Glycoproteins and glycolipids of rat small intestinal microvillus and basolateral membranes.
Glycoprotein and glycolipid constituents were examined in purified microvillus and basolateral membranes isolated from rat small intestinal epithelial cells. SDS-polyacrylamide gel electrophoresis showed that the molecular weights of most of the major proteins from microvillus membranes were over 100 kD, whereas the majority of those from basolateral membranes tended to have lower molecular weights. Glycoprotein profiles were also examined using three labeling methods, and in each case marked differences were observed between microvillus and basolateral membranes. In both membranes, lectins with a specificity toward N-linked sugar chains bound to the majority of the glycoproteins, in contrast to those lectins which preferentially bind to O-linked sugar chains. Glycolipids were labeled in vivo and isolated from both membrane fractions. Some differences were observed in the fucolipids and neutral glycolipids suggesting a more complex pattern in microvillus membranes. These results indicate that there are differences in the glycoprotein and glycolipid compositions of microvillus and basolateral membranes that may reflect the functional polarity of intestinal epithelial cells.


Clinical report on external irradiation combined with californium-252 neutron intraluminal brachytherapy for cervical carcinoma treatment.
Neutron rays produce high linear energy transfer radiation, which has particular radiobiological characteristics. The aim of the study was to observe the curative effects and complications of external irradiation combined with californium-252 (252Cf) neutron intraluminal brachytherapy for treatment of cervical carcinoma. From December 2000 to December 2004, 128 cases of cervical carcinoma staged IIA to IIIB were treated with 252Cf neutron intraluminal brachytherapy using 8-10 Gy-eq per fraction, once a week. The total dose at reference point A was 36-40 Gy-eq in 4 to 5 fractions. From the second day after 252Cf neutron intraluminal brachytherapy, the whole pelvic cavity was treated with 6 MV X-ray external irradiation, applying 2 Gy per fraction 4 times per week. After 20-24 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield; the total dose of external irradiation was 44-50 Gy. The short-term curative effects were 95.3% complete remissions and 4.7% partial remissions. The 3-year and 5-year local control rates were 93.5% and 87.9%, respectively. The 3-year and 5-year survival rates were 87.5% and 70%, respectively. The rates of radiation complications were 4.7% for radiation cystitis, 7.8% for radiation proctitis, 6.3% for vaginal contracture and adhesion, and 5.5% for protracted radiation proctitis. The results of univariate and multivariate analysis indicated that differentiation of tumor cells and lymphatic metastasis are the main factors related to the clinical prognosis of cervical carcinoma. A combination of external irradiation with 252Cf neutron intraluminal brachytherapy for treatment of cervical carcinoma can be well tolerated by patients. The rate of local tumor control is high and radiation complications are few.


Economic impact of early detection and early intervention of psychosis.
Whilst there is a growing body of evidence relating to the effectiveness of early detection and early intervention services there have been relatively few studies which have provided information on whether they are cost-effective. The aim of this paper is to review the cost-effectiveness evidence for early detection and early intervention in psychosis. Full economic evaluations, cost studies, and studies which do not report costs but do provide important resource use information were included in the review. All cost effectiveness analysis to date suggest that it is possible to offer help early in the development of psychosis in a cost effective manner. The potential longer term economic benefits of early detection and early intervention are required.


Epithelioid cell histiocytoma: a report of two cases.
Epithelioid cell histiocytoma is a rarely reported tumor derived from factor-XIIIa-positive dermal dendrocytes. Two additional cases are presented including their clinical, histologic and immunohistochemical features.


[Clinical development of a new inactivated hepatitis A vaccine].
An attenuated vaccine against hepatitis A was developed from the GBM strain of the virus, cultured on human diploid MRC5 cells. Each dose contained 160 antigen units, inactivated by formalin and adsorbed onto 0.3 mg aluminum hydroxide, in a volume of 0.5 ml. Intramuscular injection of the vaccine conferred immunity to hepatitis A, with antibody titers greater than those obtained by passive immunization with immunoglobulin. In clinical studies, immunocompromised subjects became immune shortly after the first injection and more than 90% were found to be protected after 14 days (titer above 20 mIU/ml by RIA). All subjects (100%) were protected one month after the first injection. Immunity persisted for at least six months and was strengthened by a booster injection. The antibody titers determined after the first booster injection were consistent with a projected period of protection of ten years. Adverse reactions were mild and occurred within the first few days after vaccination, with the patient usually recovering spontaneously. The most common reaction was mild local pain, usually associated with redness of the skin. A nodule was observed at the injection site in a small number of cases. Mild fever, asthenia, headache, myalgia/arthralgia and gastrointestinal tract disorders were also reported. Reactions were reported less frequently after the booster injection than after the initial dose. The vaccine was as well tolerated by patients seropositive for the hepatitis A virus as by seronegative subjects. Thus, this vaccine can be used for active immunization against hepatitis A in adults and adolescents. It can be administered as primary immunization and as a booster injection.


Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain.
High-fat diets cause peripheral leptin resistance, and dietary lipid composition affects sensitivity to leptin. We examined the role of n-3 polyunsaturated fatty acid (PUFA) in peripheral leptin resistance. Dietary PUFAs (0.4% wt/wt) caused insensitivity to peripherally but not intracerebroventricularly administered leptin. n-3 PUFA increased body weight, associated with a significant reduction of leptin concentration in the cerebrospinal fluid. Dietary n-3 PUFA reduced transport of endogenous or exogenously administered leptin into the brain, associated with increased expression of hypothalamic occludin, but caused no change in expression of leptin receptors, proteins associated with leptin signaling or other tight junction proteins. Continuous intracerebroventricular infusion of an antisense morpholino oligonucleotide targeted to occludin mRNA reversed n-3 PUFA-induced insensitivity to peripherally administered leptin. We conclude that n-3 PUFA induces peripheral leptin resistance via an increase in the expression of hypothalamic occludin, reducing paracellular transport of leptin into the brain.


Monoamine abnormalities in the brain of scrapie-infected rats.
The effects of the scrapie agent on the levels of monoamines and their metabolites, and on choline acetyltransferase (CAT) activity have been investigated in discrete brain areas in the rat. Two strains of scrapie (8745 from sheep brain and C506 M3 from mice brain) were inoculated. Scrapie-infected rats showed a reduction in the levels of serotonin (prefrontal cortex, hippocampus, striatum) and dopamine (striatum) and an elevation of 5-HIAA levels (cerebral cortex, striatum, thalamus). Noradrenaline levels were decreased only in the cerebral cortex and cerebellum of rats infected with the scrapie strain C506 M3. CAT activity remained unchanged. These data suggest that the scrapie agent causes a derangement of noradrenergic, serotonergic and dopaminergic systems in the rat brain.


Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.
BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.


Contractile properties of in situ perfused skeletal muscles from rats with congestive heart failure.
We hypothesized that in congestive heart failure (CHF) slow-twitch but not fast-twitch muscles exhibit decreased fatigue resistance in the sense of accelerated reduction of muscle force during activity. Experiments were carried out on anaesthetized rats 6 weeks after induction of myocardial infarction or a sham operation (Sham). Animals with left ventricular end-diastolic pressure (LVEDP) > 15 mmHg under anaesthesia were selected for the CHF group. There was no muscle atrophy in CHF. Force generation by in situ perfused soleus (Sol) or extensor digitorum longus (EDL) muscles was recorded during stimulation (trains at 5 Hz for 6 s (Sol) or 10 Hz for 1.5 s (EDL) at 10 or 2.5 s intervals, respectively) for 1 h in Sol and 10 min in EDL at 37 degrees C. Initial force was almost the same in Sol from CHF and Sham rats, but relaxation was slower in CHF. Relaxation times (95-5 % of peak force) were 177 +/- 55 and 131 +/- 44 ms in CHF and Sham, respectively, following the first stimulation train. After 2 min of stimulation the muscles transiently became slower and maximum relaxation times were 264 +/- 71 and 220 +/- 45 ms in CHF and Sham, respectively (P < 0.05). After 60 min they recovered to 204 +/- 60 and 122 +/- 55 ms in CHF and Sham, respectively (P < 0.05). In CHF but not in Sham rats the force of contraction of Sol declined from the second to the sixtieth minute to 70 % of peak force. The EDL of both CHF and Sham fatigued to 24-28 % of initial force, but no differences in contractility pattern were detected. Thus, slow-twitch muscle is severely affected in CHF by slower than normal relaxation and significantly reduced fatigue resistance, which may explain the sensation of both muscle stiffness and fatigue in CHF patients.


Civilian Helicopter Search and Rescue Accidents in the United States: 1980 Through 2013.
Helicopters are commonly used in search and rescue operations, and accidents have occurred during helicopter search and rescue (HSAR) missions. The purposes of this study were to investigate whether the HSAR accident rate in the United States could be determined and whether any common contributing factors or trends could be identified. Searches were conducted of the National Transportation Safety Board aviation accident database, the records of the major search and rescue and air medical organizations, and the medical and professional literature for reports of HSAR accidents. A total of 47 civilian HSAR accidents were identified during the study. Of these, 43% involved fatal injuries, compared with a 19% fatality rate for US helicopter general aviation accidents during the same time period and a 40% rate for helicopter emergency medical services. The HSAR accidents carried a significantly higher risk of fatal outcomes when compared with helicopter general aviation accidents (2-tailed Fisher's exact test, P < .0005). Accidents that occurred at night and under instrument meteorological conditions did not have a statistically significant increase in percentage of fatal outcomes (P > .05). The number of HSAR missions conducted annually could not be established, so an overall accident rate could not be calculated. Although the overall number of HSAR accidents is small, the percentage of fatal outcomes from HSAR accidents is significantly higher than that from general helicopter aviation accidents and is comparable to that seen for helicopter emergency medical services operations. Further study could help to improve the safety of HSAR flights.


Neurite-myelin interaction in the control of purkinje axon growth and regeneration.
The limited regenerative capability of adult central neurons results from an interplay between the intrinsic growth potential of injured nerve cells and environmental growth-inhibitory signals, such as myelin-associated molecules. These molecules, which are known to inhibit axonal regeneration, are expressed in the adult intact central nervous system, suggesting that they also exert a constitutive regulatory function on uninjured neurites. However, most of the mechanisms underlying this function of myelin-associated factors are still unclear. To address this issue, we examined Purkinje cells, which show extremely poor regenerative capabilities. Such a weak intrinsic growth potential is attributed, at least in part, to inhibitory activity exerted by the myelin-associated molecule Nogo-A on growth-associated gene expression and axon plasticity of adult Purkinje cells. Indeed, the regenerative potential of these neurons declines during postnatal development in parallel with myelin deposition. In addition, myelin-associated factors regulate the development of the Purkinje axon intracortical plexus, contributing to the shaping of mature cerebellar connectivity. The action of environmental inhibitory factors can be partially counteracted by overexpression of neuronal growth-associated molecules. In fact, following axotomy, transgenic Purkinje cells that overexpress GAP-43 are able to sprout their axons into white matter and show a pronounced tendency to lose myelin. Altogether, these results suggest that the control exerted by myelin on Purkinje axon plasticity plays an important role in preventing aberrant growth and in stabilizing intracortical connectivity. Such a constitutive regulation may eventually hamper compensatory mechanisms set up by the same neurons in response to injury and thus determine their weak regenerative abilities.


Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.
The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs.


miR-223 reverses the resistance of EGFR-TKIs through IGF1R/PI3K/Akt signaling pathway.
Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, is a critical issue for the treatment of EGFR mutant-positive non-small cell lung cancer (NSCLC). Recent evidence supports the role of microRNA-223 (miR‑223) in modulating chemotherapeutic drug sensitivity, but its role in the resistance to EGFR-TKIs in NSCLC remains unclear. To this end, we investigated the involvement of miR‑223 in erlotinib resistance, using two pairs of TKI-sensitive or resistant cell lines, PC9 vs PC9/ER, and HCC827 vs HCC827/ER, as well as PC9/CD133+, which are lung cancer stem-like cells derived from PC9 cells. Downregulation of miR‑223 expression in PC9/ER and PC9/CD133+ cells was detected, and the reverse correlation of miR-233 and insulin-like growth factor 1 receptor (IGF1R) in these cells was also revealed. Next, levels of IGF1R mRNA and p-Akt were significantly reduced in miR‑223 stably transfected PC9/ER and PC9/CD133+ cells. However, the sensitivity of PC9/ER and PC9/CD133+ cells to erlotinib was partially restored, after overexpression of miR‑223 in those cells. Similar results were also observed in vivo. Furthermore, miR‑223-mediated inhibition of the IGF1R/PI3K/Akt signaling pathway may have been reversed by the agonist of IGF1R in miR‑223 transfected cells. Our findings indicated that downregulation of miR‑223, which can induce activation of the IGF1R/phosphatidylinositol 3-kinase (PI3K)/Akt pathway in PC9/ER and PC9/CD133+ cells, may be responsible for the resistance of PC9/ER and PC9/CD133+ cells to erlotinib, suggesting that miR‑223 is a potential therapeutic target for overcoming EGFR-TKIs resistance.


Multi-element features and trace metal sources of road sediment from a mega heavy industrial city in North China.
As the primary carrier of harmful elements, road sediment poses severe hazards to human health and ecological environment, especially in megacities. Based on the industrial cities in North China, this research focused on the multi-element features and the pollution levels, sources, and spatial distributions of trace metals in road sediment of Shijiazhuang. The mean levels of P (928.4 mg kg-1), S (1446.2 mg kg-1), Cl (783.9 mg kg-1), Br (5.3 mg kg-1), Na2O (2.0%), CaO (9.9%), Co (36.0 mg kg-1), Pb (38.0 mg kg-1), Cu (34.7 mg g-1), Zn (149.1 mg kg-1), Ba (518.1 mg kg-1), and Sr (224.9 mg kg-1) in road sediment were greater than their soil background values. Trace metals in most samples was moderately (75%) and heavily contaminated (15.6%). The industrial areas, congested roads, and residential areas in the northeast, middle and south of Shijiazhuang are the hotspots of trace metals pollution. A comprehensive analysis of trace metals sources indicated that Ni, V, Ga, Rb, Y, Sc, La, Ce, Zr, and Hf were mainly from natural source, which contributed to 34.2% of the total trace metals concentrations. Cu, Pb, Zn, Cr, Ba, Sr, and Mn primarily originated from mixed source, which accounted for 46.5%. Co principally came from building source, which accounted for 19.3%. This study shows that industrial discharges, construction dust and traffic emissions are the primary anthropogenic sources of trace metals in road sediment in the study area.


A comparative evaluation of the Adaptive knee and Catech knee joints: a preliminary study.
The Adaptive knee joint is a microprocessor-controlled prosthetic knee that incorporates both pneumatic and hydraulic control in one electronic unit. Pneumatic control is said to provide control during swing phase and the hydraulic control during the stance phase of the gait. This hybrid controller is triggered by a computer contained within the knee that responds to input from force, time and angle sensors. The microprocessor then selects an appropriate speed and stability setting. The Catech knee joint is a conventional hydraulic knee joint. The aim of this study was to compare the Adaptive and Catech knee joints in established trans-femoral amputees. The patients meeting the inclusion criteria were all established trans-femoral amputees using the Catech knee joint. The study was carried out by performing gait analysis, assessing energy requirements using the Physiological Cost Index (PCI) and using questionnaires. There was no significant benefit gained from the use of the Adaptive knee over the Catech knee joint in our small study group.


Effect of metal stress on photosynthetic pigments in the Cu-hyperaccumulating lichens Cladonia humilis and Stereocaulon japonicum growing in Cu-polluted sites in Japan.
To understand the ecology and physiology of metal-accumulating lichens growing in Cu-polluted sites, we investigated lichens near temple and shrine buildings with Cu roofs in Japan and found that Stereocaulon japonicum Th. Fr. and Cladonia humilis (With.) J. R. Laundon grow in Cu-polluted sites. Metal concentrations in the lichen samples collected at some of these sites were determined by inductively coupled plasma mass spectroscopy (ICP-MS). UV-vis absorption spectra of pigments extracted from the lichen samples were measured, and the pigment concentrations were estimated from the spectral data using equations from the literature. Secondary metabolites extracted from the lichen samples were analyzed by high-performance liquid chromatography (HPLC) with a photodiode array detector. We found that S. japonicum and C. humilis are Cu-hyperaccumulating lichens. Differences in pigment concentrations and their absorption spectra were observed between the Cu-polluted and control samples of the 2 lichens. However, no correlation was found between Cu and pigment concentrations. We observed a positive correlation between Al and Fe concentrations and unexpectedly found high negative correlations between Al and pigment concentrations. This suggests that Al stress reduces pigment concentrations. The concentrations of secondary metabolites in C. humilis growing in the Cu-polluted sites agreed with those in C. humilis growing in the control sites. This indicates that the metabolite concentrations are independent of Cu stress.


Volume-controlled inverse ratio ventilation in oleic acid induced lung injury. Effects on gas exchange, hemodynamics, and computed tomographic lung density.
To compare volume-controlled inverse ratio ventilation (VCIRV) with volume-controlled ventilation with conventional inspiratory to expiratory (I:E) ratio (VCV PEEP) at equal levels of end-expiratory pressure. Animal study using an oleic acid lung injury model with random application of VCV PEEP and VCIRV. Experimental investigation at the Department of Clinical Physiology at Uppsala University. Seven pigs. VCV PEEP, VCIRV at an end-expiratory pressure level of 10 cm H2O. Lung mechanics, hemodynamics, gas exchange, and functional residual capacity. Recruitment of lung tissue, regional lung density, and distribution of inspired gas by computed tomography. Mean and peak airway pressures were 22 +/- 4 and 41 +/- 8 cm H2O with VCIRV and 18 +/- 2 and 45 +/- 7 cm H2O with VCV PEEP. Cardiac output and arterial oxygen tension were equal with VCV PEEP and VCIRV as were static compliance, physiologic dead space, and functional residual capacity. End-expiratory, end-inspiratory, and CT densities during a full ventilatory cycle were not statistically different and the amounts of nonaerated and poorly aerated lung areas were of equal size with VCV PEEP and VCIRV. VCIRV was comparable to VCV PEEP at similar PEEP levels in alveolar recruitment, aeration of the lung tissues, and in oxygenating the blood. Since cardiac output also remained unchanged, oxygen delivery to peripheral tissues did not differ significantly between the two modes. Neither method has thus proved superior to the other one.


Potential pitfalls of reproductive direct-to-consumer testing.
The availability of direct-to-consumer (DTC) testing has dramatically increased over the past 2 decades, particularly those targeted at reproduction and fertility. Several ethical concerns exist with regard to DTC tests, including the lack of governmental regulation and consumer protection, standardized laboratory methodology, and clinical validity and actionability. Physicians must familiarize themselves with the pitfalls of DTC tests to best aid patients in interpreting DTC test results and guide them toward evidence-based treatment plans.


The first reporting of prevalence Vibrio species and expression of HSP genes in rayed pearl oyster (Pinctada radiata) under thermal conditions.
The main goal of the present study was to evaluate the influence of thermal exposure on Vibrio population and HSP genes expression (HSP 90, HSP70, and HSP20) in rayed pearl oyster (P. radiata). To this end, the oysters were reared for 30 days at temperatures of 22 °C (control), 25 °C, 27 °C, and 29 °C. The results showed that five dominate Vibrio strains including Vibrio hepatarius, V. harveyi, V. alginolyticus, V. parahaemolyticus, and V. rotiferianus were identified. The highest population of V. parahaemolyticus, V. alginolyticus, and V. harveyi, was found in 29οC group. According to real-time PCR, mantle exhibited the highest expression levels of HSP20, HSP70, and HSP90 genes. A higher level of HSP20 expression was observed at high temperatures (25 °C, 27 °C, and 29 °C) in the gonad and mantle compared to the control group (22 °C) while decrease in HSP90 expression level was recorded in 25 °C, 27 °C, and 29 °C groups. HSP20 expression level in adductor muscle was remarkably down-regulated in 27 °C and 29 °C groups. In this tissue, HSP70 was detected at highest levels in the 29οC group. In mantle, HSP90 gene expression was lowest at 22 °C water temperature. Several Vibrio strains have been identified from pearl Gulf oyster that haven't been previously reported. The identification of dominant Vibrio species is essential for epidemiological management strategies to control and prevent Vibrio outbreaks in pearl oyster farms. The expression pattern of HSP genes differs in rayed pearl oyster tissues due to differences in their thermal tolerance capability and physiological and biological characteristics. The present study provides useful molecular information for the ecological adaptation of rayed pearl oysters after exposure to different temperature levels.


Trace element analysis reveals bioaccumulation in the squid Gonatus fabricii from polar regions of the Atlantic Ocean.
The boreoatlantic gonate squid (Gonatus fabricii) represents important prey for top predators-such as marine mammals, seabirds and fish-and is also an efficient predator of crustaceans and fish. Gonatus fabricii is the most abundant cephalopod in the northern Atlantic and Arctic Ocean but the trace element accumulation of this ecologically important species is unknown. In this study, trace element concentrations (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn) were analysed from the mantle muscle and the digestive gland tissue of juveniles, adult females, and adult males that were captured south of Disko Island off West-Greenland. To assess the feeding habitat and trophic position of this species, stable isotopes of carbon (δ13C) and nitrogen (δ15N) were measured in their muscle tissue. Mercury concentrations were positively correlated with size (mantle length) and trophic position. The Hg/Se ratio was assessed because Se has been suggested to play a protective role against Hg toxicity and showed a molar surplus of Se relative to Hg. Cadmium concentrations in the digestive gland were negatively correlated with size and trophic position (δ15N), which suggested a dietary shift from Cd-rich crustaceans towards Cd-poor fish during ontogeny. This study provides trace element concentration data for G. fabricii from Greenlandic waters, which represents baseline data for a northern cephalopod species. Within West-Greenland waters, G. fabricii appears to be an important vector for the transfer of Cd in the Arctic pelagic food web.


Evolutionary Rescue in a Linearly Changing Environment: Limits on Predictability.
Populations subject to substantial environmental change that decreases absolute fitness (expected number of offspring per individual) to less than one must adapt to persist. The probability of adaptive evolutionary rescue may be influenced by factors intrinsic to the organism itself, or by features specific to the individual population and its environment. An important question (given the increasing prevalence of environmental change) is the predictability of evolutionary rescue. We used an individual-based simulation model and a related analytic model to examine population persistence, given a continuously changing environment that leads to a linear change in the optimum for a phenotypic trait under selection. Population persistence was not well predicted by the population genetics at the start of environmental change, which contrasts strongly with the results shown in prior work for persistence after a sudden environmental change. Larger populations, which had a greater scope for the generation and maintenance of beneficial genetic variation, showed a clear advantage, but increasing the rate of environmental change always decreased the probability of persistence. Extinctions occurred throughout the period of continuous change, and populations that went extinct showed little sign of their eventual fate until shortly before extinction. Partially clonal populations showed less predictability and greater vulnerability to extinction when impacted by continuous change than did fully sexual populations-any advantage gained by the initial transmission of well-adapted phenotypes via clonal reproduction is lost as the phenotypic optimum continues to shift and the generation of novel variation is required for continuous adaptation.


Expression and characterization of a cold-adapted, thermotolerant and denaturant-stable GH5 endoglucanase Celal_2753 that withstands boiling from the psychrophilic bacterium Cellulophaga algicola IC166(T).
To characterize a novel endoglucanase, Celal_2753, from the psychrophilic bacterium Cellulophaga algicola IC166(T). Celal_2753 was purified to homogeneity with a yield of 81 % and with a molecular weight of 40 kDa on SDS-PAGE. It had maximum hydrolytic activity towards carboxymethyl cellulose at 40 °C and pH 6. It showed 33 % of the maximum activity at 10 ºC. Its activity increased to 272-316 % in the presence of 0.25-2 M NaCl and KCl at 40 °C. Celal_2753 was stable in the presence of 10 % (v/v) Tween 20, 10 % (v/v) Triton X-100, 16 mM SDS, 6 M urea or 2 M guanidine hydrochloride. Celal_2753 that had been boiled for 5 min recovered 55 % of its initial activity by incubating at 30 °C for 60 min. Because of its cold-adapted, thermotolerant and denaturant-stable properties, endoglucanase Celal_2753 is promising in detergent industry and bioethanol production.


Does hyaluronan affect inflammatory cytokines in knee osteoarthritis?
Our aim was to investigate the effects of hyaluronan on inflammatory cytokines in the synovial fluid of patients with knee osteoarthritis. The study was single blind, placebo-controlled, and randomized. We administered hyaluronan to 22 patients in the study group and placebo to 19 in the control group. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines. Both HA and placebo caused a significant decrease in interleukin (IL)-6 levels (P=0.0001 and P=0.04, respectively). But it was more significant in the study group. However, IL-8 and tumor necrosis factor alpha (TNF-alpha) levels did not change in either group (P>0.05). The amount of effusion decreased significantly in the study group (P=0.001) but not in the control group (P=0.133). It can be concluded that hyaluronan considerably decreased IL-6 levels, which correlated with clinical improvement, but had no effect on IL-8 and TNF-alpha levels in synovial fluid. However, larger studies with longer follow-up periods are needed to explain the effect of hyaluronan on cytokines.


Reaction to the death of the oldest female in a group of chimpanzees at the Municipal Zoological Garden, Warsaw.
In March 2017, the oldest female of a group of chimpanzees living in the Municipal Zoological Garden in Warsaw, died in her sleep at the age of 53, due to natural causes. The article reports reactions of the eight other individuals in the group, four males and four females, including the daughter and the granddaughter of the old female, the following day. The corpse generally elicited more interest in the females than in the adult males. The females touched the body gently and groomed it more often than the males, who tended simply to look at and sniff it. However, the most diverse reactions, ranging from gentle touching to jumping on and hitting the corpse, were seen in the youngest male. By contrast, the oldest male never approached the corpse. In general, the chimpanzees at the zoo reacted in a manner much milder than is often reported from the wild.


Attempts to quantity Clostridium botulinum type A toxin and antitoxin in serum of two cases of infant botulism in Japan.
Serum samples taken from two infant botulism cases during hospitalization were titrated for botulinum toxin by both the intraperitoneal (ip) injection method and the score method in mice. By the ip method, in which death is the only parameter, such low levels of toxin as lower than 4 ip LD50/ml may not be titrated even though the surviving mice show abdominal palsy. By the score method based on the degree of abdominal palsy, such low levels of toxin as 1.1 and 0.8 ip LD50/ml were detected in specimens of one of the patient's serum. No antitoxin was demonstrated in either case of infant botulism by applying the score method. It is not known whether spontaneous recovery from infant botulism is due to the antitoxin production.


A topological analysis of targeted In-111 uptake in SPECT images of murine tumors.
Single-photon emission computed tomography images of murine tumors are interpreted as the values of functions on a three-dimensional domain. Motivated by Morse theory, the local maxima of the tumor image functions are analyzed. This analysis captures tumor heterogeneity that cannot be identified with standard measures. Utilizing decreasing sequences of uptake values to filter the images, a modified form of the standard persistence diagrams for 0-dimensional persistent homology as well as novel childhood diagrams are constructed. Applying statistical methods to time series of persistence and childhood diagrams detects heterogeneous uptake of radioactive antibody within tumors over time and distinguishes uptake in two groups of mice injected with different labeled antibodies.


Neurotrophic keratopathy as a complication of scleral fixated intraocular lens implantation.
To report a series of patients who developed neurotrophic keratopathy following scleral fixation of intraocular lenses. Retrospective case series of patients undergoing implantation of scleral fixated IOLs with various techniques. Three patients developed NK in the immediate post-operative period following scleral fixation of IOLs. Scleral fixation of IOL was performed using three different techniques (4-point fixation, "Yamane" flanged intrascleral and tunneled intrascleral haptic fixation). None of the patient had any prior risk factors for the development of NK. In all patients, intrascleral haptics or scleral sutures were positioned on the horizontal meridian. All patients also underwent light peripheral retinal endolaser. NK can rarely occur following scleral fixation of IOLs. The combination of suturing or intrascleral fixation of the IOL on the horizontal meridian and peripheral retinal endolaser may synergistically damage to the long ciliary nerves with a "two-hit" mechanism and cause NK.


α-Conotoxin as Potential to α7-nAChR Recombinant Expressed in Escherichia coli.
α7 nicotinic acetylcholine receptors (nAChR) is an important nicotinic acetylcholine receptors subtype and closely associated with cognitive disorders, such as Alzheimer's and schizophrenia disease. The mutant ArIB (V11L, V16A) of α-conotoxin ArIB with 17-amino acid residues specifically targets α7 nAChR with no obvious effect on other nAChR subtypes. In the study, the synthetic gene encoding mature peptide of ArIB and mutant ArIB (V11L, V16A) carried a fusion protein Trx and 6 × His-tag was separately inserted in pET-32a (+) vector and transformed into Escherichia coli strain BL21(DE3) pLysS for expression. The expressions of Trx-ArIB-His6 and Trx-ArIB (V11L, V16A)-His6 were soluble in Escherichia coli, which were purified by Ni-NTA affinity chromatography column and cleaved by enterokinase to release rArIB and rArIB (V11L, V16A). Then, rArIB and rArIB (V11L, V16A) were purified by high-performance liquid chromatography (HPLC) and identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Bioactivity of rArIB and rArIB (V11L, V16A) was assessed by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing human nAChR subtypes. The results indicated that the yield of the fusion proteins was approximately 50 mg/L and rArIB (V11L, V16A) antagonized the α7 nAChR subtype selectively with 8-nM IC50. In summary, this study provides an efficient method to biosynthesize α-conotoxin ArIB and rArIB (V11L, V16A) in Escherichia coli, which could be economical to obtain massively bioactive disulfide-rich polypeptides at fast speed.


Case report: metachronous central nervous system desmoid tumours and thyroid carcinoma in a young familial adenomatous polyposis patient.
We report a familial adenomatous polyposis patient with a known truncating mutation on exon 15 of the APC gene who developed an invasive follicular thyroid cancer in addition to multiple intra-cranial and spinal desmoids. This combination of manifestations has not previously been recorded in the literature.


Cloning and expression of the alpha-amylase gene from Bacillus stearothermophilus in several staphylococcal species.
The plasmid-coded alpha-amylase gene of Bacillus stearothermophilus (amy) was cloned in Staphylococcus carnosus using plasmid pCA43 as a vector. The amy gene was located on a 5.4-kb HindIII DNA fragment of the hybrid plasmid pamy7. When transformed into other staphylococcal species, plasmid pamy7 exhibited marked differences in the production of alpha-amylase (alpha Amy). Most active for heterospecific alpha Amy production was Staphylococcus aureus. In its culture supernatant nearly half as much alpha Amy activity was found as for the donor strain B. stearothermophilus. All staphylococcal species were able to secrete alpha Amy, since more than 80% of the enzyme activity was found in the culture supernatant. The extracellular alpha Amy of S. aureus [pamy7] was purified to homogeneity. The enzyme exhibited an Mr of approx. 58 000, an optimum activity at pH 5.3-6.3 and at 65 degrees C. Although the enzyme was stable at 65 degrees C for at least 3 h, its thermostability was not unusual. The enzymatic properties of the alpha Amy from S. aureus were similar to those previously reported for various B. stearothermophilus strains.


A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan using oral ciclosporin in advanced colorectal cancer: results of the Panitumumab, Irinotecan & Ciclosporin in COLOrectal cancer therapy trial (PICCOLO).
The main toxicity of irinotecan in advanced colorectal cancer (CRC) is delayed diarrhoea. Intestinal SN-38, released by deconjugation of the parent glucuronide excreted into the bile or produced in situ by intestinal carboxylesterase, is toxic to the intestinal epithelium. The canalicular transport of irinotecan and SN-38G is mediated by ABCC2 (MRP2) and ABCB1 (MDR1) which are both inhibited by ciclosporin. We tested whether irinotecan and ciclosporin was non-inferior for anti-cancer efficacy and superior for toxicity compared with single-agent irinotecan. Six hundred and seventy-two patients with advanced, measurable CRC following prior fluoropyrimidine-containing chemotherapy were randomised to either irinotecan 3-weekly 350 mg/m(2) (or 300 mg/m(2) if age >70 or performance status (PS)=2) or 3-weekly irinotecan at 140 mg/m(2) (120 mg/m(2) if age >70 or PS=2) with ciclosporin 3mg/kg t.d.s. for three days by mouth starting on the morning before irinotecan. The primary end-point was the proportion of patients alive and progression-free at 12 weeks. The key secondary end-point was the incidence of grade ≥3 diarrhoea within 12 weeks of randomisation. The proportion of patients progression-free at 12 weeks with irinotecan was 53.4% compared to 47.2% with irinotecan plus ciclosporin (difference=-6.3%, 95% confidence interval (CI) [-13.8%, 1.3%]). Since the lower limit of the 95% CI crossed the pre-specified non-inferiority margin of -10.6%, non-inferiority of irinotecan plus ciclosporin compared to irinotecan alone was not statistically demonstrated. 15.0% patients developed severe diarrhoea on irinotecan compared to 13.8% on irinotecan plus ciclosporin, a non-significant difference. The pharmacokinetic biomodulation of irinotecan using oral ciclosporin does not improve the therapeutic index of irinotecan in advanced CRC. The trial was funded by Cancer Research UK and supported by Amgen Pharma.


Replicative efficiency and pathogenicity of hepatitis B virus e-minus precore variant.
To study the replicative efficiency and pathogenicity of hepatitis B virus precore variant (A1896), anti-hepatitis B virus e antigen (HBe) titre was studied in naturally occurring wild-type virus infection, A1896 variant infection and dual infection. Higher titre of anti-HBe was found in patients with no virus replication and in patients coinfected with the wild-type virus and A1896 variant, which suggest that anti-HBe may either act as an inhibitor of virus replication or as selective pressure for the A1896 variant. Three site-directed mutants were constructed in the duck hepatitis B virus (DHBV) precore region. A frame shift in the encapsidation signal region abolished replication of DHBV; mutation in the initiation codon of the precore and mutation to generate a termination codon at the distal region of the precore resulted in decreased replication in the duck model. More significant pathological changes were found in the liver tissues of ducks infected with the mutant which mimicked the HBV A1896 variant.


Ferrocyanide adsorption on aluminum oxides.
Ferrocyanide (Fe(CN)6(4-)) adsorption onto gamma-alumina ( gamma-Al2O3(s) ) and gibbsite (Al(OH)3(s)) was investigated over a wide pH range and at various solid loadings. Batch experiments were performed using 100-ml solutions (I = 0.01 M NaCl) dosed with 1.0 mgl(-1) Fe(CN)6(4-) as CN. Equilibrium adsorption-pH edges were developed for 0.3, 0.6, 1.2, and 2.0 gl(-1) gamma-Al(2)O3(s) and 25 gl(-1) Al(OH)3(s). Ferrocyanide adsorption increased as pH decreased, consistent with the general pH dependence for adsorption of anions onto oxide minerals. Ferrocyanide adsorption onto Al(OH)3(s) was approximately 300 times lower than onto gamma-Al(2)O3(s) on a unit weight basis due to the higher surface reactivity of the gamma-Al(2)O3(s). Ferrocyanide adsorption onto gamma-Al(2)O3(s) was significantly greater than has been reported for goethite (FeOOH(s)), and both gamma-Al(2)O3(s) and FeOOH(s) adsorbed ferrocyanide to a greater extent than Al(OH)3(s) . The investigation showed that ferrocyanide can adsorb significantly onto aluminum oxides spanning a range of crystallinity and properties, with the extent of adsorption highly dependent on pH, the solid crystalline structure, and associated surface reactivity.


Similar regulation of two distinct UL24 promoters by regulatory proteins of equine herpesvirus type 1 (EHV-1).
To characterise the pattern of the transcriptional regulation of equine herpesvirus type 1 (EHV-1) UL24 by regulatory proteins, we identified two distinct promoter regions and two transcription initiation (Tci) sites located upstream of the UL24 open reading frame (ORF). The ORF proximal promoter exhibited higher cis-activity than that of the distal one. Contrary to the former, the latter performed its function dependent on an initiator (INR) due to its lack of a TATA box. Our results showed that the EHV-1 regulatory proteins EICP0, EICP22 and ETIF trans-activated the two promoters, whereas IEP and IR2P displayed negative regulation. In summary, the regulatory proteins exhibited similar regulatory patterns for the two distinct promoters of EHV-1 UL24.


Antibodies to 4-hydroxyandrostenedione--a new anti-breast cancer agent suitable for use in a radioimmunoassay.
A specific antiserum suitable for radioimmunoassay (RIA) of 4-hydroxy-4-androstene-3,17 dione (4-OHA) has been developed. Sheep antiserum was raised by injecting two different conjugates prepared by coupling 4-OHA to ovalbumin. Antisera obtained from a sheep immunised with 4-hydroxy-testosterone-17-hemisuccinate ovalbumin conjugate were of higher titre and more specific than antisera obtained from sheep immunised with 4-hydroxyandrostenedione-7 alpha-carboxyethylthioether. The antiserum bound 50% of 20 picograms of [6,7-3H]-4-OHA at an initial dilution of 1:270. The most relevant steroids, androstenedione (AD) and testosterone (T) were tested and showed cross reactivity of 2.7% and 5.1% respectively. The lower limit of detection was 4.5 pg/tube. Antisera from this animal will prove useful as the basis of a sensitive and specific RIA for clinical pharmacokinetic studies of 4-OHA.


The production of macrophage inflammatory protein-2 induced by soluble intercellular adhesion molecule-1 in mouse astrocytes is mediated by src tyrosine kinases and p42/44 mitogen-activated protein kinase.
Severe traumatic brain injury stimulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) into CSF. Studies in cultured mouse astrocytes suggest that sICAM-1 induces the production of macrophage inflammatory protein-2 (MIP-2). In the present study, we investigated the underlying mechanisms for MIP-2 induction. sICAM-1 induced MIP-2 in astrocytes lacking membrane-bound ICAM-1, indicating that its action is due to heterophilic binding to an undescribed receptor rather than homophilic binding to surface ICAM-1. Signal transduction may be mediated by src tyrosine kinases, as the src tyrosine kinase inhibitors herbimycin A and PP2 abolished MIP-2 induction by sICAM-1. Phosphorylation of p42/44 mitogen-activated protein kinase (MAPK), but not of p38 MAPK, occurred further downstream, as evidenced by western blot analysis combined with the use of herbimycin A and specific MAPK inhibitors. By contrast, induction of MIP-2 by tumour necrosis factor-alpha (TNF-alpha) involved both p42/44 MAPK and p38 MAPK. Following stimulation with either sICAM-1 or TNF-alpha, astrocyte supernatants promoted chemotaxis of human neutrophils and incubation of these supernatants with anti-MIP-2 antibodies more efficiently suppressed the migration induced by sICAM-1 than by TNF-alpha. These results show that sICAM-1 induces the production of biologically active MIP-2 in astrocytes by heterophilic binding to an undefined receptor and activation of src tyrosine kinases and p42/44 MAPK.


The formation of glutathione-chromium complexes and their possible role in chromium disposition.
The reduction of Cr(VI) to Cr(III) by glutathione (GSH) in vitro resulted in the formation of two different GSH-chromium complexes with an approximate molecular-weight of 10,000 and 5000, respectively. Both complexes exhibited strong fluorescence. The molar ratio between oxidized glutathione (GSSG) and chromium was calculated by determining the chromium content of the two isolated complex species by flameless Atomic Absorption Spectrometry (AAS).


Magnetic field modulation of receptor binding.
Although it is widely held that the magnetic fields encountered during magnetic resonance imaging (MRI) and other procedures have no discernible effect on biological systems, we find that at early times of incubation, the amount of binding of the neurotoxin, alpha-bungarotoxin, to nicotinic acetylcholine receptor is significantly reduced in a constant 2.0-T magnetic field. This finding suggests that steady magnetic fields can directly affect the functional activity of biologically important macromolecules, in this particular case a neurotransmitter receptor.


Antimicrobial capabilities of non-spermicidal concentrations of tea tree (Melaleuca alternifolia) and rosemary (Rosmarinus officinalis) essential oils on the liquid phase of refrigerated swine seminal doses.
Antimicrobial resistance is increasing within the porcine industry with consequential high impact on human health, leading to a need for new antimicrobials. Lately, the scientific community has turned its interest towards natural compounds, and different essential oils have been tested on spermatozoa for preliminary assessment of toxicity before considering them as good substitutes for standard antibiotics. The aim of the present work was to investigate the potential antimicrobial effect of Melaleuca alternifolia and Rosmarinus officinalis essential oils, already evaluated for toxicity, on swine artificial insemination doses deprived of spermatozoa and stored at 16 °C for 5 days. This was accomplished by setting up an in vitro model with a standardized quantity of E. coli. Essential oils, previously chemo-characterized by means of gas chromatography, were tested at 0.2 and 0.4 mg/ml. Analyses, performed at 24 and 120 h, included optical density evaluation, bacterial DNA quantification by qPCR, and colony count. The results demonstrate that both Melaleuca alternifolia and Rosmarinus officinalis essential oils, at a concentration of 0.4 mg/ml, are capable of delivering similar effects to ampicillin, used as control, on the experimental samples. At the lower concentration, M. alternifolia essential oil seemed more effective when compared to R. officinalis. Overall, these findings strengthen the hypothesis of the potential use of phyto-complexes as antimicrobial agents for reproductive biotechnologies.


Variation in Leishmania chemokine suppression driven by diversification of the GP63 virulence factor.
Leishmaniasis is a neglected tropical disease with diverse outcomes ranging from self-healing lesions, to progressive non-healing lesions, to metastatic spread and destruction of mucous membranes. Although resolution of cutaneous leishmaniasis is a classic example of type-1 immunity leading to self-healing lesions, an excess of type-1 related inflammation can contribute to immunopathology and metastatic spread. Leishmania genetic diversity can contribute to variation in polarization and robustness of the immune response through differences in both pathogen sensing by the host and immune evasion by the parasite. In this study, we observed a difference in parasite chemokine suppression between the Leishmania (L.) subgenus and the Viannia (V.) subgenus, which is associated with severe immune-mediated pathology such as mucocutaneous leishmaniasis. While Leishmania (L.) subgenus parasites utilize the virulence factor and metalloprotease glycoprotein-63 (gp63) to suppress the type-1 associated host chemokine CXCL10, L. (V.) panamensis did not suppress CXCL10. To understand the molecular basis for the inter-species variation in chemokine suppression, we used in silico modeling to identify a putative CXCL10-binding site on GP63. The putative CXCL10 binding site is in a region of gp63 under significant positive selection, and it varies from the L. major wild-type sequence in all gp63 alleles identified in the L. (V.) panamensis reference genome. Mutating wild-type L. (L.) major gp63 to the L. (V.) panamensis sequence at the putative binding site impaired cleavage of CXCL10 but not a non-specific protease substrate. Notably, Viannia clinical isolates confirmed that L. (V.) panamensis primarily encodes non-CXCL10-cleaving gp63 alleles. In contrast, L. (V.) braziliensis has an intermediate level of activity, consistent with this species having more equal proportions of both alleles. Our results demonstrate how parasite genetic diversity can contribute to variation in immune responses to Leishmania spp. infection that may play critical roles in the outcome of infection.


Operative expectations for Mohs surgery in patients with chronic lymphocytic leukemia: A multicenter retrospective cohort study.
Patients with chronic lymphocytic leukemia (CLL) are immunocompromised and have both a higher incidence of and more aggressive skin cancers, often requiring treatment with Mohs micrographic surgery. Characterize operative expectations for Mohs surgery in patients with CLL. Multicenter retrospective cohort study. One hundred fifty-nine tumors from 99 patients with CLL were matched 1:4 with controls. Cases had higher odds for requiring at least 3 stages during Mohs surgery compared to controls (odds ratio = 1.91; 95% CI [1.21-3.02]; P = .01). The mean number of Mohs stages in cases was 1.97 (±0.92) compared with 1.67 (±0.87) in controls (P = .0001). A regression analysis showed that cases had larger postoperative tumor areas (cm2) versus controls (mean = 5.57 vs 4.47; estimate difference Δβ = 1.10 cm2; 95% CI [0.18-2.03]; P = .02). In logistic regression, cases were twice as likely to receive a flap repair compared to controls (odds ratio = 2.45; 95% CI [1.58-3.8]). Retrospective cohort study and lack of histologic subtyping of tumors. Patients with CLL require more Mohs stages to attain clear surgical margins, have larger postoperative defect areas, and require more advanced repair techniques compared to a control population without CLL. These findings are essential for preoperative planning and patient counseling and further support the use of Mohs surgery in patients with CLL.


Redistribution of subcellular calcium and its effect on apoptosis in primary cultures of rat proximal tubular cells exposed to lead.
Previous studies have shown that cytosolic Ca(2+) ([Ca(2+)]c) overload was involved in Pb-induced apoptosis in primary cultures of rat proximal tubular (rPT) cells, but the source of elevated Ca(2+) and the effect of potential subcellular Ca(2+) redistribution on apoptosis are still unknown. In this study, variations of [Ca(2+)]c in two culture media (Ca(2+)-containing and Ca(2+)- free) were analyzed, indicating that Pb-induced elevation of [Ca(2+)]c was primarily generated intracellularly. Fluo-4-AM, dihydro-Rhod-2-AM and Mag-Fluo-4-AM was loaded to Pb-exposed rPT cells to monitor the imaging of Ca(2+) concentrations in the cytoplasm ([Ca(2+)]c), mitochondria ([Ca(2+)]mit) and endoplasmic reticulum (ER) ([Ca(2+)]ER), respectively, under the confocal microscope. Data indicate that elevations of [Ca(2+)]c and [Ca(2+)]mit with depletion of [Ca(2+)]ER were revealed in Pb-treated rPT cells, but this subcellular Ca(2+) redistribution could be significantly suppressed by 2-APB, a specific inhibitor of inositol 1,4,5-trisphosphate receptor (IP3R) that functions to release Ca(2+) from ER stores. Simultaneously, Pb-mediated mitochondrial Ca(2+) overload can be partially suppressed by the cytosolic Ca(2+) chelator BAPTA-AM, suggesting that Ca(2+) uptake into mitochondria occurs via diverse pathways and ER Ca(2+) storage was the chief source. Furthermore, Pb-induced apoptosis was markedly inhibited by 2-APB and BAPTA-AM, respectively. Additionally, elevated IP3 levels with up-regulated IP3R-1 and IP3R-2 (mRNA and protein) levels were revealed in Pb-exposed rPT cells. In summary, IP3R-mediated ER Ca(2+) release promoted the elevations of [Ca(2+)]c and [Ca(2+)]mit in Pb-exposed rPT cells, which played a chief role in apoptosis induced by impaired calcium homeostasis.


Febrile inpatients: house officers' use of blood cultures.
The so-called "fever work-up" is time-consuming and costly. The authors examined the practices of medical house officers in obtaining blood cultures, an important part of this evaluation, as well as the ability of these physicians to predict bacteremia in febrile patients. They studied all 344 medical inpatients who experienced episodes of fever during two 30-day periods, as well as all 50 cases of bacteremia detected during these and two additional 30-day periods. House officers drew blood for culture within one day after the onset of fever in 52% of fever episodes. In 20% of these episodes only one set of cultures (representing one venipuncture) was obtained. House officers estimated the likelihood of bacteremia to be 20% or less in 15 of 40 bacteremic patients. They failed to obtain blood cultures promptly in 10% of bacteremic episodes and in 27% of episodes where the cause of fever was a nonbacteremic bacterial infection. They obtained prompt blood cultures in only a bare majority of febrile episodes, frequently underestimated the likelihood of bacteremia, and inadequately sampled blood for bacteremia. In this study, clinical judgment was not an adequate substitute for routinely obtaining blood cultures for febrile medical inpatients.


Predicting late-onset growth abnormalities using growth velocity between trimesters.
To determine whether growth velocity parameters derived from routine prenatal ultrasound measurements at first, second and third trimester can identify normal growth at term as well as late-onset growth abnormalities. Longitudinal study of fetal growth in normal singleton pregnancies with three normal ultrasound examinations and delivered at term. Fetuses were classified into 3 groups (<10th percentile, 10-90th percentile, >90th percentile) based on birth weight. Multiple regression on birth weight classification was used to build up a prediction equation of fetal growth potential (FGP) based on fetal biometry and fetal growth velocity parameters between ultrasound examinations. Best cut-off value for FGP predicting growth restriction and macrosomia were defined. 356 pregnancies were included. Fetal biometry growth velocities between examinations were calculated for all measurements. Using best cut-off values, the estimated sensitivity, specificity and odds ratio were: 60% [44;74], 91% [89;92] and 14.55 [6.30;33.98] and 53% [36;69], 89% [88;91] and 10 [4.27;23.49] for the prediction of growth restriction and macrosomia, respectively. Fetal growth potential can be derived and calculated from standard ultrasound measurements. It can improve identification of these fetuses at risk for late-onset growth abnormalities and their related morbidity.


Prevalence of vitamin D deficiency in mothers and their newborns in a Tunisian population.
To assess vitamin D status in mothers and their newborns and identify predictive factors of vitamin D deficiency. A cross-sectional study was undertaken of healthy women and their full-term newborns delivered at the Charles Nicolle Hospital, Tunis, Tunisia, between October and November 2012. Maternal and neonatal serum 25-hydroxy vitamin D (25(OH)D) concentrations were measured. Correlations were tested. Overall, 87 mothers and their newborns were enrolled. No mother or neonate had an adequate vitamin D status. Mean maternal and neonatal serum 25(OH)D concentrations were 6.82±5.14ng/mL (range 3.60-23.77) and 5.92±4.15ng/mL (range 3.60-22.28), respectively. Vitamin D deficiency (serum 25(OH)D<20ng/mL) was found in 84 (97%) mothers and 85 (98%) neonates, of whom 76 (87%) and 78 (90%), respectively, had severe deficiency (serum 25(OH)D<12ng/mL). Maternal serum 25(OH)D showed a strong positive correlation with neonatal serum 25(OH)D (r=0.69, P<0.001). Maternal dietary vitamin D intake was the only factor shown to be associated with serum 25(OH)D concentrations (P<0.05). Vitamin D deficiency is prevalent among Tunisian mothers and their neonates.


Endophthalmitis after Nd:YAG laser capsulotomy.
A 63-year-old patient underwent a Nd:YAG laser capsulotomy, 5 months after an extracapsular cataract extraction. One day later endophthalmitis had developed. Staphylococcus epidermidis was cultured from the vitreous. We assume that this micro-organism, a pathogen of low virulence, had been sequestered in the capsular bag and was released into the vitreous after Nd:YAG capsulotomy.


The hemoglobins of Artemia salina. V. Genetic variation in hemoglobin 1, hemoglobin 2, and hemoglobin 3.
Electrophoretic mobilities of three hemoglobins (Hb1, Hb2, and Hb3) were studied in 15 populations of brine shrimps. Genetic segregation data support the model that Hb2 contains n alpha-polypeptides and n beta-polypeptides; Hb1 contains 2n alpha-polypeptides- Hb3 contains neither alpha- nor beta-polypeptides. There is no evidence of linkage of alpha and beta loci with each other or with the locus (or loci) which governs Hb3 or with the nonhomologous portion of the sex chromosomes. Hemoglobins of different populations may be hybridized in vitro by incubation at high temperature. Reversible dissociation to subunits which contain only one (alpha or beta) polypeptide occurs at 40 C (for Hb1) and at 50 C (for Hb2).


Adapting HIV patient and program monitoring tools for chronic non-communicable diseases in Ethiopia.
Chronic non-communicable diseases (NCDs) have become a huge public health concern in developing countries. Many resource-poor countries facing this growing epidemic, however, lack systems for an organized and comprehensive response to NCDs. Lack of NCD national policy, strategies, treatment guidelines and surveillance and monitoring systems are features of health systems in many developing countries. Successfully responding to the problem requires a number of actions by the countries, including developing context-appropriate chronic care models and programs and standardization of patient and program monitoring tools. In this cross-sectional qualitative study we assessed existing monitoring and evaluation (M&E) tools used for NCD services in Ethiopia. Since HIV care and treatment program is the only large-scale chronic care program in the country, we explored the M&E tools being used in the program and analyzed how these tools might be adapted to support NCD services in the country. Document review and in-depth interviews were the main data collection methods used. The interviews were held with health workers and staff involved in data management purposively selected from four health facilities with high HIV and NCD patient load. Thematic analysis was employed to make sense of the data. Our findings indicate the apparent lack of information systems for NCD services, including the absence of standardized patient and program monitoring tools to support the services. We identified several HIV care and treatment patient and program monitoring tools currently being used to facilitate intake process, enrolment, follow up, cohort monitoring, appointment keeping, analysis and reporting. Analysis of how each tool being used for HIV patient and program monitoring can be adapted for supporting NCD services is presented. Given the similarity between HIV care and treatment and NCD services and the huge investment already made to implement standardized tools for HIV care and treatment program, adaptation and use of HIV patient and program monitoring tools for NCD services can improve NCD response in Ethiopia through structuring services, standardizing patient care and treatment, supporting evidence-based planning and providing information on effectiveness of interventions.


Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1.
Regulation of the volume and electrolyte composition of the cerebrospinal fluid (CSF) is vital for brain development and function. The Na-K-Cl co-transporter NKCC1 in the choroid plexus (ChP) plays key roles in regulating CSF volume by co-transporting ions and mediating same-direction water movements. Our previous study showed ChP NKCC1 is highly phosphorylated in neonatal mice as the CSF K+ level drastically decreases and that overexpression of NKCC1 in the ChP accelerates CSF K+ clearance and reduces ventricle size [1]. These data suggest that NKCC1 mediates CSF K+ clearance following birth in mice. In this current study, we used CRISPR technology to create a conditional NKCC1 knockout mouse line and evaluated CSF K+ by Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES). We demonstrated ChP-specific reduction of total and phosphorylated NKCC1 in neonatal mice following embryonic intraventricular delivery of Cre recombinase using AAV2/5. ChP-NKCC1 knockdown was accompanied by a delayed perinatal clearance of CSF K+. No gross morphological disruptions were observed in the cerebral cortex. We extended our previous results by showing embryonic and perinatal rats shared key characteristics with mice, including decreased ChP NKCC1 expression level, increased ChP NKCC1 phosphorylation state, and increased CSF K+ levels compared to adult. Collectively, these follow up data support ChP NKCC1's role in age-appropriate CSF K+ clearance during neonatal development.


Predicting neurite extension for varying extracellular matrix stiffness and topography.
Neurite extension is a dynamic process and is dependent on the microenvironment. The mechanical properties of the extracellular matrix (ECM), such as stiffness and topography influence the microenvironment and affects neurite extension; however, the mechanistic basis for this dynamic response of neurite extension remains elusive. In this study, we develop a computational model that predicts neurite extension dynamics process as the stiffness and patterned topography of ECM changes. The model includes the contribution of receptors integrin and neural cellular adhesion molecule toward the growth of neurite tip. We use non-linear finite element analysis (FEA) to model the neuronal cell, neurite, and the ECM, which is then coupled to the force-deformation receptor properties obtained from molecular dynamics simulations. Using an empirical relation, we develop a neurite extension algorithm that simulates the dynamic process of growth cone induced by growth cone extension, receptor density, and rupture. We investigate the dependence of neurite extension on ECM stiffness using three distinct materials, the effect of width and spacing of continuous (cylindrical) and discontinuous (pillar) patterned topography, as well as the topography steepness and stiffness gradient. We find that an increasing stiffness and width of patterned topography results in increased neurite extension, but the magnitude of the increase differs depending on the growth cone extension and receptor density between them. These findings will aid in vitro studies in determining an ECM with appropriate mechanical properties, such as stiffness and topography that will improve neurite extension, thus resulting in the formation of functional neurons.


Massive jugular and dural sinus reflux associated with cerebral death.
Radionuclide cerebral angiograms demonstrated massive jugular venous reflux in two children with clinical and electroencephalographic evidence of cerebral death. With an antecubital injection, the tracer flowed up the jugular vein, through the transverse dural sinus, and down the contralateral jugular vein. No arterial flow was seen. We hypothesize that this unusual pattern reflects the absence of normal antegrade flow through the venous system. The appearance of jugular reflux is distinct from arterial flow and should not be confused with it. These cases illustrate communication between the systemic venous system and the dural sinuses. Although this pattern in not diagnostic of cerebral death, the appearance of radiotracer in the dural sinuses does not establish the presence of cerebral perfusion.


Shrimp laccase degrades polycyclic aromatic hydrocarbons from an oil spill disaster in Brazil: A tool for marine environmental bioremediation.
Our work aims to purify, characterize and evaluate a laccase from by-products of the shrimp farming industry (Litopenaeus vannamei) for the degradation of Polycyclic Aromatic Hydrocarbons (PAHs) from 2019 oil spill in Brazilian coast. The enzyme was purified by affinity chromatography and characterized as thermostable, with activity above 90 °C and at alkaline pH. In addition, the laccase was also tolerant to copper, lead, cadmium, zinc, arsenic, hexane and methanol, with significant enzymatic activation in acetone and 10 mM mercury. Concerning PAHs' degradation, the enzyme degraded 42.40 % of the total compounds, degrading >50 % of fluorene, C4-naphthalenes, C3-naphthalenes, C2-naphthalenes, anthracene, acenaphthene, 1-methylnaphthalene and 2-methylnaphthalene. Thus, this laccase demonstrated important characteristics for bioremediation of marine environments contaminated by crude oil spills, representing a viable and ecological alternative for these purposes.


Extradural compression of the sensorimotor cortex delays the acquisition but not the recalling of a lever-pressing task in Wistar rats.
The learning and recalling of a lever-press task (LPT) after brief unilateral extradural compression (EC) of the right sensorimotor cortex was studied in Wistar rats. All rats, regardless of the time-point for EC, were trained to lever press for food from D(day)1 to D6. On D8, the position of the active lever was changed to the right side of the operant box and performance was tested until D14. Total and active lever presses, as well as % errors were used to analyse the performance. Rats submitted to EC 24 h before initiating the LPT schedule (naïve-compressed group) showed delayed task acquisition and impaired performance until D10. No significant impairments were detected by D3 on a beam-walking test, excluding paresis as the cause to the delay. Rats submitted to EC after they learned the LPT (trained-compressed group) showed only mildly impaired post-compression performance with no effects on the recalling of the task. Using a progressive ratio LPT, the maximum number of presses to obtain a food-pellet (breaking point) was significantly reduced 24h after EC suggesting reduced motivation for the task early after brain injury. The delayed acquisition of the LPT in naïve-compressed rats was accompanied by consistent cortical, striatal and thalamic degeneration detected by Fluoro-Jade and anti-glial fibrillary acidic protein (GFAP) staining, whereas the improvement in the performance of this group was accompanied by a reduction of the cortical damage on D10. Recall of the LPT in trained-compressed rats was not altered by EC, suggesting the contribution of compensatory mechanisms.


Topographic distribution of bacteria associated with oral malodour on the tongue.
To investigate the topographic distribution of bacterial types and loads associated with mid-morning oral malodour on the tongue surface. Fifty subjects with good oral health and at least 20 natural uncrowned teeth were included. Samples were taken with sterile brushes from the dorsal anterior (DA), dorsal middle (DM), dorsal posterior (DP), dorsal posterior to the circumvallate papillae (DPCP), lateral posterior (LP) and ventral posterior (VP) tongue surfaces. Samples were cultured on appropriate media for anaerobic bacteria, aerobic bacteria, Gram-negative anaerobic bacteria, volatile sulphur compound (VSC)-producing bacteria and Streptococcus saliuarius. Malodour was assessed by trained judges on an intensity basis. The counts of all bacterial groups were consistently highest at the DPCP surface. Mean VSC-producing bacterial counts (colony forming units/brush x10(5)) were 1.45, 5.67, 32.52, 88.94, 6.46 and 0.33 at DA, DM, DP, DPCP, LP and VP surfaces, respectively. Anaerobic, Gram-negative and VSC counts at DPCP surfaces increased with malodour intensity, whereas aerobic and S. saliuarius counts decreased; however these differences were not statistically significant. It is concluded that the DPCP area consistently carries the highest load of bacteria capable of contributing to oral malodour. The study demonstrates that tongue surfaces not accessible to routine oral hygiene procedures can significantly contribute to oral malodour.


Sensory components facilitating jaw-closing muscle activities in the rabbit.
The role of oral and facial sensory receptors in the control of masticatory muscle activities was assessed from the effect of acute deafferentiation on cortically induced rhythmic jaw movements (CRJMs) in anesthetized rabbits. When a thin polyurethane-foam strip (1.5, 2.5 or 3.5 mm thick) was placed between opposing molars during CRJMs, masseteric activities were facilitated in association with an increase in the medial excursion of the mandible during the power phase. The effects varied with the pattern of CRJMs, and the rate of facilitation was greater for small circular movements than for the crescent-shaped movements. Furthermore, the response of the masseter muscle was greater in the anterior half of the muscle, where muscle spindles are most dense, than in its posterior half. It was also demonstrated that the response increased with an increase in the thickness of the test strip. In contrast, the activities of the jaw-opening muscle were not affected significantly. The duration of masseteric bursts increased during application of the test strip and the chewing rhythm tended to slow down. However, the latter effect was not significant. After locally anesthetizing the maxillary and inferior alveolar nerves, the facilitative responses of the masseter muscle to the test strip was greatly reduced but not completely abolished. Lesioning of the mesencephalic trigeminal nucleus (Mes V) where the primary ganglion cells of muscle spindle afferents from jaw-closing muscles and some periodontal afferents are located, also reduced the facilitative effects. Similar results were obtained in the animals with the kainic acid injections into the Mes V 1 week before electrical lesioning of this nucleus. In these animals the effects of electrical lesioning of the Mes V could be attributed to the loss of muscle receptor afferents since the neurons in the vicinity of the Mes V were destroyed and replaced by glial cells, whereas the Mes V neurons are resistant to kainic acid. When electrical lesioning of the Mes V and sectioning of the maxillary and inferior alveolar nerves were combined in animals with a kainic acid injection into the Mes V, the response of the masseter muscle to application of the strip was almost completely abolished. From these findings, we conclude that both periodontal receptors and muscle spindles are primarily responsible for the facilitation of jaw-closing muscle activities.(ABSTRACT TRUNCATED AT 400 WORDS)


Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.
To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011). We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.


Nucleotide sequence-directed mapping of the nucleosomes of SV40 chromatin.
In our previous work we have shown by comparison of experimental and computational data that the positions of the histone octamers bound to the DNA molecule appear to be completely sequence-dependent. This provides a convenient and quick method for locating the nucleosomes along the DNA molecule, as soon as the nucleotide sequence is known. Using this computational approach, the complete nucleosomal map of the SV40 minichromosome has been constructed. The map consists of 25 nucleosomes, with their coordinates (centers) being specified with high accuracy. The map is found to be in remarkable agreement with available experimental data.


[Features of regional peripheral hemodynamics in radicular syndromes of the sacro-lumbar region].
Different causes leading to lesions of the peripheral nerve trunk result in instability of the state of regional hemodynamics values. Vegetative-vascular disorders determining the characteristic aspects of the peripheral hemodynamics may result in the development of intratruncal edematous compression of the nerve trunks.


Recoarctation after the norwood I procedure for hypoplastic left heart syndrome: incidence, risk factors, and treatment options.
Early survival after the Norwood I procedure has improved over the years, but subsequent morbidity is not yet well assessed. The aim of this study was to review the incidence of recoarctation, evaluate risk factors, and analyze treatment options. We reviewed the medical records of 124 consecutive patients with hypoplastic left heart syndrome (HLHS) who underwent the Norwood I procedure. Reconstruction of the aortic arch was performed in a standardized manner, removing all visible ductal tissue and enlarging the distal anastomosis with a Y incision into the descending aorta. Angiographic assessment with measurement of the peak gradient across the aortic arch was performed before the second stage was performed. Recoarctation of the aorta was documented in 13 patients (13.4%) at a mean time of 6.4 ± 5 months after the Norwood procedure. One patient died before the recoarctation could be treated. Right ventricular function was good in all except 1 patient at the time of diagnosis. Ten patients underwent 16 percutaneous balloon angioplasties, and 2 patients underwent operative enlargement of the neoaorta. The pretreatment peak gradient of 24.1 ± 16 mm Hg (10-64 mm Hg) across the aortic arch was significantly reduced to 6.3 ± 4 mm Hg (0-14 mm Hg) after angioplasty or operation (p = 0.003). There were no procedure-related deaths. No risk factor for recoarctation could be identified. A standardized surgical technique for reconstruction of the aorta leads to a low recoarctation rate. Balloon angioplasty can be performed in the majority of patients before the second-stage procedure.


Interacting effects of aromatic plants and female age on nest-dwelling ectoparasites and blood-sucking flies in avian nests.
Some avian species incorporate aromatic plants to their nests. The "nest protection hypothesis", which posits that volatile secondary compounds contained in these plants may have antiparasite properties, has not received full support. All previous tests of this hypothesis have only considered effects on nest-dwelling ectoparasites, but not on blood-sucking flies. The "drug hypothesis" posits that aromatic plants may stimulate nestling immune system, development, or condition. We tested these hypotheses experimentally in wild blue tits, Cyanistes caeruleus, a species that adds aromatic plants to their nests. We supplemented aromatic plants to half of a sample of nests, while adding grass to the other half of nests. We quantified abundance of two groups of blood-sucking flies (blackflies and biting midges) at two different stages of the reproductive period, and abundance of three nest-dwelling ectoparasites (fleas, mites, and blowflies). Experimental supplementation of aromatic plants reduced abundance of fleas only in nests of yearling females and not in nests of older females. Blackflies and biting midges were both more numerous in nests of yearling females than in nests of older females. Mass of aromatic plants added by females was negatively related with abundance of fleas in control nests but not in experimental nests supplied with aromatic plants. Mass of plants added by females was also positively related with abundance of blackflies during the nestling stage. Finally, aromatic plants did not affect nestling growth or immune responses. We conclude that several factors such as female experience and their ability to add plants to the nest interact to explain effects of aromatic plants on different parasites.


Safety of Foregoing Operation for Small Bowel Obstruction in the Virgin Abdomen: Systematic Review and Meta-Analysis.
Our objective was to assess the safety of foregoing surgery in patients without abdominopelvic surgery history presenting with small bowel obstruction (SBO). Classic dogma has counseled early surgical intervention for SBO in the virgin abdomen-patients without abdominopelvic surgery history-given their presumed higher risk of malignant or potentially catastrophic etiologies compared with those who had undergone previous abdominal operations. The term virgin abdomen was coined before widespread use of CT, which now elucidates many SBO etiologies. Despite recent efforts to re-evaluate clinical management standards, the prevalence of SBO etiologies in the virgin abdomen and the current management landscape (nonoperative vs operative) in these patients remain unclear. Our random-effects meta-analysis of 6 studies including 442 patients found the prevalence of malignant etiologies in patients without abdominopelvic surgery history presenting with SBO varied from 7.7% (95% CI 3.0 to 14.1) to 13.4% (95% CI 7.6 to 20.3) on sensitivity analysis. Most malignant etiologies were not suspected before surgery. De novo adhesions (54%) were the most common etiology. More than half of patients underwent a trial of nonoperative management, which often failed. Subgroups of patients likely have variable risk profiles for underlying malignant etiologies, yet no study had consistent follow-up data and we did not find convincing evidence that foregoing operative management altogether in this population can be generally recommended.


Structure-activity relationships in a series of piperazine-2,3-dione containing penicillins and cephalosporins. II. Derivatives substituted at N(4) of the piperazine ring.
The structure-activity relationships within a series of penicillins and cephalosporins containing an N(4)-substituted piperazine-2,3-dione moiety in the C(6)/C(7)-beta-side chain are discussed.


Clinical efficacy and safety of imidafenacin as add-on treatment for persistent overactive bladder symptoms despite α-blocker treatment in patients with BPH: the ADDITION study.
To evaluate the effects of add-on treatment with an anticholinergic (imidafenacin) on persistent overactive bladder (OAB) symptoms despite α-blocker (tamsulosin) treatment in patients with benign prostatic hyperplasia (BPH). Patients with BPH ≥50 years old, with urinary urgency at least once per week and total OAB symptom score (OABSS) ≥3 points after ≥8-week treatment with tamsulosin were enrolled in a multicenter, open-label study (not double-blinded). Patients were randomized to receive tamsulosin (0.2 mg/day) alone or tamsulosin (0.2 mg/day) + imidafenacin (0.1 mg 2 times a day). Primary endpoint was 12-week change in OABSS; secondary endpoints were changes in OABSS, International Prostate Symptom Score (IPSS), micturition time chart (MTC), hours of undisturbed sleep (HUS), and quality of life (IPSS-QOL and BPH impact index [BII]). For statistical analysis, a mixed-effects model and t test were used. In total, 308 men were enrolled. The change from baseline to 12 weeks in total OABSS was significantly greater with add-on imidafenacin than tamsulosin alone (2.11, 95% confidence interval [CI] 1.47-2.74, P <.0001). Improvements in frequencies of daytime urination, nighttime urination, urinary urgency, urgency incontinence, IPSS, HUS, IPSS-QOL, and BII, were significantly greater from 4 weeks through 12 weeks in the imidafenacin group. Between-group difference in postvoid residual volume at 12 weeks was not significant (-1.74 mL, 95% CI -8.19 to 4.72), and no events of urinary retention were reported. Combined tamsulosin and imidafenacin treatment is effective and safe in patients with BPH with persistent OAB symptoms after tamsulosin monotherapy. Furthermore the combination treatment improved the QOL in BPH patients with OAB.


Assessment of indocyanine green-labeled cetuximab to detect xenografted head and neck cancer cell lines.
The aim of this study is to determine the efficacy of indocyanine green (ICG) conjugated to antiepidermal growth factor receptor antibody (cetuximab) to image head and neck cancer. Mice (n = 3) were injected with unconjugated ICG and imaged at 100-second intervals for a total of 1000 seconds to assess imaging characteristics. Mice (n = 10) xenografted with SCC-1 cells were then systemically injected with cetuximab conjugated to indocyanine green and imaged over a 72-hour period. To assess the sensitivity and specificity, xenografted tumors underwent subtotal resections and then were assessed for residual disease by fluorescence stereomicroscopy and confirmed by histology. Tumors demonstrated excellent fluorescence 24 hours after injection of cetuximab-ICG. There was a direct relationship between fluorescence and the given dose of cetuximab-ICG. Following subtotal resection, we found fluorescence correlated with a sensitivity of 78.4% and specificity of 96%. This study provides evidence that supports further preclinical investigation of cetuximab in the evaluation of surgical margins, but linkage to ICG lacks the sensitivity for use in a clinical setting.


A young child with pediatric multisystem inflammatory syndrome successfully treated with high-dose immunoglobulin therapy.
Pediatric multisystem inflammatory syndrome (MIS-C) is a disease that presents mainly in older children after coronavirus disease 2019 (COVID-19) and is associated with Kawasaki-like symptoms and multiple-organ failure. The number of cases of MIS-C has increased since April 2020, with reports mainly from Europe and the United States. The reason is unclear, but few cases of MIS-C have been reported in Asian countries, including Japan. No treatment has been established for MIS-C. In this study, we report the case of a young boy treated with IVIg for MIS-C by measuring the cytokine profile over time. A 4-year-old boy presented with Kawasaki disease-like symptoms 28 days after a positive result from polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), meeting the World Health Organization criteria for MIS-C diagnosis. Blood tests showed lower levels of C-reactive protein and ferritin, and no decrease in lymphocyte count (<1000/μL) or more increase in fibrinogen than those reported in Japan for MIS-C in school-aged children and older. Neopterin, interleukin (IL)-6, IL-18, soluble tumor necrosis factor receptor (sTNF-R)I and sTNF-RII were all high at disease onset, but neopterin, IL-6, and sTNF-RII rapidly decreased with fever resolution after the second dose of IVIg, while IL-18 and sTNF-RI decreased bimodally. As far as we can determine, this case represents the youngest identified in Japan. The key point of difference between MIS-C and Kawasaki disease is older age in MIS-C, but attention is also needed in infants.


Erbium, chromium:yttrium scandium gallium garnet laser for caries removal: influence on bonding of a self-etching adhesive system.
This study evaluated the influence of the dental substrates obtained after the use of different caries removal techniques on bonding of a self-etching system. Forty, extracted, carious, human molars were ground to expose flat surfaces containing caries-infected dentine surrounded by sound dentine. The caries lesions of the specimens were removed or not (control--G1) either by round steel burs and water-cooled, low speed, handpiece (G2), or by irradiation with an erbium, chromium:yttrium scandium gallium garnet (Er,Cr:YSGG) laser (2W, 20 Hz, 35.38 J/cm(2), fiber G4 handpiece with 0.2826 mm(2), non-contact mode at a 2 mm distance, 70% air/20% water--G3) or using a chemo-mechanical method (Carisolv--G4). Caries-infected, caries-affected and sound dentines were submitted to a bonding system followed by construction of a resin-based composite crown. Hour-glass shaped samples were obtained and submitted to a micro-tensile bond test. The bond strength data were compared by analysis of variance (ANOVA), complemented by Tukey's test (P <or= 0.05). The samples of sound dentine presented higher bond strengths than did samples of caries-affected dentine, except for the groups treated with the Er,Cr:YSGG laser. The highest bond strengths were observed with the sound dentine treated with burs and Carisolv. The bond strengths to caries-affected dentine were similar in all groups. Additionally, bonding to caries-affected dentine of the Er,Cr:YSGG laser and Carisolv groups was similar to bonding to caries-infected dentine. Thus, caries-affected dentine is not an adequate substrate for adhesion. Moreover, amongst the caries removal methods tested, the Er,Cr:YSGG laser irradiation was the poorest in providing a substrate for bonding with the tested self-etching system.


Vitamin D supplementation for irritable bowel syndrome: A systematic review and meta-analysis.
Irritable bowel syndrome (IBS) is a prevalent and complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Observational studies have suggested a relationship between serum vitamin D levels and IBS symptoms. This systematic review and meta-analysis aimed to investigate the clinical effects of vitamin D supplementation on IBS symptom severity and quality of life (QoL) measures. Medline, Embase, Scopus, Web of Science, and The Cochrane Library databases were systematically searched. Data abstraction and quality assessment were conducted by four authors independently, and discrepancies were resolved through consensus from the senior author. Continuous data were pooled with standardized mean difference (SMD) using the DerSimonian and Laird's random-effects model. Sensitivity analysis by risk of bias and potentially "predatory" publication were performed as well. A total of 685 patients across eight studies were included in the meta-analysis. Vitamin D supplementation significantly improved IBS symptom severity scale scores, with a SMD of -0.77 (95% confidence interval [CI] -1.47 to -0.07, P = 0.04, I2 = 91%). Improvements in IBS-QoL scores were also observed, albeit not statistically significant (SMD 0.54; 95% CI -0.34 to 1.41, P = 0.15, I2 = 87%). However, small sample sizes, a relatively young study population, limited ethnicities, and varied vitamin D dosing strategies across the studies were notable limitations. Vitamin D supplementation could be part of our clinical armamentarium when managing IBS patients due to the potential efficacy and good safety profile. Further randomized, controlled trials are required to confirm the therapeutic effects.


Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning.
To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03. Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.4 Gy for average-risk patients and 36-39.6 Gy for high-risk patients. The boost dose was 55.8 Gy to the tumor bed. Patients underwent cognitive testing at baseline and once yearly for 5 years. Performance on tests of memory (associative memory and working memory) and processing speed (composite processing speed and perceptual speed) was analyzed. Mixed-effects models were used to estimate longitudinal trends in neurocognitive outcomes. Reliable change index and logistic regression were used to define clinically meaningful neurocognitive decline and identify variables associated with decline. One hundred and twenty-four patients were eligible for inclusion, with a median neurocognitive follow-up of 5 years. Mean right and left hippocampal doses were significantly associated with decline in associative memory in patients without posterior fossa syndrome (all P < .05). Mean CC and frontal WM doses were significantly associated with decline in both measures of processing speed (all P < .05). Median brain substructure dose-volume histograms were shifted to the right for patients with a decline in associative memory or processing speed. The odds of decline in associative memory and composite processing speed increased by 23%-26% and by 10%-15% for every 1-Gy increase in mean hippocampal dose and mean CC or frontal WM dose, respectively. Increasing RT dose to the CC or frontal WM and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure-informed RT planning may mitigate neurocognitive impairment.


Abciximab and left ventricular thrombus formation in early period of acute myocardial infarction treated with successful primary stenting.
Left ventricular (LV) thrombus related to acute myocardial infarction (AMI) has been rarely diagnosed since primary stenting has become the routine treatment. The salvage of myocardium at risk is considered as a reason for low frequency of this complication. The impact of glycoprotein IIb/IIIa inhibitors on LV thrombus formation remains unknown. This study investigated the relationship between abciximab treatment and presence of LV thrombus in the first few days after primary stenting. A total of 3,078 patients with AMI, who underwent successful primary stenting, were retrospectively analyzed. There were 1,614 patients, who received abciximab and 1,414 treated without it. All patients received aspirin and clopidogrel. LV thrombus was diagnosed by two-dimensional echocardiography within 3-5 days after invasive treatment. This complication appeared equally frequently in both the abciximab and no-abciximab group (2.9% vs. 2.1%, respectively). According to results of multiple log-regression analysis, both groups did not differ in predictors of thrombus formation, such as infarct size and degree of LV dysfunction. Treatment with abciximab was not proved to be an independent predictor of LV thrombus absence. Abciximab does not have a direct influence on LV thrombus formation in the early period of AMI.


[Identification of bacterial flora of conjunctival sac in congenital nasolacrimal duct obstruction in children].
The aim of the study was to evaluate the species of the microorganisms and their susceptibility to antibiotics in congenital nasolacrimal duct obstruction in children. The pus secretion after lacrimal sac massage was obtained from 81 children with congenital nasolacrimal duct obstruction. The laboratory diagnostics was performed using typical microbiological procedures. The modification of these procedures was 24-hour pre-incubation in sugar boullion. The most frequently isolated bacteria were Staphylococcus epidermidis (28%) and Staphylococcus aureus (22%). The isolated staphylococci (only coagulase-negative species MRSE) were resistant to methicillin in 2 cases. Streptococci were obtained in 20% isolations: Streptococcus pneumoniae (14%), Streptococcus viridans (6%). Gram-negative bacilli Pseudomonas aeruginosa and Moraxella spp. and Candida albicans were isolated in a few cases. Negative results of the cultures were obtained in 25% cases. The microorganisms typically constituting physiological flora of conjunctival sac may become the pathogens in the complications of congenital nasolacrimal duct obstruction in children.


Systemic mast cell disease associated with primary ovarian mixed malignant germ cell tumor.
A 12-year-old girl with a mixed malignant germ cell tumor of the ovary, treated by surgery and chemotherapy, developed systemic mast cell disease (SMCD) approximately 3 months after chemotherapy. Hematologic malignancies have previously been noted in patients with mediastinal germ cell tumors but this is the first report of a primary ovarian germ cell neoplasm associated with SMCD.