Ektachem slides for direct potentiometric determination of sodium in plasma: effect of natremia, blood pH, and type of electrolyte reference fluid on concordance with flame photometry and other potentiometric methods.
With electrolyte reference fluid (ERF)00, results from Kodak Ektachem slides for the direct potentiometric assay of sodium in plasma were significantly correlated with results from flame photometry, but also appeared to be systematically higher, especially in hypernatremic patients. Indirect potentiometry with the Technicon RA-1000 yielded intermediate values. In 23 hypernatremic patients with greater than or equal to 6 mmol/L difference in sodium between Ektachem ERF00 and flame photometry, a clinical survey disclosed the frequent association of large between-method differences with renal failure, diabetes mellitus, and gastrointestinal disease. However, there was no correlation between differences in sodium on the one hand and anion gaps or (lipo)protein concentrations on the other, nor did in vitro addition studies implicate metabolites that often accumulate in the above-mentioned disorders. Unlike indirect methods, sodium measurements by direct potentiometry on Ektachem and Corning were influenced by in vitro changes of pH between 7.0 and 7.9. However, in a group of patients that included many acidotic individuals, between-method differences in sodium appeared not significantly correlated with in vivo blood pH. Use of the equitransferant ERF04 on Ektachem strongly diminishes the systematic differences with flame photometry, reduces the pH-dependency of the results to that of the direct Corning method, and brings the mean analytical recovery of sodium to below 95% (instead of 115% previously) without affecting the ability of Ektachem slides to avoid spuriously low results in the presence of increased (monoclonal) protein concentrations.


Characterization of Listeria monocytogenes strains involved in invasive and noninvasive listeriosis outbreaks by PCR-based fingerprinting techniques.
A total of 32 Listeria monocytogenes strains (16 from a recent outbreak of invasive listeriosis and 16 from two outbreaks of noninvasive listeriosis, all three occurring in Italy) were characterized by PCR-ribotyping, arbitrarily primed PCR (AP-PCR), and the recently developed infrequent-restriction-site PCR (IRS-PCR). The discriminatory ability of the techniques, first evaluated on 29 unrelated L. monocytogenes food isolates using Simpson's index of diversity, was 0.714 for PCR-ribotyping, 0.690 for AP-PCR, and 0.919 for IRS-PCR. IRS-PCR was also more capable of distinguishing among strains from the invasive listeriosis outbreak: three different clusters were identified by IRS-PCR compared to two clusters identified by both PCR-ribotyping and AP-PCR. Within each of the two outbreaks of noninvasive listeriosis, the patterns were practically identical, as demonstrated by all three techniques. Only IRS-PCR succeeded in clearly discriminating the strains related to noninvasive listeriosis from all of the other strains included in this study, including those from the outbreak of invasive listeriosis. This finding may suggest the presence of unique differences in their DNA sequences.


Longevity of restorations: survey results of dentists' estimates and attitudes.
A cross-sectional survey of 571 clinicians was conducted to obtain information about expected and observed restoration longevity. Clinicians believed that average large amalgam, small amalgam, and cast restorations lasted 6, 11, and 13 years, respectively. Patients were thought to be responsible for 47%, dentists for 30%, and materials used for 23% of restoration failures. The clinicians perceived the restorations that they placed to be more long-lasting than those placed by other clinicians. Clinical measurements of restoration longevity were shown to be influenced by the judgment criteria used by clinicians.


Molecular activation of the NLRP3 Inflammasome in fibrosis: common threads linking divergent fibrogenic diseases.
Over the past 10 years, there has been a plethora of investigations centering on the NLRP3 inflammasome and its role in fibrosis and other disease pathologies. To date, the signaling pathways from the inflammasome to myofibroblast differentiation and chronic collagen synthesis have not been fully elucidated, and many questions are left to be answered. Recent studies have demonstrated the significant and critical role of reactive oxygen species (ROS) and calcium signaling in the assembly of the inflammasome, and this may result in autocrine signaling maintaining the myofibroblast phenotype, leading to fibrotic disease. Traditionally, myofibroblasts under tight regulation aid in wound healing and then, once the wound has closed, undergo apoptosis and the collagen in the wound remodels. During fibrosis, however, the myofibroblast maintains an activated state via a chronically activated inflammasome, leading to the continual synthesis of collagens and other extracellular matrix proteins that result in damage to the tissue or organ. The mechanism that is driving this abnormality has not been fully elucidated. However, studies have been conducted to suggest that modulating the calcium or the ROS axis may be of therapeutic value in regulating inflammasome activation. A number of novel drugs are currently being developed that may prove beneficial to patients suffering from fibrotic diseases.


Atomic force microscope anodization lithography using pulsed bias voltage synchronized with resonance frequency of cantilever.
An applied bias voltage between the atomic force microscope tip and the substrate is one of the important factors related to the growth of oxide patterns. A pulse modulator was used to apply a pulsed bias voltage that synchronizes with the resonance frequency of the cantilever between the tip and the substrate in tapping mode. The height of the protruded oxide structure was increased for short duration times of the pulsed bias due to the reduction of built-up space charge in oxide. The aspect ratio of patterns using pulsed bias voltage was about two times higher than that using continuous bias voltage. This study revealed that the pulsed bias has an advantage for obtaining a higher aspect ratio pattern than the continuous bias by reducing the effect of space charge in oxide.


The body ego from the point of view of psychophysical fusion.
Freud introduced the concept of body ego as a basis for all later ego development. He did not describe it in detail, however, and the nature of the body ego has remained unclear. I suggest that the original body ego in the infant is the outcome of psychophysical fusion, i.e. fusion of experienced pleasure with sense impressions coming from without (the mother). The result of this leads to the establishment of primal repression and the psychosomatic boundary. The experiences of fusion are gradually internalized to form a stable ego nucleus. It is further suggested that the remarkable hypnagogic and dream phenomena described by Isakower and Lewin reflect the internalized result of this process and offer a chance to investigate these early and developmentally central phenomena.


Rapid structural remodeling of peripheral taste neurons is independent of taste cell turnover.
Taste bud cells are constantly replaced in taste buds as old cells die and new cells migrate into the bud. The perception of taste relies on new taste bud cells integrating with existing neural circuitry, yet how these new cells connect with a taste ganglion neuron is unknown. Do taste ganglion neurons remodel to accommodate taste bud cell renewal? If so, how much of the structure of taste axons is fixed and how much remodels? Here, we measured the motility and branching of individual taste arbors (the portion of the axon innervating taste buds) in mice over time with two-photon in vivo microscopy. Terminal branches of taste arbors continuously and rapidly remodel within the taste bud. This remodeling is faster than predicted by taste bud cell renewal, with terminal branches added and lost concurrently. Surprisingly, blocking entry of new taste bud cells with chemotherapeutic agents revealed that remodeling of the terminal branches on taste arbors does not rely on the renewal of taste bud cells. Although terminal branch remodeling was fast and intrinsically controlled, no new arbors were added to taste buds, and few were lost over 100 days. Taste ganglion neurons maintain a stable number of arbors that are each capable of high-speed remodeling. We propose that terminal branch plasticity permits arbors to locate new taste bud cells, while stability of arbor number supports constancy in the degree of connectivity and function for each neuron over time.


Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes.
Decomposition of hydrogen peroxide (H2O2 ) at physiological levels was studied in human erythrocytes by means of a recently developed sensitive H2O2 assay. The exponential decay of H2O2 in the presence of purified erythrocyte catalase was followed down to 10(-9) mol/L H2O2 at pH 7.4. H2O2 decomposition by purified erythrocyte glutathione peroxidase (GPO) could be directly observed down to 10(-7) mol/L H2O2 . No enzyme inhibition was observed at these low H2O2 concentrations. Catalase and GPO activities can be determined separately in a titrated mixture of purified enzymes, which simulates the conditions of H2O2 removal by the erythrocyte. Experiments with fresh human hemolysate allowed us to determine H2O2 decomposition by catalase and GPO using these enzymes in their original quantitative ratio. The different kinetics of these enzymes are shown: H2O2 decomposition by catalase depends linearly on H2O2 concentration, whereas that by GPO becomes saturated at concentrations above 10(-6) mol/L H2O2. Even at very low H2O2 concentrations GPO reaches only approximately 8% of the rate at which catalase simultaneously degrades H2O2. These data indicate an almost exclusive role for catalase in the removal of H2O2 in normal human erythrocytes.


Total cholesterol and high density lipoprotein cholesterol levels in populations differing in fat and carbohydrate intake.
This paper reviews epidemiological studies on the relationship between diet and high density lipoproteins (HDL), with emphasis on the authors' studies of boys and men from different countries and with different dietary habits. Sera were collected from boys (ages 7 to 9 years) and men (ages 33 to 48 years) in 20 countries, and these were analyzed in one standardized laboratory. In boys, total and HDL cholesterol changed in parallel, from low values in populations in developing countries with low-fat, high-carbohydrate diets to high values in affluent populations. The correlation between HDL and total cholesterol was 0.90 (n = 16 populations). A similar trend was seen in groups of vegetarian and omnivorous boys within one region. Detailed analyses of individual diets of boys in five countries showed a negative relation between carbohydrate intake and HDL cholesterol both for group means (r = -0.99, n = 5) and for individual boys within one country (r = -0.26 to 0.04, n = 109 to 133 boys per country). In these boys, differences in obesity and physical activity were slight, and unrelated to differences in HDL. Total cholesterol rose with saturated fat intake (r = 0.87 for five population means; r = 0.07 to 0.26 within population groups). In adult men, total and HDL cholesterol also tended to rise simultaneously with affluence. However, the relation was much weaker (r = 0.60, n = 13 population groups).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion.
Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats. The I/R-related injury was modeled using occlusion and reperfusion of the middle cerebral artery (MCAO/R) in Sprague-Dawley rats. VNS was concurrently applied to the vagus nerve using a stimulation intensity of 1 mA at a fixed frequency of 20 Hz with a 0.4-ms bipolar pulse width. The stimulation duration and inter-train interval were both 3 s. Next, Morris water maze and shuttle-box behavioral experiments were conducted to assess the effects of VNS on the recovery of learning, memory, and inhibitory avoidance following I/R injury. Intracerebroventricular injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a selective neurotoxin for noradrenergic neurons, was used to evaluate the role of norepinephrine (NE) as a mediator of therapeutic effects of VNS on cognitive recovery. Compared with the MCAO/R group, the VNS+MCAO/R group had improved spatial memory as indicated by swimming path lengths and escape latencies in the Morris water maze, and fear memory, as indicated by the avoidance conditioned response rate, mean shock duration, and avoidance time in shuttle-box behavior experiments. Compared with the VNS+MCAO/R group, the DSP-4+VNS+MCAO/R group, which had reduced NE levels in cortical and hippocampal brain regions, showed a reversal of the VNS-induced benefits on spatial and fear memory performance. VNS improves spatial and fear memory in a rat model of MCAO/R injury. However, a reduction in NE from the administration of DSP-4 blocks these protective effects, suggesting that NE may contribute to the influence exhibited by VNS on memory performance in rats with cerebral I/R-related injury.


Students' negative emotions and their rational and irrational behaviors during COVID-19 outbreak.
The pandemic has posed an intense threat to the mental health of younger adults. Despite significant efforts in studying various aspects of COVID-19, there is a dearth of evidence on how negative emotions are associated with behaviors. A comparison across associated factors to different negative emotions by means of a unified model is especially missing from the literature. This study was conducted by using the results of a survey conducted across 2,534 students enrolled in 7 states in the US. Various feelings such as sad, irritable, stress and guilt were analyzed in a unified model by means of seemingly unrelated regression (SUR). Questions were asked related to rationally limiting the spread of virus, and questions related to behaviors that seem to be extreme. Irrational behaviors, such as limiting exercise at home due to COVID-19 could be due to experiencing negative emotions, which distort the meaning of events for the students. That behavior, for instance, was found to be positively associated with various negative feelings. In addition, the results highlighted significant differences across emotions in terms of demographic characteristics such as gender and age, and various precautionary actions that students take, such as limiting outdoor activities or limiting social gathering. For instance, it was highlighted while avoiding a large group of people, in spite of its importance in curbing the spread of virus, is negatively associated with various negative emotions, taking a possible nonconsequential precaution of completely limiting all people outside the immediate family result in a higher level of negative emotions. Also, it was found that having a higher body mass index (BMI), self-rated worse health conditions, and limiting outdoor activities have detrimental effects on the mental health of students.


Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model.
We describe the results of adding a new biological agent HEMO2life® to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMO2life® is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex®) was compared with Perfadex® associated with HEMO2life® and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO2life® group led to significant improvement in functional parameters: reduction of graft vascular resistance (p < .05) and increase in graft oxygenation ratio (p < .05). Several ischemia-reperfusion related biomarkers showed positive trends in the HEMO2life® group: expression of HMG B1 in serum tended to be lower in comparison (2.1 ± 0.8 vs. 4.6 ± 1.5) with Perfadex® group, TNF-α and IL-8 in BALF were significantly higher in the two experimental groups compared to control (p < .05). During cold ischemia, expression of HIF1α and histology remained unchanged and similar to control. Supplementation of the Perfadex® solution by an innovative oxygen carrier HEMO2life® during hypothermic static preservation improves early graft function after prolonged cold ischemia in lung transplantation.


Several aspects of formation of auto-transplant and re-transplant vascular pedicle.
The purpose of the work was the simplification of technical side of autotransplantation and replantation by pre-preparation of vascular pedicle. 173 patients were observed and treated. Microsurgical autotransplantation of tissues was done in 29 cases, fingers autotransplantation in 44 cases (35 patients), fingers replantation in 66 cases (38 patients), replantation of thick parts of extremities in 34 cases (3 patients). Thoracodorsal flap on the neuro-vascular flap was transplntated in 16 cases, groin flap in 3 cases, deltoid flap -- in 3 cases, scapular flap -- in 1 case, saphenal -- 1 case, gracilis muscle in 3 cases, iliac crest flap in 2 cases, rib segment on vascular pedicle -- in 8 cases. Rib segment was transplanted as an isolated and with pre-prepared thoracodorsal bone-soft tissue complex also. II toe-finger and II-III toe-fingers block were transplanted for the abnormalities of the hand. Good and satisfactory functional and aesthetic results were obtained in all cases of autotransplantation and replantation. Original method of anastomosing of vessels was used in vein transplantation. We could simplify and increased the number of good results of operations by pre-preparing vascular pedicle. The results of treatment were improved by optimal election of donor site and preliminary forming of vascular pedicle of flaps and replants.


A model for dysfunctions in smooth pursuit eye movement.
In this paper, I have introduced and solved a simple deterministic model of eye tracking that produces rich dynamical behavior. Some of its main features, notably the existence of a chaotic regime, are reminiscent of the anomalies reported in smooth pursuit eye tracking experiments with schizophrenia patients. By obtaining the state diagram of such a model as a function of target frequency and amplitude, we showed the existence of a chaotic regime characterized by a strange attractor in phase-space and associated random velocity arrests in the eye dynamics. Moreover, the power spectrum contains features similar to those reported in the literature. The correctness of this model could in principle be determined by performing experiments where the target parameters (i.e., amplitude and frequency) could be varied in a systematic manner and by taking Poincaré maps from the corresponding time series. Although the present status of such experiments prevents us from verifying the validity of the model, the available data does not seem to contradict the main predictions. Furthermore, we showed that the inevitable noise expected to be present in actual experiments would only enhance the observability of our predictions. If this model were proven incorrect, then the focus of research into mechanisms will have to shift into a search for an intrinsic source of the fluctuations. If, on the other hand, this deterministic theory has any validity, it will point to the nonlinearities in eye tracking mechanisms as the main culprits for the observed anomalies.


Meconium thorax: A case of Bochdalek hernia and cecal perforation in a neonate with Job's syndrome.
Meconium peritonitis most often is associated with congenital intestinal obstruction and meconium ileus. Uncommonly, other etiologies are identified. Hyperimmunoglobulin E syndrome (Job's syndrome) is a rare genetic disorder that is characterized by recurrent staphylococcal respiratory and skin infections in addition to elevated serum IgE levels. There have been 2 previously reported cases of intestinal complications associated with Job's syndrome. The current case is the third such case and is the first report of meconium peritonitis in a patient with hyperimmunoglobulin E syndrome. The patient presented with a meconium thorax as a result of a concurrent congenital diaphragmatic hernia.


Evolutional trends and palaeobiogeography of the Ordovician trilobite Ovalocephalus Koroleva 1959.
Ovalocephalus has a long stratigraphic range and wide geographical distribution in Ordovician peri-Gondwana. Based largely on the well-preserved specimens recently collected from China, all known forms are revised and listed. Phylogenetic analysis was conducted on the genus, involving 10 species. As suggested by the strict consensus tree, evolutional trends of the genus include mainly the isolation of the anterior glabellar portion anterior to S1, the forward shifting of eyes and the related lengthening (exsag.) of the posterior fixigena, the reduction of the number of pygidial axial segments and pleural abaxial rounded free tips, the shortening of the pygidial postaxial region, and the development of cranidial genal spines. Ovalocephalus may have originated in shallow-water sites of the South China Plate in the Early Floian, but migrated into the deep-water regions from the Darriwilian onwards. All the records of the genus from the Early Floian to Early Katian were confined to eastern peri-Gondwanan plates and terranes in low-latitude zones. It was only restricted to the South China, Tarim and North China plates until the Middle Darriwilian, but the Late Darriwilian eustatic sea-level rise and especially the Sandbian-Early Katian immense transgression may have brought about its dispersal to Alborz, Sibumasu and central Asian terranes. Following the closure of the Tornquist Sea, the genus was even able to spread to Baltica during the latest Katian, and the pre-Hirnantian warming (the Boda event) may have promoted a wider distribution of Ovalocephalus to western peri-Gondwana (the Taurides and Armorica terranes) in the then-high latitudes.


The current status and outlook of trachea transplantation.
The trachea is an enigmatic organ due to its complex morphology. Although circumferential tracheal defects are extremely difficult to repair with autologous tissue or with an allotransplant, the trachea has been touted as the first organ that could be regenerated. This review provides a comprehensive evaluation of the published evidence in tracheal tissue replacement surgery. In recent years, reports of successful tracheal regeneration have attracted great interest. Despite descriptions of the trachea as a perhaps uniquely regeneratable tissue since 2008, critical reporting provided insights into the more complex realities of tracheal regeneration attempts and led to the retraction of some articles making tracheal regeneration claims. Allotransplantation of the trachea is hindered by numerous difficult obstacles. The most promising approach developed thus far for difficult-to-repair patch airway defects is tracheal allotransplantation, which allows for tapering and withdrawal of immunosuppressive therapy. Restoration of a long-segment circumferential tracheal defect remains an unmet challenge. Future clinical studies require thoroughly documented visual evidence of outcomes to reduce confusion surrounding tracheal replacement and to prevent future scandals like those seen previously in the tracheal regeneration story. VIDEO ABSTRACT: http://links.lww.com/COOT/A6.


Exposure estimate for FD&C colour additives for the US population.
Dietary exposures to the seven food, drug, and cosmetic (FD&C) colour additives that are approved for general use in food in the United States were estimated for the US population (aged 2 years and older), children (aged 2-5 years) and teenage boys (aged 13-18 years) based on analytical levels of the FD&C colour additives in foods. Approximately 600 foods were chosen for analysis, based on a survey of product labels, for the levels of FD&C colour additives. Dietary exposure was estimated using both 2-day food consumption data from the combined 2007-10 National Health and Nutrition Examination Survey (NHANES) and 10-14-day food consumption data from the 2007-10 NPD Group, Inc. National Eating Trends - Nutrient Intake Database (NPD NET-NID). Dietary exposure was estimated at the mean and 90th percentile using three different exposure scenarios: low exposure, average exposure and high exposure, to account for the range in the amount of each FD&C colour additive for a given food. For all populations and all exposure scenarios, the highest cumulative eaters-only exposures in food were determined for FD&C Red No. 40, FD&C Yellow No. 5 and FD&C Yellow No. 6. In addition, the eaters-only exposure was estimated for individual food categories in order to determine which food categories contributed the most to the exposure for each FD&C colour additive. Breakfast Cereal, Juice Drinks, Soft Drinks, and Frozen Dairy Desserts/Sherbet (also referred to as Ice Cream, Frozen Yogurt, Sherbet (including Bars, Sticks, Sandwiches)) were the major contributing food categories to exposure for multiple FD&C colour additives for all three populations.


Making finance work for you.
Every organization has a process for reviewing requests against their own guidelines, which are not always well defined. Normally, all requests must be able to demonstrate an adequate financial return on any investment of dollars and/or resources. Quality and service improvement benefits sometimes are accepted, but often must be translated into documentable dollars and cents. In this article, the author shows how understanding the basic concepts of revenue and expense is a good first step toward improving your chances of gaining approval. Forming an effective two-way partnership with the staff in your finance department will improve your chances even more.


A presentation of attentional semantics.
The paper presents the two main assumptions of Attentional Semantics--(A) and (B), and its main aim (C). (A) Conscious experience is determined by attention: there cannot be consciousness without attention. Consciousness is explained as the product of attentional activity. Attentional activity can be performed thanks to a special kind of energy: nervous energy. This energy is supplied by the organ of attention. When we perform attentional activity, we use our nervous energy. This activity directly affects the organ of attention, causing a variation in the state of the nervous energy. This variation constitutes the phenomenal aspect of consciousness. (B) Words are tools to pilot attention. The meanings of words isolate, de-contextualize, "freeze" and classify in an articulated system the ever-changing and multiform stream of our conscious experiences. Each meaning is composed of the sequence of invariable elements that, independently of any individual occurrence of a given conscious experience, are responsible for the production of any instance of that conscious experience. The elements composing the meanings of words are attentional operations: each word conveys the condensed instructions on the attentional operations one has to perform if one wants to consciously experience what is expressed through and by it. (C) Attentional Semantics aims at finding the attentional instruction conveyed by the meanings of words. To achieve this goal, it tries: (1) to identify the sequence of the elementary conscious experiences that invariably accompany, and are prompted by, the use of the word being analyzed; (2) to describe these conscious experiences in terms of the attentional operations that are responsible for their production; and (3) to identify the unconscious and non-conscious operations that, directly or indirectly, serve either as the support that makes it possible for the attentional operations to take place, be completed, and occur in a certain way, or as the necessary complement that makes it possible to execute and implement the activities determined and triggered by the conscious experiences. The origins of Attentional Semantics are also presented, and the methodological problems researchers encounter when analyzing meanings in attentional terms are discussed. Finally, a brief comparison with the other kinds of semantics is made.


Combined treatment of periorbital arteriovenous malformation: a case report.
A 54-year-old woman had a gradually growing subcutaneous mass for more than three decades over her right zygomatic bone and below the right inferior orbital rim. The tumor was slightly pulsatile and non-tender. MRI scans demonstrated an unusually vascularized soft tissue mass with many large-caliber vessels. Selective angiography showed the mass to be an arteriovenous malformation with the principal feeder being the internal maxillary artery. A combined treatment scheme which consisted of an initial embolization of the lesion followed by surgical extirpation was carried out. This sequential approach allowed safer surgery and a satisfactory cosmetic outcome.


Survival of an islet β-cell in type-2 diabetes: curbing the effects of amyloid cytotoxicity.
Type 2 diabetes mellitus is a chronic hyperglycaemic disorder caused by defective action and secretion of insulin. It is characterized by a progressive decline in pancreatic β-cell function and mass and the occurrence of insoluble amyloid deposits within the islets of Langerhans. These amyloid deposits comprise predominantly of fibrillar aggregates of the 37-amino acid human amylin (hA) monomer, also known as islet amyloid polypeptide (IAPP), which is co-secreted with insulin from pancreatic islet β-cells via the regulated secretory pathway. hA has a propensity to aggregate in vitro into fibrillar structures through the self-association of monomers that is largely mediated by an amyloidogenic region spanning amino acids 20-29 (reviewed in ref. 8).


Vision deficits precede structural losses in a mouse model of mitochondrial dysfunction and progressive retinal degeneration.
Current animal models of retinal disease often involve the rapid development of a retinal disease phenotype; however, this is at odds with age-related diseases that take many years to manifest clinical symptoms. The present study was performed to examine an apoptosis-inducing factor (Aif)-deficient model, the harlequin carrier mouse (X(hq)X), and determine how mitochondrial dysfunction and subsequent accelerated aging affect the function and structure of the mouse retina. Vision and eye structure for cohorts of 6 X(hq)X and 6 wild type mice at 3, 11, and 15 months of age were studied using in vivo electroretinography (ERG), and optical coherence tomography (OCT). Retinal superoxide levels were determined in situ using dihydroethidium (DHE) histochemistry. Retinal cell counts were quantified post mortem using hematoxylin and eosin (H&E) staining. ERG analysis of X(hq)X retinal function indicated a reduction in b-wave amplitude significant at 3 months of age (p < 0.05), declining further with age. However, retinal neuron counts demonstrated the absence of physical degeneration at 3 and 11 months of age despite significant reduction in ERG b-wave amplitude. Superoxide anion levels were elevated in the ganglion cell, inner nuclear and outer nuclear layers of the retina (p < 0.01, p < 0.01, and p < 0.001, respectively) of 11-month-old X(hq)X mice in comparison to wild type, preceding the structural losses observed at 15 mos. Early onset of retinal function deficits occurred independently of neuron loss. Changes in neurotransmitter localization in the stressed retina may account for the early and significant reduction in retinal function. This remodeling of retinal neurochemistry in response to stress may be a relevant mechanism in the progression of normal retinal aging and early stages of some retinal degenerative diseases.


Model-independent analysis of QCM data on colloidal particle adsorption.
Quartz crystal microbalance (QCM) is widely used for studying soft interfaces in liquid environment. Many of these interfaces are heterogeneous in nature, in the sense that they are composed of discrete, isolated entities adsorbed at a surface. When characterizing such interfaces, one is interested in determining parameters such as surface coverage and size of the surface-adsorbed entities. The current strategy is to obtain this information by fitting QCM data--shifts in resonance frequency, DeltaF, and bandwidth, DeltaGamma--with the model derived for smooth, homogeneous films using the film acoustic thickness and shear elastic moduli as fitting parameters. Investigating adsorption of liposomes and icosahedral virus particles on inorganic surfaces of titania and gold, we demonstrate that the predictions of this model are at variance with the experimental observations. In particular, while the model predicts that the ratio between the bandwidth and frequency shifts, DeltaGamma/DeltaF (the Df ratio), should increase with both surface coverage and particle size, we observe that this ratio increases with increasing particle size but decreases with increasing surface coverage, demonstrating that QCM response in heterogeneous films, such as those composed of adsorbed colloidal particles, does not conform with the predictions of the homogeneous film model. Employing finite element method (FEM) calculations, we show that hydrodynamic effects are the cause of this discrepancy. Finally, we find that the size of the adsorbed colloidal particles can be recovered from a model-independent analysis of the plot of the DeltaGamma/DeltaF ratio versus the frequency shift on many overtones.


Papillomas and carcinomas associated with a papillomavirus in European harvest mice (Micromys minutus).
Papillomaviruses, group-specific papillomavirus antigens, or extrachromosomal papillomavirus DNA were detected in cutaneous, mucocutaneous, and pulmonary tumors affecting a colony of European harvest mice (Micromys minutus). Skin lesions were classified as acanthomatous hyperplasia, epidermal inclusion cysts, squamous papillomas, inverted papillomas, trichoepitheliomas, and sebaceous carcinomas. Cutaneous horns (hyperkeratotic papillomas) were on mucocutaneous junctions of one animal. One mouse, with a cutaneous sebaceous carcinoma, had multiple pulmonary keratinaceous cysts. Papillomavirus antigens, detected by the avidin-biotin technique, were in 20 of 31 lesions tested. In contrast, by Southern blot hybridization all 28 lesions tested contained papillomavirus DNA. Papillomavirus DNA was demonstrated in two of ten benign cutaneous lesions by in situ hybridization.


[An immunoblot technique].
After a protein is separated by various types of gel electrophoresis, it is transferred onto a nitrocellulose membrane, where a specified protein is detected through immunological reactions. This procedure, called an immunoblot technique, combines gel electrophoresis, which is capable of separating materials and immunological detection with specificity and high sensitivity. It has recently been used widely as a useful method for analyzing proteins in the fields of medicine, biochemistry, molecular biology and human genetics. The aim of this technique is to transfer a target protein, which is present in the gel, as efficiently as possible onto a membrane so that it can react uniquely on the membrane. To achieve this end, it is necessary to select the following; 1) a transfer system, 2) a transfer membrane, 3) a transfer buffer and additive, 4) optimal transfer conditions, and 5) a specific and highly sensitive means of immunological detection, to be combined with the technique. Since the immunoblot technique is, in principle, capable of analyzing all types of proteins as long as there is an antibody specific to the target protein, it can be used widely to determine the physiopathology of human proteins.


Vitamin K, circulating cytokines, and bone mineral density in older men and women.
Vitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro. The objective of this study was to assess 1) associations between measures of vitamin K status [plasma phylloquinone and serum percentage of undercarboxylated osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP) concentrations and 2) the effect of daily 500 mug phylloquinone supplementation for 3 y on cytokine concentrations. Concentrations of IL-6, osteoprotegerin, and CRP and bone mineral density (BMD) were measured at baseline and after 3 y of follow-up in 379 healthy men and women (60-81 y; 58.5% women) participating in a randomized trial that studied the effect of vitamin K supplementation on bone loss. Cross-sectionally, plasma phylloquinone was inversely associated with IL-6 and CRP, whereas serum %ucOC was inversely associated with IL-6. Osteoprotegerin was associated positively with plasma phylloquinone and inversely with %ucOC. No differences were observed in the 3-y change in IL-6, osteoprotegerin, and CRP concentrations between participants who received phylloquinone supplementation and those who did not. Overall, no association was observed between the 3-y changes in circulating cytokines and BMD. Poor vitamin K status was associated with high concentrations of cytokines involved in bone turnover, but vitamin K supplementation did not confer a decrease in cytokine concentrations. The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations. This trial was registered with www.clinicaltrials.gov as NCT00183001.


Telehealth and digital health innovations: A mixed landscape of access.
In the wake of emergent natural and anthropogenic disasters, telehealth presents opportunities to improve access to healthcare when physical access is not possible. Yet, since the beginning of the COVID pandemic, lessons learned reveal that various populations in the United States do not or cannot adopt telehealth due to inequitable access. We explored the Digital Determinants of Health (DDoHs) for telehealth, characterizing the role of accessibility, broadband connectivity and electrical grids, and patient intersectionality. In addition to its role as an existing Social Determinant of Health, Policies and Laws directly and indirectly affect these DDoHs, making access more complex for marginalized populations. Digital systems lack the flexibility, accessibility, and usability to inclusively provide the essential services patients need in telehealth. We propose the following recommendations: (1) design technology and systems using accessibility and value sensitive design principles; (2) support a range of technologies and settings; (3) support multiple and diverse users; and (4) support clear paths for repair when technical systems fail to meet users' needs. Addressing these requires change not only from providers but also from the institutions providing these systems.


[Progress on treatment and research of quadrilateral plate fractures of acetabular].
Acetabular is an important human joint for weight bearing. Quadrilateral plate is a crucial structure of medial acetabulum with special morphology and important function. Quadrilateral plate fractures are common fracture in acetabulum. Quadrilateral plate fracture is hard to expose and reduction because it is in the medial of acetabulum. At the same time,the bone in the quadrilateral plate is not easy to fixed for thinning bones and adjacent to the articular cavity. The operator should know well about the anatomy and choose the suitable internal fixation. After quadrilateral plate fractures, the femur head maybe displace medially even break into pelvis. That make reduction and treatment always be a challenge. With different kinds of fractures,the efficacy of treatment is not the same. This paper intend to review the relation of anatomic features,approaches, internal fixations, key point of treatment and efficacy.


A heterogeneous microbial consortium producing short-chain fatty acids from lignocellulose.
Microbial consortia are a promising alternative to monocultures of genetically modified microorganisms for complex biotransformations. We developed a versatile consortium-based strategy for the direct conversion of lignocellulose to short-chain fatty acids, which included the funneling of the lignocellulosic carbohydrates to lactate as a central intermediate in engineered food chains. A spatial niche enabled in situ cellulolytic enzyme production by an aerobic fungus next to facultative anaerobic lactic acid bacteria and the product-forming anaerobes. Clostridium tyrobutyricum, Veillonella criceti, or Megasphaera elsdenii were integrated into the lactate platform to produce 196 kilograms of butyric acid per metric ton of beechwood. The lactate platform demonstrates the benefits of mixed cultures, such as their modularity and their ability to convert complex substrates into valuable biochemicals.


Long noncoding RNAs in biology and hematopoiesis.
Genome and transcriptome sequencing have revealed a rich assortment of noncoding RNAs in eukaryote cells, including long noncoding RNAs (lncRNAs), which regulate gene expression independent of protein coding potential. LncRNAs modulate protein coding gene expression in many cell types by regulating multiple processes, including epigenetic control of transcription, mRNA stability, and protein localization. Although little is known about lncRNAs in hematopoiesis, they are likely to exert widespread roles in this process.


Occupation, gender, and work satisfaction in a comprehensive human services department.
Workers employed in a comprehensive human services department were surveyed to determine factors predictive of work satisfaction by occupational classification and gender. Various patterns emerged for the different groups. Specific recommendations, based upon the results of the study, are provided for departmental executives wishing to improve employee morale.


[Supportive therapy of lung cancer patients]
The effectiveness of cancer treatment given to lung cancer patients is indicated by the asymptomatic and non-toxic survival time. The goal is not to prolong the patients' suffering, but to lengthen the duration of the best quality of life lived (Time Without Symptoms and Toxicity-TWIST). Supportive care is the prevention and management of side effects which occur during therapy (chemotherapy, radiotherapy, surgery) given to patients suffering from cancer. Supportive care is the widespread activity of doctors, nurses and social workers, including psychosocial assistance and rehabilitation through the various stages of illness till death. Though palliative therapy is understood to be the high level and professional treatment of terminally ill patients in those cases where curative measures are not possible anymore, supportive and palliative treatment often overlap (e.g. pain control, cachexia, obstructive syndromes). Palliative care is part of supportive therapy. The goal of supportive care is to reduce the patients' subjective symptoms to the minimum ("well being") during therapy, follow up and consequently until death. The essence of supportive care is to keep the patients' quality of life on the highest possible level. This article summarizes the pathophysiology, prevention and therapy of the most frequently occuring side effects observed during the management of lung cancer patients.


Canine ceroid lipofuscinosis, a model for ageing of the human isocortex.
In canine ceroid lipofuscinosis (one case studied), isocortical layer IIIab pyramidal cells develop spindle-shaped enlargements of their proximal axon filled with lipopigment, a feature that can be observed in juvenile and adult type of human neuronal ceroid lipofuscinosis and in normal ageing of the human isocortex as well.


Blood pressures and cardiovascular homeostasis in mice having reduced or absent angiotensin-converting enzyme gene function.
We studied cardiovascular phenotypes in wild-type (+/+), heterozygous (+/-), and homozygous mutant (-/-) mice for an insertional inactivation of the angiotensin-converting enzyme (ACE) gene (Ace in mice, ACE in humans). Compared with +/+ mice, baseline mean arterial pressure was not significantly altered in +/- mice but was reduced by 51+/-4 mm Hg in -/- mice. Although the pressor response to injected angiotensin II did not differ significantly in the three genotypic groups, the pressor response to angiotensin I was strongly affected by Ace genotype: Compared with the response in the +/+ group (+26% of baseline), the response to Ang I was close to half normal (+12%) in the +/- group and virtually abolished (+1%) in the -/- group. The depressor response to injected bradykinin was significantly enhanced in the +/- and -/- groups compared with the +/+ group. Ace expression and ACE activity were directly related to functional Ace copy number, and renin and angiotensinogen mRNA levels were inversely related to Ace copy number. Angiotensin type 1A receptor mRNA levels were not significantly different in the +/+, +/-, and -/- groups. We conclude that (1) ACE is essential for the maintenance of normal blood pressure; (2) subnormal levels of ACE affect the blood pressure responses to infused angiotensin I and bradykinin in vivo; and (3) compensations for inactivation of one Ace copy, which include increased expression of renin, normalize blood pressure in heterozygotes.


[A hyperthermic perfusion therapy using peplomycin and ethanol for bladder cancer].
Distilled water containing 40 micrograms/ml peplomycin and 2% ethanol was used as a perfusate in 8 patients with superficial bladder tumors and 2 with deep bladder tumors for 2 hours at 43 degrees C. In addition, immediately before the perfusion treatment, 5 mg of peplomycin was injected intramuscularly. Prior to treatment, the nature and extent of the tumors were determined by ultrasonography, cystoscopy and cystography. The therapeutic effect of the hyperthermic perfusion was evaluated by the same manner as used previously. Partial tumor regression was obtained in 6 of the 8 patients with superficial bladder tumors. The 2 patients with deep bladder tumors showed no tumor regression. Most of the patients had bladder discomfort such as irritation, pollakisuria and so on, during and/or after perfusion. No patient developed acute pyelonephritis.


Acizzia errabunda sp. nov. and Ctenarytaina insularis sp. nov.: Descriptions of two new species of psyllids (Hemiptera: Psylloidea) discovered on exotic host plants in New Zealand.
A recent molecular-based assessment of the psyllid fauna of New Zealand reported two genetically distinct, undescribed psyllid taxa on host plants not native to that country. Here, a morphological examination confirmed species-level variation that resulted in the description of two new psyllid species: Acizzia errabunda sp. nov. (Hemiptera: Psyllidae) from Acacia baileyana F. Muell and Ctenarytaina insularis sp. nov. (Hemiptera: Aphalaridae) from Syzygium smithii (Poir.) Nied. Furthermore, the examination of specimens from entomological collections and from observations recorded on an online database enabled a better understanding of the distribution and host plant associations of these psyllid species. The description of A. errabunda is based on material collected in both New Zealand and Australia from the same plant species, A. baileyana, whereas the psyllid C. insularis has been found to be present in Brunei and New Zealand on S. smithii and in New Caledonia on Melaleuca quinquenervia (Cav.) S. T. Blake.


Human 7T MRI: First Clinical and Neuroscientific Applications.
After many years of development and niche applications in a very limited number of laboratories, human 7T magnetic resonance imaging systems are becoming available to a number of clinical and neuroscientific researchers. The spectrum of available methods and their robustness is increasing and the first studies are underway to evaluate the potential applications and benefits for larger clinical studies or even clinical diagnosis. A number of technical and methodological challenges currently limit the application mainly to examinations of the brain. Some of the current possibilities of ultra-high field systems and examples of first applications in patient and research studies are demonstrated to give the reader an overview.


Notes from the Field: Respiratory Symptoms and Skin Irritation Among Hospital Workers Using a New Disinfection Product - Pennsylvania, 2015.
In March 2014, a new disinfection product, consisting of hydrogen peroxide, peroxyacetic acid, and acetic acid, was introduced at a Pennsylvania hospital to aid in the control of health care-associated infections. The product is an Environmental Protection Agency-registered non-bleach sporicide advertised as a one-step cleaner, disinfectant, and deodorizer. According to the manufacturer's safety data sheet, the product requires no personal protective equipment when it is diluted with water by an automated dispenser before use. On January 30, 2015, CDC's National Institute for Occupational Health (NIOSH) received a confidential employee request to conduct a health hazard evaluation at the hospital. The request cited concerns about exposure of hospital environmental services staff members to the product and reported symptoms among persons who had used the product that included eye and nasal problems, asthma-like symptoms, shortness of breath, skin problems, wheeze, chest tightness, and cough.


Maternal programming of reproductive function and behavior in the female rat.
Parental investment can be used as a forecast for the environmental conditions in which offspring will develop to adulthood. In the rat, maternal behavior is transmitted to the next generation through epigenetic modifications such as methylation and histone acetylation, resulting in variations in estrogen receptor alpha expression. Natural variations in maternal care also influence the sexual strategy adult females will adopt later in life. Lower levels of maternal care are associated with early onset of puberty as well as increased motivation to mate and greater receptivity toward males during mating. Lower levels of maternal care are also correlated with greater activity of the hypothalamus-pituitary-gonadal axis, responsible for the expression of these behaviors. Contrary to the transition of maternal care, sexual behavior cannot simply be explained by maternal attention, since adoption studies changed the sexual phenotypes of offspring born to low caring mothers but not those from high caring dams. Indeed, mothers showing higher levels of licking/grooming have embryos that are exposed to high testosterone levels during development, and adoption studies suggest that this androgen exposure may protect their offspring from lower levels of maternal care. We propose that in the rat, maternal care and the in utero environment interact to influence the reproductive strategy female offspring display in adulthood and that this favors the species by allowing it to thrive under different environmental conditions.


The Attend Study: A Retrospective Observational Study of Emergency Department Attendances During the Early Stages of the COVID-19 Pandemic.
The coronavirus disease-19 (COVID-19) pandemic was associated with a large reduction in the number of attendances at emergency departments (EDs) in March 2020 in the United Kingdom (UK). We sought to identify which patient groups attended EDs least. Single-centre before and after study. We used routine administrative data from March 2020 and compared this to a composite control of March 2019 and February 2020. Results: Mean daily attendance fell by 30% from 342 patients per day in the composite control months to 242 patients per day in March 2020. Reductions in attendance were seen in almost all patient groups but were greatest in patients with injuries, those referred by another clinician, those arriving at the weekend, and in patients who received no investigations. Multivariate analysis revealed that the proportion of patients who were admitted to hospital fell, despite the patients being sicker, older, needing more investigations, and more likely to arrive by ambulance. The reduction in ED attendances seen in the early phases of the UK pandemic occurred in all patient groups, but was greatest in the lower acuity patients. Reasons for this are complex and likely to be multifactorial.


An investigation into how the European Working Time Directive has affected anaesthetic training.
The European Working Time Directive (EWTD) became law in 1993 but only applied to doctors in training in the United Kingdom in 2004. The trainees have in consequence had a reduction in their working hours but also a change to a shift pattern of working. For craft specialities, such as anaesthesia, there are concerns that a reduction in working hours has also led to a reduction in the time available for learning and that ultimately this may affect patient care. However, there is scant research on the perceptions of trainees concerning the impact of the EWTD on their training and working lives. This study investigated what the anaesthetic Specialist Registrars (SpRs) on the Mersey Deanery SpR rotation perceived to be training and also what effect the EWTD has had on that training and their quality of life, both within and outside work. The project was a cross sectional survey, using a quantitative questionnaire with qualitative free text comments which were aggregated into overarching themes and sub themes. 117 SpRs were sent questionnaires in April 2005; 73 completed questionnaires were returned (response rate 62.4%). Hierarchies of training opportunities emerged with training by consultants being most valued. 71.8% (95% CI 60.7-81.3) of trainees believed the EWTD has had a deleterious effect on their training and experience and 74.3% (95% CI 63.2-83.4) thought that they will be less prepared for a consultant post. 69.9% (95% CI 58.7-79.5) considered that their quality of life outside work had deteriorated, with only 15% (95% CI 8.3-24.6) finding improvement. 38.6% (95% CI 27.8-50.3) felt that they were not functioning as well as doctors, only 14.3% (95% CI 7.6-23.9) noting improvement. The trainees were still positive about anaesthesia and 73.2% (95% CI 62.2-82.5) would recommend this specialty to a student. The majority of anaesthetic SpRs in the Mersey Deanery have not welcomed the changes brought by the EWTD to their training, experience and quality of life outside work.


[Effect of interleukin-18 gene modified human umbilical cord mesenchymal stem cells on proliferation of breast cancer cell].
To establish human umbilical cord mesenchymal stem cells (HUMSCs) strain transfected with interleukin-18 (IL-18) gene and examine its effects on the proliferation of breast cancer cell (MCF-7). HUMSCs were isolated and cultured. And the lentivirus-IL-18 vector containing human IL-18 gene was constructed and transfected into HUMSCs. The expressions of IL-18 gene mRNA and protein were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. After co-culturing for 1, 3, 5 days, Transwell and cell counting kit-8 (CCK-8) assays were performed on MCF-7 to plot the cell growth curve. IL-18-HUMSCs could stably express of IL-18 gene and inhibit the proliferation of breast cancer cells. The IL-18 mRNA relative expression amounts were 1.40 ± 0.21 for experimental group (IL-18-HUMSCs), 0.59 ± 0.09 for negative control group (NV-HUMSCs) and 0.71 ± 0.05 for blank control group (HUMSCs). As compared with control group, the difference was statistically significant (F = 31.81, P = 0.001). The relative expressions of IL-18 protein were 1.54 ± 0.27 for experimental group (IL-18-HUMSCs), 0.57 ± 0.04 for negative control group (NV-HUMSCs) and 0.59 ± 0.23 for blank control group (HUMSCs). As compared with control group, the difference was statistically significant (F = 22.32, P = 0.002). After co-culturing for 5 days, the cellular proliferation was significantly inhibited. IL-18 gene has been successfully transfected into HUMSCs and has a stable expression. And IL-18-HUMSCs can effectively inhibit the proliferation of breast cancer cells in vitro.


Detection of breast cancer cells in blood samples by immunostaining of the Thomsen-Friedenreich antigen.
Disseminated tumor cells are found in the bone marrow of patients with epithelial carcinoma and are correlated with a poor prognosis of the disease. Their detection is a technical challenge. This report describes a model system for the detection of cancer cells by co-immunostaining of Thomsen-Friedenreich and Her-2 antigens. Small numbers of cancer cells from different cancer cell lines were mixed with blood samples of healthy donors. Cytospins were prepared and double immunostaining against Thomsen-Friedenreich antigen and Her-2 was carried out by fluorochrome-coupled antibodies. Quantification of Thomsen-Friedenreich and/or Her-2-positive cells was performed with an epifluorescence microscope. On average, 83% of cancer cells were recovered by this method. Immunostaining is a useful method for the detection of cancer cells in blood samples. Results of this model system will be transferred to bone marrow patient samples to prove the benefits for detection of disseminated tumor cells.


Trends in Surgical Practices for Lateral Epicondylitis Among Newly Trained Orthopaedic Surgeons.
Much controversy exists regarding the optimal surgical intervention for lateral epicondylitis because of a multitude of options available and the lack of comparative studies. Knowledge of the current practice trends would help guide the design of comparative studies needed to determine which surgical technique results in the best outcome. To review the latest practice trends for the surgical treatment of lateral epicondylitis among newly trained surgeons in the United States utilizing the American Board of Orthopaedic Surgery (ABOS) database. Cross-sectional study; Level of evidence, 3. The ABOS database was utilized to identify surgical cases for lateral epicondylitis submitted by Part II board certification examination candidates from 2004 through 2013. Inclusion criteria were predetermined using a combination of International Classification of Diseases, Ninth Revision (ICD-9) and Current Procedural Terminology (CPT) codes. Cases were organized by open and arthroscopic treatment groups and by fellowship training and were analyzed to determine differences in surgical techniques, complication rates, and concomitant procedures. In total, 1150 surgeons submitted 2106 surgical cases for the treatment of lateral epicondylitis. The number of surgical cases for lateral epicondylitis performed per 10,000 submitted cases significantly decreased from 26.7 in 2004 to 21.1 in 2013 (P = .002). Among all cases, 92.2% were open and 7.8% were arthroscopic, with no change in the incidence of arthroscopic surgeries over the study period. Shoulder and elbow (18.1%) and sports medicine (11.4%) surgeons were more likely to perform surgery arthroscopically compared with hand surgeons (6.1%) (P < .001). There was no difference in overall self-reported complication rates between open (4.4%) and arthroscopic (5.5%) procedures (P = .666). Percutaneous tenotomy, debridement only, and debridement with tendon repair comprised 6.4%, 46.3%, and 47.3% of open treatment, respectively. Sports medicine, hand, and shoulder and elbow surgeons were more likely to repair the tendon after debridement compared with other surgeons, who were more likely to perform debridement alone (P < .001). Hand surgeons were most likely to perform concomitant procedures, of which the majority were neuroplasties. Although comparative studies are ultimately necessary for determining the optimal surgical technique, researchers should be mindful of the differences in practices according to training and the extent to which concomitant procedures are being performed, as both these factors may confound any future results.


Zinc(II) tolerance in Escherichia coli K-12: evidence that the zntA gene (o732) encodes a cation transport ATPase.
A transposon (Tn 10dCam) insertion mutant of Escherichia coli K-12 was isolated that exhibited hypersensitivity to zinc(II) and cadmium(II) and, to a lesser extent, cobalt(II) and nickel (II). The mutated gene, located between 75.5 and 76.2 min on the chromosome, is named zntA (for Zn(II) transport or tolerance). The metal-sensitive phenotype was complemented by a genomic DNA clone mapping at 3677.90-3684.60 kb on the physical map. Insertion of a kanamycin resistance (KnR) cassette at a SalI site in a subcloned fragment generated a plasmid that partially complemented the zinc(II)-sensitive phenotype. DNA sequence analysis revealed that the KnR cassette was located within the putative promoter region of an ORF (o732 or yhhO) predicted to encode a protein of 732 amino acids, similar to cation transport P-type ATPases in the Cpx-type family. Inverse PCR and sequence analysis revealed that the Tn 10dCam element was located within o732 in the genome of the zinc(II)-sensitive mutant. The zntA mutant had elevated amounts of intracellular and cell surface-bound Zn(II), consistent with the view that zntA+ encodes a zinc(II) efflux protein. Exposure of the zntA mutant to cobalt(II) and cadmium(II) also resulted in elevated levels of intracellular and cell surface-bound metal ions.


Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia.
On the basis of the glutamatergic dysfunction hypothesis of schizophrenia, we have been conducting a systematic study of the association of glutamate receptor genes with schizophrenia. Here we report association studies of schizophrenia with polymorphisms in three kainate receptor genes: GRIK3, GRIK4 and GRIK5. We selected 16, 24 and 5 common single nucleotide polymorphisms (SNPs) distributed in the entire gene regions of GRIK3 (>240 kb), GRIK4 (>430 kb) and GRIK5 (>90 kb), respectively. We tested associations of the polymorphisms with schizophrenia using 100 Japanese case-control pairs (the Kyushu set). We observed no significant "single marker" associations with the disease in any of the 45 SNPs tested except for one (rs3767092) in GRIK3 showing a nominal level of significance. The significant association, however, disappeared after the application of the Bonferroni correction. We also observed significant haplotype associations in seven SNP pairs in GRIK3 and in four SNP pairs in GRIK4. None, however, remained significant after Bonferroni correction. We also failed to replicate the nominally significant haplotype associations in a second sample set, the Aichi set (106 cases and 100 controls). We conclude that SNPs in the gene regions of GRIK3, GRIK4 or GRIK5 do not play a major role in schizophrenia pathogenesis in the Japanese population.


Volatile anaesthetics and the atmosphere: atmospheric lifetimes and atmospheric effects of halothane, enflurane, isoflurane, desflurane and sevoflurane.
The atmospheric lifetimes of the halogenated anaesthetics halothane, enflurane, isoflurane, desflurane and sevoflurane with respect to reaction with the hydroxyl radical (OH.) and UV photolysis have been determined from observations of OH. reaction kinetics and UV absorption spectra. Rate coefficients for the reaction with OH radicals for all halogenated anaesthetics investigated ranged from 0.44 to 2.7 x 10(-14) cm3 molec-1 s-1. Halothane, enflurane and isoflurane showed distinct UV absorption in the range 200-350 nm. In contrast, no absorption in this wavelength range was detected for desflurane or sevoflurane. The total atmospheric lifetimes, as derived from both OH. reactivity and photolysis, were 4.0-21.4 yr. It has been calculated that up to 20% of anaesthetics enter the stratosphere. As a result of chlorine and bromine content, the ozone depletion potential (ODP) relative to chlorofluorocarbon CFC-11 varies between 0 and 1.56, leading to a contribution to the total ozone depletion in the stratosphere of approximately 1% for halothane and 0.02% for enflurane and isoflurane. Estimates of the greenhouse warming potential (GWP) relative to CFC-12 yield values of 0.02-0.14, resulting in a relative contribution to global warming of all volatile anaesthetics of approximately 0.03%. The stratospheric impact of halothane, isoflurane and enflurane and their influence on ozone depletion is of increasing importance because of decreasing chlorofluorocarbons globally. However, the influence of volatile anaesthetics on greenhouse warming is small.


Improved Bat Algorithm Based on Multipopulation Strategy of Island Model for Solving Global Function Optimization Problem.
The bat algorithm (BA) is a heuristic algorithm that globally optimizes by simulating the bat echolocation behavior. In order to improve the search performance and further improve the convergence speed and optimization precision of the bat algorithm, an improved algorithm based on chaotic map is introduced, and the improved bat algorithm of Levy flight search strategy and contraction factor is proposed. The optimal chaotic map operator is selected based on the simulation experiments results. Then, a multipopulation parallel bat algorithm based on the island model is proposed. Finally, the typical test functions are used to carry out the simulation experiments. The simulation results show that the proposed improved algorithm can effectively improve the convergence speed and optimization accuracy.


Regulation of expression of carbon-assimilating enzymes by nitrogen in maize leaf.
We have utilized the cellular differentiation gradient of the developed, youngest leaf to examine the regulation by nitrogen of levels of phosphoenolpyruvate carboxylase (PEPCase), pyruvate orthophosphate dikinase (PPDK), and ribulose 1,5-bisphosphate carboxylase in maize (Zea mays L.). The protein whose level regulated most preferentially by N availability was PEPCase, followed by PPDK, and the changes in level occurred most conspicuously at the photosynthetically maturing cells. Pulse and pulse-chase experiments to analyze photosynthetic fixation of [(14)C]CO(2) indicate that maize leaf primarily exploited a C(4)-mode of photosynthetic fixation of carbon dioxide even under a selective reduction in levels of these proteins. The effects of N on the synthesis of these proteins and the accumulation of corresponding mRNAs during recovery from a deficiency were examined by pulse and pulse-chase labeling with [(35)S]Met and by hybridization, respectively. The rate of turnover of PPDK was substantially higher than that of the other proteins. Results also showed that the reduced accumulation of PEPCase, as well as PPDK, under N deficiency could largely be accounted for a reduced level of synthesis of protein with a concomitant reduction in level of their mRNAs. This indicates that the N-dependent selective accumulation of these enzymes is primarily a consequence of level of its mRNAs.


Redox Potential and ROS-Mediated Nanomedicines for Improving Cancer Therapy.
The overabundance of reactive oxygen species (ROS) and antioxidants in cancer cells represents a challenge for therapeutic intervention, while also providing an opportunity for the development of new strategies to improve clinical therapeutic outcomes. Recent Advances: Nanotechnology has advanced tremendously in recent decades and now offers many potential opportunities to leverage altered redox status to improve conventional therapies. Highly tunable nanoparticle delivery systems have shown great promise for improving the following: (i) chemotherapy via selective redox-sensitive drug release in tumor cells and limited systemic toxicity; (ii) photodynamic therapy via enhancing photoactivation and/or ROS production; and (iii) radiation therapy via enhancing ROS production. Great progress has also been made regarding novel nanoparticle-mediated therapies to enhance tumor cell death via ROS generation and angiogenic inhibition. Current anticancer therapies are limited by systemic side effects and resistance. The inherent heterogeneity and hypoxic status of solid tumors impose significant barriers for even the most rationally designed nanoparticle systems. In addition, few comprehensive biodistribution and toxicity evaluations exist, and clinical efficacy remains to be established. The practicality of many nanoparticle systems is compromised by variable in vivo responses and scale-up difficulties due to complicated chemistry and prohibitive manufacturing costs. As nanoparticle design continues to advance, improved therapeutic efficacy will likely follow. Actively targeted systems may improve distribution specificity but more positive clinical demonstrations are needed. Further investigation into systemic and intracellular distribution as well as toxicity will improve understanding of how these nanoparticle systems can be applied to improve existing therapies.


An outline of object-oriented philosophy.
This article summarises the principles of object-oriented philosophy and explains its similarities with, and differences from, the outlook of the natural sciences. Like science, the object-oriented position avoids the notion (quite common in philosophy) that the human-world relation is the ground of all others, such that scientific statements about the world would only be statements about the world as it is for humans. But unlike science, object-oriented metaphysics treats artificial, social, and fictional entities in the same way as natural ones, and also holds that the world can only be known allusively rather than directly.


Genome-Wide Identification and Analysis of MicroRNAs Involved in Witches'-Broom Phytoplasma Response in Ziziphus jujuba.
MicroRNAs (miRNAs) play an important role in responding to biotic and abiotic stresses in plants. Jujube witches'-broom a phytoplasma disease of Ziziphus jujuba is prevalent in China and is a serious problem to the industry. However, the molecular mechanism of the disease is poorly understood. In this study, genome-wide identification and analysis of microRNAs in response to witches'-broom was performed. A total of 85 conserved miRNA unique sequences belonging to 32 miRNA families and 24 novel miRNA unique sequences, including their complementary miRNA* strands were identified from small RNA libraries derived from a uninfected and witches'-broom infected Z. jujuba plant. Differentially expressed miRNAs associated with Jujube witches'-broom disease were investigated between the two libraries, and 12 up-regulated miRNAs and 10 down- regulated miRNAs identified with more than 2 fold changes. Additionally, 40 target genes of 85 conserved miRNAs and 49 target genes of 24 novel miRNAs were predicted and their putative functions assigned. Using the modified 5'-RACE method, we confirmed that SPL and MYB were cleaved by miR156 and miR159, respectively. Our results provide insight into the molecular mechanisms of witches'-broom disease in Z. jujuba.


PVAC (Corixa/Genesis/Medicis).
Corixa, Genesis and Medicis are developing PVAC, an immunomodulator derived from killed Mycobacterium vaccae and licensed from SR Pharma [309860], [312958], for the potential treatment of psoriasis [365490]. In February 2001, phase II trials were ongoing in the US, the Philippines and Brazil for the treatment of moderate-to-severe psoriasis [399066], [405985]. In January 2001, an NDA filing was expected to take place in 2003 [396733]. In January 2002, Medicis and Corixa planned to initiate another phase IIb trial [436398], and by June 2002, two studies in patients with mild-to-moderate plaque psoriasis had began in the US and New Zealand, with the former designed to investigate the use of PVAC in combination with ultraviolet B (UVB) light [453772], [456657], [456836].


Lost in translation or deliberate falsification? Genetic analyses reveal erroneous museum data for historic penguin specimens.
Historic museum specimens are increasingly used to answer a wide variety of questions in scientific research. Nevertheless, the scientific value of these specimens depends on the authenticity of the data associated with them. Here we use individual-based genetic analyses to demonstrate erroneous locality information for archive specimens from the late nineteenth century. Specifically, using 10 microsatellite markers, we analysed 350 contemporary and 43 historic yellow-eyed penguin (Megadyptes antipodes) specimens from New Zealand's South Island and sub-Antarctic regions. Factorial correspondence analysis and an assignment test strongly suggest that eight of the historic specimens purportedly of sub-Antarctic origin were in fact collected from the South Island. Interestingly, all eight specimens were obtained by the same collector, and all are currently held in the same museum collection. Further inspection of the specimen labels and evaluation of sub-Antarctic voyages did not reveal whether the erroneous data are caused by incorrect labelling or whether deliberate falsification was at play. This study highlights a promising extension to the well-known applications of assignment tests in molecular ecology, which can complement methods that are currently being applied for error detection in specimen data. Our results also serve as a warning to all who use archive specimens to invest time in the verification of collection information.


Evaluation of the interfractional biological effective dose (BED) variation in MammoSite high dose rate brachytherapy.
The objective of this work is to evaluate the interfractional biological effective dose (BED) variation in MammoSite high dose rate (HDR) brachytherapy. Dose distributions of 19 patients who received 34 Gy in 10 fractions were evaluated. A method was employed to account for nonuniform dose distribution in the BED calculation. Furthermore, a range of alpha/beta values was utilized for specific clinical end points: fibrosis, telangiectasia, erythema, desquamation and breast carcinoma. Two scenarios were simulated to calculate the BED value using: i) the same dose distribution of fraction 1 over fractions 2-10 (constant case, CC), and ii) the actual delivered dose distribution for each fraction 1-10 (interfractiondose variation case, IVC). Although the average BED difference (IVC - CC) was < 0.7 Gy for all clinical endpoints, the range of difference for fibrosis and telangiectasia reached -11% to +3% and -9% to +9% for one of the patients, respectively. By disregarding high inhomogeneity in HDR brachytherapy, the conventional BED calculation tends to overestimate the BED for fibrosis by 16% on average, while it underestimates the BED for erythema (7.6%) and desquamation (10.2%). In conclusion, the BED calculation accounting for the nonuniform dose distribution provides a more clinically relevant description of the clinical delivered dose. Though the average BED difference was clinically insignificant, the maximum difference of BED for late effects can differ by a single fractional dose (10%) for a specific patient due to the interfraction dose variation in MammoSite treatment.


A case of transcatheter prosthetic aortic valve endocarditis.
Transcatheter aortic valve implantation (TAVR) constitutes an established treatment in inoperable or high perioperative risk patients with severe aortic stenosis. Prosthetic valve endocarditis after ΤΑVR occurs with an incidence of 0.3-1% per patient-year. Infective endocarditis may stem from hematogenous dissemination or contact with infected adherent tissue. Few cases of infective endocarditis after TAVR have been reported. We present an interesting case of a 79-year-old male with a history of severe aortic stenosis status post TAVR greater than one year ago, and pulmonary vein isolation for atrial fibrillation six weeks ago was found to have infective endocarditis with a vegetation on the prosthetic valve leading to multiple embolic strokes as a result of Enterococcus faecalis bacteremia. The patient was not a surgical candidate with his Society of Thoracic Surgery (STS) risk score being 18%; therefore, he was managed conservatively on intravenous antibiotics. Our case had endocarditis from enterococcus bacteremia; however, the patient never had any gastrointestinal or genitourinary procedure.


DNA distortion mechanism for transcriptional activation by ZntR, a Zn(II)-responsive MerR homologue in Escherichia coli.
MerR-like DNA distortion mechanisms have been proposed for a variety of stress-responsive transcription factors. The Escherichia coli ZntR protein, a homologue of MerR, has recently been shown to mediate Zn(II)-responsive regulation of zntA, a gene involved in Zn(II) detoxification. To determine whether the MerR DNA distortion mechanism is conserved among MerR family members, we have purified ZntR to homogeneity and shown that it is a zinc receptor that is necessary and sufficient to stimulate Zn-responsive transcription at the zntA promoter. Biochemical, DNA footprinting, and in vitro transcription assays indicate that apo-ZntR binds in the atypical 20-base pair spacer region of the promoter and distorts the DNA in a manner that is similar to apo-MerR. The addition of Zn(II) to ZntR converts it to a transcriptional activator protein that introduces changes in the DNA conformation. These changes apparently make the promoter a better substrate for RNA polymerase. We propose that this zinc-sensing homologue of MerR restructures the target promoter in a manner similar to that of other stress-responsive transcription factors. The ZntR metalloregulatory protein is a direct Zn(II) sensor that catalyzes transcriptional activation of a zinc efflux gene, thus preventing intracellular Zn(II) from exceeding an optimal but as yet unknown concentration.


Macrolide Allergic Reactions.
Macrolides are antimicrobial agents that can be used to treat a variety of infections. Allergic reactions to macrolides occur infrequently but can include minor to severe cutaneous reactions as well as systemic life-threatening reactions such as anaphylaxis. Most reports of allergic reactions occurred in patients without prior exposure to a macrolide. Cross-reactivity among macrolides may occur due to the similarities in their chemical structures; however, some published literature indicates that some patients can tolerate a different macrolide. Most published reports detailed an allergic reaction to erythromycin. Desensitization protocols to clarithromycin and azithromycin have been described in the literature. The purpose of this article is to summarize macrolide-associated allergic reactions reported in published literature. An extensive literature search was conducted to identify publications linking macrolides to hypersensitivity reactions.


Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer.
Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 µM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.


[Specialized products for nutrition of children with mucoviscidosis].
Mucoviscidosis is serious inherited disease with lesions of almost all secretory cells of mucosa and exocrine glands, following by disturbances of metabolism, digestion and nutritional status. Using of modern high effective pancreatic enzymes does not allow to reach a normalization of protein metabolism and digestion especially of fats. For success treatment of this disease the effective dietetic methods should be used including dietary intake of special food products which can supply enough energy and nutrients in small volume. The nutrient contents of a few foreign substitution of breast milk and food product for older children are given. The results of treatment of 86 children suffering from mucoviscidosis are presented. Milk proteins (casein, whey proteins), hydrolysates of milk protein and soy protein isolates are main resources of protein component in special food. Fat components are produced from middle-chain triglycerides (60-70%) and vegetable oils. Carbohydrates in special food are made from glucose polymers, glucose, fructose and sucrose. Positive results of clinical trials of foreign special food have been an example for creation of two home-produced food for treatment of children with mucoviscidosis: 1) adapted version "A" for children in age under 1 year, and 2) version "B" for older children. The products were created on basis of native milk protein with ratio casein to whey protein as 60:40. Middle-chain triglycerides compose 70-75% of fats. Carbohydrates are presented by dextrin-maltose (85%), glucose and sucrose. In present time these special products are under clinical trial in scientific medico-genetic center of Russia' Academy of Medical Science.


Geometric interpretations for resonances of plasmonic nanoparticles.
The field of plasmonics can be roughly categorized into two branches: surface plasmon polaritons (SPPs) propagating in waveguides and localized surface plasmons (LSPs) supported by scattering particles. Investigations along these two directions usually employ different approaches, resulting in more or less a dogma that the two branches progress almost independently of each other, with few interactions. Here in this work we interpret LSPs from a Bohr model based geometric perspective relying on SPPs, thus establishing a connection between these two sub-fields. Besides the clear explanations of conventional scattering features of plasmonic nanoparticles, based on this geometric model we further demonstrate other anomalous scattering features (higher order modes supported at lower frequencies, and blueshift of the resonance with increasing particle sizes) and multiple electric resonances of the same order supported at different frequencies, which have been revealed to originate from backward SPP modes and multiple dispersion bands supported in the corresponding plasmonic waveguides, respectively. Inspired by this geometric model, it is also shown that, through solely geometric tuning, the absorption of each LSP resonance can be maximized to reach the single channel absorption limit, provided that the scattering and absorption rates are tuned to be equal.


[The surgical treatment of proximal humerus fractures in children and adolescent].
The aim of his study was to evaluate outcomes of the surgical treatment of proximal humerus fractures in children. The studied group consisted of 24 patients who were operated on during the period 1997-2006. Operative and postoperative complications were evaluated. For the follow up evaluation Constant-Murley Score and Oxford Shoulder Score in own modification were employed. The scores assessed the following characteristics: pain, activity level in daily living, range of motion and shoulder strength. In all reported cases a correct union was obtained as well as the anatomical axis of the bone (only in one child 20 degrees varus curve of the bone remained but without limitation in the shoulder motion range). The total of 21 patients were evaluated during follow-up visits, 13 patients obtained the result "very good" and 8 "good" in the Consant-Murley Score. According to the Oxford Schoulder Score 18 patients obtained maximum results, and 3 children results above 95% of the maximum score. In the study group the results of the surgical treatment of proximal humerus fractures were very good. We can therefore recommend this type of treatment in patients with proximal humerus fracture with large dislocation and angulation.


Experience with the colony-forming (stem cell) assay of in vitro chemosensitivity in the management of patients with advanced malignant melanoma.
Twenty-two patients with advanced malignant melanoma had tumor nodules biopsied and tumor cell colonies established in vitro in the colony-forming assay in the presence of vindesine. The patients then received iv vindesine at a dose of 3 mg/m2/week for 6 weeks. In four patients, in vitro death of cells exposed to vindesine in vitro correlated with clinical response to therapy. In the remaining 18 patients, lack of both in vitro and clinical response was noted.


High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types.
Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid beta-peptide (Abeta)-centric theory holds that Abeta is involved in the pathogenesis of sporadic AD. Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes lead to increased Abeta levels before symptoms arise. To evaluate the pattern of Pittsburgh Compound B (PiB) retention in subjects with different autosomal dominant mutations associated with familial AD vs that in healthy age-matched control subjects and subjects with probable sporadic AD, to correlate Abeta burden as measured by PiB with available clinical and cognitive data, and to compare the regional brain patterns of PiB retention and fluorodeoxyglucose F 18 (FDG) uptake. Correlation analysis of positron emission tomography (PET) imaging studies. Academic research. Seven PSEN1 mutation carriers and 1 APP mutation carrier underwent PiB and FDG PET imaging. Amyloid beta-peptide burden and FDG uptake were established using standardized uptake values normalized to pons. Primary outcomes were PET results, which were compared with those of a well-characterized cohort of 30 healthy control subjects and 30 subjects with probable sporadic AD. All mutation carriers had high PiB retention in the striatum, with some also having cortical PiB retention in ventrofrontal and posterior cingulate/precuneus areas. The striatal pattern of PiB retention was similar in the PSEN1 and APP mutation carriers. Neither striatal nor cortical Abeta burden was related to cognitive status. Consistent with previous studies, the pattern of Abeta deposition in familial AD differs from that in sporadic AD, with higher striatal and somewhat lower cortical PiB retention in familial AD. The pattern and degree of Abeta deposition were not associated with mutation type nor cognitive status.


Light-Stimulated Gibberellin Biosynthesis in Gibberella fujikuroi.
Gibberellins (GAs) are a group of plant growth hormones that were first isolated from the fungus Gibberella fujikuroi. The biosynthesis of GA in liquid cultures of the fungus has been examined using high-performance liquid chromatography and combined gas chromatography-mass spectrometry. GA(3) was the predominant GA in well-aerated cultures. GA(4) and GA(7), intermediates in GA(3) biosynthesis, accumulated in cultures with low levels of dissolved oxygen, but were not detectable in more highly aerated cultures. Light stimulated the production of GA(3) in G. fujikuroi cultures grown from young stock cultures. Cell-free enzyme studies revealed a significant stimulation in the levels of kaurenoic acid oxidation in cultures grown in the light in comparison with those grown in the dark. However, measurements of the relative rates of [(14)C]mevalonic acid incorporation into kaurene showed no effect of light on this early part of the pathway. Preliminary experiments indicated that blue light is most effective in enhancing kaurenoic acid oxidation.


Connexin43 silencing in myofibroblasts prevents arrhythmias in myocardial cultures: role of maximal diastolic potential.
Arrhythmogenesis in cardiac fibrosis remains incompletely understood. Therefore, this study aims to investigate how heterocellular coupling between cardiomyocytes (CMCs) and myofibroblasts (MFBs) affects arrhythmogeneity of fibrotic myocardial cultures. Potentially, this may lead to the identification of novel anti-arrhythmic strategies. Co-cultures of neonatal rat CMCs and MFBs in a 1:1 ratio were used as a model of cardiac fibrosis, with purified CMC cultures as control. Arrhythmogeneity was studied at day 9 of culture by voltage-sensitive dye mapping. Heterocellular coupling was reduced by transducing MFBs with lentiviral vectors encoding shRNA targeting connexin43 (Cx43) or luciferase (pLuc) as control. In fibrotic cultures, conduction velocity (CV) was lowered (11.2 ± 1.6 cm/s vs. 23.9 ± 2.1 cm/s; P < 0.0001), while action potential duration and ectopic activity were increased. Maximal diastolic membrane potential (MDP) of CMCs was less negative in fibrotic cultures. In fibrotic cultures, (n = 30) 30.0% showed spontaneous re-entrant tachyarrhythmias compared with 5% in controls (n = 60). Cx43 silencing in MFBs made the MDP in CMCs more negative, increased excitability and CV by 51% (P < 0.001), and reduced action potential duration and ectopic activity (P < 0.01), thereby reducing re-entry incidence by 40% compared with pLuc-silenced controls. Anti-arrhythmic effects of Cx43 down-regulation in MFBs was reversed by depolarization of CMCs through I(k1) inhibition or increasing extracellular [K(+)]. Arrhythmogeneity of fibrotic myocardial cultures is mediated by Cx43 expression in MFBs. Reduced expression of Cx43 causes a more negative MDP of CMCs. This preserves CMC excitability, limits prolongation of repolarization and thereby strongly reduces the incidence of spontaneous re-entrant tachyarrhythmias.


A case of peritonitis caused by Roseomonas gilardii in a patient undergoing continuous ambulatory peritoneal dialysis.
A case of peritonitis caused by Roseomonas gilardii in a patient receiving continuous ambulatory peritoneal dialysis is presented. The patient's domestic water supply was implicated as the probable source of infection. This is the first report of R. gilardii causing such an infection.


Burden of methicillin-resistant Staphylococcus aureus pneumonia among hospitalized patients in Lebanon and Saudi Arabia.
The objective of this study is to describe the real-world treatment patterns and burden of suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in Saudi Arabia and Lebanon. A retrospective chart review study evaluated 2011-2012 data from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA pneumonia, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics (eg, age and comorbidities), treatment patterns (eg, timing and use of antimicrobials), hospital resource utilization (eg, length of stay), and clinical outcomes (eg, clinical status at discharge and mortality). Descriptive results were reported using frequencies or proportions for categorical variables and mean and standard deviation for continuous variables. Chart-level data were collected for 93 patients with MRSA pneumonia, 50 in Saudi Arabia and 43 in Lebanon. The average age of the patients was 56 years, and 60% were male. The most common comorbidities were diabetes (39%), congestive heart failure (30%), coronary artery disease (29%), and chronic obstructive pulmonary disease (28%). Patients most frequently had positive cultures from pulmonary (87%) and blood (27%) samples. All isolates were sensitive to vancomycin, teicoplanin, and linezolid, and only one-third of the isolates tested were sensitive to ciprofloxacin. Beta-lactams (inactive therapy for MRSA) were prescribed 21% of the time across all lines of therapy, with 42% of patients receiving first-line beta-lactams. Fifteen percent of patients did not receive any antibiotics that were considered to be MRSA active. The mean hospital length of stay was 32 days, and in-hospital mortality was 30%. The treatment for MRSA pneumonia in Saudi Arabia and Lebanon may be suboptimal with inactive therapy prescribed a substantial proportion of the time. The information gathered from this Middle East sample provides important perspectives on the current treatment patterns.


Regulation of mesangial cell proliferation.
Regardless of the source of injury, an imbalance in the control of mesangial cell proliferation appears to play a direct role in the degree of progressive renal injury and glomerulosclerosis. Some of the regulatory mechanisms include specific soluble or non-soluble extracellular factors and a complex array of receptor-mediated signals that control the progression of the cell cycle or cell death. Understanding these regulatory processes could lead to novel therapeutic strategies to alleviate or arrest proliferative glomerular disease.


Cognitive abilities underlying performance on the modified card sorting test: novel and traditional scores.
The Modified Card Sorting Test (MCST) is a widely used variation of the Wisconsin Card Sorting Test. It is faster to administer, less frustrating for respondents and less ambiguous in its scoring but has been criticized for its task impurity and low discriminability between control participants and clinical groups prone to executive dysfunction. This study aimed to examine the executive functions (EF) underlying traditional (number of categories completed, perseverative errors) and novel scores for the MCST, and compare their ability to differentiate between control and clinical samples. Novel and traditional MCST scores were compared between 94 control participants, 87 with bipolar disorder and 64 with major depression. The relationship between MCST scores and traditional EF tasks was examined through correlation and regression analyses. All MCST scores were associated with at least one measure of EF, the most common of which were the Trail Making or Hayling Tests. IQ predicted most scores on the MCST, save for nonperseverative errors and categorizing efficiency. Traditional and novel scores differentiated between clinical and control groups. These findings support the utility of the MCST in detecting executive dysfunction and highlight the importance of new scoring methods in increasing the specificity and interpretability of this task.


Guided wave modes in porous cylinders: experimental results.
In this paper guided wave modes in porous media are investigated. A water-saturated porous cylinder is mounted in the test section of a shock tube. Between the porous sample and the wall of the shock tube a water-filled annulus exists. For very small annulus width, bulk waves are generated and one-dimensional modeling is sufficient. Otherwise two-dimensional effects become important and multiple guided wave modes occur. Using a newly developed traversable positioning system in the shock tube, the frequency-dependent phase velocities and damping coefficients in the 1-120 kHz frequency range were measured. Prony's method was used for data processing. Agreement was found between the experimental data and the two-dimensional modeling of the shock tube which was based on Biot's theory.


Phospholipid synthesis and exchange in castor bean endosperm homogenates.
Crude organelle preparations from castor bean (Ricinus communis L.) endosperm rapidly incorporate CDP-((14)C)choline and CDP-((14)C)-ethanolamine into phosphatidylcholine and phosphatidylethanolamine, respectively. Separation of organelles by sucrose density gradient centrifugation following incubation with these substrates demonstrated that most of the (14)C phospholipids thus formed were present in the endoplasmic reticulum membranes, although label was also found in mitochondria, proplastids, and glyoxysomes. The phospholipid-synthesizing enzymes, cholinephosphotransferase and ethanolaminephosphotransferase, are exclusively confined to the endoplasmic reticulum membrane fraction, suggesting that the appearance of (14)C-phospholipid in other organelles was due to phospholipid exchange. Phospholipid synthesis was inhibited by the cytoplasmic supernatant fraction. The active inhibitor in this fraction was not identified, but the inhibition was not significantly relieved by either dialyzing or boiling the supernatant. Phosphatidylcholine synthesis showed an absolute requirement for Mg(2+); the Michaelis constant was 1 mm. Ca(2+) was a potent inhibitor of Mg(2+)-stimulated phospholipid synthesis and enhanced the decay of (14)C-phospholipids from pre-labeled membranes, particularly when the membranes were resuspended in the cytoplasmic supernatant.The data are consistent with the concept that the endoplasmic reticulum is a major site of membrane proliferation where structural lipids, and possibly proteins, are inserted into, and thus expand, a pre-existing membrane fraction. Other organelle and cellular membranes could therefore originate from the proliferating endoplasmic reticulum by a process of membrane flow and differentiation.