Optimal dose of rocuronium bromide undergoing adenotonsillectomy under 5% sevoflurane with fentanyl.
Adenotonsillectomy is a short surgical procedure under general anaesthesia in children. An ideal muscle relaxant for adenotonsillectomy would create an intense neuromuscular block while having a quick recovery time without postoperative morbidity. We compared the effect of different doses of rocuronium for the tracheal intubation in children under 5% sevoflurane and fentanyl. 75 children (aged 3-10 years, ASA I) scheduled for adenotonsillectomy were enrolled. Anaesthesia was induced with propofol 2.5 mg/kg, followed by fentanyl 2 μg/kg. After mask ventilation with 5 vol% sevoflurane in 100% oxygen for 2 min, 2 ml of study drug was administered intravenously, i.e., either normal saline (S Group) or one of two doses (0.15 or 0.3 mg/kg) of rocuronium. We assessed conditions during tracheal intubation and also recorded the surgical condition, the time from discontinuation of sevoflurane to extubation and PAED scale, pain scores in PACU. Rocuronium groups (96% and 100%, respectively; P < 0.01) showed statistically superior clinically acceptable intubating conditions than the saline group (72%). The 0.3 mg/kg rocuronium (80%) treatment clearly resulted in excellent intubating conditions compared with the 0.15 mg/kg group (44%; p = 0.028). There was no significant difference in the time to extubation and surgical condition, and in the postoperative measures of emergence delirium, pain, and recovery time among the three groups. A dose of 0.3 mg/kg rocuronium may provide optimal intubating conditions without delayed recovery in 5% sevoflurane anaesthesia with fentanyl in children undergoing adenotonsillectomy. NCT02467595.


Scalp potential fields evoked by grating stimuli: effects of spatial frequency and orientation.
Visually evoked potentials were recorded from an array of 16 electrodes over the occipital cortex in 12 subjects. Grating stimuli of different spatial frequencies were presented on a circular test field, and potential fields evoked by vertical, horizontal and oblique stimuli were compared. Component latencies were determined by computing a reference-independent measure of field power. Scalp field maps were constructed at component latencies and compared over all conditions. Significant influences of both spatial frequency and orientation on component latencies were found. Component latencies were shortest for 2.3 c/deg gratings, and for vertically oriented stimuli. Latencies increased for horizontal, and further for oblique, gratings. The effect of spatial frequency or orientation on the location of the major components on the scalp was less pronounced. On the other hand, there were significant differences both in component latency and scalp distribution when upper and lower hemiretinal stimuli were compared. Upper hemiretinal stimulation yielded shorter latencies and a more anteriorly located potential peak on the scalp.


Temporal trends of hydrocarbons in sediment cores from the Pearl River Estuary and the northern South China Sea.
Concentrations and fluxes of unresolved complex mixture of hydrocarbons (UCM) and polycyclic aromatic hydrocarbons (PAHs) were analyzed for two (210)Pb dated sediment cores from the Pearl River Estuary (PRE) and the adjacent northern South China Sea (NSCS). Compound-specific stable carbon isotopic compositions of individual n-alkanes were also measured for identification of the hydrocarbon sources. The historical records of PAHs in the NSCS reflected the economic development in the Pearl River Delta during the 20th century. PAHs in the NSCS predominantly derive from combustion of coal and biomass, whereas PAHs in the PRE are a mixture of petrogenic and pyrogenic in origins. The isotopic profiles reveal that the petrogenic hydrocarbons in the PRE originate predominantly from local spillage/leakage of lube oil and crude oils. The accumulation rates of pyrogenic PAHs have significantly increased, whereas UCM accumulation has slightly declined in the NSCS in the recent three decades.


Metabolic energy-independent mechanism of internalization for the cell penetrating peptide penetratin.
Cellular uptake of vector peptides used for internalization of hydrophilic molecules into cells is known to follow two different pathways: direct translocation of the plasma membrane and internalization by endocytosis followed by release into the cytosol. These pathways differ in their energy dependence. The first does not need metabolic energy while the second requires metabolic energy. Herein we used erythrocytes and plasma membrane vesicles to study membrane perturbations induced by the cell penetrating peptide penetratin. The results show that cell penetrating peptides are able to be internalized by two metabolic energy-independent pathways: direct crossing of the plasma membrane and endocytosis-like mechanisms. The last mechanism involves the induction of membrane negative curvature resulting in invaginations that mimic the endosomal uptake in the absence of ATP. This new mechanism called "physical endocytosis" or "self-induced endocytosis" might explain different data concerning the independence or dependence on metabolic energy during cellular uptake and reveals the autonomous capacity of peptides to induce their internalization.


Immunologic effectiveness of maraviroc- and raltegravir-containing regimens (R+M+) versus raltegravir-based regimens that do not include maraviroc (R+M-).
To compare the immunologic effectiveness of raltegravir-maraviroc (R+M+)-based regimens with raltegravir-based regimens that do not include maraviroc (R+M-) in treatment-experienced patients in clinical practice. We conducted a retrospective study of treatment-experienced HIV-infected adults receiving either R+M+- or R+M--based therapy. Longitudinal CD4 counts were analyzed using a linear mixed model. One hundred and fifty-six patients were included in the analysis, of whom 32 were receiving R+M+ and 124 R+M-. Mean baseline CD4 counts in patients on R+M+ and R+M- were 463.8 and 442.3 cells/mm(3), respectively (P = .67). In multivariable mixed models, a baseline viral load ≥50 copies/mL was significantly associated with CD4 change during follow-up (P < .0001). No difference between R+M+ and R+M- was observed during follow-up (P = .81). CD4 cell recovery was similar among patients receiving either R+M+- or R+M--based therapy during a 24-month period of follow-up.


Selection of stationary phase particle geometry using X-ray computed tomography and computational fluid dynamics simulations.
The X-ray computed tomography (CT) is used to determine local parameters related to the column packing homogeneity and hydrodynamics in columns packed with spherically and irregularly shaped particles of same size. The results showed that the variation of porosity and axial dispersion coefficient along the column axis is insignificant, compared to their radial distribution. The methodology of using the data attained by CT measurements to perform a CFD simulation of a batch separation of model binary mixtures, with different concentration and separation factors is demonstrated. The results of the CFD simulation study show that columns packed with spherically shaped particles provide higher yield in comparison to columns packed with irregularly shaped particles only below a certain value of the separation factor. The presented methodology can be used for selecting a suited packing material for a particular separation task.


Effect of lower limb malalignment in the frontal plane on transverse plane mechanics during gait in young individuals with varus knee alignment.
Varus knee alignment has been identified as a risk factor for the progression of medial knee osteoarthritis (OA). This study tested the hypothesis that not only frontal plane kinematics and kinetics but also transverse plane lower extremity mechanics during gait are affected by varus malalignment of the knee. Eighteen, otherwise healthy children and adolescents with varus malalignment of the knee were studied to examine the association between static varus malalignment and functional gait parameters. Kinematic data were collected using a Vicon motion capture system (Vicon Motion Systems, Oxford, UK). Two AMTI force plates (Advanced Mechanical Technology, Inc., Watertown, MA, USA) were used to collect kinetic data. The results indicated that changes in transverse plane mechanics occur concomitantly with changes in knee malalignment in the frontal plane. A mechanical consequence of varus knee malalignment is obviously an increased endorotation of the foot (internal foot placement) and an increased internal knee rotation (tibia rotation) during stance phase. The linear correlation between the maximum external knee adduction moment in terminal stance and the internal knee rotation in terminal stance (r=0.823, p<0.001) shows that this transverse plane gait mechanics is directly in conjunction with intrinsic compressive load on the medial compartment during gait. Understanding factors that influence dynamic knee joint loading in healthy, varus malaligned knees may help us to identify risk factors that lead to OA. Thus, three-dimensional gait analysis could be used for clinical prognoses regarding the onset or progression of medial knee OA.


Measurement of benzoylecgonine and cocaine in urine, separation of various cocaine metabolites using reversed-phase high-performance liquid chromatography.
The application of reversed-phase high-performance liquid chromatography to the measurement of benzoylecgonine and cocaine in urine is described. Following a simple extraction and clean-up procedure, chromatography is performed using a column containing an octadecylsilica coated packing, elution with 17% acetonitrile in pH 2.7 phosphate buffer and ultraviolet detection at 200 or 235 nm. The detection limit is ca.0.1 microgram of drug per ml urine, and using the ethyl ester of benzoylecgonine as an internal standard, benzoylecgonine and cocaine are quantified with coefficients of variation of 7.0 and 2.8%, respectively. The procedure has been applied to urines from subjects receiving intranasal cocaine, and compared to the enzyme multiplied immunoassay technique. The chromatography procedure also permits the separation of norcocaine and benzoylnorecgonine.


Development of the blood-brain barrier to horseradish peroxidase in the chick embryo.
One to 20 mg of horseradish peroxidase (HRP) was injected into the allantoic vein of chick embryos between the 7th to 21st day of incubation and its penetration from blood into the interstitium of cerebellum and spinal cord (upper thoracic) was examined by light and electron microscopy in order to study development of the blood-brain barrier. Until the 12th day of incubation (stage 38) the reaction products, indicating the presence of peroxidase, were distributed in every region of the intercellular spaces in both cerebellum and spinal cord, whereas in 13th and 14th day embryos (stage 39 and 40) they were observed only in the medullary regions. In the embryos after 15th day (stage 41) they filled only the intravascular lumen and some micropinocytotic vesicles in the endothelium. These results show that the blood-brain barrier to HRP develops roughly synchronously in various parts of the central nervous system and evolves independently of neurogenesis, the course of which differs considerably in the cerebellum and spinal cord.


[Electro-ophthalmological findings in so-called partial "retinopathia pigmentosa" (author's transl)].
A description is given of bilateral, sectoral retinopathia pigmentosa in a female subject and her eldest son. The diagnosis is difficult without an ERG and EOG because of the paucity of symptoms. The disease is characterized by subnormal ERG potentials and a flat EOG curv. In questionable cases, periodic re-examinations and the examination of family members can be helpful.


Metabolic oligosaccharide engineering of Plasmodium falciparum intraerythrocytic stages allows direct glycolipid analysis by mass spectrometry.
A recent addition to the arsenal of tools for glycome analysis is the use of metabolic labels that allow covalent tagging of glycans with imaging probes. In this work we show that N-azidoglucosamine was successfully incorporated into glycolipidic structures of Plasmodium falciparum intraerythrocytic stages. The ability to tag glycoconjugates selectively with a fluorescent reporter group permits TLC detection of the glycolipids providing a new method to quantify dynamic changes in the glycosylation pattern and facilitating direct mass spectrometry analyses. Presence of glycosylphosphatidylinositol and glycosphingolipid structures was determined in the different extracts. Furthermore, the fluorescent tag was used as internal matrix for the MALDI experiment making even easier the analysis.


Impaired mononuclear-cell proliferation in patients with the acquired immune deficiency syndrome results from abnormalities of both T lymphocytes and adherent mononuclear cells.
Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome proliferate poorly after stimulation with soluble mitogens. The present study was undertaken to assess the relative contributions of T lymphocytes and of plastic adherent mononuclear cells to the impaired mononuclear cell responses. We employed a four-step separation procedure including terminal depletion using a monocyte-specific monoclonal antibody (61D3) to derive populations of highly purified T cells from patients and from normal subjects. Highly purified T cells proliferated poorly in response to phytohemagglutinin and pokeweed mitogen. The addition of autologous adherent cells to highly purified T cells markedly improved mitogen-driven proliferation in all subjects; however, mononuclear cells from patients with AIDS responded less well than normals (P less than or equal to 0.01) for both phytohemagglutinin and pokeweed. Allogeneic normal adherent cells fully restored both phytohemagglutinin and pokeweed responses in normal highly purified T cells. Adherent cells from patients were comparable to normal adherent cells in phytohemagglutinin-driven proliferation but performed significantly less well when pokeweed was used to stimulate normal highly purified T-cell responders (4308 cpm after coculture with patients' adherent cells vs 8244 cpm after coculture with allogeneic normal adherent cells; P = 0.05). Similarly, when patient's highly purified T cells were stimulated with pokeweed mitogen, control adherent cells functioned substantially better than patient adherent cells (1198 cpm for allogeneic patient adherent cells vs 2324 cpm for normal adherent cells; P = 0.05). Although the addition of normal adherent cells to patients' highly purified T cells significantly improved pokeweed mitogen responses, these values did not reach normal. Suppression by patients adherent cells was not demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)


Factor structure of the Yale-Brown Obsessive-Compulsive Scale: a two dimensional measure.
The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS: Goodman, Price, Rasmussen, Mazure, Fleischman, Hill, Heninger & Charney, 1989a, b, Archives of General Psychiatry, 46, 1006-1016), a widely used measure of obsessions and compulsions, is typically used by summing the items to yield a global measure of symptom severity. However obsessive-compulsive disorder (OCD) is characterized by two distinct groups of symptoms (i.e. obsessions and compulsions), and so it was hypothesized that OCD, as assessed by the Y-BOCS, may be two dimensional. In other words, the items assessing obsessions may be factorially distinct from the items assessing compulsions. A confirmatory factor analysis (CFA) was conducted using responses from 83 OCD patients to determine whether OCD as assessed with the Y-BOCS is unidimensional or forms two distinct dimensions. Results supported a two-factor solution, and suggest that items assessing obsessions should be scored as one subscale, and items assessing compulsions scored as a separate subscale. Depression, as assessed by the Beck Depression Inventory, (Beck, Ward, Mendelsohn, Mock & Erbaugh, 1961, Archives of General Psychiatry, 4, 561-571), was correlated with both subscales. Trait anxiety, as assessed by the State-Trait Anxiety Inventory (Speilberger, 1983, Manual for the State-Trait Anxiety Inventory (Form Y). Palo-Alto, CA: Consulting Psychologists Press), was correlated with the obsessions subscale but not with the compulsions subscale.


Women's preferences for sexual dimorphism in height depend on menstrual cycle phase and expected duration of relationship.
Human mate preferences are related to many morphological traits, such as female waist-to-hip ratio (WHR), body mass index (BMI), male height or facial symmetry. People also vary in preferences for sexual dimorphism in stature (SDS = male height/female height) between themselves and a potential partner. Here, we demonstrate that women adjust their preference for SDS not only in relation to their own height but also in relation to (1) the phase of menstrual cycle during which their preferences were studied and (2) the sexual strategy (short- versus long-term) they were asked to choose. Taller males (larger SDS) were preferred more often when women were in the follicular (i.e. fertile) phase of their menstrual cycle and when the partners were chosen for short-term relationships. These effects were independent of woman's height. The results show that women in a potentially fertile phase of their menstrual cycle and when choosing a partner who might be less likely to invest in children select genes of taller males.


Are pre- and postoperative true translational and angular displacement predictive of nonunion after intramedullary nail fixation of tibial shaft fractures?
To determine if there is an association between pre-/postoperative translational and angular displacement with nonunion after intramedullary nail (IMN) fixation of tibial shaft fractures. Retrospective review of 120 patients with tibial shaft fractures undergoing IMN at an urban level-one trauma center was performed. Demographics, injury characteristics, and pre-/postoperative translational and angular fracture displacement in the coronal and sagittal planes were recorded. True fracture translational and angular displacement (TTD and TAD) were calculated by combining sagittal and coronal displacement utilizing the Pythagorean theorem. 10.8% of patients (n = 13) developed nonunion with remaining patients serving as the control. Groups were similar across age, sex, and BMI. Univariate analysis revealed no difference in pre-/postoperative TAD between nonunion and union groups and an increased preoperative TTD (median difference (MD): 6.2 mm, CI: 1.4-10.8 mm) and postoperative TTD (MD: 1.8 mm, CI: 0-3.7 mm) in the nonunion group. On multivariate analysis, however, only tobacco use and type 2 or 3 open fractures were associated with nonunion (OR: 5.1, CI: 1.2-22.8 and OR: 4.9, CI: 1.2-19.2, respectively). True translational and angular displacement of tibial shaft fractures before and after IMN fixation were not independently associated with nonunion. Tobacco use and type 2 or 3 open fracture are independent factors for nonunion.


Improving lake chlorophyll-a interpreting accuracy by combining spectral and texture features of remote sensing.
Cyanobacterial blooms in lakes fueled by increasing eutrophication have garnered global attention, and high-precision remote sensing retrieval of chlorophyll-a (Chla) is essential for monitoring eutrophication. Previous studies have focused on the spectral features extracted from remote sensing images and their relationship with chlorophyll-a concentrations in water bodies, ignoring the texture features in remote sensing images which is beneficial to improve interpreting accuracy. This study explores the texture features in remote-sensing images. It proposes a retrieval method for estimating lake Chla concentration by combining spectral and texture features of remote sensing images. Remote sensing images from Landsat 5 TM and 8 OLI were used to extract spectral bands combination. The gray-level co-occurrence matrix (GLCM) of remote sensing images was used to obtain a total of 8 texture features; then, three texture indices were calculated using texture features. Finally, a random forest regression was used to establish a retrieval model of in situ Chla concentration from texture and spectral index. Results showed that texture features are significantly correlated with lake Chla concentration, and they can reflect the temporal and spatial distribution change of Chla. The retrieval model combining spectral and texture indices performs better (MAE = 15.22 μg·L-1, bias = 9.69%, MAPE = 47.09%) than the model without texture features (MAE = 15.76 μg·L-1, bias = 13.58%, MAPE = 49.44%). The proposed model performance varies in different Chla concentration ranges and is excellent in predicting higher concentrations. This study evaluates the potential of incorporating texture features of remote sensing images in lake water quality estimation and provides a novel remote sensing method to better estimate lake Chla concentration.


Motor vehicle injuries in childhood: a hospital-based study in Saudi Arabia.
Motor vehicles are a major cause of injury-related deaths in children and may also result in temporary or permanent disability. A retrospective analysis of the medical charts of children aged 12 years and younger, who were involved in motor vehicle injuries during a 10-year period, was undertaken. All children who were admitted and treated at King Fahad National Guard Hospital, Riyadh from January 1994 to December 2003 were included in this study. Data analyzed included age, gender, and mechanism of injury, type of injury, management and outcome. Motor vehicle injuries accounted for approximately 42% of all pediatric traumas. There were 664 children, 469 (71%) male and 195 (29%) female and a male: female ratio 2.4:1. Four hundred and seventy two children were injured as pedestrians (71%), 177 as auto passengers (27%), 11 as bicyclists (1.5%), and 4 as motorcyclists (0.5%). Five hundred and sixty two injured children (85%) were between the ages of 1 and 8 years. The most common injuries were to the head and extremities. Thirty-four children (5.1%) died from their injuries, 30 from head trauma. Thirty-five children (5.3%) were discharged home with neurological impairment from head trauma. In this study, the risk factors associated with high volume of motor vehicle injuries in children include, male, 1-8 years, and pedestrian. Head trauma is the most common cause of morbidity and mortality. This study suggests that nationwide programs should target the use of seatbelts and helmets, and dangerous driving practices.


Creatine and other supplements.
Ergogenic dietary supplement use is highly prevalent among adolescent and collegiate athletes, and use is increasing. To make appropriate recommendations for or against use by individual athletes, physicians who work with adolescent athletes should be knowledgeable about the most commonly used supplements and be able to access high-quality information about others. This article first discusses the legal and regulatory environment of dietary supplements. Several of the most commonly used supplements are then discussed in detail, including creatine, beta-hydroxy-beta-methylbutyrate, protein, amino acids, stimulants, alkalotic agents, glycerol, vitamins, and minerals. Finally, the "Gateway Theory" as it may relate to adolescent supplement and other drug use is discussed.


Preventive services received by adolescents with cystic fibrosis and sickle cell disease.
To determine the proportion of adolescents with cystic fibrosis (CF) or sickle cell disease (SCD) who reported speaking with their physicians about health-promoting and risky behaviors and whether the rate of discussions varied by whether the main physician was a primary care provider or specialist. Adolescents reporting a primary care provider as their main physician would be more likely to have received risk behavior counseling and other preventive services. Survey. Comprehensive CF and SCD centers in 5 North Carolina referral hospitals. Three hundred twenty-one (74%) of 437 adolescents aged 12 through 19 years (mean age, 15.6 years; 51% male) with CF or SCD identified through center registries. Sources of health care, main physician, and recall of discussions with physicians regarding sexual issues, substance use, weight or dieting, safety issues, depression, and violence. Adolescents with CF (53%) or SCD (46%) most commonly reported a specialist as their main physician. For those (83%) who saw their main physician in the past year, adolescents with SCD reported counseling rates ranging from 43% for sexuality to 15% for weapon carrying or fighting. For adolescents with CF, rates ranged from 65% for weight and dieting to 30% for sexuality and 6% for weapon carrying or fighting. Adolescents whose main physician was a primary care provider were no more or less likely to report counseling for any topic (all P>.05). Physicians, regardless of specialty, infrequently discussed common behavioral issues with these adolescents with CF or SCD. A coordinated effort between primary care physicians and specialists may be helpful in delivering optimal preventive services to this population.


Stalked protozoa identification by image analysis and multivariable statistical techniques.
Protozoa are considered good indicators of the treatment quality in activated sludge systems as they are sensitive to physical, chemical and operational processes. Therefore, it is possible to correlate the predominance of certain species or groups and several operational parameters of the plant. This work presents a semiautomatic image analysis procedure for the recognition of the stalked protozoa species most frequently found in wastewater treatment plants by determining the geometrical, morphological and signature data and subsequent processing by discriminant analysis and neural network techniques. Geometrical descriptors were found to be responsible for the best identification ability and the identification of the crucial Opercularia and Vorticella microstoma microorganisms provided some degree of confidence to establish their presence in wastewater treatment plants.


The assessment of consciousness during partial seizures.
A wide range of controversial definitions and dynamic components surround the multi-dimensional concept of consciousness, with important reflections on the phenomenological description of ictal states relevant to epileptic seizures. The inadequacies of terminology, the insufficient emphasis on the subjective nature of consciousness, as well as the intrinsic limitations of the simple versus complex dichotomy for partial seizures, are to be considered in view of a modern definition of consciousness. In this paper, we review the difficulties encountered by clinicians in assessing the ictal conscious state in patients with epilepsy, and illustrate how a more sophisticated bi-dimensional model of consciousness can prove a valuable conceptual tool for the clinical assessment of ictal consciousness and the categorization of seizures.


Sildenafil inhibits the formation of superoxide and the expression of gp47 NAD[P]H oxidase induced by the thromboxane A2 mimetic, U46619, in corpus cavernosal smooth muscle cells.
To assess the effect of sildenafil on superoxide formation and p47(phox) (the active subunit of NADPH oxidase) expression in cultured corpus cavernosal smooth muscle cells (CVSMCs). CVSMCs derived from rabbit penis were incubated with U46619 (thromboxane A2 analogue) with or without sildenafil for 1 or 16 h at 37 degrees C. Superoxide dismutase-inhibitable superoxide formation was assessed using the reduction of ferricytochrome c measured spectrophotometrically, and gp47(phox) assessed using Western blot analysis. The role of NAD[P]H oxidase and cGMP was further studied by using specific inhibitors of each. Superoxide formation was significantly greater in cells incubated with U46619 after 1 and 16 h incubation than in controls, an effect blocked by NADP(H) oxidase inhibitors. These effects of U46619 were inhibited by sildenafil (1 and 10 nmol/L), which in turn were negated by the guanylyl cyclase inhibitor, ODQ; 10 nmol/L sildenafil inhibited p47phox expression induced by U46619. Sildenafil is a potent inhibitor of superoxide formation in CVSMCs. This effect is mediated through the inhibition of PDE-5 which in turn augments the inhibitory action of the NO-cGMP axis on NAD[P]H oxidase expression and activity. This mechanism constitutes a new pharmacological action of sildenafil, consolidates the potential role of superoxide in ED, and indicates that thromboxane A(2) may be an important mediator of intrapenile oxidative stress.


Evidence for the effectiveness of techniques To change physician behavior.
To understand the theory and results of how to improve physician performance, as part of overall health-care quality improvement. In particular, to study whether and how guideline production and dissemination affects physician performance. Review of meta-analyses and structured reviews; review of behavior change theories implicit in interventions to change physician performance. Primarily the United States. Various patients and physicians, determined by reviews. None. There is no unifying theory of physician behavior change tested among physicians in practice. Attempts to affect individual physicians' performance have often met with failure. Mixed results are found for almost all interventions reviewed. Multiple interventions yield better results. The answer to the question of what works to improve an individual physician's clinical performance is not simple. Emerging theory and evidence suggests that applications of behavior-change methods should not be focused on which tools (don't) always work. Instead, guideline development and implementation methods should be theory driven and evidence based (supported by evidence that proves the theory correct). In particular, the framework of evidence-based quality assessment offers some insight into past failures and offers hope for organizing attempts at guideline implementation.


Supremum, infimum and hyperlimits in the non-Archimedean ring of Colombeau generalized numbers.
It is well-known that the notion of limit in the sharp topology of sequences of Colombeau generalized numbers R ~ does not generalize classical results. E.g. the sequence 1 n ↛ 0 and a sequence ( x n ) n ∈ N converges if and only if x n + 1 - x n → 0 . This has several deep consequences, e.g. in the study of series, analytic generalized functions, or sigma-additivity and classical limit theorems in integration of generalized functions. The lacking of these results is also connected to the fact that R ~ is necessarily not a complete ordered set, e.g. the set of all the infinitesimals has neither supremum nor infimum. We present a solution of these problems with the introduction of the notions of hypernatural number, hypersequence, close supremum and infimum. In this way, we can generalize all the classical theorems for the hyperlimit of a hypersequence. The paper explores ideas that can be applied to other non-Archimedean settings.


Next-Generation Remote Hand Assessments: Cross-Platform DIGITS Web Application.
We have previously developed DIGITS, a platform for remote evaluation of range of motion, dexterity, and swelling of fingers for reducing barriers to accessing clinical resources. The current study was aimed at evaluating DIGITS across different devices with varied operating systems and camera resolutions using a single person's hands. Our team has now developed a web application version of the DIGITS platform, which makes it accessible on any device that is equipped with a camera, including computers, tablets, and smartphones. In the present study, we aimed to validate this web application by comparing flexion and extension measurements on the same person's hands using three different devices with cameras of different resolutions. The absolute difference, SD, standard mean error, and intraclass correlation coefficient were calculated. Additionally, equivalency testing was performed using the confidence interval approach. Our findings indicated that the differences in degree measured between the devices ranged from 2° to 3° when digit extension was assessed (all hand landmarks are visible in the camera's direct view) and from 3° to 8° when digit flexion was assessed (some of the hand landmarks are hidden from view). The intraclass correlation coefficient of individual trials ranged from 0.82 to 0.96 for extension and 0.77 to 0.87 for flexion across all devices. Additionally, within a 90% confidence interval, our data showed equivalency with measurements using three different devices. The absolute differences were within an acceptable 9° tolerance for measurements taken between devices for flexion and extension. Equivalency was observed for measurements of finger range of motion taken using DIGITS, regardless of devices, platforms, or camera resolutions. In summary, the DIGITS web application has good test-retest reliability to generate data on finger range of motion for hand telerehabilitation. DIGITS can reduce costs to patients, providers, and health care facilities for conducting postoperative follow-up assessments.


Pregnancy in GNE myopathy patients: a nationwide repository survey in Japan.
GNE myopathy is an autosomal recessive adult-onset distal myopathy. While a few case reports have described the progression of GNE myopathy during pregnancy, to our knowledge, none have examined disease progression after delivery or obstetric complications. This study aimed to reveal maternal complications, newborn complications, and the impact of pregnancy on disease progression in GNE myopathy patients. We conducted a questionnaire survey on pregnancy, delivery, and newborns involving female GNE myopathy patients who are currently registered in a national registry in Japan. The response rate for the questionnaire survey was 60.0% (72/120). Of the 72 respondents, 44 (61.1%) had pregnancy experience (average, 1.8 pregnancies; 53 pregnancies before onset and 28 after onset). The incidence of threatened abortion was 26.9% among post-onset pregnancies, which was higher compared to those of the general Japanese population (p = 0.03). No other maternal or infant complications were commonly observed. Over 80% were unaware of changes in disease progression during pregnancy (mean age, 32.8 ± 3.5 years) or after delivery (32.9 ± 3.8 years), while 19.0% experienced disease exacerbation within a year after delivery (30.0 ± 1.0 years). Six patients developed myopathy within a year after delivery (29.7 ± 4.6 years), while none developed myopathy during pregnancy. There were no serious maternal or newborn complications, and subjective progression did not differ during or after delivery in the majority of GNE myopathy patients. However, our findings suggest the importance of considering the possibility of threatened abortion and disease progression after delivery.


Factors influencing levels of 17-hydroxyprogesterone in very low birth weight infants and the relationship to death and IVH.
17-Hydroxyprogesterone, an intermediary hormone in cortisol synthesis, has been shown to be elevated in premature infants. However, the relationship between levels of 17-hydroxyprogesterone with death and intraventricular hemorrhage has not been extensively explored. The objective of this study was to determine the factors influencing 17-hydroxyprogesterone and determine if there is an association between intraventricular hemorrhage, mortality, and levels of 17-hydroxyprogesterone in a population of very low birth weight infants. Cohort study of very low birth weight infants cared for at a single level 3 NICU during a 1-year period from July 2001 to July 2002. Infants had a minimum of one screen for 17-hydroxyprogesterone and one cranial sonogram. 17-Hydroxyprogesterone was measured on the fifth day of life and at 2 to 4 weeks of life as part of the State of Delaware Newborn Screening Program. Statistical analysis included chi(2), Pearson correlation, multiple-linear regression, and logistic regression. Levels of 17-hydroxyprogesterone were higher at the time of the first screen compared to the second screen (28.3+/-25.6 vs 17.0+/-18.0 ng/ml, p=0.01), respectively. After controlling for potential confounding variables, gestational age, T(4), and prenatal steroids were all independently associated with 17-hydroxyprogesterone. However, logistic regression analysis showed no association between a 1 log increase in levels of 17-hydroxyprogesterone with the outcomes of death (odds ratio 1.8, 95% CI 0.6 to 5.6), severe IVH (0.7, 0.3 to 1.7), and death and/or severe intraventricular hemorrhage (0.9, 0.4 to 2.1). In our population of very low birth weight infants, low gestational age, low T(4), and prenatal steroids were all associated with an elevation in levels of 17-hydroxyprogesterone. High levels of 17-hydroxyprogesterone were not associated with death and/or severe IVH. Our data indicate that factors such as gestational age and antenatal steroids must be considered when interpreting 17-hydroxyprogesterone results from newborn screening.


The exploitation of floral nectar in Eucalyptus incrassata by honeyeaters and honeybees.
During October and November, 1977, a study of nectar production and nectarivore foraging in Eucalyptus incrassata was conducted at Wyperfeld National Park in south-eastern Australia in order to evaluate the extent to which introduced honeybees (Apis mellifera) compete with native honeyeaters for floral nectar. Data on nectar production, nectar availability, ambient air temperature and the numbers of visiting honeyeaters and honeybees were collected. Most of the daily nectar production in E. incrassata occurs early in the morning when temperatures are too low for insects to forage. In addition, insects, particularly honeybees, are unable to exploit nectar in the youngest flowers because the stamens are clustered tightly around the style. As a result of these temporal and structural characteristics of the flowers, honeyeaters are able to harvest most of the nectar. Honeybees potentially have access to 35-47% of the average daily production of floral nectar in E. incrassata and actually harvest considerably less. These data show that E. incrassata flowers are adapted to restrict insect foragers despite their superficially unspecialized appearance. Eight forest and woodland eucalypts do not have a flower stage which excludes insects and the significance of this difference is discussed.


Mathematics of three-dimensional eye rotations.
The recording of three-dimensional eye position has become the accepted standard in oculomotor research. In this paper we review the mathematics underlying the representation of three-dimensional eye movements. Rotation matrices, rotation vectors and quaternions are presented, and their relations described. The connection between search coils and rotation matrices is explained, as well as the connection between eye position and eye velocity. While examples of applications of the formulas to vestibulo-ocular research are given, the methods and mathematical analyses are also useful for studying other motor systems.


Blurring of the vessels of the interhemispheric fissure in multislice CT angiography: a sign of meningeal carcinomatosis.
Meningeal carcinomatosis remains a challenging diagnosis to make, with both cerebrospinal fluid (CSF) analysis and radiological methods having a limited sensitivity. We aimed at describing a possible diagnostic sign of multislice CT angiography (MS-CTA) in the diagnosis of meningeal carcinomatosis. Upon retrospective analysis of MSCT angiographies of the brain, a conspicuous sign of the vessels of the interhemispheric fissure was noted in five patients. Cranial MSCT angiographies were performed with a standardized protocol (120 kV, 200 mA s, collimation of 4x1 mm, table feed per rotation 4 mm). We injected 120 ml of nonionic contrast medium as a bolus, and data acquisition was started after a fixed delay of 35 s. In order to elucidate the finding, correlation with clinical follow-up and/or CSF findings was performed for all patients. In five patients there was a blurring, an increased number, and a pathologic configuration of the vessels of the interhemispheric fissure. All five patients with this sign had clinical signs and symptoms of meningeal carcinomatosis. Three patients had positive CSF cytology, one further patient had follow-up spinal MRI 6 weeks later demonstrating meningeal carcinomatosis. One patient declined lumbar puncture. MS-CTA has the capacity to demonstrate a pathologic configuration of the vessels of the interhemispheric fissure in patients with meningeal carcinomatosis. This sign may serve as an indicator of meningeal carcinomatosis and should raise the suspicion of this disease entity.


Examining Trends in Beverage Sales in New York City During Comprehensive Efforts to Reduce Sugary Drink Consumption, 2010-2015.
Since 2006, New York City (NYC) has attempted to reduce sugary drink consumption through several population-based initiatives, media campaigns and policy proposals. We estimated trends in the relative market share of sugary drinks and other beverage categories in NYC, using over 5 years of weekly, point-of-sale data from a retailer sample. We used an interrupted time series approach to assess whether changes in NYC beverage purchasing patterns occurred following the announcement of a proposed portion cap rule for consumer purchases of sugary drinks. Overall, market share of sugary drinks declined in NYC between 2010 and 2015. While the proportion of beverage volume sold that was sugary drinks was stable prior to the May 2012 portion cap rule announcement, decreases of 1.25% per year were observed in the period following the announcement compared to the period before (95% confidence interval (CI) - 1.60, - 0.90). Water/seltzer market share was increasing prior to the announcement and increased by an additional 1.03% per year in the post-announcement period (95% CI 0.48, 1.57). City-led efforts to increase public awareness about sugary drink-associated health risks in NYC may have led to reductions in consumer purchases of these beverages. Though never implemented, the portion cap proposal and accompanying media coverage may have contributed to decreases in sugary drink sales.


Neu-Laxova syndrome: a case report.
Neu-Laxova syndrome is a rare form of congenital malformation characterized by intrauterine growth retardation, microcephaly with bizarre facial features, short neck, apparent edema, scaly skin, and perinatal death. Chromosomal analysis in reported cases has revealed a normal karyotype, and an autosomal recessive transmission has been postulated. We present a case of Neu-Laxova syndrome. The pathologic features and the prenatal radiographic appearance are described.


[Triploid clone observed at blastic crisis in chronic myelogenous leukemia with complex Ph1 translocation (9; 22; 12)].
A 56-year-old female, who was diagnosed as CML in 1983 and had been well controlled with busulfan, was admitted to our hospital because of fever and iliac bone pain. Peripheral blood showed leukocytosis (WBC 70,000/microliters and bone marrow was normocellular with 53% leukemic cells, suggesting that she was in the blastic crisis. Chromosomal analysis of bone marrow cells at that time revealed t (9; 22; 12) and some additional abnormalities. The number of chromosomes ranged from 44 to 131 and the mode of chromosome number was 65. She was treated with combination regimen consisting of vincristine, 6-mercaptopurine and prednisolone and right iliac tumor was irradiated. Three months after admission, she died of DIC and pulmonary insufficiency due to leukemic infiltration.


Nighttime blood pressure, nighttime glucose values, and target-organ damages in treated type 2 diabetes patients.
The associations between nighttime blood pressure (BP) and cardiovascular risk are well established. However, the associations between nighttime glucose values, including nocturnal hypoglycemia, and cardiovascular risk in diabetes remain unclear. In this cross-sectional study of 49 treated type 2 diabetes patients (mean, 67.3 years; 61.0% men; mean treatment duration, 9.4 years), we performed 24-h continuous glucose monitoring simultaneously with BP monitoring, and evaluated several target-organ damages (echocardiographic left ventricular mass index [LVMI], urinary albumin excretion [UAE], carotid-artery intima-media thickness [IMT], and brachial-ankle pulse wave velocity [baPWV]). Nighttime average systolic BP values were independently associated with the extent of LVMI, log-transformed UAE, or baPWV (all P < 0.05). In contrast, nighttime average glucose values, rather than daytime glucose values or glucose variability, were independently associated with the extent of common carotid-artery IMT (CCA-IMT) or baPWV (all P < 0.05). We divided the study participants into 3 groups according to the nighttime glucose values (a group with nighttime average glucose values <161 mg/dl [reference], a group with nocturnal hypoglycemia [<70 mg/dl at least one point during sleep], and a group with nighttime average glucose values ≥161 mg/dl), and compared the extent of target-organ damages among them. Patients with nighttime average glucose values ≥161 mg/dl, but not those with nocturnal hypoglycemia, had the highest values of CCA-IMT or baPWV among the 3 groups, and the differences remained significant even after adjustment for covariates (both trend P < 0.05 by ANCOVA). Among treated type 2 diabetes, high nighttime BP and/or glucose values were associated with a high degree of cardiovascular remodeling.


Clinical efficacy of intraoperative Cell Saver autologous blood salvage in emergency surgery for massive hemothorax.
The objective of this study was to investigate the efficacy of intraoperative Cell Saver blood salvage during emergency surgery for massive hemothorax on minimizing perioperative allogeneic red blood cell (RBC) transfusion. Fourteen consecutive patients of massive hemothorax with more than 800 cc of intrathoracic bleeding estimated by chest X-ray and/or chest computed tomography (CT) scan at presentation between 2009 and 2021 were retrospectively reviewed. Intraoperative Cell Saver blood salvage was performed in 11 patients (Cell Saver group) with a median volume of 820 cc (range, 421-1700 cc). The amount of perioperative allogeneic RBC transfusion in the Cell Saver group (median, 4 units) was significantly smaller than that in the non-Cell Saver group (median, 10 units) (P = 0.009). The volume of Cell Saver autologous transfusion in 6 patients without preoperative chest tube drainage (median, 1114 cc) was significantly larger than that in 5 patients who had preoperative drainage (median, 660 cc) (P = 0.0173). In conclusion, the utilization of intraoperative blood salvage in emergency surgery for massive hemothorax along with limiting the amount of preoperative chest tube drainage is an efficient strategy to minimize perioperative allogeneic RBC transfusion.


Diagnosis and management of deep vein thrombosis of the upper extremity: a review.
Deep vein thrombosis of the upper extremity is an increasing clinical problem due to the use of long-term indwelling catheters for chemotherapy or long-term feeding. The clinical diagnosis is difficult to make, and various imaging modalities have been used for this purpose. The use of (interventional) radiological procedures has been advancing in recent years. This review describes the clinical background, the imaging modalities that may be employed, treatment options and outcome of patients with upper extremity thrombosis.


Ameliorative effect of nanocurcumin and Saccharomyces cell wall alone and in combination against aflatoxicosis in broilers.
The adverse effect of aflatoxin in broilers is well known. However, dietary supplementation of Saccharomyces cell wall and/or Nanocurcumin may decrease the negative effect of aflatoxin B1 because of the bio-adsorbing feature of the functional ingredients in Yeast Cell Wall and the detoxification effect of curcumin nanoparticles. The goal of this study was to see how Saccharomyces cell wall/Nanocurcumin alone or in combination with the aflatoxin-contaminated diet ameliorated the toxic effects of aflatoxin B1 on broiler development, blood and serum parameters, carcass traits, histology, immune histochemistry, liver gene expression, and aflatoxin residue in the liver and muscle tissue of broilers for 35 days. Moreover, the withdrawal time of aflatoxin was measured after feeding the aflatoxicated group an aflatoxin-free diet. Broiler chicks one day old were distributed into five groups according to Saccharomyces cell wall and/or nanocurcumin with aflatoxin supplementation. The G1 group was given a formulated diet without any supplements. The G2 group was supplemented with aflatoxin (0.25 mg/kg diet) in the formulated diet. The G3 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in the formulated diet. The G4 group was supplemented with aflatoxin (0.25 mg/kg diet) and nanocurcumin (400 mg/kg) in the formulated diet. The G5 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in combination with nanocurcumin (200 mg/kg) in the formulated diet. According to the results of this study, aflatoxin supplementation had a detrimental impact on the growth performance, blood and serum parameters, carcass traits, and aflatoxin residue in the liver and muscle tissue of broilers. In addition, aflatoxin supplementation led to a liver injury that was indicated by serum biochemistry and pathological lesions in the liver tissue. Moreover, the shortening of villi length in aflatoxicated birds resulted in a decrease in both the crypt depth ratio and the villi length ratio. The expression of CYP1A1 and Nrf2 genes in the liver tissue increased and decreased, respectively, in the aflatoxicated group. In addition, the aflatoxin residue was significantly (P ≤ 0.05) decreased in the liver tissue of the aflatoxicated group after 2 weeks from the end of the experiment. Saccharomyces cell wall alone or with nanocurcumin attenuated these negative effects and anomalies and improved all of the above-mentioned metrics.


Tobacco smoke. Effects on pulmonary host defense.
Tobacco smoke affected both the metabolism and function of pulmonary alveolar macrophages (PAM). Phagocytosis of viable Staphylococcus aureus and inert starch particles was minimally but consistently depressed in PAM from rats exposed to tobacco smoke for six months. Oxygen consumption, superoxide and hydrogen peroxide release, and hexose monophosphate shunt activity were elevated in cells from smokers. Oxidation of glucose, labelled in the carbon-six position, remained unchanged. All observed effects of tobacco smoke on oxygen metabolism occurred during phagocytosis and did not affect the basal metabolism of the nonstimulated cell.


4-Hydroxy-3-nitrophenylglyoxal. A chromophoric reagent for arginyl residues in proteins.
The chromophoric reagent, 4-hydroxy-3-nitrophenylglyoxal, is highly selective for the modification of arginine in aqueous solution at pH 7--9. The reagent also inactivates creatine kinase (ATP:creatine N-phosphotransferase, EC 22.214.171.124) in a manner analogous to that reported with phenylglyoxal.


Rapid hemostatic antibacterial self-gelling powder based on methacryloylsulfonyl betaine and quaternized carboxymethyl chitosan.
Hemostatic powders can be used for deep wounds and wounds with irregular shapes that are frequently inaccessible to traditional hemostatic dressings like hemostatic gauze, sponges, and foams. In this study, sulfobetaine methacrylate (SBMA) and quaternized carboxymethyl chitosan (QCCS) were combined to create an antibacterial hemostatic hydrogel through photopolymerization under green LED irradiation, which was then changed into PSBMA/QCCS powder. PSBMA/QCCS powder could quickly form hydrogel with strong wet adhesion. The internal structure, water absorption capacity, and adhesion properties of the powder were evaluated. The coagulation ability, antimicrobial properties, and biocompatibility of the powder were also characterized. The PSBMA/QCCS powder could aggregate blood cells and platelets to enhance hemostasis. Meanwhile, PSBMA/QCCS powder also showed effective antibacterial ability against both gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli). In summary, PSBMA/QCCS powder is a promising hemostatic agent with the characteristics of quick hemostasis, tough wet adhesion, satisfactory biocompatibility, considerable antibacterial effect, and adaptability to any irregularly shaped wounds.


Mechanisms of charge transfer and redistribution in LaAlO3/SrTiO3 revealed by high-energy optical conductivity.
In condensed matter physics the quasi two-dimensional electron gas at the interface of two different insulators, polar LaAlO3 on nonpolar SrTiO3 (LaAlO3/SrTiO3) is a spectacular and surprising observation. This phenomenon is LaAlO3 film thickness dependent and may be explained by the polarization catastrophe model, in which a charge transfer of 0.5e(-) from the LaAlO3 film into the LaAlO3/SrTiO3 interface is expected. Here we show that in conducting samples (≥ 4 unit cells of LaAlO3) there is indeed a ~0.5e(-) transfer from LaAlO3 into the LaAlO3/SrTiO3 interface by studying the optical conductivity in a broad energy range (0.5-35 eV). Surprisingly, in insulating samples (≤ 3 unit cells of LaAlO3) a redistribution of charges within the polar LaAlO3 sublayers (from AlO2 to LaO) as large as ~0.5e(-) is observed, with no charge transfer into the interface. Hence, our results reveal the different mechanisms for the polarization catastrophe compensation in insulating and conducting LaAlO3/SrTiO3 interfaces.


[Comparative determination of the potential for activating lipid peroxidation of the adrenal cortex, liver and heart in various animals].
Studies have been made on the rate of spontaneous, ascorbate- and NADP.H-dependent lipid peroxidation in the adrenal cortex, liver heart of rats, rabbits and cattle. It was shown that in spite of some species differences in predisposition of tissues to lipid peroxidation. The highest rate of this process is characteristic of the liver of all the animals investigated.


Neutral polysaccharide from Cedrela tubiflora with anticomplementary activity.
A water-soluble polysaccharide extracted from leaves of the Meliaceae Cedrela tubiflora was separated into neutral and acidic polysaccharide fractions. The best anticomplementary activity was exhibited by the neutral product which was further purified by means of gelpermeation chromatography. The composition and methylation analysis of the purified product were determined.


Economic Burden of Surgical Management of Prosthetic Joint Infections Following Hip and Knee Replacements in Alberta, Canada: An analysis and comparison of two major urban centers.
Complex surgical site infections (SSIs) and revisions for these infectious complications following total knee and hip arthroplasties are associated with significant economic costs. To evaluate the cost of one-stage and two-stage revisions; debridement, antibiotic, and implant retention (DAIR) and DAIR with liner exchange for complex hip or knee SSIs in Alberta, Canada. We used the Alberta Health Services Infection Prevention and Control database to identify individuals >18 years old from the two major urban centers in Alberta, Calgary, and Edmonton zone, with complex hip or knee SSIs who underwent surgical intervention between April 1, 2012, and March 31, 2019. Micro-costing and gross-costing methods were used to estimate 12 and 24-month costs following the initial hospital admission for arthroplasty. Subgroup, inverse gaussian and gamma regression analysis were used to evaluate the associations of the revision procedure, age, sex, and comorbidities on cost. A total of 382 patients with complex SSIs were identified with a mean age of 66.1 years. DAIR and DAIR with liner exchange resulted in the lowest 12- and 24-month costs at $53,197 (95% CI, $38,006 - $68,388) and $57,340 (95% CI, $48,576 - $66,105), respectively; two-stage revision was the costliest procedure. Most of the incurred costs (>98%) were accrued within the first 12 months following the initial procedure. Medical costs are highest 12 months following initial arthroplasty and for two-stage revisions in hip and knee complex SSI.


Convergence of therapy-induced senescence (TIS) and EMT in multistep carcinogenesis: current opinions and emerging perspectives.
Drug induced resistance is a widespread problem in the clinical management of cancer. Cancer cells, when exposed to cytotoxic drugs, can reprogram their cellular machinery and resist cell death. Evasion of cell death mechanisms, such as apoptosis and necroptosis, are part of a transcriptional reprogramming that cancer cells utilize to mediate cytotoxic threats. An additional strategy adopted by cancer cells to resist cell death is to initiate the epithelial to mesenchymal transition (EMT) program. EMT is a trans-differentiation process which facilitates a motile phenotype in cancer cells which can be induced when cells are challenged by specific classes of cytotoxic drugs. Induction of EMT in malignant cells also results in drug resistance. In this setting, therapy-induced senescence (TIS), an enduring "proliferative arrest", serves as an alternate approach against cancer because cancer cells remain susceptible to induced senescence. The molecular processes of senescence have proved challenging to understand. Senescence has previously been described solely as a tumor-suppressive mechanism; however, recent evidences suggest that senescence-associated secretory phenotype (SASP) can contribute to tumor progression. SASP has also been identified to contribute to EMT induction. Even though the causes of senescence and EMT induction can be wholly different from each other, a functional link between EMT and senescence is still obscure. In this review, we summarize the evidence of potential cross-talk between EMT and senescence while highlighting some of the most commonly identified molecular players. This review will shed light on these two intertwined and highly conserved cellular process, while providing background of the therapeutic implications of these processes.


Cytotoxicity of wound dressing materials assessed using cultured skin equivalents.
An in vitro system, based on the Bell model of cultured composite skin equivalents, was used to assess the effect of a number of wound dressing materials on DNA synthesis. DNA synthesis was quantified using immunocytohistochemical identification of incorporated bromodeoxy-uridine and the percentage of labelled cells measured, following 7 days' exposure to the dressing material. Differences in labelling index were observed from replica gels covered by different dressing materials and between dressings of the same type of material, but made by different manufacturers.


The α-Arrestin Bul1p Mediates Lactate Transporter Endocytosis in Response to Alkalinization and Distinct Physiological Signals.
Eukaryotic α-arrestins connect environmental or stress signaling pathways to the endocytosis of plasma membrane transporters or receptors. The Saccharomyces cerevisiae lactate transporter Jen1p has been used as a model cargo for elucidating the mechanisms underlying endocytic turnover in response to carbon sources. Here, we discover a novel pathway of Jen1p endocytosis mediated by the α-arrestin Bul1p in response to the presence of cycloheximide or rapamycin, or prolonged growth in lactate. While cycloheximide or rapamycin modify cells pleiotropically, the major effect of prolonged growth in lactate was shown to be external pH alkalinization. Importantly, employment of specific inactive Jen1p versions showed that Bul1p-dependent endocytosis requires lactate transport, according to the signal imposed. Our results support a model where conformational changes of Jen1p, associated with substrate/H+ symport, are critical for the efficiency of Bul1p-dependent Jen1p turnover.


Implementing pre-exposure prophylaxis for HIV prevention in women: the role of the obstetrician-gynecologist.
Pre-exposure prophylaxis is a powerful HIV prevention tool that can reduce the risk of acquiring HIV by >90% from unprotected sex and >70% from injection drug use. The peripartum period is a time of heightened HIV risk, which underscores the need for HIV prevention counseling and the provision of biomedical interventions in all stages of a woman's reproductive life. It is important that women receive nonjudgmental care, have access to discussions of HIV risk, and are provided with pre-exposure prophylaxis counseling from their women's health practitioners. Obstetrician-gynecologists and other women's health providers are uniquely positioned to identify women who would benefit from pre-exposure prophylaxis and provide it in trusted clinical settings.


Glucose-induced Akt1 activation mediates fibronectin synthesis in endothelial cells.
Increased expression and decreased degradation of extracellular matrix (ECM) proteins are key features of chronic diabetic complications. Fibronectin, a predominant ECM protein, has been shown to be overexpressed in all target organs of diabetic complications and in endothelial cells cultured in high levels of glucose. The present study was designed to elucidate the role of protein kinase B (Akt/PKB) in glucose-induced fibronectin mRNA expression and protein production in vascular endothelial cells. Human umbilical vein endothelial cells were cultured in the presence of high glucose to study Akt/PKB activation. The upstream and downstream mediators in the Akt/PKB pathway were also investigated using dominant negative transfections and specific inhibitors of signalling pathways. Cells were subjected to real time RT-PCR, western blotting, and confocal microscopy to assess Akt1/PKBalpha activation and fibronectin mRNA expression and protein production. To detect transcription factor activation, electrophoretic mobility shift assay was carried out. Our data demonstrate that fibronectin mRNA expression and protein production that are induced by high glucose are mediated via activation of Akt/PKB, which is modulated by mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C. Glucose-induced fibronectin mRNA expression and protein production are also mediated by Akt1/PKBalpha-dependent activation of the transcription factors nuclear factor-kappaB and activating protein-1. Our study provides insight into the mechanical basis of glucose-induced increases in fibronectin mRNA expression and protein production. High levels of glucose may increase fibronectin mRNA expression and protein production by activating Akt/PKB.


Efficient design of peptide-binding polymers using active learning approaches.
Active learning (AL) has become a subject of active recent research both in industry and academia as an efficient approach for rapid design and discovery of novel chemicals, materials, and polymers. Herein, we have assessed the applicability of AL for the discovery of polymeric micelle formulations for poorly soluble drugs. We were motivated by the key advantages of this approach making it a desirable strategy for rational design of drug delivery systems due toto its ability to (i) employ relatively small datasets for model development, (ii) iterate between model development and model assessment using small external datasets that can be either generated in focused experimental studies or formed from subsets of the initial training data, and (iii) progressively evolve models towards increasingly more reliable predictions and the identification of novel chemicals with the desired properties. In this study, we compared various AL protocols for their effectiveness in finding biologically active molecules using synthetic datasets. We have investigated the dependency of AL performance on the size of the initial training set, the relative complexity of the task, and the choice of the initial training dataset. We found that AL techniques as applied to regression modeling offer no benefits over random search, while AL used for classification tasks performs better than models built for randomly selected training sets but still quite far from perfect. Using the best performing AL protocol,. Finally, the best performing AL approach was employed to discover and experimentally validate novel binding polymers for a case study of asialoglycoprotein receptor (ASGPR).


Neuroradiological features of cervical and cervicothoracic intraspinal subependymomas: a study of five cases.
To characterize the magnetic resonance imaging (MRI) findings in a series of five patients with cervical and cervicothoracic intraspinal subependymomas and to increase awareness of this neoplasm. The clinical and radiological profiles of five patients who were diagnosed with subependymoma based on histopathological findings were retrospectively studied and compared with previously reported cases. All patients underwent enhanced MRI. One patient presented with a subependymoma of the cervical spine, one patient harboured a thoracic spinal subependymoma, and the other patients presented with cervicothoracic subependymomas. All lesions were hypointense on T1-weighted images and hyperintense on T2-weighted images. One lesion grew centrally, whereas the others demonstrated eccentricity. Partially faint enhancement was noted in four cases, and one case demonstrated multinodular moderate enhancement. Cervical and cervicothoracic intraspinal subependymomas can be distinguished on MRI images. Specifically, a faintly enhanced or non-enhanced heterogeneous intramedullary lesion that exhibits a slowly deteriorating clinical course may be indicative of a subependymoma. In such cases, resection is expected to yield favourable outcomes.


Leg fat mass as measured by dual X-ray absorptiometry (DXA) impacts insulin resistance differently in obese women versus men.
To investigate the association between regional fat mass (FM) and insulin resistance and dyslipidaemia in obese women and men. Body composition was measured by dual-energy X-ray absorptiometry (DXA) in 109 obese women and 113 obese men. Insulin resistance was measured by (HOMA-IR); insulin sensitivity was estimated by metabolic clearance rate (MCRestOGTT) and insulin secretion by HOMAsecr. Serum lipids were assessed. In women, leg FM was negatively (favourably) associated with HOMA-IR and cholesterol/HDL-cholesterol ratio (p<0.05). Trunk FM was positively (unfavourably) associated with HOMA-IR. Leg/trunk FM ratio was negatively associated with HOMA-IR (p<0.001), cholesterol/HDL-cholesterol ratio (p<0.001) and triglycerides (p<0.01); positively (favourably) with MCRestOGTT (p<0.01) and HDL-cholesterol (p<0.05). No associations were found in men. In women, multiple regression analysis demonstrated that leg/trunk FM ratio was the only explanatory FM for HOMA-IR and MCRestOGTT (R(2) = 0.23 and R(2) = 0.13, respectively; p<0.001), but postmenopausal status was also of importance (R(2) = 0.23, p = 0.019 and R(2) = 0.29, p = 0.015, respectively). Leg FM has a favourable influence on insulin resistance and dyslipidaemia in obese women, but not demonstrated in this cohort of obese men.


Mutational Analysis of EZH2 Gene in Patients with Colorectal Adenoma Reveals a Genetic Variant Associated with Risk of Malignant Transformation.
Several studies have revealed that chromatin modifications lead to activation or repression of multiple genes including oncogenes and tumor suppressor genes. Inactivation mutation in EZH2 gene would result in activation of oncogenes. The aim of this case-control study was to identify mutations in the EZH2 gene, to study their prevalence among Jordanian patients with colorectal adenoma and to determine how these mutations could be related to colorectal cancer (CRC) progression. EZH2 gene sequencing was done by Sanger method for 100 DNA samples, extracted from blood of 50 patients, and 50 controls. Sequencing results were analyzed by Chromaspro and mutational effects were predicted by Mutation Taster bioinformatics tool. Four variants were identified in Jordanian patients with adenoma; Two novel variantsc.1941T>A and c.2201G>C and two reported variants, g.73038C>T and g.75508A>C. g.73038C>T is the most common germline variant identified in this study. A significant association between the presence of c.2201G>C mutation and colorectal adenoma was found (p value < 0.05). The present study identified several variants in EZH2 gene among Jordanians with colorectal adenoma.


Altered response of reperfused myocardium to repeated coronary occlusion in dogs.
It is hypothesized that myocardium subjected to a 5 minute period of coronary occlusion and a 30 minute period of reperfusion has latent abnormalities that become overt when the reperfused myocardium is "challenged" by a subsequent coronary occlusion. This hypothesis is clinically relevant because reperfused myocardium is frequently subjected to recurrent ischemia, as in patients with unstable angina, vasospastic angina or recurrent thrombosis after initial coronary occlusion and thrombolysis. In 19 open chest dogs, the response of regional myocardial function to brief coronary occlusions was studied. Systolic wall thickening and diastolic thinning were measured using a specially developed miniature 5 MHz echocardiographic transducer fixed to the epicardium by suction. All 19 dogs underwent an initial "challenge" coronary occlusion (30 seconds). Thereafter, the control group (n = 8) underwent no intervention for 30 minutes, while the intervention group (n = 11) underwent 5 minutes of coronary occlusion followed by 30 minutes of reperfusion. All dogs were then subjected to a second "challenge" coronary occlusion (30 seconds). In the control group, responses to the second challenge occlusion were the same as to the first occlusion. In the intervention group, regional and global systolic function and myocardial perfusion after the 5 minute coronary occlusion intervention returned to baseline levels, but the response to the second challenge coronary occlusion was significantly different in the intervention group.(ABSTRACT TRUNCATED AT 250 WORDS)


Unidirectional transport of orthophosphate across the envelope of isolated cauliflower-bud amyloplasts.
Isolated amyloplasts from cauliflower (Brassica oleracea L. var botrytis) buds are able to export orthophosphate unidirectionally into the incubation medium. This orthophosphate transport appears to be protein-mediated, as indicated by the following observations: (i) low temperature and the presence of inhibitors of protein-mediated transport reduced the rate of orthophosphate export, and (ii) the rate of orthophosphate export became saturated with rising internal substrate concentrations. Micromolar concentrations of 4,4'-diisothiocyano-2,2'-stilbene disulphonic acid inhibited the rate of unidirectional orthophosphate export, thus indicating the involvement of the amyloplastic glucose-6-phosphate (Glc6P)translocator in the unidirectional export of orthophosphate. The effect of rising concentrations of orthophosphate upon the activity of ADP glucose pyrophosphorylase in desalted extracts was determined. Orthophosphate given in concentrations similar to those measured in the amyloplastic stroma under conditions of steady-state rates of Glc6P-dependent starch synthesis inhibited the activity of ADP-glucose pyrophosphorylase significantly. However, even under strong limiting substrate conditions the residual activity was sufficient to catalyze the flux of carbon into starch. The maximal rates of orthophosphate transport (in the counter-exchange mode) by isolated spinach (Spinacia oleracea L.) chloroplasts and by isolated cauliflower-bud amyloplasts were also determined. These rates were compared with the maximal rates of undirectional orthophosphate export by these plastids. From these measurements we can conclude that, compared with spinach chloroplasts, isolated amyloplasts of cauliflower exhibit a fivefold greater ratio of unidirectional orthophosphate transport to maximal rate of orthophosphate transport in the counter-exchange mode compared to spinach chloroplasts. The determined rate of maximal unidirectional orthophosphate export is sufficient to catalyze the release of additional inorganic phosphate liberated in the amyloplastic stroma during the process of Glc6P-dependent starch synthesis.


Distal Brachial Artery Perforator flap: a new chimeric option for complex hand and digits defects.
Reconstruction of fingers pose unique challenges, as a thin and flexible flap is needed in order to guarantee a good functional outcome. For the first time, in this report, we present the DBAp (distal brachial artery perforator) flap, based on the distal perforator closer to the medial epicondyle. The DBAp flap was used to reconstruct complex digit defects as free flap, and to cover an elbow defect while raised as a propeller. Four patients underwent finger reconstruction (free flaps): two patients presented an unstable finger scar following previous surgery, whereas the other two patients presented a terminalized finger at the level of the middle phalanx. A further patient presented a post-traumatic loss of substance at the elbow and was reconstructed using a perforator propeller DBAP flap. Loss of tissues included skin and subcutaneous tissue in all patients and in one patient it included a bone component. Flap dimensions ranged from 48 to 18 cm2 (average: 32 cm2). Among complications, patient n.2 flap presented a marginal flap necrosis requiring a small skin graft after necrosis debridement. The DBAp flap provides a slim, glabrous and pliable skin tissue with a well-hidden donor site scar and thanks to the anatomic location of the distal perforator can be designed to include a vascularized bone graft from the medial epicondyle. Despite the low number of cases, we believe that this flap should be considered as a dependable and effective source for complex reconstructions of both soft tissue and bone in fingers.


The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage.
Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP), as a derivative from the carcinoma-stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. In a retrospective study of 63 patients with colon cancer (stage I-III, 1990-2001) the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I-III, 1980-1992). (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy.) Of 122 analyzed patients 33 (27.0%) had a low CP and 89 (73.0%) a high CP. The analysis of mean survival revealed: overall-survival (OS) 2.13 years, disease-free- survival (DFS) 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p<0.0001, DFS p<0.0001) with hazard ratio's of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OS p<0.001, OS p<0.001). The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups.


A clinicopathological study on soft tissue tumors of the head and neck.
The present study consists of 651 cases of soft tissue tumors originating in the head and neck area. Among these tumors 628 were benign (96%), while there were only 23 malignant cases (4%). In the benign group hemangiomas showed the highest incidence (47%) followed by tumors of adipose tissue (19%) and those of peripheral nerves (12%). Rare tumors consisted of nodular fascitis, hibernoma, lipoblastomatosis, glomus tumor, granular cell tumor, and chondroma. The majority of cases in the malignant group were either those of muscle origin or blood vessel origin. Excepting for two cases of rhabdomyosarcoma of the embryonal type and two cases of angiosarcoma, all showed recurrence and/or metastasis and terminated in death. Three cases of liposarcoma of either well-differentiated or myxoid type had a good prognosis with all three living for 3 or more years without any recurrence. Other malignant tumors consisted of malignant schwannoma, fibrosarcoma, malignant fibrous histiocytoma, alveolar soft part sarcoma, and chordoma. The age, sex, anatomical location, and differential diagnosis have also been described.


Facile synthesis of tunable silver nanostructures for antibacterial application using cellulose nanocrystals.
In this study, we report a facile and environmentally friendly strategy for synthesis of well dispersed and stable silver nanostructures using cellulose nanocrystals in aqueous solution without employing any other reductants, capping or dispersing agents. Importantly, it is feasible to adjust the morphology of the silver nanostructures by varying the precursor AgNO3 concentration. Silver nanospheres were formed when the AgNO3 concentration was 0.4 mM, while the dendritic nanostructures predominated when the AgNO3 concentration was increased to 250 mM. The antibacterial activity of the two different silver nanostructures against Escherichia coli and Staphylococcus aureus was characterized. Dendritic nanostructure showed a better antibacterial activity than that of silver nanosphere. The approach presented in this paper offers a very promising route to noble metal nanoparticles using renewable reducing agents.


Analysis of oseltamivir active metabolite, oseltamivir carboxylate, in biological materials by HPLC-UV in a case of death following ingestion of Tamiflu.
An HPLC-UV method was established for determination of oseltamivir carboxylate, an active metabolite of oseltamivir, in biological materials. Oseltamivir carboxylate and floropipamide (internal standard) were extracted by using a mixed mode cation exchange extraction cartridge. The recovery yields of oseltamivir carboxylate from spiked blood at concentrations 0.1microg/ml and 1.0microg/ml were 103.8+/-16.9% and 95.0+/-4.3%, respectively. Linearity was obtained in the concentration from 0.1 to 3.0microg/ml. The detection limit was 0.04microg/ml (S/N=3). This method was applied to a case of death from falling after ingestion of a Tamiflu capsule containing 75mg of oseltamivir. Concentration of oseltamivir carboxylate in the femoral blood was 0.4microg/ml. The highest concentration in all specimens was in the liver at 18.3microg/g. In all brain samples, the concentrations were not higher than the quantification limit (0.1microg/g).


Anisakiasis confirmed by radiography of the large intestine.
As yet, there has been no report of acute anisakiasis of the large intestine diagnosed by radiographic demonstration of the larvae. We present such a case, in which roentgenologic examination revealed Anisakis larvae in the ascending colon.


The modulation of voltage-gated potassium channels by anisotonicity in trigeminal ganglion neurons.
Voltage-gated potassium channels (VGPCs) play an important role in many physiological functions by controlling the electrical properties and excitability of cells. Changes in tonicity in the peripheral nervous system can activate nociceptors and produce pain. Here, using whole cell patch clamp techniques, we explore how hypo- and hypertonicity modulate VGPCs in cultured rat and mouse trigeminal ganglion (TG) neurons. We found that hypo- and hypertonicity had different effects on slow-inactivating K+ current (IK) and fast-inactivating K+ current (IA): hypotonicity increased IK but had no effect on IA while hypertonicity depressed both IK and IA. The increase of IK by hypotonicity was mimicked by transient receptor potential vanilloid 4 (TRPV4) receptor activator 4alpha-phorbol-12,13-didecanoate (4alpha-PDD) but hypotonicity did not exhibit increase in TRPV4-/- mice TG neurons, suggesting that TRPV4 receptor was involved in hypotonicity-induced response. We also found that inactivation of PKC selectively reversed the increase of IK by hypotonicity, whereas antagonism of G-protein selectively rescued the inhibitions of IK and IA by hypertonicity, indicating that different intracellular signaling pathways were required for the modulation by hypo- and hypertonicity. In summary, changes in osmolality have various effects on IK and IA and different receptors and second messenger systems are selective for the modulation of VGPCs induced by hypo- versus hypertonicity.


Reducing central venous catheter-associated primary bloodstream infections in intensive care units is possible: data from the German nosocomial infection surveillance system.
The German Nosocomial Infection Surveillance System (KISS) began in 1997 as a nationwide surveillance project for voluntary registration of nosocomial infections in intensive care units (ICUs). This study investigates trends in the rates of central venous catheter (CVC)-associated primary bloodstream infections (BSIs) in ICUs since participation in KISS. Eighty-four ICUs that had participated in KISS for at least 24 months were considered for more detailed analysis. Monthly rates of primary BSI for the 84 ICUs were pooled for the 24 months. The best model for describing the curve of reduction was sought. Additionally, incidence densities were compared using the z test. For the 212 ICUs participating, a relative 25.7% decrease (from 2.1 to 1.6 primary BSIs per 1,000 CVC-days) was observed from January 1997 to June 2001. The 84 ICUs that participated in KISS for a minimum of 24 months accumulated 552,359 patient-days and 404,897 CVC-days during their 24 months. A linear regression model was selected to explain the curve of primary BSI reduction in the 84 ICUs. It showed a decrease from 2.1 to 1.5 primary BSIs per 1,000 CVC-days, meaning an overall relative reduction of 28.6% during the 2-year observation period. These results were significant (Student's t test for the monthly reduction coefficient; P = .04). The reduction of primary BSIs was shown for both clinical sepsis and laboratory-confirmed, CVC-associated primary BSIs. Performing surveillance with KISS was associated with a reduction of the rates of CVC-associated primary BSIs in ICU patients.


The effect of blood cooling prior to granulocyte collection.
A study was designed to test the hypothesis that cooling blood before it enters a continuous-flow blood cell separator would result in increased granulocyte yields. Fifty-four granulocyte collections performed with cooling were compared with 58 collections performed on alternate days in the same donors. In blood cooled to 15 degrees C we were unable to demonstrate improved yields of granulocytes.


Hypovirulence: mycoviruses at the fungal-plant interface.
Whereas most mycoviruses lead 'secret lives', some reduce the ability of their fungal hosts to cause disease in plants. This property, known as hypovirulence, has attracted attention owing to the importance of fungal diseases in agriculture and the limited strategies that are available for the control of these diseases. Using one pathogen to control another is appealing, both intellectually and ecologically. The recent development of an infectious cDNA-based reverse genetics system for members of the Hypoviridae mycovirus family has enabled the analysis of basic aspects of this fascinating virus-fungus-plant interaction, including virus-host interactions, the mechanisms underlying fungal pathogenesis, fungal signalling pathways and the evolution of RNA silencing. Such systems also provide a means for engineering mycoviruses for enhanced biocontrol potential.


Diagnostic evaluation of intrauterine fetal deaths in Stockholm 1998-99.
To evaluate the diagnostic methods and to elucidate the etiology of intrauterine fetal death. A prospective study was conducted on all intrauterine fetal deaths occurring in Stockholm County in 1998-99. During a 24-month period, 188 cases of intrauterine fetal death with gestational ages of > or = 22 weeks were investigated in accordance with structured test protocol. All information from antenatal and delivery records as well as all test results were entered in to an Internet-based database for continuous evaluation. A presumptive explanation to the stillbirth was established in 91% of the cases. The most common factors associated with intrauterine fetal death could be identified as infections (24%), placental insufficiency/intrauterine growth restriction (22%), placental abruption (19%), intercurrent maternal conditions (12%), congenital malformations (10%), and umbilical cord complications (9%). A relevant test protocol in cases of intrauterine fetal death reduces the number of unexplained cases to a minimum. An Internet-based register on test results of fetal deaths may enable a continuous evaluation of the diagnostic tools and etiologic factors in an ever-changing panorama. The results from the present study can serve as a base for a case-control study in Sweden.


Therapeutics of aggression in children.
This paper examines the phenomenology, aetiology and therapeutics of childhood aggression that arises as part of a disruptive behaviour disorder. Phenomenology is discussed with an emphasis on treatment implications. Reviewed studies show that aggressive behaviour exhibits both episodicity and considerable individual stability. Aetiological theories are reviewed with emphasis on the interplay between biological and socio-environmental factors. Both factors are centrally involved in the development and treatment of aggression. A review of double-blind, placebo-controlled medication studies is presented. A computer-based, literature search using Medline and PsychInfo was conducted to locate all potentially relevant articles published in the past 20 years. It was found that there are various treatments available for reducing paediatric aggression including psychotherapeutic and psychopharmacological treatments. There are data to support the use of psychostimulants, lithium and antipsychotics, while data for other agents are only beginning to accumulate. Various pharmacological treatments can reduce aggression in children. However, given the role of both biological and social factors in the development of aggression, multimodal treatment may ultimately provide maximal benefits.


Acoustic tumour detection with early auditory evoked potentials and neuroradiological methods.
A total of 43 patients with surgically identified acoustic neuromas were tested. Results of early auditory evoked potentials (EAEP) and of neuroradiological methods were analysed. Abnormal EAEPs were observed in all patients. In 73% of the cases the EAEP indicated the retrocochlear site of the lesion; in 27%, however, the results did not localize the exact site of the lesion owing to a lack of waves I, II and III due to a pronounced hearing loss. Neuroradiological procedures provided an indication of the site and extent of the tumour. The number of true positives was 21 of 29 cases with polytomography of the petrous bone, 23 of 28 with computed tomography and in all cases when pontine angle cisternography and computed tomography combined with gas cisternography were performed. The EAEPs provide a screening-test for acoustic tumour detection at an early stage. Wave abnormalities indicative of a lesion at the acoustic nerve should lead to a neuroradiological investigation and are particularly valuable in cases with small intracanalicular tumours.


Menière symptoms induced by an otologic implant during MR.
A patient who had had sacculotomy with placement of a stainless steel sacculotomy tack 20 years earlier experienced vertigo and auditory sensations during MR imaging. The safety of these prosthesis in MR is questionable. A simple method of determining ferromagnetic interaction is proposed.


Preventing type 2 diabetes in communities across the U.S.: the National Diabetes Prevention Program.
There are as many as 79 million people in the U.S. with prediabetes, and their risk of developing type 2 diabetes is four to 12 times higher than it is for people with normal glucose tolerance. Although advances in diabetes treatment are still needed, there is a critical need to implement effective strategies to stem the current and projected growth in new cases of type 2 diabetes. RCTs and translation studies have demonstrated that type 2 diabetes can be prevented or delayed in those at high risk, through a structured lifestyle intervention that can be delivered cost effectively. In order to bring this compelling lifestyle intervention to communities across America, Congress authorized the CDC to establish and lead the National Diabetes Prevention Program. Several aspects of the etiology of type 2 diabetes suggest that strategies addressing both those at high risk and the general population are necessary to make a major impact on the diabetes epidemic.


Doxorubicin-induced chronic dilated cardiomyopathy-the apoptosis hypothesis revisited.
The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10-20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation. Based on recent literature evidence, we first argue why a dilated phenotype can occur when little apoptosis is detected. We then review findings suggesting that mature cardiomyocytes are protected against DOX-induced apoptosis downstream, but not upstream of mitochondrial outer membrane permeabilisation (MOMP). This lack of MOMP induction is proposed to alter the metabolic phenotype, induce hypertrophic remodeling, and lead to functional cardiac impairment even in the absence of cardiomyocyte apoptosis. We discuss findings that DOX exposure can lead to increased sensitivity to further cardiomyocyte apoptosis, which may cause a gradual loss in cardiomyocytes over time and a compensatory hypertrophic remodeling after treatment, potentially explaining the long lag time in disease onset. We finally note similarities between DOX-exposed cardiomyocytes and apoptosis-primed cancer cells and propose computational system biology as a tool to predict patient individual DOX doses. In conclusion, combining recent findings in rodent hearts and cardiomyocytes exposed to DOX with insights from apoptosis signal transduction allowed us to obtain a molecularly deeper insight in this delayed and still enigmatic pathology of DCM.


[What is Known About the Real Length of Postgraduate Medical Education in Germany?]
This study examines the real length of postgraduate medical education in Germany. The regulations define minimal time periods in months for each discipline. We especially analyze the differences between minimum and real length, as well as the percentages of interrupting or dropping out physicians by gender. Within the KarMed study, annual postal surveys were sent to graduates of seven medical faculties in Germany from their last year of undergraduate education until after six years of postgraduate training. The return rate at baseline was 48 % (n = 1012) and the 5 surveys after baseline reached rates of 85 % and more. Descriptive statistics were used for analyses. Half of the residents did not finish within the minimum time period. This proportion was higher among women (65 %) then men (43 %); among women with child/children this proportion reached 91 %. Female residents expecting a prolongation estimated an average time period of 19.6 months (SD = 14.7), male residents of 11.5 months (SD = 8.6).Female residents named problems in relation to children as the most important factor. Half of the reasons given by male residents (and 31 % of those given by females) are related to organizational and curricular problems of postgraduate education. Effective measures are needed to reduce the problem of continuation of postgraduate education in the course of getting/having children and/or to promote the return to training in the hospital. For this, curricular and organizational measures, e. g. rotation plans and better possibilities for part-time training, should be offered.


Cerebral venous sinus thrombosis following intracerebral hemorrhage after COVID-19 AstraZeneca vaccination: A case report.
The patient was a 55-year-old female patient who presented with sudden onset of left hemiplegia, facial hemiparesis, and hypoesthesia. She has received her first dose of the AstraZeneca COVID-19 vaccine. This case indicates that vaccination may raise the hypercoagulable state even in a condition of post-ICH and anticoagulant prophylaxis.


QT and JT dispersion in the drug-induced long QT syndrome in anaesthetized rabbits is accurately detected by a three-lead surface ECG measurement.
QT dispersion (QTd) can be measured from three leads of the ECG in patients with myocardial ischemia. However, whether QT and JT dispersion (QTd, JTd) can be calculated from a three-lead of the ECG in drug-induced long QT syndrome (LQTS) in animals remains elusive. Therefore, we determined to what extent a three-lead measurement of the surface ECG accurately detects dispersion of QT and JT in comparison with multi-lead assessments in anaesthetized rabbits, challenged with methoxamine and additionally infused intravenously with solvent or dofetilide. Using several ECG leads in anaesthetized rabbits challenged intravenously with an alpha(1)-adrenoceptor agonist methoxamine, we assessed the QT and JT interval, as well as QT and JT dispersion, at baseline and in response to solvent or dofetilide (0.02 or 0.04 mg/kg/min iv for 60 min), an I(Kr) blocker. For that purpose, we recorded and analyzed the surface ECG and assessed QT and JT dispersion by four methods: (1) 12-lead ECG; (2) six precordial leads (V1-V6); (3) three leads most likely to contribute to the dispersion (aVF, V1, and V4); (4) three quasi-orthogonal leads (aVF, I, and V2). QT and JT dispersion were significantly lower in 6- and 3-lead measurements than in 12-lead measurement, both at baseline and during infusion of solvent or dofetilide. At 5 and 10 min of infusion, dofetilide at 0.02 or 0.04 mg/kg/min iv markedly increased QT and JT dispersion by 100% to 500% in all four ECG lead combinations. This dose regimen of dofetilide markedly prolonged QT and JT intervals in lead II, and was associated with high incidences of polymorphous ventricular tachycardia (PVT: 30% at 0.02 mg/kg/min; 100% at 0.04 mg/kg/min) and of ventricular fibrillation (VF: 17% with 0.02 mg/kg/min; 58% with 0.04 mg/kg/min). Our present study shows that the measurement of QT and JT dispersion in three surface ECG leads only (aVF, I, V2 or aVF, V1 V4), instead of 12 ECG leads, is an appropriate approach to assess drug-induced heterogeneity or dispersion of ventricular repolarization in anaesthetized rabbits, both at baseline and during arrhythmogenic sensitization with methoxamine and challenged with dofetilide.


Indicators for chemicals: sources, impacts and policy performance.
Different types of indicators have been developed to describe the impact of chemicals on society and environment. Due to the high number of substances and their different types of use, most of these indicators are directed to specific areas of interest--regarding workplace safety, environmental health or consumer health. They address a specific subset of chemicals and can be used for monitoring enterprise-specific, national or international management measures. A survey of existing indicators for chemicals has shown that indicators already exist for a remarkable number of problem fields. As soon as the release and the environmental fate of chemicals are taken into account, the complexity of the approaches increases considerably. The distinction between indicators for drivers, pressures, state, impacts and responses, as proposed by the European Environmental Agency, supports the identification of proper indicators for a specific type of problem. No single indicator exists which is able to cover the whole range of chemicals and their applications. Several indicator approaches cover at least a subset of the most relevant substances. If they are intended to be used for European monitoring, robust data must be provided by EU Member States. Chemicals in enterprises (ancillary inputs as well as process chemicals) are an important element of in-plant material flow management--in terms of occupational safety and health as well as environmental protection. Existing indicators for hazardous chemicals can be a valuable tool for process and product refinement regarding hazardous chemicals, especially for enterprises. Indicators for production and impact of chemicals, as well as policy performance indicators, are essential elements in order to monitor the management of chemicals. They have to be established for the national and for the EU level.


Physical aspects of biophotons.
By comparing the theoretically expected results of photon emission from a chaotic (thermal) field and those of an ordered (fully coherent) field with the actual experimental data, one finds ample indications for the hypothesis that 'biophotons' originate from a coherent field occurring within living tissues. A direct proof may be seen in the hyperbolic relaxation dynamics of spectral delayed luminescence under ergodic conditions. A possible mechanism has to be founded on Einstein's balance equation and, under stationary conditions, on energy conservation including a photochemical potential. It is shown that the considered equations deliver, besides the thermal equilibrium, a conditionally stable region far away from equilibrium, which can help to describe both 'biophoton emission' and biological regulation.