Chromatin immunoprecipitation (ChIP) method for non-model fruit flies (Diptera: Tephritidae) and evidence of histone modifications.
Interactions between DNA and proteins located in the cell nucleus play an important role in controlling physiological processes by specifying, augmenting and regulating context-specific transcription events. Chromatin immunoprecipitation (ChIP) is a widely used methodology to study DNA-protein interactions and has been successfully used in various cell types for over three decades. More recently, by combining ChIP with genomic screening technologies and Next Generation Sequencing (e.g. ChIP-seq), it has become possible to profile DNA-protein interactions (including covalent histone modifications) across entire genomes. However, the applicability of ChIP-chip and ChIP-seq has rarely been extended to non-model species because of a number of technical challenges. Here we report a method that can be used to identify genome wide covalent histone modifications in a group of non-model fruit fly species (Diptera: Tephritidae). The method was developed by testing and refining protocols that have been used in model organisms, including Drosophila melanogaster. We demonstrate that this method is suitable for a group of economically important pest fruit fly species, viz., Bactrocera dorsalis, Ceratitis capitata, Zeugodacus cucurbitae and Bactrocera tryoni. We also report an example ChIP-seq dataset for B. tryoni, providing evidence for histone modifications in the genome of a tephritid fruit fly for the first time. Since tephritids are major agricultural pests globally, this methodology will be a valuable resource to study taxa-specific evolutionary questions and to assist with pest management. It also provides a basis for researchers working with other non-model species to undertake genome wide DNA-protein interaction studies.


Prevalence study of hospital-acquired infections in 14 Greek hospitals: planning from the local to the national surveillance level.
A prevalence study of hospital-acquired infections (HAI) was carried out in 14 of 112 Greek hospitals (15.7%), scattered throughout Greece. Five of seven Greek university hospitals and nine regional hospitals participated in the one-day study, and 3925 hospitalized patients (10.5% of the total hospital beds in Greece) were recorded. The aim of this project was to organize a surveillance of HAI with the participation of the greatest possible number of Greek hospitals, transferring the experience from the local Cretan infection control network in an effort to create a nationwide network. Special attention was paid to recruit all Greek university hospitals in our attempt to expand the study base. Co-ordination of the participating centres, education of the infection control teams on surveillance methods, preparation of agreed definitions, and elaboration of the protocol for the collection of the data were the major objectives of this study. The difficulties, however, were limited resources and the lack of skilled personnel. The overall prevalence of HAI was found to be 9.3%. The most common HAI recorded involved lower respiratory tract infections (30.3%), followed by urinary tract infections (22.7%), bloodstream infections (15.8%), and surgical site infections (14.8%). The greatest prevalence rate was found in the adult ICU (48.4%), followed by the neonatal ICU (30.3%). The duration of hospitalization, the number of operations, the total number of used devices and invasive procedures were significantly correlated with HAI. Positive cultures were found in 51.5% of the cases. The most frequently isolated micro-organisms were: Pseudomonas aeruginosa (16.6%), Escherichia coli (10.8%), Klebsiella pneumoniae (10.3%), Staphylococcus epidermidis (8.1%) and Staphylococcus aureus (7.6%). The administration of antibiotics was also recorded. The prevalence of antibiotic use was 51.4%.


Carvedilol and nebivolol improve left ventricular systolic functions in patients with non-ischemic heart failure.
It is unclear whether carvedilol and nebivolol produce different effects on short-term left ventricle (LV) systolic function in heart failure (HF). These drugs could improve systolic and diastolic functions of the LV. Thus, we aimed to compare their effects on LV systolic functions in patients with non-ischemic HF. This study included 61 symptomatic non-ischemic HF patients with low ejection fraction (EF) (EF≤40%) between September 2008 and November 2010. The patients were randomized to carvedilol (n=31, 16 males) or nebivolol (n=30, 19 male). They were evaluated clinically and echocardiographically at baseline and 3 and 6 months after target dose; 42% of patients in the carvedilol group and 47% in the nebivolol group achieved the target dose before randomization. LV systolic functions were evaluated with ventricle diameters, EF, ejection time (ET), isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), and myocardial performance index (MPI). At 6 months, carvedilol and nebivolol similarly improved EF (from 33±4% to 36±5%, p<0.01 and from 34±5% to 37±5%, p<0.01, inter-group p=0.30, respectively) and MPI (from 0.71±0.10 to 0.53±0.07, p<0.01 and from 0.69±0.13 to 0.52±0.08, p<0.01, intergroup p=0.45, respectively). LV diameter was reduced by a similar extent in both groups. In each group, IVCT and IVRT were significantly shortened and ET was prolonged, but there was no inter-group difference. Functional capacity improved similarly (from NYHA Class II-III to Class I-0) in both groups, as did heart rate and blood pressure. Reduction of pro-B-type natriuretic peptide levels was also comparable in both groups (p=0.41). Carvedilol and nebivolol can similarly improve LV systolic functions in non-ischemic HF patients.


Do you want to promote recall, perceptions, or behavior? The best data visualization depends on the communication goal.
Data visualizations can be effective and inclusive means for helping people understand health-related data. Yet numerous high-quality studies comparing data visualizations have yielded relatively little practical design guidance because of a lack of clarity about what communicators want their audience to accomplish. When conducting rigorous evaluations of communication (eg, applying the ISO 9186 method), describing the process simply as evaluating "comprehension" or "interpretation" of visualizations fails to do justice to the true range of outcomes being studied. We present newly developed taxonomies of outcome measures and tasks that are guiding a large-scale systematic review of the health numbers communication literature. Using these taxonomies allows a designer to determine whether a specific data presentation format or feature supports or inhibits the desired audience cognitions, feelings, or behaviors. We argue that taking a granular, outcomes-based approach to designing and evaluating information visualization research is essential to deriving practical, actionable knowledge from it.


Off-pump coronary artery bypass grafting in a high-risk dextrocardia patient: a case report.
We present an interesting but high-risk case of an obese male patient aged 56 years with dextrocardia and a left diaphragmatic hernia. Anterior myocardial infarction was diagnosed in 1994, and the patient later presented with a history of unstable angina. The diagnosis for this chronic smoker was triple-vessel disease, impaired left ventricular function, chronic renal failure, chronic bronchitis, impaired lung function, pulmonary hypertension, hypertension, diabetes, and chronic active gastritis (EuroSCORE of 10). The patient underwent successful off-pump coronary artery bypass grafting with 3 saphenous vein grafts to the left anterior descending, obtuse marginal, and right posterior descending arteries. He was discharged home 8 days later.


[Ancient clinical application of herb-participated moxibustion on umbilicus].
In order to further improve the curative effect of the herb-participated moxibustion on umbilicus, we collected a wide range of literature on herb-participated moxibustion on umbilicus and then systematically arranged them to analyze and summarize the technology and operating methods of herb-participated moxibustion on umbilicus. We also briefly discussed issues on application of medicine, locust tree skin and ginger, the method of kneading dough for medical uses, and the appropriate size of moxa cone and its using frequency in order to form clear concepts and standardized operations to provide theories and operational basis for the clinical application of modern herb-participated moxibustion on umbilicus.


Prescription of renin-angiotensin system inhibitors in Japan during the COVID-19 pandemic: interrupted time series study.
We surveyed changes in angiotensin-converting enzyme inhibitor (ACEIs) and angiotensin II receptor blocker (ARBs) prescription trends during the coronavirus disease 2019 (COVID-19) pandemic in Japan. Data of 1,605,708 outpatients with hypertension were extracted from the Medical Data Vision database. Trends for prescription of ACEIs and ARBs were assessed by analyzing the proportion of these prescriptions in each month, between April 2018 and November 2020. The proportion of ARBs prescriptions changed significantly in trend between the peri-pandemic and pre-pandemic periods (-0.05%/month, P = 0.012). In contrast, the proportion of ACEIs prescriptions did not change significantly in trend in the peri-pandemic period (0.01%/month, P = 0.189). There was no suggestion that the prescribing of ACEIs and ARBs was affected by the COVID-19 pandemic.


U.S. Cattle Producer Adoption of Secure Beef Supply Plan Enhanced Biosecurity Practices and Foot-and-Mouth Disease Preparedness.
The prospect of a foot-and-mouth disease (FMD) outbreak in U.S. livestock populations has motivated the development of the Secure Beef Supply (SBS) Plan, which includes a comprehensive list of enhanced biosecurity practices that aim to prevent FMD transmission and facilitate continuity of business during an outbreak. While FMD poses a serious threat to livestock production in the United States, little is known about producers' uptake of the enhanced biosecurity practices included in the SBS Plan. In this study, we benchmark adoption and feasibility-of-adoption perceptions for U.S. cattle producers. Our results show adoption of the 13 enhanced biosecurity practices is generally low. Especially concerning is the low adoption of the three strongly-recommended pre-outbreak practices-having a biosecurity manager, having a written operation-specific enhanced biosecurity plan, and having a line of separation. Adoption of the pre-outbreak practices is likely low because the benefits of adopting the practices depend on a low probability, uncertain event. That said, producers who have adopted the pre-outbreak practices are more likely to have higher feasibility ratings for the remaining enhanced biosecurity practices, suggesting that adoption of the strongly recommended practices is associated with adoption of all enhanced biosecurity during an FMD outbreak. Complementarity is examined and shows that adoption of the pre-outbreak practices coincides with adoption of the outbreak-specific practices. Taken together, our results suggest that adoption of the strongly recommended pre-outbreak practices could help facilitate a quicker and more effective U.S. cattle industry response to an FMD outbreak in the United States.


[DETERMINANTS OF QUALITY OF LIFE AND MORBIDITY IN THE ADULT POPULATION].
In the Russian Federation, the number of working-age population is growing annually: in 2014, the number of able-bodied population was 33.8 million people(23.5%), while in 2018 this figure increased to 37.3 million (25.9%) [6]. In the Republic of Tatarstan, at the beginning of 2019 the number of able-bodied citizens reached 986 thousand people(26.0%). The purpose of this study was to analyze the determinants of the adult living standarts and the impact of these determinants on morbidity rates. A survey of 897 people using the SF-36 international questionnaire "SF-36 Health Status Survey". The majority of the working-age population under study was aged 60-64 (30%) and 65-69 (26%), aged 55-59 and 70-74 were 12% and 18% respectively. The smallest number of those under study was aged 75-79 (8%) and 80 and older (6%). Thus, our research has shown that the living standarts of over working-age population living in a large metropolis tends to significantly decrease depending on the age and gender. There was discovered a high level of prevalence of medical and social risk factors in these individuals, which are involved in the formation of the determinant of living standarts. For the first time, it was revealed that in people over the working age, the intensity of morbidity depends on the level of determinants of living standarts. The data obtained make it possible to develop measures to improve the quality of life of people over the working age and reduce their morbidity.


Vaccination with recombinant RgpA peptide protects against Porphyromonas gingivalis-induced bone loss.
Following Porphyromonas gingivalis infection in mice, the efficacy of vaccination by recombinant and native RgpA in modulating the early local anti-inflammatory and immune responses and periodontal bone loss were examined. Using the subcutaneous chamber model, exudates were analyzed for cytokines after treatment with native RgpA and adjuvant (test), or adjuvant and saline alone (controls). Mice were also immunized with recombinant RgpA after being orally infected with P. gingivalis. After 6 wk, serum was examined for anti-P. gingivalis IgG1 and IgG2a titers and for alveolar bone resorption. Immunization with native RgpA shifted the immune response toward an anti-inflammatory response as demonstrated by decreased proinflammatory cytokine IL-1β production and greater anti-inflammatory cytokine IL-4 in chamber exudates. Systemically, immunization with recombinant RgpA peptide prevented alveolar bone loss by 50%, similar to immunization with heat-killed whole bacteria. Furthermore, recombinant RgpA shifted the humoral response toward high IgG1 and low IgG2a titers, representing an in vivo anti-inflammatory response. The present study demonstrates the potential of RgpA to shift the early local immune response toward an anti-inflammatory response while vaccination with recRgpA protected against P. gingivalis-induced periodontitis.


An experimental study of the job demand-control model with measures of heart rate variability and salivary alpha-amylase: Evidence of increased stress responses to increased break autonomy.
We assessed in an experimental design whether the stress response towards a work task was moderated by the autonomy to choose a break during the assigned time to complete the task. This setting is defined in accordance with the theoretical framework of the job-demand-control (JDC) model of work related stress. The findings from naturalistic investigations of a stress-buffering effect of autonomy (or 'buffer hypothesis') are equivocal and the experimental evidence is limited, especially with relation to physiological indices of stress. Our objective was to investigate if increased autonomy in a particular domain (break time control) was related with adaptive physiology using objective physiological markers of stress; heart rate variability (HRV) and salivary alpha amylase (sAA). We used a within-subject design and the 60 female participants were randomly assigned to an autonomy (free timing of break) and standard conditions (fixed timing of break) of a word processing task in a simulated office environment in a random order. Participants reported increased perceptions of autonomy, no difference in demand and performed worse in the task in the break-time autonomy versus the standard condition. The results revealed support for the manipulation of increased autonomy, but in the opposing direction. Increased autonomy was related with dysregulated physiological reactivity, synonymous with typical increased stress responses. Potentially, our findings may indicate that autonomy is not necessary a resource but could become an additional stressor when it adds additional complexity while the amount of work (demands) remains unchanged. Further, our findings underscore the need to collect objective physiological evidence of stress to supplement self-reported information. Self-report biases may partially explain the inconsistent findings with the buffer hypothesis.


The Drosophila zfh-1 and zfh-2 genes encode novel proteins containing both zinc-finger and homeodomain motifs.
Two of the most common DNA-binding motifs found in eukaryotic transcriptional regulatory proteins are the homeodomain and the C2-H2 zinc finger. In Drosophila, homeodomain and zinc-finger proteins have been implicated in a wide variety of developmental processes. Until now, no proteins have been described in which both these DNA-binding motifs are present. We report here the isolation of genes encoding two such Drosophila proteins from a cDNA expression library. The product of the zfh-1 gene (zinc-finger homeodomain protein 1) contains one homeodomain and nine C2-H2 zinc fingers. The product of the zfh-2 gene possesses three homeodomains and sixteen C2-H2 zinc fingers. For zfh-1, antisera raised against nonoverlapping regions of the gene product all recognize a 145 kDa protein on protein immunoblots, suggesting that the different DNA-binding motifs are actually all present in the mature gene product. The novel arrangement of interspersed homeodomain and zinc-finger motifs in the primary sequences of the zfh-1 and zfh-2 gene products may signify an unusual mechanism of transcriptional regulation by these proteins.


Phenomenology of future-oriented mind-wandering episodes.
Recent research suggests that prospective and non-prospective forms of mind-wandering possess distinct properties, yet little is known about what exactly differentiates between future-oriented and non-future-oriented mind-wandering episodes. In the present study, we used multilevel exploratory factor analyses (MEFA) to examine the factorial structure of various phenomenological dimensions of mind-wandering, and we then investigated whether future-oriented mind-wandering episodes differ from other classes of mind-wandering along the identified factors. We found that the phenomenological dimensions of mind-wandering are structured in four factors: representational format (inner speech vs. visual imagery), personal relevance, realism/concreteness, and structuration. Prospective mind-wandering differed from non-prospective mind-wandering along each of these factors. Specifically, future-oriented mind-wandering episodes involved inner speech to a greater extent, were more personally relevant, more realistic/concrete, and more often part of structured sequences of thoughts. These results show that future-oriented mind-wandering possesses a unique phenomenological signature and provide new insights into how this particular form of mind-wandering may adaptively contribute to autobiographical planning.


[New method for the long-term cannulation of the common bile duct in the dog].
A new method for long term cannulation of the common bile duct in dogs is reported. The procedure is carried out with a T-tube, which is brought out through the abdominal wall. There it is rolled up in the hole of an implanted Thomas cannula. - A reliable protection from removal by the animal. The result in 9 dogs was very good, the longest duration of cannulation was 9 months.


Cavity-Free Continuum Solvation: Implementation and Parametrization in a Multiwavelet Framework.
We present a multiwavelet-based implementation of a quantum/classical polarizable continuum model. The solvent model uses a diffuse solute-solvent boundary and a position-dependent permittivity, lifting the sharp-boundary assumption underlying many existing continuum solvation models. We are able to include both surface and volume polarization effects in the quantum/classical coupling, with guaranteed precision, due to the adaptive refinement strategies of our multiwavelet implementation. The model can account for complex solvent environments and does not need a posteriori corrections for volume polarization effects. We validate our results against a sharp-boundary continuum model and find a very good correlation of the polarization energies computed for the Minnesota solvation database.


Postoperative Events in Incompatible Living Donor Kidney Transplant Recipients Undergoing Prior Desensitization.
Living donor kidney transplantation (LDKT) is one of the best options for patients with chronic renal failure, but approximately one-third of cases are limited by incompatibility ABO and/or HLA between recipient and donor. This study aims to analyze the surgical complications and bleeding events presented in ABO-incompatible (ABOi) and HLA-incompatible (HLAi) patients within a pre-transplant desensitization program compared with ABO-compatible (ABOc) recipients. We performed a retrospective analysis of ABOi and HLAi recipients undergoing LKDT between 2009 and 2019, resulting in a total of 62 patients that we compared with the same number of ABOc performed consecutively before 2019. The following variables were analyzed: surgical complications, presence, size and rate of reintervention of peri-graft hematomas, and number of transfusions received in the postoperative period. No statistical differences were shown in donor and recipient age, BMI, or sex; in the case of pre-surgical hematocrit, the ABOi group presented slightly lower figures. In the incompatible group (ABOi + HLAi), we found a greater number of postoperative surgical complications when analyzing the number of hematomas, size, need for surgical reintervention, and the number of blood units transfused; incompatible patients showed higher rates of hematomas, need for surgical reinterventions, and transfused units (P < .05). Desensitized patients need more transfusions, have a greater number and size of hematomas, and have higher reintervention rates. Although these are present in greater numbers, we did not observe statistically significant differences in the number of surgical complications.


The combined effect of nitrous oxide and oxygen and electrical stimulation during restorative dental treatment.
A total of 124 adult patients were treated with nitrous oxide (N2O) and oxygen (O2), an electrical analgesic, or a combination of N2O/O2 and an electrical analgesic during restorative dental procedures. The use of electrical analgesic or N2O/O2 without local anesthetics resulted in a high failure rate and poor patient acceptance. However, combining N2O/O2 sedation with electrically induced analgesia resulted in a statistically significant improvement over either technique used alone, and provided an overall 81% success rate when used during restorative dentistry.


Hypomagnesemia is a common complication of aminoglycoside therapy.
Normal therapeutic dosages of aminoglycosides can cause hypomagnesemia in more than one-third of patients. Hypomagnesemia occurs early in therapy, results in renal Mg++ wasting and may produce hypocalcemia and hypokalemia. Patients who are NPO, eating poorly or not receiving supplemental Mg++ are at high risk for hypomagnesemia. Hypomagnesemia, hypocalcemia and hypokalemia respond to Mg++ replacement therapy. We recommend serial monitoring of serum Mg++ levels in patients receiving aminoglycoside therapy.


Effect of sample holding time on bioaccessibility and sediment ecotoxicological assessments.
The ecotoxicological effects of hydrophobic organic compound (HOC) contamination in sediment are often assessed using laboratory exposures of cultured invertebrates to field-collected sediment. The use of a sediment holding time (storage at 4 °C) between field sampling and the beginning of the bioassay is common practice, yet the effect of holding time on the reliability of bioassay results is largely unknown, especially for current-use HOCs, such as pyrethroid insecticides. Single-point Tenax extraction can be used to estimate HOC concentrations in the rapidly desorbing phase of the organic carbon fraction of sediment (i.e., bioaccessible concentrations), which relate to sediment toxicity and bioaccumulation in invertebrates. In this study, repeated measurements of bioaccessible concentrations (via Tenax), were made as a function of sediment holding time using pyrethroid-contaminated field sediment, and Hyalella azteca 10-d survival and growth was measured concurrently for comparison. Similarly, bioaccessible concentrations and 14-d bioaccumulation were measured in Lumbriculus variegatus as a comparison using the legacy HOCs, polychlorinated biphenyls (PCBs). While the bioaccessible and bioaccumulated PCB concentrations did not change significantly through 244 d of holding time, the bioaccessible pyrethroid concentrations were more varied. Depending on when pyrethroid-contaminated sediments were sampled, the bioaccessible pyrethroid concentrations showed first-order loss with half-lives ranging from 3 to 45 d of holding, or slower, linear decreases in concentrations up to 14% decrease over 180 d. These findings suggest that at least for some contaminants in sediments, holding the sediments prior to bioassays can bias toxicity estimates.


Synthesis, properties, and reactions of a series of stable dialkyl-substituted silicon-chalcogen doubly bonded compounds.
The first dialkyl-substituted silicon-chalcogen doubly bonded compounds [R2Si=X; R2=1,1,4,4-tetrakis(trimethylsilyl)butane-1,4-diyl, X = S (4), Se (5), and Te (6)]were synthesized by the reactions of an isolable dialkylsilylene R2Si: (3) with phosphine sulfide, elemental selenium, and elemental tellurium, respectively. Systematic changes of characteristics of silicon-chalcogen double bonds are elucidated by X-ray analysis, UV-vis spectroscopy, and DFT calculations. In the solid state, the unsaturated silicon atom in 4-6 adopts planar geometry and the extent of the shortening of Si=X double bonds from the corresponding Si-X single bonds decreases in the order 4 > 5 > 6. In the absorption spectra of 4-6, pi -->pi* transition bands are observed distinctly in addition to n -->pi* transition bands. Both the n -->pi* and pi -->pi* transitions are red-shifted in the order 4 < 5 < 6, and the difference between the energies of the two transitions is kept almost constant among 4-6. The tendency is explained using the qualitative perturbation theory and is reproduced by the DFT calculations for model silanechalcogenones. Addition reactions of water, methanol, and isoprene to 4-6 are reported.


The creation of an advance care planning process for patients with ESRD.
Comprehensive care of patients with end-stage renal disease (ESRD) requires expertise in advance care planning (ACP), including attention to ethical, psychosocial, and spiritual issues related to starting, continuing, withholding, and stopping dialysis therapy. ACP currently is under evolution from a document-driven decision-focused event. This article describes a new approach to ACP that emphasizes a relational patient-centered process that focuses on broader goals of care for a particular dialysis patient with known medical problems and is designed to serve as a guide to help nephrologists, social workers, and other health care professionals explore ACP discussions with their patients with ESRD. Specifically, we define ACP, highlight goals and key features of this facilitated ACP process, and provide an interview guide with examples of questions that can be used to explore the various aspects of ACP with patients and their families. Outcomes of such an ACP process will not be measured by increasing the number of completed advance directives, but by improving satisfaction with the entire end-of-life experience and having outcomes match patient preferences. It is expected that such a process will enhance shared decision making among patient, surrogate, and health care provider and help build strong and intimate relationships that can only serve to enhance end-of-life care. Throughout this process, patients are not abandoned as they confront the realities of declining health and functional status, but rather are supported through their illness and life on dialysis treatment.


Security Techniques for the Electronic Health Records.
The privacy of patients and the security of their information is the most imperative barrier to entry when considering the adoption of electronic health records in the healthcare industry. Considering current legal regulations, this review seeks to analyze and discuss prominent security techniques for healthcare organizations seeking to adopt a secure electronic health records system. Additionally, the researchers sought to establish a foundation for further research for security in the healthcare industry. The researchers utilized the Texas State University Library to gain access to three online databases: PubMed (MEDLINE), CINAHL, and ProQuest Nursing and Allied Health Source. These sources were used to conduct searches on literature concerning security of electronic health records containing several inclusion and exclusion criteria. Researchers collected and analyzed 25 journals and reviews discussing security of electronic health records, 20 of which mentioned specific security methods and techniques. The most frequently mentioned security measures and techniques are categorized into three themes: administrative, physical, and technical safeguards. The sensitive nature of the information contained within electronic health records has prompted the need for advanced security techniques that are able to put these worries at ease. It is imperative for security techniques to cover the vast threats that are present across the three pillars of healthcare.


Estimating risk factors and causes for postpartum febrile morbidity in teenage mothers.
In this cohort study, our objective was to identify potentially modifiable risk factors and causes for febrile morbidity in teenage mothers. We identified all cases of febrile morbidity using the United States Joint Commission on Maternal Welfare definition in a cohort of teenage deliveries over a 4-year period at one institution. Of the 730 included teenage deliveries, 49 (7%) women suffered postpartum febrile morbidity. Higher maternal pre-pregnancy body mass index (BMI: 34.0 ± 8.6 vs 30.3 ± 6.0 kg/m(2), p = 0.0001), caesarean delivery (RR 21.3, 95% CU 8.9-54.9) and postpartum haemorrhage (RR 3.0, 95% CI 1.1-6.7) were associated with postpartum febrile morbidity. Risk factors for febrile morbidity in the teenage parturient include obesity, caesarean delivery and postpartum haemorrhage. Considering the increasing rates of teenage obesity and overall caesarean delivery rates, attention must be focused on these modifiable risk factors to avoid this complication during a tenuous time for the teenage parent.


The impact of porous silicon nanoparticles on human cytochrome P450 metabolism in human liver microsomes in vitro.
Engineered nanoparticles are increasingly used as drug carriers in pharmaceutical formulations. This study focuses on the hitherto unaddressed impact of porous silicon (PSi) nanoparticles on human cytochrome P450 (CYP) metabolism, which is the major detoxification route of most pharmaceuticals and other xenobiotics. Three different surface chemistries, including thermally carbonized PSi (TCPSi), aminopropylsilane-modified TCPSi (APTES-TCPSi) and alkyne-terminated thermally hydrocarbonized PSi (Alkyne-THCPSi), were compared for their effects on the enzyme kinetics of the major CYP isoforms (CYP1A2, CYP2A6, CYP2D6, and CYP3A4) in human liver microsomes (HLM) in vitro. The enzyme kinetic parameters, Km and Vmax, and the intrinsic clearance (CLint) were determined using FDA-recommended, isoenzyme-specific model reactions with and without PSi nanoparticles. Data revealed statistically significant alterations of most isoenzyme activities in HLM in the presence of nanoparticles at 1mg/ml concentration, and polymorphic CYP2D6 was the most vulnerable to enzyme inhibition. However, the observed CYP2D6 inhibition was shown to be dose-dependent in case of TCPSi and Alkyne-THCPSi nanoparticles and attenuated at the concentrations below 1μg/ml. Adsorption of the probe substrates onto the hydrophobic Alkyne-THCPSi particles was also observed and taken into account in the determination of the kinetic parameters. Three polymer additives commonly used in pharmaceutical nanoformulations (Pluronics F68 and F127, and polyvinylalcohol) were also separately screened for their effects on CYP isoenzyme activities. These polymers had less effect on the enzyme kinetic parameters, and resulted in increased activity rather than enzyme inhibition, in contrast to the PSi nanoparticles. Although the chosen subcellular model (HLM) is not able to predict the cellular disposition of PSi nanoparticles in hepatocytes and thus provides limited information of probability of CYP interactions in vivo, the present study suggests that mechanistic interactions by the PSi nanoparticles or the polymer stabilizers may appear if these are effectively uptaken by the hepatocytes.


Torque value accuracy of preadjusted metal brackets for upper and lower incisors.
The more accurate the adjustments built into the brackets, the less the need of additional bends in orthodontic archwires during treatment. The aim of this study was to investigate the torque value accuracy of Roth prescription brackets from several commercially available brands. A total of 360 upper and lower incisor brackets from six different commercial brands (i.e. 3M Abzil, KiriumLine; Dentsply GAC, Ovation; Morelli, Roth Light; Ormco, Synthesis; Rocky Mountain Orthodontics, Integra; and 3M Unitek, Miniature Twin) were selected and divided into 18 experimental groups (N.=20). The brackets were submitted to SEM examination to acquire clear photomicrographs of all edges. The angles formed by the slot's walls and bracket's base were measured to calculate the torque values. The measured torque values were submitted to Student's t-test or Mann-Whitney test (global α=0.05) for comparing the experimental groups to Roth prescription values, depending on the bracket indication: +12°, +8° or -1°. A tolerance of ±1° (ISO 27020:2010) was considered. Only experimental groups using upper central incisor brackets from Rocky Mountain Orthodontics (P=0.037) and 3M Unitek (P=0.001) were statistically different compared to the Roth prescription ones (+12°). However, all the groups presented great variability (standard deviation) regarding the same brand and indication, showing that there is no accuracy in the fabrication process. It is evident that the manufacturing methods of orthodontic brackets need to reach higher degrees of precision and homogeneity.


Gastric mucosal protection via enhancement of MUC5AC and MUC6 by geranylgeranylacetone.
The mucus layer that covers gastric mucosa is a powerful barrier that protects tissues from the hazardous gastric environment; however, the role of each gastric MUC type, such as MUC1, MUC5AC, and MUC6, has not been evaluated. The purpose of this study is to identify the MUC type, which plays a predominant role in this protective process by use of geranylgeranylacetone (GGA), a promising cytoprotective agent. In addition, the mechanism of mucus secretion promoted by GGA was investigated. Rat gastric mucosal damage was provoked using ethanol, and GGA was pretreated 1 hour before ethanol. GGA was found to significantly protect rats from ethanol-induced gastric damage by increasing mucus levels, MUC5AC and MUC6, especially at ethanol-induced ulcer margins, but not by MUC1. When expression of heat shock protein 70 (HSP70) and neuronal nitric oxide synthase (nNOS) was evaluated by Western blotting, both were found to be increased in GGA-treated ethanol rats. In addition, the cytoprotective effect of GGA was blocked by L-NMMA, a nonspecific NOS inhibitor, but not blocked by aminoguanidine, a specific inducible nitric oxide synthase inhibitor, thus indicating the participation of nNOS. In conclusion, GGA protected ethanol-induced gastric damage by upregulating MUC5AC and MUC6 rather than MUC1. In addition, HSP70 and nNOS were found to be involved in GGA cytoprotection, probably by increasing mucus production or secretion.


Prenatal Depression Risk Factors, Developmental Effects and Interventions: A Review.
This narrative review based on a literature search in PubMed and PsycInfo on the two terms prenatal and antenatal depression includes empirical studies, reviews and meta-analyses that have been published during the last 5 years on risk factors, developmental effects and interventions for prenatal depression. Risk factor studies that met criteria feature demographic measures (lower socioeconomic status, less education, non-marital status, non-employment, less social support and health locus of control, unintended pregnancy, partner violence and history of child abuse) and physiological variables (cortisol, amylase, and pro-inflammatory cytokines and intrauterine artery resistance). The negative effects include postpartum depression, paternal depression, and prematurity and low birth weight. Negative effects on infants include greater right frontal EEG, amygdala connectivity, cortical thinning and more difficult temperament. In childhood, externalizing and internalizing problems have been reported. The data on prenatal antidepressants (specifically SSRIs) reveal negative effects including internalizing problems as well as a greater risk for autism spectrum disorder. Prenatal interventions that have been effective include interpersonal psychotherapy, peer support, massage therapy, yoga, tai chi, and aerobic exercise. Potential underlying mechanisms are discussed as well as methodological limitations including homogeneity of samples and lack of randomization to intervention groups. Despite these limitations, the literature highlights the need for prenatal depression screening and intervention.


Exploring the additive bio-agent impacts upon ectoine production by Halomonas salina DSM5928T using corn steep liquor and soybean hydrolysate as nutrient supplement.
Ectoine production using inexpensive and renewable biomass resources has attracted great interest among the researchers due to the low yields of ectoine in current fermentation approaches that complicate the large-scale production of ectoine. In this study, ectoine was produced from corn steep liquor (CSL) and soybean hydrolysate (SH) in replacement to yeast extract as the nitrogen sources for the fermentation process. To enhance the bacterial growth and ectoine production, biotin was added to the Halomonas salina fermentation media. In addition, the effects addition of surfactants such as Tween 80 and saponin on the ectoine production were also investigated. Results showed that both the CSL and SH can be used as the nitrogen source substitutes in the fermentation media. Higher amount of ectoine (1781.9 mg L-1) was produced in shake flask culture with SH-containing media as compared to CSL-containing media. A total of 2537.0 mg L-1 of ectoine was produced at pH 7 when SH-containing media was applied in the 2 L batch fermentation. Moreover, highest amount of ectoine (1802.0 mg L-1) was recorded in the SH-containing shake flask culture with addition of 0.2 μm mL-1 biotin. This study demonstrated the efficacy of industrial waste as the nutrient supplement for the fermentation of ectoine production.


Endothelial cell leptin receptors, leptin and interleukin-8 in the pathogenesis of preeclampsia: An in-vitro study.
Increased leptin hormone and leptin receptor may enhance the generation of proinflammatory cytokines by endothelial cells and lead to endothelial dysfunction. This study assessed the umbilical cord endothelial leptin receptor levels in preeclampsia and investigated the effect of leptin on endothelial interleukin-8 (IL-8) production. The association between IL-8 levels with leptin stimulation was investigated in leptin-treated human endothelial cells. Endothelial cell leptin receptor levels were evaluated using immunohistochemistry staining, and endothelial IL-8 protein expression by Western blot analysis. Data are presented as mean ± standard error of the mean (SEM). Statistical significance was analyzed using Student's t-test or Mann-Whitney U test and one-way analysis of variance. Leptin receptor immunoreactivity increased significantly in umbilical cord venous and arterial endothelial cells in normal pregnancy (n=12) compared with preeclampsia (n=7) endothelial cells. The corresponding preeclampsia versus control histologic scores (mean ± SEM) were 67.9±8.8 vs. 127.6±23.1, (p=0.011) for the leptin receptor and 55.4±8,0 vs. 93.7±17.1 (p=0.035), respectively, for the vein endothelial cells. Leptin treatment significantly increased IL-8 protein levels (control vs. 100 and 1000 ng/mL, p=0.003). The findings of increased umbilical cord endothelial leptin receptor levels in preeclampsia and increased endothelial IL-8 expression with exposure to higher leptin concentrations may indicate the contribution of leptin to endothelial dysfunction and increased neutrophil-endothelial interaction, which are significant pathophysiologic features of preeclampsia.


An optimised glucose oxidase bioelectrode exhibiting high performance direct electron transfer.
A glucose oxidase (GOd) bioelectrode exhibiting high performance, direct electron transfer (DET) has been prepared. Unprecedented redox peak current densities of 1 mA cm(-2) were observed alongside a clear electrochemical response to glucose. This system shows potential as a low cost, high performance enzymatic bioelectrode.


Prevalence of Beta Thalassemia Trait in Denizli.
Beta thalassemia, characterized by the deficiency or the absence of beta globulin production, is the most widespread inherited disorder in the world and is also common in Turkey. To determine the prevalence of carriers for beta thalassemia, we screened the couples before their marriage. For this aim, from 1994 to 1999, a total of 14.200 people were screened. The complete blood count and red blood cell indices (hemoglobin: Hb, hematocrite: Hct, median corpusculer volume: MCV, median corpusculer hemoglobin: MCHb, median corpusculer hemoglobin concentration: MHbC, concentration were measured by automated cell counter on the same day of collection. Then for the samples with MCV values of 78 fL or below, hemoglobin electrophoresis were employed. Testing for beta thalassemia was carried out by the conventional cellulose asetate electropheresis at pH 8.4. People who have elevated HbA2 (≥ 3.5%) were accepted as beta-thalassemia carrier or patient. We detected 3300 people with MCV levels of 78 fL or below and 311 cases of beta thalassemia carrier and 11 cases of beta thalassemia. The prevalence of carriers for beta thalassemia in Denizli was 2.2%. This result indicated that the people with anemia in our region should be investigated for the existence of hemoglobinopathy.


Effect of 2, 5-substituents on the stability of cyclic nitrone superoxide spin adducts: A density functional theory approach.
In the present study, five cyclic nitrone superoxide spin adducts, i.e. DMPO-OOH, M(3)PO-OOH, EMPO-OOH, DEPMPO-OOH and DEPDMPO-OOH, were chosen as model compounds to investigate the effect of 2,5-subsitituents on their stability, through structural analysis and decay thermodynamics using density functional theory (DFT) calculations. Analysis of the optimized geometries reveals that none of the previously proposed stabilizing factors, including intramolecular H-bonds, intramolecular non-bonding interactions, bulky steric protection nor the C(2)-N(1) bond distance can be used to clearly explain the effect of 2,5-substituents on the stability of the spin adducts. Subsequent study found that spin densities on the nitroxyl nitrogen and oxygen are well correlated with the half-lives of the spin adducts and consequently are the proper parameters to characterize the effect of 2,5-substituents on their stability. Examination of the decomposition thermodynamics further supports the effect of the substituents on the persistence of cyclic nitrone superoxide spin adducts.


Macitentan in pulmonary arterial hypertension: The SERAPHIN trial.
Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the history of clinical trials in PAH being the largest and longest clinical study conducted thus far in PAH patients with morbidity and mortality events as primary endpoint. SERAPHIN trial investigated whether long-term treatment with the new endothelin receptor antagonist macitentan would reduce the risk of mortality and morbidity in PAH patients.


Femoral neck abnormalities in spina bifida.
Femoral neck abnormalities in spina bifida can be of two types: Type A, consisting of widening of the physis and often associated with varus deformity, and Type B, characterized by marked narrowing of the femoral neck, resulting in a typical mushroom appearance. The Type A deformity is usually associated with an abduction contracture of the hip. This physeal lysis seems to be secondary to microtrauma sustained during persistent exercise done by the parents and therapist to overcome the abduction contracture. No treatment is required, even when varus deformity is present. These patients require an orthosis with a pelvic band for ambulation, and their mobility will not be affected by the deformity.


The role of phosphatidylinositol-3-OH-kinase (PI3-kinase) and respiratory burst enzymes in the [omim][BF4]-mediated toxic mode of action in mussel hemocytes.
The present study investigates the role of phosphatidylinositol-3-OH-kinase (PI3-kinase) and respiratory burst enzymes, NADPH oxidase and NO synthase, in the 1-methyl-3-octylimidazolium tetrafluoroborate ([omim][BF4])-mediated toxic mode of action in mussel hemocytes. Specifically, cell viability (using the neutral red uptake assay) was primarily tested in hemocytes treated with different concentrations of [omim][BF4] (0.1-10 mg L-1) and thereafter [omim][BF4]-mediated oxidative (in terms of superoxide anions/O2- and nitric oxide/NO generation, as well as the enhancement of lipid peroxidation by-products, in terms of malondialdehyde/MDA) and genotoxic (in terms of DNA damage) effects were determined in hemocytes treated with 1 mg L-1 [omim][BF4]. Moreover, in order to investigate, even indirectly and non-entirely specific, the role of PI3-kinase, NADPH oxidase and NO synthase, the [omim][BF4]-mediated effects were also investigated in hemocytes pre-incubated with wortmannin (50 nM), diphenyleneiodonium chloride (DPI 10 μM) and NG-nitro-l-arginine methyl ester (l-NAME 10 μM), respectively. The results showed that [omim][BF4] ability to enhance O2-, NO, MDA and DNA damage, via its interaction with cellular membranes, was significantly attenuated in the presence of each inhibitor in almost all cases. The current findings revealed for the first time that certain signaling molecules, such as PI3-kinase, as well as respiratory burst enzymes activation, such as NADPH oxidase and NO synthase, could merely attribute to the [omim][BF4]-mediated mode of action, thus enriching our knowledge for the molecular mechanisms of ILs toxicity.


[Influencing the fibrinolytic activity by antithrombotics in patients with atherosclerosis].
In 106 atherosclerotic patients receiving an anticoagulant therapy and 91 patients receiving acetylsalicylic acid, fibrinogen and fibrin degradation products were determined as well as euglobulin lysis before and after venous occlusion. Platelet function data and thromboxane (TXB2) were also determined. Since "moderate" anticoagulant therapy with thromboplastin time values 26-40% results in deteriorated fibrinolysis data, anticoagulant therapy is strictly to remain within the therapeutic range of 15-20% up to 25% thromboplastin time at maximum. Treatment with acetylsalicylic acid proved useful on condition that the required dose was determined individually. This type of treatment will then be able to reduce the thromboxane level and positively influence the fibrinolytic potential.


[Women who have sex with women: their sexual biography, reproductive health and experience with violence].
To compare sociodemographic characteristics, sexual and reproductive biographies and experience of violence according to the fact that women have or have not had homosexual relationship. From the national survey on violence against women in France carried out in 2000 by phone, two groups have been compared: 78 women who have had at least one woman sexual partner and 6332 women who have had only male partners during lifetime. Women who have had sexual relationships with women more often have high level social positions and live in large cities. They have a more diverse sexual life that they begin younger and more partners, mainly men. They use contraception less often. They have more sexually transmitted infections and are more often tested for HIV. They visit gynaecologists as often as other women. They are more often victims of violence, especially physical violence as adults. These results, in an understudied field in France, are consistent with findings from the international literature. They attest to the difficulties women may be confronted with in situations where autonomy and marginality are combined. Doctors need to be better informed about the diversity of their trajectories in order to provide appropriate medical care.


Ambulatory Versus Laboratory Polysomnography in Obstructive Sleep Apnea: Comparative Assessment of Quality, Clinical Efficacy, Treatment Compliance, and Quality of Life.
This study has as its primary objective to evaluate the quality and effectiveness of type II ambulatory polysomnography (Amb-PSG) versus type I attended laboratory polysomnography (Lab-PSG) in diagnosing obstructive sleep apnea (OSA). Its secondary objective is to evaluate the clinical efficacy, quality of life (QoL), and treatment adherence after diagnosis. An observational study of patients with OSA (n = 225) in whom diagnosis was made via Amb-PSG (n = 114) or Lab-PSG (n = 111). Patients' clinical data were retrospectively assessed (including general demographic and clinical data, Epworth Sleepiness Scale, blood pressure, indices from polysomnography, and treatment adherence. Cross-sectional assessment (patient questionnaire) was used to evaluate clinical efficacy indicators, comorbidities, current treatment, and QoL. Polysomnography indices were comparable between Amb-PSG and Lab-PSG (apnea-hypopnea index: 38.9 ± 22.5 versus 35.8 ± 23.1 events/h; P > .05), except for an elevation of total sleep time (510 ± 54.7 versus 476.3 ± 79.4 minutes; P < .01) and loss of oximetry signal (9.8% versus 0.0%; P < .05). Based on polysomnography parameters, OSA was severe in 119 patients (52.9%), moderate in 88 (39.1%), and mild in 18 (8.0%). Diagnostic effect of Amb-PSG in clinical (body mass index, blood pressure, Epworth Sleepiness Scale) and treatment follow-up (CPAP adherence and QoL) indicators was comparable to that of Lab-PSG. Amb-PSG showed an OSA diagnostic capacity comparable to Lab-PSG. Secondary analyses (diagnostic quality, clinical efficacy, treatment compliance, QoL) underline the value of Amb-PSG as an emerging alternative to improve accessibility to care.


GnRH in the male dog: dose-response relationships with LH and testosterone.
Dose-response relationships between GnRH and LH, and between GnRH and testosterone, were investigated in six male dogs by intravenous administration of a GnRH analogue at different doses. Each dose of GnRH analogue induced an immediate rise in the plasma concentration of LH and then a rise in plasma testosterone concentration. Irrespective of the dose used, the rise in testosterone began 10 min after the GnRH injection. Administration of GnRH at doses of 0.01, 0.1, 1, 10 and 100 micrograms kg-1 resulted in maximum LH concentrations in plasma (mean +/- SEM; n = 6) of 22 +/- 7, 27 +/- 6, 40 +/- 7, 57 +/- 13 and 56 +/- 10 micrograms l-1, respectively. These doses induced maximum concentrations of testosterone in plasma (mean +/- SEM; n = 6) of 16 +/- 4, 20 +/- 4, 22 +/- 3, 22 +/- 4 and 24 +/- 7 nmol l-1, respectively. The lag time between peak concentrations of LH and testosterone varied from 35 to 55 min. The calculated maximum response of testosterone to LH, secreted by the anterior pituitary after GnRH injection, was 1.8 times higher than to GnRH. It was concluded that intravenous administration of GnRH induced marked and dose-dependent increases in plasma concentrations of LH and testosterone, and that there does not appear to be a direct effect of GnRH on Leydig cells in male dogs.


Fibrinogen Houston: a dysfibrinogen exhibiting defective fibrin monomer aggregation and alpha-chain cross-linkages.
A 38-year-old male patient with a life-long history of easy bruising and mild bleeding had a prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Reptilase (Bathrops atrox) clotting time was normal. His undiluted and diluted plasma prolonged the APTT, PT, and TT of normal plasma. Fibrin produced from patient plasma was insoluble in 5 M urea. Plasma fibrinogen level was increased when measured as clottable protein and by Laurell electroimmunoassay. Specific assays of plasma factors II, V, VII, X, VIII, IX, XI, and XII were normal. A circulating antithrombin in patient plasma was excluded by demonstrating normal thrombin-induced platelet aggregation of gel-separated platelets in the presence of patient plasma. Purified patient fibrinogen reproduced the anticoagulant effect of patient plasma. Patient fibrinogen antigen was similar to normal fibrinogen antigen by immunodiffusion, immunoelectrophoresis (pH 5.2 and 8.6), and crossed immunoelectrophoresis. His unreduced purified fibrinogen had normal migration on polyacrylamide slab gels. Also, the migration in gel slabs of A alpha, B beta and gamma-polypeptide chains, produced by mercaptoethanol reduction of purified patient fibrinogen, was similar to reduced normal fibrinogen. Thrombin-induced total fibrinopeptide release was normal. However, fibrin monomers produced from patient fibrinogen by thrombin (devoid of fibrinopeptides A and B) reaggregated abnormally; fibrin monomers produced by reptilase (devoid of only fibrinopeptides A) reaggregated normally. Fibrin generated from patient plasma in the presence of factor XIII and calcium, was defective in the formation of covalently bonded alpha-alpha polymers and demonstrated an increased susceptibility to the lytic effects of plasmin (generated in vitro by the addition of streptokinase).


Rosacea fulminans: unusual clinical presentation of rosacea.
Rosacea fulminans or pyoderma faciale is a rare cutaneous disorder that usually affects women usually between the ages of 15-46. The disease is characterized by sudden onset of papules, pustules, cysts, and painful coalescing nodules with red-cyanotic centrofacial erythema. Although its etiology remains unknown, hormonal, immunological, and vascular factors have been reported. Early diagnosis and prompt treatment should minimize unsightly scars. We report a case of a 33-year-old female patient treated with traditional doses of doxycycline, with improvement of the lesions and regression of the condition in two months.


Structural insights into substrate recognition in proton-dependent oligopeptide transporters.
Short-chain peptides are transported across membranes through promiscuous proton-dependent oligopeptide transporters (POTs)--a subfamily of the major facilitator superfamily (MFS). The human POTs, PEPT1 and PEPT2, are also involved in the absorption of various drugs in the gut as well as transport to target cells. Here, we present a structure of an oligomeric POT transporter from Shewanella oneidensis (PepTSo2), which was crystallized in the inward open conformation in complex with the peptidomimetic alafosfalin. All ligand-binding residues are highly conserved and the structural insights presented here are therefore likely to also apply to human POTs.


Electrostimulation of the white matter of the posterior insula and medial operculum: perception of vibrations, heat, and pain.
This study aimed to characterize the sensory responses observed when electrically stimulating the white matter surrounding the posterior insula and medial operculum (PIMO). We reviewed patients operated on under awake conditions for a glioma located in the temporoparietal junction. Patients' perceptions were retrieved from operative reports. Stimulation points were registered in the Montreal Neurological Institute template. A total of 12 stimulation points in 8 patients were analyzed. Painful sensations in the contralateral leg were reported (5 sites in 5 patients) when stimulating the white matter close to the parcel OP2/3 of the Glasser atlas. Pain had diverse qualities: burning, tingling, crushing, or electric shock. More laterally, in the white matter of OP1, pain and heat sensations in the upper part of the body were described (5 sites in 2 patients). Intermingled with these sites, vibration sensations were also reported (3 sites in 2 patients). Based on the tractograms of 44 subjects from the Human Connectome Project data set, we built a template of the pathways linking the thalamus to OP2/3 and OP1. Pain sites were located in the thalamo-OP2/3 and thalamo-OP1 tracts. Heat sites were located in the thalamo-OP1 tract. In the 227 awake surgeries performed for a tumor located outside of the PIMO region, no patients ever reported pain or heat sensations when stimulating the white matter. Thus, we propose that the thalamo-PIMO connections constitute the main cortical inputs for nociception and thermoception and emphasize that preserving these fibers is of utmost importance to prevent the postoperative onset of a debilitating insulo-opercular pain syndrome.


General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines.
This study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. We continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. Mean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. The general health, particularly ear health, of little children in remote Australian Indigenous communities remains in crisis. In particular, transition to PCV13 did not show substantial further improvement in ear health. Possible vaccine-related differences in microbiology, including potential beneficial effects of PHiD-CV10 on NTHi infection, need to be further evaluated in randomised trials.


Pharmacokinetic analysis driven letermovir dosing in pediatric hematopoietic cell transplantation patients with resistant CMV disease.
Reactivation of cytomegalovirus (CMV) in CMV-seropositive patients after haploidentical T-cell receptor αβ+ /CD19+ depleted hematopoietic cell transplant (HCT) is common. Due to delayed CMV-specific immune reconstitution, patients may require prolonged antiviral therapy, including secondary prophylaxis (SP). We present our clinical experience with the off-label use of letermovir for SP in a severely immunocompromised 2-year-old toddler with refractory pre-B-cell ALL and bilateral retinitis caused by resistant CMV (A594V UL97 mutation) following a haploidentical TCRαβ+ /CD19+ depleted HCT. The patient underwent measurement of two separate sets of letermovir serum concentrations, drawn at pre-dose, 1 and 4 h (and 8 h during the second therapeutic drug monitoring) post-dose. Pharmacokinetic parameters, including AUC0-24 were calculated, and dose adjustment was performed based on the drug level. While receiving oral letermovir 240 mg once daily without cyclosporine, the observed AUC0-24 was high (75 815 ng h/mL) with a Cmin of 209 ng/mL. The dose was reduced by 25% to 180 mg once daily. Despite the dose reduction, both AUC0-24 and Cmin values further increased to 119 095 ng h/L and 959 ng/mL, respectively. The patient continued oral letermovir 180 mg once daily for about 3 months, with adequate viral suppression (CMV viral load in plasma <150 IU/mL) and no recurrent CMV end-organ disease or adverse events. Given limited options for anti-CMV therapy in young children with resistant CMV, letermovir could be considered as an alternative antiviral for SP. Further studies are warranted to evaluate the pharmacokinetics of letermovir in pediatric allogeneic HCT recipients.


Tunable-wavelength nanosecond laser tailoring of plasmon resonance spectra of gold nanoparticle colloids.
Metal nanoparticles have applications across a range of fields of science and industry. While there are numerous existing methods to facilitate their large-scale production, most face limitations, particularly in achieving reproducible processes and minimizing undesirable impurities. Common issues are varying particle sizes and aggregates with unfavorable spectral properties. Researchers are currently developing methods to separate or modify nanoparticle sizes and shapes post-synthesis and to eliminate impurities. One promising approach involves laser light irradiation and enables the changing of nanoparticle sizes and shapes while controlling crucial spectral parameters. In this work, we present a novel extension of this method by irradiating nanoparticle colloids with variable-wavelength nanosecond laser pulses on both sides of the extinction band. Our results demonstrate the use of gradual laser wavelength tuning to optimize the photothermal reshaping of gold nanorods and achieve precise control over the plasmon resonance band. By irradiating both sides of the plasmon resonance band, we execute a multistep tuning process, controlling the band's width and spectral position. A statistical analysis of SEM images reveals differences in the nanorod morphology when irradiated on the long- or short-wavelength side of the plasmon resonance band. The fine-tuning of plasmonic spectral properties is desirable for various applications, including the development of sensors and filters and the exploitation of the photothermal effect. The findings of this study can be extended to other plasmonic nanostructures.


Interleukin-1beta-induced increases of plasma catecholamine levels in rats: enhancement by superior cervical ganglionectomy.
In urethane-anesthetized rats, we examined the effect of bilateral superior cervical ganglionectomy on interleukin-1beta (IL-1beta)-induced elevation of plasma catecholamines. In sham-operated rats, intracerebroventricularly (i.c.v.) administered IL-1beta (100 ng/animal) effectively elevated plasma noradrenaline rather than plasma adrenaline. In superior cervical ganglionectomized rats, however, IL-1beta significantly elevated adrenaline to a greater extent than noradrenaline, and they were attenuated by i.c.v. administration of melatonin (100 ng/animal). Superior cervical ganglionectomy effectively reduced the plasma level of melatonin and urinary excretion of 6-sulfatoxymelatonin (a main urinary melatonin metabolite). These results suggest that superior cervical ganglia inhibit central sympatho-adrenomedullary outflow (especially adrenomedullary outflow) by increasing melatonin synthesis in the pineal gland of rats.


Microenvironment promotes tumor cell reprogramming in human breast cancer cell lines.
The microenvironment drives mammary gland development and function, and may influence significantly both malignant behavior and cell growth of mammary cancer cells. By restoring context, and forcing cells to properly interpret native signals from the microenvironment, the cancer cell aberrant behavior can be quelled, and organization re-established. In order to restore functional and morphological differentiation, human mammary MCF-7 and MDA-MB-231 cancer cells were allowed to grow in a culture medium filled with a 10% of the albumen (EW, Egg White) from unfertilized chicken egg. That unique microenvironment behaves akin a 3D culture and induces MCF-7 cells to produce acini and branching duct-like structures, distinctive of mammary gland differentiation. EW-treated MDA-MB-231 cells developed buds of acini and duct-like structures. Both MCF-7 and MDA-MB-231 cells produced β-casein, a key milk component. Furthermore, E-cadherin expression was reactivated in MDA-MB-231 cells, as a consequence of the increased cdh1 expression; meanwhile β-catenin - a key cytoskeleton component - was displaced behind the inner cell membrane. Such modification hinders the epithelial-mesenchymal transition in MDA-MB-231 cells. This differentiating pathway is supported by the contemporary down-regulation of canonical pluripotency markers (Klf4, Nanog). Given that egg-conditioned medium behaves as a 3D-medium, it is likely that cancer phenotype reversion could be ascribed to the changed interactions between cells and their microenvironment.


Electrospun Nanofibers Loaded with Quercetin Promote the Recovery of Focal Entrapment Neuropathy in a Rat Model of Streptozotocin-Induced Diabetes.
In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion.


Development and Evaluation of a Nutritional Smartphone Application for Making Smart and Healthy Choices in Grocery Shopping.
This study developed a smartphone nutritional application (app) for making smart and healthy choices when purchasing food in grocery stores and tested its feasibility, usability, satisfaction and acceptability. "MyNutriCart" was developed following the ADDIE (analysis, design, development, implementation, and evaluation) model. The goals of the app were to improve food selection when purchasing foods in the grocery stores based on a pre-defined budget, to improve dietary patterns based on the Dietary Guidelines for Americans, and to improve weight status. It was evaluated within a pilot randomized trial using a convenient sample of 26 overweight or obese adults aged 21-45 years for 8 weeks. The developed app provided a grocery list of healthy foods to meet the individual requirements of all family members within a budget following the recommendations of the Dietary Guidelines for Americans. The average use of the app was 75% on each purchase and only 37% of the recommended products were purchased. The main reasons for not purchasing the recommended items were that participants did not like these (28.5%) and that the item was unavailable in the supermarket (24.3%). Over 50% of participants considered the app as feasible, usable, satisfactory, and acceptable (p < 0.05). "MyNutriCart" is the first available app for making smart and healthy choices when purchasing food in grocery stores. This app could be used as a tool to translate recommendations into a practical grocery list that meet the needs of a family within a budget.


Influence of zinc, sodium bicarbonate, and citric acid on the antibacterial activity of ovotransferrin against Escherichia coli O157:H7 and Listeria monocytogenes in model systems and ham.
The influence of NaHCO(3) and citric acid on the antibacterial activity of apo-ovotransferrin in model systems and ham was investigated. The antibacterial activity of 20 mg/mL of ovotransferrin solution with added NaHCO(3) (0, 25, 50, or 100 mM) or citric acid (0.25 or 0.5%) was evaluated against Escherichia coli O157:H7 and Listeria monocytogenes in brain heart infusion broth. The antimicrobial activity of ovotransferrin saturated with Fe(2+) or Zn(2+) against both pathogens was also measured. In addition, ovotransferrin solutions containing either 100 mM NaHCO(3) or 0.5% citric acid were applied to commercial hams inoculated with E. coli O157:H7 or L. monocytogenes and stored at 4 degrees C for 4 wk. The antimicrobial activity of ovotransferrin increased as the concentration of added NaHCO(3) increased. Sodium bicarbonate (100 mM) significantly improved the antibacterial activity of ovotransferrin against E. coli O157:H7 and L. monocytogenes. Citric acid (0.5%) combined with ovotransferrin resulted in a synergistic antibacterial effect against E. coli O157:H7, and L. monocytogenes was susceptible to 0.5% citric acid alone. Sodium bicarbonate diminished the strong antibacterial activity of ovotransferrin + citric acid against E. coli O157:H7, and use of sodium citrate instead of citric acid did not produce any antibacterial activity against the pathogens. The antimicrobial activity of ovotransferrin increased significantly under acidic conditions. The Zn-bound ovotransferrin prevented the growth of L. monocytogenes as detected in the apo-ovotransferrin combined with 100 mM NaHCO(3) treatment, but Fe-bound ovotransferrin had little or no inhibitory activity against E. coli O157:H7 and L. monocytogenes. Ovotransferrin + 100 mM NaHCO(3) did not exhibit any antibacterial activity against the 2 pathogens in commercial hams, whereas ovotransferrin + 0.5% citric acid suppressed the growth of L. monocytogenes in irradiated hams. In conclusion, combinations of ovotransferrin with NaHCO(3), citric acid, or Zn(2+) enhanced the antibacterial activity of ovotransferrin against E. coli and L. monocytogenes, but there are some limitations as discussed for applying ovotransferrin to meat or meat products.


Construction of a genetic switch for inducible trans-activation of gene expression in eucaryotic cells.
The cotransfection of selectable marker genes and the gene for the nonstructural proteins NS1 and NS2 of the autonomous parvovirus H-1 failed to produce cell lines that constitutively expressed NS1. A plasmid, pP38NS1cat, was constructed that expressed the NS1-NS2 gene from the H-1 P38 coat protein promoter in place of the natural P4 promoter. The P38 promoter is constitutively weak and is trans-activated by NS1. Stable cell lines were isolated that contained pP38NS1cat that was constitutively silent, but inducible with exogenous NS1 by superinfection or by treatment with sodium butyrate. The cells that were induced for this self-stimulatory genetic circuit did not remain in the culture, suggesting that expression of NS1-NS2 is cytotoxic or that the expression is not sustained. The properties of these cell lines and an example of the construction of a cell line inducible for expression of the viral coat protein gene and the bacterial gene for chloramphenicol acetyltransferase (cat) are described.


Analytic reconstruction algorithms for triple-source CT with horizontal data truncation.
This paper explores a triple-source imaging method with horizontal data truncation to enlarge the field of view (FOV) for big objects. The study is conducted by using theoretical analysis, mathematical deduction, and numerical simulations. The proposed algorithms are implemented in c + + and matlab. While the basic platform is constructed in matlab, the computationally intensive segments are coded in c + +, which are linked via a mex interface. A triple-source circular scanning configuration with horizontal data truncation is developed, where three pairs of x-ray sources and detectors are unevenly distributed on the same circle to cover the whole imaging object. For this triple-source configuration, a fan-beam filtered backprojection-type algorithm is derived for truncated full-scan projections without data rebinning. The algorithm is also extended for horizontally truncated half-scan projections and cone-beam projections in a Feldkamp-type framework. Using their method, the FOV is enlarged twofold to threefold to scan bigger objects with high speed and quality. The numerical simulation results confirm the correctness and effectiveness of the developed algorithms. The triple-source scanning configuration with horizontal data truncation cannot only keep most of the advantages of a traditional multisource system but also cover a larger FOV for big imaging objects. In addition, because the filtering is shift-invariant, the proposed algorithms are very fast and easily parallelized on graphic processing units.


Steroids in traditional Chinese medicine: what is the evidence?
Local healthcare providers often question the possible steroidal activity of traditional Chinese medicine (TCM) herbs or herbal products and implicate them as a cause for adrenal insufficiency or Cushing's syndrome in patients with a history of TCM intake. We conducted a comprehensive database search for evidence of potential glucocorticoid, mineralocorticoid, androgenic or oestrogenic activity of herbs or herbal products. Overall, there are not many herbs whose steroidal activity is well established; among these, most cases were based on preclinical studies. Liquorice root may cause pseudoaldosteronism through interference with the steroidogenesis pathway. Although ginseng and cordyceps have some in vitro glucocorticoid activities, the corroborating clinical data is lacking. Deer musk and deer antler contain androgenic steroids, while epimedium has oestrogenic activity. On the other hand, adulteration of herbal products with exogenous glucocorticoids is a recurrent problem encountered locally in illegal products masquerading as TCM. Healthcare providers should stay vigilant and report any suspicion to the relevant authorities for further investigations.


[Management of pediatric deep partial-thickness burn wounds].
Deep partial-thickness burns are the most common type of pediatric burns, in which hypertrophic scars usually develop, causing functional and cosmetic impairment. The choice of wound management method and surgical procedures for deep partial-thickness burn are often the issues that concern burn surgeon and the family members of patients. The development of modern functional wound dressings, the establishment of the concept of full rehabilitation of pediatric burns, and the implementation of comprehensive rehabilitation therapy for hypertrophic scars will inevitably change the traditional therapeutic strategies for pediatric deep partial-thickness burn wounds to a certain extent.


Cognitive-Behavioral Therapy in Older Panic Disorder Patients.
Although there are a number of studies reporting the efficacy of cognitive-behavioral therapy for panic disorder in younger patients, such studies are lacking for older adults. This study used a subject sample (N = 20; 5 dropouts, 15 completers) of self-referred, community-dwelling older adults who met DSM-III-R criteria for panic disorder. Ten sessions of cognitive-behavioral therapy were provided over a 12-week period. Cognitive, behavioral, physiological, affective, and global domains (dimensions) were assessed by self-report measures. Statistically significant results of pretreatment, posttreatment, and 3-month follow-up means were found across domains, suggesting that treatment was efficacious.


The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation.
Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to NBAT-1 differential expression. Loss of NBAT-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. NBAT-1 loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors.


Dental fear and anxiety in children and adolescents: qualitative study using YouTube.
Dental fear and anxiety (DFA) refers to the fear of and anxiety towards going to the dentist. It exists in a considerable proportion of children and adolescents and is a major dilemma in pediatric dental practice. As an Internet social medium with increasing popularity, the video-sharing website YouTube offers a useful data source for understanding health behaviors and perceptions of the public. Using YouTube as a platform, this qualitative study aimed to examine the manifestations, impacts, and origins of DFA in children and adolescents from the public's perspective. To retrieve relevant information, we searched YouTube using the keywords "dental fear", "dental anxiety", and "dental phobia". Videos in English expressing a layperson's views or experience on children's or adolescent's DFA were selected for this study. A video was excluded if it had poor audiovisual quality, was irrelevant, was pure advertisement or entertainment, or contained only the views of professionals. After the screen, we transcribed 27 videos involving 32 children and adolescents, which were reviewed by a panel of 3 investigators, including a layperson with no formal dental training. Inductive thematic analysis was applied for coding and interpreting the data. The videos revealed multiple manifestations and impacts of DFA, including immediate physical reactions (eg, crying, screaming, and shivering), psychological responses (eg, worry, upset, panic, helplessness, insecurity, resentment, and hatred), and uncooperativeness in dental treatment. Testimonials from children, adolescents, and their parents suggested diverse origins of DFA, namely personal experience (eg, irregular dental visits and influence of parents or peers), dentists and dental auxiliaries (eg, bad manner, lack of clinical skills, and improper work ethic), dental settings (eg, dental chair and sounds), and dental procedures (eg, injections, pain, discomfort, and aesthetic concerns). This qualitative study suggests that DFA in children and adolescents has multifaceted manifestations, impacts, and origins, some of which only became apparent when using Internet social media. Our findings support the value of infodemiological studies using Internet social media to gain a better understanding of health issues.


[Toxic metabolites from Fusarium causing alimentary toxic aleukia (author's transl)].
The toxicity of extracts from Fusarium poae and F. sporotrichioides, incriminated as agents of alimentary toxic aleukia, is attributed to the presence of 12-13-epoxytrichothecenes. This is specially the case of T2 toxin and diacetoxyscirpenol.


Flat-panel digital radiology with amorphous selenium and active-matrix readout.
Future imaging techniques will be capable of high image quality, fast acquisition, compactness, and versatile operation. A flat-panel imager that is expected to achieve these goals is under development. It consists of a thin layer of amorphous selenium that converts x rays directly to an electric charge and a thin-film electronic circuit, or active matrix, to read out the electronic signal directly to a computer host. The advantages of amorphous selenium include high resolution and low noise without loss of signal strength. The advantages of the active matrix are real-time readout, flexible design parameters, and compactness of the readout structures. A prototype of this imager has been built and operated, and initial images (of an x-ray test bar pattern and a hand phantom) have been acquired. Although the prototype was built to test scientific principles and many possibilities for optimization remain, the images already possess the quality necessary for many radiographic procedures. A large range of current and new applications exist for this imager.


Ultrastructural viewpoints on the interaction events of Scedosporium apiospermum conidia with lung and macrophage cells.
Scedosporium apiospermum is a ubiquitous, emerging and multidrug-resistant fungal pathogen with still rather unknown virulence mechanisms. The cellular basis of the in vitro interaction between fungi and host cells/tissues is the determinant factor for the development of a successful in vivo infection. Herein, we evaluated the interaction of S. apiospermum conidia with lung epithelial (A549), lung fibroblast (MRC-5) and RAW 264.7 macrophages by light and scanning/transmission electron microscopy. After 4 h of fungi-host cell contact, the percentage of infected mammalian cells and the number of fungi per infected cell was measured by light microscopy, and the following association indexes were calculated for A549, MRC-5 and macrophage cells: 73.2 ± 25.9, 69.7 ± 22.5 and 59.7 ± 11.1, respectively. Both conidia and germinated conidia were regularly observed interacting with the evaluated cells, with a higher prevalence of non-germinated conidia. Interestingly, nests of germinated conidia were evidenced at the surface of lung cells by scanning electron microscopy. Some germination projections and hyphae were seen penetrating/evading the mammalian cells. Furthermore, internalised conidia were seen within vacuoles as visualised by transmission electron microscopy. The present study contributes to a better understanding of S. apiospermum pathogenesis by demonstrating the first steps of the infection process of this opportunistic fungus.


A new minimally invasive experimental spinal cord injury model in rabbits.
The aim of this experimental study was to evaluate the effectivity of epidural microballoon inflation into the unroofed spinal column for the creation of a new experimental spinal cord injury model in rabbits. 10 New Zealand white rabbits were used for this study. Before operation and after anasthesia with 50 mg/kg ketamine and 8 mg/kg xylazine, spinal evoked potentials (SEP) were recorded in all rabbits. A midline skin incision was done on the lomber skin at the level of L1-L4. Paravertebral muscles were dissected bilaterally. A microhemilaminotomy was done in the right L3 lamina close to the midline by using Midas-rex micro-diamond drill instruments. The ligamentum flavum was opened and removed with microscissors. A microballoon was inserted into the spinal column between the bone and dura mater to the level of T12. The microballoon was inflated by using a pressure- and volume-controlled microballoon inflation device. Pre-injury and post-injury SEPs were recorded. The microballoon was deflated 15 minutes later and removed completely from the epidural space. 24 hours later the SEP study was repeated. Following microballoon inflation the SEP waves dropped to the basal level. All rabbits were paraplegic after the operation. In conclusion, this experimental study demonstrated that the microballoon inflation technique is a very successful method for the evaluation of spinal cord injury in rabbits. Unroofing of the spinal column is extremely important because decompression may be an effective treatment in spinal cord injury. Also the traumatic effect of aneurysm clips represents a different type of injury to the spinal cord. This new model may be used in experimental studies of spinal cord injury in rabbits.


Luminal STAT5 mediates H2AX promoter activity in distinct population of basal mammary epithelial cells.
Deregulated STAT5 activity in the mammary gland causes parity-dependent tumorigenesis. Epithelial cell cultures transfected with constitutively active STAT5 express higher levels of the histone H2AX than their non-transfected counterparts. Higher H2AX expression may be involved in tumorigenesis. Here, we aimed to link high STAT5 activity to H2AX-GFP expression by looking for distinct types of mammary cells that express these proteins. In vitro and in transgenic mice, only 0.2 and 0.02%, respectively, of the cells expressed the H2AX-GFP hybrid gene. Its expression correlated with that of the endogenous H2AX gene, suggesting that detectable H2AX-GFP expression marks high levels of H2AX transcript. Methylation of the H2AX promoter characterized non-GFP-expressing H2AX-GFP cells and was inversely correlated with promoter activity. Administration of 5-azacytidine increased H2AX promoter activity in an activated STAT5-dependent manner. In transgenic mice, H2AX-GFP expression peaked at pregnancy. The number of H2AX-GFP-expressing cells and GFP expression decreased in a Stat5a-null background and increased in mice expressing the hyperactivated STAT5. Importantly, H2AX-GFP activity was allocated to basal mammary cells lacking stem-cell properties, whereas STAT5 hyperactivity was detected in the adjacent luminal cells. Knockdown of RANKL by siRNA suggested its involvement in signaling between the two layers. These results suggest paracrine activation of H2AX via promoter demethylation in specific populations of basal mammary cells that is induced by a signal from neighboring luminal cells with hyper STAT5 activity. This pathway provides an alternative route for the luminally confined STAT5 to affect basal mammary cell activity.


Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years.
The relationship between the entorhinal cortex (EC) and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the EC and in the granular layer of the dentate gyrus (DG) of the hippocampus. We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the DG and the adjacent EC were stained according to the Klüver-Barrera method, then the ImageJ software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the EC and layer II of the DG. Statistical analysis was subsequently performed. We observed an age-related reduction in the cell population of the external pyramidal layer of the EC, and in the number of neurons in the granular layer of the DG. Our results indicate that ageing causes a decrease in the size and density of grid cells of the EC and place cells of the DG.


Rutin has intestinal antiinflammatory effects in the CD4+ CD62L+ T cell transfer model of colitis.
Rutin, one of the most abundant flavonoids in nature, has been shown to exert intestinal antiinflammatory effects in experimental models of colitis. Our aim was to study the antiinflamatory effect of rutin in the CD4+ CD62L+ T cell transfer model of colitis, one of the closest to the human disease. Colitis was induced by transfer of CD4+ CD62L+ T cells to Rag1(-/-) mice. Rutin was administered by gavage as a postreatment. Treatment with rutin improved colitis at the dose of 57mg/kg/day, while no effect was noted with 28.5mg/kg/day. Therapeutic benefit was evidenced by a reduced disease activity index, weight loss and damage score, plus a 36% lower colonic myeloperoxidase and a 54% lower alkaline phosphatase activity. In addition, a decreased secretion of proinflammatory cytokines (IFNγ and TNFα) by mesenteric lymph node cells was observed ex vivo. The colonic expression of proinflammatory genes, including IFNγ, TNFα, CXCL1, S100A8 and IL-1β, was significantly reduced by more than 80% with rutin as assessed by RT-qPCR. Flavonoid treated mice exhibited decreased activation of splenic CD4+ cells (STAT4 phosphorylation and IFNγ expression) and reduced plasma cytokine levels. This effect was also apparent in mucosal lymphocytes based on reduced STAT4 phosphorylation. The protective effect was comparable to that of 3mg/kg/day budesonide. Rutin had no effect on splenocytes or murine T cells in vitro, while its aglycone, quercetin, exhibited a concentration dependent inhibition of proinflammatory cytokines, including IFNγ. Rutin but not quercetin showed vectorial basolateral to apical transport in IEC18 cells, associated with reduced biotransformation. We conclude that rutin exerts intestinal antiinflammatory activity in chronic, T lymphocyte dependent colitis via quercetin release and actions involving mucosal and lymph node T cells. Our results suggest that rutin may be useful in the management of inflammatory bowel disease in appropriate dosage conditions.


How physical education teacher education majors should be prepared to teach students with hearing loss: a national needs assessment.
A national needs assessment survey is described that gathered information on current practices in physical education in both center-based schools for the deaf and mainstream programs serving deaf and hard of hearing students, grades K-12. The manner in which deaf and hard of hearing students are being served in physical education programs, the depth and breadth of curricula, and the credentials needed to teach are described. The study compares similarities and differences among physical education programs in center-based deaf institutions and mainstream schools. In summary, the study identifies areas of concentration needed in curriculum, and methods of teaching appropriate for student teacher candidates. This information has value for physical education programs that are considering revising their curricula to prepare teacher candidates who wish to work with deaf students.


Within-patient early versus delayed treatment of migraine attacks with almotriptan: the sooner the better.
Migraine sufferers typically have been instructed to delay triptan therapy until headache intensity is at least moderate. Recent data suggest that earlier use of triptans may be more beneficial. To address the potential "within-patient" benefit of intervention with almotriptan 12.5 mg for migraine headache of mild intensity. We performed a post hoc analysis of a subgroup of patients from a large, open-label, long-term clinical trial wherein 762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity. Specifically, we evaluated the efficacy and safety of treatment in those patients who had treated at least 3 "mild" attacks and 3 "moderate/severe" attacks, examining rates of pain-free status, use of rescue medication, early recurrence, and adverse events for the first 3 mild and the first 3 moderate/severe attacks treated. There were 118 migraineurs and 708 attacks available for analysis. At 1 hour following treatment, pain-free status was achieved in 47% of mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2 hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue medication was required in 8% of mild attacks and in 13% of moderate/severe attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and 33% for moderate/severe attacks (P<.01). There was no difference in the incidence of adverse events for mild versus moderate/severe attacks (6% versus 7%). These results support early intervention with oral triptan therapy. When used for mild intensity head pain, almotriptan 12.5 mg produced a significantly higher incidence of pain-free status at 1 and 2 hours and lower incidences of early headache recurrence or need for rescue medication.


The use of premixed drugs in commodity packets in the population: prevalence and correlates revealed by the 2018 National Survey of Substance Use in Taiwan.
Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug packet users. Data were derived from a survey of 18,626 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs and other psychoactive substances, among others. Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had a lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were similar to those of the exclusive use of other drugs except that there was a lack of gender differences in the use of drugs in commodity packets but not in the exclusive use of other drugs. Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug packet use.


Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells.
Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs) were determined by neutral red staining. The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase-3 and -9, increase of annexin V(+)PI(+) cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown). Our data implicate that 2-MCA could be a potential agent for anticancer therapy.