcomes After Arthroscopic Rotator Cuff Repair as Compared With Nondelaminated Rotator Cuff Tears: A Study of 1043 Consecutive Cases.
Limited information is available regarding the characteristics of delaminated rotator cuff tears as compared with nondelaminated tears. Furthermore, there is conflicting information regarding the effects of delamination on the anatomic healing of repaired cuffs. To evaluate the characteristics and anatomic outcomes of delaminated rotator cuff tears in comparison with nondelaminated tears to determine whether delamination is a negative prognostic factor affecting rotator cuff repair outcomes. Cohort study; Level of evidence, 3. Between 2010 and 2014, 1043 patients were enrolled in the study to assess the prevalence of delamination. Among them, the findings from 531 patients who underwent magnetic resonance imaging or computed tomographic arthrography at least 1 year after surgery were included to determine whether delamination was a negative prognostic factor affecting the anatomic outcomes of arthroscopic rotator cuff repair. Delamination was assessed intraoperatively and defined by distinguishable edge cleavage tearing or interstitial horizontal gap between the articular and bursal surfaces of the torn tendon. One of 3 repair techniques (modified Mason Allen, single row, or double row) was used according to tear configuration and tendon mobilization. The authors evaluated visual analog scale scores for pain and satisfaction and American Shoulder and Elbow Surgeons scores to quantify clinical outcomes. The incidence of delamination was 42.9% (447 of 1043). As compared with those with nondelaminated tears, patients with delaminated tears were older ( P < .001) and had longer symptom duration ( P = .019), larger tear sizes and retractions ( P < .001 for both), higher grades of fatty infiltration of the rotator cuff muscles (all P < .001), and poorer tendon quality ( P < .001). The overall healing failure rate was 19.0% (101 of 531). In univariate analysis, the rate of healing failure for the repaired cuffs was significantly higher in the delaminated group (delaminated tears, 60 of 238, 25.2%; nondelaminated tears, 41 of 293, 14.0%; P = .001). However, results of subgroup and multivariate analyses showed that the presence of delamination was ultimately not an independent risk factor for the failure of cuff healing. Between the delaminated and nondelaminated groups, there was no significant difference in postoperative functional outcomes. The results suggest that delaminated rotator cuff tears might represent chronic degenerative tears of longer symptom duration, with larger tear sizes and higher grades of fatty infiltration in older patients. It appears that delamination could be a confounding factor, not an independent prognostic factor, affecting rotator cuff healing.


Monoclonal antibodies differentiate between the haemagglutinating and the receptor-destroying activities of bovine coronavirus.
A relatively simple and sensitive method is described which enables the effect of monoclonal antibodies (MAbs) on the receptor-destroying enzyme (RDE) and the haemagglutination (HA) activity of bovine coronavirus (BCV) to be analysed in one assay. A lysate of HRT-18 cells infected with the L9 strain of BCV was found to have a higher RDE:HA ratio than purified virus. At 4 degrees C the lysate induced an HA pattern which completely disappeared upon raising of the temperature to 37 degrees C. This L9-infected cell lysate was used to determine the HA inhibition (HAI) titres of MAbs directed against the surface glycoproteins S and HE of BCV. Thereafter, the test plates were incubated at 37 degrees C to enable the ability of the MAbs to prevent elution of virus from BCV-erythrocyte complexes to be assessed. No inhibition of RDE was detectable with MAbs against glycoprotein S, which had HAI titres ranging from 1:16 to 1:128. On the other hand, MAbs directed against glycoprotein HE had similar HAI titres, but they inhibited elution of 8 HA units of BCV at titres of up to 1:65,000.


The Johns Hopkins Urban Health Institute: A collaborative response to urban health issues.
The authors provide background on the poor health and economic status of the residents of East Baltimore, Maryland--the neighborhood surrounding a significant part of Johns Hopkins University, including the School of Medicine, the School of Nursing, the Bloomberg School of Public Health, and the Johns Hopkins Hospital. The president of the Johns Hopkins University established a council on urban health, consisting of a broad array of individuals from across the university and the community to develop a recommended course of action to help deal with these conditions. Based on the recommendations of the council, the Johns Hopkins Urban Health Institute was established with the mission to marshall the resources of the university and external groups to improve the health and well-being of the residents of East Baltimore and to promote evidence-based interventions to solve urban health problems nationwide. After becoming fully operational in 2001, the institute established three major goals: (1) strengthen research and learning, (2) reduce disparities in health and health care for East Baltimore residents, and (3) promote economic growth in East Baltimore. The article describes the institute's major activities, including community-based participatory research projects, the Journal of Community-Based Participatory Research, and programs for research fellows to promote research and learning; HIV/AIDS counseling and testing centers and a primary care clinic for the uninsured to reduce health disparities; and a technology resource center providing training and job opportunities to promote economic growth. The authors conclude by outlining the next steps planned for the institute.


Racial disparities in adoption of axillary sentinel lymph node biopsy and lymphedema risk in women with breast cancer.
Racial disparities exist in many aspects of breast cancer care. Sentinel lymph node biopsy (SLNB) was developed to replace axillary lymph node dissection (ALND) for staging early breast cancer to minimize complications. Racial disparities in the use of SLNB remain incompletely characterized, and their effect on lymphedema risk is not known. To determine racial differences in SLNB use among patients with pathologically node-negative breast cancer during the period when SLNB became the preferred method for axillary staging as well as whether such differences affect lymphedema risk. A retrospective study was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 through 2007 to identify cases of incident, nonmetastatic, pathologically node-negative breast cancer in women aged 66 years or older. Sentinel lymph node biopsy use and 5-year cumulative incidence of lymphedema by race. Of 31 274 women identified, 1767 (5.6%) were black, 27 856 (89.1%) were white, and 1651 (5.3%) were of other or unknown race. Sentinel lymph node biopsy was performed in 73.7% of white patients and 62.4% of black patients (P < .001). The use of SLNB increased by year for both black and white patients (P < .001); however, a fixed disparity of approximately 12 percentage points in SLNB use persisted through 2007. In adjusted analysis, black patients were significantly less likely than white patients to undergo SLNB (odds ratio, 0.67; 95% CI, 0.60-0.75; P < .001). Overall, the 5-year cumulative lymphedema risk was 8.2% in whites and 12.3% in blacks (hazard ratio [HR], 1.43; 95% CI, 1.23-1.67; P < .001). When stratified by type of axillary surgery, 5-year lymphedema risk was 6.8% in whites undergoing SLNB (HR, 1 [reference]), 8.8% in blacks undergoing SLNB (HR, 1.28; 95% CI, 1.02-1.60; P = .03), 12.2% in whites undergoing ALND (1.79; 1.63-1.96; P < .001), and 18.0% in blacks undergoing ALND (2.76; 2.25-3.39; P < .001). Although SLNB use increased in both black and white patients with pathologically node-negative breast cancer from 2002 through 2007, the rates of SLNB remained lower in black than white patients during this entire period by approximately 12 percentage points. This racial disparity in SLNB use contributed to racial disparities in lymphedema risk. Improvements in the dissemination of new techniques are needed to avoid disparities in breast cancer care and patient outcomes, particularly in disadvantaged groups.


Rewired metabolism in drug-resistant leukemia cells: a metabolic switch hallmarked by reduced dependence on exogenous glutamine.
Cancer cells that escape induction therapy are a major cause of relapse. Understanding metabolic alterations associated with drug resistance opens up unexplored opportunities for the development of new therapeutic strategies. Here, we applied a broad spectrum of technologies including RNA sequencing, global untargeted metabolomics, and stable isotope labeling mass spectrometry to identify metabolic changes in P-glycoprotein overexpressing T-cell acute lymphoblastic leukemia (ALL) cells, which escaped a therapeutically relevant daunorubicin treatment. We show that compared with sensitive ALL cells, resistant leukemia cells possess a fundamentally rewired central metabolism characterized by reduced dependence on glutamine despite a lack of expression of glutamate-ammonia ligase (GLUL), a higher demand for glucose and an altered rate of fatty acid β-oxidation, accompanied by a decreased pantothenic acid uptake capacity. We experimentally validate our findings by selectively targeting components of this metabolic switch, using approved drugs and starvation approaches followed by cell viability analyses in both the ALL cells and in an acute myeloid leukemia (AML) sensitive/resistant cell line pair. We demonstrate how comparative metabolomics and RNA expression profiling of drug-sensitive and -resistant cells expose targetable metabolic changes and potential resistance markers. Our results show that drug resistance is associated with significant metabolic costs in cancer cells, which could be exploited using new therapeutic strategies.


[Evaluation of the severity and degree of myocardial infarct by indicators of fractional determination of protein-bound hexoses in the blood serum].
The time course of the content of hexose fractions was compared with the size of the myocardial infarction appraised from the ECG and with the clinical course of the acute period of myocardial infarction in 100 patients. The degree and duration of the increase in the blood glucosaminoglycane content were determined by the size of the focus of myocardial damage and the severity of its clinical course. The extent of the damage to the myocardium was found to be in accord with the increase in the content of the fraction of glucosaminoglycane hexoses. The results of the study suggest that determination of the content of glucosaminoglycane hexoses in blood may serve as an index of the severity of the myomalacia processes in the myocardium. A decrease in the level of the fraction coincides in time with the average terms of the onset of reparative processes in the myocardium which are determined from the findings of pathology.


A novel player: cyclosporine therapy in the management of inflammatory bowel disease.
Amongst other indications, cyclosporine therapy has emerged as a novel agent for the management of severe refractory ulcerative colitis (UC). In the historic population of patients receiving cyclosporine therapy-namely solid organ transplant patients-renal toxicity has proven to be a significant mitigating side effect limiting the therapeutic window. However, dose-limiting sequelae amongst patients receiving cyclosporine for inflammatory bowel disease (IBD) have not been as significant. As a result, the fear of renal toxicity as an adverse effect is less of a concern in IBD patients. The goal of this manuscript is to emphasize the need for future research to explore optimal drug dosing and extended use of cyclosporine therapy in the treatment of IBD-given its pathophysiology, efficacy, and safety profile in patients with IBD.


Limited role of the receptor for advanced glycation end products during Streptococcus pneumoniae bacteremia.
Streptococcus pneumoniae is one of the most common causes of sepsis. Sepsis is associated with the release of 'damage-associated molecular patterns' (DAMPs). The receptor for advanced glycation end products (RAGE) is a multiligand receptor, abundantly expressed in the lungs, that recognizes several of these DAMPs. Triggering of RAGE leads to activation of the NF-κB pathway and perpetuation of inflammation. Earlier investigations have shown that the absence of RAGE reduces inflammation and bacterial dissemination and increases survival in sepsis caused by S. pneumoniae pneumonia. We hypothesized that the detrimental role of RAGE depends on the level of RAGE expression in the primary organ of infection. By directly injecting S. pneumoniae intravenously, thereby circumventing the extensive RAGE-expressing lung, we here determined whether RAGE contributes to an adverse outcome of bacteremia or whether its role is restricted to primary lung infection. During late-stage infection (48 h), rage(-/-) mice had an attenuated systemic inflammatory response, as reflected by lower plasma levels of proinflammatory cytokines, reduced endothelial cell activation (as measured by E-selectin levels) and less neutrophil accumulation in lung tissue. However, RAGE deficiency did not influence bacterial loads or survival in this model. In accordance, plasma markers for cell injury were similar in both mouse strains. These results demonstrate that while RAGE plays a harmful part in S. pneumoniae sepsis originating from the respiratory tract, this receptor has a limited role in the outcome of primary bloodstream infection by this pathogen.


Human leptin: an adipocyte hormone with weight-regulatory and endocrine functions.
Leptin is synthesized and secreted primarily by adipocytes, and is present in serum in direct proportion to the amount of adipose tissue. The primary role of leptin is to provide to the central nervous system a signal of energy intake and energy stores in the body so that the hypothalamus can efficiently maintain a stable body weight. The receptor for leptin in the hypothalamus signals by activation of an associated janus kinase which phosphorylates signal transducer and activator of transcription (STAT) proteins that regulate neuronal gene expression. Genetic mutations in leptin and its receptor can result in obesity in both rodents and humans, supporting a central role for leptin in the regulation of body weight. Leptin has also been implicated in a variety of physiological processes other than body weight homeostasis. Many of these functions are mediated through the central nervous system; however, the presence of leptin receptors in tissues throughout the body suggests that leptin can also have direct effects on cells and tissues. Serum leptin levels have been associated with cardiovascular risk factors after correction for adiposity. Leptin can promote platelet aggregation, which requires expression of functional leptin receptors on the platelet. Leptin-induced increases in sympathetic nerve activity have been suggested to contribute to hypertension, and leptin has been observed to increase oxidative stress in cultured endothelial cells. Many of these pathophysiologic effects of leptin on the vasculature are most likely of importance when leptin levels are elevated in obese subjects due to resistance to the weight-reducing effects of the hormone. An improved understanding of the effects of leptin on the vasculature will provide valuable insight into the relationship between obesity and cardiovascular disease.